bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting SLC1a5‐mediated glutamine dependence in non‐small cell lung cancer
Authors: Hassanein Mohamed , Qian Jun , Hoeksema Megan D. , Wang Jing , Jacobovitz Marie , Ji Xiangming , Harris Fredrick T. , Harris Bradford K. , Boyd Kelli L. , Chen Heidi , Eisenberg Rosana , Massion Pierre P.
Published: March 2015

We previously elucidated the pleotropic role of solute carrier family A1 member 5 (SLC1A5) as the primary transporter of glutamine (Gln), a modulator of cell growth and oxidative stress in non‐small cell lung cancer (NSCLC). The aim of our study was to evaluate SLC1A5 as a potential new therapeutic target and candidate biomarker predictive of survival and response to therapy. SLC1A5 targeting was examined in a panel of NSCLC and human bronchial cell lines by RNA interference and by a small molecular inhibitor, gamma‐l‐glutamyl‐p‐nitroanilide (GPNA). The effects of targeting SLC1A5 on cell growth, Gln uptake, ATP level, autophagy and cell death were examined. Inactivation of SLC1A5 genetically or pharmacologically decreased Gln consumption, inhibited cell growth, induced autophagy and apoptosis in a subgroup of NSCLC cell lines that overexpress SLC1A5. Targeting SLC1A5 function decreased tumor growth in NSCLC xenografts. A multivariate Cox proportional hazards analysis indicates that patients with increased SLC1A5 mRNA expression have significantly shorter overall survival (p = 0.01, HR = 1.24, 95% CI: 1.05–1.46), adjusted for age, gender, smoking history and disease stage. In an immunohistochemistry study on 207 NSCLC patients, SLC1A5 protein expression remained highly significant prognostic value in both univariate (p < 0.0001, HR = 1.45, 95% CI: 1.15–1.50) and multivariate analyses (p = 0.04, HR = 1.22, 95% CI: 1.01–1.31). These results position SLC1A5 as a new candidate prognostic biomarker for selective targeting of Gln‐dependent NSCLC.
F2RL3 methylation, lung cancer incidence and mortality
Authors: Zhang Yan , Schöttker Ben , Ordóñez‐Mena José , Holleczek Bernd , Yang Rongxi , Burwinkel Barbara , Butterbach Katja , Brenner Hermann
Published: March 2015

Smoking accounts for a large share of lung cancer. F2RL3 methylation was recently identified as a biomarker closely reflecting both current and past smoking exposure. We aimed to assess the associations of F2RL3 methylation with lung cancer incidence and mortality. In a large population‐based cohort study, F2RL3 methylation was measured in baseline blood samples of 4,987 participants by MassARRAY. Associations of F2RL3 methylation and smoking with lung cancer incidence/mortality during a median follow‐up of 10.9 years were assessed by Cox regression, controlling for potential confounders. The ability of F2RL3 methylation to predict lung cancer was examined by Harrell's C statistics. Hypomethylation at F2RL3 was strongly associated with both lung cancer incidence and mortality, with age‐ and sex‐adjusted hazard ratios (HR; 95% CI) of 9.99 (5.61–17.79) and 16.86 (8.53–33.34), respectively, for participants whose methylation intensity were ≤0.54 compared with whose methylation intensity were ≥0.75. Strongly elevated HRs of 2.88 (1.42–5.84) and 5.17 (2.28–11.70) persisted even after controlling for multiple covariates including smoking status and pack‐years. With fully adjusted HRs of 9.92 (2.88–34.12) and 16.48 (4.10–66.15), the associations between methylation and the two outcomes were particularly strong among participants≥65 years. Combination of F2RL3 methylation and pack‐years predicted lung cancer incidence with high accuracy (optimism‐corrected Harrell's C statistics = 0.86 for participants≥65 years). These findings suggested that F2RL3 methylation is a very strong predictor of lung cancer risk and mortality, particularly at older age. The potential implications of F2RL3 methylation for early detection, risk stratification and prevention of lung cancer warrant further exploration.
From small fullerenes to the graphene limit: A harmonic force‐field method for fullerenes and a comparison to density functional calculations for Goldberg–Coxeter fullerenes up to C980
Authors: Wirz Lukas N. , Tonner Ralf , Hermann Andreas , Sure Rebecca , Schwerdtfeger Peter
Published: March 2015

We introduce a simple but computationally very efficient harmonic force field, which works for all fullerene structures and includes bond stretching, bending, and torsional motions as implemented into our open‐source code Fullerene. This gives accurate geometries and reasonably accurate vibrational frequencies with root mean square deviations of up to 0.05 Å for bond distances and 45.5 cm−1 for vibrational frequencies compared with more elaborate density functional calculations. The structures obtained were used for density functional calculations of Goldberg–Coxeter fullerenes up to C980. This gives a rather large range of fullerenes making it possible to extrapolate to the graphene limit. Periodic boundary condition calculations using density functional theory (DFT) within the projector augmented wave method gave an energy difference between −8.6 and −8.8 kcal/mol at various levels of DFT for the reaction C60→graphene (per carbon atom) in excellent agreement with the linear extrapolation to the graphene limit (−8.6 kcal/mol at the Perdew–Burke–Ernzerhof level of theory). © 2015 Wiley Periodicals, Inc.
The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels
Authors: Campiglio Marta , Flucher Bernhard E.
Published: March 2015

Voltage‐gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore‐forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice‐variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre‐existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc.
The relation between circulation types and regional Alpine climate. Part I: synoptic climatology of Trentino
Authors: Panziera L. , Giovannini L. , Laiti L. , Zardi D.
Published: March 2015

A comprehensive data set of surface temperature, rainfall, solar radiation and wind measurements was composed to investigate the relation between synoptic circulation types and the climate of Trentino, a mountainous region in the South‐Eastern Alps. Synoptic patterns are classified over different levels by means of an existing classification method according to their degree of zonality, meridionality and vorticity. Distinct seasonal anomalies of mean daily temperature, total daily rainfall, daily solar irradiation and mean daily wind intensity are associated with most circulation types. Their magnitude varies not only among weather types, but also within the same type for different isobaric levels and seasons. The largest positive temperature anomalies are observed in correspondence with high‐pressure and westerly circulations, whereas southerly circulation in the upper levels and low‐pressure systems at lower altitudes produce the largest positive deviations of daily rainfall. Daily solar irradiation and mean daily wind intensity are larger than average with northerly circulations. Particular emphasis is given to extreme meteorological events, which occur with preferential circulation types. In fact, the frequency of occurrence of extremes of any variable for each synoptic pattern rarely coincides with the climatological value. Even though extremes in daily rainfall are observed with almost all synoptic circulations, most of them occur with the south‐westerly circulation at 500 hPa, a frequent configuration contributing more than 50% to the total rainfall. Moreover, they occur with a larger variety of weather types at the lower levels and in spring and summer with respect to the upper levels and the colder seasons. The large number of statistical indices presented in this paper reveals that the climate of Trentino is strongly influenced not only by the synoptic circulation, but also by the mesoscale mechanisms resulting from the interaction of the large‐scale flow with the local orography.
Levels of potential bioactive compounds including carotenoids, vitamin C and phenolic compounds, and expression of their cognate biosynthetic genes vary significantly in different varieties of potato (Solanum tuberosum L.) grown under uniform cultural conditions
Authors: Valcarcel Jesus , Reilly Kim , Gaffney Michael , O'Brien Nora M
Published: March 2015

BACKGROUND

In addition to their high carbohydrate content, potatoes are also an important dietary source of vitamin C and bioactive secondary metabolites, including phenolic compounds and carotenoids, which have been suggested to play a role in human health. The expression of genes encoding key enzymes involved in the synthesis of these compounds was assessed by reverse transcription–quantitative polymerase chain reaction and compared to the accumulation of the corresponding product in seven potato varieties showing contrasting levels of metabolite accumulation.

RESULTS

Strong positive correlations were found between phenolic content in the flesh of tubers and transcript levels of phenylalanine ammonia lyase (PAL) and chalcone synthase (CHS) genes. The expression of PAL and CHS was also related to that of AN1, a transcription factor involved in the synthesis of anthocyanins, suggesting that these genes are regulated in a coordinated manner. No clear relationship was found between transcript levels of phytoene synthase (PSY) or l‐galactono‐1,4‐lactone dehydrogenase (GLDH) genes and total carotenoid or vitamin C accumulation, respectively.

CONCLUSION

Data indicate that levels of total phenolic and flavonoid compounds in potato are controlled primarily by PAL and CHS gene expression. Transcript levels of PSY and GLDH did not control accumulation of carotenoids or vitamin C. © 2015 Society of Chemical Industry
Effect of borojo (Borojoa patinoi Cuatrecasas) three‐phase composition and gum arabic on the glass transition temperature
Authors: Rodríguez‐Bernal Jenny M , Tello Edisson , Flores‐Andrade Enrique , de Jesús Perea‐Flores Maria , Vallejo‐Cardona Alba A , Gutiérrez‐López Gustavo F , Quintanilla‐Carvajal Maria X
Published: March 2015

BACKGROUND

The search for natural, novel, high‐quality, stable food ingredients is an ongoing practice in the food industry. Pulp of borojo (Borojoa patinoi Cuatrecasas), which is a fruit of the Colombian Pacific region, can be separated into three phases: liquid (LP), medium (MP) and solid (SP) phases. The objective of this work was to evaluate the effect of the three‐phase composition and gum arabic on their glass transitions temperatures (Tg). The best mixture, LP‐MP, MP‐SP and LP‐SP and gum arabic (GA) was identified by response surface methodology.

RESULTS

When adding GA to SP borojo phase in a 1:1 proportion, the resulting Tg of the mixture was 132.27 °C whereas Tg for GA and SP‐phase were 154.89 °C and 79.86 °C respectively, which supported this combination as attractive from a processing perspective and supports an industrial advantage of using borojo as food ingredient. Phases were characterized by high‐performance liquid chromatography, Fourier transform infrared spectroscopy, confocal laser scanning microscopy and mass spectrometry. Low molecular weight compounds such as fructose for MP lowered Tg whereas the presence of lignin increased Tg of the mixtures as with the SP.

CONCLUSIONS

The addition of GA significantly increased Tg of borojo phases so leading to propose them as novel food processing materials. © 2015 Society of Chemical Industry
Surveying Treatment Preferences in U.S. Iraq–Afghanistan Veterans With PTSD Symptoms: A Step Toward Veteran‐Centered Care
Authors: Crawford Eric F. , Elbogen Eric B. , Wagner H. Ryan , Kudler Harold , Calhoun Patrick S. , Brancu Mira , Straits‐Troster Kristy A.
Published: March 2015

This study examined health care barriers and preferences among a self‐selected sample of returning U.S. veterans drawn from a representative, randomly selected frame surveyed about posttraumatic stress disorder (PTSD) symptomatology and mental health utilization in the prior year. Comparisons between treated (n = 160) and untreated (n = 119) veterans reporting PTSD symptoms were conducted for measures of barriers and preferences, along with logistic models regressing mental health utilization on clusters derived from these measures. Reported barriers corroborated prior research findings as negative beliefs about treatment and stigma were strongly endorsed, but only privacy concerns were associated with lower service utilization (B = −0.408, SE = 0.142; p = .004). The most endorsed preference (91.0%) was for assistance with benefits, trailed by help for physical problems, and particular PTSD symptoms. Help‐seeking veterans reported stronger preferences for multiple interventions, and desire for services for families (B = 0.468, SE = 0.219; p = .033) and specific PTSD symptoms (B = 0.659, SE = 0.302; p = .029) were associated with increased utilization. Outcomes of the study suggested PTSD severity drove help‐seeking in this cohort. Results also support the integration of medical and mental health services, as well as coordination of health and benefits services. Finally, the study suggested that outreach about privacy protections and treatment options could well improve engagement in treatment.
RAFT Polymerization of Phenyl Vinyl Sulfide Using Trithiocarbonate Mediating Agents and Synthesis of Block Copolymers
Authors: Abiko Yohei , Nakabayashi Kazuhiro , Mori Hideharu
Published: March 2015

Reversible addition‐fragmentation chain transfer (RAFT) polymerization of phenyl vinyl sulfide (PVS), in which the thioether moiety is directly connected to the vinyl group, was investigated using trithiocarbonates as chain transfer agents (CTAs). A trithiocarbonate with a 2‐cyano‐2‐propyl group in the R moiety was found to be effective in achieving controlled radical polymerization of the S‐vinyl monomer. Reasonable control of the polymerization of PVS was indicated by the formation of a narrow dispersity polymer, molecular weight controlled by the monomer/CTA molar ratio, a linear increase in molecular weight with the conversion, and preserved chain end structure (determined by 1H NMR). Well‐defined block copolymers were synthesized by RAFT polymerization of PVS using polystyrene macro‐CTA.
The Impact of Monitoring and Sanctions on Cheating: Experimental Evidence from Tunisia
Authors: Békir Insaf , Harbi Sana El. , Grolleau Gilles , Mzoughi Naoufel , Sutan Angela
Published: March 2015

Using a laboratory experiment in a developing country (Tunisia, North Africa), we investigate whether the level of monitoring and both the nature (monetary versus moral) and magnitude of sanctions influence cheating levels. Our findings show that the introduction of weak monetary sanctions and monitoring is likely to increase cheating. However, a perfect monitoring is found to decrease the level of cheating. Moreover, when combined with a perfect monitoring, moral sanctions matter and may be even more effective than strong monetary sanctions in reducing cheating. We draw some policy implications regarding cheating in various domains. Copyright © 2015 John Wiley & Sons, Ltd.
Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development
Authors: Muellner Julia , Delmaire Christine , Valabrégue Romain , Schüpbach Michael , Mangin Jean‐François , Vidailhet Marie , Lehéricy Stéphane , Hartmann Andreas , Worbe Yulia
Published: March 2015

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre‐ and post‐central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive‐compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive‐compulsive disorder measured by Yale Global Tic severity scale and Yale‐Brown Obsessive‐Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS. © 2015 International Parkinson and Movement Disorder Society
Encapsulation of PV Modules Using Ethylene Vinyl Acetate Copolymer as the Encapsulant
Authors: Jiang Shan , Wang Kemin , Zhang Hongwen , Ding Yonghong , Yu Qiang
Published: March 2015

Ethylene vinyl acetate (EVA) encapsulation materials have attracted a lot of attention due to their extensive applications in solar cells. Nearly 80% of photovoltaic (PV) modules are encapsulated by EVA materials. EVA has lots of advantages, such as good light transmittance and elasticity, low processing temperature, excellent melt fluidity, and adhesive property. In addition, the price is low, which makes it very suitable as a solar cell encapsulation material. However, there are also some problems with EVA. Its damp‐heat aging resistance and ultraviolet aging resistance are not good. It also easily degrades and becomes yellow, reducing the energy conversion efficiency of the solar cell. This article pays special attention to improving the performance of EVA encapsulation films. In addition, it differentiates between different properties, including the aging resistance, adhesive strength and energy conversion efficiency.
Alternation of Pore Architecture of Ziegler–Natta Catalysts through Modification of Magnesium Ethoxide
Authors: Funako Toshiki , Chammingkwan Patchanee , Taniike Toshiaki , Terano Minoru
Published: March 2015

The present article proposes a simple way to dramatically alter the pore architecture of Mg(OEt)2‐based Ziegler–Natta catalysts by the addition of a small amount of i‐propanol during the synthesis of Mg(OEt)2. The incorporated i‐propoxide distorts the crystalline structure of Mg(OEt)2, finally causing the phase transformation and significant densification of particles. Such modifications completely alternate the pore architecture of resultant catalysts, which contribute to the design of catalytic properties.
Measurement of distinctive features of cortical spreading depolarizations with different MRI contrasts
Authors: Umesh Rudrapatna S. , Hamming Arend M. , Wermer Marieke J. H. , van der Toorn Annette , Dijkhuizen Rick M.
Published: March 2015

Growing clinical evidence suggests critical involvement of spreading depolarizations (SDs) in the pathophysiology of neurological disorders such as migraine and stroke. MRI provides powerful tools to detect and assess co‐occurring cerebral hemodynamic and cellular changes during SDs. This study reports the feasibility and advantages of two MRI scans, based on balanced steady‐state free precession (b‐SSFP) and diffusion‐weighted multi‐spin‐echo (DT2), heretofore unexplored for monitoring SDs. These were compared with gradient‐echo MRI. SDs were induced by KCl application in rat brain. Known for high SNR, the T2‐ and T1‐based b‐SSFP contrast was hypothesized to provide higher spatiotemporal specificity than ‐based gradient‐echo scanning. DT2 scanning was designed to provide simultaneous T2 and apparent diffusion coefficient (ADC) measurements, thus enabling combined quantitative assessment of hemodynamic and cellular changes during SDs.

Procedures were developed to automate identification of SD‐induced responses in all the scans. These responses were analyzed to determine detection sensitivity and temporal characteristics of signals from each scanning method. Cluster analysis was performed to elucidate unique temporal patterns for each contrast.

All scans allowed detection of SD‐induced responses. b‐SSFP scans showed significantly larger relative intensity changes, narrower peak widths and greater spatial specificity compared with gradient‐echo MRI. SD‐induced effects on ADC, calculated from DT2 scans, showed the most pronounced signal changes, displaying about 20% decrease, as against 10–15% signal increases observed with b‐SSFP and gradient‐echo scanning. Cluster analysis revealed additional temporal sub‐patterns, such as an initial dip on gradient‐echo scans and temporally shifted T2 and proton density changes in DT2 data.

To summarize, b‐SSFP and DT2 scanning provide distinct information on SDs compared with gradient‐echo MRI. DT2 scanning, with its potential to simultaneously provide cellular and hemodynamic information, can offer unique information on the inter‐relationship between these processes in pathologic brain, which may improve monitoring of spreading depolarizations in (pre)clinical settings. Copyright © 2015 John Wiley & Sons, Ltd.
A GPU‐based preconditioned Newton‐Krylov solver for flexible multibody dynamics
Authors: Serban Radu , Melanz Daniel , Li Ang , Stanciulescu Ilinca , Jayakumar Paramsothy , Negrut Dan
Published: March 2015

This paper describes an approach to numerically approximate the time evolution of multibody systems with flexible (compliant) components. Its salient attribute is that at each time step, both the formulation of the system equations of motion and their numerical solution are carried out using parallel computing on graphics processing unit cards. The equations of motion are obtained using the absolute nodal coordinate formulation, yet any other multibody dynamics formalism would fit equally well the overall solution strategy outlined herein. The implicit numerical integration method adopted relies on a Newton–Krylov methodology and a parallel direct sparse solver to precondition the underlying linear system. The proposed approach, implemented in a software infrastructure available under an open‐source BSD‐3 license, leads to improvements in overall simulation times of up to one order of magnitude when compared with matrix‐free parallel solution approaches that do not use preconditioning. Copyright © 2015 John Wiley & Sons, Ltd.
Solving quasi‐static equations with the material‐point method
Authors: Sanchez J. , Schreyer H. , Sulsky D. , Wallstedt P.
Published: March 2015

The material‐point method models continua by following a set of unconnected material points throughout the deformation of a body. This set of points provides a Lagrangian description of the material and geometry. Information from the material points is projected onto a background grid where equations of motion are solved. The grid solution is then used to update the material points. This paper describes how to use this method to solve quasi‐static problems. The resulting discrete equations are a coupled set of nonlinear equations that are then solved with a Jacobian‐free, Newton–Krylov algorithm. The technique is illustrated by examining two problems. The first problem simulates a compact tension test and includes a model of material failure. The second problem computes effective, macroscopic properties of a polycrystalline thin film. Copyright © 2015 John Wiley & Sons, Ltd.
A non‐intrusive model reduction approach for polynomial chaos expansion using proper orthogonal decomposition
Authors: Raisee M. , Kumar D. , Lacor C.
Published: March 2015

In this paper, a non‐intrusive stochastic model reduction scheme is developed for polynomial chaos representation using proper orthogonal decomposition. The main idea is to extract the optimal orthogonal basis via inexpensive calculations on a coarse mesh and then use them for the fine‐scale analysis. To validate the developed reduced‐order model, the method is implemented to: (1) the stochastic steady‐state heat diffusion in a square slab; (2) the incompressible, two‐dimensional laminar boundary‐layer over a flat plate with uncertainties in free‐stream velocity and physical properties; and (3) the highly nonlinear Ackley function with uncertain coefficients. For the heat diffusion problem, the thermal conductivity of the slab is assumed to be a stochastic field with known exponential covariance function and approximated via the Karhunen–Loève expansion. In all three test cases, the input random parameters are assumed to be uniformly distributed, and a polynomial chaos expansion is found using the regression method. The Sobol's quasi‐random sequence is used to generate the sample points. The numerical results of the three test cases show that the non‐intrusive model reduction scheme is able to produce satisfactory results for the statistical quantities of interest. It is found that the developed non‐intrusive model reduction scheme is computationally more efficient than the classical polynomial chaos expansion for uncertainty quantification of stochastic problems. The performance of the developed scheme becomes more apparent for the problems with larger stochastic dimensions and those requiring higher polynomial order for the stochastic discretization. Copyright © 2015 John Wiley & Sons, Ltd.
Irisin levels before and after physical activity among school‐age children with different BMI: A direct relation with leptin
Authors: Palacios‐González Berenice , Vadillo‐Ortega Felipe , Polo‐Oteyza Ernestina , Sánchez Teresa , Ancira‐Moreno Monica , Romero‐Hidalgo Sandra , Meráz Noemi , Antuna‐Puente Barbara
Published: March 2015

Objective

Irisin is a novel myokine that seems to mediate the beneficial effects of exercise. Levels of circulating irisin before and after an 8‐month physical activity program (PAP) in school‐age children were evaluated.

Methods

Irisin and leptin were measured at baseline and at follow‐up among 85 children with different BMI.

Results

Of the 85 children (mean age 8.9; 47% female), 25 children had normal weight, 23 were overweight, and 37 had obesity. We observed no significant difference in irisin serum levels between boys and girls. Irisin was positively associated with BMI before and after the PAP (rbefore = 0.42; rafter = 0.37, P < 0.001), with the highest levels in children with obesity. There was a slight decrease of circulating irisin after PAP, but this decrease was not of statistical significance. We observed a high and positive association between irisin and leptin levels before and after the PAP (rbefore = 0.78; rafter = 0.82, P < 0.001). Moreover, changes in leptin correlated with changes in irisin (r = 0.72, P < 0.001).

Conclusions

Circulating irisin is positively linked to BMI and leptin in school‐age children, supporting the notion that that irisin is produced by adipose tissue. As in previous reports, this study failed to observe changes in irisin levels after exercise, likely because higher irisin levels are produced only during exercise.
Systematic review and meta‐analysis of objective and subjective quality of life among pediatric, adolescent, and young adult bone tumor survivors
Authors: Stokke Jamie , Sung Lillian , Gupta Abha , Lindberg Antoinette , Rosenberg Abby R.
Published: March 2015

Background

Pediatric, adolescent, and young adult survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta‐analysis to summarize the literature describing QOL in this population and differences in QOL based on local control procedures.

Procedure

Included studies described ≥5 patients <25 years old who had completed local control treatment for bone sarcoma, defined QOL as a main outcome, and measured it with a validated instrument. Data extraction and quality assessments were conducted with standardized tools. Meta‐analyses compared QOL based on surgical procedure (limb‐sparing vs. amputation) and were stratified by assessment type (objective physical function, clinician‐assessed disability, patient‐reported disability, and patient‐reported QOL). Effect sizes were reported as the standard mean difference when multiple instruments were used within a comparison and weighted mean difference otherwise. All were weighted by inverse variance and modeled with random effects.

Results

Twenty‐two of 452 unique manuscripts were included in qualitative syntheses, eight of which were included in meta‐analyses. Manuscripts were heterogeneous with respect to included patient populations (age, tumor type, time since treatment) and QOL instruments. Prospective studies suggested that QOL improves over time, and that female sex and older age at diagnosis are associated with poor QOL. Meta‐analyses showed no differences in outcomes between patients who underwent limb‐sparing versus amputation for local control.

Conclusion

QOL studies among children and AYAs with bone sarcoma are remarkably diverse, making it difficult to detect trends in patient outcomes. Future research should focus on standardized QOL instruments and interpretations. Pediatr Blood Cancer 2015;62:1616–1629. © 2015 Wiley Periodicals, Inc.
L‐Asparaginase lowers plasma antithrombin and mannan‐binding‐lectin levels: Impact on thrombotic and infectious events in children with acute lymphoblastic leukemia
Authors: Merlen Clémence , Bonnefoy Arnaud , Wagner Eric , Dedeken Laurence , Leclerc Jean‐Marie , Laverdière Caroline , Rivard Georges‐Etienne
Published: March 2015

Background

L‐asparaginase, a key therapeutic agent in the management of patients with acute lymphoblastic leukemia (ALL), dramatically impairs hepatic protein synthesis. We investigated the effects of prolonged exposure to L‐asparaginase on antithrombin (AT), fibrinogen and mannan‐binding‐lectin (MBL) levels, and on the occurrence of thrombotic events (TE) and febrile neutropenia episodes (FN) in pediatric patients.

Procedure

Protein levels were measured in 97 children during 30 weeks of chemotherapy with L‐asparaginase and up to 1 year following remission. TE and FN episodes were recorded during this period.

Results

Median AT level decreased from 0.96 IU/mL prior to treatment (range: 0.69–1.38) to 0.55 IU/mL (0.37–0.76) during therapy. Fibrinogen and MBL decreased from 3.18 g/L (1.29–7.28) and 1,177 ng/mL (57–5,343) to 1.56 g/L (0.84–2.13) and 193 ng/mL (57–544), respectively. All three proteins had recovered 1–4 weeks after L‐asparaginase cessation. TE were reported in 22 (23%) patients. Of these, 11 occurred after a median of 10 administrations of L‐asparaginase. Fifty‐one FN were associated with infections, of which 36 occurred during treatment with L‐asparaginase. Patients with low levels of MBL at diagnosis were at higher risk of FN associated with infections (RR = 1.59, 95%CI: 1.026–2.474). Both AT and MBL decreases were moderately correlated with fibrinogen (r = 0.51 and 0.58, respectively).

Conclusions

Children with ALL are exposed to significant decrease in AT, fibrinogen and MBL levels, and concomitant increased risk of thrombosis and FN with infection during L‐asparaginase treatment. Measuring plasma levels of these liver‐derived proteins could help predict the occurrence of adverse events. Pediatr Blood Cancer 2015;62:1381–1387. © 2015 Wiley Periodicals, Inc.
Energetics and structural characterization of isomers using ion mobility and gas‐phase H/D exchange: Learning from lasso peptides
Authors: Hanozin Emeline , Morsa Denis , De Pauw Edwin
Published: March 2015

State‐of‐the‐art characterization of proteins using MS namely relies on fragmentation methods that allow exploring featured dissociative reaction pathways. These pathways are often initiated by a series of potentially informative mass‐constant conformational changes that are nonetheless frequently overlooked by lack of adequate investigation techniques. In the present study, we propose a methodology to readily address both structural and energetic aspects of stereoisomerization reactions using ion mobility coupled with MS. To this end, a commercial spectrometer was used as a reactor comprising an energy resolved collisional activation step intended at promoting controlled conformational changes and a structural assignment step dedicated to the identification of the generated isomers. This identification relies on ion mobility and other on‐line coupled techniques, namely an originally designed gas‐phase H/D exchange experiment. We here apply this methodology to characterize the isomerization kinetics of capistruin, a 19‐residue long lasso‐folded peptide. We expect this approach to bring insights into the physical origin of global dissociation thresholds monitored in MS/MS experiments and to set a promising basis for quantitative investigations of the stability of different molecular folds.
Moisture Proofing of Spray Dried Particles Comprising Ammonium Nitrate/Potassium Nitrate/Polymer
Authors: Nagayama Seiichiro , Katoh Katsumi , Higashi Eiko , Hayashi Masahiko , Kumagae Kosuke , Habu Hiroto , Wada Yuji , Nakano Katsuyuki , Arai Mitsuru
Published: March 2015

The aim of this study was to fabricate moisture‐proof, phase‐stabilized, ammonium nitrate/potassium nitrate (AN/PN) particles, with a polymer used as the moisture‐proofing agent. The particles were prepared with a spray drying technique. Water solutions (or water dispersions) containing AN/PN and one of five different types of polymer were spray‐dried, which produced white powders with particle diameters of approximately 20–40 μm. Scanning electron microscopy and energy‐dispersive X‐ray spectroscopy indicated that each component was homogeneously distributed throughout the particles. The particles exhibited little aggregation compared to the reagent AN, even when left for 7 d or more. In addition, the moisture absorption of the particles at less than 40 % relative humidity (RH) was lower than that of the polymer‐free particles. Even under high‐moisture conditions (83 % RH), the particles did not deliquesce immediately, and they retained their original shape for 30–60 min, whereas the polymer‐free particles were transformed into droplets within 5 min.
Defect‐enabled electrical current leakage in ultraviolet light‐emitting diodes
Authors: Moseley Michael W. , Allerman Andrew A. , Crawford Mary H. , Wierer Jonathan J. , Smith Michael L. , Biedermann Laura B.
Published: March 2015

Electrical current leakage paths in AlGaN‐based ultraviolet (UV) light‐emitting diodes (LEDs) are identified using conductive atomic force microscopy. Open‐core threading dislocations are found to conduct current through insulating Al0.7Ga0.3N layers. A defect‐sensitive H3PO4 etch reveals these open‐core threading dislocations as 1–2 µm wide hexagonal etch pits visible with optical microscopy. Additionally, closed‐core threading dislocations are decorated with smaller and more numerous nanometer‐scale pits, which are quantifiable by atomic‐force microscopy. The performances of UV‐LEDs fabricated on similar Si‐doped Al0.7Ga0.3N templates are found to have a strong correlation to the density of these electrically conductive open‐core dislocations, while the total threading dislocation densities of the UV‐LEDs remain relatively unchanged.
High‐pressure effects on the intersubband optical absorption coefficient and relative refractive index change in an asymmetric double ‐doped GaAs quantum well
Authors: Rodríguez‐Magdaleno K. A. , Martínez‐Orozco J. C. , Rodríguez‐Vargas I. , Mora‐Ramos M. E. , Duque C. A.
Published: March 2015

In the framework of the effective mass approximation and using a Thomas–Fermi‐like model for the conduction band potential energy profile, the effects of hydrostatic pressure on the linear and nonlinear intersubband optical response of an asymmetric double ‐doped quantum well are studied. In particular, the intersubband coefficients of light absorption and the relative refractive index change in the system were calculated. It is found that the pressure causes a redshift of the signal response as well as a reduction in the coefficients's amplitudes. We have also found that the asymmetry of the potential profile clearly affects the relative refractive index change because, as long as the system becomes more asymmetric, this physical property becomes diminished.
Effective Control Charts for Monitoring the NGINAR(1) Process
Authors: Li Cong , Wang Dehui , Zhu Fukang
Published: March 2015

In recent years, there has been a growing interest in the control of autocorrelated count data. Existing results focus on the Poisson integer‐valued autoregressive (INAR) process, but this process cannot deal with overdispersion (variance is greater than mean), which is a common phenomenon in count data. We propose to control the autocorrelated count data based on a new geometric INAR (NGINAR) process, which is an alternative to the Poisson one. In this paper, we use the combined jumps chart, the cumulative sum chart, and the combined exponentially weighted moving average chart to detect the shift of parameters in the process. We compare the performance of these charts for the case of an underlying NGINAR(1) process in terms of the average run lengths. One real example is presented to demonstrate good performances of the charts. Copyright © 2015 John Wiley & Sons, Ltd.
Study on Yield Function and Plastic Potential Under Non‐Associated Flow for Accurate Earing Prediction in Cup Drawing
Authors: Paulino Mariana , Yoon Jeong Whan
Published: March 2015

Prediction of more than four ears in a cup drawing process can be successfully achieved by considering r‐value and stress directionalities. Yld2004‐18p based on associated flow ruleand Yld2000‐2D based on non‐associated flow ruleare the examples. The former, however, is more costly in terms of computational efficiency than the latter. In this work, an anisotropic constitutive model based on non‐associated flow rule which combines two different functions, Hill (1948) and Yld2000‐2d, is implemented to a user defined material model. The accuracy of the anisotropic directionalities (yield stresses and plastic strain ratios) is evaluated. Simulation of a mini‐die cup drawing with a body stock alloy predicted eight ears, in good agreement with the experimental results. The use of Hill (1948) model for the yield function and Yld2000‐2d for plastic potential under the framework of non‐associated flow rule led to accurate prediction of up to eight ears at the lower computational cost.
Optimal sample planning for system state analysis with partial data collection
Authors: Heller Martin , Hannig Jan , Leadbetter Malcolm R.
Published: March 2015

We develop optimal and computationally practical procedures to minimize uncertainty concerning the presence of dangerous levels of a contaminant within a building when neither replication nor complete data collection is feasible. More generally, we address inference about the state of a finite system when the state is related to information collected over components of the system when only partial data collection is feasible. When there is no correlation between sample locations, a simple random sample or maximum a priori trait presence would provide optimal sampling choices. When complicated probability models describe trait manifestation, the need to collect only partial data precludes a full fitting of complicated models, and one must rely heavily on prior information naturally leading to a Bayesian approach. Herein, we introduce a computationally efficient heuristic algorithm to simultaneously find optimal sample locations and decision rule parameterizations and then show that it drastically outperforms both random selection and maximum a priori methods. Copyright © 2015 John Wiley & Sons, Ltd.
Preparation, characterization, water solubility, and targeted delivery of linear dextrin‐conjugated linoleic acid inclusion complex
Authors: Chang Qingqing , Zhou Xing , Wu Chunsen , Xu Xueming , Jin Zhengyu
Published: March 2015

A linear dextrin (LD)‐conjugated linoleic acid (CLA) inclusion complex was prepared using LD obtained from debranched waxy corn starch as an encapsulation wall material. The aim was to prepare a nontoxic CLA product with improved water solubility and controlled release in small intestine by encapsulating CLA with the water‐soluble LD. The optimal complexation temperature, volume of ethanol used to dissolve CLA, and mass ratio of LD to CLA were 30°C, 1 mL, 12:1, respectively. Thermogravimetric analysis and Fourier transform infrared spectroscopy showed that CLA was successfully encapsulated by LD. The solubility of the LD‐CLA complex greatly improved from 62.64 to 91.05% when the temperature was increased from 20 to 90°C. A total of 34.1% CLA of the LD‐CLA complex was released into a simulated small intestine environment. Therefore, LD can improve the solubility of the complex and enable the targeted delivery of functional lipids and other bioactive components to the small intestine.
Patterning, specification, and differentiation in the developing hypothalamus
Authors: Bedont Joseph L. , Newman Elizabeth A. , Blackshaw Seth
Published: March 2015

Owing to its complex structure and highly diverse cell populations, the study of hypothalamic development has historically lagged behind that of other brain regions. However, in recent years, a greatly expanded understanding of hypothalamic gene expression during development has opened up new avenues of investigation. In this review, we synthesize existing work to present a holistic picture of hypothalamic development from early induction and patterning through nuclear specification and differentiation, with a particular emphasis on determination of cell fate. We will also touch on special topics in the field including the prosomere model, adult neurogenesis, and integration of migratory cells originating outside the hypothalamic neuroepithelium, and how these topics relate to our broader theme. WIREs Dev Biol 2015, 4:445–468. doi: 10.1002/wdev.187

This article is categorized under:

Nervous System Development > Vertebrates: General Principles
One‐Pot Lipase Entrapment Within Silica Particles to Prepare a Stable and Reusable Biocatalyst for Transesterification
Authors: Katiyar Madhu , Ali Amjad
Published: March 2015

In order to enhance the reusability, Rhizomucor miehei lipase was entrapped in a single step within silica particles having an oleic acid core (RML@SiO2). Characterization of RML@SiO2 by scanning and transmission electron microscopy and Fourier transform infrared studies supported the lipase immobilization within silica particles. The immobilized enzyme was employed for transesterification of cottonseed oil with methanol and ethanol. Under the optimum reaction conditions of a methanol‐to‐oil molar ratio of 12:1 or ethanol‐to‐oil molar ratio of 15:1, stirring speed of 250 revolutions/min (flask radius = 3 cm), reaction temperature of 40 °C, and biocatalyst concentration of 5 wt% (with respect to oil), more than 98 % alkyl ester yield was achieved in 16 and 24 h of reaction duration in case of methanolysis and ethanolysis, respectively. The immobilized enzyme did not require any buffer solution or organic solvent for optimum activity; hence, the produced biodiesel and glycerol were free from metal ion or organic molecule contamination. The activation energies for the immobilized enzyme‐catalyzed ethanolysis and methanolysis were found to be 34.9 ± 1.6 and 19.7 ± 1.8 kJ mol−1, respectively. The immobilized enzyme was recovered from the reaction mixture and reused in 12 successive runs without significant loss of activity. Additionally, RML@SiO2 demonstrated better reusability as well as stability in comparison to the native enzyme as the former did not lose the activity even upon storage at room temperature (25–30 °C) over an 8‐month period.
Palliative medicine fellows attend to compassion fatigue using John Stone’s ‘Talking to the Family’
Authors: Groninger Hunter
Published: March 2015

For graduate medical education trainees, as well as contemporary practitioners, developing skills in recognizing compassion fatigue and practising self-care is vital to professional sustainability. The field of palliative medicine is no exception. In our fellowship programme, we use John Stone’s poem, ‘Talking to the Family,’ to engage trainees in a professional development workshop on personal experiences and strategies for self-care.
‘Humeanism’
Authors: STRAWSON GALEN
Published: March 2015

In metaphysics, the adjective ‘Humean’ is used to describe positions that deny the existence of any necessary connection or causal influence in concrete reality. This usage has been significantly reinforced by David Lewis's employment of ‘Humean’ in the phrase ‘Humean supervenience’. It is, however, not at all clear that this usage is appropriate. Lewis himself raised a doubt about it.
David Lewis, Donald C. Williams, and the History of Metaphysics in the Twentieth Century
Authors: FISHER A. R. J.
Published: March 2015

The revival of analytic metaphysics in the latter half of the twentieth century is typically understood as a consequence of the critiques of logical positivism, Quine's naturalization of ontology, Kripke's Naming and Necessity, clarifications of modal notions in logic, and the theoretical exploitation of possible worlds. However, this explanation overlooks the work of metaphysicians at the height of positivism and linguisticism that affected metaphysics of the late twentieth century. Donald C. Williams is one such philosopher. In this paper I explain how Williams's fundamental ontology and philosophy of time influenced in part the early formation of David Lewis's metaphysics. Thus, Williams played an important role in the revival of analytic metaphysics.