Abstract: The present invention relates to variants of a vitamin K-dependent serine protease of the coagulation cascade, preferably variants of factor IX (F.IX), wherein the variant is characterized in that it has clotting activity in absence of its cofactor. The present invention furthermore relates to the use of these variants for the treatment and/or prophylaxis of bleeding disorders, in particular hemophilia A and/or hemophilia B or hemophilia caused or complicated by inhibitory antibodies to F.VIII. The present invention also relates to further variants of factor IX (F.IX) which have desired properties and can, thus be tailored for respective specific therapeutic applications.

Abstract: A method for confirming a diagnosis of autism in an individual comprises obtaining a sample of feces from an individual, determining a quantitative level of chymotrypsin present in the sample, and comparing the quantitative level of fecal chymotrypsin in the stool sample of the person having autism to a stool sample from an individual that has a normal fecal chymotrypsin level and does not have autism and confirming a diagnosis of autism based on the measurement of the quantitative level of fecal chymoptrypsin.

Abstract: A method for identifying a protease secretion deficient strain of a microorganism involves producing a mutant of the microorganism, followed by adding the mutant to gel-filled wells of a microtitration plate, incubating the mutant in the gel-filled wells under conditions call sing the mutant to secrete proteins, separating the mutant from the gel, and measuring activity of a secretion protease of the microorganism in the gel, wherein either (i) the gel is a substrate for the secretion protease or (ii) the gel contains a substrate for the secretion protease.

Abstract: Methods for determining the efficiency of a therapeutic. In at least one embodiment of a method of determining the efficacy of a therapeutic compound, the method comprises the steps of treating a subject having a disease state with an effective amount of therapeutic compound, harvesting at least one cell from the subject following a treatment with the therapeutic compound, bringing the at least one cell into contact with a stabilizing compound capable of completely or substantially preventing the degradation or inactivation of a diagnostic marker for the disease state, analyzing the at least one stabilized cell for the at least one diagnostic marker, creating a marker profile from at least one result determined from analyzing the at least one stabilized cell, and comparing the marker profile with at least one previous marker profile to determine efficacy of the therapeutic compound on the disease state.

Abstract: Systems and methods for identifying allergies. In at least one embodiment of a system of the present disclosure, the system comprises a stabilizing agent useful to completely or substantially prevent degradation or inactivation of a diagnostic marker for a non-food allergy in a body fluid comprising the diagnostic marker and a detection agent capable of detecting the diagnostic marker.

Abstract: Systems and methods for detecting pregnancy. In at least one embodiment of a system of the present disclosure, the system comprises a stabilizing agent useful to completely or substantially prevent degradation or inactivation of a diagnostic marker for pregnancy in a body fluid comprising the diagnostic marker, and a detection agent capable of detecting the diagnostic agent.

Abstract: The invention provides enzymatic methods for direct determination of percentage of glycated hemoglobin in blood samples without the need of a separated measurement of total hemoglobin content in blood samples. The methods utilizes one or two different types of oxidizing agents which selectively oxidize low-molecular weight reducing substances and high-molecular weight (mainly hemoglobin) reducing substances in blood samples, coupled with enzymatic reactions catalyzed by proteases, fructosyl amino acid oxidase, and peroxidase. The invention provides kits for performing the methods of the invention.

Abstract: The present invention relates to methods and systems for adding a reagent to an analyte in a gel. The invention further provides methods and systems for transferring liquid analyte reagent mixtures from a gel to a second vessel, such as a microtitre plate. The invention is useful in the manipulation of biological molecules such as nucleic acids, carbohydrates, proteins and peptides. In particular, the invention has utility for manipulating proteins and peptides in isoelectric focusing gels.

Abstract: A method for measuring a generation of thrombin in a sample of whole blood as a function of time includes adding to a sample of whole blood a fluorogenic substrate and a thrombin activator to form an activated sample. A conversion product is permitted to form in the activated sample. Fluorescence is measured as a function of time from a fluorescent group that is released during the formation of the conversion product with the use of a fluorescence detector. The fluorescence detector operates in an extended range mode and has an increased sensitivity. Thrombin generation as a function of time can then be calculated from the measured fluorescence as a function of time.

Abstract: The present invention provides a method for enhancing expression of angiotensin converting enzyme ACE2 in the vasculature of a mammal, particularly in the renal vasculature and podocytes. The method comprises administering to a mammal in need of such enhancement (e.g., a mammal suffering from, or at risk of developing renal damage or hypertension), an amount of an angiotensin II antagonist sufficient to promote a protective level of ACE2 expression in the vasculature of the mammal. Preferably, the angiotensin II antagonist is administered in an angiotensin II blocking amount, more preferably in an amount sufficient to achieve and maintain a desired level of ACE2 expression in the vasculature of the mammal. The methods of the invention are useful for ameliorating kidney damage from diseases, such as diabetes, as well as hypertension.

Abstract: This document relates to methods and materials for detecting premalignant and malignant neoplasms. For example, methods and materials for determining whether or not a stool sample from a mammal contains nucleic acid markers or polypeptide markers of a neoplasm are provided.

Abstract: A method of analyzing cellular samples that include a chemically crosslinked analyte is provided. The analysis typically involves the use of mass spectrometry.

Abstract: The present invention relates to the assessment of lung cancer. It discloses the use of protein ASC in the assessment of lung cancer. It also relates to a method for assessing lung cancer in vitro using a liquid sample, derived from an individual by measuring ASC in the sample. Measurement of ASC can, e.g., be used in the early detection or in the follow-up of patients with lung cancer.

Abstract: This invention provides reagents, methods and pharmaceutical compositions for treating and preventing malaria. Specifically, the invention provides methods for inhibiting a Plasmodium parasite, especially Plasmodium falciparum, from invading or replicating in a cell as well as vaccines for preventing malaria.

Abstract: A reaction medium for detecting and/or identifying Methicillin-resistant Staphylococcus aureus (MRSA) bacteria, comprising a predetermined combination of two antibiotics, a first antibiotic which belongs to the cephalosporin family and a second antibiotic, said first and second antibiotics each being at a sub-inhibitory concentration.

Abstract: A novel carboxypeptidase and the encoding gene thereof were successfully identified by screening a human hippocampus extract using brain-APP-cleaving activity as an index. This protein and its gene are useful in, for example, preventing, treating, examining, and diagnosing diseases that cause accumulation of A? in the brain, including senile dementia, Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage, and cephalic contusion.

Abstract: The present invention relates to methods of measuring the activity of a hydrolytic agent comprising contacting a biomolecule with a hydrolytic agent in the presence of a fluorescent dye under conditions that allow digestion of the biomolecule by the hydrolytic agent. The fluorescence of the dye is monitored over time and a change in fluorescence signifies digestion of the biomolecule by the hydrolytic agent. The biomolecule is preferably a protein, peptide or proteome but can also be a carbohydrate, oligonucleotide or lipid. Further methods relate to determining an end point for digestion of a biomolecule by a hydrolytic agent, and methods of monitoring digestion of a biomolecule by a hydrolytic agent. The monitoring can be performed on the reaction mixture in real time or via sampling. The invention also relates to kits for carrying out the method.

Abstract: A dry mixture, a liquid menstrum, and a method, are described for use in detecting the presence or absence of Methicillin Resistant Staphylococcus aureus (“MRSA”) in a first generation biological or environmental specimen sample. First generation specimen samples that can be analyzed include nasal swabs, lesion swabs, skin swabs, throat swabs, food swabs, tanning salon swabs, gym swabs, restaurant swabs, hotel swabs, and the like. The menstrum and method include an anti-ribosomal antibiotic component that will selectively prevent Methicillin Susceptible Staphylococcus aureus (“MSSA”) from growing in the menstrum, while allowing MRSA to grow in the menstrum. The menstrum also includes components which will stimulate growth of MRSA, plus coagulase reacting factors which will cause the menstrum to clot in the event that MRSA is present in the sample. The menstrum also includes components which will produce a detectable signal in the clot, which signal indicates the presence of MRSA in the sample.

Abstract: The invention provides a method of determining the prognosis of cancer in a subject. The method comprises (a) obtaining a sample from the subject, (b) analyzing the sample for the expression level of a carboxypeptidase E (CPE) splice variant, and (c) correlating the expression level in the sample with the prognosis of cancer in the subject. The invention further provides a method of diagnosing cancer, methods of treatment, kits for detecting mRNA expression of a CPE-?N, and inhibitors of CPE-?N and compositions thereof.

Abstract: A diagnostic test kit for detecting the presence or quantity of an enzyme or enzyme inhibitor is provided. The diagnostic kit utilizes reactive complexes to facilitate the detection of the enzyme or enzyme inhibitor. The reactive complexes include a substrate joined (e.g., covalently bonded, physically adsorbed, etc.) to a reporter and specific binding member. In one embodiment, for example, a peptide, protein, or glycoprotein substrate is joined to a reporter (e.g., dyed latex particle) and specific binding member (e.g., biotinylated compound). In this embodiment, the substrate provides a cleavage target for a proteolytic enzyme. Specifically, upon contacting the reactive complexes, the proteolytic enzyme cleaves the substrate and releases the reporter and/or specific binding member. The signal exhibited by the released reporters may then be used to indicate the presence or quantity of an enzyme or enzyme inhibitor within the test sample.

Abstract: The present invention is directed to methods for sustaining eNOS activity to inhibit platelet aggregation, clot retraction, and enhance fibrinolysis. One embodiment of the invention provides methods of treating thrombosis by inhibiting the activity of the syk kinase. Another embodiment provides assays for the discovery of improved compounds to treat thrombosis, by screening for compounds which sustain eNOS activity. Yet another embodiment provides assays for the discovery of improved compounds to treat thrombosis, by identifying inhibitors of calpain and IIbIIIa by screening for compounds which act through calpain or IIbIIIa to sustain eNOS activity. Yet another embodiment provides for enhancing fibrinolysis, by inhibiting the activity of the syk kinase or calpain.

Abstract: The present invention discloses a mutant blue fluorescent protein (BFP) exhibiting, at an aerobic or anaerobic system, larger fluorescent intensity than a BFPvv D7 of SEQ ID NO:2 derived from a wild type BFP, BfgV of SEQ ID NO:1, obtained from Vibrio vulnificus, wherein a set of mutation positions of the mutant BFP corresponding to SEQ ID NO:2 comprises position 176 or position 178. In a preferred embodiment, the set of mutation positions of the mutant BFP corresponding to SEQ ID NO:2 comprises a S176R mutation or a V178I mutation. Moreover, methods of using the blue fluorescent proteins from Vibrio vulnificus for fluorescence resonance energy transfer (FRET) and a blue fluorescent fish are also provided.

Abstract: A device for fluorescence-based imaging and monitoring of a target comprising: a light source emitting light for illuminating the target, the emitted light including at least one wavelength or wavelength band causing at least one biomarker associated with the target to fluoresce; and a light detector for detecting the fluorescence.

Abstract: A method for the analysis of mixtures of components includes separating or partially separating different components of a mixture of a sample by means that causes the components to elute sequentially over a period of time, forming precursor ions from the components in the eluent, repeatedly switching, altering or varying an Electron Transfer Dissociation fragmentation device back and forth between a hi-fragmentation mode and a low-fragmentation mode to alternately produce product ions from the precursor ions in the hi-fragmentation mode and to produce substantially fewer product ions in the low-fragmentation mode, and obtaining mass spectra during the period of time from the precursor and product ions received from the Electron Transfer Dissociation fragmentation device.

Abstract: The present invention relates to a diagnostic method for identifying persons with genetically related hetero- or homozygous expression of the MR I variant of factor VII-activating protease (FSAP). The heterozygous or homozygous presence of an MR I polymorphism can be identified by a differential modulation of the FSAP activity.

Abstract: The invention provides methods and compositions for the detection and/or quantification of a microbial contaminant, for example, a bacterial endotoxin or a glucan, in a sample. In particular, the invention provides a test cartridge useful in the practice of hemocyte lysate-based assays for the detection and/or quantification of a microbial contaminant in a sample. In addition, the invention provides methods of making and using such cartridges. In addition, the invention provides a rapid, sensitive, multi-step kinetic hemocyte lysate-based assay for the detection and/or quantification of a microbial contaminant in a sample. In addition, the invention provides a glucan-specific lysate that can be used in a variety of assay formats, including, for example, a test cartridge, optionally configured to perform a kinetic assay.

Abstract: Enzymatic phenoxazinone substrates of formula (I): in reaction media containing the same are used for detecting, identifying and/or quantifying microorganisms expressing at least one peptidase activity.

Abstract: Present invention concerns the use of Cathepsin C. Other aspects of the invention concern methods for screening pharmaceuticals, for diagnosing pain susceptibility and for the treatment of pain.

Abstract: Administering an effective dose of glutenase to a Celiac or dermatitis herpetiformis patient reduces levels of toxic gluten oligopeptides, thereby attenuating or eliminating the damaging effects of gluten.

Abstract: Administering an effective dose of glutenase to a Celiac or dermatitis herpetiformis patient reduces levels of toxic gluten oligopeptides, thereby attenuating or eliminating the damaging effects of gluten.

Abstract: The invention provides a process for producing polysaccharide gum comprising extracting a plant material with an aqueous solvent to produce a polysaccharide gum-containing extract; contacting the extract with at least one proteolytic enzyme to at least partially digest proteins in the extract; adding an organic solvent to the extract to precipitate the polysaccharide gum; and collecting the precipitated polysaccharide gum.

Abstract: Disclosed are isolated polypeptides of Alicyclobacillus sp. having glutamic peptidase activity.

Abstract: The invention relates to a method for the determination of a cancer diagnostic/therapeutic biomarker assay and drug-targets including the following steps: (a) identification of potential candidate protein/peptide biomarkers and drug-targets based on the measurement of protein/peptide constituent concentrations in tissue sample proteomes as well as serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healthy non-human mammalian individuals as well as from cancerous non-human mammalian individuals and qualitatively selecting as potential candidate protein/peptide biomarkers those which show a pronounced differential behaviour between healthy and cancerous sample proteomes; (b) optional verification of the potential candidate protein/peptide biomarkers as identified in step (a) by quantitative mass spectrometric measurement of the potential candidate protein biomarkers in serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healt

Abstract: The present invention is to provide a novel marker for diagnosing pancreatic cancer, a method for determining if a subject has pancreatic cancer utilizing the marker, etc. The present inventors collected blood from patients of 78 cases in total including patients of 24 cases with pancreaticobiliary-duct benign disorder (16 gallstone cases and 8 pancreatitis cases) and patients of 54 cases with pancreatic cancer, and mass spectrometry was performed on N-linked sugar chains in plasma. From the 74 mass-spectrometric peaks detected, 65 sugar chains were extracted based on the results of PAM analysis. These extracted sugar chains were then used to predict pancreatic cancer or pancreaticobiliary-duct benign disorder, to correctly diagnose 74% cases.

Abstract: As described herein, signaling events occurring in neurons or at neuronal synapses have been identified that involve Cdk5 and various other molecules which bind to, are activated by, and/or activate Cdk5. Of particular relevance are interactions that stimulate calpain cleavage of p35 into p25, which binds Cdk5 in pathologic states. Assays to identify modulators of these interactions are provided.

Abstract: A method of interfering with quorum sensing regulation of genes to promote cell growth is disclosed. The method of is aimed at accessing microbial biodiversity. The method involves obtaining an environmental sample comprising at least one novel (uncultivated in the laboratory) microorganism, contacting the environmental sample with an effective amount of an agent or combination of agents which interferes with the quorum sensing regulation of genes, growing the treated sample in a culture medium containing the quorum sensing signal disrupting agent or agents, and analyzing the colonies of microorganisms grown to demonstrate genetic novelty.

Abstract: A diagnostic test kit for detecting the presence or quantity of an enzyme or enzyme inhibitor is provided. The diagnostic kit utilizes reactive complexes to facilitate the detection of the enzyme or enzyme inhibitor. The reactive complexes include a substrate joined (e.g., covalently bonded, physically adsorbed, etc.) to a reporter and specific binding member. In one embodiment, for example, a peptide, protein, or glycoprotein substrate is joined to a reporter (e.g., dyed latex particle) and specific binding member (e.g., biotinylated compound). In this embodiment, the substrate provides a cleavage target for a proteolytic enzyme. Specifically, upon contacting the reactive complexes, the proteolytic enzyme cleaves the substrate and releases the reporter and/or specific binding member. The signal exhibited by the released reporters may then be used to indicate the presence or quantity of an enzyme or enzyme inhibitor within the test sample.

Abstract: Provided herein are methods for the diagnosis, prognosis, or management of proliferative hematological disorders and other diseases using profiles of the ubiquitin-proteasome system determined from acellular body fluids or cell-containing samples. Further provided are methods of predicting response to therapy in certain populations of leukemia patients.

Abstract: The invention describes methods that are useful for treating cancer by administering a Chk1 inhibitor which can induce apoptosis in p53-defective cells when combined with a chemotherapy and/or radiotherapy. Methods for screening candidates for a Chk1 inhibitor-based cancer treatment regimen are also described.

Abstract: Provided herein are methods for the diagnosis, prognosis, or management of neoplastic diseases, i.e. cancer, and other diseases using profiles of the ubiquitin-protcasome system determined from acellular body fluids or cell-containing samples. Further provided are methods of predicting response to therapy in certain populations of cancer patients.

Abstract: A lateral flow assay device for detecting the presence or quantity of an enzyme or enzyme inhibitor is provided. The lateral flow assay device utilizes a molecular substrate to facilitate the detection of an enzyme or enzyme inhibitor via detection of the substrate and/or a product formed in an enzyme-catalyzed reaction of the substrate. In one embodiment, for example, upon contacting a molecular substrate, an enzyme catalyzes a reaction with the molecular substrate and forms a product. The lateral flow assay device also includes a detectable substance that may generate a detectable signal for determining the presence or amount of enzyme in a test sample. For example, the detectable substance may be directly or indirectly attached to a specific binding member that has affinity for the product. Following the enzyme catalyzed reaction, the product may bind the detectable substance which may, in turn, generate the detectable signal.

Abstract: A use of vivapain-4 (VX-4), which is a cysteine protease of Plasmodium vivax, showing pH-dependent switching of substrate specificity, is provided. More specifically, a method of treating a parasitic disease caused by Plasmodium vivax by inhibiting VX-4; a method of screening a protease inhibitor acting on VX-4, wherein the protease inhibitor is useful as an anti-malarial agent acting on Plasmodium species, for example, Plasmodium vivax; and a method of identifying the activity of VX-4, are provided.

Abstract: A reaction medium for detecting and/or identifying methicillin-resistant Staphylococcus aureus (MRSA) bacteria includes a chromogenic substrate, a first antibiotic that belongs to the cephalosporin family and a second antibiotic that belongs to the aminoglycoside family.

Abstract: Provided herein is are polypeptides that include the protease domain of a type II transmembrane serine protease (MTSP) as a single chain. Methods using the polypeptides to identify compounds that modulate the protease activity of an MTSP are provided. Also provided are MTSPs designated MTSP3 and MTSP4 and a form of an MTSP designated MTSP6.

Abstract: The present invention relates to a method of qualifying ovarian cancer status in a subject comprising: (a) measuring at least one biomarker in a sample from the subject and (b) correlating the measurement with ovarian cancer status. The invention further relates to kits for qualifying ovarian cancer status in a subject.

Abstract: Targeted antimicrobials are described and related, compositions, methods and systems.

Abstract: The present invention relates to compositions and an apparatuses for determining protease activity. The compositions of the invention contain a reporter protein fused to at least one protease cleavage sequence, and a linker for attaching the protease cleavage sequence to a solid support. Methods for determining protease activity and characterizing proteases are also provided.

Abstract: The present invention provides for novel reagents whose fluorescence increases in the presence of particular proteases. The reagents comprise a characteristically folded peptide backbone conjugated to two fluorophores such that the fluorophores are located opposite sides of a cleavage site. When the folded peptide is cleaved, as by digestion with a protease, the fluorophores provide a high intensity fluorescent signal at a visible wavelength. Because of their high specificity and their high fluorescence signal in the visible wavelengths, these protease indicators are particularly well suited for detection of protease activity in biological samples, in particular in frozen tissue sections. Thus this invention also provides for methods of detecting protease activity in situ in frozen sections.

Abstract: The present invention relates to inhibitors of insulin-regulated aminopeptidase (IRAP) and methods for inhibiting same, as well as compositions comprising said inhibitors. In particular, the inhibitors of the present invention may be useful in therapeutic applications including enhancing memory and learning functions.

Abstract: A peptide substrate selectively recognisable by a botulinum toxin A, BoNT/A containing a Nop-(Z)-Pya fragment in the peptide structure thereof, wherein Z is an aminoacid chain, preferably RA and the fragment is cleaved by the toxin.