Abstract: A method for nucleic acid sequencing includes receiving a plurality of observed or measured signals indicative of a parameter observed or measured for a plurality of defined spaces; determining, for at least some of the defined spaces, whether the defined space comprises one or more sample nucleic acids; processing, for at least some of the defined spaces, the observed or measured signal to improve a quality of the observed or measured signal; generating, for at least some of the defined spaces, a set of candidate sequences of bases for the defined space using one or more metrics adapted to associate a score or penalty to the candidate sequences of bases; and selecting the candidate sequence leading to a highest score or a lowest penalty as corresponding to the correct sequence for the one or more sample nucleic acids in the defined space.

Abstract: Provided are methods, systems, and computer readable media for comparing word statistics between a significant amino acid sequence and a significant nucleotide sequence wherein the comparison instructs further research.

Abstract: This invention relates to a binomial calculation of copy number of data obtained from a mixed sample having a first source and a second source.

Abstract: A computer system for visualizing recombination events in a group of individuals is provided. According to one aspect of the invention, high-density SNP genotype data is obtained from related individuals in a family. A pedigree is created, haplotypes are reconstructed and likely recombination breakpoints are identified with the use of publicly available computer programs. A software tool is then used facilitate the visualization of the recombination events in the family.

Abstract: Haplotypes of one or more portions of a chromosome of an organism from sequencing information of DNA or RNA fragments can be determined. Heterozygous loci (hets) can be used to determine haplotypes. One allele on a first het can be connected (likely to be on the same haplotype) to an allele on a second het, thereby defining a particular orientation between the hets. Haplotypes can be assembled through these connections. Errors can be identified through redundant connection information, particularly using a confidence value (strength) for a particular connection. The connections among a set of hets can be analyzed to determine likely haplotypes for that set, e.g., an optimal tree of a graph containing the hets. Furthermore, haplotypes of different contiguous sections (contig) of the chromosome can be matched to a particular chromosome copy (e.g., to a particular parental copy). Thus, the phase of an entire chromosome can be determined.

Abstract: Provided is a method for quantifying an initial concentration of a nucleic acid from a real-time nucleic acid amplification data. Nucleic acid (DNA or RNA) extracted from organism or virus is amplified using an enzyme. Then, the initial concentration of the nucleic acid is found by calculating the characteristic amplification cycle number or the characteristic amplification time at which the fluorescence intensity of the nucleic acid subtracted by the background fluorescence intensity of the nucleic acid has half of its maximum value, or the characteristic amplification cycle number or the characteristic amplification time at which the amplification efficiency has the maximum or the minimum value, or the prior-to-amplification fluorescence intensity of the nucleic acid subtracted by the background fluorescence intensity of the nucleic acid. Accordingly, the initial concentration of the nucleic acid can be calculated without differentiation or integration.

Abstract: Methods, computer-accessible medium, and systems for generating a genome wide probe map and/or a genome wide haplotype sequence are provided. In particular, a genome wide probe map can be generated by obtaining a plurality of detectable oligonucleotide probes hybridized to at least one double stranded nucleic acid molecule cleaved with at least one restriction enzyme, and detecting the location of the detectable oligonucleotide probes. For example, genome wide haplotype sequence can be generated by analyzing at least one genome wide restriction map in conjunction with at least one genome wide probe map to determine distances between restriction sites of the genome wide restriction map(s) and locations of detectable oligonucleotide probes of the genome wide probe map(s) and defining a consensus map indicating restriction sites based on the genome wide restriction map(s) and/or locations of detectable oligonucleotide probes based on each of the genome wide probe map(s).

Abstract: The present invention relates generally to the field of investigational bioinformatics and more particularly to secondary structure defining databases. The present invention further relates to methods for interrogating a database as a source of molecular masses of known bioagents for comparing against the molecular mass of an unknown or selected bioagent to determine either the identity of the selected bioagent, and/or to determine the origin of the selected bioagent. The identification of the bioagent is important for determining a proper course of treatment and/or irradication of the bioagent in such cases as biological warfare. Furthermore, the determination of the geographic origin of a selected bioagent will facilitate the identification of potential criminal identity.

Abstract: Systems to obtain a chemical array layout are provided. Systems of the invention include input and output managers for receiving information from and sending information to one or more users and a processing module having an array layout developer that applies rules relating to array layout design. The array layout developer develops an array layout based on the application of one or more of the rules to array request information received from one or more users. Also provided are computer program products for executing the subject methods.

Abstract: Three methods of predicting whether an unknown biological specimen of a missing person originates from a member of a particular family comprise an initial automated decision support (ADS) algorithm for determining a list of relatives of the missing person for DNA typing and which typing technologies of available technologies to use for a listed relative. The ADS algorithm may be implemented on computer apparatus including a processor and an associated memory. The ADS method comprises determining a set of relatives of available family member relatives for DNA typing via a processor from a stored list of family member relatives according to one of a rule base, a table of hierarchically stored relatives developed based on discriminatory power or by calculating the discriminatory power for available family relatives to type.

Abstract: Genomic sequence matching and alignment techniques are disclosed. In one embodiment of the invention, computerized methods are provided for analyzing sequence similarity data obtained by means of a table of all local hits recorded between query sequence and reference index. The table of local hits represents all occurrences of query subsequences in reference index that stored all transitions between single l-mer prefix to multiple m-mer suffixes. The index data structure may take a variety of forms, including an array or a tree. The base position of each transition from l-prefix to m-suffix is recorded in k-bit masked form. The positions data structure may take a variety of forms as well, including an array or a tree. The table of local hits derived from l-prefix, m-suffix and k-position reference index is used by a series of low time and space complexity algorithms for optimizing alignment between query and reference.

Abstract: The computerized method, software, and product of this invention implements a process for computationally designing proteins and/or associated molecular targets with desired quantitative stability/flexibility relationships (QSFR). QSFR is an innovative, high dimensional metric calculated using an improved Distance Constraint Model (DCM). This invention includes three distinct aspects: (i.) utilizing QSFR in computational molecular design of protein sequences, or variations of molecular structures, to have specific stability and flexibility relationships deemed important for biochemical function for specified thermodynamic and solvent conditions; (ii.) utilizing QSFR to optimize thermodynamic and/or solvent conditions necessary for a specified molecular system to exhibit protein function characteristics, such as improved catalytic efficiency; and (iii.) utilizing QSFR to computationally screen or design small molecules and/or design its putative receptor so as to exhibit a desired affect on protein function.

Abstract: The invention provides a high resolution three-dimensional structure of cycloheximide, either alone or in association with a large ribosomal subunit. The invention provides methods for designing and/or identifying cycloheximide analogs and derivatives that bind and/or modulate the protein biosynthetic activity of the ribosome.

Abstract: A method, apparatus, and computer program product for analyzing gene expressions is presented. An operation is performed for determining a gene expression pattern for a condition, wherein the gene expression pattern comprises a gene expression. Next, a spatial-expression pattern is formed by selecting a chromosomal region having an exon; and associating the gene expression within the gene expression pattern with its corresponding exon. A further operation may be performed, where in the forming of the spatial-expression pattern, a spatial-expression pattern signal is created as a representation of the spatial-expression pattern. The magnitude of the spatial-expression pattern signal at any point is determined by an expression level of the corresponding exon. Spatial patterns may be identified in the signal by means of various signal processing techniques such as Fourier or Wavelet transforms.

Abstract: The invention provides computer-implemented methods and apparatus implementing a hierarchical protocol using multiscale molecular dynamics and molecular modeling methods to predict the presence of transmembrane regions in proteins, such as G-Protein Coupled Receptors (GPCR), and protein structural models generated according to the protocol. The protocol features a coarse grain sampling method, such as hydrophobicity analysis, to provide a fast and accurate procedure for predicting transmembrane regions. Methods and apparatus of the invention are useful to screen protein or polynucleotide databases for encoded proteins with transmembrane regions, such as GPCRs.

Abstract: BioMEMS/NEMS appliance biologically monitors an individual, using biosensors to detect cellular components. Data is simulated or analyzed using systems-biology software, which provides diagnostic or therapeutic guidance.

Abstract: The present invention is generally directed to powerful and flexible methods and systems for consensus sequence determination from replicate biomolecule sequence data. It is an object of the present invention to improve the accuracy of consensus biomolecule sequence determination from replicate sequence data by providing methods for assimilating replicate sequence into a final consensus sequence more accurately than any one-pass sequence analysis system.

Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.

Abstract: The present invention relates to methods for performing surveys of the genetic diversity of a population. The invention also relates to methods for performing genetic analyses of a population. The invention further relates to methods for the creation of databases comprising the survey information and the databases created by these methods. The invention also relates to methods for analyzing the information to correlate the presence of nucleic acid markers with desired parameters in a sample. These methods have application in the fields of geochemical exploration, agriculture, bioremediation, environmental analysis, clinical microbiology, forensic science and medicine.

Abstract: A method for determining pulmonary fibrosis subtype and/or prognosis in a subject having pulmonary fibrosis comprising: a. determining an expression profile by measuring the gene expression levels of a plurality of genes selected from genes listed in Table 1, 2, 3, 4 7, 8, 9, and/or 10, in a sample from the subject; and b. classifying the subject as having a good prognosis or a poor prognosis based on the expression profile; wherein a good prognosis predicts decreased risk of post lung transplant primary graft dysfunction, and wherein a poor prognosis predicts an increased risk of post lung transplant primary graft dysfunction.

Abstract: An embodiment of a method for correcting an error associated with phasic synchrony of sequence data generated from a population of template molecules is described that comprises the steps of detecting signals generated in response to nucleotide species introduced during a sequencing reaction; generating an observed value for the signal detected from each of the nucleotide species; defining positive incorporation values and negative incorporation values from the observed values using a carry forward value and an incomplete extension value; and revising the carry forward value and the incomplete extension value using a noise value that is derived from observed values associated with the negative incorporation values.

Abstract: A highly safe system for processing information includes: (a) receiving requested information for en object and/or service; (b) obtaining positional information in accordance with the requested information from a memory having positional information representing a position in a nucleotide sequence memorized therein and transmitting the obtained positional information; (c) receiving, from among nucleotide sequence-related information associated with positional information, nucleotide sequence-related information corresponding to the positional information transmitted in step (b) and then obtaining semantic information implied by the received nucleotide sequence-related information and/or information associated with the semantic information; and (d) transmitting the semantic information and/or information associated with the semantic information obtained in step (c) in association with the positional information corresponding thereto to the party to which the positional information had been transmitted in step

Abstract: The invention relates a method of quantifying CD64 and CD163 expression in leukocytes and, specifically to a kit for use with a flow cytometer including a suspension of quantitative fluorescent microbead standards, fluorescent labeled antibodies directed to CD64 and CD163, and analytical software. The software is used to take information on the microbead suspension and fluorescent labeled antibodies from a flow cytometer and analyse data, smooth curves, calculate new parameters, provide quality control measures and notify of expiration of the assay system.

Abstract: Aspects of the present invention describe an apparatus and method for generating genotype calls for a sample. The genotyping initially models allelic signal response into an allelic model having one or more model parameters for an identified one or more sources of systematic variation. The model and parameters are then used to transform the allelic signals to a normalized normalized allelic space that serves to compensate for the one or more sources of systematic variation. By compensating for the systematic variation in this manner, the genotype for the sample is readily determined based upon its relationship to the representation of the allelic signals in normalized allelic space and in accordance with the allelic model.

Abstract: Understanding the heterogeneity within a stem cell population remains a major impediment to the development of clinically effective cell-based therapies. Gene expression patterns exhibited by individual cells are a crucial component of this heterogeneity, yet transcriptional events within a single cell are inherently stochastic and can produce tremendous variability, even among genetically identical cells. It remains unclear how mammalian cellular systems overcome this intrinsic noisiness of gene expression to produce consequential variations in function. To address these questions, we utilized a novel single cell analysis method to characterize transcriptional programs across hundreds of individual murine long-term hematopoietic stem cells (LT-SCs). We demonstrate that multiple subpopulations exist within this putatively homogeneous stem cell population, defined by nonrandom patterns that are distinguishable from noise and can predict functional properties of these cells.

Abstract: A method and system are disclosed for identifying partial order patterns of a set of motifs in a data sequence. The method comprises the steps of obtaining the data sequence, identifying a set of motifs in the data sequence, identifying a plurality of partial orders of the motifs in the data sequence, and using the identified partial orders to identify functions of the motifs. In the preferred embodiment of the invention, the step of identifying the plurality of partial orders of the motifs includes the step of converting the identified motifs to an (n×m) incidence matrix, I, of expressions. Also, in this preferred embodiment, the step of identifying the plurality of partial orders of the motifs includes the steps of computing a partial order description of each of the expressions, and computing a redescription of each of the partial order descriptions.

Abstract: The distribution and/or ratio of Thymine, Cytosine, Adenine and Guanine of a DNA sequence from a target organism are organized and analyzed. The result is then used to determine the possible impacts the target organism may have in a host such as a human body. The corresponding treatment and prevention strategies may also be determined. The goal is to provide an effective way to diagnose, treat and prevent diseases such as infectious diseases, to test the safety of food and drugs, and therefore to create natural and effective solutions for health care and food supply. For example, a DNA analysis method configured according to the invention receives a DNA sequence input and converts it into a reassembled sequence. A result based on the reassembled sequence may then be output. Determination of the analysis result, treatment and prevention strategies may also be output.

Abstract: Numerous cancer fusion genes have been identified and studied, and in some cases therapy or diagnostic techniques have been designed that are specific to the fusion protein encoded by the fusion gene. However, there has been little progress in understanding the general features of cancer fusions genes in a way that could provide the foundation for an algorithm for predicting the occurrence of a fusion gene once the chromosomal translocation points have been identified by karyotype analyses. In this study, characterization of 59 cancer fusion genes indicated that all but a small percentage of the genes involved in fusion events are either relatively large, compared to neighboring genes, or are highly conserved in evolution. These results support a basis for designing algorithms that could have a high degree of predictive value in identifying fusion genes once conventional microscopic analyses have identified the chromosomal breakpoints.

Abstract: Disclosed is a method for determining the quality, expressed in terms of a quality value, of an biomolecule sample, based on measured data of the biomolecule sample, by extracting a number of prescribed features from the measured data using data analysis, and determining the quality value from the extracted features using a quality algorithm.

Abstract: Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof. In particularly preferred embodiments, nucleic acid sequences generated by such methods are subjected to de novo assembly and/or consensus sequence determination.

Abstract: The present disclosure provides computer implemented methods and systems for analyzing datasets, such as large data sets output from nucleic acid sequenceing technologies. In particular, the present disclosure provides for data analysis comprising computing the BWT of a collection of strings in an incremental, character by character, manner. The present disclosure also provides compression boosting strategies resulting in a BWT of a reordered collection of data that is more compressible by second stage compression methods compared to non-reordered computational analysis.

Abstract: Provided is a method for quantifying an initial concentration of a nucleic acid from a real-time nucleic acid amplification data. Nucleic acid (DNA or RNA) extracted from organism or virus is amplified using an enzyme. Then, the initial concentration of the nucleic acid is found by calculating the characteristic amplification cycle number or the characteristic amplification time at which the fluorescence intensity of the nucleic acid subtracted by the background fluorescence intensity of the nucleic acid has half of its maximum value, or the characteristic amplification cycle number or the characteristic amplification time at which the amplification efficiency has the maximum or the minimum value, or the prior-to-amplification fluorescence intensity of the nucleic acid subtracted by the background fluorescence intensity of the nucleic acid. Accordingly, the initial concentration of the nucleic acid can be calculated without differentiation or integration.

Abstract: Systems and methods are disclosed for compressing and comparing data such as genomic data. The disclosed systems and methods may include selecting a segment, creating a delta representation of the segment, the delta representation comprising a script, and storing the script. Furthermore, the disclosed systems and methods may include receiving a first script comprising a compressed version of a first segment and receiving a second script comprising a compressed version of a second segment. The disclosed systems and methods may further include comparing the first script to the second script and determining if the first segment matches the second segment based upon the comparison of the first script to the second script.

Abstract: A computer implemented method of identifying potential micoRNA targets and biomarkers comprises receiving data identifying a first set of mRNA sequences into computer accessible memory. Each mRNA sequence in the first set has a region that is upstream of a translation start site, a region that is downstream of a translation stop site, and an open reading frame. The method further comprises receiving data identifying a second set of microRNA (miRNA) sequences into the computer accessible memory. Each microRNA sequence has a 5? miRNA section and a 3? miRNA section. Each mRNA sequence is characterized by an expression pattern in the first set as being up-regulated, down-regulated, or uncharged as compared to a control sample and each miRNA sequence in the second set as being up-regulated, down-regulated, or uncharged as compared to the control sample. It is then determined which mRNA sequences from the first set are susceptible to being regulated by microRNA from the second set.

Abstract: A computer implemented method of generating an identification element including storing an amount of identifiable object data obtained as a linear sequence of data elements in the memory of a computer and which can be fragmented to produce a plurality of identifiable object data fragments each having a number of data elements which corresponds to one of a set of random numbers generated by a random number generator each of the identifiable object data fragments translated into a linear sequence of DNA data elements and embedded to generate an identification element.

Abstract: A method of enhancing the efficacy of a monoclonal antibody preparation wherein antigens from patients are tested for their reactivity with the antibody. An amino acid sequence of an expressed protein is deuced from a nucleotide sequence determined by isolation and analysis of a target molecule gene in a biopsy from a patient. This is compared with the previously determined amino acid sequence recognized by the monoclonal antibody preparation in order to assess the fitness of patients for administration of the monoclonal antibody preparation.

Abstract: Systems and methods are provided for defining a nucleic acid construct for integration at locus L of an organism. Nucleic acid requests are received, each such request specifying a genetic change to L. The request are expanded into component polynucleotides which are then arranged into {AR1, . . . , ARm} different arrangements, each ARi in {AR1, . . . , ARm} defining a different arrangement of the component polynucleotides. A score Si for each ARi in {AR1, . . . , ARm} is determined based on whether source constructs encoding a portion ofARi are physically present. An ARf in {AR1, . . . , ARm} is selected based on the score for ARf. Primer pairs are calculated to amplify the portions of ARf not represented in the source constructs. The portions of ARf amplified by the primer pairs and the portions of ARf in the source constructs, ordered by ARf, define the nucleic acid construct.

Abstract: The sequencing of individual monomers (e.g., a single nucleotide) of a polymer (e.g., DNA, RNA) is improved by reducing the motion of the polymer due to thermally-driven diffusion to reduce the spatial error in the position of the polymer within a measurement device. A major system parameter, such as average translocation velocity or measurement time, is selected based on the characteristics of the sensing system utilized, and an algorithm jointly optimizes the sequencing order error rate and the monomer identification error rate of the system.

Abstract: Methods and computer readable storage mediums for identifying structurally or functionally significant amino acid sequences encoded by a genome are disclosed. At least one structurally or functionally significant amino acid sequence encoded by a genome may be identified by compiling an observed frequency for each of a plurality of amino acid words encoded by the genome, calculating with a computer an expected frequency for each of the plurality of amino acid words encoded by the genome, and identifying at least one structurally or functionally significant amino acid sequence encoded by the genome based at least in part on the observed and expected frequencies for each of the plurality of amino acid words encoded by the genome.

Abstract: An improved gene sequence optimization method, the systematic optimization method, is described for boosting the recombinant expression of genes in bacteria, yeast, insect and mammalian cells. This general method takes into account of multiple, preferably most or all, of the parameters and factors affecting protein expression including codon usage, tRNA usage, GC-content, ribosome binding sequences, promoter, 5?-UTR, ORF and 3?-UTR sequences of the genes to improve and optimize the gene sequences to boost the protein expression of the genes in bacteria, yeast, insect and mammalian cells. In particular, the invention relates to a system and a method for sequence optimization for improved recombinant protein expression using a particle swarm optimization algorithm. The improved systematic optimization method can be incorporated into a software for more efficient optimization.

Abstract: A diagnosis of the health of an animal is obtained through a combination of computerized data and human interpretation. Data relates to the physical characteristics of the animal, and includes data obtained from a physical inspection of the animal. A blood or other fluid sample is used to obtain a computer generated laboratory analysis. This is reported through an internet network to the clinical pathologist. The clinical pathologist has the data relating to the physical characteristics, and thereby makes a diagnosis of the animal health. A drop-down menu on a computer screen provides supplemental reports to support the diagnosis. This can be enhanced by further input from the pathologist through keyboard entry into the computer to obtain an integrated computer report having the laboratory analysis, supplemental report, and selectively an enhanced report. The integrated report is electronically communicated to a client.

Abstract: Methods and systems of extracting extensible motifs from a sequence include assigning a significance to extensible motifs within the sequence based upon a syntactic and statistical analysis, and identifying extensible motifs having a significance that exceeds a predetermined threshold.

Abstract: A method of determining kinetic parameters for a reversible molecular interaction between a ligand immobilized to a solid support surface and a binding partner to the ligand in solution, comprises sequentially, without intermediate regeneration or renewal of the immobilized ligand, flowing a plurality of fluid volumes containing different known concentrations of the binding partner over the solid support surface, monitoring the momentary amount of binding partner bound to the solid support surface related to time and solution concentration of binding partner and collecting the binding data, and determining the kinetic parameters by globally fitting a predetermined kinetic model for the interaction between the binding partner and the immobilized ligand to the collected binding data, which model allows for mass transport limitation at the solid support surface.

Abstract: This invention relates to a cell expansion system and to a method of determining when to harvest cells from the cell expansion system.

Abstract: Methods, systems, and computer readable media for determining the quality of a CGH array, including calculating a spread of the derivative of log ratio value differences between consecutive probes representing consecutive positions along a chromosome, wherein ratio values are calculated from probe signals from a CGH array.

Abstract: The present invention relates to a method and apparatus for predicting the resistance of soybean seed samples to infection by soybean cyst nematode parasites using near-infrared spectroscopy and discriminant analysis.

Abstract: Methods, computer systems, and computer readable medium for testing a plurality of models in order to classify a biological specimen. A determination is made as to whether a model precondition associated with a model in the plurality of models has been satisfied. The model is skipped when the model precondition has not been satisfied. When the model precondition has been satisfied, the first model is tested by selecting a calculation from the first model. The selected calculation is computed using cellular constituent abundance values from the biological specimen in accordance with a calculation algorithm set forth in the selected model. This selecting and computing is repeated for one or more calculations in the selected model. Then, each of these calculations is aggregated in accordance with an aggregation algorithm associated with the selected model. These steps are repeated for at least one other model in the plurality of models.

Abstract: Non-contiguous regions of interest as well as contiguous regions of interest are similarly processed. After an isotope peak detector has identified isotope peaks on LC/MS images, a microaligner microaligns bounding areas of identified isotope peaks and redefines the bounding areas to help subsequent scoring process. Forms of isotope peaks influence formation of a peak association matrix and a mass/charge association map which creates association in the mass/charge dimension. A correlation scorer produces reproducibility scores as well as quality scores to help aid scientists to discover biological features of interest.

Abstract: Disclosed herein are methods of determining the sequence and/or positions of modified bases in a nucleic acid sample present in a circular molecule with a nucleic acid insert of known sequence comprising obtaining sequence data of at least two insert-sample units. In some embodiments, the methods comprise obtaining sequence data using circular pair-locked molecules. In some embodiments, the methods comprise calculating scores of sequences of the nucleic acid inserts by comparing the sequences to the known sequence of the nucleic acid insert, and accepting or rejecting repeats of the sequence of the nucleic acid sample according to the scores of one or both of the sequences of the inserts immediately upstream or downstream of the repeats of the sequence of the nucleic acid sample.

Abstract: A method for quantifying the extent of human-introduced variability in medical test data relative to one or more standards for comparable medical tests, the method comprising the following steps: providing user medical test data; comparing the user medical test data against one or more standards for comparable medical tests to determine the extent of deviation of the user medical test data from the one or more standards; and generating a variability-value corresponding to the maximum absolute percentage deviation of the user medical test data from the one or more standards over a predefined operating range of values for the one or more standards.