bluuebunny/crossref_metadata_2025 huggingface dataset:
Möbius Museology: Curating and Critiquing the Multiversity Galleries at the Museum of Anthropology at the University of British Columbia
Authors: Kramer Jennifer
Published: May 2015

This chapter reflects on the process, product, and reception of collaborative curation at the UBC Museum of Anthropology's new visible storage galleries by discussing the reinstallation of Kwakwaka'wakw and Nuxalk collections. The metaphor of the Möbius strip explains how collaborative museology entails mutual engagements and processual relations, and makes clear the futility of asking who is in front of and who is behind the museum display case glass. What is on display is the relationships between curators, community members, and critics. As a consequence, the museum becomes a potentially potent location for the assertion of social status and cultural knowledge. In fact, it is these acts of cultural translation and mistranslation, legitimizing of community values, and claims to authority that are being exhibited. Reception and critique feed into curation and representation, making the space of the museum engendering as well as portraying.
Chondroitin Sulfate‐Coated DNA‐Nanoplexes Enhance Transfection Efficiency by Controlling Plasmid Release from Endosomes: A New Insight into Modulating Nonviral Gene Transfection
Authors: Yan Hongji , Oommen Oommen P. , Yu Di , Hilborn Jöns , Qian Hong , Varghese Oommen P.
Published: May 2015

Degradation of plasmid DNA (pDNA) in the endosome compartment and its release to the cytosol are the major hurdles for efficient gene transfection. This is generally addressed by using transfection reagents that can overcome these limitations. In this article, the first report is presented which suggests that controlling the release of pDNA from endosome is the key for achieving efficient transfection. In this study, chondroitin sulfate (CS)‐coated DNA‐nanoplexes are developed using a modular approach where CS is coated post‐pDNA/PEI nanoplex formation. To ensure good stability of the nanoplexes, imine/enamine chemistry is exploited by reacting aldehyde‐modified chondroitin sulfate (CS‐CHO) with free amines of pDNA/PEI complex. This supramolecular nanocarrier system displays efficient cellular uptake, and controlled endosomal pDNA release without eliciting any cytotoxicity. On the contrary, burst release of pDNA from endosome (using chloroqine) results in significant reduction in gene expression. Unlike pDNA/PEI‐based transfection, the nanoparticle design presented here shows exceptional stability and gene transfection efficiency in different cell lines such as human colorectal cancer cells (HCT116), human embryonic kidney cells (HEK293), and mouse skin‐derived mesenchymal stem cells (MSCs) using luciferase protein as a reporter gene. This new insight will be valuable in designing next generation of transfection reagents.
N,N′‐Dioxide/Zinc Bis(trifluoromethylsulfonyl)imide Complex Catalyzed Enantioselective Diels–Alder Reaction of Cyclopentadiene with Alkynones
Authors: Kang Tengfei , Wang Zhen , Lin Lili , Liao Yuting , Zhou Yuhang , Liu Xiaohua , Feng Xiaoming
Published: May 2015

An N,N′‐dioxide/zinc bis(trifluoromethylsulfonyl)imide complex has been developed as an efficient catalyst for the highly enantioselective Diels–Alder reaction of cyclopentadiene with alkynones. Various 2‐acyl substituted norbornadiene derivatives were obtained in moderate to high yields (up to 99 %) with good enantiomeric excesses (up to 95 %).

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Selective Access to All Four Diastereomers of a 1,3‐Amino Alcohol by Combination of a Keto Reductase‐ and an Amine Transaminase‐Catalysed Reaction
Authors: Kohls Hannes , Anderson Mattias , Dickerhoff Jonathan , Weisz Klaus , Córdova Armando , Berglund Per , Brundiek Henrike , Bornscheuer Uwe T. , Höhne Matthias
Published: May 2015

The biocatalytic synthesis of chiral amines has become a valuable addition to the chemists’ toolbox. However, the efficient asymmetric synthesis of functionalised amines bearing more than one stereocentre, such as 1,3‐amino alcohols, remains challenging. By employing a keto reductase (KRED) and two enantiocomplementary amine transaminases (ATA), we developed a biocatalytic route towards all four diastereomers of 4‐amino‐1‐phenylpentane‐2‐ol as a representative molecule bearing the 1,3‐amino alcohol functionality. Starting from a racemic hydroxy ketone, a kinetic resolution using an (S)‐selective KRED provided optically active hydroxy ketone (86% ee) and the corresponding diketone. Further transamination of the hydroxy ketone was performed by either an (R)‐ or an (S)‐selective ATA, yielding the (2R,4R)‐ and (2R,4S)‐1,3‐amino alcohol diastereomers. The remaining two diastereomers were accessible in two subsequent asymmetric steps: the diketone was reduced regio‐ and enantioselectively by the same KRED, which yielded the (S)‐configured hydroxy ketone. Eventually, the subsequent transamination of the crude product with (R)‐ and (S)‐selective ATAs yielded the remaining (2S,4R)‐ and (2S,4S)‐diastereomers, respectively.

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Social support and the serotonin transporter genotype (5‐HTTLPR) moderate levels of resilience, sense of coherence, and depression
Authors: Reinelt Eva , Barnow Sven , Stopsack Malte , Aldinger Maren , Schmidt Carsten Oliver , John Ulrich , Grabe Hans Jörgen
Published: May 2015

Gene x environment interactions have mainly been investigated in models of psychopathology. However, the putative interplay between genes and beneficial environmental conditions on positive outcomes has rarely been addressed. We therefore examined the interaction between the serotonin transporter linked polymorphic region (5‐HTTLPR) and social support on the sense of coherence (SOC), resilience, and depressive symptoms. Furthermore, we scrutinized our examinations by differentiating between individuals with and without childhood abuse. The sample included 1,811 participants from the general population (Study of Health in Pomerania, Germany). The triallelic genotype of 5‐HTTLPR was determined and longitudinal data of social support were used. Among individuals with high social support no significant differences between 5‐HTTLPR genotypes regarding all outcome variables were found. However, among those with low social support, carriers of at least one short allele reported significantly increased levels of SOC and resilience, as well as less depressive symptoms than carriers of the l/l genotype. This result was not modified by differentiating between those with childhood abuse and those without. In less supportive social environments the impact of distinct genotypes on behavioral outcomes might be more relevant than in supportive environments where social compensation might take place. Our findings indicate that both alleles of 5‐HTTLPR contribute to the adaptability to different environmental conditions. © 2015 Wiley Periodicals, Inc.
Continuous‐Flow Technology—A Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients
Authors: Gutmann Bernhard , Cantillo David , Kappe C. Oliver
Published: May 2015

In the past few years, continuous‐flow reactors with channel dimensions in the micro‐ or millimeter region have found widespread application in organic synthesis. The characteristic properties of these reactors are their exceptionally fast heat and mass transfer. In microstructured devices of this type, virtually instantaneous mixing can be achieved for all but the fastest reactions. Similarly, the accumulation of heat, formation of hot spots, and dangers of thermal runaways can be prevented. As a result of the small reactor volumes, the overall safety of the process is significantly improved, even when harsh reaction conditions are used. Thus, microreactor technology offers a unique way to perform ultrafast, exothermic reactions, and allows the execution of reactions which proceed via highly unstable or even explosive intermediates. This Review discusses recent literature examples of continuous‐flow organic synthesis where hazardous reactions or extreme process windows have been employed, with a focus on applications of relevance to the preparation of pharmaceuticals.
Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation
Authors: Endo Tsutomu , Ito Koyu , Morimoto Junko , Kanayama Masashi , Ota Daichi , Ikesue Masahiro , Kon Shigeyuki , Takahashi Daisuke , Onodera Tomohiro , Iwasaki Norimasa , Uede Toshimitsu
Published: May 2015

Objective

Syndecan 4 has been implicated as a critical mediator of inflammatory responses because of its functions as a coreceptor and reservoir for growth factors and chemokines. Although syndecan 4 is known to be expressed on B cells, its role in immune responses remains unclear. The purpose of this study was to investigate the contribution of syndecan 4 to the development of immune arthritis in murine models.

Methods

The clinical severity of 3 immunopathologically distinct models, collagen‐induced arthritis (CIA), antigen‐induced arthritis (AIA), and collagen antibody–induced arthritis (CAIA), was evaluated in wild‐type (WT) mice and in syndecan 4–deficient (Sdc4–/–) mice. Germinal center (GC) formation, B cell profiles, humoral immune responses, and B cell migration were analyzed during the course of CIA.

Results

Sdc4–/– mice were resistant to the induction of CIA, which is T cell and B cell dependent, but AIA and CAIA, which are T cell dependent and T cell independent, respectively, occurred with equal frequency in WT mice and Sdc4–/– mice. Furthermore, Sdc4–/– mice had reduced numbers of B cells and deficient GC formation in draining lymph nodes (DLNs) during the course of CIA, resulting in reduced production of collagen‐specific autoantibodies. Compared with B cells from WT mice, B cells from Sdc4–/– mice showed reduced chemotactic migration toward stromal cell–derived factor 1 (SDF‐1) and reduced SDF‐1–mediated Akt phosphorylation. Consistent with these findings, in vivo transfer experiments showed that fewer Sdc4–/– B cells than WT B cells were found in and around the follicles in the DLNs.

Conclusion

Our findings suggest that syndecan 4 contributes to the development of CIA by promoting GC formation and autoantibody production through its regulation of SDF‐1–mediated B cell migration.
Medically Significant Infections Are Increased in Patients With Juvenile Idiopathic Arthritis Treated With Etanercept: Results From the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study
Authors: Davies Rebecca , Southwood Taunton R. , Kearsley‐Fleet Lianne , Lunt Mark , Hyrich Kimme L. ,   on behalf of the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study
Published: May 2015

Objective

The association between anti–tumor necrosis factor therapy and increased rates of infection is widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less well documented. The aims of this analysis were to compare the rates of medically significant infections (MSIs) in children with JIA treated with etanercept (ETN) versus methotrexate (MTX) and to compare the rates between combination therapy with ETN plus MTX and monotherapy with ETN.

Methods

A total of 852 ETN‐treated children and 260 MTX‐treated children had been recruited to the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR‐ETN). MSIs included infections that resulted in death or hospitalization or were deemed medically significant by the clinician. This on‐drug analysis followed the patients until the first MSI, treatment discontinuation, the last followup, or death. Cox proportional hazards models, which were adjusted using propensity deciles, were used to compare rates of MSI between cohorts. Sensitivity analyses were conducted specifically with regard to serious infections (SIs), which were defined as those requiring hospitalization or treatment with intravenous antibiotics/antivirals.

Results

The ETN‐treated cohort was older and had a longer disease duration, but the disease activity was similar between the cohorts. A total of 133 first MSIs were reported (109 with ETN and 24 with MTX). Patients receiving ETN had higher rates of MSI than did the controls (propensity decile adjusted hazard ratio 2.13 [95% confidence interval 1.22–3.74]). The risk of MSI was higher whether patients were receiving combination or monotherapy. Sensitivity analysis showed no between‐group difference in the rate of SIs, which were much less common.

Conclusion

ETN therapy is associated with an increased risk of MSI; however, this increased risk disappears when considering only SIs, which suggests that either there were differences in the severity of infections and/or there was a possible reporting bias.
Rheumatoid Arthritis, Anti–Cyclic Citrullinated Peptide Positivity, and Cardiovascular Disease Risk in the Women's Health Initiative
Authors: Mackey Rachel H. , Kuller Lewis H. , Deane Kevin D. , Walitt Brian T. , Chang Yue‐Fang , Holers V. Michael , Robinson William H. , Tracy Russell P. , Hlatky Mark A. , Eaton Charles B. , Liu Simin , Freiberg Matthew S. , Talabi Mehret Birru , Schelbert Erik B. , Moreland Larry W.
Published: May 2015

Objective

To evaluate the incidence of cardiovascular disease (CVD) morbidity and mortality over the course of 10 years among the more than 160,000 postmenopausal women in the Women's Health Initiative (WHI) in relation to self‐reported rheumatoid arthritis (RA), taking disease‐modifying antirheumatic drugs (DMARDs), anti–cyclic citrullinated peptide (anti‐CCP) positivity, rheumatoid factor (RF) positivity, CVD risk factors, joint pain, and inflammation (white blood cell count and interleukin‐6 levels).

Methods

Anti‐CCP and RF were measured in a sample of WHI participants with self‐reported RA (n = 9,988). RA was classified as self‐reported RA plus anti‐CCP positivity and/or taking DMARDs. Anti‐CCP–negative women with self‐reported RA and not taking DMARDs were classified as having “unverified RA.”

Results

Age‐adjusted rates of coronary heart disease (CHD), stroke, CVD, fatal CVD, and total mortality were higher in women with RA than in women with no reported RA, with multivariable‐adjusted hazard ratios of 1.46 (95% confidence interval [95% CI] 1.17–1.83) for CHD and 2.55 (95% CI 1.86–3.51) for fatal CVD. Among women with RA, anti‐CCP positivity and RF positivity were not significantly associated with higher risk of any outcomes, despite slightly higher risk of death for those who were anti‐CCP positive than for those who were anti‐CCP negative. Joint pain severity and CVD risk factors were strongly associated with CVD risk, even in women with no reported RA. CVD incidence was increased in women with RA versus women with no reported RA at almost all risk factor levels, except for low levels of joint pain or inflammation. Among women with RA, inflammation was more strongly associated with fatal CVD and total mortality than with CHD or CVD.

Conclusion

Among postmenopausal women, RA was associated with 1.5–2.5‐fold higher CVD risk. CVD risk was strongly associated with CVD risk factors, joint pain severity, and inflammation, but not with anti‐CCP positivity or RF positivity.
State Estimation of Stochastic Impulsive System Via Stochastic Adaptive Impulsive Observer
Authors: Ayati Moosa , Alwan Mohamad , Liu Xinzhi , Khaloozadeh Hamid
Published: May 2015

This paper develops stochastic adaptive impulsive observer (SAIO) for state estimation of stochastic impulsive systems. Proposed observer is applicable to linear and a class of nonlinear stochastic impulsive systems. In addition to stochastic noises, the observer considers effect of parametric uncertainty and estimates unknown parameters by suitable adaptation laws. Interestingly, for certain impulsive systems, SAIO gives continuous state estimations from a discrete sequence of system output measurements. New theorems related to stochastic impulsive systems' boundedness are also developed and utilized to prove the boundedness of SAIO state estimation errors. Presented simulation results illustrate the effectiveness of the observer.
High‐throughput micro‐scale cultivations and chromatography modeling: Powerful tools for integrated process development
Authors: Baumann Pascal , Hahn Tobias , Hubbuch Jürgen
Published: May 2015

Upstream processes are rather complex to design and the productivity of cells under suitable cultivation conditions is hard to predict. The method of choice for examining the design space is to execute high‐throughput cultivation screenings in micro‐scale format. Various predictive in silico models have been developed for many downstream processes, leading to a reduction of time and material costs. This paper presents a combined optimization approach based on high‐throughput micro‐scale cultivation experiments and chromatography modeling. The overall optimized system must not necessarily be the one with highest product titers, but the one resulting in an overall superior process performance in up‐ and downstream. The methodology is presented in a case study for the Cherry‐tagged enzyme Glutathione‐S‐Transferase from Escherichia coli SE1. The Cherry‐Tag™ (Delphi Genetics, Belgium) which can be fused to any target protein allows for direct product analytics by simple VIS absorption measurements. High‐throughput cultivations were carried out in a 48‐well format in a BioLector micro‐scale cultivation system (m2p‐Labs, Germany). The downstream process optimization for a set of randomly picked upstream conditions producing high yields was performed in silico using a chromatography modeling software developed in‐house (ChromX). The suggested in silico‐optimized operational modes for product capturing were validated subsequently. The overall best system was chosen based on a combination of excellent up‐ and downstream performance. Biotechnol. Bioeng. 2015;112: 2123–2133. © 2015 Wiley Periodicals, Inc.
Master crash course on “software engineering” in a multi‐cultural environment
Authors: Bothe Klaus , Putnik Zoran
Published: May 2015

In this paper, we will present our experiences with the conduction of a short crash‐course on “Software Engineering” of a master level. It represents an excellent example of a good international cooperation in education field. Namely, conducted by the professor from Germany, and assistant from Serbia, the course is presented in Tirana, Albania, on Polytechnic University, Faculty of Information Technology. The course itself was created as a part of an international educational project, comprising nine countries, and fifteen universities. So far, the course has been conducted seven times, and hopefully it helped sharing of knowledge in this very important field of computer science. What is even more important, it certainly helped in sharing good will, improving communication between people and countries, and creating multi‐cultural environment for studies. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:854–864, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21657
Gastric Schwannoma: Case report from Tanzania and brief review of literature
Authors: Manji Mohamed , Ismail Ame , Komba Ewaldo
Published: May 2015

Key Clinical Message

Upper gastrointestinal bleeding causes significant morbidity and mortality worldwide. We report a rare case of hematemesis secondary to a gastric schwannoma in a Tanzanian female. Gastric schwannomas should be considered in the differential diagnosis of gastric masses and distinguished from other etiologies, given their excellent postresection prognosis.
Rheological Properties of Nanoemulsions Stabilized by Polysorbate 80
Authors: Jaworska Małgorzata , Sikora Elżbieta , Ogonowski Jan
Published: May 2015

The rheological properties of nanoemulsions based on three types of oil phases, namely, Crodamol GTCC, Crodamol PC, and oleic acid, were analyzed and determined. The emulsions were stabilized by Polysorbate 80. Geranic acid was selected as a model active substance. The obtained results confirm that the studied nanoemulsions are pseudoplastic non‐Newtonian fluids. The Herschel‐Bulkley model accurately describes the rheological properties of the developed systems. The phase inversion point for the Crodamol GTCC/Polysorbate 80/water system was observed at 50 wt % dispersed‐phase concentration. The rheological results served as the basis for calculation of a theoretical diffusion coefficient of the active ingredient in the studied nanoemulsions.
Cobalt‐Catalyzed Dual Annulation of o‐Halobenzaldimine with Alkyne: A Powerful Route toward Bioactive Indenoisoquinolinones
Authors: Liu Chuan‐Che , Hsieh Jen‐Chieh , Korivi Rajendra Prasad , Cheng Chien‐Hong
Published: May 2015

A cobalt‐catalyzed dual annulation reaction for the synthesis of variously substituted indenoisoquinolinones from 2‐bromobenzaldehydes, amines, and methyl 2‐(ethynyl)benzoates has been developed. This method could also be applied to the synthesis of an array of highly functionalized bioactive indenoisoquinolinones and their derivatives. A possible mechanism of the cobalt catalysis is proposed, involving imine formation from bromobenzaldehyde and the amine, followed by a series of oxidative addition, alkyne insertion, cyclization reactions, and carbon–carbon double‐bond migration. The regioselective alkyne insertion plays an important role for the success of the second annulation.
Chip‐level and multi‐node analysis of energy‐optimized lattice Boltzmann CFD simulations
Authors: Wittmann Markus , Hager Georg , Zeiser Thomas , Treibig Jan , Wellein Gerhard
Published: May 2015

Memory‐bound algorithms show complex performance and energy consumption behavior on multicore processors. We choose the lattice Boltzmann method on an Intel Sandy Bridge cluster as a prototype scenario to investigate if and how single‐chip performance and power characteristics can be generalized to the highly parallel case. First, we perform an analysis of a sparse‐lattice lattice Boltzmann method implementation for complex geometries. Using a single‐core performance model, we predict the intra‐chip saturation characteristics and the optimal operating point in terms of energy‐to‐solution as a function of implementation details, clock frequency, vectorization, and number of active cores per chip. We show that high single‐core performance and a correct choice of the number of active cores per chip are the essential optimizations for the lowest energy‐to‐solution at minimal performance degradation. Then we extrapolate to the Message Passing Interface (MPI)‐parallel level and quantify the energy‐saving potential of various optimizations and execution modes, where we find these guidelines to be even more important, especially when communication overhead is non‐negligible. In our setup, we could achieve energy savings of 35% in this case, compared with a naive approach. We also demonstrate that a simple non‐reflective reduction of the clock speed leaves most of the energy‐saving potential unused. Copyright © 2015 John Wiley & Sons, Ltd.
Sparse support vector machine for pattern recognition
Authors: Chen Guangyi , Bui Tien. D. , Krzyżak Adam
Published: May 2015

Support vector machine (SVM) is one of the most popular classification techniques in pattern recognition community. However, because of outliers in the training samples, SVM tends to perform poorly under such circumstances. In this paper, we borrow the idea from compressive sensing by introducing an extra term to the objective function of the standard SVM in order to achieve a sparse representation. Furthermore, instead of using the l0 norm, we adopt the l1 norm in our sparse SVM. In most cases, our method achieves higher classification rates than the standard SVM because of sparser support vectors and is more robust to outliers in the datasets. Experimental results show that our proposed SVM is efficient in pattern recognition applications. Copyright © 2015 John Wiley & Sons, Ltd.
Highly pure 1,3‐propanediol: Separation and purification from crude glycerol‐based fermentation
Authors: Wang Shizhen , Qiu Longhui , Dai Hongfei , Zeng Xiaofei , Fang Baishan
Published: May 2015

A new separation and purification process was developed for recovering 1,3‐propanediol (1,3‐PD) from crude glycerol‐based fermentation broth with high purity. The downstream process integrated chitosan flocculation, activated carbon decolorization, fixed bed cation exchange resin adsorption, and vacuum distillation. Breakthrough curves were measured considering the effect of sample concentration, flow rate, temperature, and resin stack height. Yoon–Nelson model was proposed to fit the fixed bed adsorption. The characteristic column parameters were calculated. Optimal condition for adsorption was 1,3‐PD, 30.0 g/L; flow rate, 1.00 mL/min; stacking height, 30.0 cm; and temperature, 298 K. Ethanol‐water (75%, 1 mL/min) was used as eluent to separate 1,3‐PD and glycerol with 95.3% 1,3‐PD elution rate. After vacuum distillation, the overall purity and yield of 1,3‐PD were 99.2% and 80.8% in the purification process, respectively. This is a simple and efficient downstream strategy for 1,3‐PD purification.
Antioxidant and antimicrobial properties of thyme essential oil encapsulated in zein particles
Authors: Bilenler Tugca , Gokbulut Incilay , Sislioglu Kubra , Karabulut Ihsan
Published: May 2015

Zein has been used successfully for encapsulation of functional foods. Thyme essential oil was encapsulated in zein particles by liquid‐liquid dispersion method. Functional properties of thyme essential oil can be enhanced by encapsulation technology. Based on the SEM images, size of the particles was in micron scale. A centrifugation step was applied to separate encapsulated particles during production. This treatment caused some differences in structural and functional properties. The highest encapsulation efficiency value of 97.02 % was achieved at 503 × g for 10 min centrifugation. Interaction time between samples and DPPH radicals was extended by encapsulation. Advantage of encapsulation in terms of antioxidant actions was highlighted by Rancimat test. A fast release rate of thyme essential oil encapsulated in zein was observed in triacylglycerols media. Antimicrobial activity of encapsulated thyme essential oil was lower than that of free form in 24 h incubation. A better encapsulation efficiency rate was obtained compared to reported values. Rancimat test can be effectively used to measure antioxidant activity when essential oils are used as antioxidants in encapsulated form. A fast release rate of thyme essential oil encapsulated in zein was observed in TAGs media. Copyright © 2015 John Wiley & Sons, Ltd.
Biology‐Driven Gene‐Gene Interaction Analysis of Age‐Related Cataract in the eMERGE Network
Authors: Hall Molly A. , Verma Shefali S. , Wallace John , Lucas Anastasia , Berg Richard L. , Connolly John , Crawford Dana C. , Crosslin David R. , de Andrade Mariza , Doheny Kimberly F. , Haines Jonathan L. , Harley John B. , Jarvik Gail P. , Kitchner Terrie , Kuivaniemi Helena , Larson Eric B. , Carrell David S. , Tromp Gerard , Vrabec Tamara R. , Pendergrass Sarah A. , McCarty Catherine A. , Ritchie Marylyn D.
Published: May 2015

Bioinformatics approaches to examine gene‐gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge‐driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty‐three SNP‐SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell‐to‐cell adhesion signaling, cell‐cell junction organization, and cell‐cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP‐SNP models, which included signal transduction and PI3K‐Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology‐driven method, applicable for any genome‐wide association study dataset.
Effect‐directed identification of endocrine disruptors in plastic baby teethers
Authors: Berger Elisabeth , Potouridis Theodoros , Haeger Astrid , Püttmann Wilhelm , Wagner Martin
Published: May 2015

Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect‐directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography–mass spectrometry non‐target screening revealed that methyl‐, ethyl‐ and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well‐established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved. Copyright © 2015 John Wiley & Sons, Ltd.
Acute and subchronic toxicity of 20  kHz and 60  kHz magnetic fields in rats
Authors: Nishimura Izumi , Oshima Atsushi , Shibuya Kazumoto , Mitani Takashi , Negishi Tadashi
Published: May 2015

Despite increasing use of intermediate frequency (IF) magnetic fields (MFs) in occupational and domestic settings, scientific evidence necessary for health risk assessments of IF MF is insufficient. Male and female Crl:CD(SD) rats (12 per sex per group) were exposed to 20 kHz, 0.20 mT(root mean square, rms) or 60 kHz, 0.10 mT(rms) sinusoidal MFs for 22 h day−1 for 14 days (acute) or 13 weeks (subchronic). Experiments were duplicated for each frequency to ensure outcome reproducibility, and examinations were blinded for quality assurance. All rats survived without significant clinical signs until the end of experiments. Some changes in body weight between the MF‐exposed and control groups were observed over the course of exposure, although the directions of the changes were inconsistent and not statistically significant after subchronic exposure. There were significant differences between MF‐exposed and control groups in some organ weights and parameters in hematology and clinical chemistry, but these were minor in magnitude and not repeated in duplicate experiments. Histopathological findings reflecting toxicity were sporadic. Frequencies of other findings were similar to historic data in this rat strain, and findings had no specific relationship to changes in organ weight or parameters of hematology and clinical chemistry in each animal. The changes observed throughout this study were considered biologically isolated and were attributable to chance associations rather than to MF exposure. The results, in particular the histopathological evidence, indicate an absence of toxicity in IF MF‐exposed rats and do not support the hypothesis that IF MF exposure produces significant toxicity. Copyright © 2015. The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd.
Color‐Coded Imaging of Breast Cancer Metastatic Niche Formation in Nude Mice
Authors: Suetsugu Atsushi , Momiyama Masashi , Hiroshima Yukihiko , Shimizu Masahito , Saji Shigetoyo , Moriwaki Hisataka , Bouvet Michael , Hoffman Robert M.
Published: May 2015

We report here a color‐coded imaging model in which metastatic niches in the lung and liver of breast cancer can be identified. The transgenic green fluorescent protein (GFP)‐expressing nude mouse was used as the host. The GFP nude mouse expresses GFP in all organs. However, GFP expression is dim in the liver parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to produce experimental lung metastasis and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using very high resolution imaging systems. In the lung, GFP host‐mouse cells accumulated around as few as a single MMT‐RFP cell. In addition, GFP host cells were observed to form circle‐shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle‐shaped niches. Liver and lung metastases were removed surgically and cultured in vitro. MMT‐RFP cells and GFP host cells resembling cancer‐associated fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as a metastatic niche. J. Cell. Biochem. 116: 2730–2734, 2015. © 2015 Wiley Periodicals, Inc.
Differential Potential of Pharmacological PARP Inhibitors for Inhibiting Cell Proliferation and Inducing Apoptosis in Human Breast Cancer Cells
Authors: Węsierska‐Gądek Józefa , Mauritz Matthias , Mitulovic Goran , Cupo Maria
Published: May 2015

BRCA1/2‐mutant cells are hypersensitive to inactivation of poly(ADP‐ribose) polymerase 1 (PARP‐1). We recently showed that inhibition of PARP‐1 by NU1025 is strongly cytotoxic for BRCA1‐positive BT‐20 cells, but not BRCA1‐deficient SKBr‐3 cells. These results raised the possibility that other PARP‐1 inhibitors, particularly those tested in clinical trials, may be more efficacious against BRCA1‐deficient SKBr‐3 breast cancer cells than NU1025. Thus, in the presented study the cytotoxicity of four PARP inhibitors under clinical evaluation (olaparib, rucaparib, iniparib and AZD2461) was examined and compared to that of NU1025. The sensitivity of breast cancer cells to the PARP‐1 inhibition strongly varied. Remarkably, BRCA‐1‐deficient SKBr‐3 cells were almost completely insensitive to NU1025, olaparib and rucaparib, whereas BRCA1‐expressing BT‐20 cells were strongly affected by NU1025 even at low doses. In contrast, iniparib and AZD2461 were cytotoxic for both BT‐20 and SKBr‐3 cells. Of the four tested PARP‐1 inhibitors only AZD2461 strongly affected cell cycle progression. Interestingly, the anti‐proliferative and pro‐apoptotic potential of the tested PARP‐1 inhibitors clearly correlated with their capacity to damage DNA. Further analyses revealed that proteomic signatures of the two studied breast cancer cell lines strongly differ, and a set of 197 proteins was differentially expressed in NU1025‐treated BT‐20 cancer cells. These results indicate that BT‐20 cells may harbor an unknown defect in DNA repair pathway(s) rendering them sensitive to PARP‐1 inhibition. They also imply that therapeutic applicability of PARP‐1 inhibitors is not limited to BRCA mutation carriers but can be extended to patients harboring deficiencies in other components of the pathway(s). J. Cell. Biochem. 116: 2824–2839, 2015. © 2015 Wiley Periodicals, Inc.
Novel 7‐Nitro‐1‐(Piperidin‐4‐yl)‐4,5‐Dihydro‐[1,2,4] Triazolo[4,3‐a]Quinoline‐Sulphonamide Derivatives as Antimicrobial Agents: Design, Synthesis, and Bio‐Activity
Authors: Reddy Bijivemula N. , Reddy Peddiahgari Vasu Govardhana , Reddy Bhoomireddy Rajendra Prasad , Reddy Sirigi Reddy Sudharsan , Reddy S. M. , Pathak Madhvesh
Published: May 2015

In attempt to search for more potent antimicrobial agents, a series of 7‐nitro‐1‐(piperidin‐4‐yl)‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinoline‐derived sulphonamides were synthesized. Their structures were established by elemental analyses, IR, and NMR (1H and 13C) spectral data. The antibacterial activity of the obtained compounds was investigated against different Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis and Staphylococcus aureus) bacteria and antifungal activity against two fungal strains (Aspergillus niger and Aspergillus clavatus) using disk diffusion method at various concentrations (20, 40, 60, and 80 μg/mL). The study reveals that most of the title compounds showed significant antibacterial and fungal activity when compared with their respective standards streptomycin and griseofulvin.
Target‐directed screening of the bioactive compounds specifically binding to β2‐adrenoceptor in Semen brassicae by high‐performance affinity chromatography
Authors: An Yuxin , Li Xia , Sun Huanmei , Bian Wenhai , Li Zijian , Zhang Youyi , Zhao Xinfeng , Zheng Xiaohui
Published: May 2015

The bioactive ingredients in Semen sinapis were rapidly screened by immobilized β2‐adrenoceptor (β2‐AR) and target‐directed molecular docking. The methods involved the attachment of β2‐AR using any amino group in the receptor, the simultaneous separation and identification of the retention compounds by high‐performance affinity chromatography; the binding mechanism of the interesting compound to the receptor was investigated by zonal elution and molecular docking. Sinapine in Semen sinapis was proved to be the bioactive compound that specifically binds to the immobilized receptor. The association constant of sinapine to β2‐AR was determined to be 1.36 × 105 M−1 with a value of 1.27 × 10−6 M for the number of binding sites. Ionic bond was believed to be the driving force during the interaction between sinapine and β2‐AR. It is possible to become a powerful alternative for rapid screening of bioactive compounds from a complex matrix such as traditional Chinese medicine and further investigation on the drug–receptor interaction. Copyright © 2015 John Wiley & Sons, Ltd.
IL‐9 inhibits HTB‐72 melanoma cell growth through upregulation of p21 and TRAIL
Authors: Fang Yujiang , Chen Xuhui , Bai Qian , Qin Chenglu , Mohamud Abdimalik O. , Zhu Ziwen , Ball Tyler W. , Ruth Caleb M. , Newcomer Dylan R. , Herrick Elizabeth J. , Nicholl Michael B.
Published: May 2015

Background

IL‐9 is a pleiotropic cytokine produced mainly by Th9 cells. IL‐9 may have an anti‐proliferative role in murine melanoma, however, its effect on human melanoma is unknown.

Methods

We examined the effects of IL‐9 on proliferation and apoptosis in four human melanoma cell lines, HTB‐65, HTB‐72, CRL‐11147, and SK‐Mel‐5. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase‐3 activity assay were used to assess proliferation and apoptosis, as appropriate.

Results

We found that IL‐9 decreased the percentage of colonies of HTB‐72 and SK‐Mel‐5 cells but not that of HTB‐65 or CRL‐11147 cells. PCNA mRNA, PCNA+ cells, PCNA staining intensity, and the OD value of HTB‐72 melanoma cells were consistently decreased in the present of IL‐9. IL‐9 also increased TUNEL+ cells and the relative caspase‐3 activity in HTB‐72 melanoma cells. We further investigated the possible molecular mechanisms using RT‐PCR and immunohistochemical staining. The anti‐proliferative effect of IL‐9 on HTB‐72 cells correlated with higher expression of anti‐proliferative molecule p21. Its pro‐apoptotic effect on HTB‐72 cells correlated with higher expression of the pro‐apoptotic molecule TRAIL.

Conclusions

IL‐9 inhibits melanoma HTB‐72 cell growth by upregulation of p21 and TRAIL. Understanding the interactions between IL‐9 and melanoma may help direct strategies for cytokine‐based immunotherapy development. J. Surg. Oncol. 2015 111:969–974. © 2015 Wiley Periodicals, Inc.
Dialkyl phosphates determination by gas chromatography: Evaluation of a microwave‐assisted derivatization†
Authors: Silvério Alessandra Cristina Pupin , Machado Simone Caetani , Boralli Vanessa Bergamin , Martins Isarita
Published: May 2015

Dialkyl phosphates are organophosphate insecticide metabolites and their urinary analysis is useful for assessing human exposure to these compounds. This study presents a sample preparation method with microwave‐assisted derivatization for two dialkyl phosphates to make the process faster before gas chromatographic analysis. The optimized conditions for derivatization procedure were: 250 μL of 2,3,4,5,6‐pentafluorobenzyl bromide 3% in acetonitrile for derivative; microwave for 5 min with intensity of 160 W. The electron ionization mass spectrometric analysis was performed using a gas chromatography with mass spectrometry QP‐2010 from the Shimadzu® equipped with RTx®‐5MS capillary column. Ions were monitored at selected‐ion monitoring mode at m/z 350 for diethyl thiophosphate and m/z 366 for diethyl dithiophosphate. The developed method was linear for both metabolites. The intra‐assay precision was the values ranged between 1.1 and 9.1%, for diethyl thiophosphate, and between 4.06 and 6.9%, for diethyl dithiophosphate. The interassay precision showed relative standard deviation between 10.3 and 15.1%, for diethyl thiophosphate and between 4.9 and 11.9%, for diethyl dithiophosphate. The results obtained suggests that derivatization assisted by microwave, before gas chromatography with mass spectrometry analysis, can be applied to monitoring of exposure to organophosphates once is fast, sensible, and precise method to determinate dialkyl phosphates.
Ultra high performance liquid chromatography with mass spectrometry method for the simultaneous determination of phenolic constituents in honey from various floral sources using multiwalled carbon nanotubes as extraction sorbents
Authors: Wabaidur Saikh Mohammad , Ahmed Yacine Badjah Hadj , Alothman Zeid Abdullah , Obbed Munir Saeed , AL‐Harbi Nasser Mohamed , AL‐Turki Turki Mohammad
Published: May 2015

An ultra high performance liquid chromatography with mass spectrometry method has been developed for the simultaneous separation, identification and determination of 22 phenolic constituents in honey from various floral sources from Yemen. Solid‐phase extraction was used for extraction of the target phenolic constituents from honey samples, while multiwalled carbon nanotubes were used as solid‐phase adsorbent. The chromatographic separation of all phenolic constituents was performed on a BEH C18 column using a linear gradient elution with a binary mobile phase mixture of aqueous 0.1% formic acid and methanol. The quantitation was carried out in selected ion reaction monitoring acquisition mode. The total amount of phenolic acids, flavonoids and other phenols in each analyzed honey was found in the range of 338–3312, 122–5482 and 2.4–1342 μg/100 g of honey, respectively. 4‐Hydroxybenzoic acid was found to be the major phenolic acid. The main detected flavonoid was chrysin, while cinnamic acid was found to be the major other phenol compound. The regeneration of solid phase adsorbent to be reused and recovery results confirm that the proposed method could be potentially used for the routine analysis of phenolic constituents in honey extract.
A priori time regularity estimates and a simplified proof of existence in perfect plasticity
Authors: Solombrino Francesco
Published: May 2015

We revisit the time‐incremental method for proving existence of a quasistatic evolution in perfect plasticity. We show how, as a consequence of a priori time regularity estimates on the stress and the plastic strain, the piecewise affine interpolants of the solutions of the incremental minimum problems satisfy the conditions defining a quasistatic evolution up to some vanishing error. This allows for a quicker proof of existence: furthermore, this proof bypasses the usual variational reformulation of the problem and directly tackles its original mechanical formulation in terms of an equilibrium condition, a stress constraint, and the principle of maximum plastic work.
Multi‐atlas and label fusion approach for patient‐specific MRI based skull estimation
Authors: Torrado‐Carvajal Angel , Herraiz Joaquin L. , Hernandez‐Tamames Juan A. , San Jose‐Estepar Raul , Eryaman Yigitcan , Rozenholc Yves , Adalsteinsson Elfar , Wald Lawrence L. , Malpica Norberto
Published: May 2015

Purpose

MRI‐based skull segmentation is a useful procedure for many imaging applications. This study describes a methodology for automatic segmentation of the complete skull from a single T1‐weighted volume.

Methods

The skull is estimated using a multi‐atlas segmentation approach. Using a whole head computed tomography (CT) scan database, the skull in a new MRI volume is detected by nonrigid image registration of the volume to every CT, and combination of the individual segmentations by label‐fusion. We have compared Majority Voting, Simultaneous Truth and Performance Level Estimation (STAPLE), Shape Based Averaging (SBA), and the Selective and Iterative Method for Performance Level Estimation (SIMPLE) algorithms.

Results

The pipeline has been evaluated quantitatively using images from the Retrospective Image Registration Evaluation database (reaching an overlap of 72.46 ± 6.99%), a clinical CT‐MR dataset (maximum overlap of 78.31 ± 6.97%), and a whole head CT‐MRI pair (maximum overlap 78.68%). A qualitative evaluation has also been performed on MRI acquisition of volunteers.

Conclusion

It is possible to automatically segment the complete skull from MRI data using a multi‐atlas and label fusion approach. This will allow the creation of complete MRI‐based tissue models that can be used in electromagnetic dosimetry applications and attenuation correction in PET/MR. Magn Reson Med 75:1797–1807, 2016. © 2015 Wiley Periodicals, Inc.
Biodegradable polymer blends: miscibility, physicochemical properties and biological response of scaffolds
Authors: Goonoo Nowsheen , Bhaw‐Luximon Archana , Jhurry Dhanjay
Published: May 2015

This review provides an overview of synthetic biodegradable polymer blends prepared for tissue engineering applications and aims at establishing structure‐physicochemical‐biological properties relationships. The characteristics of blends consisting of semi‐crystalline/semi‐crystalline and semi‐crystalline/amorphous polymers are presented. Their biological properties such as degradability and biocompatibility and their biological performance as scaffolds in relation to cell adhesion, proliferation, infiltration, morphology and type are discussed. From available data, it can be deduced that miscibility influences physicochemical properties of the corresponding biodegradable polymeric blend scaffold, which in turn impacts on biological response. Immiscibility in polymer blends generally translates into good cell adhesion and proliferation. However, better cellular infiltration has been noted in compatible blends compared to immiscible blends. Factors such as crystallinityversusamorphous character, chirality, surface properties, degradation rate/products, mechanical properties and scaffold fabrication techniques are shown to have a major bearing on cell growth. © 2015 Society of Chemical Industry