bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical regime for the insulator–metal transition in highly ordered conjugated polymers gated with ionic liquid
Authors: Ito Hiroshi , Harada Tomonori , Tanaka Hisaaki , Kuroda Shin-ichi
Published: February 2016

We report the room-temperature and low-temperature transport properties of a poly(2,5-bis(3-hexadecylthiophene-2-yl)thieno[3,2-b]thiophene) (PBTTT) film gated with an ionic liquid based on 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide at different annealing temperatures of the PBTTT film. By annealing the film up to 235 °C and subsequently cooling it, we observed a ribbonlike structure, as reported. For the 235-°C-annealed (ribbon phase) film, we could apply a higher voltage without any decrease in the channel conductivity than for the 180-°C-annealed (terrace phase) film. As a result, a charge mobility as high as 10 cm2 V−1 s−1 was achieved for the ribbon-phase film. The power-law behavior of the temperature dependence of the electrical conductivity at low temperatures, indicating the critical regime for the insulator–metal transition, was observed. The ribbon-phase film exhibits an even weaker temperature dependence with a smaller exponent of β = 0.10 than the terrace-phase film.
Taxonomic and systematic revisions to the North American Nimravidae (Mammalia, Carnivora)
Authors: Barrett Paul Z.
Published: February 2016

The Nimravidae is a family of extinct carnivores commonly referred to as “false saber-tooth cats.” Since their initial discovery, they have prompted difficulty in taxonomic assignments and number of valid species. Past revisions have only examined a handful of genera, while recent advances in cladistic and morphometric analyses have granted us additional avenues to answering questions regarding our understanding of valid nimravid taxa and their phylogenetic relationships. To resolve issues of specific validity, the phylogenetic species concept (PSC) was utilized to maintain consistency in diagnosing valid species, while simultaneously employing character and linear morphometric analyses for confirming the validity of taxa. Determined valid species and taxonomically informative characters were then employed in two differential cladistic analyses to create competing hypotheses of interspecific relationships. The results suggest the validity of twelve species and six monophyletic genera. The first in depth reviews ofPogonodonandDinictisreturned two valid species (P. platycopis,P. davisi) for the former, while only one for the latter (D. felina). The taxonomic validity ofNanosmilusis upheld. Two main clades with substantial support were returned for all cladistic analyses, the Hoplophoneini and Nimravini, with ambiguous positions relative to these main clades for the European taxa:Eofelis,Dinailurictis bonali, andQuercylurus major; and the North American taxaDinictisandPogonodon.Eusmilusis determined to represent a non-valid genus for North American taxa, suggesting non-validity for Old World nimravid species as well. Finally,Hoplophoneus mentalisis found to be a junior synonym ofHoplophoneus primaevus, while the validity ofHoplophoneus oharraiis reinstated.
Is type-D personality trait(s) or state? An examination of type-D temporal stability in older Israeli adults in the community
Authors: Zohar Ada H.
Published: February 2016

Background.Type D personality was suggested as a marker of poorer prognosis for patients of cardiovascular disease. It is defined by having a score of 10 or more on both sub-scales of the DS14 questionnaire, Social Inhibition (SI) and Negative Affectivity (NA). As Type D was designed to predict risk, its temporal stability is of prime importance.

Methods.Participants in the current study were 285 community volunteers, who completed the DS14, and other personality scales, at a mean interval of six years.

Results.The prevalence of Type D did not change. The component traits of Type D showed rank order stability. Type D caseness temporal stability was improved by using the sub-scales product as a criterion. Logistic hierarchical regression predicting Type D classification from Time1 demonstrated that the best predictors were Time1 scores on NA and SI, with the character trait of Cooperation, and the alexithymia score adding some predictive power.

Conclusions.The temporal stability of the component traits, and of the prevalence of Type D were excellent. Temporal stability of Type D caseness may be improved by using a product threshold, rather than the current rule. Research is required in order to formulate the optimal timing for Type D measurement for predictive purposes.
Expansion of Human Hematopoietic Stem/Progenitor Cells on Decellularized Matrix Scaffolds
Authors: Tiwari Abhilasha , Tursky Melinda L. , Nekkanti Lakshmi P. , Jenkin Graham , Kirkland Mark A. , Pande Gopal
Published: February 2016

Umbilical cord blood (UCB) is one of the richest sources for hematopoietic stem/progenitor cells (HSPCs), with more than 3000 transplantations performed each year for the treatment of leukemia and other bone marrow, immunological, and hereditary diseases. However, transplantation of single cord blood units is mostly restricted to children, due to the limited number of HSPC per unit. This unit develops a method to increase the number of HSPCs in laboratory conditions by using cell‐free matrices from bone marrow cells that mimic ‘human‐body‐niche‐like’ conditions as biological scaffolds to support the ex vivo expansion of HSPCs. In this unit, we describe protocols for the isolation and characterization of HSPCs from UCB and their serum‐free expansion on decellularized matrices. This method may also help to provide understanding of the biochemical organization of hematopoietic niches and lead to suggestions regarding the design of tissue engineering–based biomimetic scaffolds for HSPC expansion for clinical applications. © 2016 by John Wiley & Sons, Inc.
Identifying Adult Stem Cells Using Cre‐Mediated Lineage Tracing
Authors: Carlone Diana L.
Published: February 2016

Lineage‐tracing has been used for decades to establish cell fate maps during development. Recently, with the advent of genetic lineage‐tracing techniques (employing Cre‐lox recombination), it has been possible to permanently mark progenitor/stem cell populations within somatic tissues. In addition, pulse‐chase studies have shown that only stem cells are capable of producing labeled progeny after an extensive period of chase. This unit focuses on the protocols used to target putative adult stem cells in vivo. Using these techniques, one should be able to functionally confirm or deny the stem cell capacity of a given cell population. © 2016 by John Wiley & Sons, Inc.
Obtaining High Quality DNA from Diverse Clinical Samples
Authors: Melton‐Kreft Rachael , Spirk Tracy
Published: February 2016

Nucleic acids can be obtained in numerous ways from clinical specimens; however, the quality of the nucleic acid is only as good as the sampling and isolation protocol. While nucleic acids may be extracted they may not be representative of the original source. Large areas of tissue and explanted hardware must be successfully surveyed to reflect the overall clinical picture. Once good sampling technique has been established, successful bacterial nucleic acid isolation is essential. Clinical samples may be difficult to process because of the presence of scar tissue, bone, implants, and bacterial biofilms. The following protocols provide details on sampling techniques and DNA isolation from a variety of clinical samples which can then be used in downstream molecular applications including PCR‐MS‐ESI‐TOF technology. © 2016 by John Wiley & Sons, Inc.
Investigation of Viral and Host Chromatin by ChIP‐PCR or ChIP‐Seq Analysis
Authors: Günther Thomas , Theiss Juliane M. , Fischer Nicole , Grundhoff Adam
Published: February 2016

Complex regulation of viral transcription patterns and DNA replication levels is a feature of many DNA viruses. This is especially true for those viruses which establish latent or persistent infections (e.g., herpesviruses, papillomaviruses, polyomaviruses, or adenovirus), as long‐term persistence often requires adaptation of gene expression programs and/or replication levels to the cellular milieu. A key factor in the control of such processes is the establishment of a specific chromatin state on promoters or replication origins, which in turn will determine whether or not the underlying DNA is accessible for other factors that mediate downstream processes. Chromatin immunoprecipitation (ChIP) is a powerful technique to investigate viral chromatin, in particular to study binding patterns of modified histones, transcription factors or other DNA‐/chromatin‐binding proteins that regulate the viral lifecycle. Here, we provide protocols that are suitable for performing ChIP‐PCR and ChIP‐Seq studies on chromatin of large and small viral genomes.© 2016 by John Wiley & Sons, Inc.
Construction of a Transcription Map for Papillomaviruses using RACE, RNase Protection, and Primer Extension Assays
Authors: Wang Xiaohong , Zheng Zhi‐Ming
Published: February 2016

Papillomaviruses are a family of small, non‐enveloped DNA tumor viruses. Knowing a complete transcription map of each papillomavirus genome can provide guidance for various papillomavirus studies. This unit provides detailed protocols to construct a transcription map of human papillomavirus type 18. The same approach can be easily adapted to other transcription map studies of any other papillomavirus genotype due to the high degree of conservation in genome structure, organization, and gene expression among papillomaviruses. The focused methods are 5′‐ and 3′‐rapid amplification of cDNA ends (RACE), which are techniques commonly used in molecular biology to obtain full‐length RNA transcript or to map a transcription start site (TSS) or an RNA polyadenylation (pA) cleavage site. Primer walking RT‐PCR is a method for studying the splicing junction of RACE products. In addition, RNase protection assay and primer extension are also introduced as alternative methods in the mapping analysis. © 2016 by John Wiley & Sons, Inc.
Mechanical, Structural, and Chemical Analysis of Athrombogenic Multilayer Wall of Ventricular Assist Device Tested in Hydrodynamic Fatigue Tests
Authors: Kopernik Magdalena , Kąc Sławomir , Gawlikowski Maciej , Cios Grzegorz
Published: February 2016

The purpose of the paper is to assess an impact of short‐ and long‐term operational load on continuity and composition of TiN/Au layers deposited on the polymer Bionate II that the pulsatile ventricular assist device Religa Heart Ext is made of. The additional objective is to determine mechanical properties of the TiN/Au layers deposited on the polymer. The physical model of circulatory system was built using the Windkessel model. The tests with the use of energy dispersive spectroscopy and scanning electron microscopy were made on surfaces of samples made of the Religa Heart Ext material examined in the fatigue tests. Mechanical properties of the TiN/Au coatings deposited on the polymer were measured in the nanoindentation test by comparison of the coated and the uncoated samples.
Facile and Selective Synthesis of Imidazobenzimidazoles via a Copper‐Catalysed Domino Addition/Cycloisomerisation/ Coupling Process
Authors: Xu Bingqing , Peng Bo , Cai Bili , Wang Shishi , Wang Xiaoxia , Lv Xin
Published: February 2016

A copper(I)‐catalysed domino transformation for the synthesis of tricyclic imidazobenzimidazole derivatives was developed. Using readily available primary propargylic amines and o‐haloarylcarbodiimides as the starting materials, a variety of substituted benzo[d]imidazo[1,2‐a]imidazoles was efficiently and selectively assembled. Further investigations indicated that the domino reaction was likely the result of a novel addition/cycloisomerisation/coupling process.

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Recent Developments and Understanding of Novel Mixed Transition‐Metal Oxides as Anodes in Lithium Ion Batteries
Authors: Zhao Yang , Li Xifei , Yan Bo , Xiong Dongbin , Li Dejun , Lawes Stephen , Sun Xueliang
Published: February 2016

Mixed transition‐metal oxides (MTMOs), including stannates, ferrites, cobaltates, and nickelates, have attracted increased attention in the application of high performance lithium‐ion batteries. Compared with traditional metal oxides, MTMOs exhibit enormous potential as electrode materials in lithium‐ion batteries originating from higher reversible capacity, better structural stability, and high electronic conductivity. Recent advancements in the rational design of novel MTMO micro/nanostructures for lithium‐ion battery anodes are summarized and their energy storage mechanism is compared to transition‐metal oxide anodes. In particular, the significant effects of the MTMO morphology, micro/nanostructure, and crystallinity on battery performance are highlighted. Furthermore, the future trends and prospects, as well as potential problems, are presented to further develop advanced MTMO anodes for more promising and large‐scale commercial applications of lithium‐ion batteries.
A new case of malonyl‐CoA decarboxylase deficiency with mild clinical features
Authors: Liu Huan , Tan Dongqiong , Han Lianshu , Ye Jun , Qiu Wenjuan , Gu Xuefan , Zhang Huiwen
Published: February 2016

Malonyl‐CoA decarboxylase deficiency is an extremely rare autosomal recessive inborn error of fatty acid metabolism. It usually follows a severe disease course and presents poor prognosis without treatment. Here, we report an affected female juvenile with a mild clinical and biochemical phenotype who mainly featured poor schooling without cardiomyopathy and metabolic acidosis. She was suspected of malonyl‐CoA decarboxylase deficiency due to a 57‐kb deletion in 16q23.3 encompassing the MLCYD gene revealed by chromosome microarray. Malonyl‐CoA decarboxylase deficiency was then confirmed by acylcarnitine analysis and organic acid analysis. Real‐time PCR analysis of the patient revealed the first three exon deletion of the MLYCD gene, which was maternally inherited. DNA sequencing of the MLYCD gene of the patient identified a novel heterozygous mutation (c.911G>A, p.G304E) in exon 4 that was paternally inherited. The patient urine malonic acid dissolved and had a better school record in 6 month after initiation of fat‐limited diet. At 1 year post treatment, the blood malonylcarnitine level decreased remarkably. Our result expands the phenotype of malonyl‐CoA decarboxylase deficiency and suggests attentions should be paid to the mild form of disorders, for example, malonyl‐CoA decarboxylase deficiency, which usually present a severe disease course. © 2016 Wiley Periodicals, Inc.
Fe3O4@SiO2@l‐arginine@Pd(0): a new magnetically retrievable heterogeneous nanocatalyst with high efficiency for C–C bond formation
Authors: Ghorbani‐Choghamarani Arash , Azadi Gouhar
Published: February 2016

The surface of Fe3O4@SiO2 nanoparticles was modified using l‐arginine as a green and available amino acid to trap palladium nanoparticles through a strong interaction between the metal nanoparticles and functional groups of the amino acid. The proposed green synthetic method takes advantage of nontoxic reagents through a simple procedure. Characterization of Fe3O4@SiO2@l‐arginine@Pd(0) was done using Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, X‐ray diffraction, vibrating sample magnetometry and inductively coupled plasma analysis. The catalytic activity of Fe3O4@SiO2@l‐arginine@Pd(0) as a new nanocatalyst was investigated in C–C coupling reactions. Waste‐free, use of green medium, efficient synthesis leading to high yield of products, eco‐friendly and economic catalyst, excellent reusability of the nanocatalyst and short reaction time are the main advantages of the method presented. Copyright © 2016 John Wiley & Sons, Ltd.
Polylactic acid bioconjugated with glutathione: Thermosensitive self‐healed networks
Authors: Djidi Dalila , Mignard Nathalie , Taha Mohamed
Published: February 2016

Polylactic acid was bioconjugated with glutathione (GSH) in a solvent‐free one step process. Thermo‐reversible networks were first obtained as a consequence of the supramolecular interactions induced by GSH moieties. Then dynamic covalent reactions were added to the networks' synthesis process using dialcohol‐functionalized Diels−Alder (DA) adducts. The main properties of these networks were analyzed in relation with their structures and the proportions of supramolecular and DA reactions. The thermo‐mechanical properties of the obtained transparent materials and their healing efficiency were evaluated by dynamic mechanical spectroscopy and tensile analyses. Crosslinking/de‐crosslinking temperatures varied from 36 to 112°C. The obtained networks showed self‐healing ability without external stimuli. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43436.
Distributed algorithm for empty vehicles management in personal rapid transit (PRT) network
Authors: Daszczuk Wiktor B. , Mieścicki Jerzy , Grabski Waldemar
Published: February 2016

In this paper, an original heuristic algorithm of empty vehicles management in personal rapid transit network is presented. The algorithm is used for the delivery of empty vehicles for waiting passengers, for balancing the distribution of empty vehicles within the network, and for providing an empty space for vehicles approaching a station. Each of these tasks involves a decision on the trip that has to be done by a selected empty vehicle from its actual location to some determined destination. The decisions are based on a multi‐parameter function involving a set of factors and thresholds.

An important feature of the algorithm is that it does not use any central database of passenger input (demand) and locations of free vehicles. Instead, it is based on the local exchange of data between stations: on their states and on the vehicles they expect. Therefore, it seems well‐tailored for a distributed implementation.

The algorithm is uniform, meaning that the same basic procedure is used for multiple tasks using a task‐specific set of parameters. Copyright © 2016 John Wiley & Sons, Ltd.
Patient outcomes and provider perceptions following implementation of a standardized perioperative care pathway for open liver resection
Authors: Page A J , Gani F , Crowley K T , Lee K H K , Grant M C , Zavadsky T L , Hobson D , Wu C , Wick E C , Pawlik T M
Published: February 2016

Background

Enhanced recovery after surgery (ERAS) pathways have been associated with improved perioperative outcomes following several surgical procedures. Less is known, however, regarding their use following hepatic surgery.

Methods

An evidence-based, standardized perioperative care pathway was developed and implemented prospectively among patients undergoing open liver surgery between 1 January 2014 and 31 July 2015. Perioperative outcomes, including length of hospital stay, postoperative complications and healthcare costs, were compared between groups of patients who had surgery before and after introduction of the ERAS pathway. Provider perceptions regarding the perioperative pathway were assessed using an online questionnaire.

Results

There were no differences in patient or disease characteristics between pre-ERAS (42 patients) and post-ERAS (75) groups. Although mean pain scores were comparable between the two groups, patients treated within the ERAS pathway had a marked reduction in opioid use on the first 3 days after surgery compared with those treated before introduction of the pathway (all P < 0·001). Duration of hospital stay was shorter in the post-ERAS group (median 5 (i.q.r. 4–7) days versus 6 (5–7) days in the pre-ERAS group; P = 0·037) and there was a lower incidence of postoperative complications (1 versus 10 per cent; P = 0·036). Implementation of the ERAS pathway was associated with a 40·7 per cent decrease in laboratory costs (−US $333; −€306, exchange rate 4 January 2016) and a 21·5 per cent reduction in medical supply costs (−US $394; −€362) per patient. Although 91·0 per cent of providers endorsed the ERAS pathway, 33·8 per cent identified provider aversion to a standardized protocol as the greatest hurdle to implementation.

Conclusion

The introduction of a multimodal ERAS programme following open liver surgery was associated with a reduction in opioid use, shorter hospital stay and decreased hospital costs. ERAS was endorsed by an overwhelming majority of providers.
Systematic characterization of the metabolites of echinacoside and acteoside from Cistanche tubulosa in rat plasma, bile, urine and feces based on UPLC‐ESI‐Q‐TOF‐MS
Authors: Cui Qingling , Pan Yingni , Bai Xuewei , Zhang Wei , Chen Lixia , Liu Xiaoqiu
Published: February 2016

Echinacoside (ECH) and acteoside (ACT), as the most and major active components of Cistanche tubulosa, were reported to possess cardioactive, neuroprotective and hepatocyte protective effects, as well as antibacterial, antioxidative effects. Recently, more studies have focused on their pharmacological activities. However, their metabolic profiles in vivo have not been sufficiently investigated. This study proposes an approach for rapidly identifying the complicated and unpredictable metabolites of ECH and ACT in rat plasma, bile, urine and feces, and systematically and comprehensively revealing their major metabolic pathways, based on powerful ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. Plasma, bile, urine and feces were collected from rats after a single 200 mg/kg oral dose. A total of 49 metabolites were detected in rat biological samples. Through analyzing metabolites in bile samples, it was found that ECH and ACT were subjected to a marked hepatic first‐pass effect in liver. Copyright © 2016 John Wiley & Sons, Ltd.
Reconsideration of Membership Dues: New International Fee Structure Adopted
Authors: Sonnenwald Diane H.
Published: February 2016

EDITOR'S SUMMARY

To increase international membership, Special Interest Group/International Information Issues (SIG/III) successfully proposed in 2012 to lower membership fees for ASIS&T members working in developing nations. The ASIS&T Board later lowered fees for students and early and transitional professionals from these countries. Though these moves boosted member numbers, other disparities became evident, including fees that remain prohibitive for institutions in developing nations and even for many potential individual and institutional members in countries rated “high” or “very high” in the United Nations Human Development Index. The Board approved the International Relations Committee's proposal to base membership rates on countries’ gross national income (GNI) per capita, sorting countries into three tiers. Membership fees for countries in the middle tier would be 30% of the usual fee and 20% for the lower tier and exclude print publications, the fee strategy used by the Association for Computing Machinery (ACM).
Raising a Hand: Notes from an ASIS&T Volunteer
Authors: Miller Karen
Published: February 2016

EDITOR'S SUMMARY

In accepting the 2015 James M. Cretsos Leadership Award, Karen Miller recalled her path from first tentatively raising her hand to volunteer as a SIG program coordinator at her first ASIS&T Annual Meeting. Miller soon came to realize the critical importance of engaged and dedicated volunteers throughout many of the Association's operations. The organization benefits from the time invested in innumerable volunteer efforts, all of which further goals and education efforts, while each volunteer benefits by building experience, growing a professional network and mentoring others. With volunteers making time in their personal schedules for Association activities, regular communication is crucial to help a team solidify and get tasks accomplished. Communication extends to recruiting and training volunteers to assure smooth leadership transitions. With the Association heavily dependent on volunteer activity, change may evolve slowly, suggesting the need for additional volunteer help. Miller encourages all to deepen their engagement with the Association by volunteering time, knowledge and talent.
Follow 10‐step proactive approach to improve travel safety for your student‐athletes
Authors: McCarthy Claudine
Published: February 2016

Crime and accidents impact significantly higher percentages of student‐athletes than the general student population, according to recent statistics.
Strengthen Title IX compliance by reviewing 4 key strategies
Authors: Werner Melody A.
Published: February 2016

Title IX has played a significant role in intercollegiate athletics ever since the law's inception in 1972. But the scope of Title IX broadened when the U.S. Department of Education's Office for Civil Rights began implementing comprehensive sexual violence guidelines.
Take time to reflect upon your career
Authors: Hodges Dawn Z.
Published: February 2016

I recently celebrated my 35th anniversary working in higher education. Around this time each year I take time to reflect upon my career. I suggest that you set an annual time to do the same. It might be around the new year, or on your work anniversary, or on your career anniversary, or any time that makes sense for you. It's important to do so if what you want is a meaningful, well‐planned‐out career and not just a string of jobs.
Did timing prevent university from disciplining a student‐athlete for sexual assault, harassment charges?
Authors: Gelpi Aileen
Published: February 2016

The Iowa State University Office of Judicial Affairs charged student‐athlete Yempabou Palo with sexual assault and sexual harassment of a female student in September 2012.
The relationship between chronic obstructive pulmonary disease and transcatheter aortic valve implantation—A systematic review and meta‐analysis
Authors: Liao Yan‐Biao , He Ze‐Xia , Zhao Zhen‐Gang , Wei Xin , Zuo Zhi‐liang , Li Yi‐Jian , Xiong Tian‐Yuan , Xu Yuan‐Ning , Feng Yuan , Chen Mao
Published: February 2016

Objective

The present study was performed to investigate the relationship between chronic obstructive pulmonary disease (COPD) and transcatheter aortic valve implantation (TAVI). Background: Controversies regarding the relationship between COPD and TAVI have intensified. Methods: A literature review of the PubMed online database was performed, and articles published between January 1, 2002 and March 20, 2015 were analyzed. Random‐effect and fixed‐effect models were used, depending on the between‐study heterogeneity. Results: A total of 28 studies, involving 51,530 patients, were identified in our review. The burden of COPD ranged from 12.5% to 43.4%, and COPD negatively impacted both short‐term and long‐term all‐cause survival (30 days: odds ratio [OR], 1.43, 95% CI, 1.14–1.79; >2 years: hazard ratio [HR], 1.34, 95% CI, 1.12–1.61). COPD was also associated with increased short‐term and mid‐term cardiac‐cause mortality (30 days: OR, 1.29, 95% CI, 1.02–1.64; 1 year: HR: 1.09, 1.02–1.17). Moreover, COPD (OR, 1.97, 95% CI, 1.29–3.0) predicted post‐TAVI acute kidney disease. Importantly, chronic kidney disease (CKD) (HR, 1.2, 95% CI, 1.1–1.32) and the distance of the 6 minute walk test (6MWT) (HR, 1.16, 1.06–1.27) predicted TAVI futility in patients with COPD. Conclusion: COPD is common among patients undergoing TAVI, and COPD impacts both short‐ and long‐term survival. COPD patients, who had a lower BMI, shorter distance of 6MWT and CKD, were at higher risk for TAVI futility. © 2016 Wiley Periodicals, Inc.
Activity prediction and identification of mis‐annotated chemical compounds using extreme descriptors
Authors: Borysov Petro , Hannig Jan , Marron J. S. , Muratov Eugene , Fourches Denis , Tropsha Alexander
Published: February 2016

Data pre‐processing that includes removal of descriptors with low variance is a standard first step in quantitative structure–activity relationship modeling. In this paper, we study low‐variance descriptors and show that some of them contain significant amounts of useful information. In particular, we define the notion of extreme descriptors (those variables that have the same value for almost all compounds and only a few values that are different from the common median). We show that extreme descriptors can be helpful for activity prediction in a standard binary classification setting. Moreover, we demonstrate using two case studies (M2muscarinic receptors and skin sensitization) that extreme descriptors can be used for the identification of possibly mislabeled compounds. Because of these previously unknown, but important, properties, extreme descriptors should be considered in quantitative structure–activity relationship modeling studies. Copyright © 2016 John Wiley & Sons, Ltd.
Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network
Authors: Bush WS , Crosslin DR , Owusu‐Obeng A , Wallace J , Almoguera B , Basford MA , Bielinski SJ , Carrell DS , Connolly JJ , Crawford D , Doheny KF , Gallego CJ , Gordon AS , Keating B , Kirby J , Kitchner T , Manzi S , Mejia AR , Pan V , Perry CL , Peterson JF , Prows CA , Ralston J , Scott SA , Scrol A , Smith M , Stallings SC , Veldhuizen T , Wolf W , Volpi S , Wiley K , Li R , Manolio T , Bottinger E , Brilliant MH , Carey D , Chisholm RL , Chute CG , Haines JL , Hakonarson H , Harley JB , Holm IA , Kullo IJ , Jarvik GP , Larson EB , McCarty CA , Williams MS , Denny JC , Rasmussen‐Torvik LJ , Roden DM , Ritchie MD
Published: February 2016

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE‐PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE‐PGx data release includes sequence‐derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation‐Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.
Three‐month‐old infants’ sensitivity to horizontal information within faces
Authors: de Heering Adélaïde , Goffaux Valérie , Dollion Nicolas , Godard Ornella , Durand Karine , Baudouin Jean‐Yves
Published: February 2016

Horizontal information is crucial to face processing in adults. Yet the ontogeny of this preferential type of processing remains unknown. To clarify this issue, we tested 3‐month‐old infants’ sensitivity to horizontal information within faces. Specifically, infants were exposed to the simultaneous presentation of a face and a car presented in upright or inverted orientation while their looking behavior was recorded. Face and car images were either broadband (UNF) or filtered to only reveal horizontal (H), vertical (V) or this combined information (HV). As expected, infants looked longer at upright faces than at upright cars, but critically, only when horizontal information was preserved in the stimulus (UNF, HV, H). These results first indicate that horizontal information already drives upright face processing at 3 months of age. They also recall the importance, for infants, of some facial features, arranged in a top‐heavy configuration, particularly revealed by this band of information. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 536–542, 2016.
Liposomes as potential masking agents in sport doping. Part 1: analysis of phospholipids and sphingomyelins in drugs and biological fluids by aqueous normal‐phase liquid chromatography‐tandem mass spectrometry
Authors: Esposito Simone , Colicchia Sonia , de la Torre Xavier , Mazzarino Monica , Botrè Francesco
Published: February 2016

In the present work, aqueous normal‐phase liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS), in different acquisition modes, was employed for the direct analysis and profiling of nine phospholipid classes (phosphatidic acids, phosphatidylserines, phosphatidylethanolamines, lysophosphatidylethanolamines, phosphatidylglycerols, phosphatidylinositols, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins) in biological and pharmaceutical matrices.

After chromatographic separation by a diol column, detection and elucidation of phospholipid and sphingomyelin classes and molecular species were performed by different scan acquisition modes. For screening analysis, molecular ions [M + H]+ were detected in positive precursor ion scan of m/z 184 for the classes of phosphatidylcholines, lyso‐phosphatidylcholines and sphingomyelins; while phosphatidylethanolamines and lyso‐phosphatidylethanolamines were detected monitoring neutral loss scan of 141 Da; and phosphatidylserines detected using neutral loss scan of 184 Da. Molecular ions [M‐H]‐ were instead acquired in negative precursor ion scan of m/z 153 for the classes of phosphatidic acids and phosphatidylglycerols; and of m/z 241 for the phosphatidylinositols. For the identification of the single molecular species, product ion scan mass spectra of the [M + HCOO]‐ ions for phosphatidylcholines and [M + H]+ ions for the other phospholipids considered were determined for each class and compared with the fragmentation pattern of model phospholipid reference standard. By this approach, nearly 100 phospholipids and sphingomyelins were detected and identified. The optimized method was then used to characterize the phospholipid and sphingomyelin profiles in human plasma and urine samples and in two phospholipid‐based pharmaceutical formulations, proving that it also allows to discriminate compounds of endogenous origin from those resulting from the intake of pharmaceutical products containing phospholipidic liposomes. Copyright © 2016 John Wiley & Sons, Ltd.
A demographic model for sex ratio evolution and the effects of sex‐biased offspring costs
Authors: Shyu Esther , Caswell Hal
Published: February 2016

The evolution of the primary sex ratio, the proportion of male births in an individual's offspring production strategy, is a frequency‐dependent process that selects against the more common sex. Because reproduction is shaped by the entire life cycle, sex ratio theory would benefit from explicitly two‐sex models that include some form of life cycle structure. We present a demographic approach to sex ratio evolution that combines adaptive dynamics with nonlinear matrix population models. We also determine the evolutionary and convergence stability of singular strategies using matrix calculus. These methods allow the incorporation of any population structure, including multiple sexes and stages, into evolutionary projections. Using this framework, we compare how four different interpretations of sex‐biased offspring costs affect sex ratio evolution. We find that demographic differences affect evolutionary outcomes and that, contrary to prior belief, sex‐biased mortality after parental investment can bias the primary sex ratio (but not the corresponding reproductive value ratio). These results differ qualitatively from the widely held conclusions of previous models that neglect demographic structure.
Noninvasive genetic sampling reveals intrasex territoriality in wolverines
Authors: Bischof Richard , Gregersen Espen R. , Brøseth Henrik , Ellegren Hans , Flagstad Øystein
Published: February 2016

Due to its conspicuous manifestations and its capacity to shape the configuration and dynamics of wild populations, territorial behavior has long intrigued ecologists. Territoriality and other animal interactions in situ have traditionally been studied via direct observations and telemetry. Here, we explore whether noninvasive genetic sampling, which is increasingly supplementing traditional field methods in ecological research, can reveal territorial behavior in an elusive carnivore, the wolverine (Gulo gulo). Using the locations of genotyped wolverine scat samples collected annually over a period of 12 years in central Norway, we test three predictions: (1) male home ranges constructed from noninvasive genetic sampling data are larger than those of females, (2) individuals avoid areas used by other conspecifics of the same sex (intrasexual territoriality), and (3) avoidance of same‐sex territories diminishes or disappears after the territory owner's death. Each of these predictions is substantiated by our results: sex‐specific differences in home range size and intrasexual territoriality in wolverine are patently reflected in the spatial and temporal configuration of noninvasively collected genetic samples. Our study confirms that wildlife monitoring programs can utilize the spatial information in noninvasive genetic sampling data to detect and quantify home ranges and social organization.
Functional integrity of freshwater forested wetlands, hydrologic alteration, and climate change
Authors: Middleton Beth A. , Souter Nicholas J.
Published: February 2016

Climate change will challenge managers to balance the freshwater needs of humans and wetlands. The Intergovernmental Panel on Climate Change predicts that most regions of the world will be exposed to higher temperatures,
2
, and more erratic precipitation, with some regions likely to have alternating episodes of intense flooding and mega-drought. Coastal areas will be exposed to more frequent saltwater inundation as sea levels rise. Local land managers desperately need intra-regional climate information for site-specific planning, management, and restoration activities. Managers will be challenged to deliver freshwater to floodplains during climate change-induced drought, particularly within hydrologically altered and developed landscapes. Assessment of forest health, both by field and remote sensing techniques, will be essential to signal the need for hydrologic remediation. Studies of the utility of the release of freshwater to remediate stressed forested floodplains along the Murray and Mississippi Rivers suggest that brief episodes of freshwater remediation for trees can have positive health benefits for these forests. The challenges of climate change in forests of the developing world will be considered using the Tonle Sap of Cambodia as an example. With little ecological knowledge of the impacts, managing climate change will add to environmental problems already faced in the developing world with new river engineering projects. These emerging approaches to remediate stressed trees will be of utmost importance for managing worldwide floodplain forests with predicted climate changes.
Climate extremes and ozone pollution: a growing threat to china’s food security
Authors: Tian Hanqin , Ren Wei , Tao Bo , Sun Ge , Chappelka Art , Wang Xiaoke , Pan Shufen , Yang Jia , Liu Jiyuan , S. felzer Ben , M. melillo Jerry , Reilly John
Published: February 2016

Ensuring global food security requires a sound understanding of climate and environmental controls on crop productivity. The majority of existing assessments have focused on physical climate variables (i.e., mean temperature and precipitation), but less on the increasing climate extremes (e.g., drought) and their interactions with increasing levels of tropospheric ozone (O
3
). Here we quantify the combined impacts of drought and O
3
on China's crop yield using a comprehensive, process-based agricultural ecosystem model in conjunction with observational data. Our results indicate that climate change/variability and O
3
together led to an annual mean reduction of crop yield by 10.0% or 55 million tons per year at the national level during 1981–2010. Crop yield shows a growing threat from severe episodic droughts and increasing O
3
concentrations since 2000, with the largest crop yield losses occurring in northern China, causing serious concerns in food supply security in China. Our results imply that reducing tropospheric O
3
levels is critical for securing crop production in coping with increasing frequency and severity of extreme climate events such as droughts. Improving air quality should be a core component of climate adaptation strategies.
Biocatalytic synthesis of poly(ε‐caprolactone) using modified lipase in ionic liquid media
Authors: Yuan Jiugang , Dai Yaping , Yu Yuanyuan , Wang Ping , Wang Qiang , Fan Xuerong
Published: February 2016

Ionic liquids have been used as exceptional nonaqueous reaction media for enzymatic transformation. The ring‐opening polymerization of ε‐caprolactone catalyzed by Novozyme‐435 lipase was successfully conducted in 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([Bmim]PF6) ionic liquid. 1H‐NMR and MALDI‐TOF analyses of poly(ε‐caprolactone) (PCL) formed by Novozyme‐435 lipase‐catalyzed reaction revealed an asymmetric telechelic α‐hydroxy‐ω‐carboxylic acid end group. The effects of enzyme concentration, temperature, reaction time, and water activities on monomer conversion and Mn were systematically evaluated. Through the optimization of reaction conditions, PCL was produced in 85% monomer conversion, with an Mn of 5942, in [Bmim]PF6 at 60°C for 48 h. DSC results demonstrated that high‐molecular‐weight PCL exhibited an excellent thermal property. SEM results showed that PCL had a clear spherulites structure, which could provide a large surface area for cell adhesion. These results showed that [Bmim]PF6 ionic liquid was suitable for the biocatalytic synthesis of PCL using Novozyme‐435 lipase, and could be used as alternative environmentally friendly media to replace the traditional organic solvents.
Estimation of extreme quantiles conditioning on multivariate critical layers
Authors: Bernardino E. Di , Palacios‐Rodríguez F.
Published: February 2016

Let Ti:=[Xi|X∈∂L(α)], for i = 1,…,d, where X = (X1,…,Xd) is a risk vector and ∂L(α) is the associated multivariate critical layer at level α∈(0,1). The aim of this work is to propose a non‐parametric extreme estimation procedure for the (1 − pn)‐quantile of Ti for a fixed α and when pn→0, as the sample size n→+∞. An extrapolation method is developed under the Archimedean copula assumption for the dependence structure of X and the von Mises condition for marginal Xi. The main result is the central limit theorem for our estimator for p = pn→0, when n tends towards infinity. A set of simulations illustrates the finite‐sample performance of the proposed estimator. We finally illustrate how the proposed estimation procedure can help in the evaluation of extreme multivariate hydrological risks. Copyright © 2016 John Wiley & Sons, Ltd.
Frequency of MED12 mutations in phyllodes tumors: Inverse correlation with histologic grade
Authors: Yoon Nara , Bae Go Eun , Kang So Young , Choi Mi Sun , Hwang Hye Won , Kim Seok Won , Lee Jeong Eon , Nam Seok Jin , Gong Gyungyub , Lee Hee Jin , Bae Young Kyung , Lee Ahwon , Cho Eun Yoon
Published: February 2016

Phyllodes tumor (PT) is a rare breast biphasic tumor with a potential risk of recurrence and metastasis. In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of these mutations in malignant type PT was evaluated. Analysis of MED12 mutations was performed by Sanger sequencing targeting the hotspot mutation region (exon 2) of MED12. Immunohistochemistry was also applied for evaluation of MED12 protein expression on tissue microarray blocks for 133 PTs including 50 benign, 50 borderline, and 33 malignant cases. A notable difference in the frequency of MED12 mutations was found according to histologic grade (71.4% of benign PTs, 51% of borderline PTs, 26.9% of malignant PTs; P < 0.001). MED12 protein expression was not correlated with MED12 mutation status. Patients with malignant PTs that harbored MED12 mutations demonstrated improved disease‐free survival (DFS) compared with those without MED12 mutation (P = 0.07). MED12 mutation was a common molecular alteration in PT and the frequency of MED12 mutation decreased with increasing histologic grade. In malignant PT, MED12 exon 2 mutations showed improved DFS but without significance. © 2016 Wiley Periodicals, Inc.
Genome‐wide association study in mice identifies loci affecting liver‐related phenotypes including Sel1l influencing serum bile acids
Authors: Wu Wei , Patel Ami , Kyöstilä Kaisa , Lohi Hannes , Mladkova Nikol , Kiryluk Krzysztof , Sun Xiaoyun , Lefkowitch Jay H. , Worman Howard J. , Gharavi Ali G.
Published: February 2016

Using publicly available data from inbred mouse strains, we conducted a genome‐wide association study to identify loci that accounted for liver‐related phenotypes between C57BL/6J and A/J mice fed a Paigen diet. We confirmed genome‐wide significant associations for hepatic cholesterol (chromosome 10A2) and serum total bile acid concentration (chromosome 12E) and identified a new locus for liver inflammation (chromosome 7C). Analysis of consomic mice confirmed that chromosome 12 A/J alleles accounted for the variance in serum total bile acid concentrations and had pleiotropic effects on liver mass, serum cholesterol, and serum alanine aminotransferase activity. Using an affected‐only haplotype analysis among strains, we refined the chromosome 12E signal to a 1.95 Mb linkage disequilibrium block containing only one gene, sel‐1 suppressor of lin‐12‐like (Sel1l). RNA sequencing and immunoblotting demonstrated that the risk allele locally conferred reduced expression of SEL1L in liver and distantly down‐regulated pathways associated with hepatocyte nuclear factor 1 homeobox A (Hnf1a) and hepatocyte nuclear factor 4A (Hnf4a), known modifiers of bile acid transporters and metabolic traits. Consistent with these data, knockdown of SEL1L in HepG2 cells resulted in reduced HNF1A and HNF4A and increased bile acids in culture media; it further captured multiple molecular signatures observed in consomic mouse livers with reduced SEL1L. Finally, dogs harboring a SEL1L mutation and Sel1l
+/− mice fed a Paigen diet had significantly increased serum total bile acid concentrations, providing independent confirmation linking SEL1L to bile acid metabolism. Conclusion: Genetic analyses of inbred mouse strains identified loci affecting different liver‐related traits and implicated Sel1l as a significant determinant of serum bile acid concentration. (Hepatology 2016;63:1943‐1956)
The effects of pioglitazone adjuvant therapy on negative symptoms of patients with chronic schizophrenia: a double‐blind and placebo‐controlled trial
Authors: Iranpour Negar , Zandifar Atefeh , Farokhnia Mehdi , Goguol Amirhossein , Yekehtaz Habibeh , Khodaie‐Ardakani Mohammad‐Reza , Salehi Bahman , Esalatmanesh Sophia , Zeionoddini Atefeh , Mohammadinejad Payam , Zeinoddini Arefeh , Akhondzadeh Shahin
Published: February 2016

Objective

The evident central role of inflammation, oxidative stress, and metabolic derangement in pathophysiology of negative symptoms of schizophrenia has opened new insights into probable pharmacological options for these symptoms. Pioglitazone is an antidiabetic agent with anti‐inflammatory and antioxidant properties. In this study, we evaluated the efficacy of pioglitazone as an adjunct to risperidone for reduction of negative symptoms in schizophrenia.

Methods

In this randomized, double‐blind, placebo‐controlled trial, 40 patients with chronic schizophrenia and a minimum score of 20 on the negative subscale of Positive and Negative Syndrome Scale (PANSS) were randomly allocated to receive risperidone plus either pioglitazone (30 mg/day) or placebo for 8 weeks. Patients' symptoms and adverse events were rated at baseline and weeks 2, 4, 6, and 8. The difference between the two groups in decline of PANSS negative subscale scores was considered as the primary outcome of this study.

Results

At the study endpoint, patients in the pioglitazone group showed significantly more improvement in PANSS negative subscale scores (p < 0.001) as well as PANSS total scores (p = 0.01) compared with the placebo group.

Conclusion

These findings suggest the probable efficacy of pioglitazone as an augmentation therapy in reducing the negative symptoms of schizophrenia. Copyright © 2016 John Wiley & Sons, Ltd.