bluuebunny/crossref_metadata_2025 huggingface dataset:
Status Has Its Privileges: The Psychological Benefit of Status‐Reinforcing Behaviors
Authors: Ivanic Aarti S.
Published: June 2015

Many firms use loyalty programs to stratify their customers into status tiers and reward those with high status with special privileges. This research documents how consumers with high status willingly incur a cost to utilize the exclusive privileges, termed “status‐reinforcing behaviors,” that accompany their high status because doing so reinforces their high‐status identity. They do so in the absence of threats to their high status or self‐worth and also in the absence of an opportunity to conspicuously signal their high status to others through face‐to‐face interactions. This suggests that the behavior is undertaken neither for compensatory nor conspicuous reasons. Across two studies, results indicate that consumers who hold high status in a loyalty program engage in “status‐reinforcing behaviors,” even when doing so offers no material or conspicuous signaling benefit and in fact causes them to incur some costs. Engaging in status‐reinforcing behaviors yields a distinct psychological outcome—elevated feelings of prestige. Results indicate that when high status is made salient, individuals demonstrate a greater propensity to engage in status‐reinforcing behaviors. However, individuals who have a reinforced sense of status (i.e., already validated their high‐status position) are less likely to engage in status‐reinforcing behaviors, which suggests that utilizing status privileges does serve as a reinforcing behavior, even in the absence of a status threat.
Pharmacodynamics and Pharmacokinetics of Fluticasone Furoate/Vilanterol in Healthy Chinese Subjects
Authors: Chen Xia , Zheng Xin , Jiang Ji , Hu Pei , Wu Kai , Zhuang Lihong , Liu Lian , Du Xin , Kempsford Rodger , Allen Ann
Published: June 2015

Study Objective

To investigate the pharmacodynamic and pharmacokinetic profiles of fluticasone furoate (FF)/vilanterol (VI) – a fixed‐dose combination of an inhaled corticosteroid (ICS) and a long‐acting β2‐agonist for the treatment of asthma and chronic obstructive pulmonary disease – after single and repeat administration in healthy Chinese subjects.

Design

Double‐blind, placebo‐controlled, single‐site, randomized, four‐way crossover study.

Setting

The Clinical Pharmacological Research Centre at Peking Union Medical College Hospital [PUMCH]) in Beijing, China.

Subjects

Sixteen healthy, nonsmoking Chinese adults.

Intervention

Subjects were randomized to receive FF/VI 50/25, 100/25, or 200/25 μg, or placebo once/daily in the morning, delivered by the Ellipta dry powder inhaler, for 7 consecutive days. The subjects then received the other three treatments, with each treatment period separated by a 7‐day washout period.

Measurements and Main Results

The co‐primary outcome measures reflected pharmacodynamic responses relating to recognized class effects of the two drug classes: reduced serum cortisol level (ICSs), and increased Fridericia's corrected QT interval (QTcF) and reduced serum potassium level (long‐acting β2‐agonists). Co‐primary pharmacodynamic endpoints were 0–24‐hour weighted mean serum cortisol level on day 7 (cortisol0–24 hr, Day 7), and 0–4‐hour weighted mean and maximum QTcF and weighted mean and minimum serum potassium level on days 1 and 7. Fluticasone furoate and VI plasma concentrations, derived pharmacokinetic parameters, and safety were also assessed. Of the 16 subjects randomized, 15 completed the study. Reductions in cortisol0–24 hour, Day 7 of 15% and 25% were observed with FF/VI 100/25 and 200/25 μg, respectively, versus placebo. Minor increases (< 10 msec) in maximum QTcF on day 7 were seen with FF/VI 50/25 and 100/25 μg but not with 200/25 μg. Slight decreases in serum potassium level were only observed in subjects receiving FF/VI 50/25 μg on day 1 and FF/VI 50/25 and 200/25 μg on day 7. Fluticasone furoate accumulation (day 7 vs day 1) for FF/VI 50/25–200/25 μg ranged from 38 to 54% for maximum observed concentration and 63–71% for area under the concentration‐time curve from 0 to 4 hours. Fluticasone furoate pharmacokinetics were less than dose proportional. The VI pharmacokinetic profiles were similar for all three FF/VI doses. Adverse events were all mild in intensity and were reported by 13 (81%) of the 16 subjects.

Conclusion

In healthy Chinese subjects, minimal and non–clinically relevant β‐adrenergic pharmacodynamic effects were observed with FF/VI doses ranging from 50/25 to 200/25 μg. FF dose‐dependent reductions in serum cortisol levels of 15–25% were seen after administration of FF/VI 100/25 and 200/25 μg. FF/VI was safe and well tolerated in these subjects at doses ranging from 50/25 to 200/25 μg.
A systematic review of distributed Agile software engineering
Authors: Rizvi Buturab , Bagheri Ebrahim , Gasevic Dragan
Published: June 2015

The combination of Agile methods and distributed software development via remote teams represents an emerging approach to address the challenges such as late feedback, slow project timelines, and high cost, typically associated with software development projects. However, when projects are implemented using an Agile model with distributed human resources, there are a number of challenges that need to be considered and mitigated. The objectives of our work are multifold. First, we would like to understand the reasons and conditions that lead to the adoption of distributed Agile software engineering (DASE) practices. Second, we would like to investigate and find out the most important risks that threaten a DASE approach and what mitigation strategies exist to address them. Finally, we would like to highlight which of the available approaches among the existing Agile methodologies has been successfully adopted by the community. We intend to solidify our findings by exploring the strength of the evidence that has been reported in the literature.

We carried out a systematic literature review of DASE techniques and approaches. This systematic literature review found time zone difference, knowledge of resources, lack of infrastructure, missing roles, and responsibilities as being the primary challenges that needed to be addressed. Copyright © 2015 John Wiley & Sons, Ltd.
Preconditioning for classical relationships: a note relating ridge regression and OLS p‐values to preconditioned sparse penalized regression
Authors: Rohe Karl
Published: June 2015

When the design matrix has orthonormal columns, “soft thresholding” the ordinary least squares solution produces the Lasso solution. If one uses the Puffer preconditioned Lasso, then this result generalizes from orthonormal designs to full rank designs (Theorem 1). Theorem 2 refines the Puffer preconditioner to make the Lasso select the same model as removing the elements of the ordinary least squares solution with the largest p‐values. Using a generalized Puffer preconditioner, Theorem 3 relates ridge regression to the preconditioned Lasso; this result is for the high‐dimensional setting, p > n. Where the standard Lasso is akin to forward selection, Theorems 1, 2, and 3 suggest that the preconditioned Lasso is more akin to backward elimination. These results hold for sparse penalties beyond; for a broad class of sparse and non‐convex techniques (e.g. SCAD and MC+), the results hold for all local minima. Copyright © 2015 John Wiley & Sons, Ltd.
Stories, proverbs, and anecdotes as scaffolds for learning science concepts
Authors: Mutonyi Harriet
Published: June 2015

Few research studies in science education have looked at how stories, proverbs, and anecdotes can be used as scaffolds for learning. Stories, proverbs, and anecdotes are cultural tools used in indigenous communities to teach children about their environment. The study draws on Bruner's work and the theory of border crossing to argue that stories, proverbs, and anecdotes can be useful tools in the teaching of science concepts. The study uses a qualitative approach to understand how students in a secondary school in Uganda were appropriating stories, proverbs, and anecdotes to explain their understanding on health and HIV‐related issues. The data collection methods included interviews, focus group discussions, journaling, and document collection. The major finding is that use of stories, proverbs, and anecdotes drawn from the students' cultural context helps them understand science concepts. The main argument of the article is that cultural tools (stories, proverbs, anecdotes) can be used to scaffold students' learning of scientific concepts. The implications are that stories, proverbs, and anecdotes can be used to help students may not be inclined to science, to enter into the world of science by linking their everyday world to the culture of science. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 53: 943–971, 2016
The Bare Minimum: The Reality of Global Anaesthesia and Patient Safety
Authors: McQueen Kelly , Coonan Tom , Ottaway Andrew , Hendel Simon , Bagutifils Paulin R. , Froese Alison , Neighbor Robert , Perndt Haydn
Published: June 2015

Introduction

Current guidelines for the provision of safe anaesthesia from the World Health Organization and the World Federation of Societies of Anaesthesiologists (WFSA) are unachievable in a majority of low and middle‐income countries (LMICs) worldwide.

Methods

Current guidelines for anaesthesia and patient safety provisions from the WHO and WFSA are compared with local ability to achieve these recommendations in LMICs.

Conclusions

Influential international organizations have historically published anaesthesia guidelines, but for the most part, without impacting substantial documentable changes or outcomes in low‐income environments. This analysis, and subsequent recommendations, reviews the effectiveness of existing strategies for international guidelines, and proposes practical, step‐wise implementation of patient safety approaches for LMICs.
Do clinical features of Lesch‐Nyhan disease correlate more closely with hypoxanthine or guanine recycling?
Authors: Schretlen David J. , Callon Wynne , Ward Rebecca E. , Fu Rong , Ho Tiffany , Gordon Barry , Harris James C. , Jinnah H. A.
Published: June 2015

Lesch‐Nyhan disease (LND) is a rare, X‐linked recessive neurodevelopmental disorder caused by deficiency of hypoxanthine‐guanine phosphoribosyltransferase (HGprt), an enzyme in the purine salvage pathway. HGprt has two functions; it recycles hypoxanthine and guanine. Which of these two functions is more relevant for pathogenesis is unclear because some evidence points to hypoxanthine recycling, but other evidence points to guanine recycling. In this study, we selectively assayed hypoxanthine (Hprt) and guanine (Gprt) recycling in skin fibroblasts from 17 persons with LND, 11 with an attenuated variant of the disease (LNV), and 19 age‐, sex‐, and race‐matched healthy controls (HC). Activity levels of both enzymes differed across groups (p < 0.0001), but only Gprt distinguished patients with LND from those with LNV (p < 0.05). Gprt also showed slightly stronger correlations than Hprt with 13 of 14 measures of the clinical phenotype, including the severity of dystonia, cognitive impairment, and behavioral abnormalities. These findings suggest that loss of guanine recycling might be more closely linked to the LND/LNV phenotype than loss of hypoxanthine recycling.
Stereotactic Radiosurgery for Metastases in Eloquent Central Brain Locations
Authors: Hsu Fred , Nichol Alan , Ma Roy , Kouhestani Para , Toyota Brian , McKenzie Michael
Published: June 2015

Background: To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. Methods: We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. Results: For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Conclusions: Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.
Law, Regulation, and Safety Crime: Exploring the Boundaries of Criminalizing Powerful Corporate Actors
Authors: Bittle Steven , Snider Laureen
Published: June 2015

This article interrogates the laws that govern safety crimes, harmful but typically unintentional acts of negligence that occur in the production of goods and services. Acts that injure employees at work are commonly depicted in legal discourses as accidents and penalized through administrative laws, although other negligent acts such as driving offences causing injury or death are treated as potentially criminal events. Through a discourse analysis of legal and regulatory texts and documents, the authors argue that the constitution of workplace safety crime is rooted in complex historical factors that shape state responses to corporate wrongdoing. This article documents the roots of this “common sense” view of workplace crime, empirically focusing on Canadian corporate negligence law, and concludes with tentative strategies of resistance and change.
Movement in Sound/Sound in Movement: Choreographic Answer
Authors: Lee Jean
Published: June 2015

This essay illustrates the working of the process of music and dance collaboration that has been developed since 2010 by composer Elo Masing and choreographer Jean Lee. It includes exemplification of their empirical work from a first person viewpoint, presented in chronological order. This paper questions how performer(s) to performer(s) interrelationship will affect the performer(s) to spectator(s) interrelationship in live performance, encompassing improvisation and examining spectatorship.
Secrets Under the Skin: Blurred Boundaries, Shifting Enactments, and Repositioning in Research-Based Dance in Ghana and Cuba
Authors: Crosby Jill Flanders , Jeffery Brian , Kim Marianne , Matthews Susan
Published: June 2015

This roundtable reflects on the processes of de-centering from multiple lenses and temporal placements inside the research and creative process. It is based on a collaborative, intermedia, and multitemporal contemporary performance/art installation informed by long-term ethnographic research of dance and ritual in Ghana and Cuba. Roundtable participants will excavate the process of conducting the research and creating the installation that continues to exhibit internationally at venues ranging from art galleries and libraries to rural research field sites. The installation offers a matrix of layered artistic exploration grounded in ethnographic inquiry that does not sit squarely inside a singular discipline. Inherently transdisciplinary, with multiple entanglements and porous boundaries, it offers “interpretive frictions” at the borders of ethnography, performance, material culture, research-based choreography, and embodiment of lived experience.
Samah—Kardeşlik Töreni: A Dynamic Bodily Archive for the Alevi Semah
Authors: De Rosa Sinibaldo
Published: June 2015

In this paper, the current practices and discourses surrounding the Alevisemahare analysed in a peculiar reflexive and embodied manner. The semah is comprehended here as a “dynamic structured body system,” which is differently recognized asibadet(devotional practice),dans(dance), ormeditasyon(meditation), and whose practice is alleged to support ideals of inter-religious peace and gender equity. Its analysis resorts to data collected during an intensive fieldwork that was carried out between 2008 and 2011 by following the experimental theater piece with the titleSamah—Kardeşlik Töreni(Samah—the Ritual of Brotherhood) of the Ankara Deneme Sahnesi amateur group based in Ankara (Turkey). This play is the result of a re-elaboration of ethnographic data that were collected throughout the Anatolian peninsula since the early 1980s by a team of students and researchers affiliated with the Theatre Department of Ankara University. In this process of re-adaptation for the stage, the semah was singled out of its religious source (theAyin-i Cemritual) for which it started to display a mirror image offering a condensed exposition of the Alevi rituals to an audience. This paper contextualizes these formal adaptations on the stage into the frame of the abrupt history of migration and urbanization in late twentieth century Turkey. Such historical processes played a major role in the current circulation of the semah in Turkey as well as abroad, resulting also in its perspective inscription as world intangible heritage.
Whole-grain foods and chronic disease: evidence from epidemiological and intervention studies
Authors: Seal Chris J. , Brownlee Iain A.
Published: June 2015

Cereal-based foods are key components of the diet and they dominate most food-based dietary recommendations in order to achieve targets for intake of carbohydrate, protein and dietary fibre. Processing (milling) of grains to produce refined grain products removes key nutrients and phytochemicals from the flour and although in some countries nutrients may be replaced with mandatory fortification, overall this refinement reduces their potential nutritional quality. There is increasing evidence from both observational and intervention studies that increased intake of less-refined, whole-grain (WG) foods has positive health benefits. The highest WG consumers are consistently shown to have lower risk of developing CVD, type 2 diabetes and some cancers. WG consumers may also have better digestive health and are likely to have lower BMI and gain less weight over time. The bulk of the evidence for the benefits of WG comes from observational studies, but evidence of benefit in intervention studies and potential mechanisms of action is increasing. Overall this evidence supports the promotion of WG foods over refined grain foods in the diet, but this would require adoption of standard definitions of ‘whole grain’ and ‘whole-grain foods’ which will enable innovation by food manufacturers, provide clarity for the consumer and encourage the implementation of food-based dietary recommendations and public health strategies.
EVALUATION OF PATIENT INVOLVEMENT IN A HEALTH TECHNOLOGY ASSESSMENT
Authors: Dipankui Mylène Tantchou , Gagnon Marie-Pierre , Desmartis Marie , Légaré France , Piron Florence , Gagnon Johanne , Rhiands Marc , Coulombe Martin
Published: June 2015

Objectives: We sought to evaluate patient involvement (consultation and direct participation) in the assessment of alternative measures to restraint and seclusion among adults in short-term hospital wards (in psychiatry) and long-term care facilities for the elderly.

Methods: We conducted individual semi-structured interviews with thirteen stakeholders: caregivers, healthcare managers, patient representatives, health technology assessment (HTA) unit members, researchers, and members of the local HTA scientific committee. Data were collected until saturation. We carried out content analysis of two HTA reports and four other documents that were produced in relation with this HTA. We also used field notes taken during formal meetings and informal discussions with stakeholders. We performed thematic analysis based on a framework for assessing patient involvement in HTA. We then triangulated data.

Results: For the majority of interviewees, patient consultation enriched the content of the HTA report and its recommendations. This also made it possible to suggest other alternatives that could reduce the use of restraint and seclusion and helped confirm some views and comments from healthcare professionals consulted in this HTA. The direct participation of patient representatives enabled rephrasing of some findings so as to bring the patient perspective to the HTA report.

Conclusions: Patient consultation was seen as having directly influenced the content of the HTA report while direct participation made it possible to rephrase some findings. This is one of few studies to assess the impact of patient involvement in HTA and more such studies are needed to identify the best ways to improve the input of such involvement.
INTEGRATING ETHICS IN HEALTH TECHNOLOGY ASSESSMENT: MANY WAYS TO ROME
Authors: Hofmann Björn , Oortwijn Wija , Bakke Lysdahl Kristin , Refolo Pietro , Sacchini Dario , van der Wilt Gert Jan , Gerhardus Ansgar
Published: June 2015

Objectives: The aim of this study was to identify and discuss appropriate approaches to integrate ethical inquiry in health technology assessment (HTA).

Methods: The key question is how ethics can be integrated in HTA. This is addressed in two steps: by investigating what it means to integrate ethics in HTA, and by assessing how suitable the various methods in ethics are to be integrated in HTA according to these meanings of integration.

Results: In the first step, we found that integrating ethics can mean that ethics is (a) subsumed under or (b) combined with other parts of the HTA process; that it can be (c) coordinated with other parts; or that (d) ethics actively interacts and changes other parts of the HTA process. For the second step, we found that the various methods in ethics have different merits with respect to the four conceptions of integration in HTA.

Conclusions: Traditional approaches in moral philosophy tend to be most suited to be subsumed or combined, while processual approaches being close to the HTA or implementation process appear to be most suited to coordinated and interactive types of integration. The article provides a guide for choosing the ethics approach that appears most appropriate for the goals and process of a particular HTA.
Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women
Authors: DARENG E. O. , MA B. , FAMOOTO A. O. , AKAROLO-ANTHONY S. N. , OFFIONG R. A. , OLANIYAN O. , DAKUM P. S. , WHEELER C. M. , FADROSH D. , YANG H. , GAJER P. , BROTMAN R. M. , RAVEL J. , ADEBAMOWO C. A.
Published: June 2015

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array®HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance ofLactobacillusspp. in 50% of participants; CST III (dominated byL. iners) in 39·2%; CST I (dominated byL. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance ofLactobacillussp. with increased abundance of anaerobes particularly of the generaPrevotellaandLeptotrichiain HIV-negative women (P< 0·05). These results are hypothesis generating and further studies are required.
Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression
Authors: Yang H , Pellegrini L , Napolitano A , Giorgi C , Jube S , Preti A , Jennings C J , De Marchis F , Flores E G , Larson D , Pagano I , Tanji M , Powers A , Kanodia S , Gaudino G , Pastorino S , Pass H I , Pinton P , Bianchi M E , Carbone M
Published: June 2015

High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information.
Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus
Authors: Xiong Xiaorui R. , Liang Feixue , Zingg Brian , Ji Xu-ying , Ibrahim Leena A. , Tao Huizhong W. , Zhang Li I.
Published: June 2015

Defense against environmental threats is essential for animal survival. However, the neural circuits responsible for transforming unconditioned sensory stimuli and generating defensive behaviours remain largely unclear. Here, we show that corticofugal neurons in the auditory cortex (ACx) targeting the inferior colliculus (IC) mediate an innate, sound-induced flight behaviour. Optogenetic activation of these neurons, or their projection terminals in the IC, is sufficient for initiating flight responses, while the inhibition of these projections reduces sound-induced flight responses. Corticocollicular axons monosynaptically innervate neurons in the cortex of the IC (ICx), and optogenetic activation of the projections from the ICx to the dorsal periaqueductal gray is sufficient for provoking flight behaviours. Our results suggest that ACx can both amplify innate acoustic-motor responses and directly drive flight behaviours in the absence of sound input through corticocollicular projections to ICx. Such corticofugal control may be a general feature of innate defense circuits across sensory modalities.
AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia
Authors: Ruozi Giulia , Bortolotti Francesca , Falcione Antonella , Dal Ferro Matteo , Ukovich Laura , Macedo Antero , Zentilin Lorena , Filigheddu Nicoletta , Cappellari Gianluca Gortan , Baldini Giovanna , Zweyer Marina , Barazzoni Rocco , Graziani Andrea , Zacchigna Serena , Giacca Mauro
Published: June 2015

Functional screening of expression libraries in vivo would offer the possibility of identifying novel biotherapeutics without a priori knowledge of their biochemical function. Here we describe a procedure for the functional selection of tissue-protective factors based on the in vivo delivery of arrayed cDNA libraries from the mouse secretome using adeno-associated virus (AAV) vectors. Application of this technique, which we call FunSel, in the context of acute ischaemia, revealed that the peptide ghrelin protects skeletal muscle and heart from ischaemic damage. When delivered to the heart using an AAV9 vector, ghrelin markedly reduces infarct size and preserves cardiac function over time. This protective activity associates with the capacity of ghrelin to sustain autophagy and remove dysfunctional mitochondria after myocardial infarction. Our findings describe an innovative tool to identify biological therapeutics and reveal a novel role of ghrelin as an inducer of myoprotective autophagy.
Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling
Authors: Zuckermann Marc , Hovestadt Volker , Knobbe-Thomsen Christiane B. , Zapatka Marc , Northcott Paul A. , Schramm Kathrin , Belic Jelena , Jones David T. W. , Tschida Barbara , Moriarity Branden , Largaespada David , Roussel Martine F. , Korshunov Andrey , Reifenberger Guido , Pfister Stefan M. , Lichter Peter , Kawauchi Daisuke , Gronych Jan
Published: June 2015

In vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited to validate their role in tumorigenesis. For tumour suppressor genes this has proven more challenging due to technical aspects. To provide a flexible and effective method for investigating somatic loss-of-function alterations and their influence on tumorigenesis, we have established CRISPR/Cas9-mediated somatic gene disruption, allowing for in vivo targeting of TSGs. Here we demonstrate the utility of this approach by deleting single (Ptch1) or multiple genes (Trp53, Pten, Nf1) in the mouse brain, resulting in the development of medulloblastoma and glioblastoma, respectively. Using whole-genome sequencing (WGS) we characterized the medulloblastoma-driving Ptch1 deletions in detail and show that no off-targets were detected in these tumours. This method provides a fast and convenient system for validating the emerging wealth of novel candidate tumour suppressor genes and the generation of faithful animal models of human cancer.
The molecular size of the extra-membrane domain influences the diffusion of the GPI-anchored VSG on the trypanosome plasma membrane
Authors: Hartel Andreas J. W. , Glogger Marius , Guigas Gernot , Jones Nicola G. , Fenz Susanne F. , Weiss Matthias , Engstler Markus
Published: June 2015

A plethora of proteins undergo random and passive diffusion in biological membranes. While the contribution of the membrane-embedded domain to diffusion is well established, the potential impact of the extra-membrane protein part has been largely neglected. Here, we show that the molecular length influences the diffusion coefficient of GPI-anchored proteins: smaller proteins diffuse faster than larger ones. The distinct diffusion properties of differently sized membrane proteins are biologically relevant. The variant surface glycoprotein (VSG) of African trypanosomes, for example, is sized for an effective diffusion-driven randomization on the cell surface, a process that is essential for parasite virulence. We propose that the molecular sizes of proteins dominating the cell surfaces of other eukaryotic pathogens may also be related to diffusion-limited functions.
Emergence of scale-free characteristics in socio-ecological systems with bounded rationality
Authors: Kasthurirathna Dharshana , Piraveenan Mahendra
Published: June 2015

Socio–ecological systems are increasingly modelled by games played on complex networks. While the concept of Nash equilibrium assumes perfect rationality, in reality players display heterogeneous bounded rationality. Here we present a topological model of bounded rationality in socio-ecological systems, using the rationality parameter of the Quantal Response Equilibrium. We argue that system rationality could be measured by the average Kullback–-Leibler divergence between Nash and Quantal Response Equilibria and that the convergence towards Nash equilibria on average corresponds to increased system rationality. Using this model, we show that when a randomly connected socio-ecological system is topologically optimised to converge towards Nash equilibria, scale-free and small world features emerge. Therefore, optimising system rationality is an evolutionary reason for the emergence of scale-free and small-world features in socio-ecological systems. Further, we show that in games where multiple equilibria are possible, the correlation between the scale-freeness of the system and the fraction of links with multiple equilibria goes through a rapid transition when the average system rationality increases. Our results explain the influence of the topological structure of socio–ecological systems in shaping their collective cognitive behaviour and provide an explanation for the prevalence of scale-free and small-world characteristics in such systems.
Identification of the Conformational transition pathway in PIP2 Opening Kir Channels
Authors: Li Junwei , Lü Shouqin , Liu Yuzhi , Pang Chunli , Chen Yafei , Zhang Suhua , Yu Hui , Long Mian , Zhang Hailin , Logothetis Diomedes E. , Zhan Yong , An Hailong
Published: June 2015

The gating of Kir channels depends critically on phosphatidylinositol 4,5-bisphosphate (PIP2), but the detailed mechanism by which PIP2 regulates Kir channels remains obscure. Here, we performed a series of Targeted molecular dynamics simulations on the full-length Kir2.1 channel and, for the first time, were able to achieve the transition from the closed to the open state. Our data show that with the upward motion of the cytoplasmic domain (CTD) the structure of the C-Linker changes from a loop to a helix. The twisting of the C-linker triggers the rotation of the CTD, which induces a small downward movement of the CTD and an upward motion of the slide helix toward the membrane that pulls the inner helix gate open. At the same time, the rotation of the CTD breaks the interaction between the CD- and G-loops thus releasing the G-loop. The G-loop then bounces away from the CD-loop, which leads to the opening of the G-loop gate and the full opening of the pore. We identified a series of interaction networks, between the N-terminus, CD loop, C linker and G loop one by one, which exquisitely regulates the global conformational changes during the opening of Kir channels by PIP2.
Adiponectin exacerbates collagen-induced arthritis via enhancing Th17 response and prompting RANKL expression
Authors: Sun Xiaoxuan , Feng Xiaoke , Tan Wenfeng , Lin Na , Hua Minhui , Wei Yu , Wang Fang , Li Ningli , Zhang Miaojia
Published: June 2015

We previously reported adiponectin (AD) is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in Rheumatoid arthritis (RA) patients. Here, we investigate the role of adiponectin in regulating Th17 response and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in mice with CIA mice by intraarticularly injection of adiponectin into knee joints on day 17, day 20 and day 23 post first collagen immunization. The increased adiponectin expression was found in inflamed joint tissue of collagen-induced arthritis (CIA) mice. Adiponectin injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia, bone erosion and osteoporosis in CIA mice. CD4+IL-17+ Th17 cells, IL-17 mRNA and RANKL mRNA expression were markedly increased in the joint tissue of adiponectin treated CIA mice. Moreover, adiponectin treatment markedly enhanced Th17 cell generation from naive CD4+ T cells in vitro, which accompanied by the high expression of Th17 transcription factor ROR-γt and Th17 cytokine genes included IL-22 and IL-23. This study reveals a novel effect of adiponectin in exacerbating CIA progression by enhancing Th17 cell response and RANKL expression.
Whole genome sequencing and analysis of Swarna, a widely cultivated indica rice variety with low glycemic index
Authors: Rathinasabapathi Pasupathi , Purushothaman Natarajan , VL Ramprasad , Parani Madasamy
Published: June 2015

Swarna is a popular cultivated indica rice variety with low glycemic index (GI) but its genetic basis is not known. The whole genome of Swarna was sequenced using Illumina’s paired-end technology and the reads were mapped to the Nipponbare reference genome. Overall, 65,984 non-synonymous SNPs were identified in 20,350 genes and in silico analysis predicted that 4,847 of them in 2,214 genes may have deleterious effect on protein functions. Polymorphisms were found in all the starch biosynthesis genes, except the gene for branching enzyme IIa. It was found that T/G SNP at position 246, ‘A’ at position 2,386 and ‘C’ at position 3,378 in the granule bound starch synthase I gene and C/T SNP at position 1,188 in the glucose-6-phosphate translocator gene may contribute to the low GI phenotype in Swarna. All these variants were also found in the genome of another low GI indica rice variety from Columbia, Fedearroz 50. The whole genome analysis of Swarna helped to understand the genetic basis of GI in rice, which is a complex trait involving multiple factors.
Wrapping cytochrome c around single-wall carbon nanotube: engineered nanohybrid building blocks for infrared detection at high quantum efficiency
Authors: Gong Youpin , Liu Qingfeng , Wilt Jamie Samantha , Gong Maogang , Ren Shenqiang , Wu Judy
Published: June 2015

Biomolecule cytochrome c (Cty c), a small molecule of a chain of amino acids with extraordinary electron transport, was helically wrapped around a semiconductive single-wall carbon nanotube (s-SWCNT) to form a molecular building block for uncooled infrared detection with two uniquely designed functionalities: exciton dissociation to free charge carriers at the heterojunction formed on the s-SWCNT/Cty c interface and charge transport along the electron conducting chain of Cty c (acceptor) and hole conducting channel through s-SWCNT (donor). Such a design aims at addressing the long-standing challenges in exciton dissociation and charge transport in an SWCNT network, which have bottlenecked development of photonic SWCNT-based infrared detectors. Using these building blocks, uncooled s-SWCNT/Cyt c thin film infrared detectors were synthesized and shown to have extraordinary photoresponsivity up to 0.77 A W−1 due to a high external quantum efficiency (EQE) in exceeding 90%, which represents a more than two orders of magnitude enhancement than the best previously reported on CNT-based infrared detectors with EQE of only 1.72%. From a broad perspective, this work on novel s-SWCNT/Cyt c nanohybrid infrared detectors has developed a successful platform of engineered carbon nanotube/biomolecule building blocks with superior properties for optoelectronic applications.
Rational molecular engineering of cyclopentadithiophene-bridged D-A-π-A sensitizers combining high photovoltaic efficiency with rapid dye adsorption
Authors: Chai Qipeng , Li Wenqin , Liu Jingchuan , Geng Zhiyuan , Tian He , Zhu Wei-hong
Published: June 2015

Dye-sensitized solar cell (DSSC) is considered as a feasible route to the clean and renewable energy conversion technique. The commercial application requires further enhancements on photovoltaic efficiency and simplification on the device fabrication. For avoiding the unpreferable trade-off between photocurrent (JSC) and photovoltage (VOC), here we report the molecular engineering and comprehensive photovoltaic characterization of three cyclopentadithiophene-bridged D-A-π-A motif sensitizers with a change in donor group. We make a careful choice on the donor and conjugation bridge for synergistically increasing JSC and VOC. Comparing with the reference dye WS-2, the photovoltaic efficiency with the single component dye of WS-51 increases by 18%, among one of the rare examples in pure metal-free organic dyes exceeding 10% in combination with traditional iodine redox couples. Moreover, WS-51 exhibits several prominent merits on potentially scale-up industrial application: i) facile synthetic route to target molecule, ii) simple dipping procedure without requirement of co-sensitization and iii) rapid dye adsorption capability.
In-Situ Welding Carbon Nanotubes into a Porous Solid with Super-High Compressive Strength and Fatigue Resistance
Authors: Lin Zhiqiang , Gui Xuchun , Gan Qiming , Chen Wenjun , Cheng Xiaoping , Liu Ming , Zhu Yuan , Yang Yanbing , Cao Anyuan , Tang Zikang
Published: June 2015

Carbon nanotube (CNT) and graphene-based sponges and aerogels have an isotropic porous structure and their mechanical strength and stability are relatively lower. Here, we present a junction-welding approach to fabricate porous CNT solids in which all CNTs are coated and welded in situ by an amorphous carbon layer, forming an integral three-dimensional scaffold with fixed joints. The resulting CNT solids are robust, yet still highly porous and compressible, with compressive strengths up to 72 MPa, flexural strengths up to 33 MPa and fatigue resistance (recovery after 100,000 large-strain compression cycles at high frequency). Significant enhancement of mechanical properties is attributed to the welding-induced interconnection and reinforcement of structural units and synergistic effects stemming from the core-shell microstructures consisting of a flexible CNT framework and a rigid amorphous carbon shell. Our results provide a simple and effective method to manufacture high-strength porous materials by nanoscale welding.
Monitoring the wheat straw fermentation process using an electronic nose with pattern recognition methods
Authors: Mei Congli , Yang Ming , Shu Dongxin , Jiang Hui , Liu Guohai
Published: June 2015

To monitor the wheat straw solid-state fermentation process in real time, an electronic nose (e-nose) was attempted in this study.
A short GC rich DNA derived from microbial origin targets tubulin/microtubules and induces apoptotic death of cancer cells
Authors: Jana Batakrishna , Sarkar Jayita , Mondal Prasenjit , Barman Surajit , Mohapatra Saswat , Bhunia Debmalya , Pradhan Krishnangsu , Saha Abhijit , Adak Anindyasundar , Ghosh Subhajit , Ghosh Surajit
Published: June 2015

A short GC rich DNA interacts with tubulin/microtubules, activates p53 over expression and induces apoptotic death of human breast cancer (MCF-7) cells.
Bis(phenothiazine)arene diradicaloids: isolation, characterization and crystal structures
Authors: Wang Xingyong , Zhang Zaichao , Song You , Su Yuanting , Wang Xinping
Published: June 2015

A series of bis(phenothiazine)arene diradicaloids featuring tunable ground states by orthogonal alignment of spin-carrying π-systems were isolated and structurally characterized.
Design of tumor-homing and pH-responsive polypeptide–doxorubicin nanoparticles with enhanced anticancer efficacy and reduced side effects
Authors: Hu Jin , Xie Lining , Zhao Wenguo , Sun Mengmeng , Liu Xinyu , Gao Weiping
Published: June 2015

Precision design of tumor-homing and pH-responsive polypeptide–doxorubicin nanoparticles with enhanced anticancer efficacy and reduced side effects for targeted cancer therapy.
Sperm DNA-mediated reduction of nonspecific fluorescence during cellular imaging with quantum dots
Authors: Lee Jonghwan , Choi Kyung-ju , Choi Youngsok , Ali Bahy A. , Al-Khedhairy Abdulaziz A. , Kim Soonhag
Published: June 2015

Salmon sperm DNA was used as a blocking agent to reduce background fluorescence signals from gelatin-coated cell culture dishes.
Induction of the superoxide anion radical scavenging capacity of dried ‘funori’ Gloiopeltis furcata by Lactobacillus plantarum S-SU1 fermentation
Authors: Kuda Takashi , Nemoto Maki , Kawahara Miho , Oshio Satoshi , Takahashi Hajime , Kimura Bon
Published: June 2015

To understand the beneficial properties of edible algae obtained from the north-eastern (Sanriku) Satoumi region of Japan, the antioxidant properties of hot aqueous extract solutions (AES) obtained from 18 dried algal products were determined.
Determination of rare earth elements in graphite by solid sampling electrothermal vaporization-inductively coupled plasma mass spectrometry
Authors: Mello P. A. , Pedrotti M. F. , Cruz S. M. , Muller E. I. , Dressler V. L. , Flores E. M. M.
Published: June 2015

Determination of rare earth elements in graphite samples was performed by direct solid sampling electrothermal vaporization-inductively coupled plasma mass spectrometry (ETV-ICP-MS).
Bioprinting of 3D hydrogels
Authors: Stanton M. M. , Samitier J. , Sánchez S.
Published: June 2015

This article focuses on bioprinting utilizing hydrogels as 3D scaffolds.
Highly enantioselective synthesis of non-natural aliphatic α-amino acids via asymmetric hydrogenation
Authors: Ji Jianjian , Chen Caiyou , Cai Jiayu , Wang Xinrui , Zhang Kai , Shi Liyang , Lv Hui , Zhang Xumu
Published: June 2015

A series of non-natural aliphatic α-amino acids were synthesized with high ee and yield by employing a rhodium–Duanphos complex as the catalyst. An efficient approach for the synthesis of the intermediate of the anti-diabetic drugs Alogliptin and Linagliptin in the DPP-4 inhibitor class was also developed.
Microbial rhamnolipid production in wheat straw hydrolysate supplemented with basic salts
Authors: Prabu Rajagopalan , Kuila Arindam , Ravishankar Raman , Rao Peddy V. C. , Choudary Nettem V. , Velankar Harshad R.
Published: June 2015

Rhamnolipids are important glycolipids that find application in the areas of crude oil bioremediation, enhanced oil recovery, food and pharmaceutical applications.
Multi-parametric imaging of the invasiveness-permissive acidic microenvironment in human glioma xenografts
Authors: Huang Cuiyun , Qin Huan , Qian Jun , Zhang Jingye , Zhao Shengyuan , Changyi Yinzhi , Li Bingbing , Zhang Jianping , Zhu Jianhua , Xing Da , Yang Sihua , Li Cong
Published: June 2015

Non-invasive multi-parametric imaging demonstrated the positive correlation between the invasiveness and extracellular acidity in glioma xenografts.
Irradiation of poly(l-lactide) biopolymer reinforced with functionalized MWCNTs
Authors: Chakoli Ali Nabipour , He Jinmei , Chayjan Maryam Amirian , Huang Yudong , Zhang Baode
Published: June 2015

The γirradiation increases the modulus and strength, decreases the melting point of poly(l-lactide) during sterilization. The functionalized carbon nanotubes accelerate the irradiation effect on mechanical and thermal properties of poly(l-lactide).
Isolation of a structural intermediate during switching of degree of interpenetration in a metal–organic framework
Authors: Aggarwal Himanshu , Das Raj Kumar , Bhatt Prashant M. , Barbour Leonard J.
Published: June 2015

A structural intermediate has been isolated for the first time during switching of interpenetration from twofold to threefold in the MOF [Co2(ndc)2(bpy)].
Implementation and application of ADE‐PML for higher‐order FDTD method
Authors: Liu Yawen , Chen Yiwang , Jiang Zhidong
Published: June 2015

A new implementation of a perfect matched layer with an auxiliary differential equation (ADE‐PML) is presented for the higher‐order finite‐difference time‐domain (FDTD) method. The implementation of the ADE‐PML is more straightforward and more memory saving than that of the traditional PML. A two‐dimensional (2D) case and two 3D cases with different microwave circuit components are designed to analyse the absorbing performance of the ADE‐PML and the simulation results show that the ADE‐PML can provide a quite satisfactory absorbing boundary condition.