Abstract: The invention generally relates to methods for determining whether a peptide includes aspartate or isoaspartate. In certain aspects, methods of the invention involve binding an aspartate/isoaspartate residue in a peptide with a label to produce a labeled peptide. The labeled peptide is then ionized. The ionizing process causes the label to undergo rearrangement in a gas phase at a higher rate if the label is bound to the aspartate residue as compared to if the label is bound to the isoaspartate residue. The methods of the invention then involve performing a mass spectrometry analysis to detect the rearrangement of the label, thereby determining whether the peptide includes aspartate or isoaspartate.

Abstract: A method of determining the activation energy Ea for degradation of a chemical species includes in sequence the steps of a) simultaneously incubating a plurality of samples of the chemical species in a single unitary device at a plurality of constant temperatures T, in each case for an incubation time t selected to result in loss of at most 20 mol % of the amount originally present; b) quenching each of the samples to stop degradation; c) determining the mole fraction m of the chemical species remaining in each of the quenched samples, relative to the amount present before incubating; d) determining for each sample a reaction rate coefficient kobs according to the equation k obs ? ( T ) = 1 - m ? ( T ) t ; and e) performing numerical regression of the kobs values obtained in step d) and the corresponding temperatures T in ° K to derive the activation energy Ea according to the following equation k obs = k 0 ? exp ? ( E a R ? ( 1 T - 1 T 0 ) ) , or to

Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

Abstract: Described herein are materials and methods for treating subjects having a HER-3 associated disease, by administering a first agent that binds to HER-3, in combination with a second agent that binds and/or inhibits another member of the HER family. The first and the second agent may be a biologic, such as an antigen-binding protein, or a small molecular tyrosine kinase inhibitor, for example.

Abstract: The present application relates to K-ras mutations, to polynucleotides encoding mutant K-ras polypeptides, and to methods of identifying K-ras mutations. The present application also relates to B-raf mutations, to polynucleotides encoding mutant B-raf polypeptides, to vectors containing those polynucleotides, and to methods of identifying B-raf mutations. The present application also relates to methods of diagnosing cancer; and methods and kits for predicting the usefulness of anti-EGFr specific binding agents in the treatment of tumors.

Abstract: Selected compounds are effective for treatment of pain and diseases, such as inflammation mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving pain, inflammation, and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: Disclosed are novel proteins, referred to as truncated glial cell line-derived neurotrophic factor (truncated GDNF) proteins, that promote dopamine uptake by dopaminergic cells and promote the survival of nerve cells. Also disclosed are processes for obtaining the truncated GDNF proteins by recombinant genetic engineering techniques.

Abstract: A method for genetically engineering cells to produce soluble and secretable Golgi processing enzymes instead of naturally occurring membrane-bound enzymes. Cells are genetically engineered to express glycosyltransferases which lack both a membrane anchor and a retention signal. The resulting altered enzyme becomes soluble and secretable by the cell without losing its catalytic activity. Secretion of the soluble glycosyltransferase by the cell provides for increased production and simplified recovery of glycosyltransferase.

Abstract: A hybrid promoter for controlling exogenous gene transcription is constructed by insertion of a UAS.sub.G into a GPD portable promoter. The resulting hybrid promoter is placed upstream of an exogenous gene in a hybrid yeast-bacterial plasmid, which is used to transform yeast cells. Due to the regulation imparted to the GPD promoter by the UAS.sub.G, transcription of the exogenous gene, and hence production of the exogenous gene product, may be regulated by controlling the composition of the carbon source in the yeast culture medium. Specifically, glucose is used to repress transcription and galactose is used to induce transcription.

Abstract: This disclosure relates to a novel class of serine proteases isolated from a culture medium of fungus Tritirachium album. The serine proteases disclosed have a high degree of stability in detergent formulations.In addition, this disclosure relates to a process for producing such serine proteases using recombinant techniques.

Abstract: A method and a kit for the isolation and quantitative detection of a selected target nucleic acid sequence from solution employing two probes. A first probe is complementary to one portion of the target and is covalently attached to a first complexing agent (e.g., either an antigen or an antibody). The second probe is complementary to a different portion of the target and is associated with a reporter group. Following hybridization of the target and two probes in solution, a solid support coated with a second complexing agent (i.e., a corresponding antibody or antigen) capable of binding to the first complexing agent on the first probe is employed to immobilize the target-probe hybrid complex. A plurality of types of first probes may be used. Each type is attached to the same sort of complexing agent but each includes a nucleic acid sequence which is complementary to a different portion of the target.

Abstract: A microbial shuttle vector is disclosed which is independently replicative in bacterial cells and mammalian cells and includes in its DNA sequence bacterial plasmid sequences allowing selection and replication in bacterial cells, an SV40 viral origin of replication, and either an SV40 functional "early gene" promoter and functional "early gene" terminator or an SV40 functional "late gene" promoter and functional "late gene" terminator, the vector having a unique restriction endonuclease enzyme recognition site between the promoter and terminator for insertion of an exogenous gene. The presence of restriction endonuclease enzyme recognition sites facilitative of insertion of a viral functional "late gene" into the "early gene" promoter/terminator vector in a single step allows for conversion of the shuttle vector into a lytic vector of an exogenous gene.

Abstract: Novel yeast cell transformation vectors are manufactured and employed in securing expression of exogenous polypeptides in yeast cells. Vectors include promoter/regulator DNA sequences of yeast glyceraldehyde-3-phosphate dehydrogenase gene origins. In an illustrative preferred embodiment, novel immunologically active hepatitis B surface antigen (HBsAg) preparations are isolated from yeast cells transformed with plasmid A.T.C.C. 40053. These HBsAg preparations of yeast origin may be incorporated into vaccine compositions useful in developing immunological responses protective against infection by hepatitis B virus.

Abstract: In processes for recovery of biologically active polypeptides from fermentation cultures of recombinant host organisms, cell death is frequently a prerequisite for isolation processing of the recombinant product outside the fermentation vessel. Disclosed are improved methods for effecting efficient host cell death inside the fermentation vessel through uniformly contacting host cells in culture with microbicidal concentrations of benzyl alcohol. Illustratively, E. coli, B. subtilis, and P. aeruginosa cultures are advantageously treated with from 0.5 to 10.0% (v/v) of benzyl alcohol in the absence of pH or temperature changes within the fermentor.

Abstract: Methods and constructions for controlling the copy number and for maintaining the stability of a plasmid in yeast cells involving inserting into the plasmid a centromere sequence under the transcriptional control of a regulatable promotor. The promoter is not activated when it is desirable to maintain a copy number of one per haploid cell (e.g. during a culture growth phase) but is activated when expression is desired. When the promoter is inactive, the centromere sequence causes the plasmid to behave as a minichromosome, but upon activation of the promoter transcription through the centromere sequence permits an increase in copy number. Multicopy plasmids are selected for by inserting a G418 resistance gene in the plasmid. Medium concentrations of greater than about 400 .mu.g/ml of G418 will select for cells containing multiple copies of the plasmid while lesser concentrations of G418 select for cells containing a single copy of a plasmid containing G418.sup.

Abstract: Described are rapid and highly efficient procedures for the total synthesis of linear, double stranded DNA sequences in excess of about 200 base pairs in length, which sequences may comprise entire structural genes. Novel sequences are prepared from two or more DNA subunits provided with terminal regions comprising restriction endonuclease cleavage sites facilitating insertion of subunits into a selected vector for purposes of amplification during the course of the total assembly process. The total, finally-assembled sequences include at least one, and preferably two or more, unique restriction endonuclease cleavage site(s) at intermediate positions along the sequence, allowing for easy excision and replacement of subunits and the correspondingly facile preparation of multiple structural analogs of polypeptides coded for by the sequences.

Abstract: A composition of matter consisting of recombinant human immune interferon having a near-UV circular dichroic spectrum in aqueous solution at neutral pH with positive bands at about 259 nm, 266 nm, 280 nm, and 287 nm, and with shoulders at about 270 nm and 292 nm. Also disclosed is a method for purifying human immune interferon in which proper refolding of the interferon is accomplished by unfolding in a denaturant, such as urea, dilution in ammonium acetate to approximately 0.18 mg/ml of interferon (or less), and dialysis of the solution. The properly folded, purified product which results has a four- to eight-fold greater activity than the aggregate which otherwise results.

Abstract: A method for the isolation and quantitative detection of a selected single-stranded target polynucleotide from solution. The target polynucleotide is hybridized in solution to a single-stranded mediator polynucleotide, a probe polynucleotide, and an immobilized polynucleotide sequence. The sequence of the mediator polynucleotide comprises a first sequence complementary to a first portion of the target polynucleotide sequence and a second nucleotide sequence complementary to a portion of a single-stranded immobilized polynucleotide sequence. The probe polynucleotide, which carries a detectable label, is complementary to a second portion of the necleotide sequence of the target. The immobilized polynucleotide is immobilized by attachment to a solid support, and, through hybridization to the mediator polynucleotide, functions to immobilize the entire immobilized polynucleotide/target polynucleotide/probe polynucleotide "sandwich".

Abstract: A method for the preparation of a 3' end functionalized polynucleotide is disclosed. An amine-functionalized solid phase support is treated sequentially with an anhydride, then with an .omega.-hydroxylamine. A polynucleotide is chemically synthesized on the treated support and is subsequently cleaved therefrom by hydrolysis of the amide bonds. A polynucleotide having a 3' free primary amine is recovered for use in hybridization assays and other uses.

Abstract: Disclosed are novel synthetic peptides having primary structural homology to a continuous sequence of amino acid residues of human growth hormone in a region spanning positions thirty-two to forty-six ("hGH.sub.32-46 ", or "deletion peptide"). In preferred forms, peptides of the invention comprehend: duplicate portions (i.e., sequence fragments) of hGH.sub.32-46 ; stereochemical analogs and fragment analogs of hGH.sub.32-46 including one or more amino acid residues in D-isomeric configuration; and, "interspecies" analogs and fragment analogs of hGH.sub.32-46 including one or more non-homologous amino acid residues duplicating variant residues present in corresponding positions in corresponding regions of heterologous species growth hormones. Peptides of the invention are administered to mammals contemporaneously with exogenous insulin to generate hypoglycemic effects greater than available through administration of insulin alone. A presently preferred heptapeptide has the sequence, NH.sub.