Abstract: Two variations of a continuous-time instantaneous companding filter are integrated in a 25 GHz bipolar process. Their −3 dB frequencies are tunable in the ranges of 1-30 MHz and 30-100 MHz. The dc gains are controllable up to 10 dB. The measured dynamic ranges for a 1% total harmonic distorsion are 62.5 dB and 50 dB, for the 30 MHz and 100 MHz filters respectively. At maximum cutoff frequencies, the filters dissipate 6.5 mW from a 1.2 V supply. The filters are simple, common-mode interference-resistant, class AB log-domain integrators, suitable for implementation in low-cost bipolar processes. They are suitable for realizing low-voltage filters with reasonable linearity and signal-to-noise ratio. ALL-NPN low distortion input and output interface stages can be added to the integrators. The filters can be used to realized high-frequency programmable filters.

Abstract: Modulating agents for inhibiting an interaction between &agr;-catenin and &bgr;-catenin are provided. The modulating agents comprise one or more of: (a) a &bgr;-catenin HAV motif; (b) a peptide analogue or mimetic of a &bgr;-catenin HAV motif; or (c) an antibody or antigen-binding fragment thereof that specifically binds to a &bgr;-catenin HAV motif. Methods for using such modulating agents for inhibiting cadherin-mediated cell adhesion in a variety of contexts are also provided.

Abstract: The present invention relates to a method for the treatment of Type II Diabetes Mellitus patients, which comprises administering an acidotropic agent to the patient in an amount sufficient for neutralizing intraendosomal pH or preventing lowering of intraendosomal pH; thereby activating insulin receptor kinase of the patient and preventing insulin resistance. The present invention also relates to a method for the screening of an acidotropic agent suitable for the treatment of Type II Diabetes Mellitus.

Abstract: The invention provides method of diagnosing bone disease and/or a susceptibility thereto, in an individual. The method includes screening a biological sample obtained from the individual for one or more genetic indicators of bone disease in said PTHrP gene of the individual, and diagnosing the individual based on a characterization of the genetic indictor(s) detected. A genetic indicator of the invention preferably includes a genetic segment of a PTHrP gene. More preferably, a genetic segment of a PTHrP gene includes a VNTR containing region. The invention further relates to a transgenic non-human mammal for the study of bone disease and/or bone conditions, the mammal having a disruption or inactivation of a PTHrP gene or portion thereof specifically in osteoblast cells.

Abstract: Modulating agents for inhibiting an interaction between &agr;-catenin and &agr;-catenin are provided. The modulating agents comprise one or more of: (a) a &bgr;-catenin HAV motif; (b) a peptide analogue or mimetic of a &bgr;-catenin HAV motif; or (c) an antibody or antigen-binding fragment thereof that specifically binds to a &bgr;-catenin HAV motif. Methods for using such modulating agents for inhibiting cadherin-mediated cell adhesion in a variety of contexts are also provided.

Abstract: Cyclic peptides and compositions comprising such cyclic peptides are provided. The cyclic peptides comprise a classical cadherin cell adhesion recognition sequence HAV. Methods for using such peptides and compositions for inducing apoptosis in cadherin-expressing cells, such as cancer cells, are also provided.

Abstract: The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods of making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of idendifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.

Abstract: Induction of &bgr;-cell neogenesis has been associated with ductal epithelium, however ˜80% of the pancreas is composed of acinar cells. Surprisingly, pancreatic acinar cells contribute to &bgr;-cell neogenesis. Partial duct obstruction (PDO) of the pancreas is a known inducer of &bgr;-cell neogenesis leading to expansion of &bgr;-cell mass, and the effect appears to be mediated by INGAP, an acinar cell protein originally identified in the regenerating hamster pancreas. We examined the effects of PDO on the incorporation of tritiated thymidine by acinar and &bgr;-cells of the pancreas in female Syrian hamsters. A single dose of tritiated thymidine was administered to all animals 2 weeks after PDO. Animals were then sacrificed at 1 hr, or at 6 weeks post-injection. Tritiated thymidine incorporation into acinar cells was highest at 2 weeks after PDO and declined at 8 weeks after PDO. Incorporation of tritiated thymidine into &bgr;-cells was inversely related to that observed in acinar cells.

Abstract: The present invention relates to an in vitro method for islet cell expansion, which comprises the steps of: a) preparing dedifferentiated cells derived from cells in or associated with post-natal islets of Langerhans; b) expanding the dedifferentiated cells; and c) inducing islet cell differentiation the expanded cells of step b) to become insulin-producing cells.

Abstract: The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to the use of metabolic phenotyping for the individualization of treatment with the drug, amonafide.

Abstract: The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to the use of metabolic phenotyping for the individualization of treatment with antibiotic agents.

Abstract: The present invention relates to non-cross-linked micelles as delivery vehicles for steroid compounds and more particularly to a polycaprolactone-b-poly(ethylene oxide) copolymer micelle as a delivery vehicle for steroids. The delivery system comprises a population of diblock copolymer non-cross-linked micelles, each micelle defining a non-cross-linked core for containing the steroid compound. The delivery system of the present invention maintains the release of the steroid compound in a patient having a deficient steroid level.

Abstract: The present invention relates to an in vitro method for islet cell expansion, which comprises the steps of: a) preparing dedifferentiated cells derived from cells in or associated with post-natal islets of Langerhans; b) expanding the dedifferentiated cells; and c) inducing islet cell differentiation the expanded cells of step b) to become insulin-producing cells.

Abstract: The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to the use of metabolic phenotyping for the individualization of treatment with anxiolitic agents.

Abstract: The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to the use of metabolic phenotyping for the individualization of treatment with antipsychotic agents.

Abstract: The present invention comprises an apparatus and a method of microscopy, for measuring depth dependent profiles of optical absorption, photoluminescence and light scattering in thin films on length scales of a few micrometers to a several millimeters. The principles of this invention are also directly extendable to imaging absorption and scattering at other wavelengths, and the scattering of electrons, and neutrons in thin films on the same or shorter length scales. In the optical range, this depth profile information is recovered by the direct recording of micrometer scale images of a light beam propagating along the depth axis of the material under study. The recording is implemented using a crossed beam microscope apparatus in which a collimated optical beam from a light source is propagated through the material under test.

Abstract: Cyclic peptides comprising a cadherin cell adhesion recognition sequence HAV, and compositions comprising such cyclic peptides, are provided. Methods for using such peptides for modulating cadherin-mediated endothelial cell adhesion in a variety of contexts are also provided.

Abstract: The present invention relates to an agonistic anti-human TrkA mAb 5C3 which recognizes the NGF docking site. Such antibodies may be used for the treatment, diagnosis or prevention of neurological diseases, neuromas and neoplastic tumors which express TrkA receptors. Also these antibodies may be used to develop and screen for pharmaceutical agents which are agonistic or antagonistic to NGF binding to the TrkA receptors.

Abstract: The invention provides a novel apoptosis protein: p28 Bap31. Also provided are p28 Bap31 polypeptide fragments, p28 Bap31 antisense nucleic acid molecules, anti-p28 Bap31 antibodies, and methods for modulating apoptosis and for detecting compounds which modulate apoptosis.

Abstract: The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of identifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.