bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico toxicology: computational methods for the prediction of chemical toxicity
Authors: Raies Arwa B. , Bajic Vladimir B. 
Published: January 2016

Determining the toxicity of chemicals is necessary to identify their harmful effects on humans, animals, plants, or the environment. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. However, in vivo animal tests are constrained by time, ethical considerations, and financial burden. Therefore, computational methods for estimating the toxicity of chemicals are considered useful. In silico toxicology is one type of toxicity assessment that uses computational methods to analyze, simulate, visualize, or predict the toxicity of chemicals. In silico toxicology aims to complement existing toxicity tests to predict toxicity, prioritize chemicals, guide toxicity tests, and minimize late‐stage failures in drugs design. There are various methods for generating models to predict toxicity endpoints. We provide a comprehensive overview, explain, and compare the strengths and weaknesses of the existing modeling methods and algorithms for toxicity prediction with a particular (but not exclusive) emphasis on computational tools that can implement these methods and refer to expert systems that deploy the prediction models. Finally, we briefly review a number of new research directions in in silico toxicology and provide recommendations for designing in silico models. WIREs Comput Mol Sci 2016, 6:147–172. doi: 10.1002/wcms.1240This article is categorized under:

Computer and Information Science > Chemoinformatics
Computer and Information Science > Databases and Expert Systems
Computer and Information Science > Computer Algorithms and Programming
Natural product discovery: past, present, and future
Authors: Katz Leonard , Baltz Richard H 
Published: January 2016

Abstract
Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30–50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the “biosynthetic dark matter” as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.
Relationship of cumulative dust exposure dose and cumulative abnormal rate of pulmonary function in coal mixture workers
Authors: Qian Qing‐Zeng , Cao Xiang‐Ke , Qian Qing‐Qiang , Shen Fu‐Hai , Wang Qian , Liu Hai‐Yan , Tong Jun‐Wang 
Published: January 2016

AbstractTo investigate the dose‐response relationship between cumulative dust exposure (CDE) and cumulative abnormal rate of pulmonary function in coal mixture workers. Three hundred and twenty eight coal mixture workers (exposed group) and 169 nondust‐exposed workers (control group) were recruited. Basic information data were collected and pulmonary function tests were performed. Pulmonary function was compared between the two groups after comparing smoking behaviors. Pulmonary function indices [forced vital capacity in 1 second after full inspiration (FVC)%, forced expiratory volume (FEV)1%, and FEV1/FVC%] were compared among groups stratified by service length (exposure duration). The relationship between CDE dose and cumulative abnormal rate of pulmonary function in coal mixture workers was analyzed. Abnormal rate of pulmonary function in the exposed group (35.1%) was significantly higher than the control group (10.1%; p < 0.001); FVC%, FEV1%, and FEV1/FVC% in the exposed group decreased significantly compared with the control group (all p < 0.05). Differences in FVC%, FEV1%, and FEV1/FVC% among coal mixture workers stratified by exposure duration in the exposed group were statistically significant (all p < 0.05). The discernible increase in the cumulative abnormal rate was observed, from ≥ 1000 mg/m3·years group to ≥ 1700 mg/m3·years group. Correlation analysis revealed a positive correlation between the CDE dose and the cumulative abnormal rate of pulmonary function. Higher abnormal pulmonary function rate was found among coal mixture workers, characterized by decreased pulmonary function indices. Our results suggested a positive relationship between CDE dose and cumulative abnormal pulmonary function rate, and a rapid increase in cumulative abnormal rate within a certain range of CDE dose. A lower limit value of 1000 mg/m3·years has reference significance.
Delirium Associated With Lidocaine Patch Administration: A Case Presentation
Authors: Byun Eun Kwang , Berry Kevin M. , Lee Anthony , Oh‐Park Mooyeon 
Published: January 2016

AbstractDelirium is a common complication among hospitalized elderly individuals. Systemic analgesics are known precipitating factors for delirium. However, the risk from topical pain agents is not well documented. We report a case of a woman who developed delirium after the application of a lidocaine patch. Although lidocaine patches are generally perceived as safe, clinicians should be aware of delirium as a potential adverse effect, particularly in older patients. This report also highlights the role of a systematic approach of staff education, use of a standardized protocol, and interdisciplinary communication in the identification and management of delirium in acute rehabilitation facilities.
Episodic tourmaline growth and re-equilibration in mica pegmatite from the Bihar Mica Belt, India: major- and trace-element variations under pegmatitic and hydrothermal conditions
Authors: HAZARIKA PRANJIT , UPADHYAY DEWASHISH , PRUSETH KAMAL LOCHAN 
Published: January 2016

AbstractMica pegmatites from the Bihar Mica Belt contain three distinct generations of tourmaline. The major-element composition, substitution vectors and trajectories within each group are different, which indicates that the three types of tourmalines are not a part of one evolutionary series. Rather, the differences in their chemistries as well their mutual microtextural relations, can be best explained by growth of tourmaline from pegmatitic melts followed by episodic re-equilibration during discrete geological events. The euhedral, coarse-grained brown type I tourmaline cores have relatively high Ca, Mg (XMgc.0.37) and Al with correlated variation in Sr, Sc, Ti, Zr, Y, Cr, Pb and Rare Earth elements (REEs). They are inferred to have crystallized from pegmatitic melts. Monazites included within these tourmalines give chemical ages of 1290−1242 Ma interpreted to date the crystallization of the pegmatitic tourmaline. The bluish type II and greyish type III tourmalines with low Ca and Mg contents (XMg= 0.16−0.27) and high Zn, Sn, Nb, Ta and Na, formed by pseudomorphic partial replacement of the pegmatitic tourmaline via fluid-mediated coupled dissolution–reprecipitation, are ascribed to a hydrothermal origin. The ages obtained from monazites included in these tourmalines indicate two alteration events atc.1100 Ma andc.950 Ma. The correlated variation of Ca, Mg and Fe and the trace elements Sr, Sn, Sc, Zn and REE within the tourmalines indicates that the trace-element concentrations of tourmaline are controlled not only by the fluid chemistry but also by coupled substitutions with major-element ions.
Quantifying N2O emissions from intensive grassland production: the role of synthetic fertilizer type, application rate, timing and nitrification inhibitors
Authors: BELL M. J. , CLOY J. M. , TOPP C. F. E. , BALL B. C. , BAGNALL A. , REES R. M. , CHADWICK D. R. 
Published: January 2016

SUMMARYIncreasing recognition of the extent to which nitrous oxide (N2O) contributes to climate change has resulted in greater demand to improve quantification of N2O emissions, identify emission sources and suggest mitigation options. Agriculture is by far the largest source and grasslands, occupyingc. 0·22 of European agricultural land, are a major land-use within this sector. The application of mineral fertilizers to optimize pasture yields is a major source of N2O and with increasing pressure to increase agricultural productivity, options to quantify and reduce emissions whilst maintaining sufficient grassland for a given intensity of production are required. Identification of the source and extent of emissions will help to improve reporting in national inventories, with the most common approach using the IPCC emission factor (EF) default, where 0·01 of added nitrogen fertilizer is assumed to be emitted directly as N2O. The current experiment aimed to establish the suitability of applying this EF to fertilized Scottish grasslands and to identify variation in the EF depending on the application rate of ammonium nitrate (AN). Mitigation options to reduce N2O emissions were also investigated, including the use of urea fertilizer in place of AN, addition of a nitrification inhibitor dicyandiamide (DCD) and application of AN in smaller, more frequent doses. Nitrous oxide emissions were measured from a cut grassland in south-west Scotland from March 2011 to March 2012. Grass yield was also measured to establish the impact of mitigation options on grass production, along with soil and environmental variables to improve understanding of the controls on N2O emissions. A monotonic increase in annual cumulative N2O emissions was observed with increasing AN application rate. Emission factors ranging from 1·06–1·34% were measured for AN application rates between 80 and 320 kg N/ha, with a mean of 1·19%. A lack of any significant difference between these EFs indicates that use of a uniform EF is suitable over these application rates. The mean EF of 1·19% exceeds the IPCC default 1%, suggesting that use of the default value may underestimate emissions of AN-fertilizer-induced N2O loss from Scottish grasslands. The increase in emissions beyond an application rate of 320 kg N/ha produced an EF of 1·74%, significantly different to that from lower application rates and much greater than the 1% default. An EF of 0·89% for urea fertilizer and 0·59% for urea with DCD suggests that N2O quantification using the IPCC default EF will overestimate emissions for grasslands where these fertilizers are applied. Large rainfall shortly after fertilizer application appears to be the main trigger for N2O emissions, thus applicability of the 1% EF could vary and depend on the weather conditions at the time of fertilizer application.
Laser–matter interactions: Inhomogeneous Richtmyer–Meshkov and Rayleigh–Taylor instabilities
Authors: Lugomer Stjepan 
Published: January 2016

AbstractIn this experimental study, the ablative Richtmyer–Meshkov (RM) and the Rayleigh–Taylor (RT) instabilities were generated by the laser pulse of Gaussian-like power profile. The initial multi-modal perturbation, the inhomogeneous momentum transfer and different Atwood numbers generate different shapes of spikes and bubbles in the central region (CR) and the near-central region (NCR) of the spot. A one-dimensional Gaussian-like power profile causes the formation of the wavy-like rows of aperiodic spikes. The periodic spike segments inside the rows appear due to locally coherent flow. In the NCR, the mushroom-shape spikes tend to the organization on the isotropic square and the anisotropic rhombic lattices. The increase of the lattice periods two, three, or four times indicates formation of superstructures. The growth of sharp asymmetric RM/RT spikes in the CR is fast, uncorrelated and linear, while the growth of the symmetric mushroom-shape ones in the NCR is slow, correlated, and nonlinear.
Nationwide prevalence and risk factors for faecal carriage ofEscherichia coliO157 and O26 in very young calves and adult cattle at slaughter in New Zealand
Authors: JAROS P. , COOKSON A. L. , REYNOLDS A. , PRATTLEY D. J. , CAMPBELL D. M. , HATHAWAY S. , FRENCH N. P. 
Published: January 2016

SUMMARYNationwide prevalence and risk factors for faecal carriage ofEscherichia coliO157 and O26 in cattle were assessed in a 2-year cross-sectional study at four large slaughter plants in New Zealand. Recto-anal mucosal swab samples from a total of 695 young (aged 4–7 days) calves and 895 adult cattle were collected post-slaughter and screened with real-time polymerase chain reaction (PCR) for the presence ofE. coliO157 and O26 [Shiga toxin-producingE. coli(STEC) and non-STEC]. Co-infection with either serogroup ofE. coli(O157 or O26) was identified as a risk factor in both calves and adult cattle for being tested real-time PCR-positive forE. coliO157 or O26. As confirmed by culture isolation and molecular analysis, the overall prevalence of STEC (STEC O157 and STEC O26 combined) was significantly higher in calves [6·0% (42/695), 95% confidence interval (CI) 4·4–8·1] than in adult cattle [1·8% (16/895), 95% CI 1·1–3·0] (P< 0·001). This study is the first of its kind in New Zealand to assess the relative importance of cattle as a reservoir of STEC O157 and O26 at a national level. Epidemiological data collected will be used in the development of a risk management strategy for STEC in New Zealand.
Prevalence and factors associated with demoralization syndrome in patients with advanced disease: Results from a cross-sectional Portuguese study
Authors: Julião Miguel , Nunes Baltazar , Barbosa António 
Published: January 2016

AbstractBackground:Demoralization syndrome (DS) within the context of the psychological experience at the end of life is an important and relevant medical issue and remains the subject of a growing area of research.Method:Ours was a cross-sectional study designed to assess the prevalence and associated demographic, physical, psychiatric, and psychosocial factors for demoralization syndrome in Portuguese patients with advanced disease.Results:Some 80 terminally ill patients were included in the analyses over a 28-month period of time. The prevalence of DS was found to be 52.5%. No statistical differences were observed among prevalence of DS within categories of all studied variables, with the exception of depression using DSM–IV criteria (prevalence ratio PR = 1.8, CI95% = [1.18–2.74]) and desire for death (PR = 1.8, CI95% = [1.25–2.56]). In the Poisson regression analyses predicting DS, none of the latter factors emerged as significant (DSM–IV criteria: PR = 1.6, CI95% = [0.84–3.08]; and desire for death: PR = 1.5, CI95% = [0.74–2.99]). Thirty percent of participants met both criteria for demoralization syndrome and depression using the DSM–IV.Significance of Results:Prevalence of demoralization syndrome was high in this patient sample. Based on our results, we cannot determine if DS and depression are two distinct psychological entities. Identifying factors associated with DS could help provide efficacious interventions capable of diminishing suffering in terminally ill patients.
Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures
Authors: Styrkarsdottir Unnur , Thorleifsson Gudmar , Gudjonsson Sigurjon A. , Sigurdsson Asgeir , Center Jacqueline R. , Lee Seung Hun , Nguyen Tuan V. , Kwok Timothy C.Y. , Lee Jenny S.W. , Ho Suzanne C. , Woo Jean , Leung Ping-C. , Kim Beom-Jun , Rafnar Thorunn , Kiemeney Lambertus A. , Ingvarsson Thorvaldur , Koh Jung-Min , Tang Nelson L.S. , Eisman John A. , Christiansen Claus , Sigurdsson Gunnar , Thorsteinsdottir Unnur , Stefansson Kari 
Published: January 2016

AbstractBone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4–22.6%) that associates with reduced spine BMD (P=1.0 × 10−11, β=−0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10−10, β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus.
Direct observation of mineral–organic composite formation reveals occlusion mechanism
Authors: Rae Cho Kang , Kim Yi-Yeoun , Yang Pengcheng , Cai Wei , Pan Haihua , Kulak Alexander N. , Lau Jolene L. , Kulshreshtha Prashant , Armes Steven P. , Meldrum Fiona C. , De Yoreo James J. 
Published: January 2016

AbstractManipulation of inorganic materials with organic macromolecules enables organisms to create biominerals such as bones and seashells, where occlusion of biomacromolecules within individual crystals generates superior mechanical properties. Current understanding of this process largely comes from studying the entrapment of micron-size particles in cooling melts. Here, by investigating micelle incorporation in calcite with atomic force microscopy and micromechanical simulations, we show that different mechanisms govern nanoscale occlusion. By simultaneously visualizing the micelles and propagating step edges, we demonstrate that the micelles experience significant compression during occlusion, which is accompanied by cavity formation. This generates local lattice strain, leading to enhanced mechanical properties. These results give new insight into the formation of occlusions in natural and synthetic crystals, and will facilitate the synthesis of multifunctional nanocomposite crystals.
Altered expression of mRNA profiles in blood of early-onset schizophrenia
Authors: Xu Yong , Yao Shugart Yin , Wang Guoqiang , Cheng Zaohuo , Jin Chunhui , Zhang Kai , Wang Jun , Yu Hao , Yue Weihua , Zhang Fuquan , Zhang Dai 
Published: January 2016

AbstractTo identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes . The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ.
Presence of unique glyoxalase III proteins in plants indicates the existence of shorter route for methylglyoxal detoxification
Authors: Ghosh Ajit , Kushwaha Hemant R , Hasan Mohammad R , Pareek Ashwani , Sopory Sudhir K , Singla-Pareek Sneh L 
Published: January 2016

AbstractGlyoxalase pathway, comprising glyoxalase I (GLY I) and glyoxalase II (GLY II) enzymes, is the major pathway for detoxification of methylglyoxal (MG) into D-lactate involving reduced glutathione (GSH). However, in bacteria, glyoxalase III (GLY III) with DJ-1/PfpI domain(s) can do the same conversion in a single step without GSH. Our investigations for the presence of DJ-1/PfpI domain containing proteins in plants have indicated the existence of GLY III-like proteins in monocots, dicots, lycopods, gymnosperm and bryophytes. A deeperin silicoanalysis of rice genome identified twelve DJ-1 proteins encoded by six genes. Detailed analysis has been carried out including their chromosomal distribution, genomic architecture and localization. Transcript profiling under multiple stress conditions indicated strong induction ofOsDJ-1in response to exogenous MG. A member of OsDJ-1 family,OsDJ-1C, showed high constitutive expression at all developmental stages and tissues of rice. MG depletion study complemented by simultaneous formation of D-lactate proved OsDJ-1C to be a GLY III enzyme that converts MG directly into D-lactate in a GSH-independent manner. Site directed mutagenesis of Cys-119 to Alanine significantly reduces its GLY III activity indicating towards the existence of functional GLY III enzyme in rice—a shorter route for MG detoxification.
Quantum dissipative effects on non-equilibrium transport through a single-molecular transistor: The Anderson-Holstein-Caldeira-Leggett model
Authors: Raju Ch. Narasimha , Chatterjee Ashok 
Published: January 2016

AbstractThe Anderson-Holstein model with Caldeira-Leggett coupling with environment is considered to describe the damping effect in a single molecular transistor (SMT) which comprises a molecular quantum dot (with electron-phonon interaction) mounted on a substrate (environment) and coupled to metallic electrodes. The electron-phonon interaction is first eliminated using the Lang-Firsov transformation and the spectral density function, charge current and differential conductance are then calculated using the non-equilibrium Keldysh Green function technique. The effects of damping rate and electron-electron and electron-phonon interactions on the transport properties of SMT are studied at zero temperature.