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Commercial Availability (commercial + availability)
Selected AbstractsTarget-Family-Oriented Focused Libraries for Kinases,Conceptual Design Aspects and Commercial AvailabilityCHEMBIOCHEM, Issue 3 2005Olaf Prien Dr. Tailor-made libraries may increase the likelihood of identifying potential lead candidates in early drug-discovery phases. That at least 12 commercial vendors offer their services in providing compound collections of tentative kinase inhibitors reflects the growing interest in kinases within the pharmaceutical industry. Some conceptual design approaches for focused library design for the kinase family are reviewed, and the design concepts of these commercialized libraries is discussed. [source] Learning from tobacco: bans on commercial availability are not unthinkableADDICTION, Issue 6 2003ROBERTA FERRENCE No abstract is available for this article. [source] A Simple Synthesis of Functionalized 3-Bromocoumarins by a One-Pot Three-Component ReactionEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2010Davide Audisio Abstract Functionalized 3-bromocoumarins 2 have been prepared by a simple one-pot bromination/Wittig/cyclization tandem process from methyl (triphenylphosphoranylidene)acetate, N -bromosuccinimide and a series of 2-hydroxybenzaldehydes. Owing to the commercial availability of salicylaldehyde derivatives, this approach offers such a diverse range of compounds that it fulfills the recent demand for the generation of large combinatorial chemical libraries based on the coumarin scaffold. [source] Autism-like behavioral phenotypes in BTBR T+tf/J miceGENES, BRAIN AND BEHAVIOR, Issue 2 2008H. G. McFarlane Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety-like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo. The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme-regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo, supporting further investigation into the contribution of this polymorphism to autism-like behavioral phenotypes. Robust and selective social deficits, repetitive self-grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms. [source] Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays,,HUMAN MUTATION, Issue 5 2006Jeffrey E. Ming Abstract Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytogenetic tests currently used for the detection of such chromosomal rearrangements are low resolution and limited coverage of the genome. Thus, it is likely that children with MCA may have submicroscopic chromosomal rearrangements that are not detectable by current techniques. We report the use of a commercially available, oligonucleotide-based microarray for genome-wide analysis of copy number alterations. First, we validated the microarray in patients with known chromosomal rearrangements. Next, we identified previously undetected, de novo chromosomal deletions in patients with MCA who have had a normal high-resolution karyotype and subtelomeric fluorescence in situ hybridization (FISH) analysis. These findings indicate that high-density, oligonucleotide-based microarrays can be successfully used as tools for the detection of chromosomal rearrangement in clinical samples. Their higher resolution and commercial availability make this type of microarray highly desirable for application in the diagnosis of patients with multiple congenital defects. Hum Mutat 27(5), 467,473, 2006. © Published 2006 Wiley-Liss, Inc. [source] Kinetic Analysis and Optimization for the Catalytic Esterification Step of PPT PolymerizationMACROMOLECULAR THEORY AND SIMULATIONS, Issue 1 2005Saptarshi Majumdar Abstract Summary: A well-validated kinetic scheme has been studied for PPT, poly(propylene terephthalate) polymerization process in batch and semi-batch mode with tetrabutoxytitanium (TBOT), a proven catalyst. Optimization study and analysis for PPT are rare, as the industrial relevance of PPT just became vibrant due to the commercial availability of one of its monomers in industrial scale in the recent past. Correctness of the analysis is checked by a new approach and parameters for the model are estimated from available experimental data. Solubility of terephthalic acid (TPA) is less in reaction medium and this effect is also considered along with the reaction scheme. Several simulations have been performed to see various process dynamics and this ultimately helps in formulating optimization problems. Using recently developed and well tested real-coded non-dominated sorting genetic algorithm-II, a state-of-the art evolutionary optimization algorithm, a couple of three objective optimization problems have been solved and corresponding Pareto sets are presented. Results show remarkably promising aspects of productivity enhancement with an improvement in product quality. Sensitivity analysis for relatively uncertain solubility parameter is also performed to estimate its effect over the proposed optimal solutions. Multiobjective Pareto front for 3 objectives: degree of polymerization, time and (bTPA,+,bPG). [source] Toward a cure for type 1 diabetes mellitus: diabetes-suppressive dendritic cells and beyondPEDIATRIC DIABETES, Issue 3pt2 2008Nick Giannoukakis Abstract:, Insulin has been the gold standard therapy for diabetes since its discovery and commercial availability. It remains the only pharmacologic therapy for type 1 diabetes (T1D), an autoimmune disease in which autoreactive T cells specifically kill the insulin-producing beta cells. Nevertheless, not even molecularly produced insulin administered four or five times per day can provide a physiologic regulation able to prevent the complications that account for the morbidity and mortality of diabetic patients. Also, insulin does not eliminate the T1D hallmark: beta-cell-specific autoimmunity. In other words, insulin is not a ,cure'. A successful cure must meet the following criteria: (i) it must either replace or maintain the functional integrity of the natural, insulin-producing tissue, the endocrine islets of Langerhans' and, more specifically, the insulin-producing beta cells; (ii) it must, at least, control the autoimmunity or eliminate it altogether; and (iii) it must be easy to apply to a large number of patients. Criterion 1 has been partially realized by allogeneic islet transplantation. Criterion 2 has been partially realized using monoclonal antibodies specific for T-cell surface proteins. Criterion 3 has yet to be realized, given that most of the novel therapies are currently quasi-patient-specific. Herein, we outline the current status of non-insulin-based therapies for T1D, with a focus on cell-based immunomodulation which we propose can achieve all three criteria illustrated above. [source] Tissue reaction of the rabbit urinary bladder to tension-free vaginal tape and porcine small intestinal submucosaBJU INTERNATIONAL, Issue 6 2002D.M. Rabah Objectives ,To compare the histological tissue reactions of urinary bladder in close contact with polypropylene mesh tension-free vaginal tape (TVT) or porcine small intestinal submucosal (SIS) grafts, as the commercial availability of various materials has considerably simplified sling procedures for treating urinary incontinence, but erosion and infection after using artificial sling materials remain an important concern. Materials and methods ,Thirty female New Zealand rabbits were randomized to three groups, i.e. group A (TVT, 12 animals), group B (SIS, 12) and group C (surgical control, six). Through a laparotomy under anaesthesia and an aseptic technique, the bladder was approached at its dome, where a 0.5 × 1 cm piece of TVT or SIS was fixed in direct contact with the bladder wall. The control group underwent only bladder manipulation with no material applied. Half the animals in each group were killed after 6 weeks and the other half after 12 weeks. The urinary bladder was harvested and examined histologically. Results ,The grafts in both groups were characterized by dense foreign-body type reactions and were mostly attached loosely to the bladder wall by a thin layer of fibrovascular tissue. More importantly, the bladder wall reactions showed no inflammation in all 12 animals in group A (TVT) but three of them had various grades of fibrosis. There was severe transmural inflammation in one animal in group B (SIS); one rabbit had grade I and two had grade II fibrosis. The controls, as expected, showed no bladder wall reactions. Conclusion ,In this descriptive analysis of reaction types elicited on the urinary bladder by these grafts, both materials appeared to be safe. Although TVT elicited fewer and less severe adverse reactions, no statistical conclusions can be drawn. The clinical significance of these findings should emerge from long-term clinical data when they become available. [source] | ||||||||||||||||