Abstract: Methods and compositions are provided for treating hyperproliferative disorders in patients with a PI3K inhibitor, GDC-0032 as a single agent or in combination with chemotherapeutic agents.

Abstract: The present invention relates to the field of biomarkers. More specifically, the present invention relates to biomarkers useful in diagnosing brain injuries. Brain injury can include overt or traumatic brain injury, as well as subclinical brain injury (SCI). In one embodiment, a method for diagnosing SCI in a patient comprises (a) collecting a sample from the patient; (b) measuring the levels of a panel of biomarkers in the sample collected from the patient, wherein the panel of biomarkers comprises ASTN1, BAI3, CNDP1, ERMIN, GFAP, GRM3, KLH32, MAGE2, NRG3, NRGN, OMG, SLC39A12, RTN1, and MT3; and (c) comparing the levels of the panel of biomarkers with predefined levels of the same panel of biomarkers that correlate to a patient having SCI and predefined levels of the same panel of biomarkers that correlate to a patient not having SCI, wherein a correlation to one of the predefined levels provides the diagnosis.

Abstract: Compositions and methods for increasing or decreasing DNA repair are provided. Composition includes a Brd4 polypeptide, fragment, fusion, or variant thereof. The fusion protein can include a protein transduction, a targeting domain, or a combination thereof to enhance delivery of the fusion protein to the interior of a particular target cell, such as a cancer cell. Inhibitory nucleic acids that target a Brd4 mRNA and antibodies that target a Brd4 polypeptide are also disclosed. The inhibitory nucleic acid or antibody can target a sequence or epitope on Brd4 isoform B that is absent on Brd4 isoform A and Brd4 isoform C. Methods for increasing or decreasing the sensitivity of cells to a DNA damaging agent, methods of treating cancer, and methods of determining cells' sensitivity to a DNA damaging agent are also disclosed.

Abstract: The invention provides methods for the early detection of cardiovascular injury using one or more cardiac injury biomarkers identified herein.

Abstract: The invention relates to a method for the diagnostic investigation of biological samples from a person for inflammation of the liver, in particular hepatic fibrosis and/or cirrhosis of the liver, where the sample is investigated for one or more proteins as markers of inflammation of the liver, in particular hepatic fibrosis and/or cirrhosis of the liver, where a concentration of the proteins which is elevated or decreased by comparison with the healthy state indicates the presence of an inflammation of the liver, in particular a hepatic fibrosis and/or cirrhosis of the liver.

Abstract: Compositions and methods are disclosed for treating Triple Negative Breast Cancers (TNBCs). The methods involve administering to a subject with TNBC a composition containing an Ack1 kinase inhibitor. In some embodiments, the method involves first assaying a sample from the subject for Tyr176-phosphorylated-AKT and/or Tyr284-phosphorylated-Ack1. In these embodiments, detection of the phosphorylated AKT and/or Ack1 is an indication that the subject is a suitable candidate for treatment with the Ack1 kinase inhibitor.

Abstract: Ctsk is used as a marker to identify, track, and manipulate Ctsk positive cartilaginous stem cells for cartilage repair and regeneration in vitro and in vivo.

Abstract: The present invention provides methods and fluorescent compounds that facilitate detecting and labeling of a fusion protein by being capable of selectively binding to an affinity tag. The fluorescent compounds have the general formula A(B)n, wherein A is a fluorophore, B is a binding domain that is a charged chemical moiety, a protein or fragment thereof and n is an integer from 1-6 with the proviso that the protein or fragment thereof not be an antibody or generated from an antibody. The present invention provides specific fluorescent compounds and methods used to detect and label fusion proteins that contain a poly-histidine affinity tag. These compounds have the general formula A(L)m(B)n wherein A is a fluorophore, L is a linker, B is an acetic acid binding domain, m is an integer from 1 to 4 and n is an integer from 1 to 6.

Abstract: Disclosed herein are new prognostic molecular markers for prostate cancer. More specifically, the invention has identified that overexpression or amplification of at least one of AURKA or MYCN define a distinct subgroup of prostate cancer that is predisposed to the development of lethal NEPC, who will benefit from early intervention.

Abstract: Methods of diagnosing Clostridium difficile infection and compounds used in the methods are provided. The diagnostic methods are specific and sensitive methods for detecting a host cell response and, in some aspects, a target response, i.e. a Clostridium difficile toxin, in an individual infected with Clostridium difficile. The methods comprise detecting in a stool specimen or fluid exposed to the stool specimen a Clostridium difficile toxin, or a fragment thereof, and an increase in a colonic epithelial cell protein exemplified by a non-muscle tropomyosin. Also provided are kits comprising reagents for detecting host cell proteins and Clostridium difficile toxins.

Abstract: A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R3 and R4 is H, and the other is selected from C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, and C6-12-aralkyl; or R3 and R4 are each independently selected from C1-6-alkyl and halo; R9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high efficacies for human cathepsin S, excellent selectivity verses other mammalian cathepsins and are useful for treatment of diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, transplant rejection, diabetes, Sjogrens syndrome, Grave's disease, systemic lupus erythematosis, osteoarthritis, psoriasis, idiopathic thrombocytopenic purpura, allergic rhinitis, asthma, atherosclerosis, obesity, chronic obstructive pulmonary disease and chronic pain.

Abstract: Methods of detecting or predicting the onset or magnitude of kidney diseases such as acute kidney disease (AKI), previously called acute renal failure (ARF), are provided. In various aspects, methods and kits are provided to detect specific urinary proteins associated with AKI diagnosis or prognosis such as, e.g., angiotensinogen.

Abstract: Described are MMP8 inactivating antigen binding proteins, such as antigen binding proteins comprising an amino acid sequence that comprises 4 framework regions and 3 complementary determining regions; further described is the use of such antigen binding proteins to treat inflammation, such as, but not limited to, systemic inflammatory response syndrome, sepsis, LPS induced inflammation, renal ischemia/reperfusion injury, ventilation induced lung injury, periodontal inflammation, rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, Lyme arthritis and osteoarthritis.

Abstract: The present invention relates to a method for the selective determination of the concentration of an active human protease coagulation factor in a sample, comprising the steps of binding a specific inhibitor of the human protease coagulation factor to a solid phase, letting the human protease coagulation factor contained in the sample bind to the solid phase-bound inhibitor, and detecting the human protease coagulation factor bound to the solid phase-bound inhibitor with a detection reagent.

Abstract: The present invention relates to methods of diagnosing Alzheimer's Disease in a human patient by detecting alterations in the ratio of PKC epsilon protein levels in a human patient compared with PKC epsilon levels in a control subject. The Alzheimer's disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's disease and for screening methods for the identification of compounds for treating or preventing Alzheimer's disease. The present invention also provides methods for elevating PKC epsilon protein levels comprising the steps of contacting one or more human cells with an amount of a PKC activator effective to elevate PKC epsilon levels compared to an uncontacted human cell.

Abstract: The present invention provides an assay for the identification of agents which can modulate TOR-mediated phosphorylation of substrate proteins. The assays of the invention utilize substrate proteins whose amino acid sequence contains the Ser/Thr motif recognized by TOR. Naturally occurring TOR which may be used in the methods of the invention include TOR isolated from a variety of species, particularly mammalian tissues.

Abstract: The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.

Abstract: The present invention relates to enhancing, modulating or stimulating the immune response to MMP-2 expressing tumors, including melanoma, and to the modulation and application of immune modulators and MMP-2 peptides for melanoma or other MMP-2 expressing tumor vaccines. The invention provides methods and means to activate an effective response to MMP-2 expressing tumors and modulate the ability of MMP-2 to skew CD4+ T cell responses toward that of TH2 cells, which are less effective mediators of tumor cell clearance than TH1 cells. Methods and assays are provided for screening for compounds, agents, or peptides capable of enhancing or activating immune responses, particularly to melanoma.

Abstract: A microfluidic device for glycopeptide analysis includes an enrichment column capable of binding carbohydrates; a trapping column capable of binding peptides, wherein the trapping column is configured to be connected downstream of the enrichment column; a separation column, wherein the separation column is configured to be connected downstream of the trapping column; and a plurality of ports configured to work with a switching device to form a plurality of flow paths, wherein one of the plurality of flow paths allows the trapping column to be in fluid communication with the separation column. A method for glycopeptide analysis using a microfluidic device comprising a trapping column and a separation column, the method includes applying a sample of peptides to the microfluidic device; trapping the peptides on the trapping column; eluting the peptides from the trapping column into the separation column; and separating the peptides on the separation column.

Abstract: Presented herein are polypeptide substrates based on Notch polypeptides, assay methods based on the use of these substrates, and screening methods directed toward identifying inhibitors of ?-secretase activity. The assay methods and the screening methods are adapted for use in high throughput multi-well plate assay apparatuses. In many embodiments the substrate polypeptides are labeled for ease of detection, and/or may bind specific ligands that themselves are labeled. Generally the labels promote high specificity as well as high sensitivity of detection. These features render the assay and screening methods that employ the labeled substrates especially suited for use in high throughput assay formats.

Abstract: The present invention relates to methods of diagnosing Alzheimer's Disease as well as to methods of confirming the presence or absence of Alzheimer's Disease in a subject. The present invention is also directed to methods of identifying a lead compound useful for the treatment of Alzheimer's Disease by contacting non-Alzheimers cells with an amyloid beta peptide, stimulating the cells with a protein kinase C activator, contacting the cells with a test compound, and determining the value of an Alzheimer's Disease-specific molecular biomarker. The present invention is also directed to methods of diagnosing Alzheimer's Disease in a subject by detecting alterations in the ratio of specific phosphorylated MAP kinase proteins in cells after stimulation with a protein kinase C activator.

Abstract: The present invention describes a method of diagnosis and/or progression of a disease based on the detection and quantification of the expression levels of biomarkers preferably selected from the group comprising gelsolin isoforms (SEQ. ID 1 and 2) and Vitamin D binding protein isoforms (SEQ. ID 3 and 4). Said method is applied to central nervous system diseases, preferably to Multiple Sclerosis.

Abstract: The disclosure is directed to methods of identifying compounds that modulate murine double-minute 2. More particularly, the disclosure is directed to methods of identifying compounds that modulate murine double-minute 2 neddylation activity.

Abstract: The present invention relates to a method for diagnosing, in vitro, a neurodegenerative disease in an individual, in which:—the level of the double-stranded RNA-dependent protein kinase (PKR) in a sample of cerebrospinal fluid from the individual is determined,—it is deduced therefrom whether the individual is suffering from a neurodegenerative disease.

Abstract: Methods for identifying compounds useful for treating diseases and conditions of the oral cavity are described herein.

Abstract: Novel, sensitive and specific markers and methods for diagnostics and monitoring of head and neck squamous cell carcinoma (HNSCC) are provided. Kits and methods for the use of hyaluronic acid, hyaluronidase and CD44 to diagnose HNSCC are described.

Abstract: The present invention provides methods for the preselection of a subject for therapeutic treatment with an agent based on modulated levels of hypoxia in cancerous cells in the subject. In one embodiment, the invention provides methods for the preselection of a subject for therapeutic treatment with an agent based on modulated levels of lactate dehydrogenase (LDH) in a cell, e.g., a cancerous cell. The invention also provides methods for treating cancer in a subject by administering an effective amount of an agent to the subject, wherein the subject has been selected based on a modulated level of hypoxia. The invention further provides kits to practice the methods of the invention.

Abstract: The invention relates to methods for identifying an anti-fibrotic or anti-inflammatory agent comprising determining cathepsin S expression in activated hepatic stellate cells which have been exposed to a test compound and comparing expression to non-exposed hepatic stellate cells. The invention also relates to methods for treating a disorder characterised or caused by hepatic fibrosis or inflammation, comprising administering a cathepsin S inhibitor to a subject.

Abstract: Methods for monitoring, and determining the efficacy of, a treatment for prostate cancer in a subject are provided, such methods including detecting the levels of expression of multiple polypeptide biomarkers in biological samples obtained from the subject prior to, and during, a course of treatment. Specific patterns of changes in the expression of the polypeptide biomarkers are indicative of the effectiveness of the treatment in the subject.

Abstract: Disclosed is an animal model that can be used, among other things, to generate biomarkers for the prognosis and/or diagnosis of acute kidney injury, more specifically sepsis-induced acute kidney injury. Disclosed are three such biomarkers. The disclosure specifically relates to human chitinase 3-like protein 1 for use as a biomarker.

Abstract: The invention discloses identification and therapeutic use of matrix metalloproteinase oligopeptides, SEQ ID 5-SEQ ID 21. These oligopeptides are bound to antibodies to create an immune response in the subject mammal against the matrix metalloproteinases of various diseases. This is a means of therapeutic intervention against the disease spread created by the matrix metalloproteinases. Further use of these oligopeptide-antibody responses can be extended to any and all diseases that use the matrix metalloproteinases to aid in their pathogenicity.

Abstract: The invention provides chimeric 3-phosphoinositide-dependent protein kinase 1 (PDK1), the PIF-binding pocket of which has mutations to mimic a second protein kinase, its production and use. The invention further provides a method for screening for compounds interacting with the PIF-pocket of an AGC kinase.

Abstract: The present disclosure provides a method of detecting a target analyte, by binding the target analyte and a probe with at least one fluorophore to form a fluid composition. The fluid composition is excited within a laser cavity. The method comprises measuring a laser emission from the fluid composition based on an interaction between the target analyte and the probe. In certain aspects, the method provides hybridizing the target analyte and the probe, prior to the exciting. In certain variations, the methods comprise detecting a target analyte by measuring a laser emission from the fluid composition based on an interaction between the target analyte, where the interaction is probe energy transfer, intercalation, hybridization of the target analyte and the probe, or combinations thereof. The energy transfer can include fluorescence resonance energy transfer (FRET), FRET with a molecular-beacon, or cavity-assisted radiative energy transfer, by way of non-limiting example.

Abstract: Despite initial sensitivity BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome, and as therapeutic targets. Induced in-vitro OVCA cisplatin-resistance was associated with BAD-pathway expression. Expression of the pathway was also associated with resistance of 7 different cancers cell-types to 8 chemotherapeutic agents. Phosphorylation of the BAD-protein was associated with platinum-resistance in OVCA cells and primary OVCA specimens, and also overall patient survival. Targeted modulation of BAD-phosphorylation levels influenced cisplatin-sensitivity. A 47-gene BAD-pathway signature was associated in-vitro phospho-BAD levels and with survival of 838 patients with ovarian, breast, colon, and brain cancer. The survival advantage associated with both BAD-phosphorylation and also the BAD-pathway signature was independent of surgical cytoreductive status.

Abstract: A chemically patterned modified hydrogel formed from a modified hydrogel is provided. The hydrogel is conjugated with a multiphoton photocleavable molecule. The molecule has a multiphoton-labile protective group and a protected group. The protective group is cleavable upon multiphoton excitation to deprotect the protected group, without substantial polymerization of the hydrogel. The chemically patterned modified hydrogel is formed by exposing the modified hydrogel to multiphoton excitation to deprotect a portion of the protected groups.

Abstract: A method pertains to a diagnosing the presence and/or severity of a hepatic pathology and/or of monitoring the effectiveness of a curative treatment against a hepatic pathology in an individual, comprising the establishment of at least one non-invasive diagnostic score, in particular a diagnostic score for portal and septal fibrosis and/or an estimate score for the fibrosis area and/or an estimate score for the fractal dimension.

Abstract: Stem-cell derived human neuronal models that mimic human Alzheimer's disease, including hereditary and sporadic Alzheimer's disease, comprising neural stem cells derived from human induced pluripotent stem cells. Also provided are purified human neurons developed from the neural stem cells that carry genomes from the Alzheimer's disease patients. The human neuronal models are neuronal models for hereditary and sporadic Alzheimer's disease, and are suitable for measurement of key behaviors of the Alzheimer's disease, providing further diagnostic tools for the development of sporadic Alzheimer's disease, and assisting in drug testing for the therapeutic treatment of Alzheimer's disease.

Abstract: Methods for determining whether a cancer patient is likely to benefit from treatment with a taxane compound based on Akt-Ser473 phosphorylation status are provided, together with kits for determining Akt-Ser473 phosphorylation status and methods for improving treatment of a cancer patient that include obtaining a determination of the Akt-Ser473 phosphorylation status of the cancer.

Abstract: Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.

Abstract: The present invention relates to compositions and methods for the diagnosis and treatment of obesity and related metabolic disorders. The invention provides isolated nucleic acids molecules, designated DGAT2 family member nucleic acid molecules, which encode diacylglycerol acyltransferase family members. The invention also provides recombinant expression vectors containing DGAT2 family member nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a DGAT2 family member gene has been introduced or disrupted. The invention still further provides isolated DGAT2 family member proteins, fusion proteins, antigenic peptides and anti-DGAT2 family member antibodies. Methods of use of the provided DGAT2 family member compositions for screening, diagnostic and therapeutic methods in connection with obesity disorders are also disclosed.

Abstract: The invention relates to methods for using biomarkers to identify cancer patients that will or are likely to respond to treatment. Specifically, the invention relates to the use of one or more of three association studies of cancer types, gene mutations, or gene expression levels in order to identify cancer patients that will or are likely to respond to treatment with a histone deacetylase (HDAC) inhibitor, alone or in combination with another cancer treatment. The methods may, optionally, further include treating such patient with an HDAC inhibitor, alone or in combination with another cancer treatment.

Abstract: The invention provides methods for identifying conditions of low grade cervical dysplasia and assessing the progressive potential of individual lesions to develop into high grade cervical dysplasia and cervical squamous cell cancer as well as cervical adenocarcinoma.

Abstract: This present invention provides methods of treating of assessing/monitoring the responsiveness of a cancer cell to JAK inhibitor therapy.

Abstract: The instant invention relates to the field of protein production, and in particular is relates to compositions and processes for improving the production levels of recombinant proteins expressed in host cells.

Abstract: The present invention relates to a method for the determination of the species profile of a protein-interacting compound, comprising the steps of a) providing a protein preparation derived from one species (species-1) containing a species-1-variant of said protein, b) providing a protein preparation derived from another species (species-2) containing a species-2-variant of said protein, c) mixing said preparations, d) contacting said mixed protein preparations with a ligand of said protein and with a given protein-interacting compound under conditions allowing the formation of a complex between said ligand and said protein, and e) detecting the complexes formed in step d) with the help of mass spectrometry.

Abstract: The present invention concerns an in vitro method for diagnosing invasive candidiasis (IC) in a subject which comprises detecting the presence of a Candida glycan and detecting the presence of antibody directed against a protein selected from the group consisting of fructose bisphosphate aldolase (Fba1), enolase 1 (Eno1), heat shock protein 90 (Hsp90), hyphal wall protein (Hwp1), and mannoprotein 65 (Mp65) in a blood, plasma or serum sample of the subject. The invention also relates to a method of determining a suitable treatment regimen for a patient and to a kit for implanting the methods described herein.

Abstract: The invention relates to a method for enhancing the transplantation of hematopoietic cells to supplement or fully reconstitute the hematopoietic system, such as in myeloablated patients or patients otherwise deficient in hematopoietic cells. The method involves administering CD34+ cells having enhanced expression of one or more of Musashi-2, PTEN, phospho-GSK-3?, Mcl-1, Atg7, phospho-Akt(ser473), HoxB4, Bmi-1, UBC13, phospho-Akt(thr308), GATA2, cMyc, and E47 at levels that provide desirable therapeutically effective amounts of self-renewal of the administered cells and desirable therapeutically effective amounts of differentiation of the administered cells into the various progeny cells of the hematopoietic system (i.e., therapeutically effective amounts of hematopoietic reconstitution). To provide such cells to a subject, the invention relates to detecting such cells prior to or during treatment to ascertain whether such cells are present in clinically-relevant amounts.

Abstract: Compositions, methods and kits are provided for modulating the trans-differentiation of cells for example muscle satellite cells. The compositions, methods and kits include a modulator of trans-differentiation of the muscle satellite cells selected from the group of: a transcription factor, a nucleic acid sequence or vector encoding expression of the transcription factor, and an agent that binds to the transcription factor. The transcription factor is selected for example from a homeodomain class transcription factor such as Nkx3.2 and a TATA binding protein class transcription factor such as Sox9, and includes at least one nucleotide binding-domain, so that the transcription factor modulates the process of trans-differentiation of the cells or tissue to form a phenotype selected from: cartilage, muscle, and bone.

Abstract: The present invention relates to the use of a compound, suitable for modulating the interaction between first and second partner proteins, or between homologues, mutants, or fragments of said proteins, said first and second proteins being SASPase and filaggrin-2, or FLG2, as an active agent for treating and/or preventing aesthetic defects in the skin, and/or in the appendages thereof, linked to an imbalance in the differentiation and/or proliferation of the cells of the epidermis.

Abstract: The invention is directed to a method to establish a biologically significant association of gene expression levels among two or more genes, the method comprising assaying a sample for expression levels of two or more genes and identifying statistically-significant associations using a correlation coefficient in the range of about 0.6 to about 1.0, wherein a correlation coefficient in that range signifies a biologically significant correlation.