We report the computational structural simulation of the Cry1Ab19 toxin molecule from B. thuringiensis BtX-2 based on the structure of Cry1Aa1 deduced by x-ray diffraction. Validation results showed that 93.5% of modeled residues are folded in a favorable orientation with a total energy Z-score of -8.32, and the constructed model ...

Although natural toxins such as mycotoxins or phytoestrogens are widely studied and were recently identified as micropollutants in the environment, many of their environmentally relevant physico-chemical properties have not yet been determined. Here, the sorption affinity to Pahokee peat, a model sorbent for soil organic matter, was investigated for 29 ...

OBJECTIVE: Every year, toxic exposures kill 1200 Americans. To aid in the timely diagnosis and treatment of such exposures, this research investigates the feasibility of a knowledge-based system capable of generating differential diagnoses for human exposures involving unknown toxins. METHODS: Data mining techniques automatically extract prior probabilities and likelihood ratios ...

Many toxin-antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called 'conditional cooperativity' as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion ...

Linear mixed-effects models involve fixed effects, random effects and covariance structure, which require model selection to simplify a model and to enhance its interpretability and predictability. In this article, we develop, in the context of linear mixed-effects models, the generalized degrees of freedom and an adaptive model selection procedure defined ...

Models of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been most extensively employed for the study of C. difficile and this has been used in many different areas of research, including the induction of ...

The purpose of this systematic review was to review the cost-effectiveness of first-line non-nicotine therapies (varenicline and bupropion SR) for smoking cessation, identify differences in the models used and their conclusions of cost-effectiveness, and to determine which variables, if any, impact conclusions of cost-effectiveness. A systematic literature search was conducted ...

OBJECTIVES: Co-amoxiclav is widely prescribed in hospitals. Although reports have suggested it may be linked to onset of Clostridium difficile infection (CDI), data on the risk of CDI associated with specific antibiotics is difficult to obtain, due to confounding clinical factors. We have examined the propensity of co-amoxiclav to induce ...

BACKGROUNDPostponement of childbearing since the 1970s has led to an increase in permanent involuntarily childlessness. We will address the magnitude of this trend, the effect of IVF/ICSI and the effect on total fertility rate (TFR an often used demographic measure for the level of fertility) in six EU countries.METHODSUsing a ...

Camptothecin (CPT) exhibits very strong antitumor effects by inhibiting the activity of DNA topoisomerase I, but its application is greatly limited due to its low solubility and the instability of the active lactone form. To overcome these shortcomings, in the present study, we prepared novel camptothecin nanocolloids based on N,N,N-trimethyl chitosan ...

Few empirical efforts have been devoted to differentiating status and power, and thus significant questions remain about differences in how status and power impact social encounters. We conducted 5 studies to address this gap. In particular, these studies tested the prediction that status and power would have opposing effects on ...

PURPOSE: Flibanserin is being developed for treating hypoactive sexual desire disorder in women; the main side effect is sedation. The analysis objective was to relate flibanserin plasma concentrations with acute sedative effects using a population pharmacokinetic/pharmacodynamic (PK/PD) model. METHODS: The population model was developed with NONMEM based on data from ...

Analyses of effects of mutants on many traits have enabled estimates to be obtained of the magnitude of pleiotropy, and in reviews of such data others have concluded that the degree of pleiotropy is highly restricted, with implications on the evolvability of complex organisms. We show that these conclusions are ...

Developments in behavioral assessment, autonomic and/or baseline reactivity, psychopharmacology, and genetics, have contributed significantly to the assessment of performance-enhancing drugs in animal models. Particular classes of steroid hormones: androgenic steroids are of interest. Anecdotally, the performance enhancing effects of androgens are attributed to anabolic events. However, there is a discrepancy ...

Here we introduce a new virtual reality (VR) based simulation system for training the urological procedure of intra-detrusor botulinum toxin (Botox®) injections into the bladder. 6 cases with different bladder anatomy and 3 subtasks are included in the curriculum; this design is guided by several expert urologists according to clinical ...

The occurrence of Microcystis blooms is a worldwide concern that has caused numerous adverse effects on water quality and lake ecology. Elevated ammonia and microcystin concentrations co-occur during the degradation of Microcystis blooms and are toxic to aquatic organisms; we studied the relative and combined effects of these on the ...

OBJECTIVE: To provide a cost-effectiveness analysis of dysphagia screening in the acute poststroke period with use of a videofluoroscopic swallowing study, a clinical bedside swallowing evaluation, or a combined approach. DESIGN: Decision-analysis model. METHODS: A decision-analysis model was used with information derived from multiple data sources, including meta-analyses and other ...

PURPOSE: This study explores the hypothesis that vocabulary growth can have two types of effects in morphosyntactic development. One is a general effect, where vocabulary growth globally determines utterance complexity, defined in terms of sentence length and rates of subordination. There are also specific effects, where vocabulary size has a ...

Radiotracers: The growing demand for novel radiopharmaceuticals can only be met through the development of new approaches to isotopic labeling. Effective strategies and reagents for nucleophilic and electrophilic (18) F-radiolabeling are highlighted.

Nonylphenol (NP) and Monobutyl phthalate (MBP) are two environmental endocrine disruptors (EEDs) which are widespread occurrence in our life. In present study, our purpose is to analyze style of combined effects of NP and MBP on rat testicular Sertoli cell in vitro using two mathematical models based on the Loewe ...

Despite considerable progress in ecotoxicology, it has become clear that this discipline cannot answer its central questions, such as, "What are the effects of toxicants on biodiversity?" and "How the ecosystem functions and services are affected by the toxicants?". We argue that if such questions are to be answered, a ...

ABSTRACT: BACKGROUND: Genome-wide methylation profiling has led to more comprehensive insights into gene regulation mechanisms and potential therapeutic targets. Illumina Human Methylation BeadChip is one of the most commonly used genome-wide methylation platforms. Similar to other microarray experiments, methylation data is susceptible to various technical artifacts, particularly batch effects. To ...

We review controversies associated with randomized controlled trials (RCTs) stopped early for apparent benefit (truncated RCTs or tRCTs) and present our groups' perspective. Long-established theory, simulations and recent empirical evidence demonstrate that tRCTs will on average overestimate treatment effects, and this overestimation may be large, particularly when tRCTs have small ...

Meta-analysis uses numerical tools to pool data and to estimate a summary effect size for the comparison of two interventions from a set of randomised controlled trials identified in a systematic review. An effect size is a single number that expresses the difference in outcome from the interventions. The most ...

Research in cognitive science has documented numerous phenomena that are approximated by linear relationships. In the domain of numerical cognition, the use of linear regression for estimating linear effects (e.g., distance and SNARC effects) became common following Fias, Brysbaert, Geypens, and d'Ydewalle's (1996) study on the SNARC effect. While their ...

Disasters have potential short-term and long-term impacts on employment and employment structures in affected regions. While measuring the full economic impact of a disaster requires sophisticated econometrics and mathematical simulations, conventional regional economic models such as shift-share analysis can be used to assess some of these effects. This paper applies ...

Context: Dietary botanicals are often consumed together with allopathic medicines, which may give rise to pharmacokinetic interactions. In vitro intestinal models are useful to identify botanical-drug interactions, but they may exhibit different expressions of transporters or enzymes. Objective: To compare the effects of selected dietary botanical extracts on cimetidine transport ...

The kinetic compensation effect states that there is a linear relationship between Arrhenius parameters ln A and E for a family of related processes. It is a widely observed phenomenon in many areas of science, notably heterogeneous catalysis. This paper explores mathematical, rather than physicochemical, explanations for the compensation effect ...

The need to consider in capture-recapture models random effects besides fixed effects such as those of environmental covariates has been widely recognized over the last years. However, formal approaches require involved likelihood integrations, and conceptual and technical difficulties have slowed down the spread of capture-recapture mixed models among biologists. In ...

The peculiar physical/chemical characteristics of engineered nanomaterials have led to a rapid increase of nanotechnology-based applications in many fields. However, before exploiting their huge and wide potential, it is necessary to assess their effects upon interaction with living systems. In this context, the screening of nanomaterials to evaluate their possible ...

Modern instruments together with the use of standard reference materials have improved the accuracy and long-term reproducibility of the analysis of nutrients (ammonium, nitrate, nitrite, phosphate and silicate) in sea water using segmented-flow analysis, so that errors arising from matrix effects become more significant. Colorimetric detectors with bubble-through flowcells have ...

A keyhole lymphet heamocyanin is an antigen which triggers Th1 type of immune response. A QTL for a primary immune response towards keyhole lymphet heamocyanin has been detected on chicken chromosome 14 in three populations. The results from the most recent population were inconsistent and varied depending on the applied ...

In plant breeding, a large number of progenies that will be discarded later in the breeding process must be phenotyped and marker genotyped for conducting QTL analysis. In many cases, phenotypic preselection of lines could be useful. However, in QTL analyses even moderate preselection can have a significant effect on ...

PURPOSE: To evaluate whether hemodynamic refractory effects provoked by repeated visual stimulation can be detected and quantified at the single-subject level using a recently described hemodynamic response function (HRF) fitting algorithm. MATERIALS AND METHODS: Hemodynamic refractory effects were induced with an easily applicable functional MRI (fMRI) paradigm. A fitting method ...

Several methodological issues have been identified in analysis of epidemiological data to better assess the distributional effects of exposures and hypotheses about effect modification. We discuss the hierarchical mixed model and some more complex methods. Methods of capturing inequality are a second dimension of risk assessment, and simulation studies are ...

Xenoestrogenic compounds (XCs) can disrupt endogenous hormone function and affect sperm function by binding to receptors on sperm membrane. Albeit spermatozoa are potentially a useful model for screening estrogenic activities of endocrine disruptors, high-quality in vitro test system that examination of the XCs effects on sperm function is required. The ...

In orthodontics, multiple site observations within patients or multiple observations collected at consecutive time points are often encountered. Clustered designs require larger sample sizes compared to individual randomized trials and special statistical analyses that account for the fact that observations within clusters are correlated. It is the purpose of this ...

To estimate the cost-effectiveness of dasatinib and nilotinib compared with high-dose imatinib for people with chronic phase chronic myeloid leukemia, which are resistant to normal-dose imatinib and compared with interferon-α for people intolerant to imatinib, from the perspective of the UK National Health Service. An an area under the curve ...

Characterizing the responses of key tree species to extreme climatic events may provide important information for predicting future forest responses to increased climatic variability. Here we aimed at determining which tree- and stand-level attributes were more closely associated with the effect of a severe drought on the radial growth of ...

Bioequivalence or interaction trials are commonly studied in crossover design and can be analysed by nonlinear mixed effects models as an alternative to noncompartmental approach. We propose an extension of the population Fisher information matrix in nonlinear mixed effects models to design crossover pharmacokinetic trials, using a linearisation of the ...

We combined two models to investigate the theoretical dynamics of five exotic and native blowfly species in response to the Allee effect by using demographic parameters estimated from experimental populations. Most of the results suggest stabilization of dynamic behavior in response to the Allee effect. However, the results depended on ...

There has been a substantial amount of research on the relationship between hippocampal neurogenesis and behaviour over the past 15 years, but the causal role that new neurons have on cognitive and affective behavioural tasks is still far from clear. This is partly due to the difficulty of manipulating levels ...

Response fatigue can cause measurement error and misclassification problems in survey research. Questions asked later in a long survey are often prone to more measurement error or misclassification. The response given is a function of both the true response and participant response fatigue. We investigate the identifiability of survey order ...

A penalized maximum likelihood method has been proposed as an important approach to the detection of epistatic quantitative trait loci (QTL). However, this approach is not optimal in two special situations: (1) closely linked QTL with effects in opposite directions and (2) small-effect QTL, because the method produces downwardly biased ...

The elimination kinetics of the pharmacologically active compound 1-ethyl-6-fluoro-1,2,3,4-tetrahydroquinoline (MC4) were characterized along with pharmacodynamic (PD) measurements. Four compartmental models based on ocular anatomy, physiology, and possible absorption and disposition pathways were proposed to model the pharmacokinetic (PK) data in WinNonlin and the best model was chosen based on statistical ...

Mixed models are commonly used to represent longitudinal or repeated measures data. An additional complication arises when the response is censored, for example, due to limits of quantification of the assay used. While Gaussian random effects are routinely assumed, little work has characterized the consequences of misspecifying the random-effects distribution ...

During the Antarctic summer of 1985 near the Soviet Antarctic station Vostok, firn samples for tritium measurements were obtained down to a depth of 2.40 m. The results of the tritium measurements are presented and discussed. Based on this and other data, conclusions regarding the tritium latitude effect are derived.

Abstract Structural MRI markers may serve as surrogate endpoints in clinical trials on disease modification in Alzheimer's disease (AD). Here, we used a longitudinal MRI data set of total brain and cortical grey matter volumes from 66 patients with AD recruited across seven centres of the German Dementia Competence Network. ...

Careful consideration of site effects is important in the analysis of multi-site clinical trials for drug abuse treatment. The statistical choices for modeling these effects have implications for both trial planning and interpretation of findings. Three broad approaches for modeling site effects are presented: omitting site from the analysis; modeling ...

Transforming decades' old methodology, electromechanical reshaping (EMR) may someday replace traditionally destructive surgical techniques with a less invasive means of cartilage reshaping for reconstructive and esthetic facial surgery. Electromechanical reshaping is essentially accomplished through the application of voltage to a mechanically deformed cartilage specimen. While the capacity of the method ...