bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed‐onset cytomegalovirus disease coded during hospital readmission in a multicenter, retrospective cohort of liver transplant recipients
Authors: Santos Carlos A. Q. , Brennan Daniel C. , Chapman William C. , Fraser Victoria J. , Olsen Margaret A.
Published: February 2015

Delayed‐onset cytomegalovirus (CMV) disease can occur among liver transplant recipients after CMV prophylaxis is stopped. We hypothesized that delayed‐onset CMV disease (>100 days after transplant) occurs more commonly than early‐onset CMV disease and is associated with clinical sepsis and death. Using 2004‐2010 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 4 Healthcare Cost and Utilization Project state inpatient databases, we assembled a large and more representative cohort of 7229 adult liver transplant recipients from 26 transplant centers, and we identified demographics, comorbidities, CMV disease, and clinical sepsis coded during readmission and inpatient death. Multivariate analysis was performed with Cox proportional hazards models. Delayed‐onset CMV disease occurred in 4.3% (n = 309), whereas early‐onset CMV disease occurred in 2% (n = 142). Delayed‐onset CMV disease was associated with previous transplant failure or rejection [adjusted hazard ratio (aHR), 1.4; 95% confidence interval (CI), 1.1‐1.7]. Clinical sepsis > 100 days after transplant was associated with previous CMV disease (aHR, 1.3; 95% CI; 1.0‐1.7), previous transplant failure or rejection (aHR, 2.1; 95% CI; 1.8‐2.4), female sex (aHR, 1.3; 95% CI; 1.1‐1.5), and several comorbidities. Death > 100 days after transplant was associated with delayed‐onset CMV disease (aHR, 2.0; 95% CI; 1.6‐2.6), transplant failure or rejection (aHR, 4.3; 95% CI; 3.4‐5.5), increasing age by decade (aHR, 1.1; 95% CI; 1.0‐1.2), and some comorbidities. In conclusion, delayed‐onset CMV disease is more common than early‐onset CMV disease among liver transplant recipients. Previous CMV disease may be a risk factor for clinical sepsis > 100 days after transplant, and delayed‐onset CMV disease may be a risk factor for death > 100 days after transplant. Liver Transpl 21:581–590, 2015. © 2015 AASLD.
Organic Radical Contrast Agents Based on Polyacetylenes Containing 2,2,6,6‐Tetramethylpiperidine 1‐Oxyl (TEMPO): Targeted Magnetic Resonance (MR)/Optical Bimodal Imaging of Folate Receptor Expressing HeLa Tumors in Vitro and in Vivoa
Authors: Huang Lixia , Yan Chenggong , Cui Danting , Yan Yichen , Liu Xiang , Lu Xinwei , Tan Xiangliang , Lu Xiaodan , Xu Jun , Xu Yikai , Liu Ruiyuan
Published: February 2015

Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6‐tetramethyl‐piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA‐TEMPO‐FI‐FA) without cytotoxicity. In vivo T1‐weighted MRI demonstrates the active tumor targeting ability of PA‐TEMPO‐FI‐FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post‐injection of PA‐TEMPO‐FI‐FA. These results indicate that multifunctional ORCAs may provide a tumor‐targeted delivery platform for further molecular imaging guided cancer therapy.
Cellulose Carbonates: A Platform for Promising Biopolymer Derivatives With Multifunctional Capabilities
Authors: Elschner Thomas , Heinze Thomas
Published: February 2015

Cellulose carbonates as a platform compound open new possibilities for the design of advanced materials based on the most important renewable resource cellulose. In the present feature, the chemistry of cellulose carbonates is discussed considering own research results adequately. After a short overview about methods for activation of polysaccharides for a conversion with nucleophilic compounds in particlur with amines, details about various methods for the synthesis of polysaccharide carbonates are discussed. The main issue of the feature is the synthesis and aminolysis of cellulose carbonates with low, intermediate, and high degree of substitution and the evaluation of this chemistry with respect to specific challenges. Functional cellulose carbamates, obtained from cellulose phenyl carbonate by aminolysis, show the potential use of this class of celluloses. Immunoassays and zwitterionic polymers are included as representative examples regarding properties and application of the new cellulose‐based products.
Stress corrosion cracking investigation of high Co‐Ni secondary hardening ultra‐high strength steel in neutral 3.5 wt% NaCl solution
Authors: Guo Q. , Liu J.‐H. , Yu M. , Li S.‐M.
Published: February 2015

Stress corrosion cracking (SCC) and passivation behaviour of ultra‐high strength steel 23Co14Ni12Cr3 in neutral 3.5 wt% NaCl solution were investigated by slow strain rate test, surface analysis techniques and electrochemical measurements. The passive film on the steel is mainly composed of Fe, Co, Cr and Ni oxides and hydroxides. At potentials less than −850 mVSCE, SCC is controlled by hydrogen induced cracking (HIC). The passive film decreases SCC susceptibility of the steel at −400 mVSCE. While, HIC plays a dominant role on SCC mechanism at OCP.
Solution Behavior of Hydrolyzed Gradient Methyl/Phenyl Oxazoline Copolymers and Complexation with DNA
Authors: Vlassi Eleni , Pispas Stergios
Published: February 2015

Partial hydrolysis of 2‐methyl‐2‐oxazoline/2‐phenyl‐2‐oxazoline gradient copolymers (MPOx copolymers) results in amphiphilic copolymers containing cationic ethylene imine, neutral hydrophilic 2‐methyl‐2‐oxazoline, and hydrophobic 2‐phenyl‐2‐oxazoline segments (HMPOx copolymers). The solution behavior of the HMPOx copolymers has been investigated in water, phosphate buffer saline (PBS), and fetal bovine serum (FBS) by static, dynamic, and electrophoretic light scattering and fluorescence spectroscopy. The copolymers form stable spherical aggregates in aqueous media with positive surface charge. The aggregates are found to interact extensively with proteins in FBS solutions. Soluble HMPOx/DNA complexes have also been formed in aqueous media at certain HMPOx/DNA compositions due to electrostatic interactions. The polyplexes have been studied in terms of structure and colloidal stability.

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One‐Pot Sequential Ring‐Opening Metathesis Polymerization and Acyclic Diene Metathesis Polymerization Synthesis of Unsaturated Block Polyphosphoesters
Authors: Ding Liang , Wang Chengshuang , Lin Ling , Zhu Zhenshu
Published: February 2015

A novel divergent approach is presented for the one‐pot synthesis of unsaturated block poly­phosphoester (PPE) structures by a sequential ring‐opening metathesis polymerization (ROMP) and acyclic diene metathesis (ADMET) polymerization. A linear functional PPE bearing one or two terminal acrylate groups is first prepared through the third generation Grubbs catalyst‐mediated ROMP of seven‐membered cyclic phosphate monomer, in the presence of a symmetrical multifunctional terminating agent or chain transfer agent. The functional PPE is then utilized as a selective macromolecular chain stopper in subsequent ADMET polymerization of phosphoester functional asymmetric α,ω‐diene monomer, yielding unsaturated block PPEs. The thermal properties of block PPEs are studied and their thermal degradation and flame‐retardant properties are evaluated. Furthermore, the prepared block PPEs can spontaneously self‐assemble in a selective solvent to form polymeric micelles, which are characterized in detail by dynamic light scattering, atom force microscopy, transmission electron microscopy, and scanning electron microscopy analyses.

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Distributional representations of Nκ(∞)‐functions
Authors: Langer Matthias , Woracek Harald
Published: February 2015

The subclasses of the classes of generalized Nevanlinna functions appear in the context of Pontryagin space models, where they correspond to model relations having a particular spectral behaviour. Applications are found, for instance, in the investigation of differential expressions with singular coefficients. We study representations of ‐functions as Cauchy‐type integrals in a distributional sense and characterize the class of distributions occurring in such representations. We make explicit how the Pontryagin space model of an ‐function is related to the multiplication operator in the L2‐space of the measure which describes the action of the representing distribution away from infinity. Moreover, we determine the distributional representations of a pair of functions associated with a symmetric generalized Nevanlinna function.
Significance of the superposition of cyclic mechanical and corrosive loadings in the qualification process of aluminium alloys
Authors: Bauer‐Troßmann K. , Yu L. , Melz T. , Oechsner M. , Kaufmann H.
Published: February 2015

In order to take advantage of the potential of new high strength aluminium alloys for corrosion fatigue loaded components, it is of importance to qualify their suitability regarding superposed mechanical and corrosive loadings prior to established validation tests such as the structural durability proof.

Up to now selection of potential aluminium alloys for chassis applications is based on stand‐alone mechanical and fatigue properties as well as a wide range of alloy‐specific corrosion tests not taking into account simultaneous cyclic mechanical and corrosive loadings occurring in service.

Within this paper, approaches comprising fatigue testing in air, pre‐corrosion with consecutive fatigue testing and corrosion fatigue tests are discussed regarding their suitability to assess the behaviour of aluminium alloys under operating conditions.

Aluminium alloys of different alloy series with different sensitisation conditions towards corrosion are included in this review.
Molecular investigation of the radiation resistance of edible cyanobacterium Arthrospira sp. PCC 8005
Authors: Badri Hanène , Monsieurs Pieter , Coninx Ilse , Wattiez Ruddy , Leys Natalie
Published: February 2015

The aim of this work was to characterize in detail the response of Arthrospira to ionizing radiation, to better understand its radiation resistance capacity. Live cells of Arthrospira sp. PCC 8005 were irradiated with 60Co gamma rays. This study is the first, showing that Arthrospira is highly tolerant to gamma rays, and can survive at least 6400 Gy (dose rate of 527 Gy h−1), which identified Arthrospira sp. PCC 8005 as a radiation resistant bacterium. Biochemical, including proteomic and transcriptomic, analysis after irradiation with 3200 or 5000 Gy showed a decline in photosystem II quantum yield, reduced carbon fixation, and reduced pigment, lipid, and secondary metabolite synthesis. Transcription of photo‐sensing and signaling pathways, and thiol‐based antioxidant systems was induced. Transcriptomics did show significant activation of ssDNA repair systems and mobile genetic elements (MGEs) at the RNA level. Surprisingly, the cells did not induce the classical antioxidant or DNA repair systems, such superoxide dismutase (SOD) enzyme and the RecA protein. Arthrospira cells lack the catalase gene and the LexA repressor. Irradiated Arthrospira cells did induce strongly a group of conserved proteins, of which the function in radiation resistance remains to be elucidated, but which are a promising novel routes to be explored. This study revealed the radiation resistance of Arthrospira, and the molecular systems involved, paving the way for its further and better exploitation.
Orthostatic Hypotension in Parkinson Disease: How Much You Fall or How Low You Go?
Authors: Palma Jose‐Alberto , Gomez‐Esteban Juan Carlos , Norcliffe‐Kaufmann Lucy , Martinez Jose , Tijero Beatriz , Berganzo Koldo , Kaufmann Horacio
Published: February 2015

Orthostatic hypotension (OH) is frequent in patients with Parkinson's disease (PD) and can occur with or without symptoms. Pharmacological treatments are effective, but often exacerbate supine hypertension. Guidelines exist for the diagnosis, but not for the treatment of OH. We examined the relationship between blood pressure (BP) and symptoms in a cohort of PD patients with the goal of identifying a hemodynamic target to guide treatment. We measured BP supine and upright (tilt or active standing) and identified the presence or absence of symptomatic OH by using a validated patient‐reported outcome questionnaire in 210 patients with PD. We evaluated the usefulness of the 20/10 and 30/15 mmHg diagnostic criteria (systolic/diastolic) to identify symptomatic OH. Fifty percent of the PD patient cohort met criteria for the 20/10 fall and 30% for the 30/15 BP fall. Among the patients who met either OH criteria, the percentage of those with symptoms was small (33% of those with 20/10 and 44% of those with 30/15 mmHg; 16% and 13%, respectively, overall). Symptomatic OH was associated with an upright mean BP below 75 mmHg. A mean standing BP <75 mmHg had a sensitivity of 97% and a specificity of 98% for detecting symptomatic OH. Although the prevalence of OH in PD is high, not all patients have symptoms of organ hypoperfusion. A mean standing BP below 75 mmHg appears to be a useful benchmark when deciding whether the benefits of initiating pharmacological treatment of OH outweigh the risks of exacerbating supine hypertension. © 2015 International Parkinson and Movement Disorder Society
Improving AutoDock Vina Using Random Forest: The Growing Accuracy of Binding Affinity Prediction by the Effective Exploitation of Larger Data Sets
Authors: Li Hongjian , Leung Kwong‐Sak , Wong Man‐Hon , Ballester Pedro J.
Published: February 2015

There is a growing body of evidence showing that machine learning regression results in more accurate structure‐based prediction of protein‐ligand binding affinity. Docking methods that aim at optimizing the affinity of ligands for a target rely on how accurate their predicted ranking is. However, despite their proven advantages, machine‐learning scoring functions are still not widely applied. This seems to be due to insufficient understanding of their properties and the lack of user‐friendly software implementing them. Here we present a study where the accuracy of AutoDock Vina, arguably the most commonly‐used docking software, is strongly improved by following a machine learning approach. We also analyse the factors that are responsible for this improvement and their generality. Most importantly, with the help of a proposed benchmark, we demonstrate that this improvement will be larger as more data becomes available for training Random Forest models, as regression models implying additive functional forms do not improve with more training data. We discuss how the latter opens the door to new opportunities in scoring function development. In order to facilitate the translation of this advance to enhance structure‐based molecular design, we provide software to directly re‐score Vina‐generated poses and thus strongly improve their predicted binding affinity. The software is available at http://istar.cse.cuhk.edu.hk/rf‐score‐3.tgz and http://crcm. marseille.inserm.fr/fileadmin/rf‐score‐3.tgz
Energy analysis and improved regularity estimates for multiscale deconvolution models of incompressible flows
Authors: Kim Tae‐Yeon , Dunca Argus A. , Rebholz Leo G. , Fried Eliot
Published: February 2015

This paper presents new analytical results and the first numerical results for a recently proposed multiscale deconvolution model (MDM) recently proposed. The model involves a large‐eddy simulation closure that uses a novel deconvolution approach based on the introduction of two distinct filtering length scales. We establish connections between the MDM and two other models, and, on the basis of one of these connections, we establish an improved regularity estimate for MDM solutions. We also prove that the MDM preserves Taylor‐eddy solutions of the Navier–Stokes equations and therefore does not distort this particular vortex structure. Simulations of the MDM are performed to examine the accuracy of the MDM and the effect of the filtering length scales on energy spectra for three‐dimensional homogeneous and isotropic flows. Numerical evidence for all tests clearly indicates that the MDM gives very accurate coarse‐mesh solutions and that this multiscale approach to deconvolution is effective. Copyright © 2015 John Wiley & Sons, Ltd.
A discrete Hartley transform based on Simpson's rule
Authors: Singh P. , Singh V.
Published: February 2015

The Hartley transform is an integral transformation that maps a real valued function into a real valued frequency function via the Hartley kernel, thereby avoiding complex arithmetic as opposed to the Fourier transform. Approximation of the Hartley integral by the trapezoidal quadrature results in the discrete Hartley transform, which has proven a contender to the discrete Fourier transform because of its involutory nature. In this paper, a discrete transform is proposed as a real transform with a convolution property and is an alternative to the discrete Hartley transform. Copyright © 2015 John Wiley & Sons, Ltd.
Adaptive multiscale moment method applied to the electromagnetic scattering by coastal breaking sea waves
Authors: Coatanhay A. , Scolan Y.‐M.
Published: February 2015

The adaptive multiscale moment method (AMMM) was originally developed to solve Fredholm equation. More recently, this method has demonstrated to be effective for scattering problems. In this article, we show that AMMM is a relevant approach to model and to analyze the electromagnetic scattering by coastal breaking sea waves. The shape of breaking wave results from very nonlinear fluid mechanics and is a complex target for electromagnetic scattering. This article presents an efficient hydrodynamic model and, combined with AMMM, a global realistic numerical simulation of the electromagnetic signature induced by breaking sea waves. Copyright © 2015 John Wiley & Sons, Ltd.
Sodium MRI in human heart: a review
Authors: Bottomley Paul A.
Published: February 2015

This paper offers a critical review of the properties, methods and potential clinical application of sodium (23Na) MRI in human heart. Because the tissue sodium concentration (TSC) in heart is about ~40 µmol/g wet weight, and the 23Na gyromagnetic ratio and sensitivity are respectively about one‐quarter and one‐11th of that of hydrogen (1H), the signal‐to‐noise ratio of 23Na MRI in the heart is about one‐6000th of that of conventional cardiac 1H MRI. In addition, as a quadrupolar nucleus, 23Na exhibits ultra‐short and multi‐component relaxation behavior (T1 ~ 30 ms; T2 ~ 0.5–4 ms and 12–20 ms), which requires fast, specialized, ultra‐short echo‐time MRI sequences, especially for quantifying TSC. Cardiac 23Na MRI studies from 1.5 to 7 T measure a volume‐weighted sum of intra‐ and extra‐cellular components present at cytosolic concentrations of 10–15 mM and 135–150 mM in healthy tissue, respectively, at a spatial resolution of about 0.1–1 ml in 10 min or so. Currently, intra‐ and extra‐cellular sodium cannot be unambiguously resolved without the use of potentially toxic shift reagents. Nevertheless, increases in TSC attributable to an influx of intra‐cellular sodium and/or increased extra‐cellular volume have been demonstrated in human myocardial infarction consistent with prior animal studies, and arguably might also be seen in future studies of ischemia and cardiomyopathies – especially those involving defects in sodium transport. While technical implementation remains a hurdle, a central question for clinical use is whether cardiac 23Na MRI can deliver useful information unobtainable by other more convenient methods, including 1H MRI. Copyright © 2015 John Wiley & Sons, Ltd.
Employee and Volunteer
Authors: Ariza‐Montes Antonio , Roldán‐Salgueiro José Luis , Leal‐Rodríguez Antonio
Published: February 2015

The purpose of this research is to analyze the different factors that determine the level of time devoted to volunteer activity involving employed people. To this end, we applied a logistic regression model to a sample of 5,067 employees, considering four categories of factors: family and personal, on the one hand, and contextual factors, on the other. This second group involves three factor categories: occupational, organizational, and community involvement factors. The findings of this work are especially relevant to two areas: first, to design a policy of corporate social responsibility that effectively integrates the figure of corporate volunteering, considering its pertinent factors; and second, to broaden the perspective of the third‐sector organizations beyond the traditional profile with which volunteers are commonly associated.
Which Nonprofit Gets More Government Funding?
Authors: Lu Jiahuan
Published: February 2015

Government represents one of the most important funding sources for nonprofit organizations. However, the literature has not yet provided a systematic understanding of nonprofits’ organizational factors that are associated with their receipts of government funding. This study combines interorganizational relationships and organizational institutionalism literature to examine the determinants of nonprofits’ obtainment of government funding. Based on a survey of human service nonprofits in Maryland, this research finds that nonprofits with higher bureaucratic orientation, stronger domain consensus with government, and longer government funding history are more likely to receive government contracts and grants. Nonprofits’ revenue diversification, professionalization, and board co‐optation might have very limited impacts.
How Quickly Do Catholic Bishops Become Obsolete?
Authors: Zech Charles
Published: February 2015

A well‐developed management literature exists that argues that new corporate chief executive officers’ performance initially increases, but for a variety of reasons it eventually peaks and then decreases; this pattern of performance is graphically depicted as an inverted U‐shaped form. The explanation is that although there might exist an appropriate match between the CEO and the organization's needs at the time of appointment, a CEO’s effectiveness will diminish because of factors such as a leveling off in learning on the part of the CEO; a reluctance on the part of CEOs to change their management style; an increased reliance on fewer, primarily internal, advisors; and the tendency for these advisors to provide CEOs only with the type of information that they want to hear. All of this is compounded by a dynamic external environment.

This article applies this theory to the case of US Catholic bishops in an effort to discover whether they might follow the same pattern in leading their dioceses. Using the number of seminarians recruited as a performance measure, a pooled data set was tested for the existence of an inverted U‐shaped pattern. Instead, the findings show a monotonically decreasing impact on performance as bishop tenure increases. One possible explanation is a poor initial match between a bishop's talents and the diocese's needs.
Recycling of condensation polymers via ring–chain equilibria
Authors: Hodge Philip
Published: February 2015

This short review discusses the progress made toward recycling condensation polymers using ring–chain equilibria (RCEs). RCEs are the classical equilibria that can exist between a condensation polymer and the corresponding family of macrocyclic oligomers (MCOs). Using RCE, the polymer can be converted into a family of MCOs by a process known as cyclodepolymerization, and the MCOs can then be converted back into the polymer by a process known as entropically driven ring‐opening polymerization. This review considers examples of cyclodepolymerizations that can be carried out on condensation polymers and entropically driven ring‐opening polymerizations that can be used to prepare condensation polymers. Some of the problems that need to be addressed to make the overall process commercially viable are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Exposure to aripiprazole during embryogenesis: a prospective multicenter cohort study
Authors: Bellet Florelle , Beyens Marie‐Noëlle , Bernard Nathalie , Beghin Delphine , Elefant Elisabeth , Vial Thierry
Published: February 2015

Purpose

The main purpose of this study was to evaluate the risk of major malformations after aripiprazole exposure during the embryonic period. The secondary purposes were to assess the risk of miscarriage, prematurity, fetal growth retardation and maternal complications and to describe possible neonatal adverse effects.

Methods

We conducted a cohort study using data prospectively collected by the French Pharmacovigilance Centres participating to the Terappel program and the Centre de Référence sur les Agents Tératogènes between 2004 and 2011. The exposed group consisted of pregnant women exposed to aripiprazole during embryogenesis, and the unexposed group consisted of pregnant women without exposure or exposed to non‐teratogenic agents. Two unexposed patients, matched for age and gestational age at call, were randomly selected for each exposed patient.

Results

Eighty‐six patients were included in the exposed group and 172 in the unexposed group. Exposure to aripiprazole was not significantly associated with an increased rate of major malformations (OR 2.30, 95%CI 0.32–16.7) or miscarriage (1.66, 0.63–4.38) or gestational diabetes (1.15, 0.33–4.04) compared to non‐exposure. The study revealed significantly increased rates of prematurity (OR 2.57, 95%CI 1.06–6.27) and fetal growth retardation (2.97, 1.23–7.16) in exposed newborns, difficult to interpret because of the short duration of maternal exposure. Two cases of neonatal complications were reported among the 19 newborns exposed to aripiprazole near delivery.

Conclusion

This study failed to demonstrate a significant association between aripiprazole exposure during the embryonic period and major malformations. More powerful prospective studies are required to clarify the reproductive safety profile of aripiprazole. Copyright © 2015 John Wiley & Sons, Ltd.
Exploring the possible association between montelukast and neuropsychiatric events among children with asthma: a matched nested case‐control study
Authors: Ali Mir M. , O'Brien Catherine E. , Cleves Mario A. , Martin Bradley C.
Published: February 2015

Purpose

There is conflicting evidence regarding the association between montelukast and neuropsychiatric events (NE). We sought to examine this association among children with asthma.

Methods

Using a 10% sample of the LifeLink Health Plan Claims data, subjects less than 18 years of age with a primary diagnosis of asthma between 1 January 1998 and 31 December 2009 were identified. A range of case definitions for NE was formulated based on diagnoses of psychiatric disorders and use of psychotropic medications. Using a matched nested case‐control design, three controls were matched to each case on age, gender and geographic region, and assigned a matching index date. Exposure to montelukast was measured as any exposure during the year, recency of exposure, cumulative duration of exposure, and cumulative dose. Conditional logistic regression was used to estimate unadjusted and adjusted odds ratio (OR) controlling for potential confounders.

Results

Using the broadest case definition, 1920 cases were identified. Subjects exposed to montelukast during the prior year had an unadjusted OR of 1.09 (95%CI [0.96, 1.22]) and adjusted OR of 1.01 (95%CI [0.88, 1.14]) for experiencing NE measured using the broadest definition. A clear dose–response relationship was not observed. Exposure to a moderate chronic cumulative dose of montelukast (481 mg–1050 mg) had a higher odds of being diagnosed with neuropsychiatric disturbances (OR = 1.27; 95%CI [1.03, 1.57]) while exposure to high cumulative doses (>1050 mg) had a lower odds (OR = 0.64; 95%CI [0.50, 0.82]).

Conclusions

These data did not detect a consistent significant positive association between montelukast and NE in children with asthma. Copyright © 2015 John Wiley & Sons, Ltd.
GENDER DIFFERENCES IN ACHIEVEMENT IN A LARGE, NATIONALLY REPRESENTATIVE SAMPLE OF CHILDREN AND ADOLESCENTS
Authors: Scheiber Caroline , Reynolds Matthew R. , Hajovsky Daniel B. , Kaufman Alan S.
Published: February 2015

The purpose of this study was to investigate developmental gender differences in academic achievement areas, with the primary focus on writing, using the child and adolescent portion (ages 6–21 years) of the Kaufman Test of Educational Achievement—Second Edition, Brief Form, norming sample (N = 1,574). Path analytic models with gender, parent education, age, age2, and gender‐by‐age moderation as predictors of reading, writing, and math were used to test for gender differences and for the influence of development on these differences. A small but consistent advantage was identified for females in reading. No gender differences were detected in math. The most important results of the present study pertain to a gender gap in writing in favor of females that increased as a function of age. Male students are at greater risk for writing failure than are females.
Bottom up proteomics data analysis strategies to explore protein modifications and genomic variants
Authors: Carvalho Ana Sofia , Penque Deborah , Matthiesen Rune
Published: February 2015

The quest to understand biological systems requires further attention of the scientific community to the challenges faced in proteomics. In fact the complexity of the proteome reaches uncountable orders of magnitude. This means that significant technical and data‐analytic innovations will be needed for the full understanding of biology. Current state of art MS is probably our best choice for studying protein complexity and exploring new ways to use MS and MS derived data should be given higher priority. We present here a brief overview of visualization and statistical analysis strategies for quantitative peptide values on an individual protein basis. These analysis strategies can help pinpoint protein modifications, splice, and genomic variants of biological relevance. We demonstrate the application of these data analysis strategies using a bottom‐up proteomics dataset obtained in a drug profiling experiment. Furthermore, we have also observed that the presented methods are useful for studying peptide distributions from clinical samples from a large number of individuals. We expect that the presented data analysis strategy will be useful in the future to define functional protein variants in biological model systems and disease studies. Therefore robust software implementing these strategies is urgently needed.
Unlocking proteomic heterogeneity in complex diseases through visual analytics
Authors: Bhavnani Suresh K. , Dang Bryant , Bellala Gowtham , Divekar Rohit , Visweswaran Shyam , Brasier Allan R. , Kurosky Alex
Published: February 2015

Despite years of preclinical development, biological interventions designed to treat complex diseases such as asthma often fail in phase III clinical trials. These failures suggest that current methods to analyze biomedical data might be missing critical aspects of biological complexity such as the assumption that cases and controls come from homogeneous distributions. Here we discuss why and how methods from the rapidly evolving field of visual analytics can help translational teams (consisting of biologists, clinicians, and bioinformaticians) to address the challenge of modeling and inferring heterogeneity in the proteomic and phenotypic profiles of patients with complex diseases. Because a primary goal of visual analytics is to amplify the cognitive capacities of humans for detecting patterns in complex data, we begin with an overview of the cognitive foundations for the field of visual analytics. Next, we organize the primary ways in which a specific form of visual analytics called networks has been used to model and infer biological mechanisms, which help to identify the properties of networks that are particularly useful for the discovery and analysis of proteomic heterogeneity in complex diseases. We describe one such approach called subject‐protein networks, and demonstrate its application on two proteomic datasets. This demonstration provides insights to help translational teams overcome theoretical, practical, and pedagogical hurdles for the widespread use of subject‐protein networks for analyzing molecular heterogeneities, with the translational goal of designing biomarker‐based clinical trials, and accelerating the development of personalized approaches to medicine.
Enrichment or depletion? The impact of stool pretreatment on metaproteomic characterization of the human gut microbiota
Authors: Tanca Alessandro , Palomba Antonio , Pisanu Salvatore , Addis Maria Filippa , Uzzau Sergio
Published: February 2015

To date, most metaproteomic studies of the gut microbiota employ stool sample pretreatment methods to enrich for microbial components. However, a specific investigation aimed at assessing if, how, and to what extent this may impact on the final taxonomic and functional results is still lacking. Here, stool replicates were either pretreated by differential centrifugation (DC) or not centrifuged. Protein extracts were then processed by filter‐aided sample preparation, single‐run LC, and high‐resolution MS, and the metaproteomic data were compared by spectral counting. DC led to a higher number of identifications, a significantly richer microbial diversity, as well as to reduced information on the nonmicrobial components (host and food) when compared to not centrifuged. Nevertheless, dramatic differences in the relative abundance of several gut microbial taxa were also observed, including a significant change in the Firmicutes/Bacteroidetes ratio. Furthermore, some important microbial functional categories, including cell surface enzymes, membrane‐associated proteins, extracellular proteins, and flagella, were significantly reduced after DC. In conclusion, this work underlines that a critical evaluation is needed when selecting the appropriate stool sample processing protocol in the context of a metaproteomic study, depending on the specific target to which the research is aimed. All MS data have been deposited in the ProteomeXchange with identifier PXD001573 (http://proteomecentral.proteomexchange.org/dataset/PXD001573).
Nanocomposites Prepared with High Density Polyethylene and Carbon Nanofibers Modified by Ethylene Plasma
Authors: Neira‐Velázquez María Guadalupe , Borjas‐Ramos José Javier , Hernández‐Hernández Ernesto , Hernández‐Ramos Claudia Guadalupe , Narro‐Céspedes Rosa Idalia , Hernández‐Gámez José Francisco , Ramos de Valle Luis Francisco
Published: February 2015

Carbon nanofibers (CNFs) are surface‐modified by plasma polymerization using ethylene as monomer. The modified CNFs are suitable to be mixed with different polyethylenes. In this study, we mix them with high density polyethylene (HDPE). The plasma‐coated CNFs (pCNFs) are then characterized by Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Scanning Electron Microscopy (SEM) in the transmission mode (STEM). Treated and untreated CNFs are evaluated in water, chloroform, and 1,2,3‐trichlorobenzene (TCB) to evaluate their effective dispersion in these three solvents. FTIR spectra showed signals corresponding to the organic part deposited on the surface of pCNFs. The TGA analysis makes it possible to confirm that pCNFs have a higher weight loss than CNFs because of the volatilization of the plasma polymerized ethylene coating. Dispersion tests showed that pCNFs dispersed well in TCB and chloroform solvents. To prepare nanocomposites, HDPE and CNFs are mixed well in a single‐screw extruder with an attached sonication chamber at its exit. Nanocomposites containing 1% and 3% by weight of CNFs are prepared. The products are analyzed by the Young's modulus and evaluated for thermal stability.
N2/H2o Plasma Assisted Functionalization of Poly(ε‐caprolactone) Porous Scaffolds: Acidic/Basic Character versus Cell Behavior
Authors: Sardella Eloisa , Fisher Ellen R. , Shearer Jeffrey C. , Garzia Trulli Marta , Gristina Roberto , Favia Pietro
Published: February 2015

A primary research focus in tissue engineering addresses the factors that drive cell growth in scaffolds. Due to the inherent complexity of phenomena at the cell/biomaterial interface in cell‐culture media, it is not easy to unambiguously disentangle the effects of different surface properties (e.g., chemical composition, roughness, porosity, etc.) in promoting specific cell behaviors, especially on porous scaffold materials. We have investigated fast low‐pressure plasma treatments of porous PCL scaffolds for tissue engineering with neutral, acidic, and basic groups to obtain stable water absorbent materials. An increase of Saos2 cell growth was observed on plasma‐treated scaffolds with respect to native samples; amphoteric surfaces were found very suitable for cell proliferation.
Atmospheric‐Pressure Plasma‐ and TRAIL‐Induced Apoptosis in TRAIL‐Resistant Colorectal Cancer Cells
Authors: Ishaq Musarat , Han Zhao Jun , Kumar Shailesh , Evans Margaret D. M. , Ostrikov Kostya (Ken)
Published: February 2015

The ideal anti‐cancer treatments are those that can selectively kill cancer cells without harming normal cells. Tumor necrosis factor (TNF)‐related apoptosis inducing ligand (TRAIL) is an example of a molecule that can selectively kill cancer cells but not normal cells. However, some tumors are resistant to the TRAIL treatment. We have recently shown that atmospheric cold non‐equilibrium gas plasmas (AGPs) selectively induced cell death in melanoma and colorectal cancer cell lines by activating TNF and caspases 3/7 apoptosis pathways. Here, we demonstrated that AGPs can be used to make TRAIL‐resistant colorectal cancer cells sensitive to the TRAIL treatment. AGPs plus TRAIL promoted the induction of the death receptor 5 (DR5), thereby enhancing the activation and apoptosis of ROS‐dependent caspases 3/7. This study revealed the mechanisms involved in AGP‐assisted TRAIL‐induced cancer cell death and the associated synergistic effects that AGPs has on TRAIL‐resistant colorectal cancer cells.
Exosomes in bodily fluids are a highly stable resource of disease biomarkers
Authors: Boukouris Stephanie , Mathivanan Suresh
Published: February 2015

Biomarkers are measurable indicators of a biological state. As our understanding of diseases meliorates, it is generally accepted that early diagnosis renders the best chance to cure a disease. In the context of proteomics, the discovery phase of identifying bonafide biomarkers and the ensuing validation phase involving large cohort of patient samples are impeded by the complexity of bodily fluid samples. High abundant proteins found in blood plasma make it difficult for the detection of low abundant proteins that may be potential biomarkers. Extracellular vesicles (EVs) have reignited interest in the field of biomarker discovery. EVs contain a tissue‐type signature wherein a rich cargo of proteins and RNA are selectively packaged. In addition, as EVs are membranous structures, the luminal contents are protected from degradation by extracellular proteases and are highly stable in storage conditions. Interestingly, an appealing feature of EV‐based biomarker analysis is the significant reduction in the sample complexity compared to whole bodily fluids. With these prescribed attributes, which are the rate‐limiting factors of traditional biomarker analysis, there is immense potential for the use of EVs for biomarker detection in clinical settings. This review will discuss the current issues with biomarker analysis and the potential use of EVs as reservoirs of disease biomarkers.
The role of quantitative ADME proteomics to support construction of physiologically based pharmacokinetic models for use in small molecule drug development
Authors: Heikkinen Aki T. , Lignet Floriane , Cutler Paul , Parrott Neil
Published: February 2015

Pharmacokinetics (PK) refers to the time course of drug concentrations in the body and since knowledge of PK aids understanding of drug efficacy and safety, numerous PK studies are performed in animals and humans during the drug development process. In vitro to in vivo extrapolation and physiologically based pharmacokinetic (PBPK) modeling are tools that integrate data from various in silico, in vitro, and in vivo sources to deliver mechanistic quantitative simulations of in vivo PK. PBPK models are used to predict human PK and to evaluate the effects of intrinsic factors such as organ dysfunction, age, and genetics as well as extrinsic factors such as co‐administered drugs. In recent years, the use of PBPK within the industry has greatly increased. However, insufficient data on how the abundance of metabolic enzymes and membrane transporters vary in different human patient populations and in different species has been a limitation. A major advance is therefore expected through reliable quantification of the abundance of these proteins in tissues. This review describes the role of PBPK modeling in drug discovery and development, outlines the assumptions involved in integrating protein abundance data, and describes the advances made and expected in determining abundance of relevant proteins through mass spectrometric techniques.
Relative versus absolute quantitation in disease glycomics
Authors: Moh Edward S.X. , Thaysen‐Andersen Morten , Packer Nicolle H.
Published: February 2015

The glycome of a diagnostic biological material such as blood, urine, saliva, tissue, or cell cultures comprises of a vast array of structurally distinct glycans attached to the protein complement. Aberrant glycan structures and distributions result from changes in specific glycosyltransferase activities and have different biological significance, making proper quantitation of glycans highly important. In this review, common HPLC/CE and LC‐MS/MS‐based methods for glycomics, their advantages and disadvantages, will be discussed with respect to the main quantitative strategies. With the increasing interest in absolute quantitation for glycomics, we discuss absolute and relative glycome quantitation and how it affects the resulting conclusions drawn from glycomics studies. We argue that while absolute quantitation of glycomes may be attractive for some areas of clinical glycomics, relative quantitation of glycans remains the most informative and time/cost‐effective method to obtain biological insight into the regulation of the cellular glycosylation machinery and the synthesis of the resultant glycan structures in most research questions due to the enzymatic relatedness of the biosynthesized glycans. Recent developments in multiplexing of glycomes by the introduction of stable isotopic labeling of glycans show promise for providing another level of information to the existing benefits of relative quantitation.
The emerging role of native mass spectrometry in characterizing the structure and dynamics of macromolecular complexes
Authors: Boeri Erba Elisabetta , Petosa Carlo
Published: February 2015

Mass spectrometry (MS) is a powerful tool for determining the mass of biomolecules with high accuracy and sensitivity. MS performed under so‐called “native conditions” (native MS) can be used to determine the mass of biomolecules that associate noncovalently. Here we review the application of native MS to the study of protein−ligand interactions and its emerging role in elucidating the structure of macromolecular assemblies, including soluble and membrane protein complexes. Moreover, we discuss strategies aimed at determining the stoichiometry and topology of subunits by inducing partial dissociation of the holo‐complex. We also survey recent developments in "native top‐down MS", an approach based on Fourier Transform MS, whereby covalent bonds are broken without disrupting non‐covalent interactions. Given recent progress, native MS is anticipated to play an increasingly important role for researchers interested in the structure of macromolecular complexes.
Designing InGaN/GaN nano‐LED arrays for étendue‐limited applications
Authors: Fox Sophia , O'Kane Simon , Lis Szymon , Allsopp Duncan
Published: February 2015

This paper presents the far field results of a study by simulation using the finite‐difference time‐domain (FDTD) method of vertical light emitting diode structures with an incorporated ordered nanorod array in place of the typical surface roughened region. For a dipole placed directly below the centre nanorod in the FDTD model, highly collimated light is achieved by changing the radii of the nanorods, for a fixed array pitch, which we attribute mainly to Bragg diffraction. By changing the pitch only, higher diffraction orders are observed in the far field emission as the pitch is increased and a relative increase in the directionality of emission is predicted. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Recent advances in the linearized semiclassical initial value representation/classicalWigner model for the thermal correlation function
Authors: Liu Jian
Published: February 2015

This article focuses on most recent advances in the linearized semiclassical initial value representation (LSC‐IVR)/classical Wigner model that includes quantum effects with classical trajectories and recovers exact thermal correlation functions (of even nonlinear operators, that is, nonlinear functions of position or momentum operators) in the classical, high temperature, and harmonic limits. Two methods for implementing the LSC‐IVR/classical Wigner which are in principle feasible to be combined with general force fields or evenab initioelectronic structure methods have been reviewed. One is the local Gaussian approximation with the imaginary time path integral approach, the other is the quantum thermal bath method. The article emphasizes on the theory and the algorithms for implementation, while it also covers recent applications and limitations of the LSC‐IVR/classical Wigner. © 2015 Wiley Periodicals, Inc.
Theoretical studies on excited states of biorelated systems from gas phase to aqueous solution
Authors: Li Junfeng , Guo Xugeng , Zhao Yuan , Cao Zexing
Published: February 2015

Excited‐state properties of molecules play a pivotal role in understanding their photophysical and photochemical behaviors. With the fast development of computational methodologies, the low‐lying states of biorelated systems have been extensively investigated theoretically. Here, we review our recent works on the excited states of selected nucleobases and their related systems in the gas and condensed phases. The simulated electronic spectra of coumarin reproduce the band shape of experimental spectra and provide a basis to reasonably assign the observed bands. The absorption spectra and the excited‐state dynamics of nucleic acid bases and their analogs in the gas phase and in aqueous solution have been explored by the combined quantum mechanics and molecular mechanics (QM/MM) calculations and QM/MM‐based dynamics simulations with surface hopping. Based on extensive calculations and dynamics simulations, the solvent effects on the excited states and their dynamical behaviors have been discussed. © 2015 Wiley Periodicals, Inc.