Patent Grant
8563250
This invention relates to the field of forensic and epidemiological investigations. The methods provide rapid identification of known or suspected terrorists or criminals based on forensic evidence. Additionally, the methods provide tracking of the geographic locations of the terrorists or criminals by microbial geographic profiling of bioagents associated with the terrorists or criminals. Furthermore, the methods provide genotyping of bioagents such as those associated with acts of biowarfare, terrorism or criminal activity.
The ease with which small countries and terrorist groups can now obtain biological warfare agents has escalated the need to provide the war fighter and civilians alike with miniature, easy to use, disposable instruments for detection and identification of potentially hazardous biological agents (Iqbal et al. Biosensors & Bioelectronics 2000, 15, 549-578; Christel, L. A., et al. J. Biomech. Eng. 1999, 121, 22-27; Higgins, J. A., et al. Ann. NY Acad. Sci. 1999, 894, 130-148; and Hood, E. Environ. Health Perspect. 1999, 107, 931-932). Traditional methods for detection and identification of microorganisms, viruses and/or their products lack the speed and sensitivity to be of field usage since they are not real time or even typically completed in a single day. Microbial and viral identification assays have as their basis, the principle that dates back to the days of Pasteur, i.e. the growth of the organism in culture or replication of virus in a suitable host (Reischl, U., Frontiers Biosci., 1996, 1, Application of molecular biology-based methods to the diagnosis of infectious diseases. 1, e72-e77). Toxin identification has typically relied on biological assays, which although relatively rapid, usually requires purification of the toxin prior to testing (Feng, P. Mol. Biotechnol. 1997, 7, 267-278; van der Zee, H. et al. J. AOAC Int. 1997, 80, 934-940). Depending upon the nature of the agent to be detected, this process can take from days to months (Pillai, S. D. Arch. Virol. 1997, 13 Suppl., 67-82; van der Zee, H. et al. J. AOAC Int. 1997, 80, 934-940). Clearly, this is not practical in situations where detection and identification may be required for protecting a population from hazardous biological agents. Molecular recognition systems that can be used for rapid identification can improve response time and thus avert or reduce the number of casualties associated with a potential bioterrorism or biowarfare event.
Biological threat agents can be either infectious or toxigenic organisms or simply toxins (Hood, E. Environ. Health Perspect. 1999, 107, 931-932; Haines, J. D. et al J. Okla. State Med. Assoc. 1999, 93, 187-196). Examples of the former are Bacillus anthracis (anthrax) and Yersinia pestis (plague) while the latter is exemplified by staphylococcal enterotoxin B or botulinum toxin. Detection of toxins has followed a similar track as that observed for detection of chemical threat agents. Typically, toxins are detected on the basis of their respective chemical structures. Detection of mycotoxins has been accomplished using traditional analytical chemistry tools such as gas chromatography-mass spectrometry (GC-MS) (Black, R. M et al. J. Chromatogr. 1986, 367, 103-116). Although precise and highly sensitive, GC-MS does not lend itself to field applications and cannot be easily applied to complex target analytes such as bacteria. Specific compounds, i.e. signature components might be identified in targeted bacterial agents but this approach tends to be too complex for routine, high throughput analysis (van der Zee, H. et al. J. AOAC Int. 1997, 80, 934-940; Hood, E. Environ. Health Perspect. 1999, 107, 931-932).
A number of technological innovations have provided tools that have made detection and identification of microorganisms, viruses and their products faster and more sensitive. Two significant technologies that have had dramatic impact on potentially rapid detection are: (1) generation of monoclonal antibodies; and (2) collection of individual methodological advances that have formed the basis of recombinant DNA technology. A key event in the latter technology is the development of polymerase chain reaction (PCR) technology which as a singular process, has significantly reshaped the authors' thinking with respect to detection of biological agents.
Identification of biological threat agents involves recognition of bacteria (vegetative cells and spores), viruses and toxins. Nucleic acid and immunology-based methods for identification of bacteria, viruses and their products (antigens and toxins) have found wide application including testing of food, clinical and environmental samples. Extension of these applications for detection and identification of biological threat agents is reasonable since basic principles involved are identical. Two essential features characterize these applications, i.e. the need to: (1) develop a target specific identification method; and (2) formulate an assay that will work on the requisite sample. However, the majority of the methods developed meet the first criterion, i.e. identify the target organism or toxin, but fail to be sufficiently robust to work on “real” samples.
Mass spectrometry provides detailed information about the molecules being analyzed, including high mass accuracy. It is also a process that can be easily automated. Low-resolution MS may be unreliable when used to detect some known agents, if their spectral lines are sufficiently weak or sufficiently close to those from other living organisms in the sample. DNA chips with specific probes can only determine the presence or absence of specifically anticipated organisms. Because there are hundreds of thousands of species of benign bacteria, some very similar in sequence to threat organisms, even arrays with 10,000 probes lack the breadth needed to detect a particular organism.
Antibodies face more severe diversity limitations than arrays. If antibodies are designed against highly conserved targets to increase diversity, the false alarm problem will dominate, again because threat organisms are very similar to benign ones. Antibodies are only capable of detecting known agents in relatively uncluttered environments.
Several groups have described detection of PCR products using high resolution electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS). Accurate measurement of exact mass combined with knowledge of the number of at least one nucleotide allowed calculation of the total base composition for PCR duplex products of approximately 100 base pairs. (Aaserud et al., J. Am. Soc. Mass Spec., 1996, 7, 1266-1269; Muddiman et al., Anal. Chem., 1997, 69, 1543-1549; Wunschel et al., Anal. Chem., 1998, 70, 1203-1207; Muddiman et al., Rev. Anal. Chem., 1998, 17, 1-68). Electrospray ionization-Fourier transform-ion cyclotron resistance (ESI-FT-ICR) MS may be used to determine the mass of double-stranded, 500 base-pair PCR products via the average molecular mass (Hurst et al., Rapid Commun. Mass Spec. 1996, 10, 377-382). The use of matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for characterization of PCR products has been described. (Muddiman et al., Rapid Commun. Mass Spec., 1999, 13, 1201-1204). However, the degradation of DNAs over about 75 nucleotides observed with MALDI limited the utility of this method.
U.S. Pat. No. 5,849,492 describes a method for retrieval of phylogenetically informative DNA sequences which comprise searching for a highly divergent segment of genomic DNA surrounded by two highly conserved segments, designing the universal primers for PCR amplification of the highly divergent region, amplifying the genomic DNA by PCR technique using universal primers, and then sequencing the gene to determine the identity of the organism.
U.S. Pat. No. 5,965,363 discloses methods for screening nucleic acids for polymorphisms by analyzing amplified target nucleic acids using mass spectrometric techniques and to procedures for improving mass resolution and mass accuracy of these methods.
WO 99/14375 describes methods, PCR primers and kits for use in analyzing preselected DNA tandem nucleotide repeat alleles by mass spectrometry.
WO 98/12355 discloses methods of determining the mass of a target nucleic acid by mass spectrometric analysis, by cleaving the target nucleic acid to reduce its length, making the target single-stranded and using MS to determine the mass of the single-stranded shortened target. Also disclosed are methods of preparing a double-stranded target nucleic acid for MS analysis comprising amplification of the target nucleic acid, binding one of the strands to a solid support, releasing the second strand and then releasing the first strand which is then analyzed by MS. Kits for target nucleic acid preparation are also provided.
PCT WO97/33000 discloses methods for detecting mutations in a target nucleic acid by nonrandomly fragmenting the target into a set of single-stranded nonrandom length fragments and determining their masses by MS.
U.S. Pat. No. 5,605,798 describes a fast and highly accurate mass spectrometer-based process for detecting the presence of a particular nucleic acid in a biological sample for diagnostic purposes.
WO 98/21066 describes processes for determining the sequence of a particular target nucleic acid by mass spectrometry. Processes for detecting a target nucleic acid present in a biological sample by PCR amplification and mass spectrometry detection are disclosed, as are methods for detecting a target nucleic acid in a sample by amplifying the target with primers that contain restriction sites and tags, extending and cleaving the amplified nucleic acid, and detecting the presence of extended product, wherein the presence of a DNA fragment of a mass different from wild-type is indicative of a mutation. Methods of sequencing a nucleic acid via mass spectrometry methods are also described.
WO 97/37041, WO 99/31278 and U.S. Pat. No. 5,547,835 describe methods of sequencing nucleic acids using mass spectrometry. U.S. Pat. Nos. 5,622,824, 5,872,003 and 5,691,141 describe methods, systems and kits for exonuclease-mediated mass spectrometric sequencing.
Thus, there is a need for methods for bioagent detection and identification which is both specific and rapid, and in which no nucleic acid sequencing is required. The present invention addresses this need as well as other needs.
The present invention is directed to methods of identification of a bioagent associated with an act of biowarfare, terrorism or criminal activity by determining a first molecular mass of a first amplification product of a first bioagent identifying amplicon obtained from a sample taken at the scene of biowarfare, terrorism or criminal activity and comparing the first molecular mass to a second molecular mass of a second bioagent identifying amplicon wherein both first and second bioagent identifying amplicons are correlative.
The present invention is also directed to forensic methods for tracking the geographic location of a bioagent associated with an act of biowarfare by determining a first molecular mass of a first amplification product of a first bioagent identifying amplicon from a forensic sample obtained from a given geographic location; and comparing the first molecular mass to a second molecular mass of a second bioagent identifying amplicon wherein both first and second bioagent identifying amplicons are correlative, wherein a match between the first molecular mass and the second molecular mass indicates at least transient presence of the bioagent associated with an act of biowarfare at the given geographic location.
The present invention is also directed to methods of genotyping a bioagent, by determining a first molecular mass of a first amplification product of a first bioagent identifying amplicon that contains genotyping information and comparing the first molecular mass to a second molecular mass of a second bioagent identifying amplicon that contains genotyping information, wherein the first and second bioagent identifying amplicons are correlative, and wherein a match between the first molecular mass and the second molecular mass identifies a genotype of the bioagent.
The present invention is also directed to methods of tracking a known or suspected terrorist or criminal by determining a first molecular mass of a first amplification product of a first bioagent identifying amplicon containing microbial geographic profiling information from a forensic sample known to be associated with the terrorist or criminal and comparing the first molecular mass to a second molecular mass of a second bioagent identifying amplicon wherein the second bioagent identifying amplicon contains microbial geographic profiling information, wherein both first and second bioagent identifying amplicons are correlative, and wherein a match between the first molecular mass and the second molecular mass indicates at least transient presence of the known or suspected criminal at the geographic location indicated by the microbial geographic profiling information.
A. Introduction
The present invention provides, inter alia, methods for detection and identification of bioagents in an unbiased manner using “bioagent identifying amplicons.” “Intelligent primers” are selected to hybridize to conserved sequence regions of nucleic acids derived from a bioagent and which bracket variable sequence regions to yield a bioagent identifying amplicon which can be amplified and which is amenable to molecular mass determination. The molecular mass then provides a means to uniquely identify the bioagent without a requirement for prior knowledge of the possible identity of the bioagent. The molecular mass or corresponding “base composition signature” (BCS) of the amplification product is then matched against a database of molecular masses or base composition signatures. Furthermore, the method can be applied to rapid parallel “multiplex” analyses, the results of which can be employed in a triangulation identification strategy. The present method provides rapid throughput and does not require nucleic acid sequencing of the amplified target sequence for bioagent detection and identification.
B. Bioagents
In the context of this invention, a “bioagent” is any organism, cell, or virus, living or dead, or a nucleic acid derived from such an organism, cell or virus. Examples of bioagents include, but are not limited, to cells, (including but not limited to, human clinical samples, bacterial cells and other pathogens) viruses, fungi, and protists, parasites, and pathogenicity markers (including but not limited to: pathogenicity islands, antibiotic resistance genes, virulence factors, toxin genes and other bioregulating compounds). Samples may be alive or dead or in a vegetative state (for example, vegetative bacteria or spores) and may be encapsulated or bioengineered. In the context of this invention, a “pathogen” is a bioagent which causes a disease or disorder.
Despite enormous biological diversity, all forms of life on earth share sets of essential, common features in their genomes. Bacteria, for example have highly conserved sequences in a variety of locations on their genomes. Most notable is the universally conserved region of the ribosome. But there are also conserved elements in other non-coding RNAs, including RNAse P and the signal recognition particle (SRP) among others. Bacteria have a common set of absolutely required genes. About 250 genes are present in all bacterial species (Proc. Natl. Acad. Sci. U.S.A., 1996, 93, 10268; Science, 1995, 270, 397), including tiny genomes like Mycoplasma, Ureaplasma and Rickettsia. These genes encode proteins involved in translation, replication, recombination and repair, transcription, nucleotide metabolism, amino acid metabolism, lipid metabolism, energy generation, uptake, secretion and the like. Examples of these proteins are DNA polymerase III beta, elongation factor TU, heat shock protein groEL, RNA polymerase beta, phosphoglycerate kinase, NADH dehydrogenase, DNA ligase, DNA topoisomerase and elongation factor G. Operons can also be targeted using the present method. One example of an operon is the bfp operon from enteropathogenic E. coli. Multiple core chromosomal genes can be used to classify bacteria at a genus or species level to determine if an organism has threat potential. The methods can also be used to detect pathogenicity markers (plasmid or chromosomal) and antibiotic resistance genes to confirm the threat potential of an organism and to direct countermeasures.
C. Selection of “Bioagent Identifying Amplicons”
Since genetic data provide the underlying basis for identification of bioagents by the methods of the present invention, it is necessary to select segments of nucleic acids which ideally provide enough variability to distinguish each individual bioagent and whose molecular mass is amenable to molecular mass determination. In one embodiment of the present invention, at least one polynucleotide segment is amplified to facilitate detection and analysis in the process of identifying the bioagent. Thus, the nucleic acid segments which provide enough variability to distinguish each individual bioagent and whose molecular masses are amenable to molecular mass determination are herein described as “bioagent identifying amplicons.” The term “amplicon” as used herein, refers to a segment of a polynucleotide which is amplified in an amplification reaction.
As used herein, “intelligent primers” are primers that are designed to bind to highly conserved sequence regions of a bioagent identifying amplicon that flank an intervening variable region and yield amplification products which ideally provide enough variability to distinguish each individual bioagent, and which are amenable to molecular mass analysis. By the term “highly conserved,” it is meant that the sequence regions exhibit between about 80-100%, or between about 90-100%, or between about 95-100% identity. The molecular mass of a given amplification product provides a means of identifying the bioagent from which it was obtained, due to the variability of the variable region. Thus design of intelligent primers requires selection of a variable region with appropriate variability to resolve the identity of a given bioagent. Bioagent identifying amplicons are ideally specific to the identity of the bioagent. A plurality of bioagent identifying amplicons selected in parallel for distinct bioagents which contain the same conserved sequences for hybridization of the same pair of intelligent primers are herein defined as “correlative bioagent identifying amplicons.”
In one embodiment, the bioagent identifying amplicon is a portion of a ribosomal RNA (rRNA) gene sequence. With the complete sequences of many of the smallest microbial genomes now available, it is possible to identify a set of genes that defines “minimal life” and identify composition signatures that uniquely identify each gene and organism. Genes that encode core life functions such as DNA replication, transcription, ribosome structure, translation, and transport are distributed broadly in the bacterial genome and are suitable regions for selection of bioagent identifying amplicons. Ribosomal RNA (rRNA) genes comprise regions that provide useful base composition signatures. Like many genes involved in core life functions, rRNA genes contain sequences that are extraordinarily conserved across bacterial domains interspersed with regions of high variability that are more specific to each species. The variable regions can be utilized to build a database of base composition signatures. The strategy involves creating a structure-based alignment of sequences of the small (16S) and the large (23S) subunits of the rRNA genes. For example, there are currently over 13,000 sequences in the ribosomal RNA database that has been created and maintained by Robin Gutell, University of Texas at Austin, and is publicly available on the Institute for Cellular and Molecular Biology web page on the world wide web of the Internet at, for example, “rna.icmb.utexas.edul.” There is also a publicly available rRNA database created and maintained by the University of Antwerp, Belgium on the world wide web of the Internet at, for example, “rrna.uia.ac.be.”
These databases have been analyzed to determine regions that are useful as bioagent identifying amplicons. The characteristics of such regions include: a) between about 80 and 100%, or greater than about 95% identity among species of the particular bioagent of interest, of upstream and downstream nucleotide sequences which serve as sequence amplification primer sites; b) an intervening variable region which exhibits no greater than about 5% identity among species; and c) a separation of between about 30 and 1000 nucleotides, or no more than about 50-250 nucleotides, or no more than about 60-100 nucleotides, between the conserved regions.
As a non-limiting example, for identification of Bacillus species, the conserved sequence regions of the chosen bioagent identifying amplicon must be highly conserved among all Bacillus species while the variable region of the bioagent identifying amplicon is sufficiently variable such that the molecular masses of the amplification products of all species of Bacillus are distinguishable.
Bioagent identifying amplicons amenable to molecular mass determination are either of a length, size or mass compatible with the particular mode of molecular mass determination or compatible with a means of providing a predictable fragmentation pattern in order to obtain predictable fragments of a length compatible with the particular mode of molecular mass determination. Such means of providing a predictable fragmentation pattern of an amplification product include, but are not limited to, cleavage with restriction enzymes or cleavage primers, for example.
Identification of bioagents can be accomplished at different levels using intelligent primers suited to resolution of each individual level of identification. “Broad range survey” intelligent primers are designed with the objective of identifying a bioagent as a member of a particular division of bioagents. A “bioagent division” is defined as group of bioagents above the species level and includes but is not limited to: orders, families, classes, clades, genera or other such groupings of bioagents above the species level. As a non-limiting example, members of the Bacillus/Clostridia group or gamma-proteobacteria group may be identified as such by employing broad range survey intelligent primers such as primers which target 16S or 23S ribosomal RNA.
In some embodiments, broad range survey intelligent primers are capable of identification of bioagents at the species level. One main advantage of the detection methods of the present invention is that the broad range survey intelligent primers need not be specific for a particular bacterial species, or even genus, such as Bacillus or Streptomyces. Instead, the primers recognize highly conserved regions across hundreds of bacterial species including, but not limited to, the species described herein. Thus, the same broad range survey intelligent primer pair can be used to identify any desired bacterium because it will bind to the conserved regions that flank a variable region specific to a single species, or common to several bacterial species, allowing unbiased nucleic acid amplification of the intervening sequence and determination of its molecular weight and base composition. For example, the 16S—971-1062, 16S—1228-1310 and 16S—1100-1188 regions are 98-99% conserved in about 900 species of bacteria (16S=16S rRNA, numbers indicate nucleotide position). In one embodiment of the present invention, primers used in the present method bind to one or more of these regions or portions thereof.
Due to their overall conservation, the flanking rRNA primer sequences serve as good intelligent primer binding sites to amplify the nucleic acid region of interest for most, if not all, bacterial species. The intervening region between the sets of primers varies in length and/or composition, and thus provides a unique base composition signature. Examples of intelligent primers that amplify regions of the 16S and 23S rRNA are shown in
“Division-wide” intelligent primers are designed with an objective of identifying a bioagent at the species level. As a non-limiting example, a Bacillus anthracis, Bacillus cereus and Bacillus thuringiensis can be distinguished from each other using division-wide intelligent primers. Division-wide intelligent primers are not always required for identification at the species level because broad range survey intelligent primers may provide sufficient identification resolution to accomplishing this identification objective.
“Drill-down” intelligent primers are designed with an objective of identifying a sub-species characteristic of a bioagent. A “sub-species characteristic” is defined as a property imparted to a bioagent at the sub-species level of identification as a result of the presence or absence of a particular segment of nucleic acid. Such sub-species characteristics include, but are not limited to, strains, sub-types, pathogenicity markers such as antibiotic resistance genes, pathogenicity islands, toxin genes and virulence factors. Identification of such sub-species characteristics is often critical for determining proper clinical treatment of pathogen infections.
Chemical Modifications of Intelligent Primers
Ideally, intelligent primer hybridization sites are highly conserved in order to facilitate the hybridization of the primer. In cases where primer hybridization is less efficient due to lower levels of conservation of sequence, intelligent primers can be chemically modified to improve the efficiency of hybridization.
For example, because any variation (due to codon wobble in the 3rd position) in these conserved regions among species is likely to occur in the third position of a DNA triplet, oligonucleotide primers can be designed such that the nucleotide corresponding to this position is a base which can bind to more than one nucleotide, referred to herein as a “universal base.” For example, under this “wobble” pairing, inosine (I) binds to U, C or A; guanine (G) binds to U or C, and uridine (U) binds to U or C. Other examples of universal bases include nitroindoles such as 5-nitroindole or 3-nitropyrrole (Loakes et al., Nucleosides and Nucleotides, 1995, 14, 1001-1003), the degenerate nucleotides dP or dK (Hill et al.), an acyclic nucleoside analog containing 5-nitroindazole (Van Aerschot et al., Nucleosides and Nucleotides, 1995, 14, 1053-1056) or the purine analog 1-(2-deoxy-β-D-ribofuranosyl)-imidazole-4-carboxamide (Sala et al., Nucl. Acids Res., 1996, 24, 3302-3306).
In another embodiment of the invention, to compensate for the somewhat weaker binding by the “wobble” base, the oligonucleotide primers are designed such that the first and second positions of each triplet are occupied by nucleotide analogs which bind with greater affinity than the unmodified nucleotide. Examples of these analogs include, but are not limited to, 2,6-diaminopurine which binds to thymine, propyne T which binds to adenine and propyne C and phenoxazines, including G-clamp, which binds to G. Propynylated pyrimidines are described in U.S. Pat. Nos. 5,645,985, 5,830,653 and 5,484,908, each of which is commonly owned and incorporated herein by reference in its entirety. Propynylated primers are claimed in U.S. Ser. No. 10/294,203 which is also commonly owned and incorporated herein by reference in entirety. Phenoxazines are described in U.S. Pat. Nos. 5,502,177, 5,763,588, and 6,005,096, each of which is incorporated herein by reference in its entirety. G-clamps are described in U.S. Pat. Nos. 6,007,992 and 6,028,183, each of which is incorporated herein by reference in its entirety.
D. Characterization of Bioagent Identifying Amplicons
A theoretically ideal bioagent detector would identify, quantify, and report the complete nucleic acid sequence of every bioagent that reached the sensor. The complete sequence of the nucleic acid component of a pathogen would provide all relevant information about the threat, including its identity and the presence of drug-resistance or pathogenicity markers. This ideal has not yet been achieved. However, the present invention provides a straightforward strategy for obtaining information with the same practical value based on analysis of bioagent identifying amplicons by molecular mass determination.
In some cases, a molecular mass of a given bioagent identifying amplicon alone does not provide enough resolution to unambiguously identify a given bioagent. For example, the molecular mass of the bioagent identifying amplicon obtained using the intelligent primer pair “16S—971” would be 55622 Da for both E. coli and Salmonella typhimurium. However, if additional intelligent primers are employed to analyze additional bioagent identifying amplicons, a “triangulation identification” process is enabled. For example, the “16S—1100” intelligent primer pair yields molecular masses of 55009 and 55005 Da for E. coli and Salmonella typhimurium, respectively. Furthermore, the “23S—855” intelligent primer pair yields molecular masses of 42656 and 42698 Da for E. coli and Salmonella typhimurium, respectively. In this basic example, the second and third intelligent primer pairs provided the additional “fingerprinting” capability or resolution to distinguish between the two bioagents.
In another embodiment, the triangulation identification process is pursued by measuring signals from a plurality of bioagent identifying amplicons selected within multiple core genes. This process is used to reduce false negative and false positive signals, and enable reconstruction of the origin of hybrid or otherwise engineered bioagents. In this process, after identification of multiple core genes, alignments are created from nucleic acid sequence databases. The alignments are then analyzed for regions of conservation and variation, and bioagent identifying amplicons are selected to distinguish bioagents based on specific genomic differences. For example, identification of the three part toxin genes typical of B. anthracis (Bowen et al., J. Appl. Microbiol., 1999, 87, 270-278) in the absence of the expected signatures from the B. anthracis genome would suggest a genetic engineering event.
The triangulation identification process can be pursued by characterization of bioagent identifying amplicons in a massively parallel fashion using the polymerase chain reaction (PCR), such as multiplex PCR, and mass spectrometric (MS) methods. Sufficient quantities of nucleic acids should be present for detection of bioagents by MS. A wide variety of techniques for preparing large amounts of purified nucleic acids or fragments thereof are well known to those of skill in the art. PCR requires one or more pairs of oligonucleotide primers that bind to regions which flank the target sequence(s) to be amplified. These primers prime synthesis of a different strand of DNA, with synthesis occurring in the direction of one primer towards the other primer. The primers, DNA to be amplified, a thermostable DNA polymerase (e.g. Taq polymerase), the four deoxynucleotide triphosphates, and a buffer are combined to initiate DNA synthesis. The solution is denatured by heating, then cooled to allow annealing of newly added primer, followed by another round of DNA synthesis. This process is typically repeated for about 30 cycles, resulting in amplification of the target sequence.
Although the use of PCR is suitable, other nucleic acid amplification techniques may also be used, including ligase chain reaction (LCR) and strand displacement amplification (SDA). The high-resolution MS technique allows separation of bioagent spectral lines from background spectral lines in highly cluttered environments.
In another embodiment, the detection scheme for the PCR products generated from the bioagent(s) incorporates at least three features. First, the technique simultaneously detects and differentiates multiple (generally about 6-10) PCR products. Second, the technique provides a molecular mass that uniquely identifies the bioagent from the possible primer sites. Finally, the detection technique is rapid, allowing multiple PCR reactions to be run in parallel.
E. Mass Spectrometric Characterization of Bioagent Identifying Amplicons
Mass spectrometry (MS)-based detection of PCR products provides a means for determination of BCS which has several advantages. MS is intrinsically a parallel detection scheme without the need for radioactive or fluorescent labels, since every amplification product is identified by its molecular mass. The current state of the art in mass spectrometry is such that less than femtomole quantities of material can be readily analyzed to afford information about the molecular contents of the sample. An accurate assessment of the molecular mass of the material can be quickly obtained, irrespective of whether the molecular weight of the sample is several hundred, or in excess of one hundred thousand atomic mass units (amu) or Daltons. Intact molecular ions can be generated from amplification products using one of a variety of ionization techniques to convert the sample to gas phase. These ionization methods include, but are not limited to, electrospray ionization (ES), matrix-assisted laser desorption ionization (MALDI) and fast atom bombardment (FAB). For example, MALDI of nucleic acids, along with examples of matrices for use in MALDI of nucleic acids, are described in WO 98/54751 (Genetrace, Inc.).
In some embodiments, large DNAs and RNAs, or large amplification products therefrom, can be digested with restriction endonucleases prior to ionization. Thus, for example, an amplification product that was 10 kDa could be digested with a series of restriction endonucleases to produce a panel of, for example, 100 Da fragments. Restriction endonucleases and their sites of action are well known to the skilled artisan. In this manner, mass spectrometry can be performed for the purposes of restriction mapping.
Upon ionization, several peaks are observed from one sample due to the formation of ions with different charges. Averaging the multiple readings of molecular mass obtained from a single mass spectrum affords an estimate of molecular mass of the bioagent. Electrospray ionization mass spectrometry (ESI-MS) is particularly useful for very high molecular weight polymers such as proteins and nucleic acids having molecular weights greater than 10 kDa, since it yields a distribution of multiply-charged molecules of the sample without causing a significant amount of fragmentation.
The mass detectors used in the methods of the present invention include, but are not limited to, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), ion trap, quadrupole, magnetic sector, time of flight (TOF), Q-TOF, and triple quadrupole.
In general, the mass spectrometric techniques which can be used in the present invention include, but are not limited to, tandem mass spectrometry, infrared multiphoton dissociation and pyrolytic gas chromatography mass spectrometry (PGC-MS). In one embodiment of the invention, the bioagent detection system operates continually in bioagent detection mode using pyrolytic GC-MS without PCR for rapid detection of increases in biomass (for example, increases in fecal contamination of drinking water or of germ warfare agents). To achieve minimal latency, a continuous sample stream flows directly into the PGC-MS combustion chamber. When an increase in biomass is detected, a PCR process is automatically initiated. Bioagent presence produces elevated levels of large molecular fragments from, for example, about 100-7,000 Da which are observed in the PGC-MS spectrum. The observed mass spectrum is compared to a threshold level and when levels of biomass are determined to exceed a predetermined threshold, the bioagent classification process described hereinabove (combining PCR and MS, such as FT-ICR MS) is initiated. Optionally, alarms or other processes (halting ventilation flow, physical isolation) are also initiated by this detected biomass level.
The accurate measurement of molecular mass for large DNAs is limited by the adduction of cations from the PCR reaction to each strand, resolution of the isotopic peaks from natural abundance 13C and 15N isotopes, and assignment of the charge state for any ion. The cations are removed by in-line dialysis using a flow-through chip that brings the solution containing the PCR products into contact with a solution containing ammonium acetate in the presence of an electric field gradient orthogonal to the flow. The latter two problems are addressed by operating with a resolving power of >100,000 and by incorporating isotopically depleted nucleotide triphosphates into the DNA. The resolving power of the instrument is also a consideration. At a resolving power of 10,000, the modeled signal from the [M-14H+]14− charge state of an 84mer PCR product is poorly characterized and assignment of the charge state or exact mass is impossible. At a resolving power of 33,000, the peaks from the individual isotopic components are visible. At a resolving power of 100,000, the isotopic peaks are resolved to the baseline and assignment of the charge state for the ion is straightforward. The [13C,15N]-depleted triphosphates are obtained, for example, by growing microorganisms on depleted media and harvesting the nucleotides (Batey et al., Nucl. Acids Res., 1992, 20, 4515-4523).
While mass measurements of intact nucleic acid regions are believed to be adequate to determine most bioagents, tandem mass spectrometry (MSn) techniques may provide more definitive information pertaining to molecular identity or sequence. Tandem MS involves the coupled use of two or more stages of mass analysis where both the separation and detection steps are based on mass spectrometry. The first stage is used to select an ion or component of a sample from which further structural information is to be obtained. The selected ion is then fragmented using, e.g., blackbody irradiation, infrared multiphoton dissociation, or collisional activation. For example, ions generated by electrospray ionization (ESI) can be fragmented using IR multiphoton dissociation. This activation leads to dissociation of glycosidic bonds and the phosphate backbone, producing two series of fragment ions, called the w-series (having an intact 3′ terminus and a 5′ phosphate following internal cleavage) and the a-Base series (having an intact 5′ terminus and a 3′ furan).
The second stage of mass analysis is then used to detect and measure the mass of these resulting fragments of product ions. Such ion selection followed by fragmentation routines can be performed multiple times so as to essentially completely dissect the molecular sequence of a sample.
If there are two or more targets of similar molecular mass, or if a single amplification reaction results in a product which has the same mass as two or more bioagent reference standards, they can be distinguished by using mass-modifying “tags.” In this embodiment of the invention, a nucleotide analog or “tag” is incorporated during amplification (e.g., a 5-(trifluoromethyl)deoxythymidine triphosphate) which has a different molecular weight than the unmodified base so as to improve distinction of masses. Such tags are described in, for example, PCT WO97/33000, which is incorporated herein by reference in its entirety. This further limits the number of possible base compositions consistent with any mass. For example, 5-(trifluoromethyl)deoxythymidine triphosphate can be used in place of dTTP in a separate nucleic acid amplification reaction. Measurement of the mass shift between a conventional amplification product and the tagged product is used to quantitate the number of thymidine nucleotides in each of the single strands. Because the strands are complementary, the number of adenosine nucleotides in each strand is also determined.
In another amplification reaction, the number of G and C residues in each strand is determined using, for example, the cytidine analog 5-methylcytosine (5-meC) or propyne C. The combination of the A/T reaction and G/C reaction, followed by molecular weight determination, provides a unique base composition. This method is summarized in
The mass tag phosphorothioate A (A*) was used to distinguish a Bacillus anthracis cluster. The B. anthracis (A14G9C14T9) had an average MW of 14072.26, and the B. anthracis (A1A*13G9C14T9) had an average molecular weight of 14281.11 and the phosphorothioate A had an average molecular weight of +16.06 as determined by ESI-TOF MS. The deconvoluted spectra are shown in
In another example, assume the measured molecular masses of each strand are 30,000.115 Da and 31,000.115 Da respectively, and the measured number of dT and dA residues are (30,28) and (28,30). If the molecular mass is accurate to 100 ppm, there are 7 possible combinations of dG+dC possible for each strand. However, if the measured molecular mass is accurate to 10 ppm, there are only 2 combinations of dG+dC, and at 1 ppm accuracy there is only one possible base composition for each strand.
Signals from the mass spectrometer may be input to a maximum-likelihood detection and classification algorithm such as is widely used in radar signal processing. The detection processing uses matched filtering of BCS observed in mass-basecount space and allows for detection and subtraction of signatures from known, harmless organisms, and for detection of unknown bioagent threats. Comparison of newly observed bioagents to known bioagents is also possible, for estimation of threat level, by comparing their BCS to those of known organisms and to known forms of pathogenicity enhancement, such as insertion of antibiotic resistance genes or toxin genes.
Processing may end with a Bayesian classifier using log likelihood ratios developed from the observed signals and average background levels. The program emphasizes performance predictions culminating in probability-of-detection versus probability-of-false-alarm plots for conditions involving complex backgrounds of naturally occurring organisms and environmental contaminants. Matched filters consist of a priori expectations of signal values given the set of primers used for each of the bioagents. A genomic sequence database (e.g. GenBank) is used to define the mass basecount matched filters. The database contains known threat agents and benign background organisms. The latter is used to estimate and subtract the signature produced by the background organisms. A maximum likelihood detection of known background organisms is implemented using matched filters and a running-sum estimate of the noise covariance. Background signal strengths are estimated and used along with the matched filters to form signatures which are then subtracted. the maximum likelihood process is applied to this “cleaned up” data in a similar manner employing matched filters for the organisms and a running-sum estimate of the noise-covariance for the cleaned up data.
F. Base Composition Signatures as Indices of Bioagent Identifying Amplicons
Although the molecular mass of amplification products obtained using intelligent primers provides a means for identification of bioagents, conversion of molecular mass data to a base composition signature is useful for certain analyses. As used herein, a “base composition signature” (BCS) is the exact base composition determined from the molecular mass of a bioagent identifying amplicon. In one embodiment, a BCS provides an index of a specific gene in a specific organism.
Base compositions, like sequences, vary slightly from isolate to isolate within species. It is possible to manage this diversity by building “base composition probability clouds” around the composition constraints for each species. This permits identification of organisms in a fashion similar to sequence analysis. A “pseudo four-dimensional plot” can be used to visualize the concept of base composition probability clouds (
It is important to note that, in contrast to probe-based techniques, mass spectrometry determination of base composition does not require prior knowledge of the composition in order to make the measurement, only to interpret the results. In this regard, the present invention provides bioagent classifying information similar to DNA sequencing and phylogenetic analysis at a level sufficient to detect and identify a given bioagent. Furthermore, the process of determination of a previously unknown BCS for a given bioagent (for example, in a case where sequence information is unavailable) has downstream utility by providing additional bioagent indexing information with which to populate BCS databases. The process of future bioagent identification is thus greatly improved as more BCS indexes become available in the BCS databases.
Another embodiment of the present invention is a method of surveying bioagent samples that enables detection and identification of all bacteria for which sequence information is available using a set of twelve broad-range intelligent PCR primers. Six of the twelve primers are “broad range survey primers” herein defined as primers targeted to broad divisions of bacteria (for example, the Bacillus/Clostridia group or gamma-proteobacteria). The other six primers of the group of twelve primers are “division-wide” primers herein defined as primers which provide more focused coverage and higher resolution. This method enables identification of nearly 100% of known bacteria at the species level. A further example of this embodiment of the present invention is a method herein designated “survey/drill-down” wherein a subspecies characteristic for detected bioagents is obtained using additional primers. Examples of such a subspecies characteristic include but are not limited to: antibiotic resistance, pathogenicity island, virulence factor, strain type, sub-species type, and Glade group. Using the survey/drill-down method, bioagent detection, confirmation and a subspecies characteristic can be provided within hours. Moreover, the survey/drill-down method can be focused to identify bioengineering events such as the insertion of a toxin gene into a bacterial species that does not normally make the toxin.
G. Fields of Application of the Present Invention
The present methods allow extremely rapid and accurate detection and identification of bioagents compared to existing methods. Furthermore, this rapid detection and identification is possible even when sample material is impure. The methods leverage ongoing biomedical research in virulence, pathogenicity, drug resistance and genome sequencing into a method which provides greatly improved sensitivity, specificity and reliability compared to existing methods, with lower rates of false positives. Thus, the methods are useful in a wide variety of fields, including, but not limited to, those fields discussed below.
1. Forensic Investigations of Biowarfare Agents
In other embodiments of the invention, the methods disclosed herein can be used for epidemiological and forensics investigations. As used herein, “epidemiology” refers to an investigative process which attempts to link the effects of exposure to harmful agents to disease or mortality. As used herein, “forensics” is the study of evidence discovered at a crime investigation or accident scene and which may be used in a court of law. “Forensic science” is any science used for the purposes of the law, and therefore provides impartial scientific evidence for use in the courts of law, and in a criminal investigation and trial. Forensic science is a multidisciplinary subject, drawing principally from chemistry and biology, but also from physics, geology, psychology and social science, for example.
Epidemiological and forensic investigations of biowarfare- or bioterrorism-associated events can benefit from rapid and reliable methods of genetic analysis capable of characterizing a variety of genetic marker types. Examples of such genetic marker analyses include, but are not limited to: Multiple-Locus VNTR Analysis (MLVA), Multi-Locus Sequence Typing (MLST) and Single Nucleotide Polymorphism (SNP) analysis. These methods traditionally require independent PCR-based assays followed by electrophoresis on fluorescent sequencing platforms.
In addition, epidemiologists, for example, can use the present methods to determine the geographic origin of a particular strain of a protist or fungus. For example, a particular strain of bacteria or virus may have a sequence difference that is associated with a particular area of a country or the world and identification of such a sequence difference can lead to the identification of the geographic origin and epidemiological tracking of the spread of the particular disease, disorder or condition associated with the detected protist or fungus. In addition, carriers of particular DNA or diseases, such as mammals, non-mammals, birds, insects, and plants, can be tracked by screening their mtDNA. Diseases, such as malaria, can be tracked by screening the mtDNA of commensals such as mosquitoes.
In one embodiment the methods of the present invention are employed for identification of bioagent associated with an act of biowarfare, terrorism or criminal activity.
Examples of bioagents that may be used in acts of biowarfare, or bioterrorism include, but are not limited to: viruses such as: Crimean-Congo hemorrhagic fever virus, Eastern Equine Encephalitis virus, Ebola virus, Equine Morbillivirus, Flexal virus, Guanarito virus, Hantaan or other Hanta viruses, Junin virus, Lassa fever virus, Machupo virus, Marburg virus, Omsk hemorrhagic fever virus, Rift Valley fever virus, Russian Spring-Summer encephalitis virus, Sabia virus, Tick-borne encephalitis complex viruses, Variola major virus (Smallpox virus), Venezuelan Equine Encephalitis virus, Coronavirus and Yellow fever virus; bacteria such as: Bacillus anthracis, Brucella abortus, Brucella melitensis, Brucella suis, Burkholderia (Pseudomonas) mallei, Burkholderia (Pseudomonas) pseudomallei, Clostridium botulinum, Francisella tularensis, Yersinia pestis, Rickettsiae, Coxiella burnetii, Rickettsia prowazekii, and Rickettsia rickettsii; fungi such as: Coccidioides immitis; and toxins such as: abrin, aflatoxins, Botulinum toxins, Clostridium perfringens epsilon toxin, conotoxins, diacetoxyscirpenol, ricin, saxitoxin, shigatoxin, Staphylococcal enterotoxins, Tetrodotoxin and T-2 toxin (see, for example, www.ehs.iastate.edu/publications/factsheets/bioterrorismlaws.pdf).
As an example, a bioagent such as Bacillus anthracis is identified in a sample obtained from the site of an incident of biowarfare, terrorism or crime by employing intelligent primers to amplify a bioagent identifying amplicon from the bioagent, determining molecular mass (and the base composition signature if desired) of the amplified nucleic acid and matching the molecular mass (and base composition signature, if desired) with a molecular mass or base composition indexed to a bioagent contained in a database of reference base composition signatures.
2. Epidemiologic Investigations by Genotyping of Bioagents
In another embodiment, a bioagent is genotyped. “Genotyping” as used herein, refers to characterization of a nucleic acid representing a gene or a portion of a gene. As a nonlimiting example, genotyping is carried out to investigate the presence or absence of “pathogenicity factors” defined herein as a segment of nucleic acid which confers pathogenic properties upon a bioagent. Examples of pathogenicity factors include, but are not limited to: pathogenicity islands, virulence markers and toxin components such as: protective antigen, lethal factor and edema factor, all of which are found on the plasmid pX01 and the antiphagocytic capsule found on plasmid pX02 of Bacillus anthracis. Primers targeting nucleic acid regions suspected of containing pathogenicity factors are used to amplify the nucleic acid whose, molecular mass (and base composition signature if desired) is then determined and compared to molecular masses (and base composition signatures if desired) of known pathogenicity factors to identify the pathogenicity factor.
An example of an advantage conferred by genotyping is that genetic engineering events are detected. Genetic engineering has been used in the past decade to alter the genes of biological weapon agents. Researchers in the USA, UK, Russia, Germany and other countries have introduced genes into hazardous bacteria that are likely to enhance the biowarfare possibilities of these microbes. Strains have been designed that can withstand antibiotics, are undetectable by traditional equipment, can overcome vaccines, or that cause unusual symptoms, thereby hampering diagnosis. In general, gene transfer is used to build more effective biological weapons, it could be used to broaden the military biological warfare spectrum, making it more difficult to fight and control biowarfare agents (www.sunshine-project.org/publications/pr/pr130700.html).
The present invention is particularly well suited for the task of detecting genetic engineering events since reference databases can be populated with molecular mass data or associated base composition signatures for known pathogenic factors. Primers targeting nucleic acid regions suspected of containing pathogenicity factors are used to amplify the nucleic acid whose molecular mass and base composition signature is then determined and compared to molecular masses and base composition signatures of known pathogenicity factors. A match between a molecular mass and/or base composition signature determined for genetically engineered bioagent and the base composition of a pathogenicity factor provides a means for identifying the pathogenicity factor incorporated into the genetically engineered bioagent so that appropriate countermeasures may be carried out.
In another embodiment, the present methods are used in forensic investigations which employ microbial geographic profiling information to track a known or suspected terrorist or criminal by obtaining bioagent samples from the site of incidence of an act of terrorism or crime, identifying the bioagent and correlating the identity of the bioagent with the likelihood that the bioagent is associated with the known or suspected terrorist or criminal. As used herein, “microbial geographic profiling” refers to the process of associating a particular genetic characteristic of a microbial bioagent with the geographic location in which it originates and is typically located.
In some embodiments of the invention the travels of a known terrorist are tracked. The terrorist can be a member of a known terrorist organization, such as Al Qaeda, or can be a member of an unknown terrorist organization. Alternately, the terrorist can be a single entity operating independently of any organization. Known terrorists include those individuals who are known by or listed by particular governments, such as the United States, or departments or agencies within a government, such as the Federal Bureau of Investigation, the Central Intelligence Agency, the Department of Homeland Security, the State Department, Congress, the National Security Agency, and the like. Suspected terrorists include those individuals not known to be terrorists as described above, but who are likely to be or are suspected of supporting or engaging in terroristic acts.
Travels of a known or suspected terrorist include all geographic movements of a particular individual terrorist. The travels of the individual terrorist may represent geographic movements of a terrorist organization of which the individual terrorist is a member. Geographic movements or travels of a terrorist include, foot travel, air travel, automobile travel, train travel, bus travel, or any other means of movement from one location in the world to another location in the world. Tracking of such travels or geographic movements includes determining at least one geographic location that the terrorist has occupied, other than the geographic location the terrorist is in when a sample is taken from the terrorist. For example, the travels of a terrorist that is currently located, for instance, in the United Kingdom, at the time a sample is obtained can be “tracked” to another location such as, for instance, Afghanistan. Thus, the travels of such a terrorist can be tracked from Afghanistan to the United Kingdom.
Geographic locations of interest to be tracked include every country or state in the world including, but not limited to, the Mideast (e.g., Afghanistan, Iraq, Iran, Syria, Jordan, Palestinian-occupied territory, Lebanon, Kuwait, Yemen, United Arab Emirates, and Saudi Arabia), Northern Africa (e.g., Egypt, Sudan, Somalia, Tunisia, Morocco, and Libya), Asia (e.g., North Korea, China, Pakistan, India, Philippines, and Indonesia), as well as other countries, states, or territories known or suspected of sponsoring or harboring terrorists.
A nucleic acid from a bioagent obtained from a sample associated with the terrorist is obtained. Samples associated with terrorists can be obtained knowingly from the terrorist or can be obtained covertly from the terrorist. For example, the terrorist can be detained and the sample or samples obtained from the terrorist with the terrorist's knowledge. Alternately, the sample or samples can be obtained covertly from the terrorists without the terrorist's knowledge. The sample from the terrorist can be associated with the terrorist in a direct manner or indirect manner. For example, samples associated with a terrorist can be obtained directly from the terrorist. Such samples include, but are not limited to, a sample of bodily fluid of a sample of tissue from the terrorist. Examples of bodily fluids include, but are not limited to, blood, sweat, tears, urine, saliva, and the like. Examples of bodily tissues include, but are not limited to, hair, skin, bone, and the like. In addition, types of bodily tissues include products derived therefrom such as feces, mucous, and the like. Thus, a food product containing a bioagent that has been consumed by a terrorist can be detected in samples of feces or saliva. Other samples associated with a terrorist include, but are not limited to, a sample of clothing from the terrorist, a sample of environmental material from the terrorist, a sample from a pet travelling with the terrorist, or a sample from a luggage traveling with the terrorist. Examples of environmental material include, but are not limited to, dirt, water, plant material, animal material, and the like that may be present somewhere on the terrorist or with pets, luggage, or companions traveling therewith.
In one example of the present embodiment, a terrorist from a camp in the Sahara Desert commits an act of terrorism in a European country, leaving forensic evidence at the scene of the terrorist act. Samples of the forensic evidence are analyzed by the methods of the present invention. Bacillus mojavensis is identified in the sample by employing intelligent primers to amplify nucleic acid from the bacterium, determining the base composition signature of the amplified nucleic acid and matching the base composition with a base composition indexed to Bacillus mojavensis contained in a database of reference base composition signatures. This analysis indicates that Bacillus mojavensis is present in the soil sample associated with the terrorist. Further genotyping of the bioagent using primers targeting the pTA-like plasmid rep and mob genes then provides an indication that the strain of Bacillus mojavensis is B. mojavensis IM-E-3, a strain found in the Sahara Desert (Mason, M. P. et al. FEMS Microbiol. Ecol. 2002, 42, 235-241), thus indicating that the terrorist is associated with a soil sample originating from the Sahara Desert. These analyses are optionally repeated for additional bioagents identified in the forensic sample to ascertain other geographic locations to which the known or suspected terrorist has traveled.
While the present invention has been described with specificity in accordance with certain of its embodiments, the following examples serve only to illustrate the invention and are not intended to limit the same.
In one embodiment, nucleic acid is isolated from the organisms and amplified by PCR using standard methods prior to BCS determination by mass spectrometry. Nucleic acid is isolated, for example, by detergent lysis of bacterial cells, centrifugation and ethanol precipitation. Nucleic acid isolation methods are described in, for example, Current Protocols in Molecular Biology (Ausubel et al.) and Molecular Cloning; A Laboratory Manual (Sambrook et al.). The nucleic acid is then amplified using standard methodology, such as PCR, with primers which bind to conserved regions of the nucleic acid which contain an intervening variable sequence as described below.
General Genomic DNA Sample Prep Protocol: Raw samples are filtered using Supor-200 0.2 μm membrane syringe filters (VWR International). Samples are transferred to 1.5 ml eppendorf tubes pre-filled with 0.45 g of 0.7 mm Zirconia beads followed by the addition of 350 μl of ATL buffer (Qiagen, Valencia, Calif.). The samples are subjected to bead beating for 10 minutes at a frequency of 19 l/s in a Retsch Vibration Mill (Retsch). After centrifugation, samples are transferred to an S-block plate (Qiagen) and DNA isolation is completed with a BioRobot 8000 nucleic acid isolation robot (Qiagen).
Swab Sample Protocol: Allegiance S/P brand culture swabs and collection/transport system are used to collect samples. After drying, swabs are placed in 17×100 mm culture tubes (VWR International) and the genomic nucleic acid isolation is carried out automatically with a Qiagen Mdx robot and the Qiagen QIAamp DNA Blood BioRobot Mdx genomic preparation kit (Qiagen, Valencia, Calif.).
FTICR Instrumentation: The FTICR instrument is based on a 7 tesla actively shielded superconducting magnet and modified Bruker Daltonics Apex II 70e ion optics and vacuum chamber. The spectrometer is interfaced to a LEAP PAL autosampler and a custom fluidics control system for high throughput screening applications. Samples are analyzed directly from 96-well or 384-well microtiter plates at a rate of about 1 sample/minute. The Bruker data-acquisition platform is supplemented with a lab-built ancillary NT datastation which controls the autosampler and contains an arbitrary waveform generator capable of generating complex rf-excite waveforms (frequency sweeps, filtered noise, stored waveform inverse Fourier transform (SWIFT), etc.) for sophisticated tandem MS experiments. For oligonucleotides in the 20-30-mer regime typical performance characteristics include mass resolving power in excess of 100,000 (FWHM), low ppm mass measurement errors, and an operable m/z range between 50 and 5000 m/z.
Modified ESI Source: In sample-limited analyses, analyte solutions are delivered at 150 mL/minute to a 30 mm i.d. fused-silica ESI emitter mounted on a 3-D micromanipulator. The ESI ion optics consists of a heated metal capillary, an rf-only hexapole, a skimmer cone, and an auxiliary gate electrode. The 6.2 cm rf-only hexapole is comprised of 1 mm diameter rods and is operated at a voltage of 380 Vpp at a frequency of 5 MHz. A lab-built electro-mechanical shutter can be employed to prevent the electrospray plume from entering the inlet capillary unless triggered to the “open” position via a TTL pulse from the data station. When in the “closed” position, a stable electrospray plume is maintained between the ESI emitter and the face of the shutter. The back face of the shutter arm contains an elastomeric seal that can be positioned to form a vacuum seal with the inlet capillary. When the seal is removed, a 1 mm gap between the shutter blade and the capillary inlet allows constant pressure in the external ion reservoir regardless of whether the shutter is in the open or closed position. When the shutter is triggered, a “time slice” of ions is allowed to enter the inlet capillary and is subsequently accumulated in the external ion reservoir. The rapid response time of the ion shutter (<25 ms) provides reproducible, user defined intervals during which ions can be injected into and accumulated in the external ion reservoir.
Apparatus for Infrared Multiphoton Dissociation: A 25 watt CW CO2 laser operating at 10.6 μm has been interfaced to the spectrometer to enable infrared multiphoton dissociation (IRMPD) for oligonucleotide sequencing and other tandem MS applications. An aluminum optical bench is positioned approximately 1.5 m from the actively shielded superconducting magnet such that the laser beam is aligned with the central axis of the magnet. Using standard IR-compatible mirrors and kinematic mirror mounts, the unfocused 3 mm laser beam is aligned to traverse directly through the 3.5 mm holes in the trapping electrodes of the FTICR trapped ion cell and longitudinally traverse the hexapole region of the external ion guide finally impinging on the skimmer cone. This scheme allows IRMPD to be conducted in an m/z selective manner in the trapped ion cell (e.g. following a SWIFT isolation of the species of interest), or in a broadband mode in the high pressure region of the external ion reservoir where collisions with neutral molecules stabilize IRMPD-generated metastable fragment ions resulting in increased fragment ion yield and sequence coverage.
Table 2 shows a small cross section of a database of calculated molecular masses for over 9 primer sets and approximately 30 organisms. The primer sets were derived from rRNA alignment. Examples of regions from rRNA consensus alignments are shown in
Included in the short bacterial database cross-section in Table 2 are many well known pathogens/biowarfare agents (shown in bold/red typeface) such as Bacillus anthracis or Yersinia pestis as well as some of the bacterial organisms found commonly in the natural environment such as Streptomyces. Even closely related organisms can be distinguished from each other by the appropriate choice of primers. For instance, two low G+C organisms, Bacillus anthracis and Staph aureus, can be distinguished from each other by using the primer pair defined by 16S—1337 or 23S—855 (ΔM of 4 Da).
Acinetobacter calcoaceticus
55005
54388
28448
35238
51296
30295
42651
39560
56850
Bacillus cereus
Bordetella bronchiseptica
Borrelia burgdorferi
58098
55011
28448
35854
50683
Campylobacter jejuni
55000
55007
29063
35855
50676
30295
42036
38941
56230
55006
53767
28445
35855
51291
30300
42656
39562
54999
Clostridium difficile
Enterococcus faecalis
55622
55009
28445
35857
51301
30301
42656
39562
54999
53769
54385
28445
35856
51298
Haemophilus influenzae
Klebsiella pneumoniae
55618
55626
28446
35857
51303
Mycobacterium avium
Mycobacterium leprae
Mycobacterium tuberculosis
Mycoplasma genitalium
Mycoplasma pneumoniae
Neisseria gonorrhoeae
55623
55010
28443
35858
51301
30298
43272
39558
55619
58093
55621
28448
35853
50677
30293
42650
39559
53139
58094
55623
28448
35853
50679
30293
42648
39559
53755
55622
55005
28445
35857
51301
30301
42658
55623
55009
28444
35857
51301
Staphylococcus aureus
Streptomyces
Treponema pallidum
55625
55626
28443
35857
52536
29063
30303
35241
50675
Vibrio parahaemolyticus
55620
55626
28443
35857
51299
1Molecular mass distribution of PCR amplified regions for a selection of organisms (rows) across various primer pairs (columns). Pathogens are shown in bold. Empty cells indicate presently incomplete or missing data.
14208.3890
0.016020
A11 G14 C11 T10
14079.3579
0.014940
A10 G11 C14 T11
Among the 16 compositions for the forward strand and the 18 compositions for the reverse strand that were calculated, only one pair (shown in bold) are complementary, corresponding to the actual base compositions of the B. anthracis PCR products.
A conserved Bacillus region from B. anthracis (A14G9C14T9) and B. cereus (A15G9C13T9) having a C to A base change was synthesized and subjected to ESI-TOF MS. The results are shown in
In other examples of the present invention, the pathogen Vibrio cholera can be distinguished from Vibrio parahemolyticus with ΔM>600 Da using one of three 16S primer sets shown in Table 2 (16S—971, 16S—1228 or 16S—1294) as shown in Table 4. The two mycoplasma species in the list (M. genitalium and M. pneumoniae) can also be distinguished from each other, as can the three mycobacteriae. While the direct mass measurements of amplified products can identify and distinguish a large number of organisms, measurement of the base composition signature provides dramatically enhanced resolving power for closely related organisms. In cases such as Bacillus anthracis and Bacillus cereus that are virtually indistinguishable from each other based solely on mass differences, compositional analysis or fragmentation patterns are used to resolve the differences. The single base difference between the two organisms yields different fragmentation patterns, and despite the presence of the ambiguous/unidentified base N at position 20 in B. anthracis, the two organisms can be identified.
Tables 4a-b show examples of primer pairs from Table 1 which distinguish pathogens from background.
Bacillus anthracis
Staphylococcus aureus
Vibrio cholerae
Vibrio
parahaemolyticus
Table 5 shows the expected molecular weight and base composition of region 16S—1100-1188 in Mycobacterium avium and Streptomyces sp.
Mycobac-
terium avium
Streptomyces
Table 6 shows base composition (single strand) results for 16S—1100-1188 primer amplification reactions different species of bacteria. Species which are repeated in the table (e.g., Clostridium botulinum) are different strains which have different base compositions in the 16S—1100-1188 region.
Mycobacterium avium
Streptomyces sp.
Ureaplasma urealyticum
Streptomyces sp.
Mycobacterium leprae
A
20
G
33
C
21
T
16
A
20
G
33
C
21
T
16
Fusobacterium necroforum
Listeria monocytogenes
Clostridium botulinum
Neisseria gonorrhoeae
Bartonella quintana
Enterococcus faecalis
Bacillus megaterium
Bacillus subtilis
Pseudomonas aeruginosa
Legionella pneumophila
Mycoplasma pneumoniae
Clostridium botulinum
Enterococcus faecium
Acinetobacter calcoaceti
A
23
G
26
C
24
T
15
A
23
G
26
C
24
T
15
Clostridium perfringens
A
23
G
27
C
20
T
18
A
23
G
27
C
20
T
18
A
23
G
27
C
20
T
18
Aeromonas hydrophila
Escherichia coli
Pseudomonas putida
A
23
G
29
C
22
T
15
A
23
G
29
C
22
T
15
Vibrio cholerae
A
23
G
31
C
21
T
15
A
23
G
31
C
21
T
15
Mycoplasma genitalium
Clostridium botulinum
Bordetella bronchiseptica
Francisella tularensis
A
24
G
26
C
20
T
18
A
24
G
26
C
20
T
18
A
24
G
26
C
20
T
18
Helicobacter pylori
Helicobacter pylori
Moraxella catarrhalis
Haemophilus influenzae Rd
A
24
G
28
C
21
T
16
A
24
G
28
C
21
T
16
A
24
G
28
C
21
T
16
Pseudomonas putida
A
24
G
30
C
21
T
15
A
24
G
30
C
21
T
15
A
24
G
30
C
21
T
15
Clostridium botulinum
Clostridium tetani
Francisella tularensis
Acinetobacter calcoacetic
Bacteriodes fragilis
Chlamydophila psittaci
Borrelia burgdorferi
Streptobacillus monilifor
Rickettsia prowazekii
Rickettsia rickettsii
Mycoplasma mycoides
The same organism having different base compositions are different strains. Groups of organisms which are highlighted or in italics have the same base compositions in the amplified region. Some of these organisms can be distinguished using multiple primers. For example, Bacillus anthracis can be distinguished from Bacillus cereus and Bacillus thuringiensis using the primer 16S—971-1062 (Table 7). Other primer pairs which produce unique base composition signatures are shown in Table 7 (bold). Clusters containing very similar threat and ubiquitous non-threat organisms (e.g. anthracis cluster) are distinguished at high resolution with focused sets of primer pairs. The known biowarfare agents in Table 7 are Bacillus anthracis, Yersinia pestis, Francisella tularensis and Rickettsia prowazekii.
Aeromonas
hydrophila
Aeromonas
salmonicida
Bacillus anthracis
A
21
G
27
C
22
T
22
Bacillus cereus
Bacillus
thuringiensis
Chlamydia
A
22
G
26
C
20
T
23
A
24
G
23
C
19
T
16
trachomatis
Chlamydia
pneumoniae
Leptospira
borgpetersenii
Leptospira
interrogans
Mycoplasma
A
30
G
18
C
15
T
19
A
24
G
19
C
12
T
18
genitalium
Mycoplasma
A
27
G
19
C
16
T
20
A
23
G
20
C
14
T
16
pneumoniae
Escherichia coli
A
22
G
28
C
20
T
22
Shigella
A
22
G
28
C
21
T
21
dysenteriae
Proteus vulgaris
A
23
G
26
C
22
T
21
A
26
G
24
C
19
T
14
Yersinia pestis
Yersinia
pseudo-
tuberculosis
Francisella
A
20
G
25
C
21
T
23
A
23
G
26
C
17
T
17
A
24
G
26
C
19
T
19
tularensis
Rickettsia
A
21
G
26
C
24
T
25
A
24
G
23
C
16
T
19
A
26
G
28
C
18
T
18
prowazekii
Rickettsia
A
21
G
26
C
25
T
24
A
24
G
24
C
17
T
17
A
26
G
28
C
20
T
16
rickettsii
The sequence of B. anthracis and B. cereus in region 16S—971 is shown below. Shown in bold is the single base difference between the two species which can be detected using the methods of the present invention. B. anthracis has an ambiguous base at position 20.
B. anthracis_16S_971
B. cereus_16S_971
The mass measurement accuracy that can be obtained using an internal mass standard in the ESI-MS study of PCR products is shown in
An ESI-TOF MS spectrum was obtained from an aqueous solution containing 5 μM each of synthetic analogs of the expected forward and reverse PCR products from the nucleotide 1228 region of the B. anthracis 16S rRNA gene. The results (
An ESI-FTICR-MS spectrum was obtained from an aqueous solution containing 5 μM each of synthetic analogs of the expected forward and reverse PCR products from the nucleotide 1337 region of the B. anthracis 16S rRNA gene. The results (
ESI-TOF MS spectra were obtained on a synthetic 56-mer oligonucleotide (5 μM) from the saspB gene of B. anthracis containing an internal mass standard at an ESI of 1.7 μL/min as a function of sample consumption. The results (
An ESI-TOF-MS spectrum of a 20-mer phosphorothioate mass standard was obtained following addition of 5 mM TBA-TFA buffer to the solution. This buffer strips charge from the oligonucleotide and shifts the most abundant charge state from [M-8H+]8− to [M-3H+]3− (
The molecular masses obtained through Examples 1-10 are compared to molecular masses of known bioagents stored in a master database to obtain a high probability matching molecular mass.
The same procedure as in Example 11 is followed except that the local computer did not store the Master database. The Master database is interrogated over an internet connection, searching for a molecular mass match.
The same procedure as in example 11 is followed except the local computer is connected to the internet and has the ability to store a master database locally. The local computer system periodically, or at the user's discretion, interrogates the Master database, synchronizing the local master database with the global Master database. This provides the current molecular mass information to both the local database as well as to the global Master database. This further provides more of a globalized knowledge base.
The same procedure as in example 13 is followed except there are numerous such local stations throughout the world. The synchronization of each database adds to the diversity of information and diversity of the molecular masses of known bioagents.
In accordance with the present invention, the present methods were employed for genotyping 24 globally diverse isolates of B. anthracis using both MLVA and SNP analyses.
For SNP analysis, bioagent identifying amplicons less than 100 bp long were designed around single or double SNPs from the protective antigen gene (PAG). Amplification products were obtained for the bioagent identifying amplicons. As shown in
For MLVA analysis, amplification products of bioagent identifying amplicons containing portions of pX01, pX02, vrrB2, CG3, Bavntr12, and Bavntr35 loci were examined. Results are shown in Table 8 and indicate that the present methods are capable of distinguishing the molecular masses and base compositions of the MLVA markers at the six different loci.
The results presented in this example indicate that the methods of the present invention provide a powerful means for high-throughput genotyping of B. anthracis. These same methods can be applied to similar genotyping analyses for other bioagents.
Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference cited in the present application is incorporated herein by reference in its entirety.
This application is a continuation of U.S. application Ser. No. 10/660,997 filed Sep. 12, 2003, which is continuation-in-part of U.S. application Ser. No. 09/798,007 filed Mar. 2, 2001, each of which is incorporated herein by reference in its entirety. Said application U.S. application Ser. No. 10/660,997 is also a continuation-in-part of U.S. application Ser. No. 10/323,438 filed Dec. 18, 2002, which is incorporated herein by reference in its entirety. Said application U.S. application Ser. No. 10/660,997 also claims priority to U.S. provisional application Ser. No. 60/431,319 filed Dec. 6, 2002 and to U.S. provisional application Ser. No. 60/461,494 filed Apr. 9, 2003, each of which is incorporated herein by reference in its entirety.
This invention was made with United States Government support under DARPA contract MDA972-00-C-0053. The United States Government has certain rights in the invention.
| Number | Name | Date | Kind |
|---|---|---|---|
| 4075475 | Risby et al. | Feb 1978 | A |
| 4683195 | Mullis et al. | Jul 1987 | A |
| 4683202 | Mullis | Jul 1987 | A |
| 4965188 | Mullis et al. | Oct 1990 | A |
| 4965190 | Woo et al. | Oct 1990 | A |
| 5015845 | Allen et al. | May 1991 | A |
| 5072115 | Zhou | Dec 1991 | A |
| 5143905 | Sivasubramanian et al. | Sep 1992 | A |
| 5213961 | Bunn et al. | May 1993 | A |
| 5219727 | Wang et al. | Jun 1993 | A |
| 5288611 | Kohne | Feb 1994 | A |
| 5436129 | Stapleton | Jul 1995 | A |
| 5451500 | Stapleton | Sep 1995 | A |
| 5472843 | Milliman | Dec 1995 | A |
| 5476774 | Wang et al. | Dec 1995 | A |
| 5484908 | Froehler et al. | Jan 1996 | A |
| 5502177 | Matteucci et al. | Mar 1996 | A |
| 5503980 | Cantor | Apr 1996 | A |
| 5504327 | Sproch et al. | Apr 1996 | A |
| 5504329 | Mann et al. | Apr 1996 | A |
| 5523217 | Lupski et al. | Jun 1996 | A |
| 5527669 | Resnick et al. | Jun 1996 | A |
| 5527675 | Coull et al. | Jun 1996 | A |
| 5547835 | Koster | Aug 1996 | A |
| 5567587 | Kohne | Oct 1996 | A |
| 5576204 | Blanco et al. | Nov 1996 | A |
| 5580733 | Levis et al. | Dec 1996 | A |
| 5605798 | Koster | Feb 1997 | A |
| 5608217 | Franzen et al. | Mar 1997 | A |
| 5612179 | Simons | Mar 1997 | A |
| 5622824 | Koster | Apr 1997 | A |
| 5625184 | Vestal et al. | Apr 1997 | A |
| 5639606 | Willey | Jun 1997 | A |
| 5641632 | Kohne | Jun 1997 | A |
| 5645985 | Froehler et al. | Jul 1997 | A |
| 5645994 | Huang | Jul 1997 | A |
| 5683869 | Ramsay Shaw et al. | Nov 1997 | A |
| 5686242 | Bruice et al. | Nov 1997 | A |
| 5691141 | Koster | Nov 1997 | A |
| 5700642 | Monforte et al. | Dec 1997 | A |
| 5702895 | Matsunaga et al. | Dec 1997 | A |
| 5705332 | Roll | Jan 1998 | A |
| 5707802 | Sandhu et al. | Jan 1998 | A |
| 5712125 | Uhlen | Jan 1998 | A |
| 5716825 | Hancock et al. | Feb 1998 | A |
| 5727202 | Kucala | Mar 1998 | A |
| 5745751 | Nelson et al. | Apr 1998 | A |
| 5747246 | Pannetier et al. | May 1998 | A |
| 5747251 | Carson et al. | May 1998 | A |
| 5753467 | Jensen et al. | May 1998 | A |
| 5753489 | Kistner et al. | May 1998 | A |
| 5759771 | Tilanus | Jun 1998 | A |
| 5763169 | Sandhu et al. | Jun 1998 | A |
| 5763588 | Matteucci et al. | Jun 1998 | A |
| 5770367 | Southern et al. | Jun 1998 | A |
| 5777324 | Hillenkamp | Jul 1998 | A |
| 5814442 | Natarajan et al. | Sep 1998 | A |
| 5822824 | Dion | Oct 1998 | A |
| 5828062 | Jarrell et al. | Oct 1998 | A |
| 5830653 | Froehler et al. | Nov 1998 | A |
| 5830655 | Monforte et al. | Nov 1998 | A |
| 5830853 | Backstrom et al. | Nov 1998 | A |
| 5832489 | Kucala | Nov 1998 | A |
| 5834255 | Van Gemen et al. | Nov 1998 | A |
| 5845174 | Yasui et al. | Dec 1998 | A |
| 5849492 | Rogan | Dec 1998 | A |
| 5849497 | Steinman | Dec 1998 | A |
| 5849901 | Mabilat et al. | Dec 1998 | A |
| 5851765 | Koster | Dec 1998 | A |
| 5856174 | Lipshutz et al. | Jan 1999 | A |
| 5864137 | Becker et al. | Jan 1999 | A |
| 5866429 | Bloch | Feb 1999 | A |
| 5869242 | Kamb | Feb 1999 | A |
| 5871697 | Rothberg et al. | Feb 1999 | A |
| 5872003 | Koster | Feb 1999 | A |
| 5876936 | Ju | Mar 1999 | A |
| 5876938 | Stolowitz et al. | Mar 1999 | A |
| 5885775 | Haff et al. | Mar 1999 | A |
| 5900481 | Lough et al. | May 1999 | A |
| 5928905 | Stemmer et al. | Jul 1999 | A |
| 5928906 | Koster et al. | Jul 1999 | A |
| 5965363 | Monforte et al. | Oct 1999 | A |
| 5965383 | Vogel et al. | Oct 1999 | A |
| 5972693 | Rothberg et al. | Oct 1999 | A |
| 5976798 | Parker et al. | Nov 1999 | A |
| 5981176 | Wallace | Nov 1999 | A |
| 5981190 | Israel | Nov 1999 | A |
| 5994066 | Bergeron et al. | Nov 1999 | A |
| 6001564 | Bergeron et al. | Dec 1999 | A |
| 6005096 | Matteucci et al. | Dec 1999 | A |
| 6007690 | Nelson et al. | Dec 1999 | A |
| 6007992 | Lin et al. | Dec 1999 | A |
| 6015666 | Springer et al. | Jan 2000 | A |
| 6018713 | Coli et al. | Jan 2000 | A |
| 6024925 | Little et al. | Feb 2000 | A |
| 6028183 | Lin et al. | Feb 2000 | A |
| 6043031 | Koster et al. | Mar 2000 | A |
| 6046005 | Ju et al. | Apr 2000 | A |
| 6051378 | Monforte et al. | Apr 2000 | A |
| 6054278 | Dodge et al. | Apr 2000 | A |
| 6055487 | Margery et al. | Apr 2000 | A |
| 6060246 | Summerton et al. | May 2000 | A |
| 6061686 | Gauvin et al. | May 2000 | A |
| 6063031 | Cundari et al. | May 2000 | A |
| 6074823 | Koster | Jun 2000 | A |
| 6074831 | Yakhini et al. | Jun 2000 | A |
| 6090558 | Butler et al. | Jul 2000 | A |
| 6104028 | Hunter et al. | Aug 2000 | A |
| 6110710 | Smith et al. | Aug 2000 | A |
| 6111251 | Hillenkamp | Aug 2000 | A |
| 6133436 | Koster et al. | Oct 2000 | A |
| 6140053 | Koster | Oct 2000 | A |
| 6146144 | Fowler et al. | Nov 2000 | A |
| 6146854 | Koster et al. | Nov 2000 | A |
| 6153389 | Haarer et al. | Nov 2000 | A |
| 6159681 | Zebala | Dec 2000 | A |
| 6180339 | Sandhu et al. | Jan 2001 | B1 |
| 6180372 | Franzen | Jan 2001 | B1 |
| 6187842 | Kobayashi et al. | Feb 2001 | B1 |
| 6194144 | Koster | Feb 2001 | B1 |
| 6197498 | Koster | Mar 2001 | B1 |
| 6214555 | Leushner et al. | Apr 2001 | B1 |
| 6218118 | Sampson et al. | Apr 2001 | B1 |
| 6221587 | Ecker et al. | Apr 2001 | B1 |
| 6221598 | Schumm et al. | Apr 2001 | B1 |
| 6221601 | Koster et al. | Apr 2001 | B1 |
| 6221605 | Koster | Apr 2001 | B1 |
| 6225450 | Koster | May 2001 | B1 |
| 6235476 | Bergmann et al. | May 2001 | B1 |
| 6235478 | Koster | May 2001 | B1 |
| 6235480 | Shultz et al. | May 2001 | B1 |
| 6238871 | Koster | May 2001 | B1 |
| 6238927 | Abrams et al. | May 2001 | B1 |
| 6239159 | Brown et al. | May 2001 | B1 |
| 6258538 | Koster et al. | Jul 2001 | B1 |
| 6261769 | Everett et al. | Jul 2001 | B1 |
| 6265716 | Hunter et al. | Jul 2001 | B1 |
| 6265718 | Park et al. | Jul 2001 | B1 |
| 6266131 | Hamada et al. | Jul 2001 | B1 |
| 6266144 | Li | Jul 2001 | B1 |
| 6268129 | Gut et al. | Jul 2001 | B1 |
| 6268131 | Kang et al. | Jul 2001 | B1 |
| 6268144 | Koster | Jul 2001 | B1 |
| 6268146 | Shultz et al. | Jul 2001 | B1 |
| 6270973 | Lewis et al. | Aug 2001 | B1 |
| 6270974 | Shultz et al. | Aug 2001 | B1 |
| 6274726 | Laugharn, Jr. et al. | Aug 2001 | B1 |
| 6277573 | Koster | Aug 2001 | B1 |
| 6277578 | Shultz et al. | Aug 2001 | B1 |
| 6277634 | McCall et al. | Aug 2001 | B1 |
| 6300076 | Koster | Oct 2001 | B1 |
| 6303297 | Lincoln et al. | Oct 2001 | B1 |
| 6312893 | Van Ness et al. | Nov 2001 | B1 |
| 6312902 | Shultz et al. | Nov 2001 | B1 |
| 6322970 | Little et al. | Nov 2001 | B1 |
| 6361940 | Van Ness et al. | Mar 2002 | B1 |
| 6372424 | Brow et al. | Apr 2002 | B1 |
| 6389428 | Rigault et al. | May 2002 | B1 |
| 6391551 | Shultz et al. | May 2002 | B1 |
| 6393367 | Tang et al. | May 2002 | B1 |
| 6419932 | Dale | Jul 2002 | B1 |
| 6423966 | Hillenkamp et al. | Jul 2002 | B2 |
| 6428955 | Koster et al. | Aug 2002 | B1 |
| 6428956 | Crooke et al. | Aug 2002 | B1 |
| 6432651 | Hughes et al. | Aug 2002 | B1 |
| 6436635 | Fu et al. | Aug 2002 | B1 |
| 6436640 | Simmons et al. | Aug 2002 | B1 |
| 6453244 | Oefner | Sep 2002 | B1 |
| 6458533 | Felder et al. | Oct 2002 | B1 |
| 6468743 | Romick et al. | Oct 2002 | B1 |
| 6468748 | Monforte et al. | Oct 2002 | B1 |
| 6475143 | Iliff | Nov 2002 | B2 |
| 6475736 | Stanton, Jr. | Nov 2002 | B1 |
| 6475738 | Shuber et al. | Nov 2002 | B2 |
| 6479239 | Anderson et al. | Nov 2002 | B1 |
| 6500621 | Koster | Dec 2002 | B2 |
| 6553317 | Lincoln et al. | Apr 2003 | B1 |
| 6558902 | Hillenkamp | May 2003 | B1 |
| 6563025 | Song et al. | May 2003 | B1 |
| 6566055 | Monforte et al. | May 2003 | B1 |
| 6568055 | Tang et al. | May 2003 | B1 |
| 6582916 | Schmidt et al. | Jun 2003 | B1 |
| 6586584 | McMillian et al. | Jul 2003 | B2 |
| 6589485 | Koster | Jul 2003 | B2 |
| 6602662 | Koster et al. | Aug 2003 | B1 |
| 6605433 | Fliss et al. | Aug 2003 | B1 |
| 6610492 | Stanton, Jr. et al. | Aug 2003 | B1 |
| 6613509 | Chen | Sep 2003 | B1 |
| 6613520 | Ashby | Sep 2003 | B2 |
| 6623928 | Van Ness et al. | Sep 2003 | B2 |
| 6638714 | Linnen et al. | Oct 2003 | B1 |
| 6680476 | Hidalgo et al. | Jan 2004 | B1 |
| 6682889 | Wang et al. | Jan 2004 | B1 |
| 6705530 | Kiekhaefer | Mar 2004 | B2 |
| 6706530 | Hillenkamp | Mar 2004 | B2 |
| 6783939 | Olmsted et al. | Aug 2004 | B2 |
| 6800289 | Nagata et al. | Oct 2004 | B2 |
| 6813615 | Colasanti et al. | Nov 2004 | B1 |
| 6836742 | Brekenfeld | Dec 2004 | B2 |
| 6852487 | Barany et al. | Feb 2005 | B1 |
| 6856914 | Pelech | Feb 2005 | B1 |
| 6875593 | Froehler et al. | Apr 2005 | B2 |
| 6906316 | Sugiyama et al. | Jun 2005 | B2 |
| 6906319 | Hoyes | Jun 2005 | B2 |
| 6914137 | Baker | Jul 2005 | B2 |
| 6921817 | Banerjee | Jul 2005 | B1 |
| 6977148 | Dean et al. | Dec 2005 | B2 |
| 6994962 | Thilly | Feb 2006 | B1 |
| 7022835 | Rauth et al. | Apr 2006 | B1 |
| 7024370 | Epler et al. | Apr 2006 | B2 |
| 7108974 | Ecker et al. | Sep 2006 | B2 |
| 7198893 | Köster et al. | Apr 2007 | B1 |
| 7217510 | Ecker et al. | May 2007 | B2 |
| 7226739 | Ecker et al. | Jun 2007 | B2 |
| 7255992 | Ecker et al. | Aug 2007 | B2 |
| 7285422 | Little et al. | Oct 2007 | B1 |
| 7312036 | Sampath et al. | Dec 2007 | B2 |
| 7321828 | Cowsert et al. | Jan 2008 | B2 |
| 7349808 | Kreiswirth et al. | Mar 2008 | B1 |
| 7390458 | Burow et al. | Jun 2008 | B2 |
| 7419787 | Köster | Sep 2008 | B2 |
| 7501251 | Köster et al. | Mar 2009 | B2 |
| 7666588 | Ecker et al. | Feb 2010 | B2 |
| 7718354 | Ecker et al. | May 2010 | B2 |
| 7741036 | Ecker et al. | Jun 2010 | B2 |
| 7781162 | Ecker et al. | Aug 2010 | B2 |
| 8017322 | Ecker et al. | Sep 2011 | B2 |
| 8017358 | Ecker et al. | Sep 2011 | B2 |
| 8017743 | Ecker et al. | Sep 2011 | B2 |
| 8026084 | Ecker et al. | Sep 2011 | B2 |
| 8046171 | Ecker et al. | Oct 2011 | B2 |
| 8057993 | Ecker et al. | Nov 2011 | B2 |
| 8158354 | Hofstadler et al. | Apr 2012 | B2 |
| 20010039263 | Matthes et al. | Nov 2001 | A1 |
| 20020006611 | Portugal et al. | Jan 2002 | A1 |
| 20020042112 | Koster et al. | Apr 2002 | A1 |
| 20020042506 | Kristyanne et al. | Apr 2002 | A1 |
| 20020045178 | Cantor et al. | Apr 2002 | A1 |
| 20020055101 | Bergeron et al. | May 2002 | A1 |
| 20020120408 | Kreiswirth et al. | Aug 2002 | A1 |
| 20020137057 | Wold et al. | Sep 2002 | A1 |
| 20020138210 | Wilkes et al. | Sep 2002 | A1 |
| 20020150927 | Matray et al. | Oct 2002 | A1 |
| 20020168630 | Fleming et al. | Nov 2002 | A1 |
| 20020187490 | Tiedje et al. | Dec 2002 | A1 |
| 20030017487 | Xue et al. | Jan 2003 | A1 |
| 20030027135 | Ecker et al. | Feb 2003 | A1 |
| 20030039976 | Haff | Feb 2003 | A1 |
| 20030050470 | An et al. | Mar 2003 | A1 |
| 20030064483 | Shaw et al. | Apr 2003 | A1 |
| 20030073112 | Zhang et al. | Apr 2003 | A1 |
| 20030084483 | Simpson et al. | May 2003 | A1 |
| 20030101172 | De La Huerga | May 2003 | A1 |
| 20030104410 | Mittmann | Jun 2003 | A1 |
| 20030104699 | Minamihaba et al. | Jun 2003 | A1 |
| 20030113738 | Liu et al. | Jun 2003 | A1 |
| 20030113745 | Monforte et al. | Jun 2003 | A1 |
| 20030119018 | Omura et al. | Jun 2003 | A1 |
| 20030129589 | Koster et al. | Jul 2003 | A1 |
| 20030134312 | Burgoyne | Jul 2003 | A1 |
| 20030148281 | Glucksmann | Aug 2003 | A1 |
| 20030148284 | Vision et al. | Aug 2003 | A1 |
| 20030167133 | Ecker et al. | Sep 2003 | A1 |
| 20030167134 | Ecker et al. | Sep 2003 | A1 |
| 20030175695 | Ecker et al. | Sep 2003 | A1 |
| 20030175696 | Ecker et al. | Sep 2003 | A1 |
| 20030175697 | Ecker et al. | Sep 2003 | A1 |
| 20030175729 | Van Eijk et al. | Sep 2003 | A1 |
| 20030186247 | Smarason et al. | Oct 2003 | A1 |
| 20030187588 | Ecker et al. | Oct 2003 | A1 |
| 20030187593 | Ecker et al. | Oct 2003 | A1 |
| 20030190605 | Ecker et al. | Oct 2003 | A1 |
| 20030190635 | McSwiggen | Oct 2003 | A1 |
| 20030194699 | Lewis et al. | Oct 2003 | A1 |
| 20030203398 | Bramucci et al. | Oct 2003 | A1 |
| 20030220844 | Marnellos et al. | Nov 2003 | A1 |
| 20030224377 | Wengel et al. | Dec 2003 | A1 |
| 20030225529 | Ecker et al. | Dec 2003 | A1 |
| 20030228571 | Ecker et al. | Dec 2003 | A1 |
| 20030228597 | Cowsert et al. | Dec 2003 | A1 |
| 20030228613 | Bornarth et al. | Dec 2003 | A1 |
| 20040005555 | Rothman et al. | Jan 2004 | A1 |
| 20040013703 | Ralph et al. | Jan 2004 | A1 |
| 20040014957 | Eldrup et al. | Jan 2004 | A1 |
| 20040023207 | Polansky | Feb 2004 | A1 |
| 20040023209 | Jonasson | Feb 2004 | A1 |
| 20040029129 | Wang et al. | Feb 2004 | A1 |
| 20040038206 | Zhang et al. | Feb 2004 | A1 |
| 20040038208 | Fisher et al. | Feb 2004 | A1 |
| 20040038234 | Gut et al. | Feb 2004 | A1 |
| 20040038385 | Langlois et al. | Feb 2004 | A1 |
| 20040081993 | Cantor et al. | Apr 2004 | A1 |
| 20040101809 | Weiss et al. | May 2004 | A1 |
| 20040110169 | Ecker et al. | Jun 2004 | A1 |
| 20040111221 | Beattie et al. | Jun 2004 | A1 |
| 20040117129 | Ecker et al. | Jun 2004 | A1 |
| 20040117354 | Azzaro et al. | Jun 2004 | A1 |
| 20040121309 | Ecker et al. | Jun 2004 | A1 |
| 20040121310 | Ecker et al. | Jun 2004 | A1 |
| 20040121311 | Ecker et al. | Jun 2004 | A1 |
| 20040121312 | Ecker et al. | Jun 2004 | A1 |
| 20040121313 | Ecker et al. | Jun 2004 | A1 |
| 20040121314 | Ecker et al. | Jun 2004 | A1 |
| 20040121315 | Ecker et al. | Jun 2004 | A1 |
| 20040121329 | Ecker et al. | Jun 2004 | A1 |
| 20040121335 | Ecker et al. | Jun 2004 | A1 |
| 20040121340 | Ecker et al. | Jun 2004 | A1 |
| 20040122598 | Ecker et al. | Jun 2004 | A1 |
| 20040122857 | Ecker et al. | Jun 2004 | A1 |
| 20040126764 | Lasken et al. | Jul 2004 | A1 |
| 20040137013 | Katinger et al. | Jul 2004 | A1 |
| 20040185438 | Ecker | Sep 2004 | A1 |
| 20040191769 | Marino et al. | Sep 2004 | A1 |
| 20040202997 | Ecker et al. | Oct 2004 | A1 |
| 20040209260 | Ecker et al. | Oct 2004 | A1 |
| 20040253583 | Ecker et al. | Dec 2004 | A1 |
| 20040253619 | Ecker et al. | Dec 2004 | A1 |
| 20050009053 | Boecker et al. | Jan 2005 | A1 |
| 20050026147 | Walker et al. | Feb 2005 | A1 |
| 20050026641 | Hokao | Feb 2005 | A1 |
| 20050027459 | Ecker et al. | Feb 2005 | A1 |
| 20050065813 | Mishelevich et al. | Mar 2005 | A1 |
| 20050130196 | Hofstadler et al. | Jun 2005 | A1 |
| 20050130216 | Becker et al. | Jun 2005 | A1 |
| 20050142584 | Willson et al. | Jun 2005 | A1 |
| 20050250125 | Novakoff | Nov 2005 | A1 |
| 20050266397 | Ecker et al. | Dec 2005 | A1 |
| 20050266411 | Hofstadler et al. | Dec 2005 | A1 |
| 20060020391 | Kreiswirth et al. | Jan 2006 | A1 |
| 20060121520 | Ecker et al. | Jun 2006 | A1 |
| 20060172330 | Osborn et al. | Aug 2006 | A1 |
| 20060205040 | Sampath | Sep 2006 | A1 |
| 20060240412 | Hall et al. | Oct 2006 | A1 |
| 20060259249 | Sampath et al. | Nov 2006 | A1 |
| 20070218467 | Ecker et al. | Sep 2007 | A1 |
| 20080160512 | Ecker et al. | Jul 2008 | A1 |
| 20080311558 | Ecker et al. | Dec 2008 | A1 |
| 20090004643 | Ecker et al. | Jan 2009 | A1 |
| 20090023150 | Koster et al. | Jan 2009 | A1 |
| 20090042203 | Koster | Feb 2009 | A1 |
| 20090092977 | Koster | Apr 2009 | A1 |
| 20090125245 | Hofstadler et al. | May 2009 | A1 |
| 20090148829 | Ecker et al. | Jun 2009 | A1 |
| 20090148836 | Ecker et al. | Jun 2009 | A1 |
| 20090148837 | Ecker et al. | Jun 2009 | A1 |
| 20090182511 | Ecker et al. | Jul 2009 | A1 |
| 20090239224 | Ecker et al. | Sep 2009 | A1 |
| 20100070194 | Ecker et al. | Mar 2010 | A1 |
| 20100145626 | Ecker et al. | Jun 2010 | A1 |
| 20100184035 | Hall et al. | Jul 2010 | A1 |
| 20110172925 | Ecker et al. | Jul 2011 | A1 |
| 20110238316 | Ecker et al. | Sep 2011 | A1 |
| Number | Date | Country |
|---|---|---|
| 19732086 | Jan 1999 | DE |
| 19802905 | Jul 1999 | DE |
| 19824280 | Dec 1999 | DE |
| 19852167 | May 2000 | DE |
| 19943374 | Mar 2001 | DE |
| 10132147 | Feb 2003 | DE |
| 281390 | Sep 1988 | EP |
| 0620862 | Oct 1994 | EP |
| 0620862 | Oct 1994 | EP |
| 633321 | Jan 1995 | EP |
| 0620862 | Apr 1998 | EP |
| 1035219 | Sep 2000 | EP |
| 1138782 | Oct 2001 | EP |
| 1234888 | Aug 2002 | EP |
| 1308506 | May 2003 | EP |
| 1310571 | May 2003 | EP |
| 1333101 | Aug 2003 | EP |
| 1365031 | Nov 2003 | EP |
| 1234888 | Jan 2004 | EP |
| 1234888 | Jan 2004 | EP |
| 1748072 | Jan 2007 | EP |
| 2811321 | Jan 2002 | FR |
| 2325002 | Nov 1998 | GB |
| 2339905 | Feb 2000 | GB |
| 5276999 | Oct 1993 | JP |
| 11137259 | May 1999 | JP |
| 24024206 | Jan 2004 | JP |
| 2004000200 | Jan 2004 | JP |
| 24201679 | Jul 2004 | JP |
| 2004201641 | Jul 2004 | JP |
| WO8803957 | Jun 1988 | WO |
| WO9015157 | Dec 1990 | WO |
| WO9205182 | Apr 1992 | WO |
| WO9208117 | May 1992 | WO |
| WO9209703 | Jun 1992 | WO |
| WO9219774 | Nov 1992 | WO |
| WO9303186 | Feb 1993 | WO |
| WO9305182 | Mar 1993 | WO |
| WO9308297 | Apr 1993 | WO |
| WO9416101 | Jul 1994 | WO |
| WO9419490 | Sep 1994 | WO |
| WO9421822 | Sep 1994 | WO |
| WO9504161 | Feb 1995 | WO |
| WO9511996 | May 1995 | WO |
| WO9513395 | May 1995 | WO |
| WO9513396 | May 1995 | WO |
| WO9531997 | Nov 1995 | WO |
| WO9606187 | Feb 1996 | WO |
| WO9616186 | May 1996 | WO |
| WO9629431 | Sep 1996 | WO |
| WO9632504 | Oct 1996 | WO |
| WO9635450 | Nov 1996 | WO |
| WO9637630 | Nov 1996 | WO |
| WO9733000 | Sep 1997 | WO |
| WO9734909 | Sep 1997 | WO |
| WO9737041 | Oct 1997 | WO |
| WO9747766 | Dec 1997 | WO |
| WO9803684 | Jan 1998 | WO |
| WO9812355 | Mar 1998 | WO |
| WO9814616 | Apr 1998 | WO |
| WO9815652 | Apr 1998 | WO |
| WO9820020 | May 1998 | WO |
| WO9820157 | May 1998 | WO |
| WO9820166 | May 1998 | WO |
| WO9826095 | Jun 1998 | WO |
| WO9831830 | Jul 1998 | WO |
| WO9835057 | Aug 1998 | WO |
| WO9840520 | Sep 1998 | WO |
| WO9854571 | Dec 1998 | WO |
| WO9854751 | Dec 1998 | WO |
| WO9905319 | Feb 1999 | WO |
| WO9912040 | Mar 1999 | WO |
| WO9913104 | Mar 1999 | WO |
| WO9914375 | Mar 1999 | WO |
| WO9929898 | Jun 1999 | WO |
| WO9931278 | Jun 1999 | WO |
| WO9957318 | Nov 1999 | WO |
| WO9958713 | Nov 1999 | WO |
| WO9960183 | Nov 1999 | WO |
| WO0032750 | Jun 2000 | WO |
| WO0038636 | Jul 2000 | WO |
| WO0063362 | Oct 2000 | WO |
| WO0066762 | Nov 2000 | WO |
| WO0066789 | Nov 2000 | WO |
| WO0077260 | Dec 2000 | WO |
| WO0100828 | Jan 2001 | WO |
| WO0107648 | Feb 2001 | WO |
| WO0112853 | Feb 2001 | WO |
| WO0120018 | Mar 2001 | WO |
| WO0123604 | Apr 2001 | WO |
| WO0123608 | Apr 2001 | WO |
| WO0127857 | Apr 2001 | WO |
| WO0132930 | May 2001 | WO |
| WO0140497 | Jun 2001 | WO |
| WO0146404 | Jun 2001 | WO |
| WO0151661 | Jul 2001 | WO |
| WO0151662 | Jul 2001 | WO |
| WO0157263 | Aug 2001 | WO |
| WO0157518 | Aug 2001 | WO |
| WO0173119 | Oct 2001 | WO |
| WO0173199 | Oct 2001 | WO |
| WO0177392 | Oct 2001 | WO |
| WO0196388 | Dec 2001 | WO |
| WO0202811 | Jan 2002 | WO |
| WO0210186 | Feb 2002 | WO |
| WO0210444 | Feb 2002 | WO |
| WO0218641 | Mar 2002 | WO |
| WO0221108 | Mar 2002 | WO |
| WO0222873 | Mar 2002 | WO |
| WO0224876 | Mar 2002 | WO |
| WO0250307 | Jun 2002 | WO |
| WO02057491 | Jul 2002 | WO |
| WO02070664 | Sep 2002 | WO |
| WO02070728 | Sep 2002 | WO |
| WO02070737 | Sep 2002 | WO |
| WO02077278 | Oct 2002 | WO |
| WO02099034 | Dec 2002 | WO |
| WO02099095 | Dec 2002 | WO |
| WO02099129 | Dec 2002 | WO |
| WO02099130 | Dec 2002 | WO |
| WO03001976 | Jan 2003 | WO |
| WO03002750 | Jan 2003 | WO |
| WO03008636 | Jan 2003 | WO |
| WO03012058 | Feb 2003 | WO |
| WO03012074 | Feb 2003 | WO |
| WO03014382 | Feb 2003 | WO |
| WO03016546 | Feb 2003 | WO |
| WO03018636 | Mar 2003 | WO |
| WO03020890 | Mar 2003 | WO |
| WO03033732 | Apr 2003 | WO |
| WO03054162 | Jul 2003 | WO |
| WO03054755 | Jul 2003 | WO |
| WO03060163 | Jul 2003 | WO |
| WO03075955 | Sep 2003 | WO |
| WO03088979 | Oct 2003 | WO |
| WO03093506 | Nov 2003 | WO |
| WO03097869 | Nov 2003 | WO |
| WO03100035 | Dec 2003 | WO |
| WO03100068 | Dec 2003 | WO |
| WO03102191 | Dec 2003 | WO |
| WO03104410 | Dec 2003 | WO |
| WO03106635 | Dec 2003 | WO |
| WO2004003511 | Jan 2004 | WO |
| WO2004009849 | Jan 2004 | WO |
| WO2004011651 | Feb 2004 | WO |
| WO2004013357 | Feb 2004 | WO |
| WO2004040013 | May 2004 | WO |
| WO2004044123 | May 2004 | WO |
| WO2004044247 | May 2004 | WO |
| WO2004052175 | Jun 2004 | WO |
| WO2004053076 | Jun 2004 | WO |
| WO2004053141 | Jun 2004 | WO |
| WO2004053164 | Jun 2004 | WO |
| WO2004060278 | Jul 2004 | WO |
| WO2004070001 | Aug 2004 | WO |
| WO2004072230 | Aug 2004 | WO |
| WO2004072231 | Aug 2004 | WO |
| WO2004101809 | Nov 2004 | WO |
| WO2005003384 | Jan 2005 | WO |
| WO2005009202 | Feb 2005 | WO |
| WO2005012572 | Feb 2005 | WO |
| WO2005024046 | Mar 2005 | WO |
| WO2005036369 | Apr 2005 | WO |
| WO2005054454 | Jun 2005 | WO |
| WO2005075686 | Aug 2005 | WO |
| WO2005086634 | Sep 2005 | WO |
| WO2005091971 | Oct 2005 | WO |
| WO2005098047 | Oct 2005 | WO |
| WO2005116263 | Dec 2005 | WO |
| WO2006089762 | Aug 2006 | WO |
| WO2006094238 | Sep 2006 | WO |
| WO2006135400 | Dec 2006 | WO |
| WO2007014045 | Feb 2007 | WO |
| WO2007086904 | Aug 2007 | WO |
| WO2008104002 | Aug 2008 | WO |
| WO2008118809 | Oct 2008 | WO |
| Entry |
|---|
| Klijn et al. Identification of mesophilic lactic acid bacteria by using polymerase chain reaction-amplified variable regions of 16S rRNA and specific DNA probes. Applied and Environmental Microbiology 57(11):3390-3393, Nov. 1991. |
| Examiner Interview Summary mailed Jun. 7, 2011 for U.S. Appl. No. 11/930,108, filed Oct. 31, 2007. |
| Final Office Action mailed Jun. 14, 2011 for U.S. Appl. No. 12/616,422, filed Nov. 11, 2009. |
| International Preliminary Report on Patentability and Written Opinion for Application No. PCT/US04/007236, mailed on Mar. 16, 2006, 7 pages. |
| International Preliminary Report on Patentability for Application No. PCT/US2005/018031, mailed on Nov. 29, 2006, 1 page. |
| Notice of Allowance mailed Jun. 9, 2011 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Notice of Allowance mailed Jun. 9, 2011 for U.S. Appl. No. 11/491,376, filed Jul. 21, 2006. |
| Notice of Allowance mailed May 25, 2011 for U.S. Appl. No. 11/929,707, filed Oct. 30, 2007. |
| Fujioka, S. et al., “Analysis of enterovirus genotypes using single-strand conformation polymorphisms of polymerase chain reaction products,” J. Virol. Meth. (1995) 51:253-258. |
| Haugland, R. A. et al., “Identification of putative sequence specific PCR primers for detection of the toxigenic fungal species Stachybotrys chartarum,” Mol. Cell. Probes (1998) 12:387-396. |
| Jensen, M. A. et al., “Rapid Identification of Bacteria on the Basis of Polymerase Chain Reaction-Amplified Ribosomal DNA Spacer Polymorphisms,” Appl. Environ. Microbiol. (1993) 59(4):945-952. |
| Jurinke, C. et al., “Detection of hepatitis B virus DNA in serum samples via nested PCR and MALDI-TOF mass spectrometry,” Genetic Analysis: Biomolecular Engineering (1996) 13:67-71. |
| Kilpatrick, D. R. et al., “Group-Specific Identification of Polioviruses by PCR Using Primers Containing Mixed-Base or Deoxyinosine Residues at Positions of Codon Degeneracy,” J. Clin. Microbiol. (1996) 34(12):2990-2996. |
| Van Der Vossen, J. M. B. M. et al., “DNA based typing, identification and detection systems for food spoilage microorganisms: development and implementation.” Int. J. Food Microbiol. (1996) 33(1):35-49. |
| BLAST Search results (Mar. 2006). |
| Co-pending U.S. Appl. No. 13/174,254, filed Jun. 30, 2011. |
| Co-pending U.S. Appl. No. 13/243,960, filed Sep. 23, 2011. |
| Ecker Supporting Information [online], May 23, 2005 [retrieved on Jul. 31, 2011]. Retrieved from the Internet:< URL: http://www.pnas.org/content/102/22/8012/suppl/DC1>. |
| Final Office Action mailed Oct. 19, 2011 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Final Office Action mailed Jul. 28, 2011 for U.S. Appl. No. 11/930,108, filed Oct. 31, 2007. |
| Genbank, “Mouse Hepatitis Virus Strain MHV-A59 C12 Mutant, Complete Genome,” Accession No. AF029248, Jul. 25, 2000. |
| Krenke B.E., et al., “Validation of a 16-Locus Fluorescent Multiplex System,” Journal of Forensic Sciences, 2002, vol. 47 (4), pp. 773-785. |
| Non-Final Office Action mailed Oct. 11, 2011 for U.S. Appl. No. 12/605,628, filed Oct. 26, 2009. |
| Non-Final Office Action mailed Oct. 13, 2011 for U.S. Appl. No. 11/929,930, filed Oct. 30, 2007. |
| Notice of Allowance and Examiner Interview Summary mailed Jul. 21, 2011 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Notice of Allowance mailed Aug. 9, 2011 for U.S. Appl. No. 11/930,002, filed Oct. 30, 2007. |
| Office Action mailed Aug. 3, 2011 for European Application No. 08730682.5 filed Feb. 25, 2008. |
| Office Action mailed Jul. 5, 2011 for Mexican Application No. PAa2003007927 filed Sep. 2, 2003. |
| Office Action mailed Oct. 20, 2011 for European Application No. 02709785.6 filed Mar. 4, 2002. |
| Office Action mailed Sep. 30, 2011 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Aaserud D.J., et al., “Accurate Base Composition of Double-Strand DNA by Mass Spectrometry,” American Society for Mass Spectrometry, 1996, vol. 7 (12), pp. 1266-1269. |
| Aaserud D.J., et al., “DNA Sequencing with Blackbody Infrared Radioactive Dissociation of Electrosprayed Ions,” International Journal of Mass Spectrometry and Icon Processes, 1997, vol. 167-168, pp. 705-712. |
| Adam E., et al., “Characterization of Intertype Specific Epitopes on Adenovirus Hexons,” Archives of Virology, 1998, vol. 143 (9), pp. 1669-1682. |
| Adam E., et al., “Intertype Specific Epitope Structure of Adenovirus Hexon,” Acta Microbiologica et Immunologica Hungarica, 1998, vol. 45 (3-4), pp. 311-316. |
| Adam E., et al., “Molecular Structure of the Two-Dimensional Hexon Crystalline Array and of Adenovirus Capsid,” Acta Microbiologica et Immunologica Hungarica, 1998, vol. 45 (3-4), pp. 305-310. |
| Adrian T., et al., “DNA Restriction Analysis of Adenovirus Prototypes 1 to 41,” Archives of Virology, 1986, vol. 91 (3-4), pp. 277-290. |
| Adzhar A., et al., “Universal Oligonucleotides for the Detection of Infectious Bronchitis Virus by Thepolymerase Chain Reaction,” Avian Pathology : Journal of the W.V.P.A, 1996, vol. 25 (4), pp. 817-836. |
| Agostini H.T., et al., “Complete Genome of a JC Virus Genotype Type 6 from the Brain of an African American with Progressive Multifocal Leukoencephalopathy,” Journal of Human Virology, 1998, vol. 1 (4), pp. 267-272. |
| Aires De Sousa M., et al., “Bridges from Hospitals to the Laboratory: Genetic Portraits of Methicillin-Resistant Staphylococcus aureus Clones,” FEMS Immunology and Medical Microbiology, 2004, vol. 40 (2), pp. 101-111. |
| Akalu A., et al., “Rapid Identification of Subgenera of Human Adenovirus by Serological and PCR Assays,” Journal of Virological Methods, 1998, vol. 71 (2), pp. 187-196. |
| Alba M.M., et al., “VIDA: A Virus Database System for the Organization of Animal Virus Genome Open Reading Frames,” Nucleic Acids Research, 2001, vol. 29 (1), pp. 133-136. |
| Allaouchiche B., et al., “Clinical Impact of Rapid Oxacillin Susceptibility Testing Using a PCR Assay in Staphylococcus aureus Bactaeremia,” The Journal of Infection, 1999, vol. 39 (3), pp. 198-204. |
| Allawi H.T., et al., “Thermodynamics and NMR of Internal G.T. Mismatches in DNA,” Biochemistry, 1997, vol. 36 (34), pp. 10581-10594. |
| Altschuel S.F., et al., “Basic Local Alignment Search Tool,” Journal of Molecular Biology, 1990, vol. 215 (3), pp. 403-410. |
| Altschuel S.F., et al., “Gapped BLAST and PSI-BLAST: A New Generation of Protein Database Search Programs,” Nucleic Acids Research, 1997, vol. 25 (17), pp. 3389-3402. |
| Alves-Silva J., et al., “The Ancestry of Brazilian mtDNA Linages,” The American Journal of Human Genetics, 2000, vol. 67 (2), pp. 444-461. |
| Amano Y., et al., “Detection of Influenza Virus: Traditional Approaches and Development of Biosensors,” Analytical and Bioanalytical Chemistry, 2005, vol. 381 (1), pp. 156-164. |
| Amexis G., et al., “Quantitative Mutant Analysis of Viral Quasispecies by Chip-Based Matrix Assisted LaserDesorption Ionization Time-of-Flight Mass Spectrometry,” Proceedings of the National Academy of Sciences, 2001, vol. 98 (21), pp. 12097-12102. |
| Anderson M.L.M., “Quantitative Filter Hybridization” in: Nucleic Acid Hybridization, Hames B.D. ed., IRL Press, 1985, pp. 73-111. |
| Anderson S., et al., “Sequence and Organization of the Human Mitochondrial Genome,” Nature, 1981, vol. 290 (5806), pp. 457-465. |
| Andreasson H., et al., “Mitochondrial Sequence Analysis for Forensic Identification Using Pyrosequencing Technology,” BioTechniques, 2002, vol. 32 (1), pp. 124-133. |
| Anthony R.M., et al., “Use of the Polymerase Chain Reaction for Rapid Detection of High-Level Mupirocin Resistance in Staphylococci,” European Journal of Clinical Microbiology & Infectious Diseases, 1999, vol. 18 (1), pp. 30-34. |
| Arbique J., et al., “Comparison of the Velogene Rapid MRSA Identification Assay, Denka MRSAScreen Assay, and BBL Crystal MRSA ID System for Rapid Identification of Methicillin-Resistant Staphylococcus aureus,” Diagnositic Microbiology and Infectious Diseases, 2001, vol. 40 (1-2), pp. 5-10. |
| Archer G.L., et al., “Detection of Methicillin Resistance in Staphylococci by Using a DNA Probe,” Antimicrobial Agents and Chemotherapy, 1990, vol. 34 (9), pp. 1720-1724. |
| Armstrong P., et al., “Sensitive and Specific Colorimetric Dot Assay to Detect Eastern Equine Encephalomyelitis Viral RNA in Mosquitoes After PCR Amplification,” Journal of Medicinal Entomology, 1995, vol. 32 (1), pp. 42-52. |
| Arnal C., et al., “Quantification of Hepatitis A virus in shellfish by competitive reverse transcription PCRwith coextraction of standard RNA,” Applied and Environmental Microbiology, 1999, vol. 65 (1), pp. 322-326. |
| Aronsson F., et al., “Persistence of the influenza A/WSN/33 virus RNA at midbrain levels of immunodefective mice,” Journal of Neurovirology, 2001, vol. 7 (2), pp. 117-124. |
| Ausubel F.M., et al., eds., Current Protocols in Molecular Biology, vol. 1, John Wiley & Sons Inc., 2004, Table of Contents. |
| Ausubel F.M., et al., eds., Short Protocols in Molecular Biology: A Compendium of Methods from Current Protocols in Molecular Biology, 2nd Edition, John Wiley & Sons, 1992, Units 2.9, 3.4-3.17, 4.6-4.10, and 10.8. |
| Ausubel F.M., et al., “Unit 2.11 “Synthesis and Purification of Oligonucleotides,” in: Current Protocols in Molecular Biology,” 1998, John Wiley & Sons, Inc., pp. 2.11-2.11.21. |
| Avellon A., et al., “Rapid and Sensitive Diagnosis of Human Adenovirus Infections by a Generic Polymerase Chain Reaction,” Journal of Virological Methods, 2001, vol. 92 (2), pp. 113-120. |
| Azevedo A.M., et al., “Detection of Influenza, Parainfluenza, Adenovirus and Respiratory Syncytial Virus during Asthma Attacks in Children Older than 2 Years Old,” Allergologia Immunopathologia, 2003, vol. 31 (6), pp. 311-317. |
| Baba T., et al., “Genome and Virulence Determinants of High Virulence Community-Acquired MRSA,” Lancet, 2002, vol. 359 (9320), pp. 1819-1827. |
| Bahrmahd A.R., et al., “Polymerise Chain Reaction of Bacterial Genomes with Single Universal Primer: Application to Distinguishing Mycobacteria Species,” Molecular and Cellular Probes, 1996, vol. 10 (2), pp. 117-122. |
| Bahrmahd A.R., et al., “Use of Restriction Enzyme Analysis of Amplified DNA Coding for the hsp65 Gene and Polymerase Chain Reaction with Universal Primer for Rapid Differtiation of Mycobacterium Species in the Clinical Laboratory,” Scandinavian Journal of Infectious Diseases, 1998, vol. 30 (5), pp. 477-480. |
| Bai J., et al., “Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Restriction Enzyme-Digested Plasmid DNA Using an Active Nafion Substrate,” Rapid Communications in Mass Spectrometry, 1994, vol. 8 (9), pp. 687-691. |
| Baker G.C., et al., “Review and Re-Analysis of Domain-Specific 16S Primers,” Journal of Microbiological Methods, 2003, vol. 55 (3), pp. 541-555. |
| Banik U., et al., “Multiplex PCR Assay for Rapid Identification of Oculopathogenic Adenoviruses by Amplification of the Fiber and Hexon Genes,” Journal of Clincal Microbiology, 2005, vol. 43 (3), pp. 1064-1068. |
| Barbour A.G., et al., “Identification of an Uncultivatable Borrelia Species in the hard tick Amblyomma americanum: Possible Agent of a Lyme disease-like illness,” The Journal of Infectious Diseases, 1996, vol. 173 (2), pp. 403-409. |
| Barns S.M., et al., “Detection of Diverse New Francisella-like Bacteria in Environmental Samples,” Applied and Environmental Microbiology, 2005, vol. 71 (9), pp. 5494-5500. |
| Baron E.J., “Genetic Aspects of Methicillin Resistance in Staphylococcus aureus and MethodsUsed for its Detection in Clinical Laboratories in the United States,” Journal of Chemotherapy, 1995, vol. 7 (Supl.3), pp. 87-92. |
| Barr I.G., et al., “An Influenza A(H3) Reassortant Was Epidemic in Australia and New Zealand in 2003,” Journal of Medical Virology, 2005, vol. 76 (3), pp. 391-397. |
| Barski P., et al., “Rapid Assay for Detection of Methicillin-Resistant Staphylococcus aureus Using Multiplex PCR,” Molecular and Cellular Probes, 1996, vol. 10 (6), pp. 471-475. |
| Bastia T., et al., “Organelle DNA Analysis of Solanum and Brassica Somatic Hybrids by PCR with Universal Primers,” Theoretical and Applied Genetics, 2001, vol. 102 (8), pp. 1265-1272. |
| Batey R.T., et al., “Preparation of Isotopically Labeled Ribonucleotides for Multidimensional NMR Spectroscopy of RNA,” Nucleic Acids Research, 1992, vol. 20 (17), pp. 4515-4523. |
| Baumer A., et al., “Age-Related Human mtDNA Deletions: A Heterogeneous Set of Deletions Arising at aSingle Pair of Directly Repeated Sequences,” American Journal of Human Jenetics, 1994, vol. 54 (4), pp. 618-630. |
| Beall B., et al., “Sequencing emm-Specific PCR Products for Routine andAccurate Typing of Group A Streptococci,” Journal of Clincal Microbiology, 1996, vol. 34 (4), pp. 953-958. |
| Beall B., et al., “Survey of emm Gene Sequences and T-Antigen Types fromSystemic Streptococcus pyogenes Infection Isolates Collected in San Francisco, California; Atlanta, Georgia; and Connecticut in 1994 and 1995,” Journal of Clincal Microbiology, 1997, vol. 35 (5), pp. 1231-1235. |
| Benko, M. et al., “Family Adenoviridae, Virus taxonomy. VIIIth report of the International Committee on Taxonomy of Viruses,” 2004, Academic Press, New York, pp. 213-228. |
| Benson D.A., et al., “GenBank,” Nucleic Acids Research, 1999, vol. 27 (1), pp. 12-17. |
| Benson L.M., et al, “Advantages of Thermococcus kodakaraenis (KOD) DNA polymerase for PCR-mass spectrometry based analyses,” American Society for Mass Spectrometry, 2003, vol. 14 (6), pp. 601-604. |
| Berencsi G., et al., “Molecular Biological Characterization of Adenovirus DNA,” Acta Microbiologica et Immunologica Hungarica, 1998, vol. 45 (3-4), pp. 297-304. |
| Bishop M.J., et al., “Molecular Sequence Databases” in: Nucleic Acid and Protein Sequence Analysis, 4th Chapter, Bishop M.J., et al., eds, IRL Press, 1987, pp. 83-113. |
| Bisno A.L., “Streptococcus pyogenes in Infectious Diseases and Their Etiologic Agents Principles and Practice of Infectious Diseases,” 1995, vol. 2, pp. 1786-1799. |
| Black R.M., et al., “Detection of Trace Levels of Tricothecene Mycotoxins in Human Urineby Gas Chromatography-Mass Spectrometry,” Journal of Chromatography, 1986, vol. 367 (1), pp. 103-115. |
| Blaiotta G., et al., “PCR Detection of Staphylococcal Enterotoxin Genes in Staphyiococcus Spp. Strains Isolated from Meat and Dairy Products. Evidence for New Variants of seG and Sel in S. aureus AB-8802,” Journal of Applied Microbiology, 2004, vol. 97 (4), pp. 719-730. |
| Boivin-Jahns V., et al., “Bacterial Diversity in a Deep-Subsurface Clay Environment,” Applied and Environmental Microbiology, 1996, vol. 62 (9), pp. 3405-3412. |
| Bolton E.T., et al., “A general method for the isolation of RNA complementary to DNA,” Proceedings of the National Academy of Sciences of the USA, 1962, vol. 48, pp. 1390-1397. |
| Bonk T., et al., “Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry-Based Detection of Microsatellite Instabilities in Coding DNA Sequences: A Novel Approach to Identify DNA-Mismatch Repair-Deficient Cancer Cells,” Clinical Chemistry, 2003, vol. 49 (4), pp. 552-561. |
| Borrow R., et al., “SiaD PCR Elisa for Confirmation and Identification of Serogroup Y and W135 Meningococcal Infections,” FEMS Microbiology Letters, 1998, vol. 159 (2), pp. 209-214. |
| Boubaker K., et al., “Panton-Valentine Leukocidin and Staphyloccoccal Skin Infections in Schoolchildren,” Emerging Infectious Diseases, 2004, vol. 10 (1), pp. 121-124. |
| Bowen J.E., et al., “The Native Virulence Plasmid Combination Affects the Segregational Stability of a Thetareplicating Shuttle Vector in Bacillus anthracis Var,” Journal of Applied Microbiology, 1999, vol. 87 (2), pp. 270-278. |
| Bowers K.M., et al., “Screening for Methicillin Resistance in Staphylococars aureus and Coagulasenegative Staphylococci: Evaluation of Three Selective and Mastalex-MRSA latex Agglutination,” British Journal of Biomedical Science, 2003, vol. 60 (2), pp. 71-74. |
| Brakstad O.G., et al., “Direct Identification of Staphylococcus aureus in Blood Cultures Bydetection of the Gene, Encoding the Thermostable Nuclease or the Gene Product,” Acta Pathologica, Microbiologica et Immunologica Scandinavica, 1995, vol. 103 (3), pp. 209-218. |
| Brakstad O.G., et al., “Multiplex Polymerase Chain Reaction for Detection of Genes for Staphylococcus aureus Themonuclease and Methicillin Resistance and Correlation with Oxacillin Resistance,” Acta Pathologica, Microbiologica et Immunologica Scandinavica, 1993, vol. 101 (9), pp. 681-688. |
| Brandt C.D., et al., “Infections in 18,000 Infants and Children in a Controlled Study of Respiratory Tract Disease. I. Adenovirus Pathogenicity in Relation to Serologic Type and Illness Syndrome,” American Journal of Epidemiology, 1969, vol. 90 (6), pp. 484-500. |
| Brayshaw D.P., “Methicillin-Resistant Staphylococcus aureus: Evaluation of Detection Techniques on Laboratory-Passaged Organisms,” British Journal of Biomedical Science, 1999, vol. 56 (3), pp. 170-176. |
| Brightwell G., et al., “Development of Internal Controls for PCR Detection of Bacillus anthracis,” Molecular and Cellular Probes, 1998, vol. 12 (6), pp. 367-377. |
| Brightwell G., et al., “Genetic Targets for the Detection and Identifiaction of Venezuelan Equine Encephalitis Viruses,” Archives of Virology, 1998, vol. 143 (4), pp. 731-742. |
| Bronzoni R.V.M., et al., “Duplex Reverse Transcription-PCR Followed by Nested PCR Assays for Detection and Identification of Brazilian Alphaviruses and Flaviviruses,” Journal of Clincal Microbiology, 2005, vol. 43 (2), pp. 696-702. |
| Bronzoni R.V.M., et al., “Multiplex Nested PCR for Brazilian Alphavirus Diagnosis,” Transactions of the Royal Society of Tropical Medicine and Hygiene, 2004, vol. 98 (8), pp. 456-461. |
| Brown I.H., “Advances in Molecular Diagnostics for Avian Influenza,” Developments in Biologicals, 2006, vol. 124, pp. 93-97. |
| Brownstein M.J., et al., “Modulation of Non-Templated Nucleotide Addition by Taq DNA Polymerase: Primer Modifications that Facilitate Genotyping,” BioTechniques, 1996, vol. 20 (6), pp. 1004-1010. |
| Brunaud V., et al., “T-DNA Integration into the Arabidopsis Genome Depends on Sequence of Pre-Insertion Sites,” EMBO Reports, 2002, vol. 3 (12), pp. 1152-1157. |
| Buck G.A., et al., “Design Strategies and Performance of Custom DNA Sequencing Primers,” BioTechniques, 1999, vol. 27 (3), pp. 528-536. |
| Buetow K.H., et al., “High-Throughput Development and Characterization of a Genomewide Collection of Gene-Based Single Nucleotide Polymorphism Markers by Chip-Based Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry,” Proceedings of the National Academy of Sciences, 2001, vol. 98 (2), pp. 581-584. |
| Butel J.S., et al., “Cell and Molecular Biology of Simian Virus 40: Implications for Human Infections and Disease,” Journal of the National Cancer Institute, 1999, vol. 91 (2), pp. 119-134. |
| Butler J., “DNA Profiling and Quantitation of Human DNA,” CCQM Bio Analysis Working Group, 2005. |
| Butler J.M., et al., High Throughput Genotyping of Forensic STRs and SNPs using Time-of-Flight Mass Spectrometry, 9th International Symposium on Human Identification, 1998, Orlando FL. |
| Campbell W.P., et al., “Detection of California serogroup Bunyavirus in tissue culture and mosquito pools by PCR,” Journal of Virological Methods, 1996, vol. 57 (2), pp. 175-179. |
| Carracedo A., et al., “DNA Commission of the International Society for Forensic Genetics: Guidelines Formitochondrial DNA Typing,” Forensic Science International, 2000, vol. 110 (2), pp. 79-85. |
| Carroll K.C., et al., “Rapid Detection of the Staphylococcal mecA Gene from BACTEC BloodCulture Bottles by the Polymerase Chain Reaction,” American Journal of Clincal Pathology, 1996, vol. 106 (5), pp. 600-605. |
| Case J.T., et al., “Maternal Inheritance of Mitochondrial DNA Polymorphisms in Cultured Human Fibroblasts,” Somatic Cell Genetics, 1981, vol. 7 (1), pp. 103-108. |
| Cattoli G., et al., “Comparison of Three Rapid Detection Systems for Type A Influenza Virus on Tracheal Swabs of Experimentally and Naturally Infected Birds,” Avian Pathology, 2004, vol. 33 (4), pp. 432-437. |
| Cavassini M., et al., “Evaluation of MRSA-Screen, a Simple Anti-PBP 2a Slide Latex AgglutinationKit, for Rapid Detection of Methicillin Resistance in Staphylococcus aureus,” Journal of Clincal Microbiology, 1999, vol. 37 (5), pp. 1591-1594. |
| Certificate of Correction mailed Jan. 6, 2009 for U.S. Appl. No. 10/660,996, filed Sep. 12, 2003. |
| Certificate of Correction mailed Aug. 7, 2007 for U.S. Appl. No. 10/660,997, filed Sep. 12, 2003. |
| Certificate of Correction mailed Dec. 12, 2006 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Certificate of Correction mailed Jul. 17, 2007 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Certificate of Correction mailed Mar. 31, 2008 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Certificate of Correction mailed Mar. 31, 2008 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Certificate of Correction mailed Mar. 31, 2008 for U.S. Appl. No. 10/660,997, filed Sep. 12, 2003. |
| Cespedes A., et al., “Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Analysis of a Short Fragment of the Cytochrome b Gene for Identification of Flatfish Species,” Journal of Food Protection, 1998, vol. 61 (12), pp. 1684-1685. |
| Chamberlin M., et al., “New RNA Polymerase from Escerichia coli Infected with Bacteriophage T7,” Nature, 1970, vol. 228 (5268), pp. 227-231. |
| Chandra S., et al., “Virus Reduction in the Preparation and Intravenous Globulin: In Vitro Experiments,” Transfusion, 1999, vol. 39 (3), pp. 249-257. |
| Chang P.K., et al., “afIT, a MFS Transporter-Encoding Gene Located in the Aflatoxin Gene Cluster, does not have a Significant Role in Aflatoxin Secretion,” Fungal Genetics and Biology, 2004, vol. 41 (10), pp. 911-920. |
| Chaves F., et al., “Molecular Characterization of Resistance to Mupirocin in Methicillin-Susceptible and -Resistant Isolates of Staphylococcus aureus from Nasal Samples,” Journal of Clincal Microbiology, 2004, vol. 42 (2), pp. 822-824. |
| Chelly J., et al., “Transcription of the Dystrophin Gene in Human Muscle and Non-Muscle Tissue,” Nature, 1988, vol. 333 (6176), pp. 858-860. |
| Chen C.A., et al., “Universal Primers for Amplification of Mitochondrial small Subunit Ribosomal RNA-Encoding Gene in Scleractinian Corals,” Marine Biotechnology, 2000, vol. 2 (2), pp. 146-153. |
| Chen C.H., et al., Laser Desorption Mass Spectrometry for FastDNA Sequencing [online], Nov. 1994, Retrieved from the Internet:< URL:http://www.ornl.gove/sci/techresources/Human—Genome/publicat/94SANTA/sequencing/seqtoc.shtml>. |
| Chen J., et al., “A universal PCR Primer to Detect Members of the Potyviridae and its use to Examine the Taxonomic Status of Several Members of the Family,” Archives of Virology, 2001, vol. 146 (4), pp. 757-766. |
| Chen N., et al., “The Genomic Sequence of Ectromelia Virus, the Causative Agent of Mousepox,” Virology, 2003, vol. 317 (1), pp. 165-186. |
| Chen R., et al., “Trapping, Detection, and Charge and Mass Measurement of Large Individual Ions (up to 1.1X108 Daltons) by Electrospray Ionization FTICR MS,” 42nd ASMS Conference on Mass Spectrometry, 1994. |
| Chen Y.Z., et al., “A BAC-Based STS-Content Map Spanning a 35-Mb Region of Human Chromosome 1p35-36,” Genomics, 2001, vol. 74 (1), pp. 55-70. |
| Chen Z., et al., “Genetic Mapping of the Cold-Adapted Phenotype of B/Ann Arbor/1/66, the Master Donor Virus for Live Attenuated Influenza Vaccines (FluMist),” Virology, 2006, vol. 345 (2), pp. 416-423. |
| Chiu N.H., et al., “Mass Spectrometry of Single-Stranded Restriction Fragments Captured by an Undigested Complementary Sequence,” Nucleic Acids Research, 2000, vol. 28 (8), pp. E31. |
| Chmielewicz B., et al., “Development of a PCR-Based Assay for Detection, Quantification, and Genotyping of Human Adenoviruses,” Clinical Chemistry, 2005, vol. 51 (8), pp. 1365-1373. |
| Cho M., et al., “Application of the Ribonuclease P (RNaseP) RNA Gene Sequence for Phylogenetic Analysis of the Genus Saccharomonospora,” International Journal of Systematic Bacteriology, 1998, vol. 48 (4), pp. 1223-1230. |
| Choi S., et al., “Real-Time PCR Quantification of Human Adenoviruses in Urban Rivers Indicates Genome Prevalence but Low Infectivity,” Applied and Environmental Microbiology, 2005, vol. 71 (11), pp. 7426-7433. |
| Choi Y.K., et al., “Detection and Subtying of Swine Influenza H1N1, H1 N2 and H3N2 Viruses in Clinical Samples Using Two Multiplex RT-PCR Assays,” Journal of Virological Methods, 2002, vol. 102 (1-2), pp. 53-59. |
| Christel L.A., et al., “Rapid, Automated Nucleic Acid Probe Assays Using Silicon Microstructures forNucleic Acid Concentration,” Journal of Biomechanical Engineering, 1999, vol. 121 (1), pp. 22-27. |
| Claas E.C., et al., “Internally Controlled Real-Time PCT Monitoring of Adenovirus DNA Load inSerum or Plasma of Transplant Recipients,” Journal of Clincal Microbiology, 2005, vol. 43 (4), pp. 1738-1744. |
| Cloney L., et al., “Rapid Detection of mecA in Methicillin Resistant Staphylococcus aureus Using Cycling Probe Technology,” Molecular and Cellular Probes, 1999, vol. 13 (13), pp. 191-197. |
| Collins D.W., et al., “Numerical Classification of Coding Sequences,” Nucleic Acids Research, 1992, vol. 20 (6), pp. 1405-1410. |
| Conrads G., et al., “16S-23S rDNA Internal Transcribed Spacer Sequences for Analysis of the Phylogenetic Relationships Among Species of the Genus Fusobacterium,” International Journal of Systematic and Evolutionary Microbiology, 2002, vol. 52 (2), pp. 493-499. |
| Contreras-Salazar B., et al., “Up Regulation of the Epstein-Barr Virus (EBV)-Encoded Membrane Protein LMP in the Burkitt's Lymphoma Line Daudi after Exposure to N-Butyrate and after EBV Superinfection,” Journal of Virology, 1990, vol. 64 (11), pp. 5441-5447. |
| Co-pending U.S. Appl. No. 10/318,463, filed Dec. 13, 2002. |
| Co-pending U.S. Appl. No. 10/323,186, filed Dec. 18, 2002. |
| Co-pending U.S. Appl. No. 10/323,187, filed Dec. 18, 2002. |
| Co-pending U.S. Appl. No. 10/324,721, filed Dec. 18, 2002. |
| Co-pending U.S. Appl. No. 10/521,662, filed Jul. 21, 2003. |
| Co-pending U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Co-pending U.S. Appl. No. 10/807,019, filed Mar. 23, 2004. |
| Co-pending U.S. Appl. No. 10/845,052, filed May 12, 2004. |
| Co-pending U.S. Appl. No. 10/964,571, filed Oct. 12, 2004. |
| Co-pending U.S. Appl. No. 11/209,439, filed Aug. 23, 2005. |
| Co-pending U.S. Appl. No. 11/674,538, filed Feb. 13, 2007. |
| Co-pending U.S. Appl. No. 11/929,910, filed Oct. 30, 2007. |
| Co-pending U.S. Appl. No. 11/930,108, filed Oct. 31, 2007. |
| Co-pending U.S. Appl. No. 11/930,741, filed Oct. 31, 2007. |
| Co-pending U.S. Appl. No. 90/010,209, filed Jun. 27, 2008. |
| Co-pending U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Co-pending U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Co-pending U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Co-pending U.S. Appl. No. 60/639,068, filed Dec. 22, 2004. |
| Co-pending U.S. Appl. No. 60/648,188, filed Jan. 28, 2005. |
| Co-pending U.S. Appl. No. 60/369,405, filed Apr. 1, 2002. |
| Co-pending U.S. Appl. No. 60/397,365, filed Jul. 19, 2002. |
| Co-pending U.S. Appl. No. 60/431,319, filed Dec. 6, 2002. |
| Co-pending U.S. Appl. No. 60/443,443, filed Jan. 29, 2003. |
| Co-pending U.S. Appl. No. 60/443,788, filed Jan. 30, 2003. |
| Co-pending U.S. Appl. No. 60/447,529, filed Feb. 14, 2003. |
| Co-pending U.S. Appl. No. 60/453,607, filed Mar. 10, 2003. |
| Co-pending U.S. Appl. No. 60/461,494, filed Apr. 9, 2003. |
| Co-pending U.S. Appl. No. 60/470,175, filed May 12, 2003. |
| Co-pending U.S. Appl. No. 60/501,926, filed Sep. 11, 2003. |
| Co-pending U.S. Appl. No. 60/509,911, filed Oct. 9, 2003. |
| Co-pending U.S. Appl. No. 60/604,329, filed Aug. 24, 2004. |
| Co-pending U.S. Appl. No. 60/615,387, filed Sep. 30, 2004. |
| Co-pending U.S. Appl. No. 60/701,404, filed Jul. 21, 2005. |
| Co-pending U.S. Appl. No. 60/705,631, filed Aug. 3, 2005. |
| Co-pending U.S. Appl. No. 60/720,843, filed Sep. 27, 2005. |
| Co-pending U.S. Appl. No. 60/747,607, filed Feb. 13, 2006. |
| Co-pending U.S. Appl. No. 60/771,101, filed May 18, 2006. |
| Co-pending U.S. Appl. No. 60/773,124, filed Feb. 6, 2006. |
| Co-pending U.S. Appl. No. 60/891,479, filed Feb. 23, 2007. |
| Co-pending U.S. Appl. No. 60/941,641, filed Jun. 1, 2007. |
| Cornel A.J., et al., “Polymerase Chain Reaction Species Diagnostic Assay for Anopheles quadrimaculatus Cryptic Species (Diptera:Culicidae) Based on Ribosomal DNA ITS2 Sequences,” Journal of Medical Entomology, 1996, vol. 33 (1), pp. 109-116. |
| Couto I., et al., “Development of Methicillin Resistance in Clinical Isolates of Staphylococcus sciuri by Transcriptional Activation of the mecA Homologue Native to the Species,” Journal of Bacteriology, 2003, vol. 185 (2), pp. 645-653. |
| Crain P.F., et al., “Applications of Mass Spectrometry to the Characterization of Oligonucleotides and Nucleic Acids,” Current Opinion in Biotechnology, 1998, vol. 9 (1), pp. 25-34. |
| Crawford-Miksza L., et al., “Analysis of 15 Adenovirus Hexon Proteins Reveals the Location and Structure of Seven Hypervariable Regions Containing Serotype-Specific Residues,” Journal of Virology, 1996, vol. 70 (3), pp. 1836-1844. |
| Crawford-Miksza L.K., et al., “Adenovirus Serotype Evolution is Driven by Illegitimate Recombination in the Hypervariable Regions of the Hexon Protein,” Virology, 1996, vol. 224 (2), pp. 357-367. |
| Crawford-Miksza L.K., et al., “Strain Variation in Adenovirus Serotypes 4 and 7a Causing Acute Respiratory Disease,” Journal of Clincal Microbiology, 1999, vol. 37 (4), pp. 1107-1112. |
| Crespillo M., et al., “Mitochondrial DNA Sequences for 118 Individuals from Northeastern Spain,” International Journal of Legal Medicine, 2000, vol. 114 (1-2), pp. 130-132. |
| Cui L., et al., “Contribution of a Thickened Cell Wall and Its Glutamine Nonamidated Component to the Vancomycin Resistance Expressed by Staphylococcus aureus Mu50,” Antimicrobial Agents and Chemotherapy, 2000, vol. 44 (9), pp. 2276-2285. |
| Dasen G., et al., “Classification and Identification of Propiolbacteria based on Ribosomal RNA Genes and PCR,” Systematic and Applied Microbiology, 1998, vol. 21 (2), pp. 251-259. |
| De Jong J.C., et al., “Adenoviruses from Human Immunodeficiency Virus-Infected Individuals,Including Two Strains That Represent New Candidate Serotypes Ad50 and Ad51 of Species B1 and D, Respectively,” Journal of Clincal Microbiology, 1999, vol. 37 (12), pp. 3940-3945. |
| De La Puente-Redondo V.A., et al., “Comparison of Different PCR Approaches for Typing of Francisella tularensis Strains,” Journal of Clinical Microbiology, 2000, vol. 38 (3), pp. 1016-1022. |
| Deforce D.L.D., et al., “Characterization of DNA Oligonudeotides by Coupling of Capillary zone Electrophoresis to Electrospray Ionization Q-TOF Mass Spectrometry,” Analytical Chemistry, 1998, vol. 70 (14), pp. 3060-3068. |
| Deforce D.L.et al., “Analysis of Oligonucleotides by ESI-MS,” Advances in Chromatography (New York), 2000, vol. 40, pp. 539-566. |
| Del Blanco Garcia N., et al., “Genotyping of Francisella tularensis Strains by Pulsed-field gel Electrophoresis, Amplified Fragment Length Polymorphism Fingerprinting, and 16S rRNA gene Sequencing,” Journal of Clinical Microbiology, 2002, vol. 40 (8), pp. 2964-2972. |
| Del Vecchio V.G., et al., “Molecular Genotyping of Methicillin-Resistant Staphylococcus aureus via Fluorophore-Enhanced Repetitive-Sequence PCR,” Journal of Clincal Microbiology, 1995, vol. 33 (8), pp. 2141-2144. |
| Demesure B., et al., “A set of Universal Primers for Amplification of Polymorphic Non-coding Regions of Mitochondrial and Chioroplast DNA in plants,” Molecular Ecology, 1995, vol. 4, pp. 129-131. |
| Denis M., et al., “Development of a Semiquantitative PCR Assay Using Internal Standard and Colorimetricdetection on Microwell Plate for Pseudorabies Virus,” Molecular and Cellular Probes, 1997, vol. 11 (6), pp. 439-448. |
| Deurenberg R.H., et al., “Rapid Detection of Panton-Valentine Leukocidin from Clinical Isolates of Staphylococcus aureus Strains by Real-Time PCR,” FEMS Microbiology Letters, 2004, vol. 240 (2), pp. 225-228. |
| Deurenberg R.H., et al., “The Prevalence of the Staphylococcus aureus tst Gene among Community- and Hospital-Acquired Strains and Isolates from Wegener's Granulomatosis Patients,” FEMS Microbiology Letters, 2005, vol. 245 (1), pp. 185-189. |
| Deyde V.M., et al., “Genomic Signature-Based Identification of Influenza A Viruses Using RT-PCR/Electro-Spray Ionization Mass Spectrometry (ESI-MS) Technology,” PLoS One, 2010, vol. 5 (10), pp. e13293. |
| Di Guilmi A.M., et al., “Human Adenovirus Serotype 3 (Ad3) and the Ad3 fiber Protein Bind to a 130-kDa Membrane Protein on HLa Cells,” Virus Research, 1995, vol. 38 (1), pp. 71-81. |
| Dias Neto E., et al., “Shotgun Sequencing of the Human Transcriptome with ORF Expressed Sequence Tags,” Proceedings of the National Academy of Sciences, 2000, vol. 97 (7), pp. 3491-3496. |
| Diep B.A., et al., “Complete Genome Sequence of USA300, an Epidemic Clone of Community Acquired Meticillin-Resistant Staphylococcus aureus,” Lancet, 2006, vol. 367 (9512), pp. 731-739. |
| Dinauer D.M., et al., “Sequence-based typing of HLA class II DQB1,” Tissue Antigens, 2000, vol. 55 (4), pp. 364-368. |
| Ding C., et al., “A High-Throughput Gene Expression Analysis Technique using Compettiive PCR and Matrixassisted Laser Desorption Ionization time-of-Flight MS,” Proceedings of the National Academy of Sciences, 2003, vol. 100 (6), pp. 3059-3064. |
| Donehower L.A., et al., “The Use of Primers from Highly Conserved Pol Regions to Identify Uncharacterized Retroviruses by the Polymerase Chain Reaction,” Journal of Virological Methods, 1990, vol. 28 (1), pp. 33-46. |
| Donofrio J.C., et al., “Detection of Influenza A and B in Respiratory Secretions with the Polymerase Chain Reaction,” PCR Methods and Applications, 1992, vol. 1 (4), pp. 263-268. |
| Doty P., et al., “Strand Separation and Specific Recombination in Deoxyribonucleic Acids: Physical Chemical Studies,” Proceedings of the National Academy of Sciences of USA, 1960, vol. 46 (4), pp. 461-476. |
| Drosten C., et al., “Identification ofa Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome,” New England Journal of Medicine, 2003, vol. 348 (20), pp. 1967-1976. |
| Dubernet S., et al., “A PCR-based Method for Identification of Lactobacilli at to Genus Level,” FEMS Microbiology Letters, 2002, vol. 214 (2), pp. 271-275. |
| Ebner K., et al., “Molecular Detection and Quantitative Analysis of the Entire Spectrum of Human Adenoviruses by a Two-Reaction Real-Time PCR Assay,” Journal of Clinical Microbiology, 2005, vol. 43 (7), pp. 3049-3053. |
| Ebner K., et al., “Typing of Human Adenoviruses in Specimens from Immunosuppressed Patients by PCR-Fragment Length Analysis and Real-Time Quantitative PCR,” Journal of Clinical Microbiology, 2006, vol. 44 (8), pp. 2808-2815. |
| Echavarria M., et al., “Detection of Adenoviruses (AdV) in Culture-Negative EnvironmentalSamples by PCR During an AdV-Associated Respiratory Disease Outbreak,” Journal of Clinical Microbiology, 2000, vol. 38 (8), pp. 2982-2984. |
| Echavarria M., et al., “PCR Method for Detection of Adenovirus in Urine of Healthy and Human Immunodeficiency Virus-Infected Individuals,” Journal of Clinical Microbiology, 1998, vol. 36 (11), pp. 3323-3326. |
| Echavarria M., et al., “Prediction of Severe Disseminated Adenovirus Infection by Serum PCR,” Lancet, 2001, vol. 358 (9279), pp. 384-385. |
| Echavarria M., et al., “Rapid Detection of Adenovirus in Throat Swab Specimens by PCR DuringRespiratory Disease Outbreaks among Military Recruits,” Journal of Clinical Microbiology, 2003, vol. 41 (2), pp. 810-812. |
| Echavarria M., et al., “Use of PCR to Demonstrate Presence of Adenovirus Species B, C, or F as Well as Coinfection with Two Adenovirus Species in Children with Flu-Like Symptoms,” Journal of Clinical Microbiology, 2006, vol. 44 (2), pp. 625-627. |
| Ecker D. J., et al., “Rapid Identification and Strain-Typing of Respiratory Pathogens for Epidemic Surveillance,” Proceedings of the National Academy of Sciences, 2005, vol. 102 (22), pp. 8012-8017. |
| Ecker D. J., et al., “The Ibis T5000 Universal Biosensor. An Automated Platform for Pathogen Identification and Strain Typing,” Journal of the Association for Laboratory Automation, 2006, vol. 11 (6), pp. 341-351. |
| Ecker D.J., et al., “Ibis T5000: a universal biosensor approach for microbiology,” Nature Reviews Microbiology, 2008, vol. 6 (7), pp. 553-558. |
| Edwards K.M., et al., “Adenovirus Infections in Young Children,” Pediatrics, 1985, vol. 76 (3), pp. 420-424. |
| Ellis J. S., et al., “Molecular Diagnosis of Influenza,” Reviews in Medical Virology, 2002, vol. 12 (6), pp. 375-389. |
| Ellis J.S., et al., “Multiplex Reverse Transcription-PCR for Surveillance of Influenza A and B Viruses in England and Wales in 1995 and 1996,” Journal of Clinical Microbiology, 1997, vol. 35(8), pp. 2076-2082. |
| Elnifro E.M., et al., “PCR and Restriction Endonuclease Analysis for Rapid Identification of Adenovirus Subgenera,” Journal of Clinical Microbiology, 2000, vol. 38 (6), pp. 2055-2061. |
| Elsayed S., et al., “Development and Validation of a Molecular Beacon Probe-Based Real-Time Polymerase Chain Reaction Assay for Rapid Detection of Methicillin Resistance in Staphylococcus aureus,” Archives of pathology and laboratory medicine, 2003, vol. 127 (7), pp. 845-849. |
| EMBL “Arabidopsis thaliana T-DNA flanking sequence, left border, clone 346C06,” Accession No. AJ552897, Mar. 29, 2003. |
| EMBL “Dog (Clone: CXX.147) primer for STS 147, 3′ end, sequence tagged site,” Accession No. L15697, Mar. 4, 2000. |
| EMBL “Human, muscle, Mitochondrial Mutant, 22 nt, segment 2 of 2,” Accession No. S90302, Sep. 1, 2004. |
| EMBL, “Sequence 10 from patent US 6563025,” Accession No. AR321656, Aug. 18, 2003. |
| EMBL “Synthetic Construct DNA, Reverse Primer for Human STS sts-AA031654 at 1p36” Accession No. AB068711, May 21, 2003. |
| Enright M.C., et al., “A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease,” Microbiology, 1998, vol. 144 (Pt 11), pp. 3049-3060. |
| Enright M.C., et al., “Multilocus Sequence Typing for Characterization of Methicillin-Resistant and Methicillin-Susceptible Clones of Staphylococcus aureus,” Journal of Clinical Microbiology, 2000, vol. 38(3), pp. 1008-1015. |
| Enright M.C., et al., “Multilocus Sequence Typing of Streptococcus pyogenes and theRelationships between Emm Type and Clone,” Infection and Immunity, 2001, vol. 69 (4), pp. 2416-2427. |
| Enright M.C., et al., “The Evolutionary History of Methicillin-Resistant Staphylococcus aureus(MRSA),” Proceedings of the National Academy of Sciences of USA, 2002, vol. 99 (11), pp. 7687-7692. |
| Enright M.C., “The Evolution of a Resistant Pathogen—the Case of MRSA,” Current Opinion in Pharmacology, 2003, vol. 3 (5), pp. 474-479. |
| Eremeeva M.E., et al., “Evaluation of a PCR Assay for Quantitation of Rickettsia rickettsii and Closely Related Spotted Fever Group Rickettsiae,” Journal of Clinical Microbiology, 2003, vol. 41 (12), pp. 5466-5472. |
| Erlich H.A., ed., PCR Technology: Principles and Applications for DNA Amplification, W.H. Freeman and Company, 1989. |
| Esmans E.L., et al., “Liquid Chromatography-Mass Spectrometry in Nucleoside, Nucleotide and Modified Nucleotide Characterization,” Journal of Chromatography, 1998, vol. 794, pp. 109-127. |
| Eugene-Ruellan G., et al., “Detection of Respiratory Syncytial Virus A and B and Parainfluenzavirus 3 Sequences in Respiratory Tracts of Infants by a Single PCR with Primers Targeted to the L-Polymerase Gene and Differential Hybridization,” Journal of Clinical Microbiology, 1998, vol. 36 (3), pp. 796-801. |
| European Search Report for Application No. EP10175659.1, mailed on Feb. 9, 2011, 4 pages. |
| Evans P., et al., “Practical Algorithms for Universal DNA Primer Design: An Exercise in Algorithm Engineering,” Currents in Computational Molecular Biology, 2001, Les Publications CRM, pp. 25-26. |
| Ex Parte Re-Examination Certificate for U.S. Appl. No. 90/010,209 mailed Jul. 7, 2009. |
| Ex Parte Re-Examination Certificate for U.S. Appl. No. 90/010,210, mailed Dec. 28, 2010. |
| Ex Parte Re-Examination Certificate for U.S. Appl. No. 90/010,447 mailed Feb. 15, 2011. |
| Examiner Interview Summary mailed Oct. 3, 2005 for U.S. Appl. No. 10/326,046, filed Dec. 18, 2002. |
| Examiner Interview Summary mailed Nov. 6, 2008 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Examiner Interview Summary mailed May 19, 2003 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Examiner Interview Summary mailed Oct. 24, 2008 for U.S. Appl. No. 11/582,859, filed Oct. 17, 2006. |
| Examiner Interview Summary mailed Feb. 27, 2006 for U.S. Appl. No. 10/326,644, filed Dec. 18, 2002. |
| Examiner Interview Summary mailed Jan. 27, 2006 for U.S. Appl. No. 10/323,211, filed Dec. 18, 2002. |
| Examiner Interview Summary mailed May 28, 2008 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Examiner Interview Summary mailed Oct. 28, 2008 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Examiner Interview Summary mailed Oct. 29, 2008 for U.S. Appl. No. 11/331,978, filed Jan. 13, 2006. |
| Examiner Interview Summary mailed Oct. 29, 2009 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Examiner Interview Summary mailed Jul. 31, 2006 for U.S. Appl. No. 10/326,643, filed Dec. 18, 2002. |
| Extended European Search Opinion for Application No. EP10175659.1, mailed on Feb. 21, 2011. |
| Extended European Search Report for Application No. EP10179789.2, mailed on Mar. 22, 2011, 9 pages. |
| Extended European Search Report for Application No. EP10179791.8, mailed on Mar. 17, 2011, 7 pages. |
| Extended European Search Report for Application No. EP10179795.9, mailed on Mar. 22, 2011, 9 pages. |
| Facklam R., et al., “Emm Typing and Validation of Provisional M Types for Group A Streptococci,” Emerging Infectious Diseases, 1999, vol. 5 (2), pp. 247-253. |
| Fang H., et al., “Rapid Screening and Identification of Methicillin-Resistant Staphylococcus aureus from Clinical Samples by Selective-Broth and Real-Time PCR Assay,” Journal of Clinical Microbiology, 2003, vol. 41 (7), pp. 2894-2899. |
| Farlow J., et al., “Francisella tularensis Strain Typing Using Multiple-Locus, Variable-Number Tandem Repeat Analysis,” Journal of Critical Microbiology, 2001, vol. 39 (9), pp. 3186-3192. |
| Farrell D. J., “The Reliability of Microscan Conventional and Rapid Panels to Identify Staphylococcus aureus and Detect Methicillin Resistance: An Evaluation Using the Tube Coagulase Test and mecA PCR,” Pathology, 1997, vol. 29 (4), pp. 406-410. |
| Fedele C.G., et al., “Multiplex Polymerase Chain Reaction for the Simultaneous Detection and Typing of Polyomavirus JC, BK and SV40 DNA in Clinical Samples,” Journal of Virological Methods, 1999, vol. 82 (2), pp. 137-144. |
| Fedele C.G., et al., “Quantitation of Polyomavirus DNA by a Competitive Nested Polymerase Chain Reaction,” Journal of Virological Methods, 2000, vol. 88 (1), pp. 51-61. |
| Feng P., “Impact of Molecular Biology on the Detection of Food Pathogens,” Molecular Biotechnology, 1997, vol. 7 (3), pp. 267-278. |
| Figueiredo L.M., et al., “Identification of Brazilian Flavivirus by a simplified reverse transcription-polymerase chain reaction method using Flavivirus universal primers,” American Journal of Tropical Medicine and Hygiene, 1998, vol. 59 (3), pp. 357-362. |
| Final Office Action mailed Aug. 6, 2010 for U.S. Appl. No. 11/929,910, filed Oct. 30, 2007. |
| Final Office Action mailed Jul. 8, 2010 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Final Office Action mailed May 12, 2010 for U.S. Appl. No. 11/674,538, filed Feb. 13, 2007. |
| Final Office Action mailed Apr. 14, 2011 for U.S. Appl. No. 12/049,949, filed Mar. 17, 2008. |
| Final Office Action mailed Oct. 14, 2009 for U.S. Appl. No. 10/943,344, filed Sep. 17, 2004. |
| Final Office Action mailed Nov. 17, 2009 for U.S. Appl. No. 11/582,875, filed Oct. 17, 2006. |
| Final Office Action mailed Feb. 18, 2010 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Final Office Action mailed Nov. 20, 2009 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Final Office Action mailed Jun. 23, 2010 for U.S. Appl. No. 11/930,017, filed Oct. 30, 2007. |
| Final Office Action mailed Feb. 26, 2009 for U.S. Appl. No. 11/582,863, filed Oct. 17, 2006. |
| Final Office Action mailed Jan. 30, 2009 for U.S. Appl. No. 10/844,938, filed May 12, 2004. |
| Flora J.W., et al, “Dual-Micro-ESI Source for Precise Mass Determination on a Quadrupole time-of-Flight Mass Spectrometer for Genomic and Proteomic Applications,” Analytical and Bioanalytical Chemistry, 2002, vol. 373 (7), pp. 538-546. |
| Fong W.K., et al., “Rapid Solid-Phase Immunoassay for Detection of Methicillin-ResistantStaphylococcus aureus Using Cycling Probe Technology,” Journal of Clinical Microbiology, 2000, vol. 38 (7), pp. 2525-2529. |
| Fox A., et al., “Identification and Detection of Bacteria: Electrospray MS-MS Versus Derivatization/GC-MS,” Proceedings of the ERDEC Scientific Conference on Chemical and Biological Defense Research, Aberdeen Proving Ground, MD, Nov. 15-18, 1994, pp. 39-44. |
| Fox A.,et al., “Report of the Bioterrorism Workshop,” Journal of Microbiological Methods, 2002, vol. 51 (3), pp. 247-254. |
| Fox J.P., et al., “The Virus Watch Program: A Continuing Surveillance of Viral Infections in Metropolitan New York Families,” American Journal of Epidemiology, 1969, vol. 89 (1), pp. 25-50. |
| Fox K.F., et al., “Identification of Brucella by ribosomal-spacer-region PCR and differentiation of Brucell canis from other Brucella spp. pathogenic for humans by carbohydrate profiles,” Journal of Clinical Microbiology, 1998, vol. 36 (11), pp. 3217-3222. |
| Francois J-C., et al., “Sequence-Specific Recognition and Cleavage of Duplex DNA via Triple-Helix Formation by Oligonucleotides Covalently Linked to a Phenanthroline-Copper Chelate,” Proceedings of the National Academy of Sciences of USA, 1989, vol. 86 (24), pp. 9702-9706. |
| Francois P., et al., “Rapid Detection of Methicillin-Resistant Staphylococcus aureus Directly from Sterile or Nonsterile Clinical Samples by a New Molecular Assay,” Journal of Clinical Microbiology, 2003, vol. 41 (1), pp. 254-260. |
| Fraser C.M., et al., “The Mimimal Gene Complement of Mycoplasma genitalium,” Science, 1995, vol. 270 (5235), pp. 397-403. |
| Freiberg C., et al., “Genome-Wide mRNA Profiling: Impact on Compound Evaluation and Target Identification in Anti-Bacterial Research,” Targets, 2002, vol. 1 (1), pp. 20-29. |
| Freymuth F., et al., “Comparison of Multiplex PCR Assays and Conventional Techniques for the Diagnostic of Respiratory Virus Infections in Children Admitted to Hospital With an Acute Respiratory Illness,” Journal of Medical Virology, 2006, vol. 78 (11), pp. 1498-1504. |
| Freymuth F., et al., “Detection of Respiratory Syncytial Virus, Parainfluenzavirus 3, Adenovirus Andrhinovirus Sequences in Respiratory Tract of Infants by Polymerase Chain Reaction and Hybridization,” Clinical and Diagnostic Virology, 1997, vol. 8 (1), pp. 31-40. |
| Fuerstenau S.D., et al., “Molecular Weight Determination of Megadalton DNA Electrospray Ions Using Charge Detection Time-of-flight Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1995, vol. 9 (15), pp. 1528-1538. |
| Fujimoto T., et al., “Single-Tube Multiplex. PCR for Rapid and Sensitive Diagnosis of Subgenus B and Other Subgenera Adenoviruses in Clinical Samples,” Microbiology and Immunology, 2000, vol. 44 (10), pp. 821-826. |
| Fujimura S., et al., “Characterization of the mupA Gene in Strains of Methicillin-Resistant Staphylococcus aureus with a Low Level of Resistance to Mupirocin,” Antimicrobial Agents and Chemotheraphy, 2001, vol. 45 (2), pp. 641-642. |
| Fujimura S., et al., “Isoleucyl-tRNA Synthetase Mutations in Staphylococcus aureus Clinicallsolates and in Vitro Selection of Low-Level Mupirocin-Resistant Strains,” Antimicrobial Agents and Chemotheraphy, 2003, vol. 47 (10), pp. 3373-3374. |
| Gabriel M.N., et al., “Improved mtDNA Sequence Analysis of Forensic Remains using a “Mini-Primer Set” Amplification Strategy,” Journal of Forensic Sciences, 2001, vol. 46 (2), pp. 247-253. |
| Gall J. G. D., et al., “Construction and Characterization of Hexon-Chimeric Adenoviruses: Specification of Adenovirus Serotype,” Journal of Virology, 1998, vol. 72 (12), pp. 10260-10264. |
| Gammelin M., et al., “Two Subtypes of Nucleoproteins (NP) of Influenza A Viruses,” Virology, 1989, vol. 170 (1), pp. 71-80. |
| Garcia S., et al., “Quantitative Real-Time PCR Detection of Rift Valley Fever Virus and Its Application to Evaluation of Antiviral Compounds,” Journal of Clinical Microbiology, 2001, vol. 39 (12), pp. 4456-4461. |
| Garcia-Martinez J., et al., “Use of the 16s-23s Ribosomal Genes Spacer Region in Studies of Prokaryotic Diversity,” Journal of Microbiological Methods, 1999, vol. 36 (1-2), pp. 55-64. |
| Gattermann N., et al., “Heteroplasmic Point Mutations of Mitochondrial DNA Affecting Subunit I of Cytochrome c Oxidise in Two Patients with Acquired Idiopathic Siderblastic Anemia,” Blood, 1997, vol. 90 (12), pp. 4961-4972. |
| Gaydos C.A., et al., “Adenovirus Vaccines in the U.S. Military,” Military Medicine, 1995, vol. 160 (6), pp. 300-304. |
| Geha D.J., et al., “Multiplex PCR for Identification of Methicillin-Resistant Staphylococci in the Clinical Laboratory,” Journal of Clinical Microbiology, 1994, vol. 32 (7), pp. 1768-1772. |
| Genbank, “{Deletion 6} [Human, Muscle, Mitochondrial Mutant, 22 nt, Segment 2 of 2],” Accession No. S90302.1, Jun. 10, 1992. |
| Genbank “Acinetobacter genomosp. 10 strain CIP 70.12 RNA polymerase subunit B (rpoB) gene, complete cds,” Accession No. 78099429, Mar. 11, 2006. |
| Genbank, “Bovine parainfluenza virus 3 strain Shipping Fever, complete genome,” Accesion No. AF178655, Sep. 19, 2000. |
| Genbank, “Clostridium tetani E88, complete genome,” Accession No. AE015927.1, Feb. 4, 2003. |
| Genbank “E. coli operon rpoBC coding for the beta- and beta'-subunits of RNA polymerase (genes rpoC and rpoB), and genes rplL, rlpJ, rplA, and rplK coding for 50S ribosomal subunit proteins L7/L12, L10, L1, and L11, respectively. (Map position 89-90 min.),” Accession No. 42813, Feb. 28, 1992. |
| Genbank, “E.coli 16S ribosomal RNA,” Accession No. 174375, Aug. 11, 1995. |
| Genbank, “E.coli Open Reading Frame Upstream of Leu Operon,” Accession No. M21150, Sep. 15, 1990. |
| Genbank “E.coli rRNA operon (rrnB) coding for Glu-tRNA-2, 5S, 16S and 23S rRNA,” Accession No. 147581, Sep. 14, 1992. |
| Genbank, “Enterococcus malodoratus strain ATCC43197 elongation factor Tu (tufA) gene, partial cds,” Accession No. AF274728, Dec. 11, 2000. |
| Genbank “Escherichia coli str. K-12 substr. MG1655, Complete Genome,” Accession No. NC000913, Oct. 15, 2001. |
| Genbank, “Homo sapiens Haplotype V Mitochondrion, Complete Genome”, Accession No. AF381990.1, Dec. 28, 2001. |
| Genbank, “Human Adenovirus Type 4 Hexon Gene,” for Accession No. X84646, Jun. 30, 1995. |
| Genbank, “Human coronavirus 229E, complete genome,” Accession No. AF304460, Jul. 11, 2001. |
| Genbank, “Human Isolate L34 Mitochondrion D-loop Region”, Accession No. U08081.1, Aug. 16, 1994. |
| Genbank, “il11b08.y1 Human insulinoma Homo sapiens cDNA clone Image:60295345-similar to SW:COX3—Human P00414 Cytochrome C Oxidase Polypeptide III ;, mRNA sequence”, Accession No. BQ581956.1, Jun. 20, 2002. |
| Genbank, “Influenza B Virus B/Panama/45/90 Polymerase (PB2) mRNA, Complete Cds”, Accession No. AF005737, pp. 1-3, Oct. 4, 1997. |
| Genbank, “Mastadenovirus h7 hexon gene,” Accession No. Z48571, Apr. 18, 2005. |
| Genbank, “or72a01.s1 NCI—CGAP—Lu5 Homo sapiens cDNA Clone Image:16013523-similar to SW:COX1—Human P00395 Cytochrome C Oxidase Polypeptide I ;, mRNA sequence”, Accession No. AI002209.1, Jun. 10, 1998. |
| Genbank “Staphylococcus aureus RN4220 ErmC gene, partial cds,” Accession No. 18542231, Sep. 16, 2003. |
| Genbank “Staphylococcus aureus Strain MSSA476, Complete Genome,” Accession No. BX571857.1, Jun. 24, 2004. |
| Genbank, “Staphylococcus aureus subsp. aureus Mu50, complete genome,” Accession No. 15922990, Oct. 4, 2001. |
| Genbank “Staphylococcus aureus Subsp. Aureus MW2, Complete Genome,” Accession No. GI21281729, May 31, 2002. |
| Genbank, “Staphylococcus epidermidis ATCC 12228, complete genome,” Accession No. AE015929.1, Jan. 2, 2003. |
| Genbank “Streptococcus agalactiae 2603V/R, complete genome,” Accession No. AE009948.1, Aug. 28, 2002. |
| Genbank, “Streptococcus anginosus Elongation Factor Tu (tuf) Gene, Partial cds,” Accession No. AF276257.1, Jul. 1, 2001. |
| Genbank “Streptococcus pneumoniae isolate 95.1In00S DNA gyrase subunit B (gyrB) gene, complete cds,” Accession No. 73916349, Sep. 30, 2005. |
| Genbank, “Streptococcus pyogenes strain MGAS8232, complete genome,” Accession No. AE009949.1, Apr. 3, 2002. |
| Genbank, “Venezuelan equine encephalitis virus nonstructural polyprotein and structural polyprotein genes, complete cds,” Accession No. AF375051.1, Jun. 26, 2001. |
| Gendel S.M., “Computational Analysis of the Specificity of 16S rRNA-Derived Signature Sequencesfor Identifying Food-Related Microbes,” Food Microbiology, 1996, vol. 13, pp. 1-15. |
| Gibb T.R., et al., “Development and Evaluation of a 5″″″″ Fluorogenic Nuclease Assay to Detect and Differentiate Between Ebola Virus Subtypes Zaire and Sudan,” Journal of Clinical Microbiology, 2001, vol. 39 (11), pp. 4125-4130. |
| Gilbert N., et al., “Comparison of Commercial Assays for the Quantitation of HBV DNA Load in Healthcare Workers: Calibration Differences,” Journal of Virological Methods, 2002, vol. 100 (1-2), pp. 37-47. |
| Giles R.E., et al., “Maternal Inheritance of Human Mitochondrial DNA,” Proceedings of the National Academy of Sciences, 1980, vol. 77 (11), pp. 6715-6719. |
| Gill S.R., et al., “Insights on Evolution of Virulence and Resistance from the Complete Genome Analysis of an Early Methicillin-Resistant Staphylococcus aureus Strain and a Biofilm-Producing Methicillin-Resistant Staphylococcus epidemidis Strain,” Journal of Bacteriology, 2005, vol. 187 (7), pp. 2426-2438. |
| Gilliland G., et al., “Analysis of Cytokine mRNA and DNA: Detection and Quantitation by Competitive Polymerase Chain Reaction,” Proceedings of the National Academy of Sciences of USA, 1990, vol. 87 (7), pp. 2725-2729. |
| Ginther C., et al., “Identifying Individuals by Sequencing Mitochondrial DNA from Teeth,” Nature Genetics, 1992, vol. 2 (2), pp. 135-138. |
| Gjoen K.V., et al., “Specific Detection of Coxsackie Viruses A by the Polymerase Chain Reaction,” Clinical and Diagnostic Virology, 1997, vol. 8 (3), pp. 183-188. |
| Golden M. R., et al., “Pilot Study of COBAS PCT and Ligase Chain Reaction for Detection of Rectal Infections Due to Chlamydia trachomatis,” Journal of Clinical Microbiology, 2003, vol. 41 (5), pp. 2174-2175. |
| Goto K., et al., “Applications of the Partial 16S rDNA Sequence as an Index for Rapid Identification of Species in the Genus Bacillus,” Journal of General and Applied Microbiology, 2000, vol. 46 (1), pp. 1-8. |
| Gravet A., et al., “Characterization of a Novel Structural Member, LukE-LukD, of the Bi-Component Staphylococcal Leucotoxins Family,” FEBS Letters, 1998, vol. 436 (2), pp. 202-208. |
| Gray G.C., et al., “Adult Adenovirus Infections: Loss of Orphaned Vaccines Precipitates Military Respiratory Disease Epidemics,” Clinical Infectious Diseases, 2000, vol. 31, pp. 663-670. |
| Greenberg B.D., et al., “Intraspecific Nucleotide Sequence Variability Surrounding the Origin of Replicationin Human Mitochondrial DNA,” Gene, 1983, vol. 21, pp. 33-49. |
| Griffey, et al., “Detection of Base Pair Mismatches in Duplex DNA and RNA Oligonucleotides Using Electrospray Mass Spectrometry,” SPIE, 1997, vol. 2985, pp. 82-86. |
| Griffin T.J., et al., “Direct genetic analysis by matrix-assisted laseer desorption/ionization mass spectrometry,” PNAS, 1999, vol. 96 (11), pp. 6301-6306. |
| Griffin T.J., et al., “Single-Nucleotide Polymorphism Analysis by Maldi-TOF Mass Spectrometry,” Trends in Biotechnology, 2000, vol. 18 (2), pp. 77-84. |
| Grondahl B., et al., “Rapid Identification of Nine Microorganisms Causing Acute Respiratory TractInfections by Single-Tube Multiplex Reverse Transcription-PCR: Feasibility Study,” Journal of Clinical Microbiology, 1999, vol. 37 (1), pp. 1-7. |
| Grundmann H., et al., “Emergence and Resurgence of Meticillin-Resistant Staphylococcus aureus as a Public-Health Threat,” Lancet, 2006, vol. 368 (9538), pp. 874-885. |
| Grzybowski T., et al., “Extremely High Levels of Human Mitochondrial DNA Heteroplasmy in Single Hair Roots,” Electrophoresis, 2000, vol. 21 (3), pp. 548-553. |
| Gu Z., et al., “Multiplexed, Real-Time PCR for Quantitative Detection of Human Adenovirus,” Journal of Clinical Microbiology, 2003, vol. 41 (10), pp. 4636-4641. |
| Guatelli J.C., et al., “Nucleic Acid Amplification in Vitro: Detection of Sequences with Low Copy Numbers and Application to Diagnosis of Human Immunodeficiency Virus Type 1 Infection,” Clinical Microbiology Reviews, 1989, vol. 2 (2), pp. 217-226. |
| Haff L.A., et al., “Multiplex Genotyping of PCR Products with Mass Tag-Labeled Primers,” Nucleic Acids Research, 1997, vol. 25 (18), pp. 3749-3750. |
| Hahner S., et al., “Analysis of Short Tandem Repeat Polymorphisms by Electrospray Ion Trap Mass Spectrometry,” Nucleic Acids Research, 2000, vol. 28 (18), pp. E82.1-E82.8. |
| Haines J.D., et al., “Medical Response to Bioterrorism: Are we Prepared,” Journal of Oklahoma State Medical Association, 2000, vol. 93, pp. 187-196. |
| Hall T.A., et al., “Base Composition Analysis of Human Mitochondrial DNA Using Electrospray Ionization Mass Spectrometry: A Novel Tool for the Identification and Differentiation of Humans,” Analytical Biochemistry, 2005, vol. 344 (1), pp. 53-69. |
| Hamdad F., et al., “Detection of Methicillin/Oxacillin Resistance and Typing in Aminoglycoside-Susceptible Methicillin-Resistant and Kanamycin-Tobramycin-Resistant Methicillin-Susceptible,” Microbial Drug Resistance, 2006, vol. 12 (3), pp. 177-185. |
| Hamel S., et al., “Consensus PCR and Microarray for Diagnosis of the Genus Staphylococcus, Species, and Methicillin Resistance,” Biotechniques, 2001, vol. 31 (6), pp. 1364-1372. |
| Hammerle T., et al., “A Sensitive PCR Assay System for the Quantitation of Viral Genome Equivalents:Hepatitis C Virus (HCV),” Archives of Virology, 1996, vol. 141 (11), pp. 2103-2114. |
| Hannis J.C., et al., “Accurate Characterization of the Tyrosine Hydroxylase Forensic Allele 9.3 through Development of Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1999, vol. 13 (10), pp. 954-962. |
| Hannis J.C., et al., “Detection of Double-Stranded PCR Amplicons at the Attomole Level Electrosprayed from Low Nanomolar Solutions using FT-ICR Mass Spectrometry,” Journal of Analytical Chemistry, 2001, vol. 369 (3-4), pp. 246-251. |
| Hannis J.C., et al., “Genotyping Complex Short Tandem Repeats Using Electrospray Ionzation Fourier Transform Ion Cyclotron Resonance Multi-Stage Mass Spectrometry,” Proceedings of SPIE, 2000, vol. 3926, pp. 36-47. |
| Hannis J.C., et al., “Genotyping Short Tandem repeats using flow Injection and Electrospray Ionization , Fourier Transform ion Cyclotron Resonance Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 2001, vol. 15 (5), pp. 348-350. |
| Hannis J.C., et al., “Nanoelectrospray Mass Spectrometry Using Non-Metalized, Tapered (50-10 .mu.m) Fused-silica Capillaries,” Rapid Communication in Mass spectrometry, 1998, vol. 12, pp. 443-448. |
| Hanssen A.M., et al., “Sccmecin Staphylococci: Genes on the Move,” FEMS Immuol Medical Microbiol, 2006, vol. 46, pp. 8-20. |
| Hasebe F. et al., “Combined Detection and Genotyping of Chikungunya Virus by a Specific Reverse Transcription-Polymerase Chain Reaction,” Journal of Medical Virology, 2002, vol. 67 (3), pp. 370-374. |
| Hassan A.A., et al., “Inter- and Intraspecies Variations of the 16S-23S rDNA Intergenic Spacer Region of Various Streptococcal Species,” Systematic and Applied Microbiology, 2003, vol. 26 (1), pp. 97-103. |
| Hayashi H., et al., “Phylogenetic Analysis of the Human gut Microbiota using 16S rDNA clone Libraries and Strictly Anaerobic Culture-based Methods,” Journal of Microbiology, Immunology, 2002, vol. 46 (8), pp. 535-548. |
| He L., et al, “Development of a Capillary High-performance Liquid Chromatography Tandem Mass Spectrometry System Using SWIFT Technology in an Ion Trap/Reflectron Time-of-flight Mass Spetrometer,” Biochemical and Biophysical Research Communications, 1997, vol. 11, pp. 1739-1748. |
| Heim A., et al., “Rapid and Quantitative Detection of Human Adenovirus DNA by Real-Time PCR,” Journal of Medical Virology, 2003, vol. 70, pp. 228-239. |
| Henchal E.A., et al., “Sensitivity and Specificity of a Universal Primer set for the Rapid Diagnosis of Dengue Virus Infections by Polymerase Chain Reaction and Nucleic acid Hybridization,” American Journal of Tropical Medicine and Hygiene, 1991, vol. 45 (4), pp. 418- 428. |
| Herrmann B., et al., “Differentiation of Chlamydia spp. by Sequence Determination and Restriction Endonuclease Cleavage of RNase P RNA Genes,” Journal of Clinical Microbiology, 1996, vol. 34 (8), pp. 1897-1902. |
| Higgins G.S., et al., “Competitive Oligonucleotide Single-base Extension Combined with Mass Spectrometric Detection for Mutation Screening,” Biotechniques, 1997, vol. 23 (4), pp. 710-714. |
| Higgins J.A., et al., “Sensitive and Rapid Identification of Biological Threat Agents,” Annals of the New York Academy of Sciences, 1999, vol. 894, pp. 130-148. |
| Hill F., et al., “Polymerase Recognition of Synthetic Oligodeoxyribonucleotides Incorporating Degenerate Pyrimidine and Purine Bases,” Proceedings of the National Academy of Sciences, 1998, vol. 95, pp. 4258-4263. |
| Hiramatsu K., et al., “The Emergence and Evolution of Methicillin-Resistant Staphylococcusaureus,” Trends Microbiology, 2001, vol. 9 (10), pp. 486-493. |
| Hodgson J.E., et al., “Molecular Characterization of the Gene Encoding High-Level Mupirocin Resistancein Staphylococcus aureus J2870,” Antimicrobial Agents and Chemotherapy, 1994, vol. 38 (5), pp. 1205-1208. |
| Hoffman E., et al., “Rescue of Influenza B Virus from Eight Plasmids,” Proceedings of the National Academy of Sciences, 2002, vol. 99 (17), pp. 11411-11416. |
| Hoffmann E., et al., “Universal Primer Set for the Full-Length Amplification of all Influenza A Viruses.,” Archives of Virology, 2001, vol. 146 (12), pp. 2275-2289. |
| Hofstadler S.A., et al., “Tiger: The Universal Biosensor,” International Journal of Mass Spectrometry, 2005, vol. 242, pp. 23-41. |
| Holden M.T., et al., “Complete Genomes of Two Clinical Staphylocuccus aureus Strain: Evidence for the Rapid Evolution of Virulence and Drug Resistance,” Proceedings of the National Academy of Sciences, 2004, vol. 101 (26), pp. 9786-9791. |
| Holland M.M., et al., “Mitochondria! DNA Sequence Analysis of Human Skeletal Remains: Identification of Remains from the Vietnam War,” Journal of Forensic Sciences, 1993, vol. 38 (3), pp. 542-553. |
| Holland M.M., et al., “Mitochondrial DNA Sequence Analsysis—Validation and Use for Forensic Casework,” Forensic Science Review, 1999, vol. 11 (1), pp. 22-50. |
| Holm L., et al., “Removing Near-Neighbour Redundancy from Large Protein Sequence Collections,” Bioinformatics, 1998, vol. 14 (5), pp. 423-429. |
| Holmes E.C., et al., “Whole-Genome Analysis of Human Influenza A Virus Reveals Multiple Persistent Lineages and Reassortment among Recent H3N2 Viruses,” Public Library of Science Biology, 2005, vol. 3 (9), pp. 1579-1589. |
| Honda K., et al., “Universal Method of Hypersensitive Nested PCR Toward Forensic DNA typing,” International Congress Series, 1998, vol. 7, pp. 28-30. |
| Hongoh Y., et al., “Evaluation of Primers and PCR Conditions for the Analysis of 16s rRNA Genes from a Naturalenvironment,” FEMS Microbiology Letters, 2003, vol. 221 (2), pp. 299-304. |
| Hood E., et al., “Chemical and Biological Weapons: New Questions, New Answers,” Environmental Health Perspectives, 1999, vol. 107 (12), pp. 931-932. |
| Houng H.S., et al., “Rapid Type-Specific Diagnosis of Adenovirus Type 4 Infection Using a Hexon-Based Quantitative Fluorogenic Pcr,” Diagnostic Microbiology and Infectious Disease, 2002, vol. 42 (4), pp. 227-236. |
| Howell N., et al., “Persistent Heteroplasmy of a Mutation in the Human Mtdna Control Region: Hypermutation As an Apparent Consequence of Simple-Repeat Expansion/Contraction,” American Journal of Human Genetics, 2000, vol. 66 (5), pp. 1589-1598. |
| Huber C.G., et al., “On-Line Cation Exchange for Suppression of Adduct Formation in Negative-Ion Electrospray Mass Spectrometry of Nucleic Acids,” Analytical Chemistry, 1998, vol. 70 (24), pp. 5288-5295. |
| Huletsky A., et al., “New Real-Time Pcr Assay for Rapid Detection of Methicillin-Resistant Staphylococcus aureus Directly from Specimens Containing a Mixture of Staphylococci,” Journal of Clinical Microbiology, 2004, vol. 42 (5), pp. 1875-1884. |
| Hunag C., et al., “Detection of Arboviral RNA Directly from Mosquito Homogenates by Reverse Transcription-Polymerase Chain Reaction,” Journal of Virological Methods, 2001, vol. 94 (1-2), pp. 121-128. |
| Hung E.C., et al., “Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome,” Clinical Chemistry, 2003, vol. 49 (12), pp. 2108-2109. |
| Hurdle J.G., et al., “Analysis of Mupirocin Resistance and Fitness in Staphylococcus aureus by Molecular Genetic and Structural Modeling Techniques,” Antimicrobial Agents and Chemotherapy, 2004, vol. 48 (11), pp. 4366-4376. |
| Hurst G.B., et al., “Detection of Bacterial DNA Polymerase Chain Reaction Products by Matrix-Assisted Laser Desorptionfionization Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1996, vol. 10 (3), pp. 377-382. |
| Hurst G.B., et al., “MALDI-TOF Analysis of Polymerase Chain Reaction Products from Methanotrophic Bacteria,” Analytical Chemistry, 1998, vol. 70 (13), pp. 2693-2698. |
| Hutchison C.A., et al., “Maternal Inheritance of Mammalian Mitochondrial DNA,” Nature, 1974, vol. 251 (5475), pp. 536-538. |
| Hyde-Deruyscher R., et al., “Polyomavirus Early-Late Switch is not Regulated at the Level of Transcription Initiation and is associated with changes in RNA Processing,” Proceedings of the National Academy of Sciences, 1988, vol. 85, pp. 8993-8997. |
| Ieven M., et al., “Rapid Detection of Methicillin Resistance in Coagulase-Negative Staphylococci by Commercially Available Fluorescence Test,” Journal of Clinical Microbiology, 1995, vol. 33 (8), pp. 2183-2185. |
| Ihle O., et al., “Efficient Purification of DNA Fragments using a Protein Binding Membrane,” Nucleic Acids Research, 2000, vol. 28 (16), pp. e76. |
| Inglis T.J., et al., “Rapid Genotypic Confirmation of Methicillin Resistance,” Pathology, 1996, vol. 28 (3), pp. 259-261. |
| Ingman M., et al., “Mitochondrial Genome Variation and the Origin of Modern Humans,” Nature, 2000, vol. 408 (6813), pp. 708-713. |
| International Preliminary Examination Report for Application No. PCT/US2002/06763, mailed on Jun. 11, 2003, 6 pages. |
| International Preliminary Examination Report for Application No. PCT/US2002/20336, mailed on May 12, 2004, 8 pages. |
| International Preliminary Examination Report for Application No. PCT/US2003/09802, mailed on Apr. 8, 2005, 7 pages. |
| International Preliminary Examination Report for Application No. PCT/US2003/22835, mailed on Mar. 5, 2005, 4 pages. |
| International Preliminary Examination Report for Application No. PCT/US2003/38505, mailed on Mar. 3, 2006, 5 pages. |
| International Preliminary Examination Report for Application No. PCT/US2003/38757, mailed on Feb. 2, 2007, 5 pages. |
| International Preliminary Examination Report for Application No. PCT/US2003/38761, mailed on Jun. 27, 2006, 6 pages. |
| International Preliminary Report on Patentability and Written Opinion for Application No. PCT/US2005/00386, mailed on Jul. 10, 2006, 6 pages. |
| International Preliminary Report on Patentability and Written Opinion for Application No. PCT/US2005/030058, mailed on Aug. 20, 2007, 6 pages. |
| International Preliminary Report on Patentability and Written Opinion for Application No. PCT/US2005/033707, mailed on Mar. 20, 2007, 6 pages. |
| International Preliminary Report on Patentability for Application No. PCT/US2004/033742, mailed on Jun. 20, 2006, 1 page. |
| International Preliminary Report on Patentability for Application No. PCT/US2006/028397, mailed on Jan. 22, 2008, 1 page. |
| International Preliminary Report on Patentability for Application No. PCT/US2008/054926, mailed on Aug. 26, 2009, 1 page. |
| International Preliminary Report on Patentability, Written Opinion and International Search Report for Application No. PCT/US2004/015123, mailed on Oct. 3, 2005, 8 pages. |
| International Search Report and the Written Opinion for Application No. PCT/US2008/064891, mailed on Jun. 29, 2009, 15 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2005/018031, mailed on Jun. 28, 2006, 14 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2006/007747, mailed on Sep. 5, 2006, 13 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2006/028397, mailed on Mar. 5, 2007, 14 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2006/040747, mailed on Mar. 17, 2009, 19 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2006/061307, mailed on Jan. 9, 2008, 21 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2007/20045 mailed on Jan. 8, 2009, 18 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2008/054926, mailed on Jan. 26, 2009, 15 pages. |
| International Search Report and Written Opinion for Application No. PCT/US2008/057901, mailed on Aug. 28, 2008, 14 pages. |
| International Search Report for Application No. PCT/US02/20336, mailed on Feb. 3, 2003, 4 pages. |
| International Search Report for Application No. PCT/US04/007236, mailed on Feb. 24, 2006, 2 pages. |
| International Search Report for Application No. PCT/US2002/06763, mailed on Oct. 23, 2002, 4 pages. |
| International Search Report for Application No. PCT/US2003/009802, mailed on Aug. 3, 2004, 2 pages. |
| International Search Report for Application No. PCT/US2003/038505, mailed on Apr. 12, 2005, 2 pages. |
| International Search Report for Application No. PCT/US2003/038830, mailed on Aug. 25, 2004, 4 pages. |
| International Search Report for Application No. PCT/US2003/22835, mailed on Dec. 12, 2003, 1 page. |
| International Search Report for Application No. PCT/US2003/38757, mailed on Jun. 24, 2004, 2 pages. |
| International Search Report for Application No. PCT/US2003/38761, mailed on Dec. 30, 2005, 5 pages. |
| International Search Report for Application No. PCT/US2003/38795, mailed on Apr. 19, 2004, 3 pages. |
| International Search Report for Application No. PCT/US2004/012671, mailed on Sep. 28, 2007, 2 pages. |
| International Search Report for Application No. PCT/US2004/015123, mailed on Oct. 3, 2005, 2 pages. |
| International Search Report for Application No. PCT/US2004/015196, mailed on Jul. 1, 2005, 3 pages. |
| International Search Report for Application No. PCT/US2004/028869, mailed onJul. 17, 2006, 4 pages. |
| International Search Report for Application No. PCT/US2004/033742, mailed on May 15, 2006, 2 pages. |
| International Search Report for Application No. PCT/US2005/000386, mailed on May 9, 2006, 3 pages. |
| International Search Report for Application No. PCT/US2005/005356, mailed on Aug. 7, 2007, 4 pages. |
| International Search Report for Application No. PCT/US2005/006133, mailed on Jul. 26, 2007, 4 pages. |
| International Search Report for Application No. PCT/US2005/009557, mailed on Sep. 19, 2005, 1 page. |
| International Search Report for Application No. PCT/US2005/018337, mailed on Oct. 10, 2006, 2 pages. |
| International Search Report for Application No. PCT/US2005/024799, mailed on Dec. 28, 2006, 4 pages. |
| International Search Report for Application No. PCT/US2005/030058, mailed on Aug. 20, 2007, 1 page. |
| International Search Report for Application No. PCT/US2005/033707, mailed on Feb. 6, 2006, 3 pages. |
| International Search Report for Application No. PCT/US2007/066194, mailed on Jan. 15, 2008, 4 pages. |
| International Search Report for Application No. PCT/US2008/057901, mailed on Jun. 29, 2009, 15 pages. |
| International Search Report for Application No. PCT/US2008/065332, mailed on Nov. 28, 2008, 4 pages. |
| International Search Report for Application No. PCT/US2009/045635, mailed on Oct. 7, 2009, 9 pages. |
| Inyaku K., et al., “Rapid Detection and Identification of Mycobacteria in Sputum Samples by NestedPolymerase Chain Reaction and Restriction Fragment Length Polymorphisms of dnaJ Heat ShockProtein Gene,” Journal of Medical Sciences, 1993, vol. 42 (1), pp. 21-31. |
| Iqbal S.S., et al., “A Review of Molecular Recognition Technologies for Detection of Biological Threat Agents,” Biosensors & Bioelectronics, 2000, vol. 15 (11-12), pp. 549-578. |
| Isola N.R., et al., “MALDI-TOF mass spectrometric method for detection of hybridized DNA oligomers,” Analytical Chemistry, 2001, vol. 73 (9), pp. 2126-2131. |
| Iteman I., et al., “Comparison of Conserved Structural and Regulatory Domains within Divergent 16S rRNA-23S rRNA Spacer Sequences of Cyanobacteria,” Microbiology, 2000, vol. 146 (Pt 6), pp. 1275-1286. |
| Ito T., et al., “Insights on Antibiotic Resistance of Staphylococcus aureus from its Whole Genome: Genomic Island Scc,” Drug Resistance Updates, 2003, vol. 6 (1), pp. 41-52. |
| Ito T., et al., “Structural Comparison of Three Types of Staphylococcal Cassette Chromosome mecIntegrated in the Chromosome in Methicillin-Resistant Staphylococcus aureus,” Antimicrobial Agents and Chemotherapy, 2001, vol. 45 (5), pp. 1323-1336. |
| Jackson P.E., et al., “Mass Spectrometry for Genotyping: an Emerging Tool for Molecular Medicine,” Molecular Medicine Today, 2000, vol. 6 (7), pp. 271-276. |
| James A.M., et al., “Borelia lonestari Infection after a Bite by an Amblyomma americanum Tick,” The Journal of Infectious Diseases, 2001, vol. 183 (12), pp. 1810-1814. |
| Jankowski K., et al., “Mass Spectrometry of DNA. Part 2 Quantitative Estimation of Base Composition,” European Journal of Mass Spectrometry, 1980, vol. 1 (1), pp. 45-52. |
| Jansen R.C., et al., “Genotype-by-environment Interaction in Genetic Mapping of Multiple Quantitative Trait Loci,” Theoretical and Applied Genetics, 1995, vol. 91, pp. 33-37. |
| Jaulhac B., et al., “Specific Detection of the Toxic Shock Syndrome Toxin-1 Gene Using the Polymerase Chain Reaction,” Molecular and Cellular Probes, 1991, vol. 5, pp. 281-284. |
| Jaulhac B., et al., “Synthetic DNA Probes for Detection of Genes for Enterotoxins A, B, C, D, E and for Tsst-1 in Staphylococcal Strains,” Journal of Applied Bacterial, 1992, vol. 72 (5), pp. 386-392. |
| Jeong J., et al., “Early Screening of Oxacillin-Resistant Staphylococcus aureus and Staphylococcus epidermidis From Blood Culture,” Journal of Korean Medical Science, 2002, vol. 17, pp. 168-172. |
| Jiang C., et al., “Multiple Trait Analysis of Genetic Mapping for Quantitative Trait Loci Genetics,” Genetics, 1995, vol. 140 (3), pp. 1111-1127. |
| Jiang Y., et al., “A Highly Efficient and Automated Method for Purifying and Desalting PCR Products for Analysis by Electrospray Ionization Mass Spectrometry,” Analytical Biochemistry, 2003, vol. 316 (1), pp. 50-57. |
| Johansson A., et al., “Evaluation of PCR-based Methods for Discrimination of Francisella species and Subspecies and Development of a Specific PCR that Distinguishes the two Major Subspecies of Francisella tularensis,” Journal of Clinical Microbiology, 2000, vol. 38 (11), pp. 4180-4185. |
| Johnson W.M., et al., “Detection of Genes for Enterotoxins, Exfoliative Toxins, and Toxic Shock Syndrome Toxin 1 in Staphylococcus aureus by the Polymerase Chain Reaction,” Journal of Clinical Microbiology, 1991, vol. 29 (3), pp. 426-430. |
| Johnson Y.A., et al., “Precise Molecular Weight Determination of PCR Products of the rRNA Intergenic Spacer Region Using Electrospray Quadrupole Mass Spectrometry for Differentiation of B. subtilis and B. atrophaeus, Closely Related Species of Bacilli,” Journal of Microbiological Methods, 2000, vol. 40 (3), pp. 241-254. |
| Jonas D., et al., “Rapid PCR-Based Identification of Methicillin-Resistant Staphylococcus aureusfrom Screening Swabs,” Journal of Clinical Microbiology, 2002, vol. 40 (5), pp. 1821-1823. |
| Jurinke C., et al., “Application of Nested PCR and Mass Specctrometry for DNA Based Virus Detection: HBV-DNA Detected in the Majority of Isolated Anti-Hbc Positive Sera,” Genetic Analysis: Biomolecular Engineering, 1998, vol. 14 (3), pp. 97-102. |
| Jurinke C., et al., “MALDI-TOF Mass Spectrometry. A Versatile Tool for High-Performance DNA Analysis,” Molecular Biotechnology, 2004, vol. 26 (2), pp. 147-163. |
| Kacian D.L., et al., “A Replicating RNA Molecule Suitable for a Detailed Analysis of Extracellular Evolution and Replication,” Proceeding of the National Academy of Sciences, 1972, vol. 69 (10), pp. 3038-3042. |
| Kageyama A., et al. “Rapid Detection of Human Fecal Eubacterium Species and Related Genera by Tested PCR Method,” Journal of Microbiology, Immunology, 2001, vol. 45 (4), pp. 315-318. |
| Kajon A.E., et al., “Genome Type Analysis of Brazilian Adenovirus Strains of Serotypes 1, 2, 3, 5,and 7 Collected Between 1976 and 1995,” Journal of Medical, 1999, vol. 58 (4), pp. 408-412. |
| Kasai H., et al., “Construction of the gyrB Database for the Identification and Classification of Bacteria,” Genome Informatics. Workshop on Genome Informatics, 1998, pp. 13-21. |
| Katano H., et al., “Identification of Adeno-Associated Virus Contamination in Cell and Virus Stocks by PCR,” Biotechniques, 2004, vol. 36 (4), pp. 676-680. |
| Katayama Y., et al., “Genetic Organization of the Chromosome Region Surrounding mecA inClinical Staphylococcal Strains: Role of IS431-Mediated mecl Deletion in Expression of Resistance inmed-Canying, Low-Level Methicillin-Resistant Staphylococcus haemolyticus,” Antimicrobial Agents and Chemotherapy, 2001, vol. 45 (7), pp. 1955-1963. |
| Ke D., et al., “Development of a PCR Assay for Rapid Detection of Enterococci,” Journal of Clinical Microbiology, 1999, vol. 37 (11), pp. 3497-3503. |
| Kearns A.M., et al., “Rapid Detection of Methicillin-Resistant Staphylococci by Multiplex PCR,” The Journal of Hospital Inspection, 1999, vol. 43 (1), pp. 33-37. |
| Keller A., et al., “Empirical Statistical Model to Estimate the Accuracy of Peptide Identifications Made by MS/MS and Database Search,” Analytical Chemistry, 2002, vol. 74 (20), pp. 5383-5392. |
| Khan A.S., et al., “An Outbreak of Crimean-Congo Haemorrhagic Fever in the United Arab Emirates, 1994-1995,” The American Journal of Tropical Medicine and Hygiene, 1997, vol. 57 (5), pp. 519-525. |
| Khan S.A., et al., “Simultaneous Detection of Erythromycin-Resistant Methylase Genes ermA and ermC from Staphylococcus Spp. By Multiplex-PCR,” Molecular and Cellular Probes, 1999, vol. 13 (5), pp. 381-387. |
| Kidd A.H., et al., “Rapid Subgenus Identification of Human Adenovirus Isolates by a General PCR,” Journal of Clinical Microbiology, 1996, vol. 34 (3), pp. 622-627. |
| Kidd-Ljunggren K., et al., “The hepatitis B virus X gene: analysis of functional domain variation and gene phylogeny using multiple sequences,” Journal of General Virology, 1995, vol. 76 (pt 9), pp. 2119-2130. |
| Kikuchi K., et al., “Restriction Fragment Length Polymorphism Analysis of Clinical Isolates of Mycobacterium haemophilum,” Journal of Clinical Microbiology, 1994, vol. 32 (7), pp. 1763-1767. |
| Kilbourne E.D., “Influenza Pandemics of the 20th Century,” Emerging Infectious Diseases Journal, 2006, vol. 12 (1), pp. 9-14. |
| Kilbourne E.D., “Influenza Pandemics: Can We Prepare for the Unpredictable,” Viral Immunology, 2004, vol. 17 (3), pp. 350-357. |
| Kim B.J., et al., “Identification of Mycobacterial Species by Comparative Sequence Analysis of the RNA Polymerase Gene (rpoB),” Journal of Clinical Microbiology, 1999, vol. 37 (6), pp. 1714-1720. |
| Kinney R.M., et al., “Nucleotide Sequences of the 26S mRNAs of the Viruses Defining the Venezuelan Equine Encephalitis Antigenic Complex,” The American Journal of Tropical Medicine and Hygiene, 1998, vol. 59 (6), pp. 952-964. |
| Kirpekar F., et al., “Matrix Assisted Laser Desorption/Ionization Mass Spectrometry of Enzymatically Synthesized RNA up to 150 kDa,” Nucleic Acids Research, 1994, vol. 22 (19), pp. 3866-3870. |
| Kitagawa Y., et al., “Rapid Diagnosis of Methicillin-Resistant Staphylococcus aureus Bacteremia by Nested Polymerase Chain Reaction,” Annals of Surgery, 1996, vol. 224 (5), pp. 665-671. |
| Knoth K., et al., “Highly Degenerate, Inosine-Containing Primers Specifically Amplify Rare cDNA using the Polymerase Chain Reaction,” Nucleic Acids Research, 1988, vol. 16 (22), pp. 10932. |
| Kolbert C.P., et al., “Branched-DNA Assay for Detection of the mecA Gene in Oxacillin-Resistant and Oxacillin-Sensitive Staphylococci,” Journal of Clinical Microbiology, 1998, vol. 36 (9), pp. 2640-2644. |
| Kowalak J.A., et al., “A Novel Method for the Determination of Post-Transcriptional Modification in RNA by Mass Spectrometry,” Nucleic Acids Research, 1993, vol. 21 (19), pp. 4577-4585. |
| Krafft A.E., et al., “Evaluation of PCR Testing of Ethanol-Fixed Nasal Swab Specimens as anAugmented Surveillance Strategy for Influenza Virus and Adenovirus Identification,” Journal of Clincal Microbiology, 2005, vol. 43 (4), pp. 1768-1775. |
| Krahmer M.T., et al., “Electrospray Quadrupole Mass Spectrometry Analysis of Model Oligonucleotides and Polymerase Chain Reaction Products: Determination of Base Substitutions, Nucleotide Additions/Deletions, and Chemical Modifications,” Analytical Chemistry, 1999, vol. 71 (14), pp. 2893-2900. |
| Krahmer M.T., et al, “MS for Identification of Single Nucleotide Polymorphisms and MS/MS for Discrimination of Isomeric PCR Products,” Analytical Chemistry, 2000, vol. 72 (17), pp. 4033-4040. |
| Kramer L.D., et al., “Dection of Encephalitis Viruses in Mosquitoes (Diptera: Culicidea) and Avian Tissues,” Journal of Medical Entomology, 2002, vol. 39 (2), pp. 312-323. |
| Kramer L.D., et al., “Dection of St. Louis Encephalitis and Western Equine Encephalomyelitis RNAin Mosquitoes Tested Without Maintainance of a Cold Chain,” Journal of the American Mosquito Control Association, 2001, vol. 17 (4), pp. 213-215. |
| Kresken M., et al., “Prevalence of Mupirocin Resistance in Clinical Isolates of Staphylococccus aureus and Staphylococcus epidermidis: Results of the Antimicrobial Resistance Surveillance Study of the Paul-Ehrlich-Society for Chemotherapy, 2001,” International Journal of Antimicrobial Agents, 2004, vol. 23 (6), pp. 577-581. |
| Krishnan P.U., et al., “Detection of Methicillin and Mupirocin Resistance in Staphylococcus aureusisolates Using Conventional and Molecular Methods: A Descriptive Study from a Burns Unit with Highprevalence of MRSA,” Journal of Clinical Pathology, 2002, vol. 55 (10), pp. 745-748. |
| Kroes I., et al., “Bacterial Diversity Within the Human Subgingival Crevice,” Proceeding of the National Academy of Sciences, 1999, vol. 96 (25), pp. 14547-14552. |
| Krossoy B., et al., “The Putative Polymerase Sequence of Infectious Salmon Anemia Virus Suggests a New Genus within the Orthomyxoviridae,” Journal of Virology, 1999, vol. 73 (3), pp. 2136-2142. |
| Ksiaxek T.G., et al., “A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome,” The New England Journal of Medicine, 2003, vol. 348 (20), pp. 1953-1966. |
| Kupke T., et al., “Molecular Characterization of Lantibiotic-Synthesizing Enzyme EpiD Reveals a Function for Bacterial Dfp Proteins in Coenzyme A Biosynthesis,” Journal of Biological Chemistry, 2000, vol. 275 (41), pp. 31838-31846. |
| Kuroda M., et al., “Whole Genome Sequencing of Meticillin-Resistant Staphylococcus aureus,” The Lancet, 2001, vol. 357 (9264), pp. 1225-1240. |
| Kwok S., et al., “Avoiding False Positives with PCR,” Nature, 1989, vol. 339 (6221), pp. 237-238. |
| Labandeira-Rey, M. et al., “Staphylococcus aureus Panton Valentine Leukocidin CausesNecrotizing Pneumonia,” Sciencexpress, 2007, 8 pages. |
| Lacroix J.M., et al, “PCR-Based Technique for the Detection of Bacteria in Semen and Urine,” Journal of Microbiological Methods, 1996, vol. 26, pp. 61-71. |
| Lacroix L., et al., “Triplex Formation by Oligonucleotides Containing 5-(1-Propynyl)-2-deoxyuridine: Decreased Magnesium Dependence and Improved Intracellular Gene Targeting,” Biochemistry, 1999, vol. 38 (6), pp. 1893-1901. |
| Laken S.J., et al., “Genotyping by Mass Spectrometric Analysis of Short DNA Fragments,” Nature Biotechnology, 1998, vol. 16 (13), pp. 1352-1356. |
| Lamb R.A., et al., “Sequence of Interrupted and Uninterrupted mRNAs and Cloned DNA Coding for the Two Overlapping Nonstructural Proteins of Influenza Virus,” Cell, 1980, vol. 21 (2), pp. 475-485. |
| Lambert A.J., et al., “Detection of North American Eastern and Western Equine EncephalitisViruses by Nucleic Acid Amplification Assays,” Journal of Clinical Microbiology, 2003, vol. 41 (1), pp. 379-385. |
| Lau L.T., et al, “A Real-Time PCR for SARS-Coronavirus Incorporating Target Gene Pre-Amplification,” Biochemical and Biophysical Research Communications, 2003, vol. 312 (4), pp. 1290-1296. |
| Lau L.T., et al., “Nucleic Acid Sequence-Based Amplification Methods to Detect Avian Influenza Virus,” Biochemical and Biophysical Research Communications, 2004, vol. 313 (2), pp. 336-342. |
| Le Cann P., et al., “Quantification of Human Astroviruses in Sewage Using Real-Time RT-PCR,” Research in Microbiology, 2004, vol. 155 (1), pp. 11-15. |
| Lebedev Y., et al., “Oligonucleotides Containing 2-Aminoadenine and 5-Methycytosine are More Effective as Primers for PCR Amplification than their Nonmodified Counterparts,” Genetic Analysis: Biomolecular Engineering, 1996, vol. 13 (1), pp. 15-21. |
| Lednicky J.A., et al., “Polyomaviruses and Human Tumors: A Brief Review of Current Concenpts and Interpretations,” Frontiers Bioscience, 1999, vol. 4, pp. D153-164. |
| Lee J.A., et al., “Rapid Identification of Human Adenovirus Types 3 and 7 from Respiratory Specimens via Multiplex Type-Specific PCR,” Journal of Clinical Microbiology, 2005, vol. 43 (11), pp. 5509-5514. |
| Lee J.H., et al., “Simultaneous Detection of Three Mosquito-Borne Encephalitis Viruses (Eastern equine, La Crosse, and St. Louis) with a Single-Tube Multiplex Reverse Transcriptase Polymerase Chaine Reaction Assay,” Journal of the American Mosquito Control Association, 2002, vol. 18 (1), pp. 26-31. |
| Leif H., et al., “Isolation and Characterization of the Proton-Translocating NADH: Ubiqu None Oxidoreductase from Escherichia coli,” European Journal of Biochemistry, 1995, vol. 230 (2), pp. 538-548. |
| Lengyel A., et al., “Characterization of the Main Protein Components of Adenovirus Virion and itsPossible Use in Laboratory Diagnostics,” Acta Microbiologica Immunologica Hungarica, 1998, vol. 43 (3-4), pp. 281-283. |
| Leroy E.M., et al., “Diagnosis of Ebola Haemorrhagic Fever by RT-PCR in an Epidemic Setting,” Journal of Medicinal Virology, 2000, vol. 60 (4), pp. 463-467. |
| Levi K., et al., “Evaluation of an Isothermal Signal Amplification Method for Rapid Detection of Methicillin-Resistant Staphylococcus aureus from Patient-Screening Swabs,” Journal of Clinical Microbiology, 2003, vol. 41 (7), pp. 3187-3191. |
| Levine S.M., et al., “PCR-Based Detection of Bacillus anthracis in Formalin-Fixed Tissue from a Patient Receiving Ciprofloxacin,” Journal of Clinical Microbiology, 2002, vol. 40 (11), pp. 4360-4362. |
| Levison P.R., et al., “Recent Developments of Magnetic Beads for Use in Nucleic Acid Purification,” Journal of Chromatography, 1998, vol. A816, pp. 107-111. |
| Lewers K.S., et al., “Detection of Linked QTL for Soybean Brown Stem Rot Resistance in “BSR 101” as Expressed in a Growth Chamber Environment,” Molecular Breeding, 1999, vol. 5, pp. 33-42. |
| Li C., et al., “Evolution of H9N2 Influenza Viruses from Domestic Poultry in Mainland China,” Virology, 2005, vol. 340 (1), pp. 70-83. |
| Li J., et al., “Single Nucleotide Polymorphism Determination Using Primer Extension and Time-of-Flight Mass Spectrometry,” Electrophoresis, 1999, vol. 20 (6), pp. 1258-1265. |
| Li Q., et al., “Genetic Variability of Hexon Loops 1 and 2 between Seven Genome Types of Adenovirus Serotype 7,” Archives of Virology, 1999, vol. 144 (9), pp. 1739-1749. |
| Li Q., et al., “Screening of the High Yield Influenza B Virus on MDCK c14d Cloning of its Whole Genome,” International Congress Series, 2004, vol. 1263, pp. 610-614. |
| Li Q.G., et al., “Analysis of 15 Different Genome Types of Adenovirus Type 7 Isolated on FiveContinents,” Journal of Virology, 1986, vol. 60 (1), pp. 331-335. |
| Li Q.G., et al., “Comparison of 17 Genome Types of Adenovirus Type 3 Identified among Strains Recovered from Six Continents,” Journal of Clinical Microbiology, 1988, vol. 26 (5), pp. 1009-1015. |
| Liebermann H., et al., “Mapping of Epitopes on the Fiber Knobs of Human Adenovirus Serotypes 8 and 15,” Intervirology, 2002, vol. 45 (1), pp. 59-66. |
| Liebermann H., et al., “Mapping of Linear Epitopes on Fibre Knob of Human Adenovirus Serotype 5,” Virus Research, 2001, vol. 73 (2), pp. 145-151. |
| Lim L.P., et al., “The MicroRNAs of Caenorhabditis elegans,” Genes and Development, 2003, vol. 17 (8), pp. 991-1008. |
| Limbach P.A., et al., “Enzymatic Sequencing of Oligonucleotides with Electrospray Mass Spectrometry,” 42nd ASMS Conference on Mass Spectrometry, 1994. |
| Limoncu M.H., et al., “Emergence of Phenotypic Resistance to Ciprofloxacin and Levofloxacin Inmethicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Strains,” International Journal of Antimicrobial Agents, 2003, vol. 21 (5), pp. 420-424. |
| Lin B., et al., “Use of Oligonucleotide Microarrays for Rapid Detection and Serotyping of Acute Respiratory Disease-Associated Adenoviruses,” Journal of Clinical Microbiology, 2004, vol. 42 (7), pp. 3232-3239. |
| Lin P.H., et al., “Oxidative Damage to Mitochondrial Dna in Atrial Muscle of Patients with Atrial Fibrillation,” Free Radical Biology and Medicine, 2003, vol. 35 (10), pp. 1310-1318. |
| Lina G., et al., “Bacterial Competition for Human Nasal Cavity Colonization: Role of Staphylococcalagr Alleles,” Applied and Environmental Microbiology, 2003, vol. 69 (1), pp. 18-23. |
| Lina G., et al., “Involvement of Panton-Valentine Leukocidin-Producing Staphylococcus aureus in Primary Skin Infections and Pneumonia,” Clinical Infectious Diseases, 1999, vol. 29 (5), pp. 1128-1132. |
| Linssen B., et al., “Development of Reverse Transcription-PCR Assays Specific for Detection of Equine Encephalitis Viruses,” Journal of Clinical Microbiology, 2000, vol. 38 (4), pp. 1527-1535. |
| Little D.P., et al., “MALDI on a Chip: Analysis of Arrays of Low-Femtomole to Subfemtomole Quantities of Synthetic Oligonucleotides and DNA Diagnostic Products Dispensed by a Piezoelectric Pipet,” Analytical Chemistry, 1997, vol. 69, pp. 4540-4546. |
| Little D.P., et al, “Rapid Sequencing of Oligonucleotides by High-Resolution Mass Spectrometry,” Journal of the American Chemical Society, 1994, vol. 116 (11), pp. 4893-4897. |
| Liu C., et al., “Improving the Microdialysis Procedure for Electrospray Ionization Mass Spectrometry of Biological Samples,” Journal of Mass Spectrometry, 1997, vol. 32 (4), pp. 425-431. |
| Liu J.H., et al., “Interregional Transmission of the Internal Protein Genes of H2 Influenza Virus in Migratory Ducks from North America to Eurasia,” Virus Genes, 2004, vol. 29 (1), pp. 81-86. |
| Liu Y., et al., “An Unusual Gene Arrangement for the Putative Chromosome Replication Origin and Circadianexpression of dnaN in Synechococcussp. Strain PCC 7942,” Gene, 1996, vol. 172 (1), pp. 105-109. |
| Livermore D.M., “The Threat from the Pink Corner,” Annals of Medicine, 2003, vol. 35 (4), pp. 226-234. |
| Loakes D., et al., “Nitroindoles as Universal Bases,” Nucleosides and Nucleotides, 1995, vol. 14 (3-5), pp. 1001-1003. |
| Loo J.A., et al., “Applying Charge Discrimination with Electrospray Ionization-Mass Spectrometry to Protein Analysis,” Journal of American Society for Mass Spectrometry, 1995, vol. 6, pp. 1098-1104. |
| Lott T.J., et al., “Nucleotide Sequence Analysis of the 5-8s rDNA and Adjacent ITS2 Region of Candidaalbicans and Related Species,” Yeast, 1993, vol. 9, pp. 1199-1206. |
| Louie L., et al., “Evaluation of Three Rapid Methods for Detection of Methicillin Resistance in Staphylococcus aureus,” Journal of Clinical Microbiology, 2000, vol. 38 (6), pp. 2170-2173. |
| Love B.C., et al., “Cloning and Sequence of the GroESL Heat-Shock Operon of Pasteurella multocida,” Gene, 1995, vol. 166 (1), pp. 179-180. |
| Lovseth A., et al., “Modified Multiplex PCR Method for Detection of Pyrogenic Exotoxin Genes in Staphylococcal Isolates,” Journal of Clinical Microbiology, 2004, vol. 42 (8), pp. 3869-3872. |
| Lowe T., et al., “A Computer Program for Selection of Oligonucleotide Primers for Polymerase Chain Reactions,” Nucleic Acids Research, 1990, vol. 18 (7), pp. 1757-1761. |
| Lu X., et al., “Molecular Typing of Human Adenoviruses by PCR and Sequencing of a Partial Region of the Hexon Gene,” Archives of Virology, 2006, vol. 151 (8), pp. 1587-1602. |
| Lubman D.M., Application for Continuation Grant by David Mitchell Lubman dated Jun. 4, 1996 and Jun. 14, 1996. |
| Lubman D.M., Application for Continuation Grant by David Mitchell Lubman dated Jun. 10, 1994 and Jun. 24, 1994. |
| Lubman D.M., Application for Grant by David Mitchell Lubman dated Sep. 1, 1994 and Sep. 27, 1994. |
| Lubman D.M., Application for Grant by David Mitchell Lubman dated Oct. 25, 1992 and Oct. 29, 1992. |
| Ludwig S.L., et al., “Prevalence of Antibodies to Adenovirus Serotypes 4 and 7 among Unimmunized US Army Trainees: Results of a Retrospective Nationwide Seroprevalence Survey,” The Journal of Infectious Diseases, 1998, vol. 178 (6), pp. 1776-1778. |
| Ludwig W., et al., “Bacterial Phylogeny Based on 16S and 23S rRNA Sequence Analysis,” FEMS Microbiolofy Reviews, 1994, vol. 15 (2-3), pp. 155-173. |
| Lukashov V.V., et al., “Evolutionary Relationships among Parvoviruses: Virus-Host Coevolution among Autonomous Primate Parvoviruses and Links between Adeno-Associated and Avian Parvoviruses,” Journal of Virology, 2001, vol. 75 (6), pp. 2729-2740. |
| Ma X.X., et al., “Novel Type of Staphylococcal Cassette Chromosome mec Identified in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strains,” Antimicrobial Agents and Chemotherapy, 2002, vol. 46 (4), pp. 1147-1152. |
| Mack D.H., et al., “A Sensitive Method for the Identification of Uncharacterized Viruses Related Toknown Virus Groups: Hepadnavirus Model System,” Proceedings of the National Academy of Sciences, 1988, vol. 85 (18), pp. 6977-6981. |
| Magnuson V.L., et al., “Substrate Nucleotide-Determined Non-Templated Addition of Adenine by TagDNA Polymerase: Implications for PCR-Based Genotyping and Cloning,” BioTechniques, 1996, vol. 21 (4), pp. 700-709. |
| Maiwald M., et al., “Characterization of Contaminating DNA in Taq Polymerase which Occurs During Amplification with a Primer Set for Legionella 5S Ribosomal RNA,” Molecular and Cellular Probes, 1994, vol. 8 (1), pp. 11-14. |
| Malasig M.D., et al., “Simplified Microneutralization Test for Serotyping Adenovirus Isolates,” Journal of Clinical Microbiology, 2001, vol. 39 (8), pp. 2984-2986. |
| Mangrum J.D., et al., “Solution Composition and Thermal Denaturation for the Production of Single-Stranded PCR Amplicons: Piperidine-Induced Destabilization of the DNA Duplex,” Journal of the American Society for Mass Spectrometry, 2002, vol. 13 (3), pp. 232-240. |
| Manian F.A., “Asymptomatic Nasal Carriage of Mupirocin-Resistant, Methicillin-Resistant Staphylococcus aureus (MRSA) in a Pet Dog Associated with MRSA Infection in Household Contacts,” Clinical Infectious Diseases, 2003, vol. 36 (2), pp. e26-e28. |
| Marks F., et al., “Genotyping of Plasmodium falciparum Pyrimethamine Resistance by Matrix-Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry,” Antimicrobial Agents and Chemotherapy, 2004, vol. 48 (2), pp. 466-472. |
| Marmur J., et al., “Strand Separation and Specific Recombination in Deoxyribonucleic Acids: Biological Studies,” Proceedings of the National Academy of Sciences, 1960, vol. 46 (4), pp. 453-461. |
| Martemyanov K.A., et al., “Extremely Thermostable Elongation Factor (3 from Aquifer aeolicus: Cloning, Expression, Purification, and Characterization in a Heterologous Translation System,” Protein Expression and Purification, 2000, vol. 18 (3), pp. 257-261. |
| Martineau F., et al., “Development of a PCR Assay for Identification of Staphylococci at Genus andSpecies Levels,” Journal of Clinical Microbiology, 2001, vol. 39 (7), pp. 2541-2547. |
| Martineau F., et al., “Species-Specific and Ubiquitous-DNA-Based Assays for Rapid Identification of Staphylococcus aureus,” Journal of Clinical Microbiology, 1998, vol. 36 (3), pp. 618-623. |
| Martin-Lopez J.V., et al., “Simultaneous PCR Detection of ica Cluster and Methicillin and Mupirocinresistance Genes in Catheter-Isolated Staphylococcus,” International Microbiology, 2004, vol. 7 (1), pp. 63-66. |
| Mason V.P., et al., “Diversity and linkage of Replication and Mobilisation Genes in Bacillus Rolling Irclereplicating Plasmids from Diverse Geographical Origins,” FEMS Microbiology Ecology, 2002, vol. 42 (2), pp. 235-241. |
| Matray T.J., et al., “Synthesis and Properties of RNA Analogs-Oligoribonucleotide N3-->p5 Phosphoramidates,” Nucleic Acids Research, 1999, vol. 27 (20), pp. 3976-3985. |
| Matsuoka M., et al., “Characteristic Expression of Three Genes, msr(A), mph(C) and erm(Y), Thatconfer Resistance to Macrolide Antibiotics on Staphylococcus aureus,” FEMS Microbiology Letters, 2003, vol. 220 (2), pp. 287-293. |
| May A.C., “Percent Sequence Identity: The Need to be Explicit,” Structure, 2004, vol. 12 (5), pp. 737-738. |
| McCabe K.M., et al., “Bacterial species identification after DNA amplification with a universal primer pair,” Molecular Genetics and Metabolism, 1999, vol. 66 (3), pp. 205-211. |
| McLafferty F.W., et al., “Comparison of Algorithms and Databases for Matching Unknown Mass Spectra,” Journal of the American Society for Mass Spectrometry, 1998, vol. 9 (1), pp. 92-95. |
| McLuckey S.A., et al., “Ion Trap Tandem Mass Spectrometry Applied to Small Multiply Charged Oligonucleotides with a Modified Base,” Journal of the American Society for Mass Spectrometry, 1994, vol. 5, pp. 740-747. |
| Mehrotra M., et al., “Multiplex PCR for Detection of Genes for Staphylococcus aureus Enterotoxins, Exfoliative Toxins, Toxic Shock Syndrome Toxin 1, and Methicillin Resistance,” Journal of Clinical Microbiology, 2000, vol. 38 (3), pp. 1032-1035. |
| Meiyu F., et al., “Detection of Flaviviruses by Reverse Transcriptase-Polymerase Chain Reaction with the Universal Primer Set,” Microbiology and Immunology, 1997, vol. 41 (3), pp. 209-213. |
| Mellor J., et al., “Genotype Dependence of Hepatitis C Virus Load Measurement in Commercially Available Quantitative Assays,” Journal of Clinical Microbiology, 1999, vol. 37 (8), pp. 2525-2532. |
| Merlino J., et al., “New Chromogenic Identification and Detection of Staphylococcus aureus andMethicillin-Resistant S. aureus,” Journal of Clinical Microbiology, 2000, vol. 38 (6), pp. 2378-2380. |
| Merlino J., et al., “Rapid Detection of Non-Multidrug-Resistant and Multidrug-Methicillin—Resistant Staphylococcus aureus Using Cycling Probe Technology for the mecA Gene,” European Journal of Clinical Microbiology & Infectious Diseases, 2003, vol. 22 (5), pp. 322-323. |
| Messmer T.O., et al., “Discrimination of Streptococcus pneumoniae from Other Upper respiratory tract Streptococci by arbitrary primed PCR,” Clinical Biochemistry, 1995, vol. 28 (6), pp. 567-572. |
| Metzgar D., et al., “PCR Analysis of Egyptian Respiratory Adenovirus Isolates, Including Identification of Species, Serotypes and Coinfections,” Journal of Clinical Microbiology, 2005, vol. 43 (11), pp. 5743-5752. |
| Miller K.W., et al., “A Compendium of Human Mitochondrial DNA Control Region: Development of an International Standard Forensic Database,” Croatian Medical Journal, 2001, vol. 42 (3), pp. 315-327. |
| Miragaia M., et al., “Genetic Diversity among Methicillin-Resistant Staphylococcus epidemidis(MRSE,” Microbial Drug Resistance, 2005, vol. 11 (2), pp. 83-93. |
| Miura-Ochiai R., et al., “Quantitative Detection and Rapid Identification of Human Adenoviruses,” Journal of Clinical Microbiology, 2007, vol. 45 (3), pp. 958-967. |
| Mollet C., et al., “rpoB Sequence Analysis as a Novel Basis for Bacterial Identification,” Molecular Microbiology, 1997, vol. 26 (5), pp. 1005-1011. |
| Monroy A.M., et al., “Exvaluation of Reverse Transcriptase Polymerase Chain Reaction for theDetection of Eastern Equine Encephalumyelitis Virus during Vector Surveillance,” Journal of Medical Entomology, 1996, vol. 33 (3), pp. 449-457. |
| Moore C., et al., “Development and Evaluation of a Real-Time Nucleic Acid Sequence Based Amplification Assay for Rapid Detection of Influenza A,” Journal of Medical Virology, 2004, vol. 74 (4), pp. 619-628. |
| Moricca S., et al., “Detection of Fusarium oxysporum f.sp. Vasinfectum in Cotton Tissue by Polymerase Chain Reaction,” Plant Pathology, 1998, vol. 47 (4), pp. 486-494. |
| Morinaga N., et al., “Purification, Cloning and Charactarizarion of Variant LukE-LukD with Strong Leukocidal Activity of Staphylococcal Bi-Component Leukotoxin Family,” Microbiology and Immunology, 2003, vol. 47 (1), pp. 81-90. |
| Morse R., et al., “Nucleotide Sequence of Part of the ropC Gene Encoding the B Subunit of DNADependentRNA Polymerase from some Gram-Positive Bacteria and Comparative Amino AcidSequence Analysis,” Systematic and Applied Microbiology, 1996, vol. 19, pp. 150-157. |
| Muddiman D.C., et al., “Application of Secondary Ion and Matrix-Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry for the Quantitative Analysis of Biological Molecules,” Mass Spectrometry Reviews, 1995, vol. 14 (6), pp. 383-429. |
| Muddiman D.C., et al., “Characterization of PCR Products from Bacilli Using Electrospray Ionization FTICR Mass Spectrometry,” Analytical Chemistry, 1996, vol. 68 (21), pp. 3705-3712. |
| Muddiman D.C., et al., “Important Aspects Concerning the Quantification of Biomolecules by Time-of-Flight Secondaryion Mass Spectrometry,” Applied Spectrometry, 1996, vol. 50 (2), pp. 161-166. |
| Muddiman D.C., et al., “Length and Base Composition of PCR-Amplified Nucleic Acids Using Mass Measurements from Electrospray Ionization Mass Spectrometry,” Analytical Chemistry, 1997, vol. 69 (8), pp. 1543-1549. |
| Muddiman D.C., et al., “Precise Mass Measurement of a Double-Stranded 500 Base-Pair (309 kDa) Polymerase Chain Reaction Product by Negative Ion Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1999, vol. 13 (2), pp. 1201-1204. |
| Muddiman D.C., et al., “Sequencing and Characterization of Larger Oligonucleotides by Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry,” Reviews in Analytical Chemistry, 1998, vol. 17 (1), pp. 1-68. |
| Muhammed W.T., et al., “Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry and Guadrupole Mass Spectrometry for Genotyping Single Nucleotide Substitutions in Intact Polymerase Chain Reaction Products in K-Ras and p53,” Rapid Communications in Mass Spectrometry, 2002, vol. 16 (24), pp. 2278-2285. |
| Murakami K., et al., “Identification of Methicillin-Resistant Strains of Staphylococci by PolymeraseChain Reaction,” Journal of Clinical Microbiology, 1991, vol. 29 (10), pp. 2240-2244. |
| Mushegian A.R., et al., “A Minimal Gene Set for Cellular Life Derived by Comparison of Complete Bacterial Genomes,” Proceedings of the National Academy of Science, 1996, vol. 93 (19), pp. 10268-10273. |
| Na B.K., et al., “Detection and Typing of Respiratory Adenoviruses in a Single-Tube Multiplex Polymerase Chain Reaction,” Journal of Medical Virology, 2002, vol. 66 (4), pp. 512-517. |
| Nagpal M.L., et al., “Utility of 16S-23S rRNA Spacer Region Methodology: How Similar are Interspace Regions within a Genome and Between Strains for Closely Related Organisms?,” Journal of Microbiological Methods, 1998, vol. 33, pp. 211-219. |
| Nagy M., et al., “Sequence Analysis of Porcine Adenovirus Serotype 5 Fibre Gene: Evidence for Recombination,” Virus Genes, 2002, vol. 24 (2), pp. 181-185. |
| Naito Y., et al., “Molecular Mass Measurement of Polymerase Chain Reaction Products Amplified from Human Blood DNA by Electrospray Ionization Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1995, vol. 9 (15), pp. 1484-1486. |
| Nakagawa S., et al., “Gene sequences and specific detection for Panton-Valentine leukocidin,” Biochemical and Biophysical Research Communications, 2005, vol. 328 (4), pp. 995-1002. |
| Nakao H., et al., “Development of a Direct PCR Assay for Detection of the Diphtheria Toxin Gene,” Journal of Clinical Microbiology, 1997, vol. 35 (7), pp. 1651-1655. |
| Narita S., et al., “Phage conversion of Panton-Valentine leukocidin inStaphylococcus aureus: molecular analysis of a PVL-converting phage, cpSLT,” Gene, 2001, vol. 268 (1-2), pp. 195-206. |
| Naumov G.I., et al., “Discrimination between the soil yeast species Williopsis saturnus and Williopsis suaveolens by the polymerase chain reaction with the universal primer N21,” Microbiology, 2000, vol. 69 (2), pp. 229-233. |
| NEB Catalog. 1998/1999 pp. 1, 79, 121 and 284. |
| Neumann G., et al., “Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic,” Emerging Infectious Diseases, 2006, vol. 12 (6), pp. 881-886. |
| Newcombe J., et al., “PCR of Peripheral Blood for Diagnosis of Meningococcal Disease,” Journal of Clinical Microbiology, 1996, vol. 34 (7), pp. 1637-1640. |
| Ng E.K., et al., “Quantitative Analysis an Prognostic Implication of SARS Coronavirus RNA in the Plasma and Serum of Patients with Severe Acute Respiratory Syndrome,” Clinical Chemistry, 2003, vol. 49 (12), pp. 1976-1980. |
| Ng E.K., et al., “Serial Analysis of the Plasma Concentration of SARS Coronavirus RNA in Pediatric Patients with Severe Acute Respiratory Syndrome,” Clinical Chemistry, 2003, vol. 49 (12), pp. 2085-2088. |
| Ni J., et al., “Interpretation of Oligonucleotide Mass Spectra for Determinationof Sequence Using Electrospray Ionization and Tandem Mass Spectrometry,” Analytical Chemistry, 1996, vol. 68 (13), pp. 1989-1999. |
| Nilsson M., et al., “Evaluation of Mitochondrial DNA Coding Region Assays for Increased Discrimination in Forensic Analysis,” Forensic Science International: Genetics, 2008, vol. 2 (1), pp. 1-8. |
| Nishikawa T., et al., “Reconstitution of Active Recombinant Ship Toxin (Stc)1 from Recombinant Stxl-A and Sbtl-B Subunits Independently Produced by E. coli Clones,” FEMS Microbiol Letters, 1999, vol. 178 (1), pp. 13-18. |
| Non-Final Office Action mailed Feb. 2, 2007 for U.S. Appl. No. 10/844,938, filed May 12, 2004. |
| Non-Final Office Action mailed Oct. 2, 2009 for U.S. Appl. No. 11/929,707, filed Oct. 30, 2007. |
| Non-Final Office Action mailed Aug. 4, 2010 for U.S. Appl. No. 12/049,949, filed Mar. 17, 2008. |
| Non-Final Office Action mailed Apr. 6, 2009 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Non-Final Office Action mailed Apr. 7, 2006 for U.S. Appl. No. 10/964,571, filed Oct. 12, 2004. |
| Non-Final Office Action mailed Aug. 7, 2007 for U.S. Appl. No. 10/844,938, filed May 12, 2004. |
| Non-Final Office Action mailed Jun. 10, 2009 for U.S. Appl. No. 10/844,938, filed May 12, 2004. |
| Non-Final Office Action mailed Jan. 12, 2010 for U.S. Appl. No. 11/491,376, filed Jul. 21, 2006. |
| Non-Final Office Action mailed Oct. 13, 2010 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Non-Final Office Action mailed Sep. 16, 2009 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Non-Final Office Action mailed Apr. 17, 2009 for U.S. Appl. No. 12/211,641, filed Sep. 16, 2008. |
| Non-Final Office Action mailed Nov. 19, 2003 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Non-Final Office Action mailed Aug. 20, 2007 for U.S. Appl. No. 11/582,863, filed Oct. 17, 2006. |
| Non-Final Office Action mailed May 20, 2008 for U.S. Appl. No. 10/844,938, filed May 12, 2004. |
| Non-Final Office Action mailed Oct. 20, 2004 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Non-Final Office Action mailed Feb. 23, 2009 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Non-Final Office Action mailed May 26, 2010 for U.S. Appl. No. 11/869,449, filed Oct. 9, 2007. |
| Non-Final Office Action mailed Jul. 27, 2006 for U.S. Appl. No. 11/209,439, filed Aug. 8, 2005. |
| Non-Final Office Action mailed Jun. 28, 2010 for U.S. Appl. No. 11/930,002, filed Oct. 30, 2007. |
| Non-Final Office Action mailed Sep. 28, 2009 for U.S. Appl. No. 11/930,017, filed Oct. 30, 2007. |
| Non-Final Office Action mailed Dec. 29, 2010 for U.S. Appl. No. 12/616,422, filed Nov. 11, 2009. |
| Non-Final Office Action mailed Apr. 30, 2010 for U.S. Appl. No. 11/930,108, filed Oct. 31, 2007. |
| Norder H., et al., “Typing of Hepatitis B Virus Genomes by a Simplified Polymerase Chain Reaction,” Journal of Medical Virology, 1990, vol. 31 (3), pp. 215-221. |
| Nordhoff E., et al., “Matrix Assisted Laser Desorption/Ionization Mass Spectrometry of Nucleic Acids with Wavelengths in the Ultraviolet and Infrared,” Rapid Communications in Mass Spectrometry, 1992, vol. 6 (12), pp. 771-776. |
| Notice of Allowance mailed Apr. 1, 2011 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Notice of Allowance mailed Jun. 3, 2009 for U.S. Appl. No. 11/331,978, filed Jan. 13, 2006. |
| Notice of Allowance mailed Aug. 5, 2010 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Notice of Allowance mailed Aug. 6, 2009 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Notice of Allowance mailed Dec. 10, 2010 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Notice of Allowance mailed Dec. 10, 2010 for U.S. Appl. No. 11/491,376, filed Jul. 21, 2006. |
| Notice of Allowance mailed Nov. 12, 2009 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Notice of Allowance mailed Dec. 15, 2008 for U.S. Appl. No. 11/331,978, filed Jan. 13, 2006. |
| Notice of Allowance mailed Sep. 18, 2009 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Notice of Allowance mailed Nov. 24, 2009 for U.S. Appl. No. 11/331,978, filed Jan. 13, 2006. |
| Notice of Allowance mailed Oct. 29, 2009 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Nubel U.,et al., “PCR primers to amplify 16S rRNA genes from Cyanobacteria,” Applied andEnvironmental Microbiology, 1997, vol. 63 (8), pp. 3327-3332. |
| Null Allison P., et al., “Enzymatic Strategies for the Characterization of Nucleic Acids by Electrospray Ionization Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 2003, vol. 17 (24), pp. 2699-2706. |
| Null A.P., et al., “Determination of a Correction to Improve Mass Measurement Accuracy of Isotopically Unresolved Polymerase Chain Reaction Amplicons by Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 2003, vol. 17 (15), pp. 1714-1722. |
| Null A.P., et al., “Evaluation of Sample Preparation Techniques for Mass Measurements of PCR Products Using ESIFT-ICR Mass Spectrometry,” The American Society for Mass Spectrometry, 2002, vol. 13 (4), pp. 338-344. |
| Null A.P., et al., “Genotyping of Simple and Compound Short Tandem Repeat Loci Using Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry,” Analytical Chemistry, 2001, vol. 73 (18), pp. 4514-4521. |
| Null A.P., et al., “Implications of Hydrophobicity and Free Energy of Solvation for Characterization of Nucleic Acids by Electrospray Ionization Mass Spectrometry,” Analytical Chemistry, 2003, vol. 75 (6), pp. 1331-1339. |
| Null A.P., et al., “Perspectives on the Use of Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Short Tandem Repeat Genotyping in the Post Genome Era,” Journal of Mass Spectrometry, 2001, vol. 36 (6), pp. 589-606. |
| Null A.P., et al., “Preparation of Single-Stranded PCR Products for Electrospray Ionization Mass Spectrometry Using the DNA Repair Enzyme Lambda Exonuclease,” Analyst, 2000, vol. 125 (4), pp. 619-626. |
| Nunes E.L., et al., “Detection of ileS-2 Gene Encoding Mupirocin Resistance in Methicillin-ResistantStaphylococcus aureus by Multiplex PCR,” Diagnostic Microbiology and Infectious Disease, 1999, vol. 34 (2), pp. 77-81. |
| Nygren M., et al., “Quantification of HIV-1 Using Multiple Quantitative Polymerase Chain ReactionStandards and Bioluminometric Detection,” Analytical Biochemistry, 2001, vol. 288 (1), pp. 28-38. |
| Oberacher H., et al., “Analysis of Polymerase Chain Reaction Products by On-Line Liquid Chromatography Mass Spectrometry for Genotyping of Polymeric Short tandem Repeat Loci,” Analytical Chemistry, 2001, vol. 73 (21), pp. 5109-5115. |
| Oberacher H., et al., “Increased foresnic efficiency of DNA fingerprints through simultaneous resolution of length and nucleotide variability by high-performance mass spectrometry,” Human Mutation, 2008, vol. 29 (3), pp. 427-432. |
| Oberste M.S., et al., “Improved molecular identification of enteroviruses by RT-PCR and amplicon sequencing,” Journal of Medical Virology, 2003, vol. 26 (3), pp. 375-377. |
| Oberste M.S., et al., “Molecular epidemiology and type-specific detection of echovirus 11 isolates fromthe Americas, Europe, Africa, Australia, southern Asia and the Middle East,” Virus Research, 2003, vol. 91 (2), pp. 241-248. |
| Oberste M.S., et al., “Molecular phylogeny and proposed classification of the Simian picornaviruses,” Journal of Virology, 2002, vol. 76 (3), pp. 1244-1251. |
| Office Action mailed Apr. 1, 2004 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Office Action mailed May 1, 2006 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Office Action mailed Feb. 2, 2011 for U.S. Appl. No. 11/869,449, filed Oct. 9, 2007. |
| Office Action mailed Jan. 2, 2009 for U.S. Appl. No. 11/060,135, filed Feb. 17, 2005. |
| Office Action mailed Jun. 2, 2006 for U.S. Appl. No. 10/933,928, filed Sep. 3, 2004. |
| Office Action mailed Jun. 2, 2008 for U.S. Appl. No. 11/331,978, filed Jan. 13, 2006. |
| Office Action mailed Oct. 2, 2008 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Office Action mailed Aug. 3, 2006 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Office Action mailed Aug. 3, 2009 for U.S. Appl. No. 11/754,174, filed May 25, 2007. |
| Office Action mailed Dec. 3, 2003 for U.S. Appl. No. 10/325,527, filed Dec. 18, 2002. |
| Office Action mailed Feb. 3, 2011 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Office Action mailed Nov. 3, 2008 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Office Action mailed Apr. 4, 2008 for U.S. Appl. No. 10/829,826, filed Apr. 22, 2004. |
| Office Action mailed Dec. 4, 2006 for Indian Application No. 1136KOLNP2003 filed Mar. 24, 002. |
| Office Action mailed Feb.4, 2009 for U.S. Appl. No. 11/404,561, filed Apr. 12, 2006. |
| Office Action mailed Jun. 4, 2009 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Office Action mailed May 4, 2010 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed May 4, 2010 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed Nov. 4, 2009 for European Application No. 02709785.6 filed Mar. 4, 2002. |
| Office Action mailed Sep. 4, 2008 for Australian Application No. 2003297687 filed Dec. 5, 2003. |
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| Office Action mailed Sep. 5, 2006 for U.S. Appl. No. 10/660,996, filed Sep. 12, 2003. |
| Office Action mailed Jan. 6, 2011 for Israel Application No. 157661 filed Mar. 4, 2002. |
| Office Action mailed Jul. 6, 2006 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Jul. 6, 2007 for U.S. Appl. No. 10/829,826, filed Apr. 22, 2004. |
| Office Action mailed Mar. 6, 2009 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Office Action mailed Nov. 6, 2002 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Apr. 7, 2009 for Canadian Application No. 2525498 filed May 13, 2004. |
| Office Action mailed Apr. 7, 2009 for European Application No. 07760292.8 filed Apr. 6, 2007. |
| Office Action mailed Apr. 7, 2009 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Office Action mailed Aug. 7, 2007 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Office Action mailed Feb. 7, 2008 for European Application No. 03796752.8 filed Dec. 5, 2003. |
| Office Action mailed Jun. 7, 2010 for European Application No. 06800205.4 filed Jul. 27, 2006. |
| Office Action mailed Jan. 8, 2003 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Jan. 8, 2007 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Mar. 8, 2005 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Mar. 8, 2007 for U.S. Appl. No. 11/060,135, filed Feb. 17, 2005. |
| Office Action mailed Sep. 8, 2006 for Chinese Application No. 02809122.1 filed Mar. 4, 2002. |
| Office Action mailed Dec. 9, 2004 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Office Action mailed Dec. 9, 2009 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Dec. 9, 2009 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed Dec. 9, 2009 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed Feb. 9, 2007 for Chinese Application No. 02809122.1 filed Mar. 4, 2002. |
| Office Action mailed Jan. 9, 2008 for Japanese Application No. 2002570692 filed Mar. 4, 2002. |
| Office Action mailed Jul. 9, 2008 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Jul. 9, 2008 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Office Action mailed Mar. 9, 2004 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Nov. 9, 2010 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Office Action mailed Aug. 10, 2004 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Aug. 10, 2004 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Aug. 10, 2004 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Office Action mailed Aug. 10, 2004 for U.S. Appl. No. 10/326,642, filed Dec. 18, 2002. |
| Office Action mailed Dec. 10, 2008 for U.S. Appl. No. 10/829,826, filed Apr. 22, 2004. |
| Office Action mailed Dec. 10, 2009 for U.S. Appl. No. 11/929,910, filed Oct. 30, 2007. |
| Office Action mailed Feb. 10, 2005 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Feb. 10, 2006 for Australian Application No. 2002244250 filed Mar. 4, 2002. |
| Office Action mailed Jun. 10, 2009 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Jun. 10, 2010 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed Jun. 10, 2010 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed Oct. 10, 2007 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Office Action mailed Sep. 10, 2008 for Australian Application No. 2003302236 filed Dec. 5, 2003. |
| Office Action mailed Aug. 11, 2005 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Aug. 11, 2010 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed Aug. 11, 2010 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed Dec. 11, 2007 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Office Action mailed Jul. 11, 2003 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Jun. 11, 2010 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Mar. 11, 2005 for U.S. Appl. No. 10/325,527, filed Dec. 18, 2002. |
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| Office Action mailed Jun. 12, 2008 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
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| Office Action mailed May 12, 2002 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Aug. 13, 2009 for U.S. Appl. No. 11/674,538, filed Feb. 13, 2007. |
| Office Action mailed Jul. 13, 2004 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Jul. 13, 2007 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Office Action mailed Jul. 13, 2010 for U.S. Appl. No. 11/929,930, filed Oct. 30, 2007. |
| Office Action mailed Mar. 13, 2006 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Office Action mailed Nov. 13, 2003 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Sep. 13, 2006 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Jul. 14, 2004 for U.S. Appl. No. 10/326,642, filed Dec. 18, 2002. |
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| Office Action mailed Apr. 16, 2008 for U.S. Appl. No. 11/233,630, filed Sep. 21, 2005. |
| Office Action mailed Apr. 16, 2009 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Aug. 16, 2004 for U.S. Appl. No. 10/325,527, filed Dec. 18, 2002. |
| Office Action mailed Aug. 16, 2010 for U.S. Appl. No. 11/929,707, filed Oct. 30, 2007. |
| Office Action mailed Feb. 16, 2011 for U.S. Appl. No. 11/929,910, filed Oct. 30, 2007. |
| Office Action mailed Jul. 16, 2007 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Office Action mailed Mar. 16, 2006 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Mar. 16, 2010 for Canadian Application No. 2616281 filed Jul. 21, 2006. |
| Office Action mailed May 16, 2008 for U.S. Appl. No. 11/404,56, filed Apr. 12, 2006. |
| Office Action mailed Nov. 16, 2009 for Japanese Application No. 2005508488 filed Dec. 5, 2003. |
| Office Action mailed Nov. 16, 2009 for Japanese Application No. 2005508560 filed Dec. 5, 2003. |
| Office Action mailed Jun. 17, 2008 for U.S. Appl. No. 11/582,863, filed Oct. 17, 2006. |
| Office Action mailed Mar. 17, 2006 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Nov. 17, 2006 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Office Action mailed Oct. 17, 2007 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Office Action mailed Oct. 17, 2008 for U.S. Appl. No. 11/331,978, filed Jan. 13, 2006. |
| Office Action mailed Sep. 17, 2008 for European Application No. 03796752.8 filed Dec. 5, 2003. |
| Office Action mailed Sep. 17, 2008 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Feb. 18, 2010 for European Application No. 03814656.9 filed Dec. 5, 2003. |
| Office Action mailed Jan. 18, 2011 for U.S. Appl. No. 11/930,108, filed Oct. 31, 2007. |
| Office Action mailed May 18, 2005 for New Zealand Application No. 527857 filed Mar. 4, 2002. |
| Office Action mailed Sep. 18, 2006 for U.S. Appl. No. 10/660,997, filed Sep. 12, 2003. |
| Office Action mailed Sep. 18, 2008 for Australian Application No. 2003298030 filed Dec. 5, 2003. |
| Office Action mailed Sep. 18, 2008 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Office Action mailed Jan. 19, 2007 for U.S. Appl. No. 11/059,776, filed Feb. 17, 2005. |
| Office Action mailed May 19, 2005 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Nov. 19, 2004 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Office Action mailed Oct. 19, 2007 for U.S. Appl. No. 11/210,516, filed Aug. 24, 2005. |
| Office Action mailed Sep. 19, 2006 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Sep. 19, 2007 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Apr. 20, 2007 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Apr. 20, 2009 for U.S. Appl. No. 10/891,337, filed Jul. 14, 2004. |
| Office Action mailed Dec. 20, 2006 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Office Action mailed Jul. 20, 2005 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Office Action mailed Jun. 20, 2002 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Nov. 20, 2003 for U.S. Appl. No. 10/323,438, filed Dec. 18, 2002. |
| Office Action mailed Nov. 20, 2006 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Nov. 20, 2006 for European Application No. 02709785.6 filed Mar. 4, 2002. |
| Office Action mailed Sep. 20, 2010 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed Sep. 20, 2010 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed Apr. 21, 2009 for U.S. Appl. No. 90/010,209, filed Jun. 27, 2008. |
| Office Action mailed Mar. 21, 2008 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed May 21, 2008 for U.S. Appl. No. 10/943,344, filed Sep. 17, 2004. |
| Office Action mailed Nov. 21, 2003 for U.S. Appl. No. 10/326,642, filed Dec. 18, 2002. |
| Office Action mailed Nov. 21, 2006 for U.S. Appl. No. 10/660,997, filed Sep. 12, 2003. |
| Office Action mailed Oct. 21, 2005 for U.S. Appl. No. 10/326,641, filed Dec. 18, 2002. |
| Office Action mailed Oct. 21, 2009 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Office Action mailed Apr. 22, 2009 for U.S. Appl. No. 11/491,376, filed Jul. 21, 2006. |
| Office Action mailed Jul. 22, 2008 for U.S. Appl. No. 90/010,209, filed Jun. 27, 2008. |
| Office Action mailed Jul. 22, 2008 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Nov. 22, 2006 for U.S. Appl. No. 10/660,996, filed Sep. 12, 2003. |
| Office Action mailed Oct. 22, 2007 for U.S. Appl. No. 11/331,987, filed Jan. 13, 2006. |
| Office Action mailed Sep. 22, 2003 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Sep. 22, 2010 for Canadian Application No. 2510007 filed Dec. 5, 2003. |
| Office Action mailed Apr. 23, 2010 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Feb. 23, 2009 for U.S. Appl. No. 10/943,344, filed Sep. 17, 2004. |
| Office Action mailed Jan. 23, 2008 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Office Action mailed Jan. 23, 2008 for U.S. Appl. No. 11/059,776, filed Feb. 17, 2005. |
| Office Action mailed May 23, 2003 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed May 23, 2005 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Office Action mailed Oct. 23, 2003 for New Zealand Application No. 527857 filed Mar. 4, 2002. |
| Office Action mailed Apr. 24, 2009 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed Apr. 24, 2009 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed Aug. 24, 2010 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Dec. 24, 2004 for New Zealand Application No. 527857 filed Mar. 4, 2002. |
| Office Action mailed Feb. 24, 2004 for U.S. Appl. No. 10/326,642, filed Dec. 18, 2002. |
| Office Action mailed Jan. 24, 2005 for U.S. Appl. No. 10/326,642, filed Dec. 18, 2002. |
| Office Action mailed Jan. 24, 2007 for U.S. Appl. No. 10/660,998, filed Sep. 12, 2003. |
| Office Action mailed Jul. 24, 2007 for Mexican Application No. PAA2003007927 filed Sep. 2, 2003. |
| Office Action mailed Jul. 24, 2007 for U.S. Appl. No. 11/060,135, filed Feb. 17, 2005. |
| Office Action mailed Jul. 24, 2009 for U.S. Appl. No. 11/754,182, filed May 25, 2007. |
| Office Action mailed Jun. 24, 2008 for European Application No. 06800205.4 filed Jul. 27, 2006. |
| Office Action mailed Mar. 24, 2011 for U.S. Appl. No. 11/929,930, filed Oct. 30, 2007. |
| Office Action mailed Nov. 24, 2009 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Sep. 24, 2009 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Aug. 25, 2009 for U.S. Appl. No. 11/754,169, filed May 25, 2007. |
| Office Action mailed Jun. 25, 2009 for U.S. Appl. No. 11/869,449, filed Oct. 9, 2007. |
| Office Action mailed Jun. 25, 2009 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Mar. 25, 2008 for U.S. Appl. No. 11/060,135, filed Feb. 17, 2005. |
| Office Action mailed Aug. 26, 2003 for U.S. Appl. No. 09/891,793, filed Jun. 26, 2001. |
| Office Action mailed Aug. 26, 2010 for Canadian Application No. 2508584 filed Dec. 5, 2003. |
| Office Action mailed Jul. 26, 2004 for U.S. Appl. No. 10/323,438, filed Dec. 18, 2002. |
| Office Action mailed May 26, 2005 for U.S. Appl. No. 10/156,608, filed May 24, 2002. |
| Office Action mailed May 26, 2006 for U.S. Appl. No. 10/660,997, filed Sep. 12, 2003. |
| Office Action mailed Feb. 27, 2003 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Feb. 27, 2007 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Office Action mailed Feb. 27, 2007 for U.S. Appl. No. 10/943,344, filed Sep. 17, 2004. |
| Office Action mailed Jul. 27, 2006 for U.S. Appl. No. 10/728,486, filed Dec. 5, 2003. |
| Office Action mailed Jul. 27, 2009 for Canadian Application No. 2439655 filed Mar. 4, 2002. |
| Office Action mailed Aug. 28, 2006 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Office Action mailed Feb. 28, 2006 for U.S. Appl. No. 10/660,996, filed Sep. 12, 2003. |
| Office Action mailed Jul. 28, 2009 for U.S. Appl. No. 11/754,163, filed May 25, 2007. |
| Office Action mailed Jul. 28, 2010 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed May 28, 2003 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Mar. 29, 2010 for Australian Application No. 2006272776 filed Jul. 21, 2006. |
| Office Action mailed May 29, 2007 for U.S. Appl. No. 11/059,776, filed Feb. 17, 2005. |
| Office Action mailed Oct. 29, 2009 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed Oct. 29, 2009 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed Aug. 30, 2007 for U.S. Appl. No. 10/754,415, filed Jan. 9, 2004. |
| Office Action mailed Jul. 30, 2008 for Australian Application No. 2004248107 filed Apr. 23, 2004. |
| Office Action mailed Jul. 30, 2009 for Japanese Application No. 2002570692 filed Mar. 4, 2002. |
| Office Action mailed Jun. 30, 2004 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Jun. 30, 2010 for U.S. Appl. No. 90/010,210, filed Jun. 27, 2008. |
| Office Action mailed Jun. 30, 2010 for U.S. Appl. No. 90/010,447, filed Apr. 9, 2009. |
| Office Action mailed Jun. 30, 2010 for U.S. Appl. No. 90/010,448, filed Apr. 9, 2009. |
| Office Action mailed May 30, 2006 for U.S. Appl. No. 10/660,996, filed Sep. 12, 2003. |
| Office Action mailed Nov. 30, 2009 for U.S. Appl. No. 10/660,122, filed Sep. 11, 2003. |
| Office Action mailed Sep. 30, 2005 for Chinese Application No. 02809122.1 filed Mar. 4, 2002. |
| Office Action mailed Jan. 31, 2003 for U.S. Appl. No. 09/798,007, filed Mar. 2, 2001. |
| Office Action mailed Jan. 31, 2007 for Philippines Application No. PH12003500824 filed Mar. 4, 2002. |
| O'Guinn M.L., et al., “Field Detection of Eastern Equine Encephalitis Virus in the Amazon BasinRegion of Peru Using Reverse Transcription-Polymerase Chain Reaction Adapted for FieldIdentification of Arthropod-Borne Pathogens,” American Journal of Tropical Medicine and Hygiene, 2004, vol. 70 (2), pp. 164-171. |
| Oizumi N., et al., “Relationship between mutations in the DNA gyrase and topoisomerase IV genes and nadifloxacin resistance in clinically isolated quinolone-resistant Staphylococcus aureus,” Journal of Infection and Chemotherapy, 2001, vol. 7 (3), pp. 191-194. |
| Okada M., et al., “Detection and sequence-based typing of human adenoviruses using sensitiveuniversal primer sets for the hexon gene,” Archives of Virology, 2007, vol. 152 (1), pp. 1-9. |
| Okuma K., et al., “Dissemination of New Methicillin-Resistant Staphylococcus aureus Clones in the Community,” Journal of Clinical Microbiology, 2002, vol. 40 (11), pp. 4289-4294. |
| Oliveira D.C., et al., “Genetic Organization of the Downstream Region of the mecA Element inMethicillin-Resistant Staphylococcus aureus Isolates Carrying Different Polymorphisms of This Region,” Antimicrobial Agents and Chemotherapy, 2000, vol. 44 (7), pp. 1906-1910. |
| Oliveira D.C., et al., “Multiplex PCR Strategy for Rapid Identification of Structural Types and Variants of the mec Element in Methicillin-Resistant Staphylococcus aureus,” Antimicrobial Agents and Chemotherapy, 2002, vol. 46 (7), pp. 2155-2161. |
| Olsen B., et al., “Transhemispheric Exchange of Lyme Disease Spyrochetes by Seabirds,” Journal of Clinical Microbiology, 1995, vol. 33 (12), pp. 3270-3274. |
| Osiowy C., et al., “Direct Detection of Respiratory Syncytial Virus, Parainfluenza Virus, and Adenovirus in Clinical Respiratory Specimens by a Multiplex Reverse Transcription-PCR Assay,” Journal of Clinical Microbiology, 1998, vol. 36 (11), pp. 3149-3154. |
| Ostrander E.A., et al., “Identification and Characterization of Dinucleotide Repeat (CA)n Markers for Genetic Mapping in Dog,” Genomics, 1993, vol. 16 (1), pp. 207-213. |
| Ounissi H., et al., “Gene Homogeneity for Aminoglycoside-Modifying Enzymes in Gram-PositiveCocci,” Antimicrobial Agents and Chemotherapy, 1990, vol. 34 (11), pp. 2164-2168. |
| Palys T., et al., “Discovery and Classification of Ecological Diversity in the Bacterial World: the Role of DNA Sequence Data,” International Journal of Systematic Bacteriology, 1997, vol. 47 (4), pp. 1145-1156. |
| Pan ZQ., et al., “Oligonucleotide-targeted degradation of U1 and U2 snRNAs reveals differential interactions of simian virus 40 pre-mRNAs with snRNPs,” Nucleic Acids Research, 1989, vol. 17 (16), pp. 6553-6568. |
| Pannetier C., et al., “Quantitative Titration of Nucleic Acids by Enzymatic Amplification Reactions run to Saturation,” Nucleic Acids Research, 1993, vol. 21 (3), pp. 577-583. |
| Parson W., et al., “Population Data for 101 Austrian Caucasian Mitochondrial DNA d-Loop Sequences: Application of mtDNA Sequence Analysis to a Forensic Case,” International Journal of Legal Medicine, 1998, vol. 111 (3), pp. 124-132. |
| Partial European Search Report for Application No. EP01106974, mailed on Dec. 16, 2002, 2 pages. |
| Pastorino B., et al., “Development of a TaqMan PCR assay without RNA extraction step for the detection and quantification of African Chikungunya viruses,” Journal of Virological Methods, 2005, vol. 124 (1-2), pp. 65-71. |
| Paterson A.H., et al., “Fine Mapping of Quantitative Trait Loci Using Selected Overlapping RecombinantChromosomes, in an Interspecies Cross of Tomato,” Genetics, 1990, vol. 124 (3), pp. 735-742. |
| Pawa A., et al., “Co-transfer of plasmids in association with conjugative transfer of mupirocin or mupirocin and penicillin resistance in methicillin-resistant Staphylococcus aureus,” Journal of Clinical Microbiology, 2000, vol. 49 (12), pp. 1103-1107. |
| Payne D., et al., “Antimicrobials: The Challenge of Antibiotic Resistant Bacterial Pathogens: The Medical Need, The Market and Prospects for New Antimicrobial Agents,” Current Opinion in Microbiology, 2004, vol. 7, pp. 435-438. |
| Peng X., et al., “Rapid Detection of Shigella Species in Environmental Sewage by an Immunocapture PCR with Universal Primers,” Applied and Environmental Microbiology, 2002, vol. 68 (5), pp. 2580-2583. |
| Perez-Roth E., et al., “Multiplex PCR for Simultaneous Identification of Staphylococcus aureus andDetection of Methicillin and Mupirocin Resistance,” Journal of Clinical Microbiology, 2001, vol. 39 (11), pp. 4037-4041. |
| Peters S.E., et al., “Quantification of the detection of Pneumocystis carinii by DNA amplification,” Molecular and Cellur Probes, 1992, vol. 6 (2), pp. 115-117. |
| Pfeffer M., et al., “Genus-Specific Detection of Alphaviruses by a Semi-Nested ReverseTranscription-Polymerase Chain Reaction,” American Journal of Tropical Medicine and Hygiene, 1997, vol. 57 (6), pp. 709-718. |
| Pfeffer M., et al., “Specific Detection of Chikungunya Virus Using a RT-PCR/Nested PCR Combination,” Journal of Veterinary Medicine B, 2002, vol. 49 (1), pp. 49-54. |
| Pieles U., et al., “Matrix-Assisted Laser Desorption Ionization Time-of-Flight Spectrometry: APowerful Tool for the Mass and Sequence Analysis of Natural and Modified Oligonucleotides, 787 reexamination,” Nucleic Acids Research, 1993, vol. 21 (14), pp. 3191-3196. |
| Pillai S.D., et al., “Rapid molecular detection of microbial pathogens: breakthroughs and challenges,” Archives of Virology, 1997, vol. 13, pp. 67-82. |
| Piper J., et al., “Commercially Available Technique for Rapid Laboratory Detection of MethicillinResistance Among Staphylococcus aureus,” Diagnostic Microbiology and Infectious Disease, 1988, vol. 11 (3), pp. 177-180. |
| Poddar S.K., et al., “Detection of adenovirus using PCR and molecular beacon,” Journal of Virological Methods, 1999, vol. 82 (1), pp. 19-26. |
| Pomerantz S.C., et al., “Determination of oligonucleotide composition from mass spectrometrically measured molecular weight,” Journal of the American Society for Mass Spectrometry, 1993, vol. 4 (3), pp. 204-209. |
| Pring-Akerblom P., et al., “Multiplex Polymerase Chain Reaction for Subgenus-Specific Detection of Human Adenoviruses in Clinical Samples,” Journal of Medical Virology, 1999, vol. 58 (1), pp. 87-92. |
| Pring-Akerblom P., et al., “PCR-based detection and typing of human adenoviruses in clinical samples,” Research in Virology, 1997, vol. 148 (3), pp. 225-231. |
| Promega. T4 Polynucleotide Kinase, Technical Bulletin No. 519, 2002. |
| Puthavathana P., et al., “Molecular characterization of the complete genome of human influenza H5N1 virus Isolates from Thailand,” Journal of General Virology, 2005, vol. 86 (2), pp. 423-433. |
| Qadri S.M., et al., “Rapid Detection of Methicillin-Resistant Staphylococcus aureus by CrystalMRSA ID System,” Journal of Clinical Microbiology, 1994, vol. 32 (7), pp. 1830-1832. |
| Raaum R.L., et al., “Catarrhine Primate Divergence Dates Estimated from Complete Mitochondria Genomes: Concordance with Fossil and Nuclear DNA Evidence,” Journal of Human Evolution, 2005, vol. 48 (3), pp. 237-257. |
| Ramisse V., et al., “Identification and characterization of Bacillus anthracis by multiplex PCR analysis of sequences on plasmids pX01 and pX02 and chromosomal DNA,” Fems Microbiology Letters, 1996, vol. 145 (1), pp. 9-16. |
| Reid S.M., et al., “Primary Diagnosis of Foot-and-Mouth Disease by Reverse Transcription Polymerase Chain Reaction,” Journal of Virological Methods, 2000, vol. 89 (1-2), pp. 167-176. |
| Reilly K., et al., “Design and Use of 16s Ribosomal DNA-Directed Primers in Competitive PCRs to Enumerate Proteolytic Bacteria in the Rumen,” Microbial Ecology, 2002, vol. 43 (2), pp. 259-270. |
| Reischl U., “Application of Molecular Biology-Based Methods to theDiagnosis of Infectious Diseases 1, e72-e77.,” Frontiers in Bioscience, 1996, vol. 1 (1), pp. e72-e77. |
| Reischl U., et al., “Rapid Identification of Methicillin-Resistant Staphylococcus aureus and Simultaneous Species Confirmation Using Real-Time Fluorescence PCR,” Journal of Clinical Microbiology, 2000, vol. 38 (6), pp. 2429-2433. |
| Roberts M.M., et al., “Three-Dimensional Structure of the Adenovirus Major Coat Protein Hexon,” Science, 1986, vol. 232 (4754), pp. 1148-1151. |
| Roberts M.S., et al., “Recombination and Migration Rates in Natural Populations of Bacillus subtilis and Bacillus mojavensis,” Evolution, 1995, vol. 49 (6), pp. 1081-1094. |
| Robinson D.A., et al., “Multilocus sequence typing and the evolution of methicillin-resistant Staphylococcus aureus,” Clinical Microbiology and Infection, 2004, vol. 10, pp. 92-97. |
| Rong S., et al., “Design and Application of 60mer Oligonucleotide Microarray in SARS Coronavirus Detection,” Chinese Science Bulletin, 2003, vol. 48 (12), pp. 1165-1169. |
| Ross P., et al., “High Level Multiplex Genotyping by MALDI-TOF Mass Spectrometry,” Nature Biotechnology, 1998, vol. 16 (13), pp. 1347-1351. |
| Ross P.L., et al., “Analysis of DNA Fragments from Conventional and Microfabricated PCR Devices Using Delayed Extraction MALDI-TOF Mass Spectrometry,” Analytical Chemistry, 1998, vol. 70 (10), pp. 2067-2073. |
| Ross P.L., et al., “Discrimination of Single-Nucleotide Polymorphisms in Human DNA Using Peptide Nucleic Acid Probes Detected by MALDI-TOF Mass Spectrometry,” Analytical Chemistry, 1997, vol. 69 (20), pp. 4197-4202. |
| Rota P.A., et al., “Sequencing of a cDNA clone of the nucleoprotein gene of influenza B/Ann Arbor/1/86,” Nucleic Acids Research, 1989, vol. 17 (9), pp. 3595. |
| Ruan Y., et al., “Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with the putative origins of infection,” The Lancet, 2003, vol. 361, pp. 1779-1785, 1832. |
| Ruest A., et al., “Comparison of the Directigen Flu A+B test, the QuickVue Influenza Test, and Clinical Case Definition to Viral Culture and Reverse Transcription-PCR for Rapid Diagnosis of Influenza Virus Infection,” Journal of Clinical Microbiology, 2003, vol. 41 (8), pp. 3487-3493. |
| Rupf S., et al., “Quantitative determination of Streptococcus mutans by using competitive polymerasechain reaction,” European Journal of Oral Sciences, 1999, vol. 107 (2), pp. 75-81. |
| Russell K.L., et al., “Transmission Dynamics and Prospective Environmental Sampling of Adenovirus in a Military Recruit Setting,” Journal of Infectious Diseases, 2006, vol. 194 (7), pp. 877-885. |
| Sabat A., et al., “Comparison of PCR-Based Methods for Typing Staphylococcus aureus Isolates” Journal of Clinical Microbiology, 2006, vol. 44 (10), pp. 3804-3807. |
| Sackesen C., et al., “Use of polymerase chain reaction for detection of adenovirus in children withor without wheezing,” Turkish Journal of Pediatrics, 2005, vol. 47 (3), pp. 227-231. |
| Sakai H., et al., “Simultaneous Detection of Staphylococcus aureus and Coagulase-Negative Staphylococci in Positive Blood Cultures by Real-Time PCR with Two Fluorescence Resonance Energy Transfer Probe Sets,” Journal of Clinical Microbiology, 2004, vol. 42 (12), pp. 5739-5744. |
| Sala M., et al., “Ambiguous Base Pairing of the Purine Analogue 1-(2-Deoxy-B-D-Ribofuranosyl)-Imidazole-4-Carboxamide During PCR,” Nucleic Acids Research, 1996, vol. 24 (17), pp. 3302-3306. |
| Sambrook J., et al., “Molecular Cloning-A Laboratory Manual,” 1989, Cold Spring Harbor Laboratory Press, Table of Contents. |
| Sampath R., et al., “Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,” Plos ONE, 2007, vol. 2 (5), pp. e489. |
| Sampath R., et al., “Rapid Identification of Emerging Infectious Agents using PCR and Electrospray Ionization Mass Spectrometry,” Annals of the New York Academy of Science, 2007, vol. 1102, pp. 109-120. |
| Sampath R., et al., “Rapid Identification of Emerging Pathogens: Coronavirus,” Emerging Infectious Diseases, 2005, vol. 11 (3), pp. 373-379. |
| Sanchez A., et al., “Detection and molecularcharacterization of Ebola viruses causing disease in human and nonhuman primates,” Journal of Infectious Diseases, 1999, vol. 179 (1), pp. S164-S169. |
| Sanchez J.L., et al., “Epidemic of Adenovirus-Induced Respiratory Illness Among US Military Recruits: Epidemiologic and Immunologic Risk Factors in Healthy, Young adults,” Journal of Medical Virology, 2001, vol. 65 (4), pp. 710-718. |
| Sanchez-Seco M.P., et al., “A Generic Nested-RT-PCR followed by Sequencing for Detection and Identification of Members of the Alphavirus Genus,” Journal of Virological Methods, 2001, vol. 95 (1-2), pp. 153-161. |
| Santos S.R., et al., “Identification and phylogenetic sorting of bacterial lineages with universally conserved genes and proteins,” Environmental Microbiology, 2004, vol. 6 (7), pp. 754-759. |
| Sarantis H., et al., “Comprehensive Detection and Serotyping of Human Adenoviruses by PCR and Sequencing,” Journal of Clinical Microbiology, 2004, vol. 42 (9), pp. 3963-3969. |
| Sauer S., et al., “A Novel Procedure for Efficient Genotyping of Single Nucleotide Polymorphisms,” Nucleic Acids Research, 2000, vol. 28 (5), pp. E13.1-E13.8. |
| Scaramozzino N., et al., “Comparison of Flavivirus universal Primer Pairs and Development of a Rapid, Highly Sensitive Heminested Reverse Transcription-PCR Assay for Detection of Flaviviruses Targeted to a Conserved Region of the NS5 Gene Sequences,” Journal of Clinical Microbiology, 2001, vol. 39 (5), pp. 1922-1927. |
| Schabereiter-Gurtner C., et al., “Application of Broad-Range 16s rRNA PCR Amplification and DGGE Fingerprinting for Detection of Tick-Infecting Bacteria,” The Journal of Microbiological Methods, 2003, vol. 52 (2), pp. 251-260. |
| Scheffner M., et al., “The E6 Oncoprotein Encoded by Human Papillomavirus Types 16 and 18 Promotes the Degradation of p53,” Cell, 1990, vol. 63 (6), pp. 1129-1136. |
| Schena M., et al., “Genome Analysis with Gene Expression Microarrays,” Bioessays, 1996, vol. 18 (5), pp. 427-431. |
| Scheuermann R.N., et al., “Polymerase chain-reaction-based mRNA quantification Using an internal standard: analysis of oncogene expression,” Methods in Enzymology, 1993, vol. 218, pp. 446-473. |
| Schlecht N. F., et al., “Viral Load as a Predictor of the Risk of Cervical Intraepithelial Neoplasia,” British Journal of Cancer, 2003, vol. 103 (4), pp. 519-524. |
| Schmidt T.M., et al., “Analysis of a marine pikoplankton community by 16s rRNA gene cloning and sequencing,” Journal of Bacteriology, 1991, vol. 173 (14), pp. 4371-4378. |
| Schmitz F.J., et al., “Development of a Multiplex-PCR for Direct Detection of the Genes for Enterotoxin B and C, and Toxic Shock Syndrome Toxin-1 in Staphylococcus aureus Isolates,” Journal of Medical Microbiology, 1998, vol. 47 (4), pp. 335-340. |
| Schmitz F.J., et al., “Development of Resistance to Ciprofloxacin, Rifampin, and Mupirocin inMethicillin-Susceptible and -Resistant Staphylococcus aureus Isolates,” Antimicrobial Agents and Chemotherapy, 2000, vol. 44 (11), pp. 3229-3231. |
| Schmitz F.J., et al., “Specific information concerning taxonomy, pathogenicity and methicillin esistance of Staphylococci obtained by a multiplex PCR,” Journal of Medical Microbiology, 1997, vol. 46 (9), pp. 773-778. |
| Schram K.H., et al., “Mass Spectrometry of Nucleic Acid Components,” Methods of Biochemical Analysis, 1990, vol. 34, pp. 203-280. |
| Schultz J.C., et al., “Polymerise Chain Reaction Products Analyzed by Charge Detection Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1999, vol. 13 (1), pp. 15-20. |
| Schwartz M., et al., “Prenatal Diagnosis of Alpha-1-Antitrypsin Deficiency Using Polymerase Chainreaction (PCR). Comparison of Conventional RFLP Methods with PCR used in Combination with Allelespecific Oligonucleotides or RFLP Analysis,” Clinical Genetics, 1989, vol. 36 (6), pp. 419-426. |
| Schweiger B., et al., “Application of a Fluorogenic PCR Assay for Typing and Subtyping of Influenza Viruses in Respiratory Samples,” Journal of Clinical Microbiology, 2000, vol. 38 (4), pp. 1552-1558. |
| Sciacchitano C.J., “Analysis of Polymerase Chain Reaction-Amplified DNA Fragments of Clostridium botulinum Type E Neurotoxin Gene by High Performance Capillary Electrophoresis,” Journal of Liquid Chromatography & Related Technologies, 1996, vol. 19 (13), pp. 2165-2178. |
| Scott-Taylor T.H., et al., “Conserved Sequences of the Adenovirus Genome for Detection of all Human Adenovirus Types by Hybridization,” Journal of Clinical Microbiology, 1992, vol. 30 (7), pp. 1703-1710. |
| Seifarth W., et al., “Rapid identification of all known retroviral reverse transcriptase sequences with a novel versatile detection assay,” AIDS Research and Human Retroviruses, 2000, vol. 16 (8), pp. 721-729. |
| Sellner L., et al., “A Single-Tube Nested RT-PCR for the Detection of Ross River Virus,” Methods in Molecular Biology, 1998, vol. 92, pp. 145-152. |
| Sellner L.N., et al., “Sensitive detection of Ross River virus—a one-tube nested RT-PCR,” Journal of Virological Methods, 1994, vol. 49 (1), pp. 47-58. |
| Senko M.W., et al., “Determination of Monoisotopic Masses and Ion Populations for Large Biomoleculesfrom Resolved Isotopic Distributions,” Journal of the American Society for Mass Spectrometry, 1995, vol. 6, pp. 229-233. |
| Seshadri R., et al., “Differential Expression of Translational Elements by Life Cycle Variants of Coxiella burnetii,” Infection and Immunity, 1999, vol. 67 (11), pp. 6026-6033. |
| Shadan F.F., et al., “n-Butyrate, a Cell Cycle Blocker, Inhibits the Replication of Polyomaviruses and Papillomaviruses but Not That of Adenoviruses and Herpesviruses,” Journal of Virology, 1994, vol. 68 (8), pp. 4785-4796. |
| Shaver Y.J., et al., “Restriction Fragment Length Polymorphism of rRNA Operons for Discrimination and Intergenic Spacer Sequences for Cataloging of Bacilus subtilis Sub-Groups,” Journal of Microbiological Methods, 2002, vol. 50 (2), pp. 215-223. |
| Shaver Y.J., et al., “Variation in 16s-23s rRNA Intergenic Spacer Regions Among Bacilus subtilis 168 Isolates,” Molecular Microbiology, 2001, vol. 42 (1), pp. 101-109. |
| Shimaoka M., et al., “Detection of the gene for toxic shock syndrome toxin 1 in Siaphylococcusaureus by enzyme-labelled oligonucleotideprobes,” Journal of Medical Microbiology, 1996, vol. 44 (3), pp. 215-218. |
| Shimaoka M., et al., “Development of Enzyme-Labeled Oligonucleotide Probe for Detection of mecA gene in Methicillin-Resistant Staphylococcus aureus,” Journal of Clinical Microbiology, 1994, vol. 32 (8), pp. 1866-1869. |
| Shrestha N. K., et al., “Rapid Identification of Staphylococcus aureus and the mecA Gene from BacT/ALERT Blood Culture Bottles by Using the Lightcycler System,” Journal of Clinical Microbiology, 2002, vol. 40 (7), pp. 2659-2661. |
| Simonsen L., et al., “The Impact of Influenza Epidemics on Hospitalizations,” Journal of Infectious Diseases, 2000, vol. 181 (3), pp. 831-837. |
| Skov R.L., et al., “Evaluation of a new 3-h hybridization method for detecting the mecA gene in Staphylococcus aureus and comparison with existing genotypic and phenotypic susceptibility testing methods,” Journal of Antimicrobial Chemotherapy, 1999, vol. 43 (4), pp. 467-475. |
| Smirnov I.P., et al., “Application of DNA-binding polymers for preparation of DNA for analysis by matrix-assisted laser desorption/ionization mass spectrometry,” Rapid Communications in Mass Spectrometry, 2001, vol. 15 (16), pp. 1427-1432. |
| Smith T.F., “Comparison of Biosequences,” Advances in Applied Mathematics, 1981, vol. 2, pp. 482-489. |
| Song F., et al., “Identification of cry11-type Genes from Bacilus thuringiensis Strains and Characterization of a Novel Cry11-Type Gene,” Applied and Environmental Microbiology, 2003, vol. 69, pp. 5207-5211. |
| Spackman E., et al., “Development of a real-time reverse transcriptase PCR assay for type A influenzavirus and the avian H5 and H7 hemagglutinin subtypes,” Journal of Clinical Microbiology, 2002, vol. 40 (9), pp. 3256-3260. |
| Spiess L., et al., “Trehalose is a potent PCR enhancer: Lowering of DNA melting temperature and thermal stabilization of Taq polymerase by the disaccharide trehalose,” Clinical Chemistry, 2004, vol. 50 (7), pp. 1256-1259. |
| Srinivasan J.R., et al., “Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry as a Rapid Screening Method to Detect Mutations Causing Tay-Sachs Disease,” Rapid Communications in Mass Spectrometry, 1997, vol. 11 (10), pp. 1144-1150. |
| Steffens D.L., et al., “Sequence Analysis of Mitochondrial DNA Hypervariable Regions Using Infrared Fluorescence Detection,” BioTechniques, 1998, vol. 24 (6), pp. 1044-1046. |
| Stephensen C.B., et al., “Phylogenetic analysis of a highly conserved region of the poymerase gene from 11 coronaviruses and development of a consensus poymerase chain reaction assay,” Virus Research, 1999, vol. 60 (2), pp. 181-189. |
| Stone B., et al., “Rapid detection and simultaneous subtype differentiation of influenza A viruses by real time PCR,” Journal of Virological Methods, 2004, vol. 117 (2), pp. 103-112. |
| Stoneking M., et al., “Population Variation of Human mtDNA Control Region Sequences Detected by Enzymatic Amplification and Sequence-Specific Oligonucleotide Probes,” American Journal of Human Genetics, 1991, vol. 48 (2), pp. 370-382. |
| Stratagene Catalog, Gene Characterization Kits, 1988, pp. 39. |
| Strommenger B., et al., “Multiplex PCR Assay for Simultaneous Detection of Nine Clinically Relevant Antibiotic Resistance Genes in Staphylococcus aureus,” Journal of Clinical Microbiology, 2003, vol. 41 (9), pp. 4089-4094. |
| Studdert M.J., et al., “Polymerase Chain Reaction Tests for the Identification of Ross River, Kunjinand Murray Valley Encephalitis Virus Infections in Horses,” Australian Veterinary Journal, 2003, vol. 81 (1-2), pp. 76-80. |
| Stuhlmeier R., et al., “Fast, Simultaneous, and Sensitive Detection of Staphylococci,” Journal of Clinical Pathology, 2003, vol. 56 (10), pp. 782-785. |
| Sumner J.W., et al., “PCR Amplification and Comparison of Nucleotide Sequences from the groESL Heat Shock Operon of Ehrlichia Species,” Journal of Critical Microbiology, 1997, vol. 35 (8), pp. 2087-2092. |
| Sundsfjord A., et al., “Genetic Methods for Detection of Antimicrobial Resistance,” APMIS : Acta Pathologica, Microbiologica, et Immunologica Scandinavica, 2004, vol. 112 (11-12), pp. 815-837. |
| Supplementary European Search Report for Application No. 04775904.8, mailed on Jul. 7, 2008, 8 pages. |
| Supplementary European Search Report for Application No. EP02709785.6, mailed Sep. 1, 2005, 5 pages. |
| Supplementary European Search Report for Application No. EP03796752.8, mailed on Aug. 7, 2007, 3 pages. |
| Supplementary European Search Report for Application No. EP03810055.8, mailed on Jun. 8, 2007, 4 pages. |
| Supplementary European Search Report for Application No. EP03814656, mailed on Oct. 16, 2007, 2 pages. |
| Supplementary European Search Report for Application No. EP04752257.8, mailed on Feb. 15, 2006, 2 pages. |
| Supplementary European Search Report for Application No. EP05753037, mailed on Aug. 21, 2009, 2 pages. |
| Supplementary Partial European Search Report for Application No. EP05751872.2, mailed on Jan. 28, 2008, 8 pages. |
| Supplementary Partial European Search Report for Application No. EP05856582.1, mailed on Oct. 27, 2008, 10 pages. |
| Swaminathan B., et al., “PulseNet: The Molecular Subtyping Network for Foodborne Bacterial Disease Surveillance, United States,” Emerging Infectious Diseases, 2001, vol. 7 (3), pp. 382-389. |
| Swanborg R.H., et al., “Human Herpesvirus 6 and Chlamydia pneumoniae as Etiologic Agents in Multiplesclerosis—a Critical Review,” Microbes and Infection / Institut Pasteur, 2002, vol. 4 (13), pp. 1327-1333. |
| Swenson J.M., et al., “Performance of Eight Methods, Including Two New Rapid Methods, for Detection of Oxacillin Resistance in a Challenge Set of Staphylococcus aureus Organisms,” Journal of Clinical Microbiology, 2001, vol. 39 (10), pp. 3785-3788. |
| Takagaki Y., et al., “Four Factors are Required for 3′-End Cleavage of Pre-mRNAs,” Genes and Development, 1989, vol. 3 (11), pp. 1711-1724. |
| Takahashi H., et al., “Characterization of gryA, gryB, grIA and grIB mutations in fluoroquinolone-resistant clinical isolates of Staphylococcus aureus,” The Journal of Antimicrobial Chemotherapy, 1998, vol. 41 (1), pp. 49-57. |
| Takahata M., et al., “Mutations in the GyrA and Gr1A Genes of Quinolone-Resistant Clinical Isolates of Methicillin-Resistant Staphylococcus aureus,” The Journal of Antimicrobial Chemotherapy, 1996, vol. 38 (3), pp. 543-546. |
| Takayama R., et al., “Quantification of Adenovirus Species B and C Viremia by Real-Time PCR in Adults and Children Undergoing Stem Cell Transplantation,” Journal of Medical Virology, 2007, vol. 79 (3), pp. 278-284. |
| Takeuchi S., et al., “Serotyping of Adenoviruses on Conjunctival Scrapings by PCR and Sequence Analysis,” Journal of Clinical Microbiology, 1999, vol. 37 (6), pp. 1839-1845. |
| Talaat A.M., et al., “Genome-Directed Primers for Selective Labeling of Bacterial Transcripts for DNA Microarray Analysis,” Nature Biotechnology, 2000, vol. 17, pp. 679-682. |
| Tan T.Y., “Use of Molecular Techniques for the Detection of Antibiotic Resistance in Bacteria,” Expert review of Molecular diagnostics, 2003, vol. 3 (1), pp. 93-103. |
| Tanabe F., et al., “The Properties and Mec A Gene of the Methicillin-Resistant Staphylococcus aureus Isolated in Fukushima Medical College Hospital,” Fukushima Journal of Medical Science, 1993, vol. 39 (1), pp. 35-42. |
| Tang K., et al., “Detection of 500-Nucleotide DNA by Laser Desorption Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1994, vol. 8 (9), pp. 727-730. |
| Tang K., et al., Double-Stranded DNA Analysis by Matrix Assisted Laser Desorption/Ionization, 42nd ASMS Conference on Mass Spectrometry, 1994. |
| Tang K., et al., “Matrix-Assisted Laser Desorption/Ionization of Restriction Enzyme-Digested DNA,” Rapid Communications in Mass Spectrometry, 1994, vol. 8 (2), pp. 183-186. |
| Tang K., et al., “Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Oligonucleotides,” Dissertation submitted to the Faculty of Vanderbilt University, 1994. |
| Tarassishin L., et al., “Adenovirus Core Protein VII Displays a Linear Epitope Conserved in a Range of Human Adenoviruses,” Journal of General Virology, 1999, vol. 80 (Pt 1), pp. 47-50. |
| Tarassishin L., et al., “An Epitope on the Adenovirus Fibre Tail is Common to all Human Subgroups,” Archives of Virology, 2000, vol. 145 (4), pp. 805-811. |
| Tatuch Y., et al., “Heteroplasmic mtDNA Mutation (T-G) at 8993 Can Cause Leigh Disease When the Percentage of Abnormal mtDNA is High,” The American Journal of Human Genetics, 1992, vol. 50 (4), pp. 852-858. |
| Taubenberger J.K., et al., “Characterization of the 1918 Influenza Virus Polymerase Genes,” Nature, 2005, vol. 437 (7060), pp. 889-893. |
| Taylor L.H., et al., “Risk Factors for Human Disease Emergence,” Philosophical Transactions of the Royal Society of London Series B, Biological Sciences, 2001, vol. 356 (1411), pp. 983-989. |
| Tenover F.C., et al., “Characterization of a Strain of Community-Associated Methicillin-ResistantSlaphylococcus aureus Widely Disseminated in the United States,” Journal of Clinical Microbiology, 2006, vol. 44 (1), pp. 108-118. |
| Teramura T., et al., “Quantitative Detection of Serum Adenovirus in a Transplant Recipient,” Lancet, 2002, vol. 359 (9321), pp. 1945. |
| Thiel V., et al., “Infectious RNA Transcribed in Vitro from a cDNA Copy of the Human Coronavirus Genome Cloned in Vaccinia Virus,” The Journal of General Virology, 2001, vol. 82 (Pt 6), pp. 1273-1281. |
| Thompson J.D., et al., “Clustal W: Improving the Sensitivity of Progressive Multiple Sequence Alignmen Through Sequence Weighting, Position-Specific Gap Penalties and Weight Matrix Choice,” Nucleic Acids Research, 1994, vol. 22 (22), pp. 4673-4680. |
| Thompson W.W., et al., “Influenza-Associated Hospitalizations in the United States,” The Journal of the American Medical Association, 2004, vol. 292 (11), pp. 1333-1340. |
| Tokue Y., et al., “Comparison of a Polymerase Chain Reaction Assay and a Conventional Microbiologic Method for Detection of Methicillin-Resistant Slaphylococcus aureus,” Antimicrobial Agents and Chemotherapy, 1992, vol. 36 (1), pp. 6-9. |
| Tong J., et al., “Ligation Reaction Specificities of an NAD+-Dependent DNA Ligase from the Hyperthermophile Aquifex aeolicus,” Nucleic Acids Research, 2000, vol. 28 (6), pp. 1447-1454. |
| Top FH Jr., “Control of Adenovirus Acute Respiratory Disease in U.S. Army Trainees,” The Yale Journal of Biology and Medicine, 1975, vol. 48 (3), pp. 185-195. |
| Torroni A., et al., “Classification of European mtDNAs from an Analysis of Three European Populations,” Genetics, 1996, vol. 144 (4), pp. 1835-1850. |
| Towner K.J., et al., “Development and Evaluation of a PCR-Based Immunoassay for the Rapid Detection of Methicillin-Resistant Staphylococcus aureus,” Journal of Medical Microbiology, 1998, vol. 47 (7), pp. 607-613. |
| Tsuneyoshi, et al., “Mass Spectrometric Gene Diagnosis of One-Base Substitution from Polymerase Chain Reaction Amplified Human DNA,” Rapid Communications in Mass Spectomerty, 1997, vol. 11 (7), pp. 719-722. |
| Tsunoda T., et al., “Time and Memory Efficient Algorithm for Extracting Palindromic and RepetitiveSubsequences in Nucleic Acid Sequences,” Pacific Symposium on Biocomputing, 1999, vol. 4, pp. 202-213. |
| Udo E.E., et al., “A Chromosomal Location of the MupA Gene in Staphylococcus aureus Expressing High-Level Mupirocin Resistance,” The Journal of Antimicrobial Chemotherapy, 2003, vol. 51 (5), pp. 1283-1286. |
| Udo E.E., et al., “Genetic Analysis of Methicillin-Resistant Staphylococcus aureus Expressing High-and Low-Level Mupirocin Resistance,” Journal of Medical Microbiology, 2001, vol. 50 (10), pp. 909-915. |
| Udo E.E., et al., “Rapid Detection of Methicillin Resistance in Staphylococci Using a Slide Latex Agglutination Kit,” International Journal of Antimicrobial Agents, 2000, vol. 15 (1), pp. 19-24. |
| Unal S., et al., “Detection of Methicillin-Resistant Staphylococci by Using the Polymerase Chain Reaction,” Journal of Clinical Microbiology, 1992, vol. 30 (7), pp. 1685-1691. |
| Upton A., et al., “Mupirocin and Staphylococcus aureus: A Recent Paradigm of Emerging Antibiotic Resistance,” The Journal of Antimicrobial Chemotherapy, 2003, vol. 51 (3), pp. 613-617. |
| Vabret A., et al., “Development of a PCR-and Hybridization-Based Assay (PCR Adenovirus Consensus) for the Detection and the Species Identification of Adenoviruses in Respiratory Specimens,” Journal of Clinical Virology, 2004, vol. 31 (2), pp. 116-122. |
| Van Aerschot A., et al., “In Search of Acyclic Analogues as Universal Nucleosides in Degenerate Probes,” Nucleosides and Nucleotides, 1995, vol. 14 (3-5), pp. 1053-1056. |
| Van Baar B.L., “Characterisation of Bacteria by Matrix-Assisted Laser Desorption/Ionisation and Electrospray Mass Spectrometry,” FEMS Microbiology Reviews, 2000, vol. 24 (2), pp. 193-219. |
| Van Camp G., et al., “Amplification and Sequencing of Variable Regions in Bacterial 23s Ribosomal RNA Genes with Conserved Primer Sequences,” Current Microbiology, 1993, vol. 27 (3), pp. 147-151. |
| Van Der Zee H., et al., “Rapid and Alternative Screening Methods for Microbiological Analysis,” Journal of AOAC International, 1997, vol. 80 (4), pp. 934-940. |
| Van Dinten L.C., et al., “Proteolytic Processing of the Open Reading Frame Ib-EncodedPart of Arterivirus Replicase Is Mediated by nsp4 Serine Protease and is Essential for Virus Replication,” Journal of Virology, 1999, vol. 73 (3), pp. 2027-2037. |
| Van Elden L.J., et al., “Clinical Diagnosis of Influenza Virus Infection: Evaluation of Diagnostic Tools in General Practice,” The British Journal of General Practice, 2001, vol. 51 (469), pp. 630-634. |
| Van Elden L.J., et al., “Simultaneous Detection of Influenza Viruses A and B Using Real-Time Quantitative PCR,” Journal of Clinical Microbiology, 2001, vol. 39 (1), pp. 196-200. |
| Van Ert M.N., et al., “Mass Spectrometry Provides Accurate Characterization of Two Genetic Marker Types in Bacillus anthracis,” Bio Techniques, 2004, vol. 37 (4), pp. 642-651. |
| Van Leeuwen W.B., et al., “Multilocus Sequence Typing of Staphylococcus aureus with DNA Array Technology,” Journal of Clinical Microbiology, 2003, vol. 41 (7), pp. 3323-3326. |
| Van Leeuwen W.B., et al., “Rapid Detection of Methicillin-Resistance in Staphylococcus aureus Isolates by the MRSA-Screen Latex Agglutination Test,” Journal of Clinical Microbiology, 1999, vol. 37 (9), pp. 3029-3030. |
| Vanchiere J.A., et al., “Detection of BK Virus and Simian Virus 40 in the Urine of Healthy Children,” Journal of Medical Virology, 2005, vol. 75 (3), pp. 447-454. |
| Vanderhallen H., et al. “Identification of Encephalomyocarditis Virus in Clinical Samples by ReverseTranscription-PCR Followed by Genetic Typing Using Sequence Analysis,” Journal of Clinical Microbiology, 1998, vol. 36 (12), pp. 3463-3467. |
| Vannuffel P., et al., “Rapid and Specific Molecular Identification of Methicillin-Resistant Staphylococcus aureus in Endotracheal Aspirates from Mechanically Ventilated Patients,” Journal of Clinical Microbiology, 1998, vol. 36 (8), pp. 2366-2368. |
| Vannuffel P., et al., “Specific Detection of Methicillin-Resistant Staphylococcus Species by Multiplex PCR,” Journal of Clinical Microbiology, 1995, vol. 33 (11), pp. 2864-2867. |
| Verma S., et al., “Modified Oligonucleotides: Synthesis and Strategy for Users,” Annual Review of Biochemistry, 1998, pp. 99-134. |
| Videla C., et al., “Genomic Analysis of Adenovirus Isolated from Argentinian Children with Acute Lower Respiratory Infections,” Journal of Clinical Virology, 1999, vol. 14 (1), pp. 67-71. |
| Vilchez R.A. et al., “Detection of Polyomavirus Simian Virus 40 Tumor Antigen DNA in AIDS-Related Systemic Non-Hodgkin Lymphoma,” Journal of Acquired Immune Deficiencysyndromes, 2002, vol. 29 (2), pp. 109-116. |
| Voelter C., et al., “Screening Human Tumor Samples with a Broad-Spectrum Polymerase Chain Reaction Method for the Detection of Polyomaviruses,” Virology, 1997, vol. 237 (2), pp. 389-396. |
| Volokhov D., et al., “Microarray Analysis of Erythromycin Resistance Determinants,” Journal of Applied Microbiology, 2003, vol. 95 (4), pp. 787-798. |
| Von Eiff C., et al., “Pathogenesis of Infections Due to Coagulase-Negative Staphylococci,” The Lancet Infectious Diseases, 2002, vol. 2 (11), pp. 677-685. |
| Von Wintzingerode F., et al., “Base-Specific Fragmentation of Amplified 16S rRNA Genes Analyzed by Mass Spectrometry: A Tool for Rapid Bacterial Identification,” Proceedings of the National Academy of Sciences, 2002, vol. 99 (10), pp. 7039-7044. |
| Walker E.S., et al., “A Decline in Mupirocin Resistance in Methicillin-Resistant Staphylococcus aureus Accompanied Administrative Control of Prescriptions,” Journal of Clinical Microbiology, 2004, vol. 42 (6), pp. 2792-2795. |
| Wallace S.S., et al., “The Enigma of Endonuclease VIII,” DNA Repair, 2003, vol. 2 (5), pp. 441-453. |
| Wallet F., et al., “Choice of a Routine Method for Detecting Methicillin-Resistance in Staphylococci,” The Journal of Antimicrobial Chemotherapy, 1996, vol. 37 (5), pp. 901-909. |
| Walters J.J., et al., “Genotyping Single Nucleotide Polymorphisms Using Intact Polymerase Chain Reaction Products by Electrospray Quadrupole Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 2001, vol. 15 (18), pp. 1752-1759. |
| Wang G., et al., “Targeted Mutagenesis in Mammalian Cells Mediated by Intracellular Triple Helix Formation,” Molecular and Cellular Biology, 1995, vol. 15 (3), pp. 1759-1768. |
| Ward C.L., et al., “Design and Performance Testing of Quantitative Real Time PCR Assays for Influenza A and B Viral Load Measurement,” Journal of Clinical Virology, 2004, vol. 29 (3), pp. 179-188. |
| Watanabe K., et al., “ICB Database: the gyrB Database for Identification and Classification of Bacteria,” Nucleic Acids Research, 2001, vol. 29 (1), pp. 344-345. |
| Weissenbacher M., et al., “Etiologic and Clinical Evaluation of Acute Lower Respiratory TractInfections in Young Argentinean Children: An Overview,” Reviews of Infectious Diseases, 1990, vol. 12 (Suppl 8), pp. S889-S898. |
| Welham K.J., et al., “The Characterization of Micro-Organisms by Matrix-Assisted Laser Desorption/Lonization Time-of-Flight Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1998, vol. 12 (4), pp. 176-180. |
| Wertheim H.F., et al., “Effect of Mupirocin Treatment on Nasal, Pharyngeal, and Perineal Carriage of Staphylococcus aureus in Healthy Adults,” Antimicrobial Agents and Chemotherapy, 2005, vol. 49 (4), pp. 1465-1467. |
| Westermann P., et al., “Inhibition of Expression of SV40 Virus Large T-Antigen by Antisense Oligodeoxyribonucleotides,” Biomedica Biochimica Acta, 1989, vol. 1, pp. 85-93. |
| Whiley D.M., et al., “Simultaneous Detection and Differentiation of Human Polyomaviruses JC and BK by a Rapid and Sensitive PCR-ELAHA Assay and a Survey of the JCV Subtypes within an Australian Population,” Journal of Medical Virology, 2004, vol. 72 (3), pp. 467-472. |
| Wichelhaus T.A., et al., “Rapid Detection of Epidemic Strains of Methicillin-Resistant Staphylococcus aureus,” Journal of Clinical Microbiology, 1999, vol. 37 (3), pp. 690-693. |
| Wickham T.J., “Targeting Adenovirus,” Gene Therapy, 2000, vol. 7 (2), pp. 110-114. |
| Widjojoatmodjo M.N., et al., “Rapid Identification of Bacterial by PCR-Single-Strand Conformation Polymorphism,” Journal of Clinical Microbiology, 1994, vol. 32 (12), pp. 3002-3007. |
| Widjojoatmodjo M.N., et al., “The Magnetic Immuno Polymerase Chain Reaction Assay for Direct Detection of Salmonellae in Fecal Samples,” Journal of Clinical Microbiology, 1992, vol. 30 (12), pp. 3195-3199. |
| Winger B.E., et al., “High Resolution Accurate Mass Measurements of Biomolecules using a new Electrospray Ionization Ion Cyclotron Resonance Mass Spectrometer,” Journal American Society for Mass Spectrometry, 1993, vol. 4 (7), pp. 566-577. |
| Wolter A., et al., “Negative ion FAB mass Spectrometric Analysis of non-Charged key Intermediates in Oligonucleotide Synthesis: Rapid Identification of Partially Protected Dinucleoside Monophosphates,” Biomedical and Environmental Mass Spectrometry, 1987, vol. 14, pp. 111-116. |
| Woo T.H., et al., “Identification of Leptospira inadai by Continuous Monitoring of Fluorescence during Rapid Cycle PCR,” Systematic and Applied Microbiology, 1998, vol. 21 (1), pp. 89-96. |
| Wood S.R., et al., “Rapid Detection and Serotyping of Adenovirus by Direct Immunofluorescence,” Journal of Medical Virology, 1997, vol. 51 (3), pp. 198-201. |
| Wright K.E., et al., “Typing and Subtyping of Influenza Viruses in Clinical Samples by PCR,” Journal of Clinical Microbiology, 1995, vol. 33 (5), pp. 1180-1184. |
| Written Opinion for Application No. PCT/US2004/33742, mailed on May 15, 2006, 5 pages. |
| Wu S., et al., “Genetic Organization of the mecA Region in Methicillin-Susceptible and Methicillin-Resistant Strains of Staphylococcus sciuri,” The Journal of Bacteriology, 1998, vol. 180 (2), pp. 236-242. |
| Wu X., et al., “Establishment of a Fluorescent Polymerase Chain Reaction Method for the Detection of SARS-Associated Coronavhus and its Clinical Application,” Chinese Medical Journal, 2003, vol. 116 (7), pp. 988-990. |
| Wunschel D., et al., “Discrimination Among the B. cereus Group, in Comparison to B. subtilis, by Structural Carbohydrate Profiles and Ribosomal RNA Spacer Region PCR,” Systematic and Applied Microbiology, 1994, vol. 17, pp. 625-635. |
| Wunschel D.S., et al., “Analysis of Double-Stranded Polymerase Chain Reaction Products from the Bacilus cereus Group by Electrospray Lonization Fourier Transform Lon Cyclotron Resonance Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 1996, vol. 10 (1), pp. 29-35. |
| Wunschel, D.S., et al., “Heterogeneity in Bacillus cereus PCR Products Detected by ESI-FTICR Mass Spectrometry,” Analytical Chemistry, 1998, vol. 70 (6), pp. 1203-1207. |
| Wunschel D.S., et al., “Mass spectrometric characterization of DNA for molecular biological applications: advances using MALDI and ESI,” Advances in Mass Spectrometry, 1998, vol. 14, Elsevier, pp. 377-406. |
| Xu L., et al., “Electrophore Mass Tag Dideoxy DNA Sequencing,” Analytical Chemistry, 1997, vol. 69 (17), pp. 3595-3602. |
| Xu W., et al., “Species-Specific Identification of Human Adenoviruses by a Multiplex PCR Assay,” Journal of Clinical Microbiology, 2000, vol. 38 (11), pp. 4114-4120. |
| Xu W., et al., “Type-Specific Identification of Human Adenovirus, 3, 7, and 21 by a Multiplex PCR Assay,” Journal of Medical Virology, 2001, vol. 64 (4), pp. 537-542. |
| Xu X., et al., “Intercontinental Circulation of Human Influenza A(H1N2) Reassortant Viruses During the 2001-2002 Influenza Season,” The Journal of Infectious Diseases, 2002, vol. 186 (10), pp. 1490-1493. |
| Yao Z.P., et al., “Mass Spectrometry Based Proteolytic Mapping for Rapid Virus Identification,” Analytical Chemistry, 2002, vol. 74 (11), pp. 2529-2534. |
| Yasui T., et al., “A Specific Oligonucleotide Primer for the Rapid Detection of Lactobacillus lindneri by Polymerase Chain Reaction,” Canadian Journal of Microbiology, 1997, vol. 43 (2), pp. 157-163. |
| Ye K., et al., “Three Distinct Promoters Direct Transcription of Different 5′ Untranslated Regions of the Human Interleukin 1 Type 1 Receptor. A Possible Mechanism for Control of Translation,” Cytokine, 1996, vol. 8 (6), pp. 421-429. |
| Yun H.J., et al., “Increased Antibacterial Activity of OW286, A Novel Fluoronaphthyridone Antibiotic, Against Staphylococcus aureus Strains with Defined Mutations in DNA Gyrase and Toposiomerase IV,” International Journal of Antimicrobial Agents, 2005, vol. 25 (4), pp. 334-337. |
| Zeng Z.B., “Precision Mapping of Quantitative Trait Loci,” Genetics, 1994, vol. 136 (4), pp. 1457-1468. |
| Zhang J., et al., “PowerBLAST: A New Network BLAST Application for Interactive or Automated Sequence Analysis and Annotation,” Genome Research, 1997, vol. 7 (6), pp. 649-656. |
| Zhang K., et al., “New Quadriplex PCR Assay for Detection of Methicillin and Mupirocin Resistance and Simultaneous Discrimination of Staphylococcus Aureus from Coagulase-Negative Staphylococci,” Journal of Clinical Microbiology, 2004, vol. 42 (11), pp. 4947-4955. |
| Zhang W.D., et al., “Detection and Identification of Human Influenza Viruses by the Polymerase Chain Reaction,” Journal of Virological Methods, 1991, vol. 33 (1-2), pp. 165-189. |
| Zhang Y.Q., et al., “Genome-Based Analysis of Virulence Genes in a Non-Biofilm-Forming Staphylococcus epidemidis Strain (ATCC 12228),” Molecular Microbiology, 2003, vol. 49 (6), pp. 1577-1593. |
| Ex Parte Quayle Action mailed Nov. 21, 2011 for U.S. Appl. No. 12/049,949, filed Mar. 17, 2008. |
| Non-Final Office Action mailed May 2, 2012 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Non-Final Office Action mailed May 8, 2012 for U.S. Appl. No. 13/174,254, filed Jun. 30, 2011. |
| Non-Final Office Action mailed Dec. 13, 2011 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Non-Final Office Action mailed Feb. 16, 2012 for U.S. Appl. No. 11/674,538, filed Feb. 13, 2007. |
| Non-Final Office Action mailed Apr. 18, 2012 for U.S. Appl. No. 12/605,628, filed Oct. 26, 2009. |
| Non-Final Office Action mailed Jan. 27, 2012 for U.S. Appl. No. 11/929,930, filed Oct. 30, 2007. |
| Notice of Allowance mailed Apr. 9, 2012 for U.S. Appl. No. 11/929,910, filed Oct. 30, 2007. |
| Notice of Allowance mailed May 11, 2012 for U.S. Appl. No. 12/049,949, filed Mar. 17, 2008. |
| Notice of Allowance mailed Mar. 19, 2012 for U.S. Appl. No. 11/930,017, filed Oct. 30, 2007. |
| Notice of Allowance mailed Nov. 21, 2011 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Notice of Allowance mailed Mar. 22, 2012 for U.S. Appl. No. 11/930,108, filed Oct. 31, 2007. |
| Notice of Allowance mailed Mar. 22, 2012 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Notice of Allowance mailed Feb. 29, 2012 for U.S. Appl. No. 11/929,910, filed Oct. 30, 2007. |
| Office Action mailed Dec. 2, 2011 for European Application No. 10179791.8 filed Mar. 4, 2002. |
| Office Action mailed Feb. 2, 2012 for Israel Application No. 157661 filed Mar. 4, 2002. |
| Office Action mailed Aug. 3, 2011 for Canadian Application No. 2439655 filed Mar. 4, 2002. |
| Office Action mailed Feb. 6, 2012 for Australian Application No. 2010202418 filed Jun. 10, 2010. |
| Office Action mailed Feb. 6, 2012 for European Application No. 06800205.4 filed Jul. 21, 2006. |
| Office Action mailed Jan. 10, 2012 for Japanese Application No. 2008522997 filed Jul. 21, 2006. |
| Office Action mailed Feb. 14, 2012 for Australian Application No. 2010200686 filed Feb. 25, 2010. |
| Office Action mailed Feb. 14, 2012 for European Application No. 10179789.2 filed Mar. 4, 2002. |
| Office Action mailed Jan. 19, 2012 for Canadian Application No. 2510007 filed Dec. 5, 2003. |
| Office Action mailed Mar. 21, 2012 for Japanese Application No. 2009245976 filed Oct. 26, 2009. |
| Office Action mailed Nov. 30, 2011 for Australian Application No. 2010202418 filed Jun. 10, 2010. |
| Notice of Allowance mailed Aug. 3, 2012 for U.S. Appl. No. 11/674,538, filed Feb. 13, 2007. |
| Notice of Allowance mailed Jul. 24, 2012 for U.S. Appl. No. 11/930,017, filed Oct. 30, 2007. |
| Office Action mailed Jun. 12, 2012 for Mexican Application No. PAa2003007927 filed Sep. 2, 2003. |
| Office Action mailed Jul. 25, 2012 for European Application No. 06800205.4 filed Jul. 21, 2006. |
| Notice of Allowance mailed May 23, 2012 for U.S. Appl. No. 12/326,800, filed Dec. 2, 2008. |
| Office Action mailed May 24, 2012 for European Application No. 10179791.8 filed Mar. 4, 2002. |
| Office Action mailed May 29, 2012 for Indian Application No. IN4504/KOLNP/2007 filed Nov. 22, 2007. |
| Office Action mailed May 31, 2012 for Canadian Application No. 2616281 filed Jul. 21, 2006. |
| Notice of Allowance mailed Oct. 2, 2012 for U.S. Appl. No. 11/930,108, filed Oct. 31, 2007. |
| Office Action mailed Sep. 14, 2012 for Australian Application No. 2010200893 filed Mar. 10, 2010. |
| Office Action mailed Aug. 29, 2012 for Canadian Application No. 2439655 filed Mar. 4, 2002. |
| Co-pending U.S. Appl. No. 13/770,648, filed Feb. 19, 2013. |
| Co-pending U.S. Appl. No. 13/850,683, filed Mar. 26, 2013. |
| Final Office Action mailed Dec. 4, 2012 for U.S. Appl. No. 13/174,254, filed Jun. 30, 2011. |
| Final Office Action mailed Dec. 17, 2012 for U.S. Appl. No. 12/616,422, filed Nov. 11, 2009. |
| Non-Final Office Action mailed Jan. 22, 2013 for U.S. Appl. No. 11/930,741, filed Oct. 31, 2007. |
| Non-Final Office Action mailed May 23, 2013 for U.S. Appl. No. 13/663,176, filed Oct. 29, 2012. |
| Notice of Allowance mailed Apr. 1, 2013 for U.S. Appl. No. 11/929,930, filed Oct. 30, 2007. |
| Notice of Allowance mailed Oct. 12, 2012 for U.S. Appl. No. 12/049,949, filed Mar. 17, 2008. |
| Notice of Allowance mailed Jan. 22, 2013 for U.S. Appl. No. 12/616,422, filed Nov. 11, 2009. |
| Notice of Allowance mailed May 22, 2013 for U.S. Appl. No. 12/616,422, filed Nov. 11, 2009. |
| Office Action mailed Dec. 6, 2012 for European Application No. 10179795.9 filed Mar. 4, 2002. |
| Office Action mailed Dec. 12, 2012 for European Application No. 10179789.2 filed Mar. 4, 2002. |
| Office Action mailed Oct. 15, 2012 for European Application No. 10175659.1 filed Dec. 5, 2003. |
| Office Action mailed Apr. 19, 2013 for Canadian Application No. 2616281 filed Jul. 21, 2006. |
| Office Action mailed Nov. 21, 2012 for Israel Application No. 157661 filed Mar. 4, 2002. |
| Office Action mailed Apr. 23, 2013 for Japanese Application No. 2009550634 filed Feb. 25, 2008. |
| Office Action mailed Sep. 25, 2012 for Japanese Application No. 2008522997 filed Jul. 21, 2006. |
| Examiner Interview Summary mailed Jun. 7, 2011 for U.S. Appl. No. 11/930,108 filed Oct. 31, 2007. |
| Final Office Action mailed Jun. 14, 2011 for U.S. Appl. No. 12/616,422 filed Nov. 11, 2009. |
| Notice of Allowance mailed Jun. 9, 2011 for U.S. Appl. No. 11/331,987 filed Jan. 13, 2006. |
| Notice of Allowance mailed Jun. 9, 2011 for U.S. Appl. No. 11/491,376 filed Jul. 21, 2006. |
| Notice of Allowance mailed May 25, 2011 for U.S. Appl. No. 11/929,707 filed Oct. 30, 2007. |
| Co-pending U.S. Appl. No. 13/174,254, filed on Jun 30, 2011. |
| Co-pending U.S. Appl. No. 13/243,960, filed on Sep 23, 2011. |
| Ecker Supporting Information [online], May 23, 2005 [retrieved on Jul. 31, 2011]. Retrieved from the Internet<URL: http://www.pnas.org/content/102/22/8012/suppl/DC1>. |
| Final Office Action mailed Oct. 19, 2011 for U.S. Appl. No. 12/326,800 filed Dec. 2, 2008. |
| Final Office Action mailed Jul. 28, 2011 for U.S. Appl. No. 11/930,108 filed Oct. 31, 2007. |
| Non-Final Office Action mailed Oct. 11, 2011 for U.S. Appl. No. 12/605,628 filed Oct. 26, 2009. |
| Non-Final Office Action mailed Oct. 13, 2011 for U.S. Appl. No. 11/929,930 filed Oct. 30, 2007. |
| Notice of Allowance and Examiner Interview Summary mailed Jul. 21, 2011 for U.S. Appl. No. 10/754,415 filed Jan. 9, 2004. |
| Notice of Allowance mailed Aug. 9, 2011 for U.S. Appl. No. 11/930,002 filed Oct. 30, 2007. |
| Office Action mailed Sep. 30, 2011 for U.S. Appl. No. 10/754,415 filed Jan. 9, 2004. |
| Non-Final Office Action mailed Jul. 3, 2013 for U.S. Appl. No. 11/929,930 filed Oct. 30, 2007. |
| Non-Final Office Action mailed Jun. 6, 2013 for U.S. Appl. No. 13/243,960 filed Sep. 23, 2011. |
| Non-Final Office Action mailed Jul. 12, 2013 for U.S. Appl. No. 13/174,254 filed Jun. 30, 2011. |
| Office Action mailed May 29, 2013 for Australian Application No. 2010200893 filed Mar. 10, 2010. |
| Number | Date | Country | |
|---|---|---|---|
| 20120122086 A1 | May 2012 | US |
| Number | Date | Country | |
|---|---|---|---|
| 60431319 | Dec 2002 | US | |
| 60461494 | Apr 2003 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10660997 | Sep 2003 | US |
| Child | 11682259 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 09798007 | Mar 2001 | US |
| Child | 10660997 | US | |
| Parent | 10323438 | Dec 2002 | US |
| Child | 09798007 | US |
