Abstract: The invention provides immunosuppressive polypeptides and nucleic acids encoding such polypeptides. In one aspect, the invention provides mutant CTLA-4 polypeptides and nucleic acids encoding mutant CTLA-4 polypeptides. Compositions and methods for utilizing such polypeptides and nucleic acids are also provided.

Abstract: The invention provides immunosuppressive polypeptides and nucleic acids encoding such polypeptides. In one aspect, the invention provides mutant CTLA-4 polypeptides and nucleic acids encoding mutant CTLA-4 polypeptides. Compositions and methods for utilizing such polypeptides and nucleic acids are also provided.

Abstract: The invention provides immunosuppressive polypeptides and nucleic acids encoding such polypeptides. In one aspect, the invention provides mutant CTLA-4 polypeptides and nucleic acids encoding mutant CTLA-4 polypeptides. Compositions and methods for utilizing such polypeptides and nucleic acids are also provided.

Abstract: Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a low in vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugated recombinant human G-CSF.

Abstract: Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a low in vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugated recombinant human G-CSF.

Abstract: The present invention relates to novel full-length interferon gamma (IFNG) polypeptide variants having interferon gamma activity. The full-length interferon gamma polypeptide variants of the invention are obtained by performing selected modifications in the C-terminal part of the molecule. The full-length interferon gamma polypeptide variants of the invention are useful in therapy, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis.

Abstract: A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.

Abstract: Integrated systems and methods for diversity generation and screening are provided. The systems use common fluid and array handling components to provide nucleic acid diversification, transcription, translation, product screening and subsequent diversification reactions.

Abstract: Apparatus and methods for high throughput mass spectrometry are provided. The methods involve sample preparation in an off-line parallel purification system. Such methods include but are not limited to the use of an appropriate buffer when generating samples or the use of a solid support for tagged components. The samples prepared in this way do not then need to be column separated. The apparatus provided includes a cell growth plate for growing cells and generating products and/or reactants, an off-line parallel purification system, a mass spectrometer, and an automatic sampler that transports samples and injects them into the mass spectrometer of the apparatus. The methods and apparatus described are used, for example, in screening enzyme reaction pathways.

Abstract: A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.

Abstract: In particular, this invention provides novel methods of populating data structures for use in evolutionary modeling. In particular, this invention provides methods of populating a data structure with a plurality of character strings. The methods involve encoding two or more a biological molecules into character strings to provide a collection of two or more different initial character strings; selecting at least two substrings from the pool of character strings; concatenating the substrings to form one or more product strings about the same length as one or more of the initial character strings; adding the product strings to a collection of strings; and optionally repeating this process using one or more of the product strings as an initial string in the collection of initial character strings.

Abstract: This invention provides improved monoxygenases, dehydrogenases, and transferases that are useful for the biocatalytic synthesis of compounds such as &agr;-hydroxycarboxylic acids, and aryl- and alkyl-hydroxy compounds. The polypeptides provided herein are improved in properties such as regioselectivity, enzymatic activity, stereospecificity, and the like. Methods for obtaining recombinant polynucleotides that encode these improved polypeptides are also provided, as are organisms that express the polypeptides and are thus useful for carrying out said biocatalytic syntheses. Also provided by the invention are methods for increasing said solvent resistance of organisms that are used in the synthetic methods.

Abstract: The invention provides for use of selective inhibitors of GSK3 for treatment of diseases that are mediated by GSK3 activity, including non-insulin dependent diabetes mellitus (NIDDM) and Alzheimer's disease. Also described are methods of identifying inhibitors of GSK3 activity. The selective GSK3 inhibitor can be a peptide, peptoid, small organic molecule, or polynucleotide.

Abstract: The invention provides for use of selective inhibitors of GSK3 for treatment of diseases that are mediated by GSK3 activity, including non-insulin dependent diabetes mellitus (NIDDM) and Alzheimer's disease. Also described are methods of identifying inhibitors of GSK3 activity. The selective GSK3 inhibitor can be a peptide, peptoid, small organic molecule, or polynucleotide.

Abstract: The invention relates to a vessel apparatus for holding and transferring liquids, in which the level of liquid may be controlled and monitored automatically. A depth sensing device, included in the apparatus, detects the presence or absence of liquid at predetermined levels. The device detects the difference in transmission of a low frequency electromagnetic signal between aerial probes based on the state of immersion (wet or dry) of the transmitting and receiving probes.

Abstract: An improved method for determining binding compounds from a mixture of similar compounds, particularly a phage peptide library, is provided. The method comprises contacting a mixture of candidate compounds with a target molecule presented on two or more different substrates.