Abstract: A structure, apparatus, and method are disclosed. A silicon substrate with a microfluidic system that receives a sample fluid and prepares an analyte solution received by a reservoir containing a sensing surface is electrically connected to a semiconductor device. The structure includes a component for receiving a sample fluid, a component for preparing the sample fluid, a CRISPR system for cleaving a reporter species when the sample fluid contains a target sequence, a sorting component for separating the cleaved reporter species from the sample fluid and the CRISPR products, a cavity for receiving an analyte solution containing the cleaved reporter species, and a sensing surface in the cavity. The sensing surface detects electrical signals induced by reaction events in the analyte solution.

Abstract: The invention provides methods for assessment of fetal DNA samples using target-enriched multiplexed parallel analysis. The methods of the invention utilize Target Capture Sequences (TACS) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods can be used with fetal or embryonic DNA samples, for example for the detection of the presence of genetic abnormalities, e.g., for purposes of IVF Pre-implantation Genetic Screening (PGS) and Diagnosis (PGD). Kits for carrying out the methods of the invention are also provided.

Abstract: Method of haplotype analysis. In an exemplary method, an aqueous phase containing nucleic acid may be partitioned into a plurality of discrete volumes. At least one allele sequence may be amplified in the volumes from each of a first polymorphic locus and a second polymorphic locus that exhibit sequence variation in the nucleic acid. At least one measure of co-amplification of allele sequences from both loci in the same volumes may be determined. A haplotype of the first and second loci may be selected based on the at least one measure of co-amplification.

Abstract: The disclosure provides modified human IgM heavy chain constant regions that include one or more amino acid substitutions, e.g., in the C?3 domain, where a modified human IgM antibody comprising the modified IgM constant region and a heavy chain variable region specific for a target antigen exhibits reduced complement-dependent cytotoxicity (CDC) of cells expressing the target antigen relative to a corresponding wild-type human IgM antibody.

Abstract: The invention relates to a method of neighbor influence compensation between a plurality of objects in at least one digital image, wherein the at least one digital image contains image information about a plurality of objects. Each of the plurality of objects is configured to receive at least one molecule comprising genetic information, wherein the at least one molecule is configured to receive a fluorescent compound, and the at least one digital image is taken by an optical imaging system during emission of electromagnetic radiation of the fluorescent compounds received by the at least one molecules.

Abstract: The invention provides a genetically modified micro-organism for intracellular biosynthesis of a cellular metabolite, comprising a synthetic error correction system having a penalty gene, whose expression leads to arrested growth or cell death (e.g. a toxin gene) in combination with a survival gene, whose expression provides an antidote that restores cell viability and normal growth (e.g. a cognate antitoxin gene). Alternatively, the system has a survival gene, alone, whose expression is essential for growth (i.e. essential gene). The synthetic error correction system further comprises a biosensor, whose function is to induce expression of the survival gene which leads to cell growth, only, when the cell produces a pre-defined level of a given metabolite.

Abstract: The present disclosure concerns aptamers which specifically bind to Legionella pneumophila which can be used to detect the presence of Legionella pneumophila in a sample.

Abstract: A separation device separates an unknown intact mAb or reduced mAb subunits of a known mAb class from a sample. An ion source device ionizes the mAb. A mass spectrometer fragments the ionized mAb using an ECD device and mass analyzes resulting product ions using a mass analyzer, producing one or more product ion spectra. Theoretical product ion peaks are calculated for one or more constant portions of the mAb class. The theoretical product ion peaks are removed from the one or more product ion spectra, producing one or more difference product ion spectra. De novo sequencing is applied to the one or more difference product ion spectra, producing one or more candidate sequences for one or more variable portions of the mAb. A genome database is searched for matches to the one or more candidate sequences, producing one or more matched sequences for the one or more variable portions.

Abstract: The present invention is directed to a yeast strain, or strains, secreting a full suite, or any subset of that full suite, of enzymes to hydrolyze corn starch, corn fiber, lignocellulose, (including enzymes that hydrolyze linkages in cellulose, hemicellulose, and between lignin and carbohydrates) and to utilize pentose sugars (xylose and arabinose). The invention is also directed to the set of proteins that are well expressed in yeast for each category of enzymatic activity. The resulting strain, or strains can be used to hydrolyze starch and cellulose simultaneously. The resulting strain, or strains can be also metabolically engineered to produce less glycerol and uptake acetate. The resulting strain, or strains can also be used to produce ethanol from granular starch without liquefaction.

Abstract: The disclosure is generally directed to methods for screening, identifying, and producing microorganisms capable of imparting beneficial properties to plants. In some aspects, improved plant-associated soil microorganisms are generated by experimental evolution using a plant root exudate or root exudate compound.

Abstract: The present invention relates to monoclonal antibodies that bind to the CD160-TM isoform. The inventors developed new monoclonal antibodies which bind to the CD160-TM isoform but dot not bind to the CD160 GPI-anchored isoform not to the CD160 soluble isoform. In particular, the antibodies of the present invention are suitable for amplifying NK cell activation and therefore cytotoxic functions NK cells.

Abstract: The present invention relates to systems, devices and methods for diagnosing cancer. In various embodiments, the present invention provides a method for quantifying a 5?-htRNA; a method for quantifying a 3?-htRNA; a method for obtaining a DNA library of 5?-htRNAs and a DNA library of 5?-htRNAs obtained therefrom; and a method for obtaining a DNA library of 3?-htRNAs and a DNA library of 3?-htRNAs obtained therefrom. The invention also teaches a method for determining the presence or absence of a cancer cell in a biological sample; a method of diagnosing cancer in a subject; and a method of prognosing cancer in a subject.

Abstract: A process includes receiving information associated with a target molecule to be synthesized via a synthetic pathway engine user interface. The process also includes determining, using a synthetic pathway engine, synthetic pathway data for synthesis of the target molecule. In some cases, the process further includes generating a synthetic pathway report user interface that includes information associated with the synthetic pathway data. In other cases, the process further includes initiating automated synthesis of the target molecule using automated chemical synthesis equipment according to the synthetic pathway data.

Abstract: The present invention provides a method of solid-phase synthesis of DNA-encoded compound library. The method includes following steps: a) reacting solid carrier G-1 with linker molecule L-1 to prepare L-G-1; b) reacting DNA with linker molecule L-0 to prepare L-2; c) reacting L-G-1 with L-2 to prepare L-G-2; d) removing protection group of the L-G-2 and obtaining L-G-2-1; e) reacting the L-G-2-1 with synthetic building block and performing DNA encoding; and f) removing the solid carrier and obtaining the DNA-encoded compound library. Compared with the prior art, the present invention can complete post-treatment purification of the reaction only by filtration and irrigation processes for several times. The present invention is simple to operate, can shorten the production cycle of DNA encoded compound library with more than 50%, significantly increases the production efficiency and the unicity as well as the purity of the final products.

Abstract: Techniques for screening homopolymers, copolymers or blends for fabrication are disclosed. A data repository stores data points. Each data point comprises a structural repeating unit (SRU) and at least one material property value for the SRU. Each SRU is a homopolymer SRU, a copolymer component SRU or a blend component SRU. A machine determines a fingerprint for at least a subset of the SRUs in the data repository. The machine stores, in the data repository, each determined fingerprint in conjunction with a corresponding SRU. The machine generates a quantitative modeling engine to predict material property values, based on SRUs, for homopolymers, copolymers or blends. The quantitative modeling engine is based, at least in part, on the fingerprints. The machine identifies, using the quantitative modeling engine, at least one homopolymer SRU, copolymer SRU set or blend SRU set that has a material property value within a given range.

Abstract: The present invention relates to systems, devices and methods for diagnosing cancer. In various embodiments, the present invention provides a method for quantifying a 5?-htRNA; a method for quantifying a 3?-htRNA; a method for obtaining a DNA library of 5?-htRNAs and a DNA library of 5?-htRNAs obtained therefrom; and a method for obtaining a DNA library of 3?-htRNAs and a DNA library of 3?-htRNAs obtained therefrom. The invention also teaches a method for determining the presence or absence of a cancer cell in a biological sample; a method of diagnosing cancer in a subject; and a method of prognosing cancer in a subject.

Abstract: The present invention provides a system and method for assessing the fidelity of a synthetic peptide population including interrogating a population of peptide features in the presence of a receptor having an affinity for a plurality of binder sequences. A first amino acid is at a defined position within a first one of the binder sequences, and the population of peptide features includes a first control peptide feature synthesized to have an amino acid sequence including the first one of the binder sequences. The system and method further includes detecting a signal output characteristic of an interaction of the receptor with the first control peptide feature. The signal output is indicative of the fidelity of incorporation of the first amino acid into the first control peptide at the defined position within the first one of the binder sequences.

Abstract: The invention provides antibodies that bind specifically to human indoleamine 2,3-dioxygenase 1 (IDO1), and methods of using the same. The antibodies are capable of binding to a sequence comprising SEQ ID NO: 1 and specifically bind to human IDO1 in formalin fixed paraffin embedded tissues. The antibodies are useful in a number of different analytical techniques, including immunohistochemistry (IHC) and immunocytochemistry (ICC).

Abstract: The present invention provides a system and method for assessing a synthetic peptide population including interrogating a population of peptide features in the presence of a receptor having an affinity for a binder sequence. The population of peptide features is synthesized over a plurality of synthesis periods and includes a plurality of control peptide features synthesized to have an amino acid sequence including the binder sequence. The control peptide features include a first feature synthesized beginning with a first one of the synthesis periods, and a second feature synthesized beginning after the first one of the synthesis periods such that synthesis of the second control peptide feature is delayed by at least one synthesis period. The method further includes detecting a signal output characteristic of an interaction of the receptor with the control peptide features, the signal output indicative of the fidelity of synthesis of the population of peptide features.

Abstract: A method for selecting and isolating aptamers that target M-Ig proteins with a microdevice including at least a first selection chamber is provided. The method includes preparing a first sample of M-Ig proteins from a serum; placing the M-Ig proteins in the first selection chamber; introducing a first group of oligomers including at least an M-Ig targeting oligomer into the first selection chamber, whereby the M-Ig targeting oligomer binds to the first sample of M-Ig proteins. The method further includes removing unbound oligomers of the first sample from the first selection chamber to isolate the M-Ig targeting oligomer.

Abstract: A method of producing novel bacteriophages with expanded host-range and bacteriophages with expanded host ranges are disclosed. The method produces mutant phage strains which are infectious to a second host and can be more infectious to their natural host than in their natural state. The method includes repeatedly passaging a selected phage strain into bacterial cultures that contain varied ratios of its natural host bacterial strain with a bacterial strain that the phage of interest is unable to infect; the target-host. After each passage the resulting phage are purified and screened for activity against the target-host via double-overlay assays. When mutant phages that are shown to infect the target-host are discovered, they are further propagated in culture that contains only the target-host to produce a stock of the resulting mutant phage.

Abstract: A method for amplifying a target nucleic acid is disclosed, which includes: (a) fragmenting a nucleic acid sample to create a target fragment comprising a target nucleic acid and two probe-complementary portions; (b) contacting said fragmented nucleic acid sample with a probe comprising two target fragment-complementary portions complementary to the probe-complementary portions of the target fragment; (c) rendering the fragmented nucleic acid sample single-stranded; (d) allowing the probe-complementary portions to hybridise with the target-fragment complementary portions; (e) if the probe in step (b) is not immobilised, immobilising the probe-target fragment hybrid on a solid phase via immobilisation moiety; (f) separating non-immobilised nucleic acid fragments from the solid phase; (g) contacting the solid phase with a ligase to ligate ligatable 5? and 3? ends of the target fragment whereby the target fragment is circularized; and (h) amplifying said circularized target fragment.

Abstract: This disclosure describes, in one aspect, a method for preparing DNA molecule for sequencing. Generally, the method includes fragmenting the DNA molecule into double-stranded fragments; amplifying at least a portion of the double-stranded fragments; circularizing the fragments so that the first end of the fragment comprises a first loop connecting the strands and the second end of the fragment comprises a second loop connecting the strands; annealing a first sequencing primer to the first loop oriented to sequence at least a portion of one strand of the fragment; and annealing a second sequencing primer to the second loop oriented to sequence at least a portion of the other strand of the fragment. In another aspect, this disclosure describes a method for sequencing a DNA molecule.

Abstract: A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set).

Abstract: Methods useful in constructing libraries that collectively display members of diverse families of peptides, polypeptides or proteins and the libraries produced using those methods. Methods of screening those libraries and the peptides, polypeptides or proteins identified by such screens.

Abstract: Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2?,4?-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

Abstract: The present invention relates generally to novel applications in combating infectious disease, cancer, allergy and autoimmune diseases. In one aspect, the invention relates to identifying one or more protein binding moieties of interest. In another aspect, the present invention relates to identifying one or more candidate vaccines.

Abstract: A method of rapidly producing a double-stranded target DNA is disclosed. The method includes the step of producing multiple single stranded primary DNA constructs having (a) partially overlapping and complementary internal regions that together define the target DNA, and (b) flanking regions on either side of the internal regions containing a PCR primer recognition site and a restriction enzyme recognition site. The primary DNA constructs are amplified to form a pool of double-stranded primary constructs, and a restriction enzyme is used to cleave off the flanking regions. The target double-stranded DNA is then assembled from the cleaved fragments. Hundreds of thousands of oligonucleotides can be synthesized and quickly and efficiently assembled into many different individual double-stranded DNA target sequences using this method.

Abstract: This invention relates in part to modifying BtBooster (BtB) peptides, in part to increase their stability in insect midgut digestive juices. Some preferred embodiments of BtB have removed proteinase cleavage sites resulting in increased stability of the modified BtB in the insect gut, while retaining the ability to enhance B.t. proteins for improved insect control. In some preferred embodiments, the protease-stable BtB is used in combination with B.t. spores and/or crystals comprising a Cry protein. Also reported herein is the significant and increased enhancement of Bt toxins against relatively Bt-tolerant insects (Helicoverpa zea, Spodoptera exigua and Agrotis ipsilon), when used with BtBs. We also describe increased toxin enhancement with cadherin fragments that are stabilized against over-digestion by insect midgut proteinases. We also report enhancement of Bt Cry1F toxin by cadherin fragments.

Abstract: A fibronectin type III (Fn3) polypeptide monobody, a nucleic acid molecule encoding said monobody, and a variegated nucleic acid library encoding said monobody, are provided by the invention. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform said methods. Further provided is a method of identifying the amino acid sequence of a polypeptide molecule capable of binding to a specific binding partner (SBP) so as to form a polypeptide:SSP complex, and a method of identifying the amino acid sequence of a polypeptide molecule capable of catalyzing a chemical reaction with a catalyzed rate constant, kcat, and an uncatalyzed rate constant, kuncat, such that the ratio of kcat/kuncat is greater than 10.

Abstract: The present disclosure describes the identification and use of aptamers and photoaptamers having slower dissociation rate constants than those obtained using previously described methods. Specifically, the present disclosure describes methods for the identification and use of aptamers to one or more targets within a histological or cytological sample, which have slow rates of dissociation. The aptamers may be used to assess localization, relative density, and presence or absence of one or more targets in cytological and histological samples. Targets may be selected that are specific and diagnostic of a given disease state for which the sample was collected. The aptamers may also be used to introduce target specific signal moieties. In addition to target identification, the aptamers may be used to amplify signal generation through a variety of methods.

Abstract: The invention relates to enzymes having xylanase, mannanase and/or glucanase activity, e.g., catalyzing hydrolysis of internal ?-1,4-xylosidic linkages or endo-?-1,4-glucanase linkages; and/or degrading a linear polysaccharide beta-1,4-xylan into xylose. Thus, the invention provides methods and processes for breaking down hemicellulose, which is a major component of the cell wall of plants, including methods and processes for hydrolyzing hemicelluloses in any plant or wood or wood product, wood waste, paper pulp, paper product or paper waste or byproduct. In addition, methods of designing new xylanases, mannanases and/or glucanases and methods of use thereof are also provided. The xylanases, mannanases and/or glucanases have increased activity and stability at increased pH and temperature.

Abstract: The present invention relates to a method for improving a repebody protein comprising repeat modules and a nucleotide library encoding a repebody protein library for improving the repebody protein. More particularly, the present invention relates to a method for improving a repebody protein using a module evolution method of sequentially mutating repeat modules constituting the repebody protein, and a nucleotide library encoding a repebody protein library used to improve the protein. According to the module evolution method of the present invention, an improved repebody protein can be screened which has a high binding affinity and accordingly increased specificity and activity, and thus it is easy to express a repebody used as an inhibitor, a therapeutic agent, and an analysis means against a target substance.

Abstract: The present invention is directed to methods, for example phage display assays, for bioengineering peptides that bind to individual distinct nucleotides. Also provided are peptides engineered by such methods. Specifically, cyclic peptides that bind individual distinct nucleotides are provided herein.

Abstract: Disclosed are methods for identifying bio-molecules with desired properties (or which are most suitable for a round of directed evolution) from complex bio-molecule libraries or sets of such libraries. Some embodiments of the present disclosure provide methods for virtually screening proteins for beneficial properties. Some embodiments of the present disclosure provide methods for virtually screening enzymes for desired activity and/or selectivity for catalytic reactions involving particular substrates. Some embodiments combine screening and directed evolution to design and develop proteins and enzymes having desired properties. Systems and computer program products implementing the methods are also provided.

Abstract: The invention provides a method for preparing a compound or a product having one or more characteristics that meet or exceed a user specification, the process comprising the step of selecting a first combination of chemical inputs, optionally together with physical inputs, and supplying those inputs to a reaction space, thereby to generate a first product; analysing one or more characteristics of the product generated; comparing the one or more characteristics against a user specification; using a genetic algorithm selecting a second combination of chemical inputs, optionally together with physical inputs, wherein the second combination differs from the first combination, and supplying those inputs to the reaction space, thereby to generate a second product; analysing one or more characteristics of the second product generated; comparing the one or more characteristics generated against the user specification; repeating the selecting and analysing steps for further individual combinations of chemical and/or p

Abstract: An object of the present invention is to develop and provide a method for efficiently producing a nucleic acid aptamer, particularly, a DNA aptamer, having higher specificity and binding activity against a target substance than those of nucleic acid aptamers obtained by conventional methods. The present invention provides a transcribable or replicable nucleic acid aptamer comprising a natural nucleotide and a non-natural nucleotide having an artificial base-pairable artificial base. The present invention also provides a method for sequencing a non-natural nucleotide-containing single-stranded nucleic acid molecule selected from a single-stranded nucleic acid library.

Abstract: The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

Abstract: The present invention relates to a method for preparing an expression vector encoding a tailored recombinase, which tailored recombinase is capable of recombining asymmetric target sequences within the long terminal repeat (LTR) of proviral DNA of a plurality of retrovirus strains inserted into the genome of a host cell, as well as to the obtained expression vector, cells transfected with this, expressed recombinase and pharmaceutical compositions comprising the expression vector, cells and/or recombinase. Pharmaceutical compositions are useful, e.g., in treatment and/or prevention of retrovirus infection. In particular, asymmetric target sequences present in a plurality of HIV strains are disclosed, as well as tailored recombinases capable of combining these sequences (Tre 3.0 and 4.0) and expression vectors encoding them.

Abstract: Methods of using a progressive cavity pump as a bioreactor are disclosed. Methods of isolating a biological product, such as pancreatic islet cells, using the bioreactor are also disclosed.

Abstract: Disclosed herein are novel synthetic prostate specific antigen (PSA)-targeted capture agents that specifically bind PSA. In certain embodiments, these PSA capture agents are biligand or triligand capture agents containing two or three target-binding moieties, respectively.

Abstract: Methods are provided to select plants and populations of epigenetically fixed crop plants with improved yield.

Abstract: The invention relates to a method for selecting a sequence set from a library of expressed nucleic acid sequences, wherein cells are provided, each cell comprises an expressed nucleic acid sequence expressed as a target protein. The cells are encapsulated by treating them with a cationic polysaccharide and subsequently treating them with an anionic polysaccharide, yielding encapsulated cells, perforating the membrane of the encapsulated cells, yielding solubilized compartments, contacting them with a ligand to said target protein, the ligand bearing a detectable label, and selecting a subset of solubilized compartments as a function of detectable label and isolating the expressed nucleic acid sequences from the selection as a selected sequence set.

Abstract: The present disclosure provides methods of integrating therapeutic protein and antibody generation and/or selection, evolution and expression in a eukaryotic host for manufacturing in a single system. Therapeutic proteins, including antibodies, are generated, optimized and manufactured in the same eukaryotic host system. The disclosed system of Comprehensive Integrated Antibody Optimization (CIAO!™) allows for simultaneous evolution of protein performance and expression optimization.

Abstract: The invention relates to a method for generating a gene mosaic by somatic in vivo recombination, comprising: e) in a single step procedure (vii) transforming a cell with at least one gene A having a sequence homology of less than 99.5% to another gene to be recombined that is an integral part of the cell genome or presented in the framework of a genetic construct, (viii) recombining said genes, (ix) generating a gene mosaic of the genes at an integration site of a target genome, wherein said at least one gene A has a single flanking target sequence either at the 5? end or 3? end anchoring to the 5? or 3? end of said integration site, and f) selecting clones comprising the gene mosaic, as well as a method of producing a diversity of gene mosaics and gene assembly.

Abstract: Methods, systems, and computer programs for designing probes or primers for nucleic acid sequencing, generating libraries of nucleic acid sequences, and mapping genomic sequences are provided herein,

Abstract: A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identification of high affinity TCRs. Several high affinities are disclosed.

Abstract: The disclosure relates to a switchable aptamer having a high affinity for a selected target such as a virus, cell or antibody when in the presence of a binding ion and a low affinity for said target in the absence of said binding ion. The switchable aptamer may be isolated from a pool comprising a mixture of aptamers by incubating the pool with the target ligand and a binding ion to form target-aptamer complexes; separating unbound aptamer molecules from the target-aptamer complexes; contacting the target-aptamer complexes with a chelating agent having affinity for the binding ion wherein a switchable aptamer specific to said target is released from the target-aptamer complexes; and isolating the switchable aptamer released in the preceding step.

Abstract: The present invention relates, inter alia, to polyspecificity reagents, methods of making the same, and methods of using the same in, inter alia, the selection, screening, enrichment, and identification of non-polyspecific, and thus developable, polypeptides.

Abstract: The present invention is directed to a method for obtaining an in vitro pharmacological model of a recombinant protein drug in a given host. A plurality of biomolecules are selected which are known or suspected to influence pharmacology of the recombinant protein in the host via a binding interaction with the recombinant protein. The recombinant protein is contacted with each selected biomolecule and the binding kinetics parameters for each interaction are determined using a binding assay. These steps are then repeated with all selected biomolecules to produce a plurality of binding kinetics parameters for the selected biomolecules. The combined results provide an in vitro pharmacological model of the recombinant protein in the host. The in vitro pharmacological model may then be used in several applications, such as optimizing new batches of recombinant protein drugs, developing biosimilar or bio-better drug candidates.