Abstract: A monitoring and alerting system for detecting a disruptive event on the Internet includes a data collection and wrapping module configured to process input data that includes messages produced by a network routing protocol, including a live stream of messages on the network, historical dumps of the message to a computer's file system, or both. An automated analysis engine includes analysis modules configured to analyze routing information and selected Internet behaviors from the input data. User output includes automated alerts to the user and an interactive analysis module. The analysis modules include a probabilistic origin hijack analysis module; a probabilistic route hijack analysis module; a Hidden Markov Model analysis module; a tensor decomposition and analysis module and a static topology analysis module; and a dynamic topology analysis module.

Abstract: Provided herein is combination therapy containing an anti-hyaluronan agent, such as a polymer-conjugated hyaluronan-degrading enzyme, and a tumor-targeted taxane, and optionally a further chemotherapeutic agent such as a nucleoside analog. The combination therapy can be used in methods of treating cancers, and in particular solid tumor cancers.

Abstract: Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Abstract: Provided herein are modified anti-EGFR antibodies and nucleic acid molecules encoding modified anti-EGFR antibodies. Also provided are methods of treatment and uses using modified anti-EGFR antibodies.

Abstract: Provided are compositions and formulations or co-formulations containing a hyaluronan degrading enzyme. The compositions, formulations or co-formulations can also contain another therapeutic agent, such as one that is suitable for treatment of Benign Prostatic Hyperplasia, for example, a 5-alpha reductase inhibitor. The compositions and formulations can be used for the treatment of Benign Prostatic Hyperplasia. The compositions and formulations can be provided in combinations with one or more other agents for the treatment of Benign Prostatic Hyperplasia.

Abstract: Methods and diagnostic agents for identification of subjects for cancer treatment with an anti-hyaluronan agent, such as a hyaluronan-degrading enzyme, are provided. Diagnostic agents for the detection and quantification of hyaluronan in a biological sample and monitoring cancer treatment with an anti-hyaluronan agent, for example a hyaluronan-degrading enzyme, are provided. Combinations and kits for use in practicing the methods also are provided.

Abstract: Methods for evolving or selecting or producing therapeutic proteins that exhibit reduced adverse side-effects and the resulting proteins are provided. For example, provided herein is an in vitro assay to identify conditionally active therapeutic proteins that exhibit better activity within one in vivo environment compared to another in vivo environment. The methods include the steps of a) testing the activity of a protein under conditions in which normal or increased activity is desired; b) testing the activity of the protein under conditions in which reduced activity compared to normal is desired; and c) comparing the activity in a) with b) and selecting/identifying a protein that has greater activity in a) compared to b). The selected/identified protein is a conditionally active protein.

Abstract: Provided herein are methods for ameliorating an adverse effect of systemic administration of a PEG hyaluronan degrading enzyme to a subject. The methods involve systemically administering a PEGylated hyaluronan degrading enzyme, particularly a PEGylated hyaluronidase, such as any of the animal or bacterial hyaluronidases, to the subject and administering an amount of a corticosteroid sufficient to ameliorate the adverse effect. Also provided are method of treating a hyaluronan-associated disease or condition for single-agent therapy or combination therapy.

Abstract: The invention provides for compositions comprising engineered Her3 multimers with improved binding affinity. Such multimers include, but are not limited to, Her1/Her 3 heterodimers in which the Her3 ligand binding domain has been optimized to increase binding to Her3. The composition also can include mixtures of Her 1 homodimers, Her 3 homodimers, and Her 1/Her 3 heterodimers.

Abstract: Provided are pan-cell surface receptor-specific therapeutics, methods for preparing them and methods of treatment using them. Among the pan-cell surface receptor-specific therapeutics are pan-HER-specific therapeutics that interact with at least two different HER receptor ligands and/or dimerize with or interact with two or more HER cell surface receptors. By virtue of these properties, the therapeutics modulate the activity of at least two cell surface receptors and are useful for therapeutic purposes.

Abstract: This invention provides novel compounds selected from the group consisting of a 1,5-substituted pyrimidine derivative or analog and substituted furano-pyrimidone analogs. The compounds are useful to treat or prevent diseases such as cancer.

Abstract: This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.

Abstract: Isoforms of cell surface receptors, including isoforms of receptor tyrosine kinases, and pharmaceutical compositions containing the isoforms are provided. Chimeras of and conjugates containing the cell surface receptors that contain a portion, such as an extracellular domain, from one cell surface receptor, and a second portion, particularly an intron-encoded portion, from a second cell surface protein also are provided. The isoforms modulate the activity of a cell surface receptor. Methods for identifying and preparing isoforms of cell surface receptors including receptor tyrosine kinases are provided. Also provided are methods of treatment with the cell surface receptor isoforms.

Abstract: A method of manufacturer incentive distribution to consumers is provided the method comprises receiving a first list from a consumer, the first list having at least one item the consumer wishes to purchase, receiving an incentive from at least one incentive provider, the incentive being associated with a keyword on a second list of keywords, comparing the keyword in the second list to the at least one item in the first list, creating a third list which includes the incentive associated with the keyword if the keyword matches the at least one item in the first list, transmitting the third list to the consumer to permit the consumer to choose the incentive, receiving the consumer's choice of the incentive; and transmitting to the consumer the incentive.

Abstract: This invention provides compounds, compositions and methods for treating cancer, infectious disease, an autoimmune disorder or an inflammatory condition.

Abstract: This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.

Abstract: This invention provides compounds, compositions and methods for treating cancer, infectious disease, an autoimmune disorder or an inflammatory condition. Therapeutic compounds useful in the methods of this invention are 5?-phosphoramidatyl, 1,5-substituted pyrimidine compounds, derivatives, analogs and pharmaceutically acceptable salts thereof.

Abstract: A method for transducing a pathologic hyperproliferative mammalian cell is provided by this invention. This method requires contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function. Also provided by this invention is a method for treating a pathology in a subject caused by the absence of, or the presence of a pathologically mutated tumor suppressor gene.

Abstract: This invention provides methods for using novel substituted pyrimidine compounds, derivatives and analogs thereof to treat diseases such as cancer. Examples of compounds and derivatives for use in the methods are (E)-5-(2-bromovinyl)-2?-deoxy-5?-uridyl phenyl L-alaninylphosphoramidate and (E)-5-(2-bromovinyl)-2?-deoxy-5?-uridyl phenyl L-alaninyl monophosphate.

Abstract: This invention provides methods for treating inflammatory or autoimmune diseases by contacting the affected cell or tissue with a therapeutic compound as described herein. Such pathologies include, but are not limited to rheumatoid arthritis, systemic lupus erythmatosus, psoriatic arthritis, reactive arthritis, Crohn's disease, ulcerative colitis and scleroderma. Therapeutic compounds useful in the methods of this invention are selected from the group consisting of a 1,5-substituted pyrimidine derivative or analog and substituted furano-pyrimidone analog.