Abstract: Some embodiments described herein relate to a substrate comprising a silane functionalized surface for reversibly immobilizing a biological molecule of interest, such as oligonucleotides, polynucleotides, or protein. Methods for immobilizing the biological molecule and the use in DNA sequencing and other diagnostic applications are also disclosed.

Abstract: An object of the invention is to provide an electroporation method for treating vesicles with exogenous material for insertion of the exogenous material into the vesicles which includes the steps of: a. retaining a suspension of the vesicles and the exogenous material in a treatment volume in a chamber which includes electrodes, wherein the chamber has a geometric factor (cm.sup.?1) defined by the quotient of the electrode gap squared (cm.sup.2) divided by the chamber volume (cm.sup.3), wherein the geometric factor is less than or equal to 0.1 cm.sup.?1, wherein the suspension of the vesicles and the exogenous material is in a medium which is adjusted such that the medium has conductivity in a range spanning 50 microSiemens/cm to 500 microSiemens/cm, wherein the suspension is enclosed in the chamber during treatment, and b. treating the suspension enclosed in the chamber with one or more pulsed electric fields.

Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Abstract: A protein scaffold based on a consensus sequence of fibronectin type III (FN3) proteins, such as the tenth FN3 repeat from human fibronectin (human Tenascin), including isolated nucleic acids that encode a protein scaffold, vectors, host cells, and methods of making and using thereof, exhibit enhanced thermal and chemical stability while presenting six modifiable loop domains which can be engineered to form a binding partner capable of binding to a target for applications in diagnostic and/or therapeutic compositions, methods and devices.

Abstract: The present invention improves in vitro virus synthesis efficiency and stability of mRNA derived from screened cDNA in a cDNA display method to improve the efficiency and reliability of the production of a peptide by a molecular evolutionary engineering technique. Provided is a ligand which comprises three fingers formed from antiparallel ?-sheets and a loop region intercalated between the antiparallel ?-sheets, wherein at least a fingertip part formed by the loop region of each of the fingers is bound to the target molecule, and wherein the ligand comprises the amino acid sequence of SEQ ID NO: 1. In the amino acid sequence of SEQ ID NO: 1, X7 represents an arbitrary amino acid residue that constitutes the fingertip part of each of the fingers, each numeric character represents the number of amino acid residues, and X7 and X4 are not composed of the same amino acid residues as each other.

Abstract: A nucleic acid patch method for amplifying target nucleic acid sequences in circulating free DNA or residual DNA samples where the defining ends of the target nucleic acid sequences are unknown.

Abstract: This invention provides expression vectors for a ribonucleic acid (RNA) molecule comprising a double-stranded region of random sequence, sets and libraries of same, methods of generating same, and methods for identifying an RNA therapeutic or RNA molecule that has an ability to affect a biological parameter, for identifying a drug target for a disease or disorder of interest, and for identifying a variant of an RNA molecule that has an altered ability to affect a biological parameter of interest.

Abstract: The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

Abstract: The present invention relates to methods for controlling pest infestation using double stranded RNA molecules. The invention provides methods for producing transgenic cells expressing the double stranded RNA molecules, as well as compositions and commodity products containing or treated with such molecules.

Abstract: This invention provides UNA oligomers for selectively inhibiting V30M TTR expression, which can be used in treating amyloidosis. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis by administering a UNA oligomer to a subject.

Abstract: This invention relates, e.g., to a method for enhancing exon skipping in a pre-mRNA of interest, comprising contacting the pre-mRNA with an effective amount of a compound such as, for example, Perphenazine, Flupentixol DiHCl, Zuclopenthixol or Corynanthine HCl, or a compound which shares a similar 2-D structure and activity level with one of these compounds, or a pharmaceutically acceptable salt, hydrate, solvate, or isomer of the compound, and, optionally, with an antisense oligonucleotide that is specific for a splicing sequence in the pre-mRNA Methods for treating Duchenne muscular dystrophy (DMD) are disclosed.

Abstract: The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.

Abstract: The invention generally relates to isolated nucleic acid ligands that are neutral under physiological conditions.

Abstract: Conserved consensus sequences from known hepatitis B virus strains and known hepatitis C virus strains, which are useful in inhibiting the expression of the viruses in mammalian cells, are provided. These sequences are useful to silence the genes of HBV and HCV, thereby providing therapeutic utility against HBV and HCV viral infection in humans.

Abstract: The present invention provides pharmaceutical formulations for oral administration of antisense oligonucleotides, such as antisense oligonucleotides against SMAD7. The pharmaceutical formulations can be used to treat Crohn's disease, ulcerative colitis and chronic inflammatory bowel disease.

Abstract: Bruton's tyrosine kinase (Btk) plays an important role in the pathophysiology of local inflammation in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). A unique two hit model of ALI induced by lipopolysaccharide (LPS)/immune complex (IC)—was developed, along with viral-induced ALI caused by influenza virus and COPD caused by second hand smoke. Two types or therapeutics (i) Anti-neutrophil antibodies, and specifically their F(ab?)2 fragments conjugated to Btk-specific siRNA or (ii) small molecule Btk inhibitors were administered to lungs and silenced or inhibited Btk specifically in alveolar neutrophils. Such silencing/inhibition had a dramatic protective effect lung damage induced by LPS/IC, influenza virus and on COPD. Btk regulates neutrophil survival and clearance of apoptotic neutrophils in these diseases. Btk-targeted neutrophil-specific therapy restores homeostasis in lungs of patients with ALI/ARDS, acute lung infection, COPD and other lung diseases.

Abstract: The present invention relates to a method and compositions for the treatment of cystic fibrosis.

Abstract: The present description relates to methods for delivering polypeptide cargos from an extracellular space to the cytosol and/or nucleus of a target eukaryotic cell. The methods involve contacting the cell with the polypeptide cargo in the presence of a peptide shuttle agent at a concentration sufficient to increase the polypeptide cargo's transduction efficiency. Also described here are parameters that may be used in the rational design of such synthetic peptide shuttle agents, peptide shuttle agents that satisfy one or more of these design parameters, as well as methods and compositions relating to the use of the synthetic peptide shuttle agents for delivery of a variety of polypeptide cargos (such as transcription factors, antibodies, CRISPR-associated nucleases and functional genome editing complexes) from an extracellular space to the cytosol and/or nucleus of target eukaryotic cells. Applications and targets for genome-editing NK cells for improved immunotherapy are also described.

Abstract: A vector for transformation into a host cell is described comprising a toxic gene encoding a product that is lethal to the host cell, wherein the toxic gene comprises: an essential sequence region whose integrity is necessary in order for the encoded toxic gene product to be lethal to the host cell; an inessential sequence region whose integrity is not essential in order for the encoded toxic gene product to be lethal to the host cell; a regulatory sequence inserted in-frame into the inessential sequence region; and a cloning site within the essential sequence region for insertion of a nucleic acid sequence, wherein the regulatory sequence and the cloning site are positioned so as to allow the regulatory sequence to be operably linked to a nucleic acid sequence when the nucleic acid sequence is inserted into the cloning site.

Abstract: It relates to a Mortierella alpine ATCC32222 uracil auxotroph strain and a construction method thereof. In the present invention, Mortierella alpine ATCC32222 is used as a material and undergoes gene knockout through an Agrobacterium tumefaciens mediated genetic manipulation technology, to obtain the Mortierella alpine uracil auxotroph. The method is of great significance for the basic theoretic researches of the oil producing fungus Mortierella alpine ATCC32222 and product development.

Abstract: Method for heterologous protein production in plant cell plastids comprising introducing into plant cells nucleic acid components that encode heterologous proteins under the control of promoters operative in plastids, vectors, host cells, plants and uses thereof.

Abstract: The present invention relates to the regulation of transgene expression in plants through a transactivation system which comprises the following: (1) a promoter comprising LexA binding sites; and (2) a fusion transactivator protein comprising a LexA DNA-binding domain and an activation domain, such as the transactivation domain of a C-repeat binding factor protein, for example, from a dehydration responsive element (DREB) factor.

Abstract: Mutant photosynthetic microorganisms having reduced chlorophyll and increased photosynthetic efficiency are provided. The mutants have a locked in high light-acclimated phenotype, in which many of the photosynthetic parameters characteristic of high light acclimated wild type cells are found in the LIHLA mutants when acclimated to low light, such as reduced chlorophyll, reduced NPQ, higher qP, higher Ek, higher Pmax per unit chlorophyll with little to no reduction in Pmax per cell, and higher rates of electron transport through photosystem II over a wide range of light intensities. Provided herein are constructs for attenuating or disrupting genes are provided for generating mutants having the LIHLA phenotype. Also provided are methods of culturing LIHLA mutants for the production of biomass or other products.

Abstract: Polynucleotides and polypeptides incorporated into expression vectors have been introduced into plants and were ectopically expressed. The polypeptides of the invention have been shown to confer at least one regulatory activity and confer increased yield, greater height, greater early season growth, greater canopy coverage, greater stem diameter, greater late season vigor, increased secondary rooting, more rapid germination, greater cold tolerance, greater tolerance to water deprivation, reduced stomatal conductance, altered C/N sensing, increased low nitrogen tolerance, increased low phosphorus tolerance, or increased tolerance to hyperosmotic stress as compared to the control plant as compared to a control plant.

Abstract: Compositions and methods for conferring pesticidal activity to bacteria, plants, plant cells, tissues and seeds are provided. The toxin coding sequences can be used in DNA constructs or expression cassettes for expression in plants and bacteria. Compositions include transformed bacteria, plants, plant cells, tissues, and seeds. In particular, polynucleotide sequences and the toxin proteins encoded thereby are provided. Also provided are antibodies specifically binding to those amino acid sequences. In particular, the invention encompasses nucleotide sequences encoding fusion proteins, as well as biologically active variants and fragments thereof, wherein the fusion protein contains the C-terminal portion of SEQ ID NO:43. The fusion protein may also contain the N-terminal portion of SEQ ID NO:45.

Abstract: The present invention provides isolated promoters, transgene expression cassettes, vectors, kits, and methods for treatment of genetic diseases that affect the cone cells of the retina.

Abstract: The present invention describes generation and the use of adenovirus variants (Ad) possessing modified capsid penton base protein where mutations in the penton based RGD loop are made to avoid Ad binding to cellular ?3-integrins. Specifically, the ablation of Ad penton base interaction with cellular ?3-integrins results in reduced activation of inflammation after intravenous Ad administration. Further, the introduction into penton RGD loop of non-RGD containing peptides, which mediate virus entry into the cell via new cellular receptors, allows for the efficient Ad-mediated gene delivery into target cells in vivo after intravascular virus administration and triggers significantly reduced toxicity associated with Ad injection.

Abstract: The disclosure provides compositions and methods for increasing efficiency of Cas9-mediated target DNA modification. Specifically, the disclosure provides compositions and methods for carrying out site-directed modification of a target DNA, the methods comprising contacting the target DNA with: a) a complex comprising a Cas9 polypeptide and a guide RNA, and b) a Rad51 polypeptide. The site-directed modification of a target DNA can be carried out in a living cell in vitro, in a living cell in vivo, or in a cell-free system in vitro.

Abstract: Described herein are methods and vectors for rational, multiplexed manipulation of chromosomes within open reading frames (e.g., in protein libraries) or any segment of a chromosome in a cell or population of cells, in which various CRISPR systems are used.

Abstract: Disclosed herein are nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Disclosed herein are engineered non-naturally occurring nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Targetable nuclease systems can be used to edit genetic targets, including recursive genetic engineering and trackable genetic engineering methods.

Abstract: The invention relates to a process for the preparation of a fermentation product from ligno-cellulosic material, comprising the following steps: a) optionally pre-treatment of the ligno-cellulosic material; b) optionally washing of the optionally pre-treated ligno-cellulosic material; c) enzymatic hydrolysis of the optionally washed and/or optionally pre-treated ligno-cellulosic material using an enzyme composition comprising at least two cellulase and whereby the enzyme composition at least comprises GH61; d) whereby less than 7.5 mg enzyme composition/g glucan (on dry matter and enzyme as protein) or less than 3.0 mg enzyme composition/g feedstock (on dry matter and enzyme as protein) is used; and e) fermentation of the hydrolysed ligno-cellulosic material to produce a fermentation product; and f) optionally recovery of a fermentation product; wherein before and/or during the enzymatic hydrolysis oxygen is added to the ligno-cellulosic material.

Abstract: Provided herein is a non-naturally occurring microbial organism having a 1,3-butanediol (1,3-BDO) pathway and comprising at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. In some embodiments, the pathway includes reducing equivalents from CO or hydrogen. In certain embodiments, a 1,3-BDO pathway proceeds by way of central metabolites pyruvate, succinate or alpha-ketoglutarate. Also provided herein is a method for producing 1,3-BDO, includes culturing such microbial organisms under conditions and for a sufficient period of time to produce 1,3-BDO.

Abstract: The present invention relates to a process for producing a syrup comprising liquefying an aqueous granular starch slurry with an alpha-amylase variant comprising an alteration at one or more positions corresponding to any of positions 1, 2, 68, 71, 126, 133, 142, 144, 156, 158, 176, 185, 201, 205, 213, 239, 279, 316, 318, 360, 416, 437 and 450 of SEQ ID NO: 1 to provide liquefied starch-containing material; saccharifying the liquefied starch-containing material in the presence of a glucoamylase, and a pullulanase derived from Bacillus deramificans, Bacillus subtilis, Bacillus amyloderamicans, or Bacillus acidopullulyticus to provide a dextrose syrup, and optionally isomerizing to provide a fructose syrup.

Abstract: Provided is a biomass hydrothermal decomposition system which includes: a biomass supply unit that supplies a biomass raw material; hydrothermally decomposing the biomass raw material using pressurized hot water; a hydrothermal decomposition unit that dissolves lignin components and hemicellulose components in the pressurized hot water; a biomass solid fraction discharge unit that discharges a biomass solid fraction from the hydrothermal decomposition unit; an enzymatic liquefaction tank that is in connection with the biomass solid fraction discharge unit, and in which the discharged biomass solid fraction is introduced, and an enzyme is supplied to the biomass solid fraction to liquefy the biomass solid fraction; and a discharge unit that discharges the liquefied biomass solid fraction.

Abstract: A method is disclosed for hydrolyzing an alpha-1,5 glucosyl-fructose linkage in a saccharide (disaccharide or oligosaccharide) such as leucrose. This method comprises contacting the saccharide with an alpha-glucosidase enzyme such as transglucosidase or glucoamylase under suitable conditions, during which contacting step the enzyme hydrolyzes at least one alpha-1,5 glucosyl-fructose linkage of the saccharide. This method is useful for reducing the amount of leucrose in a filtrate isolated from a glucan synthesis reaction, for example.

Abstract: The present invention relates to polypeptides having cellulolytic enhancing activity, catalytic domains, and carbohydrate binding domains, and polynucleotides encoding the polypeptides, catalytic domains, and carbohydrate binding domains. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains, and carbohydrate binding domains.

Abstract: A medium is described for the protein-free and serum-free cultivation of cells, especially mammalian cells, whereby the medium contains a proportion of soy hydrolysate.

Abstract: The present invention relates to Enterokinase-cleavable polypeptides comprising an Enterokinase cleavage site connected to a polypeptide and their use for making the target polypeptide by expression. The invention also relates to DNA sequences, vectors and host cells for use in expressing the Enterokinase-cleavable polypeptides.

Abstract: Provided is a rapid screening method for detecting mucopolysaccharidosis IVA and mucopolysaccharidosis VII. Biological samples containing glycosaminoglycans are enzymatically digested to converts chondroitin 6-sulfate into ?Di-6S. ?Di-6S is assayed by liquid chromatography-tandem mass spectroscopy analysis. Elevated ?Di-6S, and thus elevated chondroitin 6-sulfate present in the sample, indicates a likelihood that the test subject is afflicted with mucopolysaccharidosis IVA or mucopolysaccharidosis VII.

Abstract: A test strip or electrochemical sensor for measuring the amount of an analyte in a biological fluid, e.g. the glucose content of whole blood, includes a size self-limiting reagent formulation employing an enzyme system for reaction with the analyte, the reactive system mixed into a water-soluble swellable polymer matrix containing small water-insoluble particles having a nominal size of about 0.05 to 20 ?m, preferably about 1 to 10 ?m. The weight ratio of the water-insoluble particles to the water-soluble swellable polymer matrix is about 1/2 to 2/1. The reagent formulation is deposited onto a non-porous substrate to form a thin layer about 6-16 ?m thick, providing a rapid and stable response to application of a sample, while being insensitive to the amount of the sample.

Abstract: Methods and systems for using encapsulated microbubbles to process biological samples are disclosed. According to one aspect, a method for using encapsulated microbubbles to process a biological sample includes creating a mixture comprising encapsulated microbubbles mixed with a biological sample and adding activation energy to the mixture to cause at least some of the microbubbles to oscillate or burst and thereby process the sample, including effecting cell lysis, shearing DNA, and/or performing tissue dispersion.

Abstract: Methods and compositions for the detection and quantification of nucleic acids are provided. In certain embodiments, methods involve the use of cleavable probes that comprise a ribonucleotide position that is susceptible to endoribonuclease (e.g., RNase H) cleavage in the presence of target nucleic acid molecules. Probes of the embodiments may also comprise non-natural nucleotide linked to a reporter and/or quenching moiety.

Abstract: Methods and systems for detecting chemical and biological agents using oligonucleotide aptamers. A sensor includes a detection aptamer that has a binding domain for the chemical or biological agent, and is bound to fibers of a textile such as a patch or article of clothing. The detection aptamer can be stabilized and enhanced through a stabilization agent such as trehalose or through binding to a nanoparticle which is then bound to the fiber. Binding of the chemical and biological agent of interest to the detection aptamer can be reported to the user or wearer of the textile in a variety of ways, including visually and electrically.

Abstract: Methods are provided for multiplexed amplification of selected targets and analysis of the amplified targets. In preferred aspects the amplification and analysis take place on the same solid support and preferably in a localized area such as a bead or a feature of an array. Targets are circularized by hybridization to probes followed by ligation of the ends of the target to form a closed circle. The targets are then used as template for extension of an array bound probe resulting in extended probes having multiple copies of the target. The extended probes can then be analyzed. The methods may be used for genotyping, sequencing and analysis of copy number.

Abstract: A method for sequencing includes steps of (a) providing first and second nucleic acid templates, wherein the two templates have different sequences; (b) extending a first primer bound to the first template using a first polymerase species and a first set of nucleotide analogs; (c) extending a second primer bound to the second template using a second polymerase species and a second set of nucleotide analogs, wherein the first polymerase species is different from the second polymerase species and wherein the first set of nucleotide analog is different from the second set of nucleotide analog, (d) detecting the first and second primer extension products; and (e) repeating steps (b) through (d), thereby determining the different sequences of the first and second templates.

Abstract: Disclosed are methods for determining at least one sequence of interest of a fetus of a pregnant mother. In various embodiments, the method can determine one or more sequences of interest in a test sample that comprises a mixture of fetal cellular DNA and mother-and-fetus cfDNA. In some embodiments, methods are provided for determining whether the fetus has a genetic disease. In some embodiments, methods are provided for determining whether the fetus is homozygous in a disease causing allele when the mother is heterozygous of the same allele. In some embodiments, methods are provided for determining whether the fetus has a copy number variation (CNV) or a non-CNV genetic sequence anomaly.

Abstract: We describe ultra-high throughput polony genome sequencing that can permit, for example, generating raw data to re-sequencing the human genome in about one week (including library prep and sequencing) at a reasonable cost. The methods described herein include one or more of the following: (1) increasing polony sequencing read length, (2) improving library construction and emulsions protocols, (3) increasing bead density and/or moving to alternative clonal amplication strategies (other than emulsion PCR or ePCR), (4) extending software capabilities to allow SNP calls from our new sequencing raw data, (5) Dual Primer Emulsion PCR, and (6) diagnostic method exploiting one or more of the foregoing.

Abstract: The present invention relates to a process for determining in vitro the immune status of an individual according to which: (a) a blood sample from the individual is provided, (b) at least two reagents specific to at least two products of expression of at least two target genes are provided; (c) the expression of said at least two target genes is determined, and (d) the expression of said at least two target genes respectively is compared with a reference expression, with a change in the expression of said at least two target genes relative to their reference expression indicating that the individual's immune status has changed, and a correlation between the expression of said at least two target genes with their reference expression indicating that the individual's immune status is normal; as well as a kit for determining said immune status of the individual.

Abstract: Methods to identify markers for brain damage using fresh brain tissue and methods and compositions for detecting these markers are disclosed.

Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.