bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Estimation of Surgical Procedures Needed for Forcibly Displaced Persons
Authors: Zha Yuanting , Stewart Barclay , Lee Eugenia , Remick Kyle N. , Rothstein David H. , Groen Reinou S. , Burnham Gilbert , Imagawa David K. , Kushner Adam L.
Published: May 2016

Introduction

Sixty million people were displaced from their homes due to conflict, persecution, or human rights violations at the end of 2014. This vulnerable population bears a disproportionate burden of disease, much of which is surgically treatable. We sought to estimate the surgical needs for forcibly displaced persons globally to inform humanitarian assistance initiatives.

Methods

Data regarding forcibly displaced persons, including refugees, internally displaced persons (IDPs), and asylum seekers were extracted from United Nations databases. Using the minimum proposed surgical rate of 4669 procedures per 100,000 persons annually, global, regional, and country‐specific estimates were calculated. The prevalence of pregnancy and obstetric complications were used to estimate obstetric surgical needs.

Results

At least 2.78 million surgical procedures (IQR 2.58–3.15 million) were needed for 59.5 million displaced persons. Of these, 1.06 million procedures were required in North Africa and the Middle East, representing an increase of 50 % from current unmet surgical need in the region. Host countries with the highest surgical burden for the displaced included Syria (388,000 procedures), Colombia (282,000 procedures), and Iraq (187,000). Between 4 and 10 % of required procedures were obstetric surgical procedures. Children aged <18 years made up 52 % of the displaced, portending a substantial demand for pediatric surgical care.

Conclusion

Approximately three million procedures annually are required to meet the surgical needs of refugees, IDPs, and asylum seekers. Most displaced persons are hosted in countries with inadequate surgical care capacity. These figures should be considered when planning humanitarian assistance and targeted surgical capacity improvements.
The Fallacy of ‘compartmentalisation’: The West and Russia from Ukraine to Syria
Authors: Cornell Svante E.
Published: May 2016

In the post-Soviet space as well as the Middle East, Western leaders have largely failed to heed ample evidence that the goals of the Russian leadership are fundamentally opposed to those of the EU and the US. Whereas Moscow seeks to counter Western influence and roll back the US's role in the world, the West has proposed a win–win approach, seeking to convince Moscow that its ‘true’ interests should lead it to cooperate with the West. When this has not worked, Western leaders have ‘compartmentalised’, isolating areas of agreement from areas of disagreement. This approach has come to the end of the road because the assumptions that undergird it are false. So long as Western powers fail to understand the fundamental incompatibility of their interests with the deeply anti-Western interests of the current power brokers in the Kremlin, they are unlikely to develop policies that achieve success.
Family economic hardship and Chinese adolescents' sleep quality: A moderated mediation model involving perceived economic discrimination and coping strategy
Authors: Bao Zhenzhou , Chen Chuansheng , Zhang Wei , Zhu Jianjun , Jiang Yanping , Lai Xuefen
Published: May 2016

The association between family economic hardship and adolescent adjustment outcomes, including sleep quality, is well‐established. Few studies, however, have examined the mediating and moderating mechanisms underlying the relation between family economic hardship and adolescents' sleep quality. The aim of this study was to investigate the effect of family economic hardship on Chinese adolescents' sleep quality, as well as the role of perceived economic discrimination as a mediator and the role of coping strategy as a moderator. Survey data from a cross‐sectional sample of 997 Chinese adolescents (45% male, mean age = 15.04 years) were analyzed using path analysis in Mplus 7.0. The results of this study indicated that family economic hardship was significantly associated with adolescents' sleep quality. This association was mediated by adolescents' perceived economic discrimination. In addition, adolescents' coping strategy significantly moderated the path from perceived economic discrimination to sleep quality, with the “shift” coping strategy as a protective factor. The present study contributes to our understanding of key mechanisms underlying the association between family economic hardship and adolescent sleep quality and highlights the importance of improving sleep quality for adolescents exposed to economic hardship.
Integrating Perioperative Content in Nursing Curricula: A Case Study Approach
Authors: Byrne Michelle , Root Susan , Culbertson Laurie
Published: May 2016

Perioperative nursing care requires unique specialty knowledge, skills, and abilities. National initiatives in nursing education and health care support integrating perioperative nursing content into curricular offerings in nursing schools and health care institutions. We provide an overview of the initiatives affecting nursing education, followed by a case study example and a guide to assist educators with incorporating perioperative case studies into their education plans. These resources may enhance the integration of perioperative nursing concepts in undergraduate curricula, internships, and continuing education offerings. The purpose of this article is to provide resources for nurse educators to systematically create case studies and to encourage increased exposure to perioperative concepts and competencies in a myriad of educational environments.
An Innovative Approach to the Surgical Time Out: A Patient‐Focused Model
Authors: Kozusko Steven D. , Elkwood Lily , Gaynor Diane , Chagares Stephen A.
Published: May 2016

The surgical time out is an integral component of patient safety in OR settings. At The Center for Outpatient Surgery (TCOPS), a team of nurses and plastic and breast surgeons evaluated discrepancies, wrong‐site surgeries, near misses, team communication, and patient satisfaction to develop and implement a surgical checklist that would help improve efficiency and patient safety and reduce near misses. This checklist involves the surgical team and patient, and it includes preoperative, preincision, and postoperative time outs. Since 2011, 4,453 procedures have used the preoperative and preincision timeouts. Of those, 998 have used all three when we added the postoperative component. Since the implementation of the checklist, there have been zero discrepancies and zero wrong‐site surgeries. Patients have expressed satisfaction with their inclusion in the preoperative time out. Staff members at TCOPS have noted excellent results, and the checklist can be adopted by other specialties.
Pain Management After Total Joint Arthroplasty
Authors: McDonald Lisa T. , Corbiere Nicole C. , DeLisle Jay A. , Clark Alexander Martin , Kuxhaus Laurel
Published: May 2016

Controlling pain after total joint arthroplasty (TJA) is critical to minimizing complications, decreasing costs, and expediting patients’ return to function. We implemented a TJA multimodal pain management protocol at a Level III trauma center in a small, rural community in New York. We retrospectively reviewed 266 patient charts and collected patient demographics, pain management information, and discharge data. Our primary goals were to quantify the total number of narcotic medication doses used and length of hospital stay. The multimodal pain management protocol significantly reduced the number of narcotic doses used (P < .01). Hospital length of stay decreased slightly; although not statistically significant (P = .25), this may be clinically significant. Gender, age, and type of arthroplasty (ie, knee, hip) were not significant factors. A multimodal approach to pain management after TJA can reduce narcotic use and hospital length of stay, thereby also reducing the incidence of side effects from narcotics.
The Influence of Mating Goal Activation and Gender Differences on the Evaluation of Advertisements Containing Sexual Words
Authors: Kim Jungkeun , Kim Sungeun (Ange)
Published: May 2016

This research examines the impact of humans’ mating motivation on their attitudes toward and recall of advertising that contains words with sexual connotations (e.g., “Sexton Plumbing” and “We Sell Boxes”). Due to gender differences based on evolution-based and socialization-based approaches, this research predicts differential evaluations between men and women for advertising that contains words with sexual connotations. The results of two empirical studies reveal that men in a mating mindset condition show more positive attitudes toward advertisements containing words with sexual connotations than do men in the control condition. In contrast, a different pattern is evident for women. Women in a mating mindset show similar attitudes toward such advertisements compared to women in the control condition. A similar pattern was also found for the recall of advertisements.
Coexistence of endocrinopathies in children with rheumatic diseases
Authors: Alhomaidah Doha , Alsagheir Afaf , Al-Mayouf Sulaiman M.
Published: May 2016

Background and objectives:

To examine the frequency of endocrinopathies in children with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA).

Design and setting:

A cross-sectional study.

Patients and methods:

A study was conducted in Saudi children with SLE and JIA who were seen at King Faisal Specialist Hospital and Research Centre, Riyadh, between September 2013 and April 2015. All enrolled patients completed the clinical evaluation, which included information about family history of autoimmune disease, growth parameters and tanner stage, as well as the following assessments: vitamin D profile (parathyroid hormone and 25-OH vitamin D levels), TSH, FT4 and total T3, thyroglobulin antibodies, thyroperoxidase antibodies, random blood sugar, HbA1C, IGF1, IGFBp.3, LH, and FSH.

Results:

A total of 42 patients, 22 with JIA and 20 with SLE, were included in the study. The mean participant age was 12.2 ± 5.3 years with a mean disease duration of 3.2 ± 3.4 years. Female gender was predominant (17 SLE, 13 JIA) in the patient population. Fifteen patients (35.7%) presented with a family history of autoimmune disease. The most frequently detected endocrinopathies were vitamin D insufficiency (35%) and thyroid disease (31%). Eight JIA patients and 7 SLE patients exhibited low vitamin D levels; 10 patients presented with hyperpara-thyroidism. Thyroid dysfunction was observed in 13 patients (8 SLE, 5 JIA), and 2 patients were found to be euthyroid (normal TSH, FT4) with positive thyroid autoantibodies. Furthermore, 7 patients presented with subclinical hypothyroidism (high TSH, normal FT4), and 4 patients presented with overt hypothyroidism (high TSH, low FT4). Seven patients (4 SLE and 3 JIA) presented with short stature due to growth hormone insufficiency (low IGF1, IGFBP-3). Two patients exhibited delayed puberty accompanied by low LH levels. Diabetes mellitus was more frequently observed in patients with JIA (4 patients) than in patients with SLE (1 patient). Conclusion: Our findings demonstrated that coexistence of endocrinopathies is not uncommon in children diagnosed with JIA and SLE. Abnormal thyroid function occurs frequently and at a similar rate in children diagnosed with SLE and JIA. Thus, screening for endocrinopathies, namely thyroid disease, during the assessment of childhood SLE and JIA is worth consideration.
The Compensatory Consumer Behavior Model: How self‐discrepancies drive consumer behavior
Authors: Mandel Naomi , Rucker Derek D. , Levav Jonathan , Galinsky Adam D.
Published: May 2016

Consumer goods and services have psychological value that can equal or exceed their functional value. A burgeoning literature demonstrates that one source of value emerges from the capacity for products to serve as a psychological salve that reduces various forms of distress across numerous domains. This review systematically organizes and integrates the literature on the use of consumer behavior as a means to regulate self‐discrepancies, or the incongruities between how one currently perceives oneself and how one desires to view oneself (Higgins, 1987). We introduce a Compensatory Consumer Behavior Model to explain the psychological consequences of self‐discrepancies on consumer behavior. This model delineates five distinct strategies by which consumers cope with self‐discrepancies: direct resolution, symbolic self‐completion, dissociation, escapism, and fluid compensation. Finally, the authors raise critical questions to guide future research endeavors. Overall, the present review provides both a primer on compensatory consumer behavior and sets an agenda for future research.
Fleet management policies for humanitarian organizations: Beyond the utilization–residual value trade‐off
Authors: Eftekhar Mahyar , Van Wassenhove Luk N.
Published: May 2016

Four‐wheel drive vehicles play a pivotal role in securing the last‐mile distribution of goods and services in humanitarian development programs. To optimize the use of their fleets, humanitarian organizations recommend policies aimed at enhancing the utilization of vehicles while preserving residual value. Although these decisions have a significant impact on cost, there is limited empirical evidence to show that the recommended policies are actually implemented and that they produce the expected benefits. This paper theoretically and empirically examines the complex and inter‐related effects of vehicle‐to‐mission allocation decisions and of alternative vehicle usage patterns on vehicle utilization and residual value in humanitarian development programs. The results suggest that humanitarian organizations could break the utilization–residual value trade‐off by adopting different policies than the ones currently in place. They also reveal that organizations need to realize that what seems logical from the headquarters' perspective may be illogical or inconvenient for the field, and as a result, the field may do the opposite of what is recommended or even instructed. Therefore, they either need better data and analysis combined with audits or they need to improve mechanisms that incentivize field delegations to follow standards recommended by the headquarters.
Health-Related Education for Sustainability: Public Health Workforce Needs and the Role of Higher Education
Authors: Patrick Rebecca , Kingsley Jonathan , Capetola Teresa
Published: May 2016

Public health practitioners have important roles to play in addressing environmental sustainability imperatives that have an impact on human health. Yet, to date, the extent to which practitioners are willing and able to address these issues is an understudied subject. This article draws on the findings of two qualitative studies involving 49 interviews with public health and/or sustainability practitioners and academics from Australia to highlight the capacity-building needs of the sector within the ‘health and sustainability’ space. The findings of this study raise several issues for workforce development and partnership building, contending that content on environmental sustainability should be integrated into all university courses. Underscoring gaps and opportunities, the article also reflects themes in the literature in relation to health-related education for sustainability; in particular, requirements for generic and transferable professional competencies and the role of universities in knowledge exchange and creation.
Interactions enhance the acoustic streaming around flattened microfluidic bubbles
Authors: Mekki-Berrada F. , Combriat T. , Thibault P. , Marmottant P.
Published: May 2016

The vibration of bubbles can produce intense microstreaming when excited by ultrasound near resonance. In order to study freely oscillating bubbles in steady conditions, we have confined bubbles between the two walls of a silicone microchannel and anchored them on micropits. We were thus able to analyse the microstreaming flow generated around an isolated bubble or a pair of interacting bubbles. In the case of an isolated bubble, a short-range microstreaming occurs in the channel gap, with additional in-plane vortices at high amplitude when Faraday waves are excited on the bubble periphery. For a pair of bubbles, we have observed long-range microstreaming and large recirculations describing a ‘butterfly’ pattern. We propose a model based on secondary acoustic Bjerknes forces mediated by Rayleigh waves on the silicone walls. These forces lead to attraction or repulsion of bubbles and thus to the excitation of a translational mode in addition to the breathing mode of the bubble. The mixed-mode streaming induced by the interaction of these two modes is shown to generate fountain or anti-fountain vortex pairs, depending on the relative distance between the bubbles.
A long bubble rising in still liquid in a vertical channel: a plane inviscid solution
Authors: Fabre Jean
Published: May 2016

An analytical model is proposed for flow around a plane bubble rising steadily in a channel. The fluid surrounding the bubble is assumed to be inviscid, and the flow is assumed to be irrotational. The resulting potential flow is sought as the sum of a uniform stream and a source in the unit strip. Explicit expressions for the bubble shape and rise velocity, and for the streamlines, are given as functions of the dimensionless surface tension. The predictions are in good agreement with existing experimental and numerical results.
Pervasive near-surface stratal disruption in an accretionary prism setting: Kaczawa Complex, SW Poland
Authors: KOSTYLEW JOANNA , ZALASIEWICZ JAN A. , KRYZA RYSZARD
Published: May 2016

The tectonized and metamorphosed mudrocks within the Variscan accretionary prism of the Kaczawa Mountains in SW Poland comprise sedimentary mélanges together with more coherent stratigraphic units; some represent large olistoliths deposited in a submarine trench. We infer a trend of progressive near-surface stratal disruption in mud-dominated deposits due to dewatering that forms a continuum with subduction-related tectonic structures imposed on unconsolidated sediment during deeper burial. The assemblage of characters suggests that an accretionary prism environment can influence, and leave characteristic traces of, the total burial history of a trench succession.
Iron acquisition inLeishmaniaand its crucial role in infection
Authors: NIU QINWANG , LI SHIHONG , CHEN DALI , CHEN QIWEI , CHEN JIANPING
Published: May 2016

Iron is an essential cofactor for many basic metabolic pathways in pathogenic microbes and their hosts. It is also dangerous as it can catalyse the production of reactive free radicals. This dual character makes the host can either limit iron availability to invading microbes or exploit iron to induce toxicity to pathogens. Successful pathogens, includingLeishmaniaspecies, must possess mechanisms to circumvent host's iron limitation and iron-induced toxicity in order to survive. In this review, we discuss the regulation of iron metabolism in the setting of infection and delineate the iron acquisition strategies used byLeishmaniaparasites and their subversions to host iron metabolism to overcome host's iron-related defences.
Parasitic infection alters the physiological response of a marine gastropod to ocean acidification
Authors: MACLEOD C. D. , POULIN R.
Published: May 2016

Increased hydrogen ion concentration and decreased carbonate ion concentration in seawater are the most physiologically relevant consequences of ocean acidification (OA). Changes to either chemical species may increase the metabolic cost of physiological processes in marine organisms, and reduce the energy available for growth, reproduction and survival. Parasitic infection also increases the energetic demands experienced by marine organisms, and may reduce host tolerance to stressors associated with OA. This study assessed the combined metabolic effects of parasitic infection and OA on an intertidal gastropod,Zeacumantus subcarinatus. Oxygen consumption rates and tissue glucose content were recorded in snails infected with one of three trematode parasites, and an uninfected control group, maintained in acidified (7·6 and 7·4 pH) or unmodified (8·1 pH) seawater. Exposure to acidified seawater significantly altered the oxygen consumption rates and tissue glucose content of infected and uninfected snails, and there were clear differences in the magnitude of these changes between snails infected with different species of trematode. These results indicate that the combined effects of OA and parasitic infection significantly alter the energy requirements ofZ. subcarinatus, and that the species of the infecting parasite may play an important role in determining the tolerance of marine gastropods to OA.
Geneva's philanthropists around 1900: a field made of distinctive but interconnected social groups
Authors: DAVID THOMAS , HEINIGER ALIX , BÜHLMANN FELIX
Published: May 2016

This article analyses the social profile of Geneva's philanthropists around 1900. It shows that, contrary to what the literature on philanthropy argues, philanthropists belonged to varied social groups defined by diverse forms of capital (economic, social and cultural) and were involved in philanthropic activities related to their social status. Together, those philanthropists formed a social field. They were connected to each other and even needed to collaborate on specific issues. The article argues that interconnections between actors reinforced their social position. By examining this field through both quantitative and qualitative methods, the article highlights relationships and ties between actors and shows how they collaborated on the basis of commonly held principles.
Staffing in Ontario’s Long-Term Care Homes: Differences by Profit Status and Chain Ownership
Authors: Hsu Amy T. , Berta Whitney , Coyte Peter C. , Laporte Audrey
Published: May 2016

L’Ontario compte la plus forte proportion des maisons de soins infirmiers à but lucratif au Canada. Ces maisons de soins infirmiers, connus en Ontario comme maisons de soins de longue durée (SLD), offrent 24 heures de soins de garde et de soins infirmiers aux personnes qui sont incapables de vivre de façon autonome. De plus en plus, ces installations fonctionnent aussi comme membres de chaînes de multi-établissements, mais elles n’ont pas été largement étudiées au Canada. En utilisant des données longitudinales (1996–2011) de l’Enquête sur les établissements de soins résidentiels (n =627), notre analyse a révélé des différences perceptibles dans les niveaux du personnel selon le statut de profit et de l’affiliation aux chaînes. Nous avons trouvé que les maisons SLD à but lucratif – en particulier celles appartenant à une chaîne – ont fournies significativement moins d’heures de soins, après l’ajustement des variations de la nécessité des soins pour les résidents. Les résultats de cette étude offrent des nouveaux renseignements sur l’impact de la structure organisationnelle sur les niveaux de personnel dans les foyers de SLD de l’Ontario, et ont des implications pour d’autres juridictions où la présence de plus en plus d’opérateurs privés affiliés à des chaînes a été observée.
Morphology of gametes, post-fertilization events and the effect of temperature on the embryonic development ofAstyanax altiparanae(Teleostei, Characidae)
Authors: dos Santos Matheus Pereira , Yasui George Shigueki , Xavier Pedro Luiz Porfírio , de Macedo Adamov Nadya Soares , do Nascimento Nivaldo Ferreira , Fujimoto Takafumi , Senhorini José Augusto , Nakaghi Laura Satiko Okada
Published: May 2016

The aim of this study was to describe the morphology of gametes, post-fertilization events and subsequent temperature effects on the early developmental stages of the neotropical speciesAstyanax altiparanae. The sperm of this species presents a typical morphology of teleost sperm with a spherical head (diameter = 1.88 µm), midpiece (diameter = 0.75 µm) and a single flagellum (length = 18.67 µm). The extrusion of the second polar body and fusion of male and female pronucleus were reported for the first time in this species. Additionally, we observed the formation of the fertilization cone, which prevents polyspermic fertilization. Developmental stages at 22°C, 26°C and 30°C gave rise to fertilization rates at 91.12, 91.42 and 93.04% respectively. Hatching occurred at 25 hpf at 22°C, 16 hpf at 26°C and 11 hpf at 30°C and the hatching rates were 61.78%, 62.90% and 59.45%, respectively. At 22°C, the second polar body was extruded at ≈6 mpf and the male and female pronucleus fused at ≈10 mpf. This fundamental information is important for the field and opens up new possibilities in fish biotechnology, including micromanipulation and chromosome-set manipulation.
Analyzing lexical emergence in Modern American English online
Authors: GRIEVE JACK , NINI ANDREA , GUO DIANSHENG
Published: May 2016

This article introduces a quantitative method for identifying newly emerging word forms in large time-stamped corpora of natural language and then describes an analysis of lexical emergence in American social media using this method, based on a multi-billion-word corpus of Tweets collected between October 2013 and November 2014. In total 29 emerging word forms, which represent various semantic classes, grammatical parts-of-speech and word formation processes, were identified through this analysis. These 29 forms are then examined from various perspectives in order to begin to better understand the process of lexical emergence.
Benzodiazepin-Abhängigkeit im Alter: Wie geht man damit um?
Authors: Savaskan Egemen
Published: May 2016

Zusammenfassung. Schädlicher Gebrauch und Abhängigkeitserkrankungen von Benzodiazepinen oder Hypnotika nehmen im Alter zu. Besonders bei älteren Personen kommt es bei regelmässiger Einnahme dieser Substanzen zu schweren Nebenwirkungen. Sedation, kognitive und psychomotorische Wirkungen, Stürze, Unfälle und Verletzungen sind häufig. Der Entzug ist oft mit schwerwiegenden Komplikationen verbunden. Deswegen ist die Prävention sehr wichtig. Diese Medikamente sollten bei leichten Schlaf- und Angststörungen nicht verordnet werden, und die Verschreibung sollte zeitlich limitiert bis zu drei bis vier Wochen erfolgen. Entzugssymptome können als Insomnie, Angst, Gedächtnis- und Konzentrationsstörungen, Ataxie, und in schweren Fällen als psychotische Symptome, Delir und epileptische Anfälle auftreten. Entwöhnungstherapie beginnt bei niedergelassenen Ärzten, die weiterhin am häufigsten diese Medikamente verschreiben. Bei lang andauernder Abhängigkeitserkrankung ist oft nur eine stationäre Therapie erfolgreich.
Spatial Estimation of Accelerated Stimuli Is Based on a Linear	Extrapolation of First-Order Information
Authors: Bennett Simon J. , Benguigui Nicolas
Published: May 2016

Abstract. We examined spatial estimation of accelerating objects (−8, −4, 0, +4, or +8 deg/s2) during occlusion (600, 1,000 ms) in a spatial prediction motion task. Multiple logistic regression indicated spatial estimation was influenced by these factors such that participants estimated objects with positive acceleration to reappear behind less often than those with negative acceleration, and particularly after the longer occlusion. Individual-participant logistic regressions indicated spatial estimation was better predicted by a first-order extrapolation of the occluded object motion based on pre-occlusion velocity rather than a second-order extrapolation that took account of object acceleration. We suggest a general principle of extrapolation is involved in prediction motion tasks whereby there is a contraction of the variable of interest (i.e., displacement in spatial prediction motion and time in temporal prediction motion). Such an approach to extrapolation could be advantageous as it would offer participants better opportunity to correct for an initial estimation error.
klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis
Authors: Steed Emily , Faggianelli Nathalie , Roth Stéphane , Ramspacher Caroline , Concordet Jean-Paul , Vermot Julien
Published: May 2016

The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression offibronectin1b. We show that blood flow andklf2a, a major endocardial flow-responsive gene, control these cell behaviours andfibronectin1bsynthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis.
Stepwise phosphorylation of p65 promotes NF-κB activation and NK cell responses during target cell recognition
Authors: Kwon Hyung-Joon , Choi Go-Eun , Ryu Sangryeol , Kwon Soon Jae , Kim Sun Chang , Booth Claire , Nichols Kim E. , Kim Hun Sik
Published: May 2016

NF-κB is a key transcription factor that dictates the outcome of diverse immune responses. How NF-κB is regulated by multiple activating receptors that are engaged during natural killer (NK)-target cell contact remains undefined. Here we show that sole engagement of NKG2D, 2B4 or DNAM-1 is insufficient for NF-κB activation. Rather, cooperation between these receptors is required at the level of Vav1 for synergistic NF-κB activation. Vav1-dependent synergistic signalling requires a separate PI3K-Akt signal, primarily mediated by NKG2D or DNAM-1, for optimal p65 phosphorylation and NF-κB activation. Vav1 controls downstream p65 phosphorylation and NF-κB activation. Synergistic signalling is defective in X-linked lymphoproliferative disease (XLP1) NK cells entailing 2B4 dysfunction and required for p65 phosphorylation by PI3K-Akt signal, suggesting stepwise signalling checkpoint for NF-κB activation. Thus, our study provides a framework explaining how signals from different activating receptors are coordinated to determine specificity and magnitude of NF-κB activation and NK cell responses.
Plastic anisotropy and dislocation trajectory in BCC metals
Authors: Dezerald Lucile , Rodney David , Clouet Emmanuel , Ventelon Lisa , Willaime François
Published: May 2016

Plasticity in body-centred cubic (BCC) metals at low temperatures is atypical, marked in particular by an anisotropic elastic limit in clear violation of the famous Schmid law applicable to most other metals. This effect is known to originate from the behaviour of the screw dislocations; however, the underlying physics has so far remained insufficiently understood to predict plastic anisotropy without adjustable parameters. Here we show that deviations from the Schmid law can be quantified from the deviations of the screw dislocation trajectory away from a straight path between equilibrium configurations, a consequence of the asymmetrical and metal-dependent potential energy landscape of the dislocation. We propose a modified parameter-free Schmid law, based on a projection of the applied stress on the curved trajectory, which compares well with experimental variations and first-principles calculations of the dislocation Peierls stress as a function of crystal orientation.
CRISPR-dCas9 and sgRNA scaffolds enable dual-colour live imaging of satellite sequences and repeat-enriched individual loci
Authors: Fu Yi , Rocha Pedro P. , Luo Vincent M. , Raviram Ramya , Deng Yan , Mazzoni Esteban O. , Skok Jane A.
Published: May 2016

Imaging systems that allow visualization of specific loci and nuclear structures are highly relevant for investigating how organizational changes within the nucleus play a role in regulating gene expression and other cellular processes. Here we present a live imaging system for targeted detection of genomic regions. Our approach involves generating chimaeric transcripts of viral RNAs (MS2 and PP7) and single-guide RNAs (sgRNAs), which when co-expressed with a cleavage-deficient Cas9 can recruit fluorescently tagged viral RNA-binding proteins (MCP and PCP) to specific genomic sites. This allows for rapid, stable, low-background visualization of target loci. We demonstrate the efficiency and flexibility of our method by simultaneously labelling major and minor satellite regions as well as two individual loci on mouse chromosome 12. This system provides a tool for dual-colour labelling, which is important for tracking the dynamics of chromatin interactions and for validating epigenetic processes identified in fixed cells.
NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells
Authors: Alrefai Hani , Muhammad Khalid , Rudolf Ronald , Pham Duong Anh Thuy , Klein-Hessling Stefan , Patra Amiya K. , Avots Andris , Bukur Valesca , Sahin Ugur , Tenzer Stefan , Goebeler Matthias , Kerstan Andreas , Serfling Edgar
Published: May 2016

Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.
Tobramycin and bicarbonate synergise to kill planktonic Pseudomonas aeruginosa, but antagonise to promote biofilm survival
Authors: Kaushik Karishma S , Stolhandske Jake , Shindell Orrin , Smyth Hugh D , Gordon Vernita D
Published: May 2016

Increasing antibiotic resistance and the declining rate at which new antibiotics come into use create a need to increase the efficacy of existing antibiotics. The aminoglycoside tobramycin is standard-of-care for many types of Pseudomonas aeruginosa infections, including those in the lungs of cystic fibrosis (CF) patients. P. aeruginosa is a nosocomial and opportunistic pathogen that, in planktonic form, causes acute infections and, in biofilm form, causes chronic infections. Inhaled bicarbonate has recently been proposed as a therapy to improve antimicrobial properties of the CF airway surface liquid and viscosity of CF mucus. Here we measure the effect of combining tobramycin and bicarbonate against P. aeruginosa, both lab strains and CF clinical isolates. Bicarbonate synergises with tobramycin to enhance killing of planktonic bacteria. In contrast, bicarbonate antagonises with tobramycin to promote better biofilm growth. This suggests caution when evaluating bicarbonate as a therapy for CF lungs infected with P. aeruginosa biofilms. We analyse tobramycin and bicarbonate interactions using an interpolated surface methodology to measure the dose–response function. These surfaces allow more accurate estimation of combinations yielding synergy and antagonism than do standard isobolograms. By incorporating predictions based on Loewe additivity theory, we can consolidate information on a wide range of combinations that produce a complex dose–response surface, into a single number that measures the net effect. This tool thus allows rapid initial estimation of the potential benefit or harm of a therapeutic combination. Software code is freely made available as a resource for the community.
Improving resolution in quantum subnanometre-gap tip-enhanced Raman nanoimaging
Authors: Zhang Yingchao , Voronine Dmitri V. , Qiu Shangran , Sinyukov Alexander M. , Hamilton Mary , Liege Zachary , Sokolov Alexei V. , Zhang Zhenrong , Scully Marlan O.
Published: May 2016

Two-dimensional (2D) materials beyond graphene such as transition metal dichalcogenides (TMDs) have unique mechanical, optical and electronic properties with promising applications in flexible devices, catalysis and sensing. Optical imaging of TMDs using photoluminescence and Raman spectroscopy can reveal the effects of structure, strain, doping, edge states and surface functionalization from materials to bioscience. However, Raman signals are inherently weak and so far have been limited in spatial resolution in TMDs to a few hundred nanometres which is much larger than the intrinsic scale of these effects. Here we overcome the diffraction limit by using resonant tip-enhanced Raman scattering (TERS) of few-layer MoS2 and obtain nanoscale optical images with ~20 nm spatial resolution. This becomes possible due to electric field enhancement in an optimized subnanometre-gap resonant tip-substrate configuration. We investigate the limits of signal enhancement by varying the tip-sample gap with sub-Angstrom precision and observe a quantum quenching behavior, as well as a Schottky-Ohmic transition, for subnanometre gaps, which enable surface mapping based on this new contrast mechanism. This quantum regime of plasmonic gap-mode enhancement with a few nanometre thick MoS2 junction may be used for designing new quantum optoelectronic devices and sensors with a wide range of applications.
Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing
Authors: Kim Won-Keun , Kim Jeong-Ah , Song Dong Hyun , Lee Daesang , Kim Yong Chul , Lee Sook-Young , Lee Seung-Ho , No Jin Sun , Kim Ji Hye , Kho Jeong Hoon , Gu Se Hun , Jeong Seong Tae , Wiley Michael , Kim Heung-Chul , Klein Terry A. , Palacios Gustavo , Song Jin-Won
Published: May 2016

Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.
Ultra-high density optical data storage in common transparent plastics
Authors: Kallepalli Deepak L. N. , Alshehri Ali M. , Marquez Daniela T. , Andrzejewski Lukasz , Scaiano Juan C. , Bhardwaj Ravi
Published: May 2016

The ever-increasing demand for high data storage capacity has spurred research on development of innovative technologies and new storage materials. Conventional GByte optical discs (DVDs and Bluray) can be transformed into ultrahigh capacity storage media by encoding multi-level and multiplexed information within the three dimensional volume of a recording medium. However, in most cases the recording medium had to be photosensitive requiring doping with photochromic molecules or nanoparticles in a multilayer stack or in the bulk material. Here, we show high-density data storage in commonly available plastics without any special material preparation. A pulsed laser was used to record data in micron-sized modified regions. Upon excitation by the read laser, each modified region emits fluorescence whose intensity represents 32 grey levels corresponding to 5 bits. We demonstrate up to 20 layers of embedded data. Adjusting the read laser power and detector sensitivity storage capacities up to 0.2 TBytes can be achieved in a standard 120 mm disc.
Involvement of the P2X7-NLRP3 axis in leukemic cell proliferation and death
Authors: Salaro Erica , Rambaldi Alessia , Falzoni Simonetta , Amoroso Francesca Saveria , Franceschini Alessia , Sarti Alba Clara , Bonora Massimo , Cavazzini Francesco , Rigolin Gian Matteo , Ciccone Maria , Audrito Valentina , Deaglio Silvia , Pelegrin Pablo , Pinton Paolo , Cuneo Antonio , Di Virgilio Francesco
Published: May 2016

Lymphocyte growth and differentiation are modulated by extracellular nucleotides and P2 receptors. We previously showed that the P2X7 receptor (P2X7R or P2RX7) is overexpressed in circulating lymphocytes from chronic lymphocytic leukemia (CLL) patients. In the present study we investigated the P2X7R/NLRP3 inflammasome axis in lymphocytes from a cohort of 23 CLL patients. P2X7R, ASC and NLRP3 were investigated by Western blot, PCR and transfection techniques. P2X7R was overexpressed and correlated with chromosome 12 trisomy in CLL patients. ASC mRNA and protein were also overexpressed. On the contrary, NLRP3 was dramatically down-modulated in CLL lymphocytes relative to lymphocytes from healthy donors. To further investigate the correlation between P2X7R, NLRP3 and cell growth, NLRP3 was silenced in THP-1 cells, a leukemic cell line that natively expresses both NLRP3 and P2X7R. NLRP3 silencing enhanced P2X7R expression and promoted growth. On the contrary, NLRP3 overexpression caused accelerated apoptosis. The P2X7R was also up-modulated in hematopoietic cells from NLRP3-KO mice. In conclusion, we show that NLRP3 down-modulation stimulates P2X7R expression and promotes growth, while NLRP3 overexpression inhibits cell proliferation and stimulates apoptosis. These findings suggest that NLRP3 is a negative regulator of growth and point to a role of the P2X7R/NLRP3 axis in CLL.
A method of undifferenced ambiguity resolution for GPS+GLONASS precise point positioning
Authors: Yi Wenting , Song Weiwei , Lou Yidong , Shi Chuang , Yao Yibin
Published: May 2016

Integer ambiguity resolution is critical for achieving positions of high precision and for shortening the convergence time of precise point positioning (PPP). However, GLONASS adopts the signal processing technology of frequency division multiple access and results in inter-frequency code biases (IFCBs), which are currently difficult to correct. This bias makes the methods proposed for GPS ambiguity fixing unsuitable for GLONASS. To realize undifferenced GLONASS ambiguity fixing, we propose an undifferenced ambiguity resolution method for GPS+GLONASS PPP, which considers the IFCBs estimation. The experimental result demonstrates that the success rate of GLONASS ambiguity fixing can reach 75% through the proposed method. Compared with the ambiguity float solutions, the positioning accuracies of ambiguity-fixed solutions of GLONASS-only PPP are increased by 12.2%, 20.9%, and 10.3%, and that of the GPS+GLONASS PPP by 13.0%, 35.2%, and 14.1% in the North, East and Up directions, respectively.
RNAi down-regulation of cinnamate-4-hydroxylase increases artemisinin biosynthesis in Artemisia annua
Authors: Kumar Ritesh , Vashisth Divya , Misra Amita , Akhtar Md Qussen , Jalil Syed Uzma , Shanker Karuna , Gupta Madan Mohan , Rout Prashant Kumar , Gupta Anil Kumar , Shasany Ajit Kumar
Published: May 2016

Cinnamate-4-hydroxylase(C4H) convertstrans-cinnamic acid (CA) top-coumaric acid (COA) in the phenylpropanoid/lignin biosynthesis pathway. Earlier we reported increased expression ofAaCYP71AV1(an important gene of artemisinin biosynthesis pathway) caused by CA treatment inArtemisia annua. Hence,AaC4Hgene was identified, cloned, characterized and silenced inA. annuawith the assumption that the elevated internal CA due to knock down may increase the artemisinin yield. Accumulation oftrans-cinnamic acid in the plant due toAaC4Hknockdown was accompanied with the reduction ofp-coumaric acid, total phenolics, anthocyanin, cinnamate-4-hydroxylase (C4H) and phenylalanine ammonia lyase (PAL) activities but increase in salicylic acid (SA) and artemisinin. Interestingly, feedingtrans-cinnamic acid to the RNAi line increased the level of artemisinin along with benzoic (BA) and SA with no effect on the downstream metabolitesp-coumaric acid, coniferylaldehyde and sinapaldehyde, whereasp-coumaric acid feeding increased the content of downstream coniferylaldehyde and sinapaldehyde with no effect on BA, SA,trans-cinnamic acid or artemisinin. SA is reported earlier to be inducing the artemisinin yield. This report demonstrates the link between the phenylpropanoid/lignin pathway with artemisinin pathway through SA, triggered by accumulation oftrans-cinnamic acid because of the blockage at C4H.
Fiber-Type Random Laser Based on a Cylindrical Waveguide with a Disordered Cladding Layer
Authors: Zhang Wei Li , Zheng Meng Ya , Ma Rui , Gong Chao Yang , Yang Zhao Ji , Peng Gang Ding , Rao Yun Jiang
Published: May 2016

This letter reports a fiber-type random laser (RL) which is made from a capillary coated with a disordered layer at its internal surface and filled with a gain (laser dye) solution in the core region. This fiber-type optical structure, with the disordered layer providing randomly scattered light into the gain region and the cylindrical waveguide providing confinement of light, assists the formation of random lasing modes and enables a flexible and efficient way of making random lasers. We found that the RL is sensitive to laser dye concentration in the core region and there exists a fine exponential relationship between the lasing intensity and particle concentration in the gain solution. The proposed structure could be a fine platform of realizing random lasing and random lasing based sensing.
Synthesis and Characterization of an Alumina Forming Nanolaminated Boride: MoAlB
Authors: Kota Sankalp , Zapata-Solvas Eugenio , Ly Alexander , Lu Jun , Elkassabany Omar , Huon Amanda , Lee William E. , Hultman Lars , May Steve J. , Barsoum Michel W.
Published: May 2016

The ‘MAlB’ phases are nanolaminated, ternary transition metal borides that consist of a transition metal boride sublattice interleaved by monolayers or bilayers of pure aluminum. However, their synthesis and properties remain largely unexplored. Herein, we synthesized dense, predominantly single-phase samples of one such compound, MoAlB, using a reactive hot pressing method. High-resolution scanning transmission electron microscopy confirmed the presence of two Al layers in between a Mo-B sublattice. Unique among the transition metal borides, MoAlB forms a dense, alumina scale when heated in air. Like other alumina formers, the oxidation kinetics follow a cubic time-dependence. At room temperature, its resistivity is low (0.36–0.49 μΩm) and – like a metal – drops linearly with decreasing temperatures. It is also a good thermal conductor (35 Wm−1K−1at 26 °C). In the 25–1300 °C temperature range, its thermal expansion coefficient is 9.5 × 10−6K−1. Preliminary results suggest the compound is stable to at least 1400 °C in inert atmospheres. Moderately low Vickers hardness values of 10.6 ± 0.3 GPa, compared to other transition metal borides, and ultimate compressive strengths up to 1940 ± 103 MPa were measured at room temperature. These results are encouraging and warrant further study of this compound for potential use at high temperatures.