bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating perceptions of English as a lingua franca in Hong Kong: The case of university students
Authors: Sung Chit Cheung Matthew
Published: September 2017

English as a lingua franca (ELF) has received a great deal of attention in the field of applied linguistics in the last decade or so (Jenkins, 2007, 2014; Mauranen, 2012; Seidlhofer, 2011). As is currently conceptualized, ELF refers to the common language of choice among speakers from different lingua-cultural backgrounds (Jenkins, 2007; Seidlhofer, 2011). ELF does not imply a single, unified variety of English but primarily refers to language inusein contexts where multilingual speakers are involved (Cogo, 2010). In other words, ELF can be understood as social practice, with an emphasis on meaning-making processes. Much of the earlier research focused on identifying linguistic features characteristic of ELF communication (see Jenkins, 2000; Seidlhofer, 2001). But with the increased recognition of the variability and fluidity associated with the use of ELF, researchers have recently turned their attention to investigating communicative strategies which multilingual speakers employ to achieve mutual understanding and negotiate meaning in ELF interactions (see Cogo & Dewey, 2012; Jenkins, Cogo & Dewey, 2011). Furthermore, there exists a growing body of research into attitudes and perceptions of ELF communication (see Cogo, 2010; Jenkins, 2007; Kaloscai, 2009), given the impact of ELF perceptions on ELF-related communicative practices, especially with respect to issues relating to (non-) conformity to native-speaker norms.
AGGREGATION AND CAPITAL ALLOCATION FORMULAS FOR BIVARIATE DISTRIBUTIONS
Authors: Nadarajah Saralees , Chu Jeffrey , Jiang Xiao
Published: September 2017

Cossette, Marceau, and Perreault derived formulas for aggregation and capital allocation based on risks following two bivariate exponential distributions. Here, we derive formulas for aggregation and capital allocation for 18 mostly commonly known families of bivariate distributions. This collection of formulas could be a useful reference for financial risk management.
Comparison of boiling and chlorination on the quality of stored drinking water and childhood diarrhoea in Indonesian households
Authors: FAGERLI K. , TRIVEDI K. K. , SODHA S. V. , BLANTON E. , ATI A. , NGUYEN T. , DELEA K. C. , AINSLIE R. , FIGUEROA M. E. , KIM S. , QUICK R.
Published: September 2017

We compared the impact of a commercial chlorination product (brand name Air RahMat) in stored drinking water to traditional boiling practices in Indonesia. We conducted a baseline survey of all households with children <5 years in four communities, made 11 subsequent weekly home visits to assess acceptability and use of water treatment methods, measured Escherichia coli concentration in stored water, and determined diarrhoea prevalence among children <5 years. Of 281 households surveyed, boiling (83%) and Air RahMat (7%) were the principal water treatment methods. Multivariable log-binomial regression analyses showed lower risk of E. coli in stored water treated with Air RahMat than boiling (risk ratio (RR) 0·75, 95% confidence interval (CI) 0·56–1·00). The risk of diarrhoea in children <5 years was lower among households using Air RahMat (RR 0·43, 95% CI 0·19–0·97) than boiling, and higher in households with E. coli concentrations of 1–1000 MPN/100 ml (RR 1·54, 95% CI 1·04–2·28) or >1000 MPN/100 ml (RR 1·86, 95% CI 1·09–3·19) in stored water than in households without detectable E. coli. Although results suggested that Air RahMat water treatment was associated with lower E. coli contamination and diarrhoeal rates among children <5 years than water treatment by boiling, Air RahMat use remained low.
When Art Dies, Art Lives
Authors: Miller Mary
Published: September 2017

Carolyn Dean's essay of 2006, ‘The Trouble with (the Term) Art’, offers a provocative set of challenges to the very notion of archaeological art. This essay attempts to refocus some of Dean's questions and to answer them by exploring different lines of evidence, especially through the development of the art museum in the twentieth century. Finally, the author explores whether the twenty-first century observer can gain insight into the meanings of some ancient materials by consideration of their destruction.
Maintenance and Mutability amongst Specialist Potters on the Northeast Coast of New Guinea
Authors: Gaffney Dylan
Published: September 2017

This paper examines a central concern in archaeological research: the interplay between technological and social flux over the longue durée. This is done by describing ceramic technological continuity and change, and its correspondence with broader social processes, on the northeast coast of New Guinea in the recent past. It presents new ethnographic information from Madang, Papua New Guinea, involving Bilbil and Yabob potters, to outline the chaîne opératoire of pottery production at present. Comparisons with ethnohistorical texts then allow us to model technological change over a longer period of c. 150 years, following the direct historical approach. This shows distinct continuity, but also substantial modification throughout the nineteenth–twenty-first centuries, as the potters negotiated major social upheavals during the colonial and post-independence periods, such as forcible relocation from their offshore islands onto the mainland. This expands our understanding of how social and technological change can take place amongst small-scale, part-time pottery specialists over the longue durée and how this change is reflected in the finished products and raw materials.
MYOPIC MISERY: MATERNAL DEPRESSION, CHILD INVESTMENTS, AND THE NEUROBIOLOGICAL POVERTY TRAP
Authors: Strulik Holger
Published: September 2017

In this paper, I explore in an overlapping generations framework, a mechanism motivating a neurobiological poverty trap. Poverty causes stress and depression in individuals susceptible to depression. Poor and depressed individuals discount the future at a higher rate and invest less in the human capital of their children than mentally healthy or rich individuals. This gene–environment interaction generates a vicious cycle in which poor individuals inherit not only susceptibility to depression, but also stress and poverty. I show that a successful one-time intervention has the power to permanently eliminate the neurobiological poverty trap.
Bilinguals’ social flexibility
Authors: IKIZER ELIF G. , RAMÍREZ-ESPARZA NAIRÁN
Published: September 2017

Is bilingualism better than monolingualism? Previous work shows that bilinguals have an advantage over monolinguals in cognitive flexibility, the ability to shift between different mental sets. In this study, we explore if bilingualism also provides an advantage in social flexibility, which we define as the ability to (a) switch with ease and adapt between different social environments and (b) accurately read social cues in the environment. Data was collected from 465 monolinguals and 206 bilinguals. Bilinguals reported higher social flexibility than monolinguals. Mediation analyses demonstrated that bilinguals’ social flexibility gave them an advantage over monolinguals in the self-reported frequency of social interactions. This study reports the first evidence of a social flexibility advantage of bilinguals, and it suggests that as bilinguals alternate between two languages, they might also alternate between two cultural worlds, providing tools to adapt to different social environments and facilitating the frequency of social interactions.
Prevalence, correlates, and impact of depressive and anxiety disorder in cancer: Findings from a multicenter study
Authors: Shim Eun-Jung , Hahm Bong-Jin , Yu Eun-Seung , Kim Ha Kyoung , Cho Seong Jin , Chang Sung Man , Yang Jong-Chul , Kim Jong-Heun
Published: September 2017

Objective:

Our aim was to examine the prevalence, correlates, and association of depressive and anxiety disorders with quality of life (QoL) and such other outcomes as the need for psychosocial services in cancer patients.

Method:

A total of 400 patients participated in a multicenter survey involving five cancer centers located throughout Korea. The Short-Form Health Survey, the MD Anderson Symptom Inventory, the Mini-Mental Adjustment to Cancer (MINI-MAC), and Mini-International Neuropsychiatric Interview were administered.

Results:

The prevalence rates for depressive and anxiety disorders were 16 and 17.1%, respectively. Younger age and poor Eastern Cooperative Oncology Group performance status, and all physical symptoms, as well as helplessness/hopelessness, anxious preoccupation (AP), and cognitive avoidance (CA) on the MINI-MAC were found to be significantly related to depressive disorder (DD) in a univariate logistic regression analysis. Metastases, the symptoms of disturbed sleep, dry mouth, and numbness or tingling, as well as AP and CA were significantly correlated with anxiety disorder (AD) in the univariate analysis. In the multivariate analyses, only AP was significant for AD (odds ratio = 2.94,p< 0.001), while none reached statistical significance for DD. Psychiatric comorbidity status had a detrimental effect on various dimensions of QoL. Patients with DD or AD reported a significantly higher need for professional psychosocial services.

Significance of results:

Given the substantial prevalence and pervasive impact of DD and AD on various aspects of QoL, its assessment and care should be integrated as a regular part of oncological care throughout the cancer continuum.
Comparison of optimization methods for core subset selection from a large collection of Mexican wheat landraces characterized by SNP markers
Authors: Acuña-Matamoros Carlos L. , Reyes-Valdés M. Humberto
Published: September 2017

Core subset selection from collections hosted by seed banks, grow in importance as the number of accessions and genetic marker information rapidly increases. A data set of 20,526 single-nucleotide polymorphism (SNP) markers characterizing 7986 Mexican creole wheat landraces, was used to test 11 methods for core subset selection, through optimization criteria containing average genetic distance and genetic diversity. Allele richness was used as an additional criterion to qualify the generated core subsets. Three replications with random samples of 1500 SNP loci, each comprising a maximum of 3000 alleles, were used to perform the method evaluations through four different objective functions. The LR greedy search (LR) and LR with random first pair (LRSemi) were consistently best across all assays for maximizing the objective functions, and they performed well even for criteria not included in those functions. The Tukey's HSD (honest significant difference) multiple comparisons grouped those methods together with the sequential forward selection (SFS) and SFS with random first pair (SFSSemi) strategies as the top set of approaches. All of them are simple heuristic maximization algorithms, and outperformed two more sophisticated optimization approaches: parallel mixed replica exchange and replica exchange Monte Carlo. For their efficiency to optimize the objective functions and computing speed, the LRSemi and SFSSemi methods demonstrated to be good alternatives for core subset selection from large collections of highly homozygous accessions characterized by many biallelic markers.
Suicide-related behaviours in schizophrenia in China: a comprehensive meta-analysis
Authors: Dong M. , Wang S. B. , Wang F. , Zhang L. , Ungvari G. S. , Ng C. H. , Meng X. , Yuan Z. , Wang G. , Xiang Y. T.
Published: September 2017

Aims.

Suicide-related behaviours are common in schizophrenia and are significantly associated with premature death. The objective of this meta-analysis study was to estimate the pooled prevalence of suicide-related behaviours in schizophrenia patients in China.

Methods.

The relevant literature was searched systematically via the relevant electronic databases (PubMed, Embase, PsycINFO, Chinese National Knowledge Infrastructure, Wanfang Databases and Chinese Biological Medical Literature Database) from their inception until 14 September 2016. Only original studies that reported the prevalence of suicide-related behaviours including suicidal ideation (SI), suicide plan, suicide attempt (SA) and completed suicide were selected.

Results.

Nineteen articles met the inclusion criteria and were analysed. The pooled lifetime prevalence of SI and SA were 25.8% (95% CI 14.7–41.1%) and 14.6% (95% CI 9.1–22.8%), respectively. The 1-month prevalence of SI was 22.0% (95% CI 18.2–26.4%). Subgroup analyses of lifetime SI and SA showed that gender, sample size, survey year, study location and source of patients have no significant mediating effects on the results.

Conclusions.

Suicide-related behaviours are common in Chinese schizophrenia patients. Due to the high mortality risk, regular screening and effective suicide prevention programmes are warranted.
Association between schizophrenia and an autoimmune bullous skin disease-pemphigus: a population-based large-scale study
Authors: Kridin K. , Zelber-Sagi S. , Comaneshter D. , Cohen A. D.
Published: September 2017

Aims.

Immunological hypotheses have become increasingly prominent suggesting that autoimmunity may be involved in the pathogenesis of schizophrenia. Schizophrenia was found to be associated with a wide range of autoimmune diseases. However, the association between pemphigus and schizophrenia has not been established yet. We aimed to estimate the association between pemphigus and schizophrenia using a large-scale real-life computerised database.

Methods.

This study was conducted as a cross-sectional study utilising the database of Clalit Health Services. The proportion of schizophrenia was compared between patients diagnosed with pemphigus and age-, gender- and ethnicity-matched control subjects. Univariate analysis was performed usingχ2and Student'st-test and a multivariate analysis was performed using a logistic regression model.

Results.

A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of schizophrenia was greater in patients with pemphigus as compared to the control group (2.0%v. 1.3%, respectively;p= 0.019). In a multivariate analysis, pemphigus was significantly associated with schizophrenia (OR, 1.5; 95% CI, 1.1–2.2). The association was more prominent among females, patients older than 60 years, and Jews.

Conclusions.

Pemphigus is significantly associated with schizophrenia. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid schizophrenia and be treated appropriately.
Spatial distribution of disease-associated variants in three-dimensional structures of protein complexes
Authors: Gress A , Ramensky V , Kalinina O V
Published: September 2017

Next-generation sequencing enables simultaneous analysis of hundreds of human genomes associated with a particular phenotype, for example, a disease. These genomes naturally contain a lot of sequence variation that ranges from single-nucleotide variants (SNVs) to large-scale structural rearrangements. In order to establish a functional connection between genotype and disease-associated phenotypes, one needs to distinguish disease drivers from neutral passenger variants. Functional annotation based on experimental assays is feasible only for a limited number of candidate mutations. Thus alternative computational tools are needed. A possible approach to annotating mutations functionally is to consider their spatial location relative to functionally relevant sites in three-dimensional (3D) structures of the harboring proteins. This is impeded by the lack of available protein 3D structures. Complementing experimentally resolved structures with reliable computational models is an attractive alternative. We developed a structure-based approach to characterizing comprehensive sets of non-synonymous single-nucleotide variants (nsSNVs): associated with cancer, non-cancer diseases and putatively functionally neutral. We searched experimentally resolved protein 3D structures for potential homology-modeling templates for proteins harboring corresponding mutations. We found such templates for all proteins with disease-associated nsSNVs, and 51 and 66% of proteins carrying common polymorphisms and annotated benign variants. Many mutations caused by nsSNVs can be found in protein–protein, protein–nucleic acid or protein–ligand complexes. Correction for the number of available templates per protein reveals that protein–protein interaction interfaces are not enriched in either cancer nsSNVs, or nsSNVs associated with non-cancer diseases. Whereas cancer-associated mutations are enriched in DNA-binding proteins, they are rarely located directly in DNA-interacting interfaces. In contrast, mutations associated with non-cancer diseases are in general rare in DNA-binding proteins, but enriched in DNA-interacting interfaces in these proteins. All disease-associated nsSNVs are overrepresented in ligand-binding pockets, and nsSNVs associated with non-cancer diseases are additionally enriched in protein core, where they probably affect overall protein stability.
TNFα-YAP/p65-HK2 axis mediates breast cancer cell migration
Authors: Gao Y , Yang Y , Yuan F , Huang J , Xu W , Mao B , Yuan Z , Bi W
Published: September 2017

Clinical and experimental evidence indicates that macrophages could promote solid-tumor progression and metastasis. However, the mechanisms underlying this process remain unclear. Here we show that yes-associated protein 1 (YAP1), a transcriptional regulator that controls tissue growth and regeneration, has an important role in tumor necrosis factor α (TNF α)-induced breast cancer migration. Mechanistically, macrophage conditioned medium (CM) or TNFα triggers IκB kinases (IKKs)-mediated YAP phosphorylation and activation in breast cancer cells. We further found that TNFα or macrophage CM treatment increases the interaction between p65 and YAP. Chromatin immunoprecipitation (ChIP) assay shows that YAP/TEAD (TEA domain family member) and p65 proteins synergistically regulate the transcription of hexokinase 2 (HK2), a speed-limiting enzyme in glycolysis, and promotes TNFα-induced or macrophage CM-induced cell migration. Together, our findings indicate an important role of TNFα-IKK-YAP/p65-HK2 signaling axis in the process of inflammation-driven migration in breast cancer cells, which reveals a new molecular link between inflammation and breast cancer metastasis.
CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
Authors: Macé Aurélien , Tuke Marcus A. , Deelen Patrick , Kristiansson Kati , Mattsson Hannele , Nõukas Margit , Sapkota Yadav , Schick Ursula , Porcu Eleonora , Rüeger Sina , McDaid Aaron F. , Porteous David , Winkler Thomas W. , Salvi Erika , Shrine Nick , Liu Xueping , Ang Wei Q. , Zhang Weihua , Feitosa Mary F. , Venturini Cristina , van der Most Peter J. , Rosengren Anders , Wood Andrew R. , Beaumont Robin N. , Jones Samuel E. , Ruth Katherine S. , Yaghootkar Hanieh , Tyrrell Jessica , Havulinna Aki S. , Boers Harmen , Mägi Reedik , Kriebel Jennifer , Müller-Nurasyid Martina , Perola Markus , Nieminen Markku , Lokki Marja-Liisa , Kähönen Mika , Viikari Jorma S. , Geller Frank , Lahti Jari , Palotie Aarno , Koponen Päivikki , Lundqvist Annamari , Rissanen Harri , Bottinger Erwin P. , Afaq Saima , Wojczynski Mary K. , Lenzini Petra , Nolte Ilja M. , Sparsø Thomas , Schupf Nicole , Christensen Kaare , Perls Thomas T. , Newman Anne B. , Werge Thomas , Snieder Harold , Spector Timothy D. , Chambers John C. , Koskinen Seppo , Melbye Mads , Raitakari Olli T. , Lehtimäki Terho , Tobin Martin D. , Wain Louise V. , Sinisalo Juha , Peters Annette , Meitinger Thomas , Martin Nicholas G. , Wray Naomi R. , Montgomery Grant W. , Medland Sarah E. , Swertz Morris A. , Vartiainen Erkki , Borodulin Katja , Männistö Satu , Murray Anna , Bochud Murielle , Jacquemont Sébastien , Rivadeneira Fernando , Hansen Thomas F. , Oldehinkel Albertine J. , Mangino Massimo , Province Michael A. , Deloukas Panos , Kooner Jaspal S. , Freathy Rachel M. , Pennell Craig , Feenstra Bjarke , Strachan David P. , Lettre Guillaume , Hirschhorn Joel , Cusi Daniele , Heid Iris M. , Hayward Caroline , Männik Katrin , Beckmann Jacques S. , Loos Ruth J. F. , Nyholt Dale R. , Metspalu Andres , Eriksson Johan G. , Weedon Michael N. , Salomaa Veikko , Franke Lude , Reymond Alexandre , Frayling Timothy M. , Kutalik Zoltán
Published: September 2017

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01–0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 × 10−10, 6.0 × 10−5, and 2.9 × 10−3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.
Single-photon three-qubit quantum logic using spatial light modulators
Authors: Kagalwala Kumel H. , Di Giuseppe Giovanni , Abouraddy Ayman F. , Saleh Bahaa E. A.
Published: September 2017

The information-carrying capacity of a single photon can be vastly expanded by exploiting its multiple degrees of freedom: spatial, temporal, and polarization. Although multiple qubits can be encoded per photon, to date only two-qubit single-photon quantum operations have been realized. Here, we report an experimental demonstration of three-qubit single-photon, linear, deterministic quantum gates that exploit photon polarization and the two-dimensional spatial-parity-symmetry of the transverse single-photon field. These gates are implemented using a polarization-sensitive spatial light modulator that provides a robust, non-interferometric, versatile platform for implementing controlled unitary gates. Polarization here represents the control qubit for either separable or entangling unitary operations on the two spatial-parity target qubits. Such gates help generate maximally entangled three-qubit Greenberger–Horne–Zeilinger and W states, which is confirmed by tomographical reconstruction of single-photon density matrices. This strategy provides access to a wide range of three-qubit states and operations for use in few-qubit quantum information processing protocols.
Foxp3+ Tregs are recruited to the retina to repair pathological angiogenesis
Authors: Deliyanti Devy , Talia Dean M. , Zhu Tong , Maxwell Mhairi J. , Agrotis Alex , Jerome Jack R. , Hargreaves Emily M. , Gerondakis Steven , Hibbs Margaret L. , Mackay Fabienne , Wilkinson-Berka Jennifer L.
Published: September 2017

Neovascular retinopathies are major causes of vision loss; yet treatments to prevent the condition are inadequate. The role of regulatory T cells in neovascular retinopathy is unknown. Here we show that in retinopathy regulatory T cells are transiently increased in lymphoid organs and the retina, but decline when neovascularization is established. The decline is prevented following regulatory T cells expansion with an IL-2/anti-IL-2 mAb complex or the adoptive transfer of regulatory T cells. Further, both approaches reduce vasculopathy (vaso-obliteration, neovascularization, vascular leakage) and alter the activation of Tmem119+retinal microglia. Our in vitro studies complement these findings, showing that retinal microglia co-cultured with regulatory T cells exhibit a reduction in co-stimulatory molecules and pro-inflammatory mediators that is attenuated by CTLA-4 blockade. Collectively, we demonstrate that regulatory T cells are recruited to the retina and, when expanded in number, repair the vasculature. Manipulation of regulatory T cell numbers is a previously unrecognized, and promising avenue for therapies to prevent blinding neovascular retinopathies.
Ellipticity dependence of high-harmonic generation in solids originating from coupled intraband and interband dynamics
Authors: Tancogne-Dejean Nicolas , Mücke Oliver D. , Kärtner Franz X. , Rubio Angel
Published: September 2017

The strong ellipticity dependence of high-harmonic generation (HHG) in gases enables numerous experimental techniques that are nowadays routinely used, for instance, to create isolated attosecond pulses. Extending such techniques to solids requires a fundamental understanding of the microscopic mechanism of HHG. Here we use first-principles simulations within a time-dependent density-functional framework and show how intraband and interband mechanisms are strongly and differently affected by the ellipticity of the driving laser field. The complex interplay between intraband and interband effects can be used to tune and improve harmonic emission in solids. In particular, we show that the high-harmonic plateau can be extended by as much as 30% using a finite ellipticity of the driving field. We furthermore demonstrate the possibility to generate, from single circularly polarized drivers, circularly polarized harmonics. Our work shows that ellipticity provides an additional knob to experimentally optimize HHG in solids.
Selective enhancement of optical nonlinearity in two-dimensional organic-inorganic lead iodide perovskites
Authors: Saouma F. O. , Stoumpos C. C. , Wong J. , Kanatzidis M. G. , Jang J. I.
Published: September 2017

Reducing the dimensionality of three-dimensional hybrid metal halide perovskites can improve their optoelectronic properties. Here, we show that the third-order optical nonlinearity, n2, of hybrid lead iodide perovskites is enhanced in the two-dimensional Ruddlesden-Popper series, (CH3(CH2)3NH3)2(CH3NH3)
n-1Pb
n
I3n+1 (n = 1–4), where the layer number (n) is engineered for bandgap tuning from Eg = 1.60 eV (n = ∞; bulk) to 2.40 eV (n = 1). Despite the unfavorable relation, $${n_2} \propto E_{\rm{g}}^{ - 4}$$

n

2

∝

E

g

-
4

, strong quantum confinement causes these two-dimensional perovskites to exhibit four times stronger third harmonic generation at mid-infrared when compared with the three-dimensional counterpart, (CH3NH3)PbI3. Surprisingly, however, the impact of dimensional reduction on two-photon absorption, which is the Kramers-Kronig conjugate of n2, is rather insignificant as demonstrated by broadband two-photon spectroscopy. The concomitant increase of bandgap and optical nonlinearity is truly remarkable in these novel perovskites, where the former increases the laser-induced damage threshold for high-power nonlinear optical applications.
Flexible three-dimensional artificial synapse networks with correlated learning and trainable memory capability
Authors: Wu Chaoxing , Kim Tae Whan , Choi Hwan Young , Strukov Dmitri B. , Yang J. Joshua
Published: September 2017

If a three-dimensional physical electronic system emulating synapse networks could be built, that would be a significant step toward neuromorphic computing. However, the fabrication complexity of complementary metal-oxide-semiconductor architectures impedes the achievement of three-dimensional interconnectivity, high-device density, or flexibility. Here we report flexible three-dimensional artificial chemical synapse networks, in which two-terminal memristive devices, namely, electronic synapses (e-synapses), are connected by vertically stacking crossbar electrodes. The e-synapses resemble the key features of biological synapses: unilateral connection, long-term potentiation/depression, a spike-timing-dependent plasticity learning rule, paired-pulse facilitation, and ultralow-power consumption. The three-dimensional artificial synapse networks enable a direct emulation of correlated learning and trainable memory capability with strong tolerances to input faults and variations, which shows the feasibility of using them in futuristic electronic devices and can provide a physical platform for the realization of smart memories and machine learning and for operation of the complex algorithms involving hierarchical neural networks.
Mass extinctions drove increased global faunal cosmopolitanism on the supercontinent Pangaea
Authors: Button David J. , Lloyd Graeme T. , Ezcurra Martín D. , Butler Richard J.
Published: September 2017

Mass extinctions have profoundly impacted the evolution of life through not only reducing taxonomic diversity but also reshaping ecosystems and biogeographic patterns. In particular, they are considered to have driven increased biogeographic cosmopolitanism, but quantitative tests of this hypothesis are rare and have not explicitly incorporated information on evolutionary relationships. Here we quantify faunal cosmopolitanism using a phylogenetic network approach for 891 terrestrial vertebrate species spanning the late Permian through Early Jurassic. This key interval witnessed the Permian–Triassic and Triassic–Jurassic mass extinctions, the onset of fragmentation of the supercontinent Pangaea, and the origins of dinosaurs and many modern vertebrate groups. Our results recover significant increases in global faunal cosmopolitanism following both mass extinctions, driven mainly by new, widespread taxa, leading to homogenous ‘disaster faunas’. Cosmopolitanism subsequently declines in post-recovery communities. These shared patterns in both biotic crises suggest that mass extinctions have predictable influences on animal distribution and may shed light on biodiversity loss in extant ecosystems.
NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia
Authors: Märklin Melanie , Heitmann Jonas S. , Fuchs Alexander R. , Truckenmüller Felicia M. , Gutknecht Michael , Bugl Stefanie , Saur Sebastian J. , Lazarus Juliane , Kohlhofer Ursula , Quintanilla-Martinez Leticia , Rammensee Hans-Georg , Salih Helmut R. , Kopp Hans-Georg , Haap Michael , Kirschniak Andreas , Kanz Lothar , Rao Anjana , Wirths Stefan , Müller Martin R.
Published: September 2017

Chronic lymphocytic leukaemia (CLL) is a clonal disorder of mature B cells. Most patients are characterised by an indolent disease course and an anergic phenotype of their leukaemia cells, which refers to a state of unresponsiveness to B cell receptor stimulation. Up to 10% of CLL patients transform from an indolent subtype to an aggressive form of B cell lymphoma over time (Richter´s syndrome) and show a significantly worse treatment outcome. Here we show that B cell-specific ablation ofNfat2leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependent genes includingCbl-b,Grail,Egr2andLck. In summary, this study identifies NFAT2 as a crucial regulator of the anergic phenotype in CLL.
Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice
Authors: Vincent Jessica , Adura Carolina , Gao Pu , Luz Antonio , Lama Lodoe , Asano Yasutomi , Okamoto Rei , Imaeda Toshihiro , Aida Jumpei , Rothamel Katherine , Gogakos Tasos , Steinberg Joshua , Reasoner Seth , Aso Kazuyoshi , Tuschl Thomas , Patel Dinshaw J. , Glickman J. Fraser , Ascano Manuel
Published: September 2017

Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic GMP-AMP synthase synthesizes a cyclic dinucleotide that initiates an inflammatory cellular response. Mouse studies that recapitulate causative mutations in the autoimmune disease Aicardi-Goutières syndrome demonstrate that ablating the cyclic GMP-AMP synthase gene abolishes the deleterious phenotype. Here, we report the discovery of a class of cyclic GMP-AMP synthase inhibitors identified by a high-throughput screen. These compounds possess defined structure-activity relationships and we present crystal structures of cyclic GMP-AMP synthase, double-stranded DNA, and inhibitors within the enzymatic active site. We find that a chemically improved member, RU.521, is active and selective in cellular assays of cyclic GMP-AMP synthase-mediated signaling and reduces constitutive expression of interferon in macrophages from a mouse model of Aicardi-Goutières syndrome. RU.521 will be useful toward understanding the biological roles of cyclic GMP-AMP synthase and can serve as a molecular scaffold for development of future autoimmune therapies.
Trade-driven relocation of air pollution and health impacts in China
Authors: Wang Haikun , Zhang Yanxu , Zhao Hongyan , Lu Xi , Zhang Yanxia , Zhu Weimo , Nielsen Chris P. , Li Xin , Zhang Qiang , Bi Jun , McElroy Michael B.
Published: September 2017

Recent studies show that international trade affects global distributions of air pollution and public health. Domestic interprovincial trade has similar effects within countries, but has not been comprehensively investigated previously. Here we link four models to evaluate the effects of both international exports and interprovincial trade on PM2.5 pollution and public health across China. We show that 50–60% of China’s air pollutant emissions in 2007 were associated with goods and services consumed outside of the provinces where they were produced. Of an estimated 1.10 million premature deaths caused by PM2.5 pollution throughout China, nearly 19% (208,500 deaths) are attributable to international exports. In contrast, interprovincial trade leads to improved air quality in developed coastal provinces with a net effect of 78,500 avoided deaths nationwide. However, both international export and interprovincial trade exacerbate the health burdens of air pollution in China’s less developed interior provinces. Our results reveal trade to be a critical but largely overlooked consideration in effective regional air quality planning for China.
Mutant p53 shapes the enhancer landscape of cancer cells in response to chronic immune signaling
Authors: Rahnamoun Homa , Lu Hanbin , Duttke Sascha H. , Benner Christopher , Glass Christopher K. , Lauberth Shannon M.
Published: September 2017

Inflammation influences cancer development, progression, and the efficacy of cancer treatments, yet the mechanisms by which immune signaling drives alterations in the cancer cell transcriptome remain unclear. Using ChIP-seq, RNA-seq, and GRO-seq, here we demonstrate a global overlap in the binding of tumor-promoting p53 mutants and the master proinflammatory regulator NFκB that drives alterations in enhancer and gene activation in response to chronic TNF-α signaling. We show that p53 mutants interact directly with NFκB and that both factors impact the other’s binding at diverse sets of active enhancers. In turn, the simultaneous and cooperative binding of these factors is required to regulate RNAPII recruitment, the synthesis of enhancer RNAs, and the activation of tumor-promoting genes. Collectively, these findings establish a mechanism by which chronic TNF-α signaling orchestrates a functional interplay between mutant p53 and NFκB that underlies altered patterns of cancer-promoting gene expression.
Somatic growth, aging, and longevity
Authors: Bartke Andrzej
Published: September 2017

Although larger species of animals typically live longer than smaller species, the relationship of body size to longevity within a species is generally opposite. The longevity advantage of smaller individuals can be considerable and is best documented in laboratory mice and in domestic dogs. Importantly, it appears to apply broadly, including humans. It is not known whether theses associations represent causal links between various developmental and physiological mechanisms affecting growth and/or aging. However, variations in growth hormone (GH) signaling are likely involved because GH is a key stimulator of somatic growth, and apparently also exerts various “pro-aging” effects. Mechanisms linking GH, somatic growth, adult body size, aging, and lifespan likely involve target of rapamycin (TOR), particularly one of its signaling complexes, mTORC1, as well as various adjustments in mitochondrial function, energy metabolism, thermogenesis, inflammation, and insulin signaling. Somatic growth, aging, and longevity are also influenced by a variety of hormonal and nutritional signals, and much work will be needed to answer the question of why smaller individuals may be likely to live longer.
Flexible and biocompatible high-performance solid-state micro-battery for implantable orthodontic system
Authors: Kutbee Arwa T. , Bahabry Rabab R. , Alamoudi Kholod O. , Ghoneim Mohamed T. , Cordero Marlon D. , Almuslem Amani S. , Gumus Abdurrahman , Diallo Elhadj M. , Nassar Joanna M. , Hussain Aftab M. , Khashab Niveen M. , Hussain Muhammad M.
Published: September 2017

To augment the quality of our life, fully compliant personalized advanced health-care electronic system is pivotal. One of the major requirements to implement such systems is a physically flexible high-performance biocompatible energy storage (battery). However, the status-quo options do not match all of these attributes simultaneously and we also lack in an effective integration strategy to integrate them in complex architecture such as orthodontic domain in human body. Here we show, a physically complaint lithium-ion micro-battery (236 μg) with an unprecedented volumetric energy (the ratio of energy to device geometrical size) of 200 mWh/cm3 after 120 cycles of continuous operation. Our results of 90% viability test confirmed the battery’s biocompatibility. We also show seamless integration of the developed battery in an optoelectronic system embedded in a three-dimensional printed smart dental brace. We foresee the resultant orthodontic system as a personalized advanced health-care application, which could serve in faster bone regeneration and enhanced enamel health-care protection and subsequently reducing the overall health-care cost.
Altered brain and gut responses to corticotropin-releasing hormone (CRH) in patients with irritable bowel syndrome
Authors: Kano Michiko , Muratsubaki Tomohiko , Van Oudenhove Lukas , Morishita Joe , Yoshizawa Makoto , Kohno Keiji , Yagihashi Mao , Tanaka Yukari , Mugikura Shunji , Dupont Patrick , Ly Huynh Giao , Takase Kei , Kanazawa Motoyori , Fukudo Shin
Published: September 2017

Stress is a known trigger of irritable bowel syndrome (IBS) and exacerbates its gastrointestinal symptoms. However, underlying the physiological mechanism remains unknown. Here, we investigated hypothalamic–pituitary–adrenal (HPA) axis, colonic motility, and autonomic responses to corticotropin-releasing hormone (CRH) administration as well as brain activity alterations in IBS. The study included 28 IBS patients and 34 age and sex-matched healthy control subjects. IBS patients demonstrated greater adrenocorticotropic hormone (ACTH) responses to CRH than control subjects. Male IBS patients had greater increases in colonic motility than male HCs after CRH. Female IBS patients showed altered sympathovagal balance and lower basal parasympathetic tone relative to female control subjects. Brain responses to rectal distention were measured in the same subjects using functional magnetic resonance imaging, and their associations with individual ACTH responses to CRH were tested. A negative association between ACTH response to CRH and activity in the pregenual anterior cingulate cortex (pACC) during rectal distention was identified in controls but not in IBS patients. Impaired top-down inhibitory input from the pregenual ACC to the HPA axis may lead to altered neuroendocrine and gastrointestinal responses to CRH. Centrally acting treatments may dampen the stress induced physical symptoms in IBS.
Small ocean temperature increases elicit stage-dependent changes in DNA methylation and gene expression in a fish, the European sea bass
Authors: Anastasiadi Dafni , Díaz Noelia , Piferrer Francesc
Published: September 2017

In natural fish populations, temperature increases can result in shifts in important phenotypic traits. DNA methylation is an epigenetic mechanism mediating phenotypic changes. However, whether temperature increases of the magnitude predicted by the latest global warming models can affect DNA methylation is unknown. Here, we exposed European sea bass to moderate temperature increases in different periods within the first two months of age. We show that increases of even 2 °C in larvae significantly changed global DNA methylation and the expression of ecologically-relevant genes related to DNA methylation, stress response, muscle and organ formation, while 4 °C had no effect on juveniles. Furthermore, DNA methylation changes were more marked in larvae previously acclimated to a different temperature. The expression of most genes was also affected by temperature in the larvae but not in juveniles. In conclusion, this work constitutes the first study of DNA methylation in fish showing that temperature increases of the magnitude predicted by the latest global warming models result in stage-dependent alterations in global DNA methylation and gene expression levels. This study, therefore, provides insights on the possible consequences of climate change in fish mediated by genome-wide epigenetic modifications.
Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial
Authors: Birk Nina Marie , Nissen Thomas Nørrelykke , Kjærgaard Jesper , Hartling Hans Jacob , Thøstesen Lisbeth Marianne , Kofoed Poul-Erik , Stensballe Lone Graff , Andersen Andreas , Pryds Ole , Netea Mihai G. , Benn Christine Stabell , Nielsen Susanne Dam , Jeppesen Dorthe Lisbeth
Published: September 2017

The Bacillus Calmette–Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets, determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age. No effects of BCG were found at 4 days. However, BCG increased proportions of effector memory cells at 3 months (Geometric mean ratio (GMR) 1.62, 95% confidence interval (CI) (1.20–2.21), p = 0.002 for CD4+ T cells and GMR 1.69, 95% CI (1.06–2.70), p = 0.03 for CD8+ T cells), and reduced proportions of late differentiated CD4+ T cells (GMR = 0.62, 95% CI (0.38–1.00), p = 0.05) and apoptotic CD4+ T cells at 13 months (GMR = 0.55, 95% CI (0.32–0.92), p = 0.03). In conclusion, limited overall impact of neonatal BCG vaccination on lymphocyte subsets was found in healthy Danish infants within the first 13 months of life. This is in line with the limited clinical effects of BCG observed in our setting.
Wide-field mid-infrared hyperspectral imaging of adhesives using a bolometer camera
Authors: Sugawara Shigeru , Nakayama Yoshihiko , Taniguchi Hideya , Ishimaru Ichiro
Published: September 2017

By combining a bolometer detector with an imaging-type interferometer, an inexpensive, easy-to-handle wide-field mid-infrared hyperspectral imaging apparatus was produced. We measured the distributions of four types of thin adhesive layers on an aluminium plate and analysed the results using correlation coefficients to visualise the distribution of various adhesives that cannot be discerned by the naked eye or conventional methods such as visible/near-infrared spectroscopic/fluorescent photography. The measurement wavelength range, obtained spectrum’s wavenumber resolution, and measurement time was 8–14 μm, about 9 cm−1, and about 30 s, respectively. Using conventional methods, adhesives could not be distinguished from the others. By using this method, we found that adhesives could be precisely distinguished by setting an appropriate threshold value for the correlation coefficient. Thus, our approach can accurately measure the spatial distribution of different types of adhesive that cannot be discriminated by conventional methods.
Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes
Authors: van Krieken Pim P. , Dicker Andrea , Eriksson Maria , Herrera Pedro L. , Ahlgren Ulf , Berggren Per-Olof , Ilegems Erwin
Published: September 2017

Functional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse, a model of hyperglycemia resulting from diphtheria toxin induced beta cell ablation. A novel combination of imaging modalities was employed to study the pattern of beta cell destruction. Optical projection tomography of the pancreas and longitudinal in vivo confocal microscopy of islets transplanted into the anterior chamber of the eye allowed to investigate kinetics and tomographic location of beta cell mass decay in individual islets as well as at the entire islet population level. The correlation between beta cell mass and function was determined by complementary in vivo and ex vivo characterizations, demonstrating that beta cell function and glucose tolerance were impaired within the first two days following treatment when more than 50% of beta cell mass was remaining. Our results illustrate the importance of acquiring quantitative functional and morphological parameters to assess the functional status of the endocrine pancreas.
Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
Authors: Gaspar H. A. , Breen G.
Published: September 2017

Using successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used genome-wide association study (GWAS) summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group to build a drug repositioning model for schizophrenia. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics. Each of these therapeutical classes targets different gene subnetworks. We identify 123 Bonferroni-significant druggable genes outside the MHC, and 128 FDR-significant biological pathways related to neurons, synapses, genic intolerance, membrane transport, epilepsy, and mental disorders. These results suggest that, in schizophrenia, current well-powered GWAS results can reliably detect known schizophrenia drugs and thus may hold considerable potential for the identification of new therapeutic leads. Moreover, antiepileptics and calcium channel blockers may provide repurposing opportunities. This study also reveals significant pathways in schizophrenia that were not identified previously, and provides a workflow for pathway analysis and drug repurposing using GWAS results.
Memory characteristics of silicon nanowire transistors generated by weak impact ionization
Authors: Lim Doohyeok , Kim Minsuk , Kim Yoonjoong , Kim Sangsig
Published: September 2017

In this study, we demonstrate the static random access memory (SRAM) characteristics generated by weak impact ionization in bendable field-effect transistors (FETs) with n+-p-n+ silicon nanowire (SiNW) channels. Our bendable SiNW FETs show not only superior switching characteristics such as an on/off current ratio of ~105 and steep subthreshold swing (~5 mV/dec) but also reliable SRAM characteristics. The SRAM characteristics originate from the positive feedback loops in the SiNW FETs generated by weak impact ionization. This paper describes in detail the operating mechanism of our device and demonstrates the potential of bendable SiNW FETs for future SRAM applications.