bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest
Authors: Rai Prashant , He Fang , Kwang Jimmy , Engelward Bevin P. , Chow Vincent T.K. 
Published: March 2016

AbstractStreptococcus pneumoniae produces pneumolysin toxin as a key virulence factor against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin that forms lytic pores in host membranes and mediates pneumococcal disease pathogenesis by modulating inflammatory responses. Here, we show that pneumolysin, which is released during bacterial lysis, induces DNA double strand breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX phosphorylation (γH2AX). Pneumolysin-induced γH2AX foci recruit mediator of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end joining is inhibited. Further, we observe that cells that were undergoing DNA replication harbored DSBs in greater frequency during pneumolysin treatment. This observation raises the possibility that DSBs might be arising as a result of replication fork breakdown. Additionally, neutralizing the oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA damage and also cell cycle arrest, indicating that pneumolysin oligomerization is important for causing DNA damage. Taken together, this study reveals a previously unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with implications in the pathophysiology of S. pneumoniae infection.
Influence of humidity on the initial emittable concentration of formaldehyde and hexaldehyde in building materials: experimental observation and correlation
Authors: Huang Shaodan , Xiong Jianyin , Cai Chaorui , Xu Wei , Zhang Yinping 
Published: March 2016

AbstractHumidity is one of the main environmental factors affecting the emission rate and key parameters of formaldehyde and volatile organic compounds (VOCs) from building materials. Meanwhile, the initial emittable concentration (Cm,0) is proved to be the most sensitive key parameter to the emission behaviours. However, there is no report on the relationship between humidity and Cm,0. In this paper, Cm,0 of formaldehyde and hexaldehyde from a type of medium density fiberboard in absolute humidity (AH) range of 4.6–19.6 g/m3 at 25 °C were tested by virtue of a C-history method. Experimental results indicate that Cm,0 is dramatically dependent on AH, increased by 10 and 2 times for formaldehyde and hexaldehyde when AH rising from 4.6 g/m3 to 19.6 g/m3. A linear relationship between the logarithm of Cm,0 and AH is obtained based on the measured results. In addition, a correlation characterizing the association of emission rate and AH is derived. The effectiveness of the correlation is verified with our experimental results as well as data from literature. With the correlations, the Cm,0 or emission rate different from the test AH conditions can be conveniently obtained. This study should be useful for predicting the emission characteristics of humidity changing scenarios and for source control.
On the dynamics of Liesegang-type pattern formation in a gaseous system
Authors: Ramírez-Álvarez Elizeth , Montoya Fernando , Buhse Thomas , Rios-Herrera Wady , Torres-Guzmán José , Rivera Marco , Martínez-Mekler Gustavo , Müller Markus F. 
Published: March 2016

AbstractLiesegang pattern formations are widely spread in nature. In spite of a comparably simple experimental setup under laboratory conditions, a variety of spatio-temporal structures may arise. Presumably because of easier control of the experimental conditions, Liesegang pattern formation was mainly studied in gel systems during more than a century. Here we consider pattern formation in a gas phase, where beautiful but highly complex reaction-diffusion-convection dynamics are uncovered by means of a specific laser technique. A quantitative analysis reveals that two different, apparently independent processes, both highly correlated and synchronized across the extension of the reaction cloud, act on different time scales. Each of them imprints a different structure of salt precipitation at the tube walls.
An atomistic view of Hsp70 allosteric crosstalk: from the nucleotide to the substrate binding domain and back
Authors: Chiappori Federica , Merelli Ivan , Milanesi Luciano , Colombo Giorgio , Morra Giulia 
Published: March 2016

AbstractThe Hsp70 is an allosterically regulated family of molecular chaperones. They consist of two structural domains, NBD and SBD, connected by a flexible linker. ATP hydrolysis at the NBD modulates substrate recognition at the SBD, while peptide binding at the SBD enhances ATP hydrolysis. In this study we apply Molecular Dynamics (MD) to elucidate the molecular determinants underlying the allosteric communication from the NBD to the SBD and back. We observe that local structural and dynamical modulation can be coupled to large-scale rearrangements, and that different combinations of ligands at NBD and SBD differently affect the SBD domain mobility. Substituting ADP with ATP in the NBD induces specific structural changes involving the linker and the two NBD lobes. Also, a SBD-bound peptide drives the linker docking by increasing the local dynamical coordination of its C-terminal end: a partially docked DnaK structure is achieved by combining ATP in the NBD and peptide in the SBD. We propose that the MD-based analysis of the inter domain dynamics and structure modulation could be used as a tool to computationally predict the allosteric behaviour and functional response of Hsp70 upon introducing mutations or binding small molecules, with potential applications for drug discovery.
Mechanisms-based viscoplasticity: Theoretical approach and experimental validation for steel 304L
Authors: Zubelewicz Aleksander , Oliferuk Wiera 
Published: March 2016

AbstractWe propose a mechanisms-based viscoplasticity approach for metals and alloys. First, we derive a stochastic model for thermally-activated motion of dislocations and, then, introduce power-law flow rules. The overall plastic deformation includes local plastic slip events taken with an appropriate weight assigned to each angle of the plane misorientation from the direction of maximum shear stress. As deformation progresses, the material experiences successive reorganizations of the slip systems. The microstructural evolution causes that a portion of energy expended on plastic deformation is dissipated and the rest is stored in the defect structures. We show that the reorganizations are stable in a homogeneously deformed material. The concept is tested for steel 304L, where we reproduce experimentally obtained stress-strain responses, we construct the Frost-Ashby deformation map and predict the rate of the energy storage. The storage is assessed in terms of synchronized measurements of temperature and displacement distributions on the specimen surface during tensile loading.
Layered transition metal dichalcogenides: promising near-lattice-matched substrates for GaN growth
Authors: Gupta Priti , Rahman A. A. , Subramanian Shruti , Gupta Shalini , Thamizhavel Arumugam , Orlova Tatyana , Rouvimov Sergei , Vishwanath Suresh , Protasenko Vladimir , Laskar Masihhur R. , Xing Huili Grace , Jena Debdeep , Bhattacharya Arnab 
Published: March 2016

AbstractMost III-nitride semiconductors are grown on non-lattice-matched substrates like sapphire or silicon due to the extreme difficulty of obtaining a native GaN substrate. We show that several layered transition-metal dichalcogenides are closely lattice-matched to GaN and report the growth of GaN on a range of such layered materials. We report detailed studies of the growth of GaN on mechanically-exfoliated flakes WS2 and MoS2 by metalorganic vapour phase epitaxy. Structural and optical characterization show that strain-free, single-crystal islands of GaN are obtained on the underlying chalcogenide flakes. We obtain strong near-band-edge emission from these layers and analyse their temperature-dependent photoluminescence properties. We also report a proof-of-concept demonstration of large-area growth of GaN on CVD MoS2. Our results show that the transition-metal dichalcogenides can serve as novel near-lattice-matched substrates for nitride growth.
Dimerization of human uridine diphosphate glucuronosyltransferase allozymes 1A1 and 1A9 alters their quercetin glucuronidation activities
Authors: Liu Yan-Qing , Yuan Ling-Min , Gao Zhang-Zhao , Xiao Yong-Sheng , Sun Hong-Ying , Yu Lu-Shan , Zeng Su 
Published: March 2016

AbstractUridine diphosphate glucuronosyltransferase 1A (UGT1A) is a major phase II drug-metabolism enzyme superfamily involved in the glucuronidation of endobiotics and xenobiotics in humans. Many polymorphisms in UGT1A genes are reported to inhibit or decrease UGT1A activity. In this study, two UGT1A1 allozymes, UGT1A1 wild-type and a splice mutant, as well as UGT1A9 wild-type and its three UGT1A9 allozymes, UGT1A9*2(C3Y), UGT1A9*3(M33T) and UGT1A9*5(D256N) were single- or double-expressed in a Bac-to-Bac expression system. Dimerization of UGT1A1 or UGT1A9 allozymes was observed via fluorescence resonance energy transfer (FRET) and co-immunoprecipitation analysis. SNPs of UGT1A altered the ability of protein-protein interaction, resulting in differential FRET efficiencies and donor-acceptor r distances. Dimerization changed the chemical regioselectivity, substrate-binding affinity and enzymatic activity of UGT1A1 and UGT1A9 in glucuronidation of quercetin. These findings provide molecular insights into the consequences of homozygous and heterozygous UGT1A1 and UGT1A9 allozymes expression on quercetin glucuronidation.
Substrate complexes of human dipeptidyl peptidase III reveal the mechanism of enzyme inhibition
Authors: Kumar Prashant , Reithofer Viktoria , Reisinger Manuel , Wallner Silvia , Pavkov-Keller Tea , Macheroux Peter , Gruber Karl 
Published: March 2016

AbstractHuman dipeptidyl-peptidase III (hDPP III) is a zinc-dependent hydrolase cleaving dipeptides off the N-termini of various bioactive peptides. Thus, the enzyme is likely involved in a number of physiological processes such as nociception and is also implicated in several forms of cancer. We present high-resolution crystal structures of hDPP III in complex with opioid peptides (Met-and Leu-enkephalin, endomorphin-2) as well as with angiotensin-II and the peptide inhibitor IVYPW. These structures confirm the previously reported large conformational change of the enzyme upon ligand binding and show that the structure of the closed conformation is independent of the nature of the bound peptide. The overall peptide-binding mode is also conserved ensuring the correct positioning of the scissile peptide bond with respect to the catalytic zinc ion. The structure of the angiotensin-II complex shows, how longer peptides are accommodated in the binding cleft of hDPP III. Differences in the binding modes allow a distinction between real substrates and inhibitory peptides or “slow” substrates. The latter displace a zinc bound water molecule necessitating the energetically much less favoured anhydride mechanism as opposed to the favoured promoted-water mechanism. The structural data also form the necessary framework for the design of specific hDPP III inhibitors.
Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats
Authors: Ma Junwei , Wang Zhong , Liu Chenglin , Shen Haitao , Chen Zhouqing , Yin Jia , Zuo Gang , Duan Xiaochun , Li Haiying , Chen Gang 
Published: March 2016

AbstractPrevious studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33–36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 mg/kg body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3β signaling pathway.
Overexpression of SlUPA-like induces cell enlargement, aberrant development and low stress tolerance through phytohormonal pathway in tomato
Authors: Cui Baolu , Hu Zongli , Hu Jingtao , Zhang Yanjie , Yin Wencheng , Zhu Zhiguo , Feng Ye , Chen Guoping 
Published: March 2016

Abstractupa20 induces cell enlargement and hypertrophy development. In our research, overexpression of SlUPA-like, orthologous to upa20, severely affected the growth of vegetative and reproductive tissues. Wilted leaves curled upwardly and sterile flowers were found in transgenic lines. Through anatomical analysis, palisade and spongy tissues showed fluffy and hypertrophic development in transgenic plants. Gene expression analysis showed that GA responsive, biosynthetic and signal transduction genes (e.g. GAST1, SlGA20OXs, SlGA3OXs, SlGID1s and SlPREs) were significantly upregulated, indicating that GA response is stimulated by overproduction of SlUPA-like. Furthermore, SlUPA-like was strongly induced by exogenous JA and wounding. Decreased expression of PI-I and induced expression of SlJAZs (including SlJAZ2, SlJAZ10 and SlJAZ11) were observed in transgenic plants, suggesting that JA response is repressed. In addition, SlUPA-like overexpressed plant exhibited more opened stoma and higher water loss than the control when treated with dehydration stress, which was related to decreased ABA biosynthesis, signal transduction and response. Particularly, abnormal developments of transgenic plants promote the plant susceptibility to Xanthomonas campestris pv. campestris. Therefore, it is deduced from these results that SlUPA-like plays vital role in regulation of plant development and stress tolerance through GA, JA and ABA pathways.
Pragmatic precision oncology: the secondary uses of clinical tumor molecular profiling
Authors: Rioth Matthew J , Thota Ramya , Staggs David B , Johnson Douglas B , Warner Jeremy L 
Published: March 2016

Abstract
Background Precision oncology increasingly utilizes molecular profiling of tumors to determine treatment decisions with targeted therapeutics. The molecular profiling data is valuable in the treatment of individual patients as well as for multiple secondary uses.
Objective To automatically parse, categorize, and aggregate clinical molecular profile data generated during cancer care as well as use this data to address multiple secondary use cases.
Methods A system to parse, categorize and aggregate molecular profile data was created. A naÿve Bayesian classifier categorized results according to clinical groups. The accuracy of these systems were validated against a published expertly-curated subset of molecular profiling data.
Results Following one year of operation, 819 samples have been accurately parsed and categorized to generate a data repository of 10,620 genetic variants. The database has been used for operational, clinical trial, and discovery science research.
Conclusions A real-time database of molecular profiling data is a pragmatic solution to several knowledge management problems in the practice and science of precision oncology.
Discharge recommendation based on a novel technique of homeostatic analysis
Authors: Calvert Jacob S , Price Daniel A , Barton Christopher W , Chettipally, Uli K , Das Ritankar 
Published: March 2016

Objective: We propose a computational framework for integrating diverse patient measurements into an aggregate health score and applying it to patient stability prediction.
Materials and Methods: We mapped retrospective patient data from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) II clinical database into a discrete multidimensional space, which was searched for measurement combinations and trends relevant to patient outcomes of interest. Patient trajectories through this space were then used to make outcome predictions. As a case study, we built AutoTriage, a patient stability prediction tool to be used for discharge recommendation.
Results: AutoTriage correctly identified 3 times as many stabilizing patients as existing tools and achieved an accuracy of 92.9% (95% CI: 91.6–93.9%), while maintaining 94.5% specificity. Analysis of AutoTriage parameters revealed that interdependencies between risk factors comprised the majority of each patient stability score.
Discussion: AutoTriage demonstrated an improvement in the sensitivity of existing stability prediction tools, while considering patient safety upon discharge. The relative contributions of risk factors indicated that time-series trends and measurement interdependencies are most important to stability prediction.
Conclusion: Our results motivate the application of multidimensional analysis to other clinical problems and highlight the importance of risk factor trends and interdependencies in outcome prediction.
Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb
Authors: Wienisch Martin , Murthy Venkatesh N. 
Published: March 2016

AbstractInformation processing in early sensory regions is modulated by a diverse range of inhibitory interneurons. We sought to elucidate the role of olfactory bulb interneurons called granule cells (GCs) in odor processing by imaging the activity of hundreds of these cells simultaneously in mice. Odor responses in GCs were temporally diverse and spatially disperse, with some degree of non-random, modular organization. The overall sparseness of activation of GCs was highly correlated with the extent of glomerular activation by odor stimuli. Increasing concentrations of single odorants led to proportionately larger population activity, but some individual GCs had non-monotonic relation to concentration due to local inhibitory interactions. Individual dendritic segments could sometimes respond independently to odors, revealing their capacity for compartmentalized signalingin vivo. Collectively, the response properties of GCs point to their role in specific and local processing, rather than global operations such as response normalization proposed for other interneurons.
Small talk’s big role
Authors: Cole Graham 
Published: March 2016

Findings
Intense competition and change are two defining characteristics of today’s business world. It is therefore critical that organizations have the requisite skills and knowledge needed to achieve performance and growth objectives. Learning is clearly vital in this respect. Companies must remain alert to the range of opportunities for key personnel to broaden their horizons and enhance their awareness and understanding of current and future issues. Recognition of this has led to growing acknowledgement of the important contribution of informal types of learning. Indications are that informal conversations with workplace colleagues are especially powerful in this respect.
Factors affecting the intensity of nonfarm participation among ethnic minorities in Northwest Mountains, Vietnam
Authors: Tran Tuyen Quang , Vu Huong Van , Doan Tinh Thanh 
Published: March 2016

Purpose– Little econometric evidence exists on the determinants of nonfarm participation among ethnic minorities in Vietnam. The purpose of this paper is to examine the intensity of nonfarm participation and its correlates among ethnic minority households in Northwest Mountains – the poorest region of Vietnam.Design/methodology/approach– Factors affecting the level of nonfarm participation were examined by using a fractional logit model. In addition, regression analysis using analysis of variance models were used to compare the mean of household characteristics and assets between households with and without nonfarm employment.Findings– The study found that households depended heavily on agriculture for subsistence and their access to nonfarm employment is very limited. Households with nonfarm employment had much higher levels of education, income, assets and a much lower level of poverty than those without nonfarm participation. The intensity of nonfarm participation is positively associated with education levels, proportion of male working members and fixed assets but negatively correlated with the size of annual crop land and water surface for aquaculture. Also, the presence of nonfarm opportunities and paved roads in a commune increases the intensity of nonfarm participation for households living in that commune.Practical implications– The findings suggest that any poverty alleviation policies should aim at improving the access of ethnic minorities to education and nonfarm job opportunities.Originality/value– The study offers the first evidence of factors affecting the intensity of nonfarm participation among ethnic minorities in the study area.
Adult protection in Scotland in 1857 and in 2015: what have we learned?
Authors: Campbell Martin 
Published: March 2016

Purpose
– The purpose of this paper is to compare recent developments in adult protection legislation, policy and practice in Scotland in 2015 with the first attempts at protection of adults at risk of harm, in 1857-1862, with a particular focus on people with learning disabilities.

Design/methodology/approach
– The paper uses comparative historical research, drawing on primary archive material from 1857 to 1862 in the form of Annual Reports of the General Board of Commissioners in Lunacy for Scotland and associated papers.

Findings
– Growing public awareness of the extent of neglect and abuse, and the need for overarching legislation were common factors in the development of both the “The Lunacy Act” of 1857 and the Adult Support and Protection (Scotland) Act of 2007. Both pieces of legislation also had the common aim of “asylum”, and shared some other objectives.

Practical implications
– Total prevention of abuse of vulnerable adults is an aspiration in law and in policy. There is an evidence base of effectiveness, however, in protecting adults at risk of harm from abuse. Some ecological factors recur as challenges to effective safeguarding activity. These include problems of definition, uncovering abuse, enforcing legislation, evaluating impact and protection of people who are not a risk of harm to others.

Originality/value
– This paper compares common themes and common challenges in two separate time periods to investigate what can be learned about the development of legislation and practice in adult protection.