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Predicted
Terms modified by Predicted Selected AbstractsEarly adversity in chronic depression: clinical correlates and response to pharmacotherapy,,DEPRESSION AND ANXIETY, Issue 8 2009Daniel N. Klein Ph.D. Abstract Background: There is growing evidence suggesting that early adversity may be a marker for a distinct pathway to major depressive disorder (MDD). We examined associations between childhood adversity and a broad variety of clinical characteristics and response to pharmacotherapy in a large sample of patients with chronic forms of MDD. Methods: Subjects included 808 patients with chronic forms of MDD (chronic MDD, double depression, or recurrent MDD with incomplete recovery between episodes and a total continuous duration of >2 years) who were enrolled in a 12-week open-label trial of algorithm-guided pharmacotherapy. Baseline assessments included a semi-structured diagnostic interview, and clinician- and self-rated measures of depressive symptoms, social functioning, depressotypic cognitions, and personality traits, and childhood adversity. Patients were re-evaluated every 2 weeks. Results: A longer duration of illness; earlier onset; greater number of episodes, symptom severity, self-rated functional impairment, suicidality, and comorbid anxiety disorder; and higher levels of dysfunctional attitudes and self-criticism were each associated with multiple forms of childhood adversity. A history of maternal overcontrol, paternal abuse, paternal indifference, sexual abuse, and an index of clinically significant abuse each predicted a lower probability of remission. Among patients completing the 12-week trial, 32% with a history of clinically significant abuse, compared to 44% without such a history, achieved remission. Conclusions: These findings indicate that a history of childhood adversity is associated with an especially chronic form of MDD that is less responsive to antidepressant pharmacotherapy. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc. [source] FACS-array gene expression analysis during early development of mouse telencephalic interneuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2008Eric D. Marsh Abstract Cortical interneuron dysfunction has been implicated in multiple human disorders including forms of epilepsy, mental retardation, and autism. Although significant advances have been made, understanding the biologic basis of these disorders will require a level of anatomic, molecular, and genetic detail of interneuron development that currently does not exist. To further delineate the pathways modulating interneuron development we performed fluorescent activated cell sorting (FACs) on genetically engineered mouse embryos that selectively express green fluorescent protein (GFP) in developing interneurons followed by whole genome microarray expression profiling on the isolated cells. Bioinformatics analysis revealed expression of both predicted and unexpected genes in developing cortical interneurons. Two unanticipated pathways discovered to be up regulated prior to interneurons differentiating in the cortex were ion channels/neurotransmitters and synaptic/vesicular related genes. A significant association of neurological disease related genes to the population of developing interneurons was found. These results have defined new and potentially important data on gene expression changes during the development of cortical interneurons. In addition, these data can be mined to uncover numerous novel genes involved in the generation of interneurons and may suggest genes/pathways potentially involved in a number of human neurological disorders. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Deficit in community species richness as explained by area and isolation of sitesDIVERSITY AND DISTRIBUTIONS, Issue 3 2000Hans Henrik Bruun Abstract .,The potential community species richness was predicted for 85 patches of seminatural grassland in an agricultural landscape in Denmark. The basis of the prediction was a very large dataset on the vegetation, soil pH and topography in Danish grasslands and related communities. Species were inserted into potential species pools according to their preferences regarding soil acidity and water availability (expressed as potential solar irradiation), and to the ranges in these two factors observed in each grassland patch. The difference between the predicted and the observed patch-level species richness, community richness deficit, varied considerably among patches. Community richness deficit exhibited a negative relationship with patch area, and for small patches a positive relationship with patch isolation. [source] Prediction of metabolite identity from accurate mass, migration time prediction and isotopic pattern information in CE-TOFMS dataELECTROPHORESIS, Issue 14 2010Masahiro Sugimoto Abstract CE-TOFMS is a powerful method for profiling charged metabolites. However, the limited availability of metabolite standards hinders the process of identifying compounds from detected features in CE-TOFMS data sets. To overcome this problem, we developed a method to identify unknown peaks based on the predicted migration time (tm) and accurate m/z values. We developed a predictive model using 375 standard cationic metabolites and support vector regression. The model yielded good correlations between the predicted and measured tm (R=0.952 and 0.905 using complete and cross-validation data sets, respectively). Using the trained model, we subsequently predicted the tm for 2938 metabolites available from the public databases and assigned tentative identities to noise-filtered features in human urine samples. While 38.9% of the peaks were assigned metabolite names by matching with the standard library alone, the proportion increased to 52.2%. The proposed methodology increases the value of metabolomic data sets obtained from CE-TOFMS profiling. [source] Cyclical electrical field flow fractionationELECTROPHORESIS, Issue 9 2005Bruce K. Gale Abstract Cyclical electrical field flow fractionation (Cy/ElFFF) is demonstrated in a standard electrical field flow fractionation (ElFFF) channel for the first time. Motivation for the use of alternating current (AC) fields in a traditionally direct current (DC) technique are discussed. The function of the system over a wide range of operating conditions is explored and challenges associated with various operating conditions reported. Retention of polystyrene nanoparticle standards is accomplished and the effect of varying parameters of the applied field, such as voltage and frequency, are explored. The first separations using this technique are demonstrated. The experimental results are compared to analytical models previously reported in the literature. The general trend of the experimental results is similar to those predicted in theoretical models and possible reasons for discrepancies are elucidated. Suggestions are made for improving the separation and analysis method, and possible applications explored. [source] Quantitative structure-activity relationships for predicting potential ecological hazard of organic chemicals for use in regulatory risk assessmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2003Mike H. I. Comber Abstract The use of quantitative structure-activity relationships (QSARs) for deriving the predicted no-effect concentration of discrete organic chemicals for the purposes of conducting a regulatory risk assessment in Europe and the United States is described. In the United States, under the Toxic Substances Control Act (TSCA), the TSCA Interagency Testing Committee and the U.S. Environmental Protection Agency (U.S. EPA) use SARs to estimate the hazards of existing and new chemicals. Within the Existing Substances Regulation in Europe, QSARs may be used for data evaluation, test strategy indications, and the identification and filling of data gaps. To illustrate where and when QSARs may be useful and when their use is more problematic, an example, methyl tertiary-butyl ether (MTBE), is given and the predicted and experimental data are compared. Improvements needed for new QSARs and tools for developing and using QSARs are discussed. [source] Expression of one sponge Iroquois homeobox gene in primmorphs from Suberites domuncula during canal formationEVOLUTION AND DEVELOPMENT, Issue 3 2003Sanja Perovi SUMMARY Sponges (Porifera) represent the evolutionary oldest multicellular animals. They are provided with the basic molecules involved in cell,cell and cell,matrix interactions. We report here the isolation and characterization of a complementary DNA from the sponge Suberites domuncula coding for the sponge homeobox gene, SUBDOIRX-a. The deduced polypeptide with a predicted Mr of 44,375 possesses the highly conserved Iroquois-homeodomain. We applied in situ hybridization to localize Iroquois in the sponge. The expression of this gene is highest in cells adjacent to the canals of the sponge in the medulla region. To study the expression of Iroquois during development, the in vitro primmorph system from S. domuncula was used. During the formation of these three-dimensional aggregates composed of proliferating cells, the expression of Iroquois depends on ferric iron and water current. An increased expression in response to water current is paralleled with the formation of canal-like pores in the primmorphs. It is suggested that Iroquois expression is involved in the formation of the aquiferous system, the canals in sponges and the canal-like structures in primmorphs. [source] Determination of essential oil quality index by using energy summation indices in an elite strain of Cymbopogon citratus (DC) Stapf [RRL(J)CCA12]FLAVOUR AND FRAGRANCE JOURNAL, Issue 2 2005Ashok Kumar Shahi Abstract Out of the several accessions of Cymbopogon citratus (DC) Stapf introduced from Central and West India, one accession coded as RRL(J)CCA12, selected through a mass selection technique, was found to have citral (,80%) as the major constituent in its essential oil. Citral has tremendous application in the ,avour and perfume industries. Plant adaptation was judged by quantifying the regression coef,cient (b) value, which was 1.0 using essential oil growth indices. For prediction of essential oil quality index (EOQI), a multiple regression equation was developed for the ,rst time by using essential oil yield/plant and energy summation indices as EOQI (citral %) = 61.6 + 1.09 × essential oil yield/plant (g) - 0.005 × heat use ef,ciency + 0.675 × phenothermal index. For obtaining a better quality of essential oil (citral ,78%), the optimal value of independent variable would be: X1 = 2.49; X2 = 0.018 and X3 = 20.47, where X1, X2 and X3 denote essential oil yield/plant, heat use ef,ciency and phenothermal index, respectively. The validation of the EOQI model is done by correlating the predicted and calculated values of citral (%) which exhibited signi,cant r value = 0.955 at 5% probability level. The thermal requirement of the selectant was ,5500 degree days to exhibit plant maturity in terms of qualitative and quantitative characteristics of its essential oil at 6.0 vegetative lea,ng stage, with attainment of plant height ,1.0 m from previous date of harvest (December 2001). Prediction of essential oil quality by using the mathematical model is helpful for integrating the growth processes and evaluating crop management strategies. Copyright © 2004 John Wiley & Sons, Ltd. [source] Laissez-faire governance and the archetype laissez-faire city in the USA: exploring HoustonGEOGRAFISKA ANNALER SERIES B: HUMAN GEOGRAPHY, Issue 1 2003Igor Vojnovic This article explores the governance of Houston, the archetype laissez-faire city in the USA. The research examines the complexity of Houston's minimal government intervention rhetoric, which in practice involves extensive federal, state and local government involvement in economic development in combination with a disinterest in social service and income maintenance programmes. This governance strategy is outlined through an examination both of regional public policy and local public finances. The analysis illustrates that Houston's local governance has historically been based on a management approach that attempts actively to minimize costs for potential investors to locate in the City, through public intervention, while at the same time generating an unattractive urban environment for the socially marginalized , hence the disinterest in social services. Thus, despite the local laissez-faire rhetoric, government intervention in Houston's growth has been vital and has produced the extraordinary impacts usually expected from public involvement in local economic development. The foundations of this local governance strategy are both predicted and advocated by the public choice approach, a theoretical framework whose emphasis on inter-municipal competition advances management tactics based on maintaining low taxes and low expenditures on public welfare. The research also shows, however, that Houston is unique, when compared to other economically successful US cities, in following such an extreme approach of this management strategy. [source] Surface deformation induced by present-day ice melting in SvalbardGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 1 2009H. P. Kierulf SUMMARY The vertical movement of the Earth's surface is the result of a number of internal processes in the solid Earth, tidal forces and mass redistribution in the atmosphere, oceans, terrestrial hydrosphere and cryosphere. Close to ice sheets and glaciers, the changes in the ice loads can induce large vertical motions at intraseasonal to secular timescales. The Global Positioning System (GPS) and Very Long Baseline Interferometry (VLBI) antennas in Ny-Ålesund, Svalbard that started observations in 1991 and 1995, respectively, observe vertical uplift rates on the order of 8 ± 2 mm yr,1, which are considerably larger than those predicted by postglacial rebound (PGR) models (order 2 mm yr,1). The observations also indicate increased uplift rates starting some time in 2000. A local GPS campaign network that has been reoccupied annually since 1998, reveals a tilting away from the neighbouring glaciers. The Svalbard glaciers have been undergoing melting and retreat during the last century, with increased melting since about 2000. We compared the observed vertical motion to the motion predicted by loading models using a detailed ice model with annual time resolution as forcing. The model predictions correlate well with the observations both with respect to the interannual variations and the spatial pattern of long-term trends. The regression coefficients for predicted and observed interannual variations in height is 1.08 ± 0.38, whereas the regression coefficient for the predicted and observed spatial pattern turns out to be 1.26 ± 0.42. Estimates of the predicted secular trend in height due to PGR and present-day melting are on the order of 4.8 ± 0.3 mm yr,1 and thus smaller than the observed secular trend in height. This discrepancy between predictions and observations is likely caused by the sum of errors in the secular rates determined from observations (due to technique-dependent large-scale offsets) and incomplete or erroneous models (unaccounted tectonic vertical motion, errors in the ice load history, scale errors in the viscoelastic PGR models and the elastic models for present-day melting). [source] Marine range shifts and species introductions: comparative spread rates and community impactsGLOBAL ECOLOGY, Issue 3 2010Cascade J. B. Sorte ABSTRACT Aim, Shifts in species ranges are a predicted and realized effect of global climate change; however, few studies have addressed the rates and consequence of such shifts, particularly in marine systems. Given ecological similarities between shifting and introduced species, we examined how our understanding of range shifts may be informed by the more established study of non-native species introductions. Location, Marine systems world-wide. Methods, Database and citation searches were used to identify 129 marine species experiencing range shifts and to determine spread rates and impacts on recipient communities. Analyses of spread rates were based on studies for which post-establishment spread was reported in linear distance. The sizes of the effects of community impacts of shifting species were compared with those of functionally similar introduced species having ecologically similar impacts. Results, Our review and meta-analyses revealed that: (1) 75% of the range shifts found through the database search were in the poleward direction, consistent with climate change scenarios, (2) spread rates of range shifts were lower than those of introductions, (3) shifting species spread over an order of magnitude faster in marine than in terrestrial systems, and (4) directions of community effects were largely negative and magnitudes were often similar for shifters and introduced species; however, this comparison was limited by few data for range-shifting species. Main conclusions, Although marine range shifts are likely to proceed more slowly than marine introductions, the community-level effects could be as great, and in the same direction, as those of introduced species. Because it is well-established that introduced species are a primary threat to global biodiversity, it follows that, just like introductions, range shifts have the potential to seriously affect biological systems. In addition, given that ranges shift faster in marine than terrestrial environments, marine communities might be affected faster than terrestrial ones as species shift with climate change. Regardless of habitat, consideration of range shifts in the context of invasion biology can improve our understanding of what to expect from climate change-driven shifts as well as provide tools for formal assessment of risks to community structure and function. [source] The biogeography of prediction error: why does the introduced range of the fire ant over-predict its native range?GLOBAL ECOLOGY, Issue 1 2007Matthew C. Fitzpatrick ABSTRACT Aim, The use of species distribution models (SDMs) to predict biological invasions is a rapidly developing area of ecology. However, most studies investigating SDMs typically ignore prediction errors and instead focus on regions where native distributions correctly predict invaded ranges. We investigated the ecological significance of prediction errors using reciprocal comparisons between the predicted invaded and native range of the red imported fire ant (Solenopsis invicta) (hereafter called the fire ant). We questioned whether fire ants occupy similar environments in their native and introduced range, how the environments that fire ants occupy in their introduced range changed through time relative to their native range, and where fire ant propagules are likely to have originated. Location, We developed models for South America and the conterminous United States (US) of America. Methods, We developed models using the Genetic Algorithm for Rule-set Prediction (GARP) and 12 environmental layers. Occurrence data from the native range in South America were used to predict the introduced range in the US and vice versa. Further, time-series data recording the invasion of fire ants in the US were used to predict the native range. Results, Native range occurrences under-predicted the invasive potential of fire ants, whereas occurrence data from the US over-predicted the southern boundary of the native range. Secondly, introduced fire ants initially established in environments similar to those in their native range, but subsequently invaded harsher environments. Time-series data suggest that fire ant propagules originated near the southern limit of their native range. Conclusions, Our findings suggest that fire ants from a peripheral native population established in an environment similar to their native environment, and then ultimately expanded into environments in which they are not found in their native range. We argue that reciprocal comparisons between predicted native and invaded ranges will facilitate a better understanding of the biogeography of invasive and native species and of the role of SDMs in predicting future distributions. [source] PTCH mutations: distribution and analyses,HUMAN MUTATION, Issue 3 2006Erika Lindström Abstract Mutations in the PTCH (PTCH1) gene are the underlying cause of nevoid basal cell carcinoma syndrome (NBCCS), and are also found in many different sporadic tumors in which PTCH is thought to act as a tumor suppressor gene. To investigate the distribution pattern of these mutations in tumors and NBCCS, we analyzed 284 mutations and 48 SNPs located in the PTCH gene that were compiled from our PTCH mutation database. We found that the PTCH mutations were mainly clustered into the predicted two large extracellular loops and the large intracellular loop. The SNPs appeared to be clustered around the sterol sensing domain and the second half of the protein. The NBCCS cases and each class of tumor analyzed revealed a different distribution of the mutations in the various PTCH domains. Moreover, the types of mutations were also unique for the different groups. Finally, the PTCH gene harbors mutational hot spot residues and regions, including a slippage-sensitive sequence in the N-terminus. Hum Mutat 27(3), 215,219, 2006. © 2006 Wiley-Liss, Inc. [source] Expression and characterization of ,-glucosidase III in the dwarf honeybee, Apis florea (Hymenoptera: Apoidea: Apidae)INSECT SCIENCE, Issue 4 2007CHANPEN CHANCHAO Abstract Alpha-glucosidase is synthesized in the hypopharyngeal glands located in the head of worker bees including Apis florea. To analyze the developmental stage-specific expression of the ,-glucosidase gene in A. florea, total RNA was isolated from eggs, and the heads of nurse and forager bees. By reverse transcription polymerase chain reaction (RT-PCR), it was shown that the highest expression levels of the ,-glucosidase III gene, in the three examined developmental stadia, were found in forager bees, with much lower expression levels in nurse bees and no detectable expression in eggs. A complete ,-glucosidase III cDNA was obtained by RT-PCR and sequenced. The 1 701 bp cDNA nucleotide sequence and the predicted 567 amino acids it encodes were assayed by BLASTn, BLASTp and BLASTx programs and revealed a 95% and 94% similarity to the A. mellifera,-glucosidase III gene at the DNA and amino acid sequence levels, respectively. For purification of the active encoded enzyme, forager bee heads were homogenized in sodium phosphate buffer solution and the crude extract (0.30 U/mg) sequentially precipitated with 95% saturated ammonium sulfate (0.18 U/mg), and purified by DEAE cellulose ion exchange chromatography (0.17 U/mg), and gel filtration on Superdex 200 (0.52 U/mg). After resolution through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a single enzymically active band (73 kDa) was identified from renatured substrate gels. Excision of this band, elution of the protein and tryptic peptide digestives identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed six matching masses to the A. mellifera (Q17958) and predicted A. florea,-glucosidase III protein with 12% coverage, supporting the probable purification of the same ,-glucosidase III protein as that encoded by the cloned cDNA. [source] A new numerical algorithm for sub-optimal control of earthquake excited linear structuresINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 12 2001Mehmet Bakioglu Abstract Exact optimal classical closed,open-loop control is not achievable for the buildings under seismic excitations since it requires the whole knowledge of earthquake in the control interval. In this study, a new numerical algorithm for the sub-optimal solution of the optimal closed,open-loop control is proposed based on the prediction of near-future earthquake excitation using the Taylor series method and the Kalman filtering technique. It is shown numerically that how the solution is related to the predicted earthquake acceleration values. Simulation results show that the proposed numerical algorithm are better than the closed-loop control and the instantaneous optimal control and proposed numerical solution will approach the exact optimal solution if the more distant future values of the earthquake excitation can be predicted more precisely. Effectiveness of the Kalman filtering technique is also confirmed by comparing the predicted and the observed time history of NS component of the 1940 El Centro earthquake. Copyright © 2001 John Wiley & Sons, Ltd. [source] Sexually selected behaviour: red squirrel males search for reproductive successJOURNAL OF ANIMAL ECOLOGY, Issue 2 2009Jeffrey E. Lane Summary 1Differential male reproductive success is commonplace in mammals and frequently attributed to variation in morphological traits that provide individuals with a competitive advantage in female defence mating systems. Other mammalian mating systems, however, have received comparatively little attention and correlates of male reproductive success in them are less well understood. 2We studied a free-ranging population of North American red squirrels (Tamiasciurus hudsonicus Erxleben) exhibiting year-round individual territoriality. Males must temporarily vacate their territories to locate spatially dispersed receptive females, thereby setting the stage for a scramble competition mating system. 3We predicted that both male annual mating success (measured as the number of females copulated with) and annual reproductive success (measured as the number of offspring sired) would be positively correlated with both search ability (measured as the number of oestrous females located over the mating season) and effort (measured as mating season home range size), generating directional sexual selection on these two metrics. 4Mating season home ranges of males showed, on average, an almost 10-fold increase relative to those measured during the nonmating season, while those of females showed a more moderate twofold increase and both annual mating and reproductive success of males was positively correlated with search ability and search effort. 5The spatial dispersion of females, resulting from the strict territorial social structure of red squirrels, gave rise to a predicted scramble competition mating system. Furthermore, the strength of sexual selection on behavioural traits in this mating system equalled previous estimates for morphological traits in female defence mating systems. [source] The feasibility of developing a risk assessment for the impact of climate change on the emergence of Crimean-Congo haemorrhagic fever in livestock in Europe: a ReviewJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2010P. Gale Summary Crimean-Congo haemorrhagic fever virus (CCHFV) is one of the most widespread of all medically important arboviruses with ticks of the Hyalomma spp. serving as the main vectors. Infection of livestock by CCHFV serves as a route of exposure to humans, as a reservoir of disease and as a route of importation. This study discusses the pathways and data requirements for a qualitative risk assessment for the emergence of CCHFV in livestock in Europe. A risk map approach is proposed based on layers that include the potential routes of release (e.g. by migrating birds carrying infected ticks) together with the main components for exposure, namely the distributions of the tick vectors, the small vertebrate host reservoirs and the livestock. A layer on landscape fragmentation serves as a surrogate for proximity of livestock to the tick cycle. Although the impact of climate change on the emergence of CCHF is not clear, comparing the distribution of risk factors in each layer currently with those predicted in the 2080s with climate change can be used to speculate how potential high-risk areas may shift. According to the risk pathway, transstadial and/or transovarial transmission in the tick vector are crucial for CCHFV spread. Vector competence and tick vector switching, however, remain critical factors for CCHFV colonization of new regions in Europe. The species of migratory bird is also an important consideration in the release assessment with greater abundance and biodiversity of ground-dwelling birds in southern Europe than in northern Europe. [source] Climate-based models of spatial patterns of species richness in Egypt's butterfly and mammal faunaJOURNAL OF BIOGEOGRAPHY, Issue 11 2009Tim Newbold Abstract Aim, Identifying areas of high species richness is an important goal of conservation biogeography. In this study we compared alternative methods for generating climate-based estimates of spatial patterns of butterfly and mammal species richness. Location, Egypt. Methods, Data on the occurrence of butterflies and mammals in Egypt were taken from an electronic database compiled from museum records and the literature. Using Maxent, species distribution models were built with these data and with variables describing climate and habitat. Species richness predictions were made by summing distribution models for individual species and by modelling observed species richness directly using the same environmental variables. Results, Estimates of species richness from both methods correlated positively with each other and with observed species richness. Protected areas had higher species richness (both predicted and actual) than unprotected areas. Main conclusions, Our results suggest that climate-based models of species richness could provide a rapid method for selecting potential areas for protection and thus have important implications for biodiversity conservation. [source] Correlation between the predicted and the observed biological activity of the symmetric and nonsymmetric cyclic urea derivatives used as HIV-1 protease inhibitors.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2003A 3D-QSAR-CoMFA method for new antiviral drug design Abstract The predicted inhibition constant (Ki) and the predicted inhibitor concentration (IC90) of the HIV-1 protease (HIV-1 PR) inhibitors: symmetric and nonsymmetric - benzyl, ketone, oxime, pyrazole, imidazole, and triazole cyclic urea derivatives, were obtained by the 3D-CoMFA (Comparative Molecular Field Analysis) method. The CoMFA statistical parameters: cross-validate correlation coefficient (q2), higher than 0.5, and the fitted correlation coefficient (r2), higher than 0.90 validated the predicted biological activities. The best predictions were found for the trifluoromethyl ketoxime derivative (log 1/Ki predict = 8.42), the m-pyridineCH2 pyrazole derivative (log 1/Ki predict = 9.77) and the 1,2,3 triazole derivative (log 1/Ki predict = 7.03). We attempted to design a new potent HIV-1 protease inhibitor by addition of o-benzyl to the (p-HOPhCH2) pyrazole 12f derivative inhibitor. A favorable steric area surrounded the o-benzyl, suggesting a possible new potent HIV-1 protease inhibitor. [source] ORIGINAL ARTICLE: Investigation of the prediction accuracy of vancomycin concentrations determined by patient-specific parameters as estimated by Bayesian analysisJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2010Y. Hiraki BSc Summary Background/Objective:, There have been many studies of therapeutic drug monitoring (TDM) of vancomycin (VCM) based on Bayesian analysis, but there have been no reports of the accuracy of prediction based on Bayesian-estimated patient-specific parameters. This study was conducted to compare the accuracy of prediction based on the population pharmacokinetic (PPK) method and Bayesian-estimated parameters. Method:, The subjects were 22 patients who were treated with VCM for MRSA infection and whose blood was sampled twice or more during the administration period. The concentrations between the blood samples were predicted based on the concentrations in the first blood samples based on the PPK method using mean parameters for the Japanese population and Bayesian-estimated patient-specific pharmacokinetic parameters. The mean prediction error (ME), mean absolute error (MAE) and root mean squared error (RMSE) were compared to examine the accuracy of prediction based on Bayesian-estimated patient-specific parameters. Results and discussion:, The mean measured VCM concentration was 10·43 ± 5·19 ,g/mL, whereas the mean concentration predicted based on the PPK method was 8·52 ± 4·34 ,g/mL, with an ME of ,1·91, MAE of 2·93 and RMSE of 3·21. The mean concentration predicted based on patient-specific parameters was 9·62 ± 4·95 ,g/mL with ME of ,0·81, MAE of 1·38 and RMSE of 1·74. The ME and MAE for the concentrations predicted using patient-specific parameters were smaller compared with those predicted using the PPK method (P = 0·0471 and 0·0003, respectively), indicating superior prediction with a significant difference between approaches. Conclusion:, Prediction using Bayesian estimates of patient-specific parameters was better than by the PPK method. However, when using patient-specific parameters it is still necessary to fully understand the clinical status of the patient and frequently determine VCM concentrations. [source] Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shorteningAGING CELL, Issue 1 2010Chen-Yu Liao Summary Chronic dietary restriction (DR) is considered among the most robust life-extending interventions, but several reports indicate that DR does not always extend and may even shorten lifespan in some genotypes. An unbiased genetic screen of the lifespan response to DR has been lacking. Here, we measured the effect of one commonly used level of DR (40% reduction in food intake) on mean lifespan of virgin males and females in 41 recombinant inbred strains of mice. Mean strain-specific lifespan varied two to threefold under ad libitum (AL) feeding and 6- to 10-fold under DR, in males and females respectively. Notably, DR shortened lifespan in more strains than those in which it lengthened life. Food intake and female fertility varied markedly among strains under AL feeding, but neither predicted DR survival: therefore, strains in which DR shortened lifespan did not have low food intake or poor reproductive potential. Finally, strain-specific lifespans under DR and AL feeding were not correlated, indicating that the genetic determinants of lifespan under these two conditions differ. These results demonstrate that the lifespan response to a single level of DR exhibits wide variation amenable to genetic analysis. They also show that DR can shorten lifespan in inbred mice. Although strains with shortened lifespan under 40% DR may not respond negatively under less stringent DR, the results raise the possibility that life extension by DR may not be universal. [source] Gene structure of an antimicrobial peptide from mandarin fish, Siniperca chuatsi (Basilewsky), suggests that moronecidins and pleurocidins belong in one family: the piscidinsJOURNAL OF FISH DISEASES, Issue 6 2007B J Sun Abstract The gene of piscidin, an antimicrobial peptide, has been cloned from the mandarin fish, Siniperca chuatsi. From the first transcription initiation site, the mandarin fish piscidin gene extends 1693 nucleotides to the end of the 3, untranslated region and contains four exons and three introns. A predicted 79-residue prepropeptide consists of three domains: a signal peptide (22 aa), a mature peptide (22 aa) and a C-terminal prodomain (35 aa). The shortage of XQQ motif in the prodomain of mandarin fish piscidin and the similar gene structure between moronecidins (piscidins) and pleurocidins may indicate that they are derived from the same ancestor gene. We thus suggest that piscidin should be used as a terminology for these antimicrobial peptides in the future. The mandarin fish piscidin mRNA was abundant in intestine, spleen, pronephros and kidney analysed by real-time polymerase chain reaction. After stimulation with lipopoly saccharides (LPS), a marked increase in transcripts was observed in most tissues, indicating that piscidin is not only a constitutively expressed molecule, but also has an increased response to bacterial infection. The synthetic, amidated mandarin fish piscidin exhibited different antimicrobial activity against different fish bacterial pathogens, especially against species of Aeromonas, which may to certain extent reflect the pathogenicity of these bacteria. [source] Molecular cloning and functional analysis of Photobacterium damselae subsp. piscicida haem receptor geneJOURNAL OF FISH DISEASES, Issue 2 2005H Naka Abstract A haem receptor gene from Photobacterium damselae subsp. piscicida (formerly known as Pasteurella piscicida) has been cloned, sequenced and analysed for its function. The gene, designated as pph, has an open reading frame consisting of 2154 bp, a predicted 718 amino acid residues and exists as a single copy. It is homologous with the haem receptors of Vibrio anguillarum hupA, V. cholerae hutA, V. mimicus mhuA and V. vulnificus hupA at 32.7, 32.7, 45.6 and 30.9%, respectively, and is highly conserved, consisting of a Phe-Arg-Ala-Pro sequence (FRAP), an iron transport related molecule (TonB) and a Asn-Pron-Asn-Leu sequence (NPNL), binding motifs associated with haem receptors. As a single gene knockout mutant P. damselae subsp. piscicida was able to bind haem in the absence of pph, suggesting that other receptors may be involved in its iron transport system. This study shows that the P. damselae subsp. piscicida pph belongs to the haem receptor family, is conserved and that its iron-binding system may involve more than one receptor. [source] The modified CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down's syndromeJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 6 2004S. L. Ball Abstract Background Dementia because of Alzheimer's disease (AD) commonly affects older adults with Down's syndrome (DS). Methods are needed, with established concurrent and predictive validity, to facilitate the diagnostic assessment of dementia, when it is complicated by pre-existing intellectual disabilities (ID). We report on the reliability and validity of a modified version of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) informant interview, for use when assessing people with DS suspected as having dementia. Methods As part of a previous epidemiological study of older people with DS, the CAMDEX informant interview was used to determine the prevalence of dementia. The 74 people with DS included at that time (Time 1) had also completed the Cambridge Cognitive Examination (CAMCOG), the neuropsychological assessment from the CAMDEX schedule. Fifty-six were assessed again 6 years later (Time 2). Based on the CAMDEX informant interview, nine of the 74 at Time 1, and 11 of the 56 at Time 2, were found to meet clinical criteria for AD. Forty-one scored above floor on the CAMCOG at Time 1 and were included in the analysis of cognitive decline. Concurrent validity was established by comparing diagnosis at Time 2 with independent evidence of objective decline on cognitive tasks since Time 1. Predictive validity was established by examining how accurately diagnosis at Time 1 predicted both cognitive decline and future diagnosis. Inter-rater reliability was determined by comparing the level of agreement between two raters. Results CAMDEX-based diagnosis of AD was shown to be consistent with objectively observed cognitive decline (good concurrent validity) and to be a good predictor of future diagnosis. Although numbers are small, some support is also provided for the accuracy with which diagnosis predicts cognitive decline. Inter-rater reliability was good with Kappa > 0.8 for 91% of items and >,0.6 for all items. Conclusions The use of the modified CAMDEX informant interview enables the structured collection of diagnostic information, so that a valid and a reliable diagnosis of dementia can be made in those with pre-existing ID, using established diagnostic criteria. [source] A sequence optimization strategy for chromatographic separation in reversed-phase high-performance liquid chromatographyAICHE JOURNAL, Issue 2 2010Xueling Du Abstract A sequence optimization strategy combining an artificial neural network (ANN) and a chromatographic response function (CRF) for chromatographic separation in reversed-phase high-performance liquid chromatography has been proposed. Experiments were appropriately designed to obtain unbiased data concerning the effects of varying the mobile phase composition, flow-rate, and temperature. The ANN was then used to simultaneously predict the resolution and analysis time, which are the two most important features of chromatographic separation. Subsequently, a CRF consisting of resolution and analysis time was used to predict the optimum operating conditions for different specialized purposes. The experimental chromatograms were consistent with those predicted for given conditions, which verified the applicability of the method. Furthermore, the proposed optimization strategy was applied to literature data and very good agreement was obtained. The results show that a strategy of sequential combination of ANN and CRF can provide a more flexible and efficient optimization method for chromatographic separation. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Mass defect filter technique and its applications to drug metabolite identification by high-resolution mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2009Haiying Zhang Abstract Identification of drug metabolites by liquid chromatography/mass spectrometry (LC/MS) involves metabolite detection in biological matrixes and structural characterization based on product ion spectra. Traditionally, metabolite detection is accomplished primarily on the basis of predicted molecular masses or fragmentation patterns of metabolites using triple-quadrupole and ion trap mass spectrometers. Recently, a novel mass defect filter (MDF) technique has been developed, which enables high-resolution mass spectrometers to be utilized for detecting both predicted and unexpected drug metabolites based on narrow, well-defined mass defect ranges for these metabolites. This is a new approach that is completely different from, but complementary to, traditional molecular mass- or MS/MS fragmentation-based LC/MS approaches. This article reviews the mass defect patterns of various classes of drug metabolites and the basic principles of the MDF approach. Examples are given on the applications of the MDF technique to the detection of stable and chemically reactive metabolites in vitro and in vivo. Advantages, limitations, and future applications are also discussed on MDF and its combinations with other data mining techniques for the detection and identification of drug metabolites. Copyright © 2009 John Wiley & Sons, Ltd. [source] Prediction of pharmacokinetics prior to in vivo studies.JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2002Abstract In drug discovery and nonclinical development the volume of distribution at steady state (Vss) of each novel drug candidate is commonly determined under in vivo conditions. Therefore, it is of interest to predict Vss without conducting in vivo studies. The traditional description of Vss corresponds to the sum of the products of each tissue:plasma partition coefficient (Pt:p) and the respective tissue volume in addition to the plasma volume. Because data on volumes of tissues and plasma are available in the literature for mammals, the other input parameters needed to estimate Vss are the Pt:p's, which can potentially be predicted with established tissue composition-based equations. In vitro data on drug lipophilicity and plasma protein binding are the input parameters used in these equations. Such a mechanism-based approach would be particularly useful to provide first-cut estimates of Vss prior to any in vivo studies and to explore potential unexpected deviations between sets of predicted and in vivoVss data, when the in vivo data become available during the drug development process. The objective of the present study was to use tissue composition-based equations to predict rat and human Vss prior to in vivo studies for 123 structurally unrelated compounds (acids, bases, and neutrals). The predicted data were compared with in vivo data obtained from the literature or at Roche. Overall, the average ratio of predicted-to-experimental rat and human Vss values was 1.06 (SD,=,0.817, r,=,0.78, n,=,147). In fact, 80% of all predicted values were within a factor of two of the corresponding experimental values. The drugs can therefore be separated into two groups. The first group contains 98 drugs for which the predicted Vss were within a factor of two of those experimentally determined (average ratio of 1.01, SD,=,0.39, r,=,0.93, n,=,118), and the second group includes 25 other drugs for which the predicted and experimental Vss differ by a factor larger than two (average ratio of 1.32, SD,=,1.74, r,=,0.42, n,=,29). Thus, additional relevant distribution processes were neglected in predicting Vss of drugs of the second group. This was true especially in the case of some cationic-amphiphilic bases. The present study is the first attempt to develop and validate a mechanistic distribution model for predicting rat and human Vss of drugs prior to in vivo studies. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:129,156, 2002 [source] Brittle-Ductile Transitions in Sucrose and the Influence of Lateral Stresses During CompactionJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2000R. J. ROBERTS Sucrose, in a range of particle sizes, has been compacted to investigate both the effect of brittle-ductile transition and the effect of lateral stresses on the deformation stress as measured using Heckel plots. All particles with a diameter greater than 30 ,m exhibited cracking in line with both theoretical predictions and literature data from hammer and ball milling. In addition, crack lengths in compressed particles examined microscopically were very similar to those predicted from the deformation stress, confirming the applicability of the model. [source] NMR and DFT investigations of the substituent and solvent effect on amino,imino tautomerism in acridin-9-amines substituted at the exocyclic nitrogen atom,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 8 2005Youssif Ebead Abstract The 1H and 13C NMR spectra of 9-(methoxyamino)acridine (1) and 9-hydrazinoacridine (2) show that these compounds exist principally in the imino tautomeric form in CDCl3, acetone- d6, CD3CN, DMSO- d6 and Py- d5, all solvents with different polarities and abilities to participate in specific interactions. The spectra of the other two compounds investigated,N -(2-chloroethyl)acridin-9-amine (3) and N -(5-methylpyridin-2-yl)acridin-9-amine (4),indicate that they coexist in the amino and imino forms. The amino tautomer of compound 3 predominates in CDCl3, CD3CN and Py- d5 and that of compound 4 in CDCl3 and Py- d5. On the other hand, the amino and imino forms of compound 3 coexist in acetone- d6 and probably DMSO- d6, whereas those of compound 4 coexist in acetone- d6 and DMSO- d6. The positions of the signals in the NMR spectra compare qualitatively with those predicted computationally at the GIAO/DFT level of theory. The equilibrium constants predicted by the DFT(PCM) method are in agreement with the results of NMR spectral analysis. In general, both the data predicted at the DFT level of theory and x-ray structural data show that the imino tautomers display a ,butterfly'-type geometry, whereas the amino forms are characterized by an almost flat acridine moiety. Electron-attracting substituents at the exocyclic N atom improve the stability of the imino form, and electron-withdrawing substituents do likewise for the amino form. The importance of tautomeric phenomena in the context of the ability of acridin-9-amines to participate in specific interactions is outlined in brief, as are the possible applications of these compounds as probes of environmental properties. Copyright © 2005 John Wiley & Sons, Ltd. [source] Enantiomeric separation of aminoglutethimide by capillary electrophoresis using native cyclodextrins in single and dual systemsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2003Adel M. Abushoffa Abstract Aminoglutethimide (AGT) is one of the few examples of chiral drugs that can be enantioseparated by capillary electrophoresis using any of the three native cyclodextrins: ,-, ,-, or ,-CD. A complete resolution of the enantiomers of this compound in cationic form could be achieved with each of the three CDs, using a pH 3 phosphoric acid-triethanolamine buffer. Affinity constants for AGT enantiomers with the three native CDs were determined, confirming that the highest selectivity was given by ,-CD while the strongest complexation was obtained with ,-CD. However, an opposite affinity pattern was observed with the latter. Selectivity was lower for AGT enantiomers in dual CD systems, compared to that obtained with a single selector at its optimal concentration, which confirms that dual systems are of more limited interest when the two selectors have a similar effect on the analyte mobility. These results are in good agreement with those predicted using recently developed mathematical models. [source] | |||||||||||||||||||||||||||||||