bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionalized PEG‐b‐PAGE‐b‐PLGA triblock terpolymers as materials for nanoparticle preparation
Authors: Czaplewska Justyna A. , Majdanski Tobias C. , Barthel Markus J. , Gottschaldt Michael , Schubert Ulrich S.
Published: May 2015

A series of poly(ethylene glycol)‐block‐poly(allyl glycidyl ether) (PEG‐b‐PAGE) macroinitiators are prepared using the living anionic ring‐opening polymerization (AROP) technique, and applied for further copolymerization studies. To overcome the low reactivity of the secondary hydroxyl end‐group of the PAGE block, a primary hydroxyl group is introduced into the macroinitiators via trityl and tert‐butyl‐dimethylsilane protective groups. The modified macroinitiators are used for copolymerization by applying different amounts of PEG‐b‐PAGE (5, 10, and 15%) and different PLGA lengths. To study their properties, nanoparticles from selected polymers are prepared and characterized by dynamic light scattering and scanning electron microscopy showing spherical particles with diameters around 200 nm and low PDIparticle values of 0.03–0.1. An advantage of the obtained polymers is the presence of double bonds in the side chain, which enables the modification via, for example, thiol‐ene reactions. For this purpose tertiary 2‐(dimethylamino)ethanethiol), acetylated thiogalactose and thiomannose are attached onto the double bonds of the PAGE‐blocks. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2163–2174
One‐Pot Synthesis of Algae‐Like MoS2/PPy Nanocomposite: A Synergistic Catalyst with Superior Peroxidase‐Like Catalytic Activity for H2O2 Detection
Authors: Lei Junyu , Lu Xiaofeng , Nie Guangdi , Jiang Ziqiao , Wang Ce
Published: May 2015

A facile one‐pot synthetic route is reported to prepare algae‐like molybdenum disulfide/polypyrrole (MoS2/PPy) nanocomposite through a redox reaction between ammonium tetrathiomolybdate and pyrrole monomer under a hydrothermal condition without any other templates. The as‐prepared unique algae‐like MoS2/PPy nanocomposites are composed of few layer MoS2 nanosheets, which are covered with PPy. Structural and morphological characterizations of this unique nanocomposite are investigated by Fourier‐transform infrared spectra, Raman spectra, X‐ray diffraction pattern, X‐ray photoelectron spectra, energy‐dispersive X‐ray spectroscopy, and transmission electron microscopy. The as‐prepared MoS2/PPy nanocomposites exhibit an excellent peroxidase‐like catalytic activity toward the oxidation of 3,3,5,5‐tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2) in acetate buffer solution (pH 4.0), which provides a facile strategy for the colorimetric detection of H2O2 with a high sensitivity.
Convenient synthesis of phosphonodipeptides containing C‐terminal α‐aminoalkylphosphonic acids
Authors: Sun Biyun , Xu Jiaxi
Published: May 2015

Phosphonopeptides are important phosphorus analogs of natural peptides and have been widely applied as enzyme inhibitors and antibacterial agents. A series of phosphonodipeptides containing C‐terminal α‐aminoalkylphosphonic acids was synthesized in satisfactory to good yields conveniently from 2‐(N‐benzyloxycarbonylamino)alkanamides, aldehydes, and phosphorus trichloride via Mannich‐type reaction and subsequent sequential hydrolysis. The reaction mechanism was proposed and verified by 31P NMR tracing experiments. The current method is an efficient and convenient method for preparation of phosphonopeptides containing C‐terminal α‐aminoalkylphosphonic acids. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
Internal and International Migration in East and Southeast Asia: Exploring the Linkages
Authors: Hugo Graeme John
Published: May 2015

Internal and international migration have increased exponentially in scale, complexity and significance in the last two decades. There are often strong relationships between internal and international migration, but they remain little understood because the two types of movement are conceptualised, measured and studied separately. This paper is divided into two parts. The first summarises the areas of both convergence and divergence in the types, patterns, causes and consequences of internal and international migration in the Asian region. These are considered partially in the context of the complex relationship between migration and development. It is shown that there is more convergence than divergence conceptually and theoretically. The second part of the paper addresses the issue of linkages between internal and international migration. This model argues that on the one hand international migrants usually engage in a different pattern of internal migration than the established population at the destination. It also suggests that in some cases international migration itself may influence the internal migration patterns of the resident population. On the other hand there are also linkages in ‘origin’ countries where particular patterns of internal migration precede international migration. Copyright © 2015 John Wiley & Sons, Ltd.
Migrants' Transnationality, Societal Transformation, and Locality: an Introduction
Authors: Fauser Margit , Nijenhuis Gery
Published: May 2015

The implications of migrants' transnational engagements for processes of change and development in the regions of origin are attracting increased attention from both policymakers and academics. Rather than addressing the positive effects of migration and transnationality on local development, this special issue suggests a focus on the relationship between this phenomenon and broader societal transformation, thereby acknowledging the renewed importance of place and locality. To this end, this introduction provides an overview of the current debate on transnational dynamics in relation to societal transformation, local development, and inequality. Central to our analysis is the way in which migrants' transnationality engages with the hierarchies that exist between and within localities, and how this reproduces social inequalities. This introduction thus also reflects the key themes that are addressed in the five papers that make up this special issue on transnational dynamics, transformation, and locality. Copyright © 2015 John Wiley & Sons, Ltd.
Efficacy and Safety of White Willow Bark (Salix alba) Extracts
Authors: Shara Mohd , Stohs Sidney J.
Published: May 2015

Willow bark extract has been used for thousands of years as an anti‐inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti‐inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti‐inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor‐α and nuclear factor‐kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non‐steroidal anti‐inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate‐sensitive individuals. Copyright © 2015 John Wiley & Sons, Ltd.
Frontal‐wave cyclogenesis in the North Atlantic –a climatological characterisation
Authors: Schemm Sebastian , Sprenger Michael
Published: May 2015

The ambient conditions during cyclogenesis on fronts in the North Atlantic (NA) are characterised climatologically in the ERA‐Interim dataset. These ‘secondary’ cyclones, which grow from frontal waves, are typically small in scale, shallow and deepen rapidly, and pose a challenge to forecasters and numerical weather prediction models. Frontal‐wave development has been studied intensively in the past based on observations (e.g. FASTEX), real‐case studies or analytical models. In this study, frontal‐wave cyclogenesis is studied from a climatological perspective and is detected by a combination of two automated identification methods for the period between 1979 and 2014. A climatology of frontal‐wave cyclogenesis is presented. Horizontal composites provide an estimate of the climatological mean of conditions during frontal‐wave cyclogenesis which may prove useful in the assessment of the realism of proposed idealized models of frontogenesis. The findings are also compared with assumptions made in earlier idealized studies of frontal waves. The composites reveal coherent structures of diabatically generated low‐level PV in the lower troposphere, neutral moist static stability at cyclogenesis and an ambient lower troposphere close to saturation. The vertical PV structure in the east NA is more vertically aligned than in the west NA and PV anomalies from the upper and lower levels reach deeper into the mid‐troposphere, which indicates an enhanced phase‐lock between the two anomalies. Previous studies suggest the existence of an upper limit of along‐frontal stretching above which frontal‐wave development is strongly suppressed. The presented multi‐decadal analysis confirms its existence in a range between 0.6 and 0.8 × 10−5 s−1. Finally a climatology of along‐frontal stretching for the NA is presented and compared to the fraction of cyclogenesis forming on frontal waves.
Robot‐assisted intersphincteric resection for rectal submucosal tumour
Authors: Du Jin‐Lin , Chen Chia‐Che , Chao Hsiao‐Mei , Kuo Li‐Jen
Published: May 2015

Background

Rectal submucosal tumours are rare. The purpose of this study was to evaluate the safety and feasibility of robot‐assisted rectal surgery.

Methods

Patients who received robot‐assisted intersphincteric resection (ISR) were included in the present study. Clinical outcomes, operating time, length of hospital stay and pathological status were analysed.

Results

There were three patients with gastrointestinal tumours and three patients diagnosed with neuroendocrine tumours. The mean operating time was 369.2 min and the estimated blood loss was 66.7 ml. There were neither intraoperative complications nor conversions. On pathological examination, the mean number of lymph nodes harvested was 10.3 (range 3–16), the mean distal resection margin was 1.1 (range 0.1–3) cm and all six patients had the circumferential resection margins clear.

Conclusions

Our data show that robotic surgery is feasible and safe, with no morbidity or mortality, and that ISR provides bowel continuity and eliminates the need for colostomy. Copyright © 2015 John Wiley & Sons, Ltd.
Sealed‐bid auction: a cryptographic solution to bid‐rigging attack in the collusive environment
Authors: Howlader Jaydeep , Mal Ashis Kumar
Published: May 2015

Sealed‐Bid auction is an efficient and rational way to establish the price and trading goods in the open market. However sealed‐bid auctions are subject to bid‐rigging attack. Receipt‐free mechanisms are proposed to prevent bid‐rigging. So far, all the proposed receipt‐free mechanisms are based on strict assumptions: i) The channel between bidders and the auction authorities (like auctioneer, sealer, registering authority etc.) must be untappable, 2) the authorities are assumed to be honest (not colluded), hence ensure privacy and anonymity of bids. Moreover, the existing receipt‐free mechanisms are bandwidth intensive (estimated difference between the minimum and maximum bidding price). In this paper, we present a receipt‐free sealed‐bid auction mechanism which can withstand public channel and colluded authorities. The proposed mechanism can work even under the situation where all the authorities except one are colluded. Unlike the existing mechanisms, the computational complexity of the proposed mechanism is independent of the bandwidth and only depends on the number of valid bids. The auction mechanism requires O(mlogm) computational steps to resolve the winner, where m is the number of valid bids in the system. Copyright © 2015 John Wiley & Sons, Ltd.
Disentangling effects of noise from presence of anthropogenic infrastructure: Design and testing of system for large‐scale playback experiments
Authors: Rosa Patricia , Swider Colin R. , Leston Lionel , Koper Nicola
Published: May 2015

Anthropogenic noise may be detrimental to many bird species, and manipulative experiments would help us understand these effects. We present the design and validation of a self‐sustaining solar‐powered broadcasting system that will allow researchers to disentangle acute or chronic effects of noise from effects of the presence of infrastructure, even in remote areas. We tested the broadcasting system using a case study on noise from oil well infrastructure in southern Alberta, Canada. Recordings from 2 types of oil wells were obtained and then broadcasted through 6 independent playback units continuously for a period of 3 months in 2013, at sites undisturbed by oil development. Sound measurements at real oil wells and at sites with broadcasting systems simulating the noise from these oil wells demonstrated that real and projected noise had very similar sound pressure levels, attenuation trends, and spectral composition. Throughout this long‐term playback experiment, the system produced power and noise reliably and consistently. In conjunction with bird surveys, this experimental design and infrastructure can be used to allow researchers to dissociate the presence of anthropogenic development from associated noise, providing us with information that will help decrease the environmental impacts of human activities. © 2015 The Wildlife Society.
Quantitative analysis in femur of Wistar rats after chemotherapy treatment for breast cancer using synchrotron X‐ray microfluorescence and microtomography
Authors: Pickler A. , Alessio R. , Mota C. L. , Mantuano A. , Nogueira L. P. , Salata C. , Almeida A. P. , Sena G. , Braz D. , de Almeida C. E. V. , Barroso R. C.
Published: May 2015

In recent years, new techniques have been developed for the analysis of bone matrix. Two of the most common technologies that make use of X‐rays are X‐ray microfluorescence (μXRF) and X‐ray absorption microtomography (μCT). μXRF is a powerful analytical tool for the spectroscopic determination of almost all elements (Z > 13) present in a sample. μCT is a nondestructive technique, which can be used to create cross sections of complex objects.

In this work, both techniques were applied to bones to evaluate possible structural and elemental modifications caused by chemotherapy procedure. Ten adult female Wistar rats, clinically healthy, divided randomly into two groups: treated group (called G1) received doses of docetaxel and cyclophosphamide drugs, while control group (called G0) was not treated. The elemental distribution of Ca and morphometric parameters, cortical porosity and bone volume–total tissue volume ratio in femur head, was investigated using μXRF and μCT, respectively, with the aim of helping to obtain a better understanding of the side effects caused by chemotherapy treatment for breast cancer. Calcium distribution maps were obtained by μXRF in the X‐ray fluorescence beamline at the Brazilian Synchrotron Light Laboratory. Morphometric parameters were calculated from three‐dimensional microtomographic images carried out at the Synchrotron Radiation on Medical Physics beamline at the Elettra Synchrotron Laboratory in Trieste, Italy. As a result of this study using μXRF, Ca levels show a significant decrease in treated bones in comparison with the control group. From μCT analysis, bone volume–total tissue volume ratio shows a tendency to decrease, while cortical porosity shows significant increase in bones from G1 group. Copyright © 2015 John Wiley & Sons, Ltd.
A Critical Review of Theories and Measures of Ethics‐Related Leadership
Authors: Zhu Weichun , Zheng Xiaoming , Riggio Ronald E. , Zhang Xi
Published: May 2015

This chapter reviews the different theoretical perspectives and measurements of ethics‐related leadership models, including ethical leadership, transformational leadership, authentic leadership, servant leadership, spiritual leadership, and a virtues‐based approach to leadership ethics. The similarities and differences among these theoretical models and measures to ethics‐related leadership are discussed.
Both habitat change and local lek structure influence patterns of spatial loss and recovery in a black grouse population
Authors: Geary Matthew , Fielding Alan H. , Marsden Stuart J.
Published: May 2015

Land use change is a major driver of declines in wildlife populations. Where human economic or recreational interests and wildlife share landscapes this problem is exacerbated. Changes in UK black grouse Tetrao tetrix populations are thought to have been strongly influenced by upland land use change. In a long‐studied population within Perthshire, lek persistence is positively correlated with lek size, and remaining leks clustered most strongly within the landscape when the population is lowest, suggesting that there may be a demographic and/or spatial context to the reaction of the population to habitat changes. Hierarchical cluster analysis of lek locations revealed that patterns of lek occupancy when the population was declining were different to those during the later recovery period. Response curves from lek‐habitat models developed using MaxEnt for periods with a declining population, low population, and recovering population were consistent across years for most habitat measures. We found evidence linking lek persistence with habitat quality changes and more leks which appeared between 1994 and 2008 were in improving habitat than those which disappeared during the same period. Generalised additive models identified changes in woodland and starting lek size as being important indicators of lek survival between declining and low/recovery periods. There may also have been a role for local densities in explaining recovery since the population low point. Persistence of black grouse leks was influenced by habitat, but changes in this alone did not fully account for black grouse declines. Even when surrounded by good quality habitat, leks can be susceptible to extirpation due to isolation.
Imagining Hope from Dante's Inferno: Observations on ‘Person-centred Practice’
Authors: Rushworth Nick
Published: May 2015

Look, I’m hardly what you’d call on the speaking circuit, but I’ve gone enough rounds with rubber chickens to know only an idiot with a death wish would get between anyone and a buffet dinner – a set of bottomless (very gourmet, I’m sure, but still bottomless) chafing dishes. If it's any consolation, I won't be holding you back for too long.
A novel method of reduction for first-time acute lateral patellar dislocations in children and adolescents
Authors: Ong Gene Yong-Kwang
Published: May 2015

Five pediatric patients with acute traumatic "first-time" lateral patellar dislocations were successfully reduced using a novel, atraumatic, and simple technique. Uniquely, unlike the traditional method of patellar reduction, the patellar dislocations were reduced without any direct manipulation of the patella. In co-operative patients, no analgesia was required. Further validation of the reproducibility of the effectiveness of this method for successful patellar reduction in pediatric and adult populations are required.
Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida
Authors: Kondo Atsuo , Morota Nobuhito , Date Hiroaki , Yoshifuji Kazuhisa , Morishima Toshibumi , Miyazato Minoru , Shirane Reizo , Sakai Hideki , Pooh Kyong Hon , Watanabe Tomoyuki
Published: May 2015

The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 μg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case–control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0·48 in the first period, and 0·53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan.
The role of dietary coconut for the prevention and treatment of Alzheimer's disease: potential mechanisms of action
Authors: Fernando W. M. A. D. B. , Martins Ian J. , Goozee K. G. , Brennan Charles S. , Jayasena V. , Martins R. N.
Published: May 2015

Coconut,Cocos nuciferaL., is a tree that is cultivated to provide a large number of products, although it is mainly grown for its nutritional and medicinal values. Coconut oil, derived from the coconut fruit, has been recognised historically as containing high levels of saturated fat; however, closer scrutiny suggests that coconut should be regarded more favourably. Unlike most other dietary fats that are high in long-chain fatty acids, coconut oil comprises medium-chain fatty acids (MCFA). MCFA are unique in that they are easily absorbed and metabolised by the liver, and can be converted to ketones. Ketone bodies are an important alternative energy source in the brain, and may be beneficial to people developing or already with memory impairment, as in Alzheimer's disease (AD). Coconut is classified as a highly nutritious ‘functional food’. It is rich in dietary fibre, vitamins and minerals; however, notably, evidence is mounting to support the concept that coconut may be beneficial in the treatment of obesity, dyslipidaemia, elevated LDL, insulin resistance and hypertension – these are the risk factors for CVD and type 2 diabetes, and also for AD. In addition, phenolic compounds and hormones (cytokinins) found in coconut may assist in preventing the aggregation of amyloid-β peptide, potentially inhibiting a key step in the pathogenesis of AD. The purpose of the present review was to explore the literature related to coconut, outlining the known mechanistic physiology, and to discuss the potential role of coconut supplementation as a therapeutic option in the prevention and management of AD.
“This Story Is about Something Fundamental”: Nazi Criminals, History, Memory, and the Reichstag Fire
Authors: Hett Benjamin Carter
Published: May 2015

For more than eighty years there has been controversy about who set the fire that destroyed the plenary chamber of the Reichstag fire on the evening of February 27, 1933—thereby handing the Nazis a pretext to gut the democratic Weimar constitution through the emergency “Reichstag Fire Decree.” Since the 1960s there has been a consensus among historians that the fire was set by Marinus van der Lubbe, a twenty-four-year-old Dutch journeyman stonemason supposedly acting alone—with no Nazi involvement. Few historians, however, have been inclined to investigate the motives behind the development of this single-culprit narrative, or the reasons for its generally positive reception among postwar German historians. With the aid of newly discovered sources, this article examines the legal and political interests that have underpinned this narrative. The single-culprit narrative was developed by ex-Nazis, whereas accounts of the Reichstag fire stressing Nazi complicity came almost invariably from former resistance fighters and victims of Nazism. Postwar historians responded to these accounts in much the same way they have responded to perpetrator and victim accounts of the Holocaust: with a markedly greater preference for those of the perpetrators. This tendency has shaped the debate over the Reichstag fire in the same way it has shaped other areas of research on the Third Reich.
CHANGES IN MARRIAGE PATTERNS AMONG THE ARAB COMMUNITY IN ISRAEL OVER A 60-YEAR PERIOD
Authors: Sharkia Rajech , Mahajnah Muhammad , Athamny Esmael , Khatib Mohammad , Sheikh-Muhammad Ahmad , Zalan Abdelnaser
Published: May 2015

The aim of this study was to determine the prevalence and trends of various types of consanguineous marriage among the Arab community in Israel over a long time period (1948–2007) by religion and educational level. Data were collected by face-to-face interview of 3173 Arab couples living in Israel in 2007 and 2008. The trend in consanguineous marriages was found to decrease significantly over successive time periods, from 42.5% to 30.9% (p=0.001), and the prevalence of first-cousin and closer marriages decreased, from 23% to 12.7%. Consanguinity was found to be significantly related to religion (p=0.001) and wife’s level of education (p=0.028).
SOCIAL, HISTORICAL AND CULTURAL DIMENSIONS OF TUBERCULOSIS
Authors: Mason Paul H. , Roy Anupom , Spillane Jayden , Singh Puneet
Published: May 2015

Tuberculosis (TB) researchers and clinicians, by virtue of the social disease they study, are drawn into an engagement with ways of understanding illness that extend beyond the strictly biomedical model. Primers on social science concepts directly relevant to TB, however, are lacking. The particularities of TB disease mean that certain social science concepts are more relevant than others. Concepts such as structural violence can seem complicated and off-putting. Other concepts, such as gender, can seem so familiar that they are left relatively unexplored. An intimate familiarity with the social dimensions of disease is valuable, particularly for infectious diseases, because the social model is an important complement to the biomedical model. This review article offers an important introduction to a selection of concepts directly relevant to TB from health sociology, medical anthropology and social cognitive theory. The article has pedagogical utility and also serves as a useful refresher for those researchers already engaged in this genre of work. The conceptual tools of health sociology, medical anthropology and social cognitive theory offer insightful ways to examine the social, historical and cultural dimensions of public health. By recognizing cultural experience as a central force shaping human interactions with the world, TB researchers and clinicians develop a more nuanced consideration of how health, illness and medical treatment are understood, interpreted and confronted.
Struggles over the Use of Public Space: Exploring Moralities and Narratives of Inequality. Cartoneros and Vecinos in Buenos Aires
Authors: COSACOV NATALIA , PERELMAN MARIANO D.
Published: May 2015

Based on extensive and long-term ethnographic fieldwork carried out between 2002 and 2009, and by analysing the presence, use and struggles over public space of cartoneros and vecinos in middle-class and central neighbourhoods of the city of Buenos Aires, this article examines practices, moralities and narratives operating in the production and maintenance of social inequalities. Concentrating on spatialised interactions, it shows how class inequalities are reproduced and social distances are generated in the struggle over public space. For this, two social situations are addressed. First, we explore the way in which cartoneros build routes in middle-class neighbourhoods in order to carry out their task. Second, we present an analysis of the eviction process of a cartonero settlement in the city.
Photoswitchable fatty acids enable optical control of TRPV1
Authors: Frank James Allen , Moroni Mirko , Moshourab Rabih , Sumser Martin , Lewin Gary R. , Trauner Dirk
Published: May 2015

Fatty acids (FAs) are not only essential components of cellular energy storage and structure, but play crucial roles in signalling. Here we present a toolkit of photoswitchable FA analogues (FAAzos) that incorporate an azobenzene photoswitch along the FA chain. By modifying the FAAzos to resemble capsaicin, we prepare a series of photolipids targeting the Vanilloid Receptor 1 (TRPV1), a non-selective cation channel known for its role in nociception. Several azo-capsaicin derivatives (AzCAs) emerge as photoswitchable agonists of TRPV1 that are relatively inactive in the dark and become active on irradiation with ultraviolet-A light. This effect can be rapidly reversed by irradiation with blue light and permits the robust optical control of dorsal root ganglion neurons and C-fibre nociceptors with precision timing and kinetics not available with any other technique. More generally, we expect that photolipids will find many applications in controlling biological pathways that rely on protein–lipid interactions.
TRPM8 is a neuronal osmosensor that regulates eye blinking in mice
Authors: Quallo Talisia , Vastani Nisha , Horridge Elisabeth , Gentry Clive , Parra Andres , Moss Sian , Viana Felix , Belmonte Carlos , Andersson David A. , Bevan Stuart
Published: May 2015

Specific peripheral sensory neurons respond to increases in extracellular osmolality but the mechanism responsible for excitation is unknown. Here we show that small increases in osmolality excite isolated mouse dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons expressing the cold-sensitive TRPM8 channel (transient receptor potential channel, subfamily M, member 8). Hyperosmotic responses were abolished by TRPM8 antagonists, and were absent in DRG and TG neurons isolated from Trpm8−/− mice. Heterologously expressed TRPM8 was activated by increased osmolality around physiological levels and inhibited by reduced osmolality. Electrophysiological studies in a mouse corneal preparation demonstrated that osmolality regulated the electrical activity of TRPM8-expressing corneal afferent neurons. Finally, the frequency of eye blinks was reduced in Trpm8−/− compared with wild-type mice and topical administration of a TRPM8 antagonist reduced blinking in wild-type mice. Our findings identify TRPM8 as a peripheral osmosensor responsible for the regulation of normal eye-blinking in mice.
The evolution of spatial ordering of oil drops fast spreading on a water surface
Authors: Yamamoto Daigo , Nakajima Chika , Shioi Akihisa , Krafft Marie Pierre , Yoshikawa Kenichi
Published: May 2015

The design of dynamically self-assembled systems is of high interest in science and technology. Here, we report a unique cascade in the self-ordering of droplets accompanied by a dewetting transition. The dynamic self-emergent droplets are observed when a thin liquid layer of an immiscible fluorocarbon oil (perfluorooctyl bromide, PFOB) is placed on a water surface. Due to the gradual evaporation of PFOB, a circular PFOB-free domain appears as a result of a local dewetting transition. A circular pearling structure is generated at the rim with the growth of the dewetting hole. As the next stage, linear arrays of droplets are generated in a radial manner from the centre of the hole. These one-dimensional arrangements then evolve into two-dimensional hexagonal arrays of microdroplets through collective rhythmical shrinking/expanding motions. The emergence of such dynamic patterns is discussed in terms of the nonlinear kinetics of the dewetting transition under thermodynamically dissipative conditions.
Enhanced multi-colour gating for the generation of high-power isolated attosecond pulses
Authors: Haessler S. , Balčiūnas T. , Fan G. , Chipperfield L. E. , Baltuška A.
Published: May 2015

Isolated attosecond pulses (IAP) generated by high-order harmonic generation are valuable tools that enable dynamics to be studied on the attosecond time scale. The applicability of these IAP would be widened drastically by increasing their energy. Here we analyze the potential of using multi-colour driving pulses for temporally gating the attosecond pulse generation process. We devise how this approach can enable the generation of IAP with the available high-energy kHz-repetition-rate Ytterbium-based laser amplifiers (delivering 180-fs, 1030-nm pulses). We show theoretically that this requires a three-colour field composed of the fundamental and its second harmonic as well as a lower-frequency auxiliary component. We present pulse characterization measurements of such auxiliary pulses generated directly by white-light seeded OPA with the required significantly shorter pulse duration than that of the fundamental. This, combined with our recent experimental results on three-colour waveform synthesis, proves that the theoretically considered multi-colour drivers for IAP generation can be realized with existing high-power laser technology. The high-energy driver pulses, combined with the strongly enhanced single-atom-level conversion efficiency we observe in our calculations, thus make multi-colour drivers prime candidates for the development of unprecedented high-energy IAP sources in the near future.
Gene expression studies of a human monocyte cell line identify dissimilarities between differently manufactured glatiramoids
Authors: Kolitz Sarah , Hasson Tal , Towfic Fadi , Funt Jason M. , Bakshi Shlomo , Fowler Kevin D. , Laifenfeld Daphna , Grinspan Augusto , Artyomov Maxim N. , Birnberg Tal , Schwartz Rivka , Komlosh Arthur , Hayardeny Liat , Ladkani David , Hayden Michael R. , Zeskind Benjamin , Grossman Iris
Published: May 2015

Glatiramer Acetate (GA) has provided safe and effective treatment for multiple sclerosis (MS) patients for two decades. It acts as an antigen, yet the precise mechanism of action remains to be fully elucidated and no validated pharmacokinetic or pharmacodynamic biomarkers exist. In order to better characterize GA’s biological impact, genome-wide expression studies were conducted with a human monocyte (THP-1) cell line. Consistent with previous literature, branded GA upregulated anti-inflammatory markers (e.g.IL10) and modulated multiple immune-related pathways. Despite some similarities, significant differences were observed between expression profiles induced by branded GA and Probioglat, a differently-manufactured glatiramoid purported to be a generic GA. Key results were verified using qRT-PCR. Genes (e.g.CCL5,adj. p < 4.1 × 10−5) critically involved in pro-inflammatory pathways (e.g. response to lipopolysaccharide, adj. p = 8.7 × 10−4) were significantly induced by Probioglat compared with branded GA. Key genes were also tested and confirmed at the protein level and in primary human monocytes. These observations suggest differential biological impact by the two glatiramoids and warrant further investigation.
Generalized-stacking-fault energy and twin-boundary energy of hexagonal close-packed Au: A first-principles calculation
Authors: Wang Cheng , Wang Huiyuan , Huang Tianlong , Xue Xuena , Qiu Feng , Jiang Qichuan
Published: May 2015

Although solid Au is usually most stable as a face-centered cubic (fcc) structure, pure hexagonal close-packed (hcp) Au has been successfully fabricated recently. However, the phase stability and mechanical property of this new material are unclear, which may restrict its further applications. Here we present the evidence that hcp → fcc phase transformation can proceed easily in Au by first-principles calculations. The extremely low generalized-stacking-fault (GSF) energy in the basal slip system implies a great tendency to form basal stacking faults, which opens the door to phase transformation from hcp to fcc. Moreover, the Au lattice extends slightly within the superficial layers due to the self-assembly of alkanethiolate species on hcp Au (0001) surface, which may also contribute to the hcp → fcc phase transformation. Compared with hcp Mg, the GSF energies for non-basal slip systems and the twin-boundary (TB) energies for "Equation missing" and "Equation missing" twins are larger in hcp Au, which indicates the more difficulty in generating non-basal stacking faults and twins. The findings provide new insights for understanding the nature of the hcp → fcc phase transformation and guide the experiments of fabricating and developing materials with new structures.
Synapsin IIb as a functional marker of submissive behavior
Authors: Nesher Elimelech , Koman Igor , Gross Moshe , Tikhonov Tatiana , Bairachnaya Maryia , Salmon-Divon Mali , Levin Yishai , Gerlitz Gabi , Michaelevski Izhak , Yadid Gal , Pinhasov Albert
Published: May 2015

Dominance and submissiveness are important functional elements of the social hierarchy. By employing selective breeding based on a social interaction test, we developed mice with strong and stable, inheritable features of dominance and submissiveness. In order to identify candidate genes responsible for dominant and submissive behavior, we applied transcriptomic and proteomic studies supported by molecular, behavioral and pharmacological approaches. We clearly show here that the expression of Synapsin II isoform b (Syn IIb) is constitutively upregulated in the hippocampus and striatum of submissive mice in comparison to their dominant and wild type counterparts. Moreover, the reduction of submissive behavior achieved after mating and delivery was accompanied by a marked reduction of Syn IIb expression. Since submissiveness has been shown to be associated with depressive-like behavior, we applied acute SSRI (Paroxetine) treatment to reduce submissiveness in studied mice. We found that reduction of submissive behavior evoked by Paroxetine was paired with significantly decreased Syn IIb expression. In conclusion, our findings indicate that submissiveness, known to be an important element of depressive-like behavioral abnormalities, is strongly linked with changes in Syn IIb expression.
Hearing the light: neural and perceptual encoding of optogenetic stimulation in the central auditory pathway
Authors: Guo Wei , Hight Ariel E. , Chen Jenny X. , Klapoetke Nathan C. , Hancock Kenneth E. , Shinn-Cunningham Barbara G. , Boyden Edward S. , Lee Daniel J. , Polley Daniel B.
Published: May 2015

Optogenetics provides a means to dissect the organization and function of neural circuits. Optogenetics also offers the translational promise of restoring sensation, enabling movement or supplanting abnormal activity patterns in pathological brain circuits. However, the inherent sluggishness of evoked photocurrents in conventional channelrhodopsins has hampered the development of optoprostheses that adequately mimic the rate and timing of natural spike patterning. Here, we explore the feasibility and limitations of a central auditory optoprosthesis by photoactivating mouse auditory midbrain neurons that either express channelrhodopsin-2 (ChR2) or Chronos, a channelrhodopsin with ultra-fast channel kinetics. Chronos-mediated spike fidelity surpassed ChR2 and natural acoustic stimulation to support a superior code for the detection and discrimination of rapid pulse trains. Interestingly, this midbrain coding advantage did not translate to a perceptual advantage, as behavioral detection of midbrain activation was equivalent with both opsins. Auditory cortex recordings revealed that the precisely synchronized midbrain responses had been converted to a simplified rate code that was indistinguishable between opsins and less robust overall than acoustic stimulation. These findings demonstrate the temporal coding benefits that can be realized with next-generation channelrhodopsins, but also highlight the challenge of inducing variegated patterns of forebrain spiking activity that support adaptive perception and behavior.
Intrinsically Disordered Energy Landscapes
Authors: Chebaro Yassmine , Ballard Andrew J. , Chakraborty Debayan , Wales David J.
Published: May 2015

Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an "Equation missing"-helical conformation when bound to its partner and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.
miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn’s disease
Authors: Cheng Xiuqin , Zhang Xiaofei , Su Jiewen , Zhang Yingdi , Zhou Weimei , Zhou Jun , Wang Cheng , Liang Hongwei , Chen Xi , Shi Ruihua , Zen Ke , Zhang Chen-Yu , Zhang Hongjie
Published: May 2015

Although aberrant microRNA (miRNA) expression has frequently been observed in inflammatory bowel disease (IBD), its biological functions and targets remain largely unknown. Present study found that miR-19b was significantly downregulated in active Crohn’s disease (CD). Using bioinformatics analysis, suppressor of cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive immunity that controls several immuno-inflammatory diseases, was predicted to be a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3 protein levels, but not mRNA, was identified in active-CD intestinal tissue samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29 cells, it was experimentally validated that miR-19b is a direct regulator of SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly recognizes the 3’-untranslated region (3’-UTR) of SOCS3. Furthermore, overexpression of miR-19b decreased SOCS3 expression, leading to increased production of macrophage-inflammatory protein-3α (MIP-3α) in Caco2 cells. In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3α. Finally, intracolonically delivered miR-19b decreased the severity of colitis induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our findings suggest that miR-19b suppresses the inflammatory response by inhibiting SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and thereby prevents the pathogenesis of CD.
Electromagnetic Detection of a Perfect Carpet Cloak
Authors: Shi Xihang , Gao Fei , Lin Xiao , Zhang Baile
Published: May 2015

It has been shown that a spherical invisibility cloak originally proposed by Pendry et al. can be electromagnetically detected by shooting a charged particle through it, whose underlying mechanism stems from the asymmetry of transformation optics applied to motions of photons and charges [PRL 103, 243901 (2009)]. However, the conceptual three-dimensional invisibility cloak that exactly follows specifications of transformation optics is formidably difficult to implement, while the simplified cylindrical cloak that has been experimentally realized is inherently visible. On the other hand, the recent carpet cloak model has acquired remarkable experimental development, including a recently demonstrated full-parameter carpet cloak without any approximation in the required constitutive parameters. In this paper, we numerically investigate the electromagnetic radiation from a charged particle passing through a perfect carpet cloak and propose an experimentally verifiable model to demonstrate symmetry breaking of transformation optics.
Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects
Authors: Hashizume Osamu , Ohnishi Sakiko , Mito Takayuki , Shimizu Akinori , Ishikawa Kaori , Nakada Kazuto , Soda Manabu , Mano Hiroyuki , Togayachi Sumie , Miyoshi Hiroyuki , Okita Keisuke , Hayashi Jun-Ichi
Published: May 2015

Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects. We carried out reprogramming of human fibroblast lines derived from elderly subjects by generating their induced pluripotent stem cells (iPSCs) and examined another possibility, namely that these aging phenotypes are controlled not by mutations but by epigenetic regulation. Here, we show that reprogramming of elderly fibroblasts restores age-associated mitochondrial respiration defects, indicating that these aging phenotypes are reversible and are similar to differentiation phenotypes in that both are controlled by epigenetic regulation, not by mutations in either the nuclear or the mitochondrial genome. Microarray screening revealed that epigenetic downregulation of the nuclear-coded GCAT gene, which is involved in glycine production in mitochondria, is partly responsible for these aging phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes.
C-reactive protein and risk of breast cancer: A systematic review and meta-analysis
Authors: Guo Lanwei , Liu Shuzheng , Zhang Shaokai , Chen Qiong , Zhang Meng , Quan Peiliang , Lu Jianbang , Sun Xibin
Published: May 2015

Associations between elevated C-reactive protein (CRP) and breast cancer risk have been reported for many years, but the results remain controversial. To address this issue, a meta-analysis was therefore conducted. Eligible studies were identified by searching the PubMed and EMBASE up to December 2014. Study-specific risk estimates were combined using a random-effects model. Altogether fifteen cohort and case-control studies were included in this meta-analysis, involving a total of 5,286 breast cancer cases. The combined OR per natural log unit change in CRP for breast cancer was 1.16 (95% CI: 1.06-1.27). There was moderate heterogeneity among studies (I2 = 45.9%). The association was stronger in Asian population (OR = 1.57, 95% CI: 1.25-1.96) compared to European (OR = 1.12, 95% CI: 1.02-1.23) and American (OR = 1.08, 95% CI: 1.01-1.16). Prediagnostic high-sensitivity CRP concentrations (OR = 1.22, 95% CI: 1.10-1.35) was superior to common CRP (OR = 1.08, 95% CI: 1.01-1.15) in predicting breast cancer risk. The meta-analysis indicated that elevated CRP levels was associated with increased risk of breast cancer. Further research effort should be performed to identify whether CRP, as a marker of inflammation, plays a direct role in breast carcinogenesis.