Abstract: The present disclosure provides for systems and methods for generating and displaying a three dimensional map of a protein sequence. An exemplary method can provide for using deep learning models to predict protein folding and model protein folding using three dimensional representations. The method more effectively exploits the potential of deep learning approaches. The method approach overall involves three stages—computation, geometry, and assessment.

Abstract: An oligo- or polynucleotide analogue having one or more structures of the general formula: where B is a pyrimidine or purine nucleic acid base, or an analogue thereof, is used for treating obesity-related metabolic diseases.

Abstract: Unique compounds useful for inhibiting a proteasome in a cell, pharmaceutical compositions and methods of their use are provided herein.

Abstract: The present disclosure relates to the use of recombinant proteins for inducing epigenetic modifications at specific loci, as well as to methods of using these recombinant proteins for modulating the expression of genes in plants.

Abstract: The present invention relates to compositions and methods for the prevention or the treatment of lung cancer, wherein the compositions comprise an antibody binding to progastrin and the methods comprise the use of an antibody binding to progastrin.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: Provided herein is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g., X1, X2, R2, R3, R4, R5, R6, R7, R8, m, n) are as described herein. Compounds of Formula I, pharmaceutically acceptable salts thereof, pharmaceutical compositions of either of the foregoing, and combinations of any of the foregoing can be used to treat tyrosine kinase non-receptor 1 (TNK1)-mediated diseases, disorders and conditions.

Abstract: Methods for treating neurological and other disorders, including autoimmune disorders are described. Also described is a method of treating a disorder in which Toll-like Receptor 2 (TLR2) activation by binding to myeloid differentiation primary response 88 (MyD88) plays a role in disease pathogenesis. Further a method is described that includes the administration of a composition, including a peptide sequence, that inhibits the activation of TLR2 by MyD88.

Abstract: The current invention provides monocytic cells transfected with chimeric antigen receptor (CAR) to selectively home to tumors and upon homing differentiate into dendritic cells capable of activating immunity which is inhibitory to said tumor. In one embodiment of the invention, monocytic cells are transfected with a construct encoding an antigen binding domain, a transcellular or structural domain, and an intracellular signaling domain. In one specific aspect of the invention, the antigen binding domain interacts with sufficient affinity to a tumor antigen, capable of triggering said intracellular domain to induce an activation signal to induce monocyte differentiation into DC.

Abstract: Embodiments for the synthesis of sensitive oligonucleotides as well as insensitive oligonucleotides are provided. Sulfur-based groups are used for the protection of exo-amino groups of nucleobases, phosphate groups and 2?—OH groups, and as cleavable linker for linking oligonucleotides to a support. Oligonucleotide syntheses are achieved under typical conditions using phosphoramidite chemistry with important modifications. To prevent replacing sulfur-based protecting groups by acyl groups via cap-exchange, special capping agents are used. To retain hydrophobic tag to assist RP HPLC purification, special phosphoramidites are used in the last synthetic cycle. With the sulfur-based groups for protection and linking, oligonucleotide deprotection and cleavage are achieved via oxidation followed by beta-elimination under mild conditions.

Abstract: Provided herein are methods of activating immune cells. The method includes providing a population of immune cells and contacting the population of immune cells with a first agent and a second agent. The first agent includes an immune cell activator attached to a first binder moiety, and the second agent includes at least one capture oligomer. The at least one capture oligomer is capable of associating with the first binder moiety. Also provided are kits for activating immune cells.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: The disclosure is directed to inhibitory agents that hybridize to a GAPLINC RNA and inhibit or reduce the expression of the GAPLINC RNA. The GAPLINC RNA is a long non-coding RNA (lncRNA) located on chromosome 18 between the protein-coding genes Tgif and Dlgap1. The disclosure also features pharmaceutical compositions including the inhibitory agents and methods of using the inhibitory agents to treat an inflammatory disease, such as sepsis.

Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2?-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

Abstract: A hydrogel precursor composition includes 10 wt % to 40 wt % N-isopropylacrylamide, 0.5 wt % to 2 wt % N,N?-methylenebisacrylamide, a solvent, and a photoinitiator. The hydrogel precursor composition is photocurable and thermally responsive. A thermally responsive hydrogel is formed by photopolymerizing the hydrogel precursor composition. The thermally responsive hydrogel may be used to mimic the activity of muscle fibers.

Abstract: Systems and methods for automated imaging and evaluation of image based features are disclosed herein. Method for automated imaging and evaluation of image based features can include receiving time-lapse images of at least one human embryo contained in a multi-well culture dish that can have a plurality of micro-wells. Image based features can be automatically generated from the time-lapse images of the human embryo. The image based features, which can include a cavitation feature, can be inputted into a classifier. The classifier can automatically and directly generate a viability prediction with the classifier from the image-based features.

Abstract: Disclosed are methods for detecting remnant cancer cells in a tissue sample.

Abstract: Branching phosphoramidite monomers and molecules having comb-like structures are disclosed and described. A branching phosphoramidite monomer having the structure is provided wherein R4 and R5 are independently —(O—CH2—CH2—)n where n is 1-5 or —O—(CH2—)n where n is 1-10, and R1, R2, and R3 are each one of dimethoxytrityl (DMT)—O—, levulinyl (Lev)—O—, and a phosphoramidite.

Abstract: The present disclosure provides a method of producing uniformly sized organoids/multicellular spheroids using a microfluidic device having an array of microwells. The method involves several successive steps. First, a microfluidic device containing parallel rows of microwells that are connected with a supplying channel is filled with a wetting agent. The wetting agent is a liquid that is immiscible in water. For example, the wetting agent may be an organic liquid such as oil. In the next step, the agent in the supplying channel and the microwells is replaced with a suspension of cells in an aqueous solution that contains a precursor for a hydrogel. Next, the aqueous phase in the supplying channel is replaced with the agent, which leads to the formation of an array of droplets of cell suspension in the hydrogel precursor solution, which were compartmentalized in the wells. The droplets are then transformed into cell-laden hydrogels.

Abstract: This invention relates to anti-CD70 antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are ?CD70 antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the ?CD70 antibodies of the invention are conjugated to one or more toxins. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The present invention relates to a method for growing, rapidly and massively ex vivo, cells collected from a living subject to provide a safe and effective pharmaceutical preparation for biological tissue repair/regeneration. Specifically, the present invention relates to a method for growing cells in a sample collected from a living subject by culturing the cells in a medium containing allogeneic (including autogenic) serum. Preferably the allogeneic serum has been determined as being negative for a serum tumor marker and/or an infectious factors, and the amount of the anticoagulant (e.g., heparin, a heparin derivative, or a salt thereof) added to the collected sample is less than 5 U/mL with respect to the volume of the sample or the amount of the anticoagulant in the medium at the start of culture is less than 0.5 U/mL. The present invention further relates to use of the method.

Abstract: The invention relates to method for cultivating stem cells in vitro, comprising the following steps: providing a sample comprising stem cells and cultivating the stem cells by subjecting the sample to a treatment for a first period of time. The treatment is carried out under hypothermic conditions having a defined temperature and a defined atmosphere, wherein the temperature does not exceed 15° C. and the atmosphere has an oxygen content not exceeding 21% (v/v). Thereby, the first period of time is 4 days to 4 weeks.

Abstract: This disclosure relates to methods of generating pacemaker cells for use in therapeutic strategies that address a heart that beats abnormally. In certain embodiments, one mixes cells with an epithelial-to-mesenchymal transformation inhibitor in combination with a nucleic acid encoding a transcription factor such as a vector that encodes a transcription factor such as Tbx18 in operable combination with a eukaryotic promoter to produce pacemaker cells that are then transplanted into the heart.

Abstract: The present invention relates to a method of typing a microbiome for having a desirable or undesirable signature, comprising analyzing the composition of the population of microorganisms in the microbiome based on taxonomic variation in the DNA sequence of the microbial 16S-23S rRNA internal transcribed spacer (ITS) regions in the genomic DNA of the microorganisms, wherein the sequences of conserved DNA regions comprised in the 16S and 23S rRNA sequences flanking said ITS region in the genome of the microorganisms comprise primer binding sites for amplification of the ITS regions.

Abstract: The present invention relates to a fusion polypeptide that inhibits TLR1/2, TLR2/6, TLR7, TLR8 and TLR9 signaling pathways as well as Toll-like receptor 4 (TLR4) and TLR3, and a pharmaceutical composition for preventing or treating TLR pathway mediated diseases. The fusion peptide of the present invention has an excellent effect of inhibiting TLR4 and various TLR pathways and can be effectively used in preventing and treating various TLR pathway mediated diseases caused by the signaling pathways, such as autoimmune diseases, inflammatory diseases and degenerative neurological diseases, by inhibiting the TLR mediated immune responses.

Abstract: The present disclosure provides systems and methods for determining effects of genetic variants on selection of polyadenylation sites (PAS) during polyadenylation processes. In an aspect, the present disclosure provides a polyadenylation code, a computational model that can predict alternative polyadenylation patterns from transcript sequences. A score can be calculated that describes or corresponds to the strength of a PAS, or the efficiency in which it is recognized by the 3?-end processing machinery. The polyadenylation model may be used, for example, to assess the effects of anti-sense oligonucleotides to alter transcript abundance. As another example, the polyadenylation model may be used to scan the 3?-UTR of a human genome to find potential PAS.

Abstract: A method of growing primary human epithelial cells, in particular human epithelial cells using a basal formula containing individual (a) amino acids, (b) vitamins, (c) trace elements, and (d) other organics such as linoleic acid. The basal medium may be a mixture of amino acids, vitamins, and salts that constitute the basic media that is used to culture epithelial cells over a number of population doublings, e.g., over at least one week, while maintaining a normal phenotype and exerting low stress on the cultured cells, and maintaining lineage heterogeneity.

Abstract: A bench top incubator is described. The bench top incubator includes a multiple temperature sensors and control systems so as to provide independent data logs of temperature data from each of the multiple temperature sensors. The incubator is relatively simple and small in design and can be conveniently located to carry out temperature processing of biological samples such as fixed cells and tissues, biological fluids, and so forth.

Abstract: This invention provides a method for the in vivo delivery of oligonucleotides. The invention utilizes the presence of one or plurality of HES linked to an oligonucleotide to deliver a nucleic acid sequence of interest into the cytoplasm of cells and tissues of live organisms. The delivery vehicle is nontoxic to cells and organisms. Since delivery is sequence-independent and crosses membranes in a receptor-independent manner, the delivered oligonucleotide can target complementary sequences in the cytoplasm as well as in the nucleus of live cells. Sequences of bacterial or viral origin can also be targeted. The method can be used for delivery of genes coding for expression of specific proteins, antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs or any nucleic acid sequence in a living organism. The latter include mammals, plants, and microorganisms such as bacteria, protozoa, and viruses.

Abstract: The invention provides compositions, methods and treatment regimens for treating cancer comprising periodic subcutaneous administration of the fusion protein of SEQ ID NO:1 to a cancer patient resulting in enhanced activation of CD8+ T-cells with minimal effects on regulatory T cell (Treg) expansion and providing enhanced anti-tumor efficacy while also mitigating T cell inactivation/exhaustion.

Abstract: A collection pipette that collects a microscopic object includes a first tube part, a second tube part connected to an end of the first tube part, and a third tube part connected to the other end of the first tube part. The longitudinal direction of the third tube part intersects with the longitudinal direction of the first tube part, and is parallel to the longitudinal direction of the second tube part. For example, the length in the longitudinal direction of the third tube part is shorter than the length in the longitudinal direction of the first tube part.

Abstract: Disclosed are methods for delivering a therapeutic or diagnostic agent to the cytosol of a cell in a subject. The disclosed methods generally include administering to the subject an effective amount of a lipid nanoparticle comprising the therapeutic or diagnostic agent and an effective amount of a membrane-destabilizing polymer. Also disclosed are related compositions and delivery systems.

Abstract: Disclosed herein are antisense oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA at the 5?-end of UBE3A-AS, which is downstream of SNORD115-45 snoRNA. Also disclosed are pharmaceutical compositions and methods for treatment of Angelman syndrome.

Abstract: The present invention provides a hollow fiber membrane module which makes it possible to concentrate incubated platelets by efficiently removing water from an incubated platelet suspension liquid containing incubated platelets while suppressing deterioration of the function of the incubated platelets. The present invention provides an incubated platelet concentration module in which a plurality of hollow fiber membranes each having pores with an average pore diameter of 2 ?m or less on a surface of the hollow fiber membrane are packed in a casing having at least one inlet for supplying an incubated platelet suspension liquid before concentration into the hollow fiber membranes, wherein a value (X/Y1) obtained by dividing a total cross-sectional area (X) of the plurality of hollow fiber membranes by a total cross-sectional area (Y1) of the least one inlet is 4.0 or less.

Abstract: Disclosed are peptides that contain up to about 35 amino acids, including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated, or (ii) an amino acid comprising an ester-moiety linked via peptide bond, or both (i) and (ii), wherein the peptide is capable of self-assembly to form nanofibrils in the presence of an enzyme that hydrolyzes the phosphate group, the sulfate group, or the ester-moiety. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for in vitro and in vivo cellular imaging, treating cancerous conditions, collecting a secretome from a cell upon which the pericellular hydrogels/nanofibrils form, and screening the collected secretome.

Abstract: The present invention relates to the field of dental care, e.g., with toothpaste, tooth gel, mouth-wash, mouth spray or oral care foam. In particular, it provides an anti-inflammatory and senolytic dental care product with tooth whitening characteristics. The dental care product comprises calcium phosphate particles of a specific size, the self-assembling peptide P11-4 or oligopeptide 104 of SEQ ID NO: 1, an extract of a plant of the genus Rhododendron, preferably, an alpine rose or Alpenrose such as Rhododendron ferrugineum or Rhododendron hirsutum, and an extract of a plant of the genus Leontopodium, such as Leontopodium nivale, which is also called Edelweiss. The dental care product may further comprise an extract of a plant of the genus Eleutherococcus, such as Eleutherococcus senticosus, which is also designated Siberian ginseng or Acanthopanax senticosus.

Abstract: The present disclosure provides methods and compositions for the treatment of cancer. In some aspects, the present disclosure provides splice-switching oligonucleotides that downregulate AR or EGFR expression and methods of using these splice-switching oligonucleotides to treat cancer.

Abstract: Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, a “bandaid-like” covering, containing epithelial cells with supporting early lineage stage mesenchymal cells. The cells are incorporated into soft gel-forming biomaterials prepared under serum-free, defined conditions comprised of nutrients, lipids, vitamins, and regulatory signals that collectively support stemness of the donor cells. The graft is covered with a biodegradable, biocompatible, bioresorbable backing used to affix the graft to the target site. The cells in the graft migrate into and throughout the tissue such that within a couple of weeks they are uniformly dispersed within the recipient (host) tissue.

Abstract: An antisense oligonucleotide capable of preventing or reducing exon 80 inclusion into a human COL7A1 mRNA, and methods for preventing or reducing exon 80 inclusion into a human COL7A1 mRNA.

Abstract: Provided are a unimolecular nanoparticle, a composition thereof, and methods of use thereof, and includes 1) a dendritic polymer having a molecular weight of about 500-120,000 Da and terminating in hydroxyl, amino or carboxylic acid groups; 2) cationic polymers attached to at least a majority of the terminating groups of the dendritic polymer via a pH-sensitive linker, wherein each cationic polymer comprises a polymeric backbone attached to cationic functional groups and to weakly basic groups by disulfide bonds, wherein the molar ratio of cationic functional groups to weakly basic groups ranges from 1:1-5:1, and has a molecular weight from about 1,000-5,000 Da; and 3) poly(ethylene glycol) attached to a plurality of cationic polymers and having a terminal group selected from a targeting ligand, OH, O-alkyl, NH2, biotin, or a dye, wherein the terminal group of at least one poly(ethylene glycol) is having a molecular weight of about 1,000-15,000 Da.

Abstract: Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.

Abstract: The present disclosure relates to RNAi constructs with improved cellular uptake characteristics and methods of use of these compounds for silencing expression of long coding RNAs (IncRNAs).

Abstract: An object of the present invention is to provide a medium that comprises fewer protein components and enables the maintenance of pluripotent stem cells in an undifferentiated state. The culture medium for pluripotent stem cells comprises a GSK3? inhibitor (A) and a DYRK inhibitor (B).

Abstract: The invention relates to new identified mutations in the epidermal growth factor receptor gene, leading to amino acidic changes which highly correlate with the resistance to a therapy regimen comprising cetuximab. The invention includes peptide sequences and primers to detect the mutations, as well as kits for predicting the response of a subject to a therapy regime comprising cetuximab. In particular, the invention is useful in the therapy regimen applicable to metastasic colorectal cancer.

Abstract: Method for targeted alteration of a duplex acceptor DNA sequence in a plant cell protoplast, comprising combining the duplex acceptor DNA sequence with a donor mutagenic nucleobase, wherein the duplex acceptor DNA sequence contains a first DNA sequence and a second DNA sequence which is the complement of the first DNA sequence and wherein the donor mutagenic nucleobase comprises at least one mismatch with respect to the duplex acceptor DNA sequence to be altered, preferably with respect to the first DNA sequence, wherein the method further comprises a step of introducing the donor mutagenic nucleobase into the cell protoplasts using polyethylene glycol (PEG) mediated transformation and the use of PEG protoplast transformation for enhancing the rate of targeted mutagenesis.

Abstract: The present invention relates to a method of inhibiting p-glycoprotein (P-gp) expression in a cell. The method involves contacting a cell expressing P-gp with a composition comprising an effective amount of an A2A adenosine receptor (A2A AR) agonist to inhibit P-gp expression in the cell. Methods of enhancing the bioavailability of a chemotherapeutic in a subject having multi-drug resistant (MDR) cancer and methods of increasing P-gp-mediated efflux in a cell are also disclosed.

Abstract: Provided herein is a method of making an aligned ECM scaffold useful in refractive correction of the eye and repair of the cornea. Methods of use of the scaffold as well as a scaffold construct are provided.

Abstract: Method for reprogramming differentiated cells into lineage restricted progenitor cells is provided. The method may include contacting differentiated cells with inhibitors of tyrosine phosphatases and apoptosis to de-differentiate differentiated cells into lineage restricted progenitor cells.

Abstract: An objective of the present invention is to obtain two types of substantively homogeneous cancer stem cell populations which can be characterized using the cell surface marker Lgr5, and to provide cancer therapeutics using an antibody against a cell membrane molecule specifically expressed in these cancer stem cells by identifying said cell membrane molecule. A further objective is to provide, using an antibody against a cell membrane molecule specifically expressed in cancer stem cells, a reagent for detecting cancer stem cells, and a method for diagnosing and sorting cancer patients. The present inventors discovered that highly pure large intestine cancer stem cells (CSC) can be obtained in a large quantity, and identified the two types of conditions of large intestine CSCs distinguishable through Lgr5 expression. Moreover, the present inventors discovered that an antibody against a cell membrane molecule specifically expressed in said cancer stem cells can damage said cells.

Abstract: This invention provides compositions for use in distributing active agents for treating a malignant tumor in a subject. The compositions contain RNAi molecules targeted to a human GST-?, along with RNAi molecules targeted to a human p21, and a pharmaceutically acceptable carrier. The carrier can include nanoparticles composed of an ionizable lipid, a structural lipid, one or more stabilizer lipids, and a lipid for reducing immunogenicity of the nanoparticles. This invention further provides methods for preventing or treating a malignant tumor by administering a therapeutically effective amount of an RNAi composition.