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Product Profiles (product + profile)
Selected AbstractsAccelerating botulism therapeutic product development in the Department of Defense,DRUG DEVELOPMENT RESEARCH, Issue 4 2009Andrea M. Stahl Abstract Coordinated small-molecule drug discovery research efforts for the treatment of botulism by the public sector, especially the U.S. Department of Defense (DoD) and Department of Health and Human Services (DHHS), began in the 1990s and represent a significant resource investment. Organization of an effective botulism therapeutic drug program, however, presents formidable technical and logistical challenges. Seven distinct BoNT serotypes are known, each representing a different target. Moreover, BoNT exerts its action inside peripheral cholinergic neurons, and some serotypes may persist functionally within nerve cells for weeks or months. Clinical botulism occurs infrequently, and the effectiveness of prolonged mechanical ventilation to treat poisoning further limits experimental drug testing. The efficacy of experimental compounds must be extrapolated from disparate cell- or tissue-based or rodent models. Numerous compounds with moderate efficacy in experimental laboratory assays have been reported, but may not possess the necessary safety, efficacy, and pharmacokinetic profile to support therapeutic development. To mitigate these challenges, we propose product development tools to assist in management of the BoNT portfolio and to clearly define the desired therapeutic product. Establishing a target product profile (TPP) is proposed to guide public sector managers toward critical aspects of the desired therapeutic product. Additional product development tools to assist in shaping research portfolios and to inform decisions regarding lead candidates to pursue are also discussed. Product development tools that facilitate the characterization of the ideal therapeutic product, and assist in the maintenance of a robust portfolio, will ameliorate the inherent financial risk in drug development for treating BoNT intoxication. Drug Dev Res 70:303,326, 2009. Published 2009 Wiley-Liss, Inc. [source] Design differentiation for global companies: Value exporters and value collectorsDESIGN MANAGEMENT REVIEW, Issue 4 2001Clive Grinyer In the global marketplace, should companies maintain uniform product profiles,some with strong national characteristics,or adapt regionally? Most companies tend toward one end or the other, concludes Clive Grinyer. Clearly distinguishing between "value exporters" and "value collectors," he articulates the advantages and disadvantages of each. Companies must strike their own strategic balance, hopefully without diluting the regional diversity that makes life and consumer choices so interesting. [source] Hybrid reuteransucrase enzymes reveal regions important for glucosidic linkage specificity and the transglucosylation/hydrolysis ratioFEBS JOURNAL, Issue 23 2008Slavko Kralj The reuteransucrase enzymes of Lactobacillus reuteri strain 121 (GTFA) and L. reuteri strain ATCC 55730 (GTFO) convert sucrose into ,- d -glucans (labelled reuterans) with mainly ,-(1,4) glucosidic linkages (50% and 70%, respectively), plus ,-(1,6) linkages. In the present study, we report a detailed analysis of various hybrid GTFA/O enzymes, resulting in the identification of specific regions in the N-termini of the catalytic domains of these proteins as the main determinants of glucosidic linkage specificity. These regions were divided into three equal parts (A1,3; O1,3), and used to construct six additional GTFA/O hybrids. All hybrid enzymes were able to synthesize ,-glucans from sucrose, and oligosaccharides from sucrose plus maltose or isomaltose as acceptor substrates. Interestingly, not only the A2/O2 regions, with the three catalytic residues, affect glucosidic linkage specificity, but also the upstream A1/O1 regions make a strong contribution. Some GTFO derived hybrid/mutant enzymes displayed strongly increased transglucosylation/hydrolysis activity ratios. The reduced sucrose hydrolysis allowed the much improved conversion of sucrose into oligo- and polysaccharide products. Thus, the glucosidic linkage specificity and transglucosylation/hydrolysis ratios of reuteransucrase enzymes can be manipulated in a relatively simple manner. This engineering approach has yielded clear changes in oligosaccharide product profiles, as well as a range of novel reuteran products differing in ,-(1,4) and ,-(1,6) linkage ratios. [source] Trichlorofluoroethene: A reactive tracer for evaluating reductive dechlorination in large-diameter permeable columnsGROUND WATER MONITORING & REMEDIATION, Issue 2 2005Jennifer A. Field Trichlorofluoroethene (TCFE) was used as a reactive tracer to determine the in situ rate of reductive dechlorination in treatment zones impacted by three large-diameter permeable columns (LDPCs) that were installed at a trichloroethene (TCE),contaminated site. The LDPCs were part of a pilot study to evaluate the effectiveness of hydrogen, lactate, and zero-valent iron for remediating TCE-contaminated ground water. The rate of TCFE reductive dechlorination was determined for each LDPC by means of push-pull tests conducted in each treatment layer. In addition, the distribution of TCFE's lesser chlorinated transformation products was determined. The rates of TCFE reductive dechlorination ranged from 0.05/d to 0.20/d and corresponded to half-lives ranging from 3.5 to 13.9 d. cis -Dichlorofluoroethene was the dominant transformation product detected in all the tests, which is consistent with the findings from pilot tests conducted in the LDPCs prior to the TCFE push-pull tests. cis -Chlorofluoroethene (CFE) and 1,1-CFE also were detected and indicate the potential for vinyl chloride to form under all treatment regimes. Significant production of fluoroethene (FE), the analog of ethene, was observed for only one of the hydrogen treatments. Unambiguous and sensitive detection of the lesser chlorinated products, such as CFE and FE, is possible because TCFE and its transformation products are not found in the background ground water at contaminated sites. Good agreement between the rates and transformation product profiles for TCFE and TCE in both field and laboratory experiments indicates the suitability of TCFE as a surrogate for predicting the rates of TCE reductive dechlorination. [source] Analysis of functional divergence within two structurally related glycoside hydrolase familiesBIOPOLYMERS, Issue 6 2009Blake Mertz Abstract Two glycoside hydrolase (GH) families were analyzed to detect the presence of functional divergence using the program DIVERGE. These two families, GH7 and GH16, each contain members related by amino acid sequence similarity, retaining hydrolytic mechanisms, and catalytic residue identity. GH7 and GH16 comprise GH Clan B, with a shared ,-jelly roll topology and mechanism. GH7 contains fungal cellobiohydrolases and endoglucanases and is divided into five main subfamilies, four of the former and one of the latter. Cluster comparisons between three of the cellobiohydrolase subfamilies and the endoglucanase subfamily identified specific amino acid residues that play a role in the functional divergence between the two enzyme types. GH16 contains subfamilies of bacterial agarases, xyloglucosyl transferases, 1,3-,- D -glucanases, lichenases, and other enzymes with various substrate specificities and product profiles. Four cluster comparisons between these four main subfamilies again have identified amino acid residues involved in functional divergence between the subfamilies. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 478,495, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] | ||||||||||