bluuebunny/crossref_metadata_2025 huggingface dataset:
Capturing non-exchangeable dependence in multivariate loss processes with nested Archimedean Lévy copulas
Authors: Avanzi Benjamin , Tao Jamie , Wong Bernard , Yang Xinda
Published: December 2015

The class of spectrally positive Lévy processes is a frequent choice for modelling loss processes in areas such as insurance or operational risk. Dependence between such processes (e.g. between different lines of business) can be modelled with Lévy copulas. This approach is a parsimonious, efficient and flexible method which provides many of the advantages akin to distributional copulas for random variables. Literature on Lévy copulas seems to have primarily focussed on bivariate processes. When multivariate settings are considered, these usually exhibit an exchangeable dependence structure (whereby all subset of the processes have an identical marginal Lévy copula). In reality, losses are not always associated in an identical way, and models allowing for non-exchangeable dependence patterns are needed. In this paper, we present an approach which enables the development of such models. Inspired by ideas and techniques from the distributional copula literature we investigate the procedure of nesting Archimedean Lévy copulas. We provide a detailed analysis of this construction, and derive conditions under which valid multivariate (nested) Lévy copulas are obtained. Our results are discussed and illustrated, notably with an example of model fitting to data.
Notfall-Präsentation von älteren Erwachsenen mit unerwünschten Arzneimittelwirkungen
Authors: Malinovska Alexandra , Bingisser Roland , Nickel Christian H.
Published: December 2015

Zusammenfassung. Jede Medikamentenverschreibung ist ein Balanceakt zwischen gewünschter Wirkung und unerwünschter Arzneimittelwirkung (UAW). Das Hauptrisiko für UAWs ist die Polypharmazie. Mit jedem zusätzlichen Medikament steigt das Risiko für eine UAW. Ältere Menschen haben daher ein erhöhtes Risiko, da sie gehäuft mehrere Medikamente einnehmen. Ob das Alter per se jedoch auch ein Risikofaktor darstellt, ist umstritten. Jedoch konnte gezeigt werden, dass UAWs im Alter vermehrt auftreten und bis zu 16,3 % der Vorstellungen auf einer Notaufnahme ausmachen. Es konnte jedoch in verschiedenen Studien gezeigt werden, dass viele UAWs vermeidbar und vorhersehbar sind. Jedoch werden UAWs auf der Notfallstation selten erkannt, welches in der unterschiedlichen klinischen Präsentation von UAWs begründet sein kann. Eine Hilfestellung für die Erkennung von UAWs bilden explizite Checklisten wie beispielsweise die Beers Kriterien oder die STOPP/START Liste. Diese sind Aufzählungen von Medikamenten, die potenziell unangebracht für ältere Patienten sind. Jedoch werden UAWs auf Notfallstationen nicht nur nicht erkannt, sondern es werden auch unangebrachte Medikamente auf Notfallstationen verschrieben. Dies zeigt, dass ein Bedarf an Aufarbeitung dieses Problems besteht.
Nebenwirkungen und Interaktionen häufig eingesetzter kardiologischer Medikamente
Authors: Dieterle Thomas
Published: December 2015

Zusammenfassung. Aufgrund der Häufigkeit kardiovaskulärer Erkrankungen und der entsprechenden Verschreibung kardialer Arzneimittel muss immer mit Nebenwirkungen und Arzneimittelinteraktionen gerechnet werden. Sie beruhen auf Mechanismen, welche sich durch pharmakokinetische bzw. pharmakodynamische Interaktionen erklären lassen und können durchaus erwünscht, aber auch potentiell lebensbedrohlich sein. So sind trotz der guten Verträglichkeit der neuen oralen Antikoagulantien bestimmte einschränkende Faktoren, z. B. eine begleitende Niereninsuffizienz, bei der Indikationsstellung und Dosierung zu beachten. Unerwünschte Wirkungen und Interaktionen beim Einsatz von Antihypertensiva können durch die Hemmung bzw. die Induktion des enzymatischen Abbaus von Antihypertensiva bei gleichzeitiger Gabe entsprechender Substanzen, aber auch durch die Hemmung der renalen Medikamenten-, Elektrolyt- und Wasserausscheidung entstehen. In diesem Zusammenhang ist besonders die Interaktion von Betablockern, ACE-Hemmern, Angiotensin-Rezeptor-Blocker und Thiazid-Diuretika mit nicht-steroidalen Antirheumatika zu nennen. Besonderes Augenmerk bei einer Statintherapie ist auf muskuläre Störungen zu legen, welche sich bei ca. 5 % der Patienten als Myalgien manifestieren können, im Rahmen von Rhabdomyolysen aber auch lebensbedrohlich sein können.
Medikamentös bedingte akute Nierenschädigung
Authors: Derungs Adrian
Published: December 2015

Zusammenfassung. Die Nieren sind aufgrund ihrer physiologischen Funktion einer hohen Exposition gegenüber zahlreichen Arzneistoffen und deren Metaboliten ausgesetzt, was sie vulnerabel für medikamentös bedingte Schädigungen macht. Diuretika, ACE-Inhibitoren, Angiotensin-II-Rezeptor-Blocker und NSAID sind die häufigsten prärenalen Ursachen eines akuten Kreatinin-Anstieges. Vaskuläre Schädigungen entstehen durch thrombotische Mikroangiopathien (z. B. unter Ciclosporin, Tacrolimus, Muromonab-CD3, Mitomycin C, Chinin, Ticlopidin, Clopidogrel) oder durch Antikoagulantien und Thrombolytika. Letztere führen zu einer sekundären Gefässschädigung durch Cholesterinembolien, Embolien von Thrombusmaterial in die Peripherie oder Blutungen. Tubulopathien werden z. B. unter Ifosfamid und Cisplatin (selten unter Cyclophosphamid oder Carboplatin), Aminoglykosiden, Vancomycin und Röntgenkontrastmittel beobachtet. Interstitielle Nephritiden sind in ca. 85 % der Fälle medikamentös bedingt. Ihnen liegen immunologische Mechanismen zugrunde. Bei den medikamentös bedingten Glomerulopathien lassen sich mit Hilfe der Nierenbiopsie Rückschlüsse auf das auslösende Medikament ziehen. Eine besondere Form der Immunkomplex-Glomerulonephritis stellt der medikamentös induzierte systemische Lupus erythematodes dar, welcher durch Procainamid, Hydralazin, Isoniazid, Methyldopa, Chinidin, Chlorpromazin und Propylthiouracil ausgelöst werden kann. Eine kristallinduzierte Nierenschädigung entsteht bei der Präzipitation von Medikamenten (z. B. Aciclovir, Sulfonamid-Antibiotika, Methotrexat, Indinavir) in den Nierentubuli und den harnableitenden Wegen mit konsekutiver Obstruktion derselben.
Pharmakovigilanz – Das Spontanmeldesystem in der Schweiz
Authors: Schäublin Martina
Published: December 2015

Zusammenfassung. Das Ziel der Pharmakovigilanz besteht darin, unser Wissen über die Sicherheit der Medikamente laufend zu aktualisieren und zu erweitern, um damit die Arzneimitteltherapie für Patienten sicherer zu gestalten. Die wichtigste Methode der Überwachung von Arzneimitteln nach deren Zulassung ist das Spontanmeldesystem. Es dient als Frühwarnsystem, um bislang unbekannte und seltene bzw. ungenügend beschriebene Reaktionen und Risiken aufzuspüren. Hierbei kann eine breite Basispopulation, in der alle potentiellen Risikogruppen eingeschlossen sind, über einen langen Zeitraum überwacht werden. Der Erfolg des Systems ist entscheidend von der Aufmerksamkeit der beobachtenden medizinischen Fachpersonen sowie der Qualität und Quantität der Informationen abhängig. Ein Nachteil des Systems ist die fehlende Möglichkeit, Aussagen zur Inzidenz einer unerwünschte Arzneimittelwirkung oder zum relativen Risiko zu machen, da keine genauen Daten zur Anzahl der Personen, die einen Medikament einnehmen, vorliegen und ausserdem nur ein geringer Teil der unerwünschten Arzneimittelwirkungen gemeldet wird. In der Schweiz ist seit 2002 die gesetzliche Meldepflicht für medizinische Fachpersonen und pharmazeutische Unternehmen im Heilmittelgesetz festgehalten. Sechs regionale Pharmacovigilance-Zentren nehmen die Meldungen der medizinischen Fachpersonen entgegen, bearbeiten sie und leiten sie anonymisiert an das nationale Pharmacovigilance-Zentrum bei Swissmedic weiter. Hier werden alle Meldungen auf ihren Signalwert hin geprüft und bei Bedarf entsprechende Massnahmen eingeleitet. Alle eingegangenen Meldungen werden von Swissmedic an die internationale Datenbank der WHO in Uppsala/Schweden weitergeleitet.
The α7‐nicotinic receptor is upregulated in immune cells from HIV‐seropositive women: consequences to the cholinergic anti‐inflammatory response
Authors: Delgado‐Vélez Manuel , Báez‐Pagán Carlos A , Gerena Yamil , Quesada Orestes , Santiago‐Pérez Laura I , Capó‐Vélez Coral M , Wojna Valerie , Meléndez Loyda , León‐Rivera Rosiris , Silva Walter , Lasalde‐Dominicci José A
Published: December 2015

Antiretroviral therapy partially restores the immune system and markedly increases life expectancy of HIV‐infected patients. However, antiretroviral therapy does not restore full health. These patients suffer from poorly understood chronic inflammation that causes a number of AIDS and non‐AIDS complications. Here we show that chronic inflammation in HIV+ patients may be due to the disruption of the cholinergic anti‐inflammatory pathway by HIV envelope protein gp120IIIB. Our results demonstrate that HIV gp120IIIB induces α7 nicotinic acetylcholine receptor (α7) upregulation and a paradoxical proinflammatory phenotype in macrophages, as activation of the upregulated α7 is no longer capable of inhibiting the release of proinflammatory cytokines. Our results demonstrate that disruption of the cholinergic‐mediated anti‐inflammatory response can result from an HIV protein. Collectively, these findings suggest that HIV tampering with a natural strategy to control inflammation could contribute to a crucial, unresolved problem of HIV infection: chronic inflammation.
A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection
Authors: Lundie Rachel J , Webb Lauren M , Marley Angela K , Phythian‐Adams Alexander T , Cook Peter C , Jackson‐Jones Lucy H , Brown Sheila , Maizels Rick M , Boon Louis , O'Keeffe Meredith , MacDonald Andrew S
Published: December 2015

Dendritic cells (DCs) are the key initiators of T‐helper (Th) 2 immune responses against the parasitic helminth Schistosoma mansoni. Although the liver is one of the main sites of antigen deposition during infection with this parasite, it is not yet clear how distinct DC subtypes in this tissue respond to S. mansoni antigens in vivo, or how the liver microenvironment might influence DC function during establishment of the Th2 response. In this study, we show that hepatic DC subsets undergo distinct activation processes in vivo following murine infection with S. mansoni. Conventional DCs (cDCs) from schistosome‐infected mice upregulated expression of the costimulatory molecule CD40 and were capable of priming naive CD4+ T cells, whereas plasmacytoid DCs (pDCs) upregulated expression of MHC class II, CD86 and CD40 but were unable to support the expansion of either naive or effector/memory CD4+ T cells. Importantly, in vivo depletion of pDCs revealed that this subset was dispensable for either maintenance or regulation of the hepatic Th2 effector response during acute S. mansoni infection. Our data provides strong evidence that S. mansoni infection favors the establishment of an immunogenic, rather than tolerogenic, liver microenvironment that conditions cDCs to initiate and maintain Th2 immunity in the context of ongoing antigen exposure.
The impact of climate change on photovoltaic power generation in Europe
Authors: Jerez Sonia , Tobin Isabelle , Vautard Robert , Montávez Juan Pedro , López-Romero Jose María , Thais Françoise , Bartok Blanka , Christensen Ole Bøssing , Colette Augustin , Déqué Michel , Nikulin Grigory , Kotlarski Sven , van Meijgaard Erik , Teichmann Claas , Wild Martin
Published: December 2015

Ambitious climate change mitigation plans call for a significant increase in the use of renewables, which could, however, make the supply system more vulnerable to climate variability and changes. Here we evaluate climate change impacts on solar photovoltaic (PV) power in Europe using the recent EURO-CORDEX ensemble of high-resolution climate projections together with a PV power production model and assuming a well-developed European PV power fleet. Results indicate that the alteration of solar PV supply by the end of this century compared with the estimations made under current climate conditions should be in the range (−14%;+2%), with the largest decreases in Northern countries. Temporal stability of power generation does not appear as strongly affected in future climate scenarios either, even showing a slight positive trend in Southern countries. Therefore, despite small decreases in production expected in some parts of Europe, climate change is unlikely to threaten the European PV sector.
Leukotriene C4 is the major trigger of stress-induced oxidative DNA damage
Authors: Dvash Efrat , Har-Tal Michal , Barak Sara , Meir Ofir , Rubinstein Menachem
Published: December 2015

Endoplasmic reticulum (ER) stress and major chemotherapeutic agents damage DNA by generating reactive oxygen species (ROS). Here we show that ER stress and chemotherapy induce leukotriene C4 (LTC4) biosynthesis by transcriptionally upregulating and activating the enzyme microsomal glutathione-S-transferase 2 (MGST2) in cells of non-haematopoietic lineage. ER stress and chemotherapy also trigger nuclear translocation of the two LTC4 receptors. Acting in an intracrine manner, LTC4 then elicits nuclear translocation of NADPH oxidase 4 (NOX4), ROS accumulation and oxidative DNA damage. Mgst2 deficiency, RNAi and LTC4 receptor antagonists abolish ER stress- and chemotherapy-induced ROS and oxidative DNA damage in vitro and in mouse kidneys. Cell death and mouse morbidity are also significantly attenuated. Hence, MGST2-generated LTC4 is a major mediator of ER stress- and chemotherapy-triggered oxidative stress and oxidative DNA damage. LTC4 inhibitors, commonly used for asthma, could find broad clinical use in major human pathologies associated with ER stress-activated NOX4.
Structure of a bacterial type III secretion system in contact with a host membrane in situ
Authors: Nans Andrea , Kudryashev Mikhail , Saibil Helen R. , Hayward Richard D.
Published: December 2015

Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform–ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking ‘pump-action’ conformational changes that underpin effector injection.
The genetic basis of natural variation in mushroom body size in Drosophila melanogaster
Authors: Zwarts Liesbeth , Vanden Broeck Lies , Cappuyns Elisa , Ayroles Julien F. , Magwire Michael M. , Vulsteke Veerle , Clements Jason , Mackay Trudy F. C. , Callaerts Patrick
Published: December 2015

Genetic variation in brain size may provide the basis for the evolution of the brain and complex behaviours. The genetic substrate and the selective pressures acting on brain size are poorly understood. Here we use the Drosophila Genetic Reference Panel to map polymorphic variants affecting natural variation in mushroom body morphology. We identify 139 genes and 39 transcription factors and confirm effects on development and adult plasticity. We show correlations between morphology and aggression, sleep and lifespan. We propose that natural variation in adult brain size is controlled by interaction of the environment with gene networks controlling development and plasticity.
Association between cadmium exposure and renal cancer risk: a meta-analysis of observational studies
Authors: Song Ju kun , Luo Hong , Yin Xin hai , Huang Guang lei , Luo Si yang , Lin Du ren , Yuan Dong Bo , Zhang Wei , Zhu Jian guo
Published: December 2015

Cadmium (Cd) is a widespread environmental pollutant and has been a recognized carcinogen for several decades. Many observational studies reported Cd exposure might be one cause of renal cancer. However, these findings are inconsistent. We conducted a meta-analysis to evaluate the relationship between cadmium exposure and renal cancer risk. A comprehensive PubMed and Embase search was conducted to retrieve observational studies meeting our meta-analysis criteria. A combined odds ratio (OR) and corresponding 95% confidence interval (CI) were applied to assess the association between Cd exposure and renal cancer risk. The meta-analysis showed that a high Cd exposure significantly increased renal cancer 1.47 times (OR = 1.47; 95% CI = 1.27 to 1.71, for highest versus lowest category of cadmium categories). The significant association remained consistent when stratified by geographic region and gender, however mixed results were produced when stratified by sample size, study design, NOS score, adjustment for covariates, effects measure and exposure type. Our results indicated that a high Cd exposure was associated with increased renal cancer risk and the association was higher for occupational exposure compared with non-occupational exposure. This meta-analysis suggests that a high Cd exposure may be a risk factor for renal cancer in occupational population.
Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance
Authors: Hsu Alan Yi-Hui , Wu Shang-Rung , Tsai Jih-Jin , Chen Po-Lin , Chen Ya-Ping , Chen Tsai-Yun , Lo Yu-Chih , Ho Tzu-Chuan , Lee Meed , Chen Min-Ting , Chiu Yen-Chi , Perng Guey Chuen
Published: December 2015

The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development.
Negative differential resistance and characteristic nonlinear electromagnetic response of a Topological Insulator
Authors: Lee Ching Hua , Zhang Xiao , Guan Bochen
Published: December 2015

Materials exhibiting negative differential resistance have important applications in technologies involving microwave generation, which range from motion sensing to radio astronomy. Despite their usefulness, there has been few physical mechanisms giving rise to materials with such properties, i.e. GaAs employed in the Gunn diode. In this work, we show that negative differential resistance also generically arise in Dirac ring systems, an example of which has been experimentally observed in the surface states of Topological Insulators. This novel realization of negative differential resistance is based on a completely different physical mechanism from that of the Gunn effect, relying on the characteristic non-monotonicity of the response curve that remains robust in the presence of nonzero temperature, chemical potential, mass gap and impurity scattering. As such, it opens up new possibilities for engineering applications, such as frequency upconversion devices which are highly sought for terahertz signal generation. Our results may be tested with thin films of Bi2Se3 Topological Insulators and are expected to hold qualitatively even in the absence of a strictly linear Dirac dispersion, as will be the case in more generic samples of Bi2Se3 and other materials with topologically nontrivial Fermi sea regions.
Global land moisture trends: drier in dry and wetter in wet over land
Authors: Feng Huihui , Zhang Mingyang
Published: December 2015

The “dry gets drier, wet gets wetter” (DGDWGW) paradigm is widely accepted in global moisture change. However, Greve et al.1 have declared that this paradigm has been overestimated. This controversy leaves a large gap in the understanding of the evolution of water-related processes. Here, we examine the global moisture trends using satellite soil moisture for the past 35 years (1979–2013). Our results support those of Greve et al., although there are quantitative differences. Generally, approximately 30% of global land has experienced robust moisture trends (22.16% have become drier and 7.14% have become wetter). Only 15.12% of the land areas have followed the DGDWGW paradigm, whereas 7.77% have experienced the opposite trend. A new finding is that there is a significant “drier in dry, wetter in wet” (DIDWIW) trend paradigm; 52.69% of the drying trend occurred in arid regions and 48.34% of the wetter trend occurred in the humid regions. Overall, 51.63% of the trends followed the DIDWIW paradigm and 26.93% followed the opposite trend. We also identified the DGDWGW and DIDWIW paradigms in low precipitation-induced arid regions in which the dry soil led to an increasing sensible heat flux and temperature and subsequently potential evapotranspiration.
Improvement of genome assembly completeness and identification of novel full-length protein-coding genes by RNA-seq in the giant panda genome
Authors: Chen Meili , Hu Yibo , Liu Jingxing , Wu Qi , Zhang Chenglin , Yu Jun , Xiao Jingfa , Wei Fuwen , Wu Jiayan
Published: December 2015

High-quality and complete gene models are the basis of whole genome analyses. The giant panda (Ailuropoda melanoleuca) genome was the first genome sequenced on the basis of solely short reads, but the genome annotation had lacked the support of transcriptomic evidence. In this study, we applied RNA-seq to globally improve the genome assembly completeness and to detect novel expressed transcripts in 12 tissues from giant pandas, by using a transcriptome reconstruction strategy that combined reference-based and de novo methods. Several aspects of genome assembly completeness in the transcribed regions were effectively improved by the de novo assembled transcripts, including genome scaffolding, the detection of small-size assembly errors, the extension of scaffold/contig boundaries and gap closure. Through expression and homology validation, we detected three groups of novel full-length protein-coding genes. A total of 12.62% of the novel protein-coding genes were validated by proteomic data. GO annotation analysis showed that some of the novel protein-coding genes were involved in pigmentation, anatomical structure formation and reproduction, which might be related to the development and evolution of the black-white pelage, pseudo-thumb and delayed embryonic implantation of giant pandas. The updated genome annotation will help further giant panda studies from both structural and functional perspectives.
A Mechanistic Understanding of a Binary Additive System to Synergistically Boost Efficiency in All-Polymer Solar Cells
Authors: Kim Yu Jin , Ahn Sunyong , Wang Dong Hwan , Park Chan Eon
Published: December 2015

All-polymer solar cells are herein presented utilizing the PBDTTT-CT donor and the P(NDI2OD-T2) acceptor with 1,8-diiodooctane (DIO) and 1-chloronaphthalene (CN) binary solvent additives. A systematic study of the polymer/polymer bulk heterojunction photovoltaic cells processed from the binary additives revealed that the microstructures and photophysics were quite different from those of a pristine system. The combination of DIO and CN with a DIO/CN ratio of 3:1 (3 vol% DIO, 1 vol% CN and 96 vol% o-DCB) led to suitable penetrating polymer networks, efficient charge generation and balanced charge transport, which were all beneficial to improving the efficiency. This improvement is attributed to increase in power conversion efficiency from 2.81% for a device without additives to 4.39% for a device with the binary processing additives. A detailed investigation indicates that the changes in the polymer:polymer interactions resulted in the formation of a percolating nasnoscale morphology upon processing with the binary additives. Depth profile measurements with a two-dimensional grazing incidence wide-angle X-ray scattering confirm this optimum phase feature. Furthermore impedance spectroscopy also finds evidence for synergistically boosting the device performance.
Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells
Authors: Giladi Moshe , Schneiderman Rosa S , Voloshin Tali , Porat Yaara , Munster Mijal , Blat Roni , Sherbo Shay , Bomzon Zeev , Urman Noa , Itzhaki Aviran , Cahal Shay , Shteingauz Anna , Chaudhry Aafia , Kirson Eilon D , Weinberg Uri , Palti Yoram
Published: December 2015

Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells.
Environmental transmission of Mycobacterium ulcerans drives dynamics of Buruli ulcer in endemic regions of Cameroon
Authors: Garchitorena Andrés , Ngonghala Calistus N. , Texier Gaëtan , Landier Jordi , Eyangoh Sara , Bonds Matthew H. , Guégan Jean-François , Roche Benjamin
Published: December 2015

Buruli Ulcer is a devastating skin disease caused by the pathogen Mycobacterium ulcerans. Emergence and distribution of Buruli ulcer cases is clearly linked to aquatic ecosystems, but the specific route of transmission of M. ulcerans to humans remains unclear. Relying on the most detailed field data in space and time on M. ulcerans and Buruli ulcer available today, we assess the relative contribution of two potential transmission routes –environmental and water bug transmission– to the dynamics of Buruli ulcer in two endemic regions of Cameroon. The temporal dynamics of Buruli ulcer incidence are explained by estimating rates of different routes of transmission in mathematical models. Independently, we also estimate statistical models of the different transmission pathways on the spatial distribution of Buruli ulcer. The results of these two independent approaches are corroborative and suggest that environmental transmission pathways explain the temporal and spatial patterns of Buruli ulcer in our endemic areas better than the water bug transmission.
Time-resolved observation of band-gap shrinking and electron-lattice thermalization within X-ray excited gallium arsenide
Authors: Ziaja Beata , Medvedev Nikita , Tkachenko Victor , Maltezopoulos Theophilos , Wurth Wilfried
Published: December 2015

Femtosecond X-ray irradiation of solids excites energetic photoelectrons that thermalize on a timescale of a few hundred femtoseconds. The thermalized electrons exchange energy with the lattice and heat it up. Experiments with X-ray free-electron lasers have unveiled so far the details of the electronic thermalization. In this work we show that the data on transient optical reflectivity measured in GaAs irradiated with femtosecond X-ray pulses can be used to follow electron-lattice relaxation up to a few tens of picoseconds. With a dedicated theoretical framework, we explain the so far unexplained reflectivity overshooting as a result of band-gap shrinking. We also obtain predictions for a timescale of electron-lattice thermalization, initiated by conduction band electrons in the temperature regime of a few eVs. The conduction and valence band carriers were then strongly non-isothermal. The presented scheme is of general applicability and can stimulate further studies of relaxation within X-ray excited narrow band-gap semiconductors.
Enhanced performance of an innovative dengue IgG/IgM rapid diagnostic test using an anti-dengue EDI monoclonal antibody and dengue virus antigen
Authors: Lee Jihoo , Kim Young-Eun , Kim Hak-Yong , Sinniah Mangalam , Chong Chom-Kyu , Song Hyun-Ok
Published: December 2015

High levels of anti-dengue IgM or IgG can be detected using numerous rapid diagnostic tests (RDTs). However, the sensitivity and specificity of these tests are reduced by changes in envelope glycoprotein antigenicity that inevitably occur in limited expression systems. A novel RDT was designed to enhance diagnostic sensitivity. Dengue viruses cultured in animal cells were used as antigens to retain the native viral coat protein. Monoclonal antibodies (mAbs) were then developed, for the first time, against domain I of envelope glycoprotein (EDI). The anti-dengue EDI mAb was employed as a capturer and EDII and EDIII, which are mainly involved in the induction of neutralizing antibodies in patients, were fully available to bind to anti-dengue IgM or IgG in patients. A one-way automatic blood separation device prevented reverse migration of plasma and maximize the capture of anti-dengue antibodies at the test lines. A clinical evaluation in the field proved that the novel RDT (sensitivities of 96.5% and 96.7% for anti-dengue IgM and IgG) is more effective in detecting anti-dengue antibodies than two major commercial tests (sensitivities of 54.8% and 82% for SD BIOLINE; 50.4% and 75.3% for PanBio). The innovative format of RDT can be applied to other infectious viral diseases.
Dipole-allowed direct band gap silicon superlattices
Authors: Oh Young Jun , Lee In-Ho , Kim Sunghyun , Lee Jooyoung , Chang Kee Joo
Published: December 2015

Silicon is the most popular material used in electronic devices. However, its poor optical properties owing to its indirect band gap nature limit its usage in optoelectronic devices. Here we present the discovery of super-stable pure-silicon superlattice structures that can serve as promising materials for solar cell applications and can lead to the realization of pure Si-based optoelectronic devices. The structures are almost identical to that of bulk Si except that defective layers are intercalated in the diamond lattice. The superlattices exhibit dipole-allowed direct band gaps as well as indirect band gaps, providing ideal conditions for the investigation of a direct-to-indirect band gap transition. The fact that almost all structural portions of the superlattices originate from bulk Si warrants their stability and good lattice matching with bulk Si. Through first-principles molecular dynamics simulations, we confirmed their thermal stability and propose a possible method to synthesize the defective layer through wafer bonding.
One node driving synchronisation
Authors: Wang Chengwei , Grebogi Celso , Baptista Murilo S.
Published: December 2015

Abrupt changes of behaviour in complex networks can be triggered by a single node. This work describes the dynamical fundamentals of how the behaviour of one node affects the whole network formed by coupled phase-oscillators with heterogeneous coupling strengths. The synchronisation of phase-oscillators is independent of the distribution of the natural frequencies, weakly depends on the network size, but highly depends on only one key oscillator whose ratio between its natural frequency in a rotating frame and its coupling strength is maximum. This result is based on a novel method to calculate the critical coupling strength with which the phase-oscillators emerge into frequency synchronisation. In addition, we put forward an analytical method to approximately calculate the phase-angles for the synchronous oscillators.
miR-140-5p regulates adipocyte differentiation by targeting transforming growth factor-β signaling
Authors: Zhang Xin , Chang Ailing , Li Yongmei , Gao Yifei , Wang Haixiao , Ma Zhongshu , Li Xiaoxia , Wang Baoli
Published: December 2015

Recent emerging studies of miRNAs in adipocyte commitment provide new insights to understand the molecular basis of adipogenesis. The current study indicated that miR-140-5p was altered in primary cultured marrow stromal cells and established progenitor lines after adipogenic and/or osteogenic treatment. miR-140-5p was increased in adipose tissue in db/db obese mice vs. lean mice. Supplementing miR-140-5p activity induced stromal cell ST2 and preadipocyte 3T3-L1 to differentiate into mature adipocytes. Conversely, inhibition of the endogenous miR-140-5p repressed ST2 and 3T3-L1 to fully differentiate. By contrast, knockdown of the endogenous miR-140-5p enhanced osteoblast differentiation. Transforming growth factor-β receptor I (Tgfbr1) was shown to be a direct target of miR-140-5p. Supplementing miR-140-5p in ST2 reduced the level of TGFBR1 protein, while suppression of endogenous miR-140-5p increased TGFBR1. Overexpression of Tgfbr1 inhibited, whereas knockdown of Tgfbr1 promoted adipogenic differentiation of ST2 cells. Further investigation of mechanisms that control miR-140-5p expression revealed that C/EBPα induced transcriptional activity of the miR-140-5p promoter. Removal of the putative response element of C/EBP from the promoter abolished the enhancement of the promoter activity by C/EBPα, suggesting that C/EBPα transcriptionally controls miR-140-5p expression. Taken together, our study provides evidences that miR-140-5p regulates adipocyte differentiation through a C/EBP/miR-140-5p/TGFBR1 regulatory feedback loop.
Fancb deficiency impairs hematopoietic stem cell function
Authors: Du Wei , Amarachintha Surya , Erden Ozlem , Wilson Andrew , Meetei Amom Ruhikanta , Andreassen Paul R. , Namekawa Satoshi H. , Pang Qishen
Published: December 2015

Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure, variable congenital malformations and a predisposition to malignancies. FANCB (also known as FAAP95), is the only X-linked FA gene discovered thus far. In the present study, we investigated hematopoiesis in adult Fancb deficient (Fancb−/y) mice and found that Fancb−/y mice have decreased hematopoietic stem cell (HSC) quiescence accompanied by reduced progenitor activity in vitro and reduced repopulating capacity in vivo. Like other FA mouse models previously reported, the hematopoietic system of Fancb−/y mice is hypersensitive to DNA cross-linking agent mitomycin C (MMC), which induces bone marrow failure in Fancb−/y mice. Furthermore, Fancb−/y BM exhibits slower recovery kinetics and less tolerance to myelotoxic stress induced by 5-fluorouracil than wild-type littermates. RNA-seq analysis reveals altered expression of genes involved in HSC function and cell cycle regulation in Fancb−/y HSC and progenitor cells. Thus, this Fancb−/y mouse model provides a novel approach for studying the critical role of the FA pathway not only in germ cell development but also in the maintenance of HSC function.
Intrinsic Localized Modes in Proteins
Authors: Nicolaï Adrien , Delarue Patrice , Senet Patrick
Published: December 2015

Protein dynamics is essential for proteins to function. Here we predicted the existence of rare, large nonlinear excitations, termed intrinsic localized modes (ILMs), of the main chain of proteins based on all-atom molecular dynamics simulations of two fast-folder proteins and of a rigid α/β protein at 300 K and at 380 K in solution. These nonlinear excitations arise from the anharmonicity of the protein dynamics. The ILMs were detected by computing the Shannon entropy of the protein main-chain fluctuations. In the non-native state (significantly explored at 380 K), the probability of their excitation was increased by a factor between 9 and 28 for the fast-folder proteins and by a factor 2 for the rigid protein. This enhancement in the non-native state was due to glycine, as demonstrated by simulations in which glycine was mutated to alanine. These ILMs might play a functional role in the flexible regions of proteins and in proteins in a non-native state (i.e. misfolded or unfolded states).
Extremely Coherent Microwave Emission from Spin Torque Oscillator Stabilized by Phase Locked Loop
Authors: Tamaru Shingo , Kubota Hitoshi , Yakushiji Kay , Yuasa Shinji , Fukushima Akio
Published: December 2015

Spin torque oscillator (STO) has been attracting a great deal of attention as a candidate for the next generation microwave signal sources for various modern electronics systems since its advent. However, the phase noise of STOs under free running oscillation is still too large to be used in practical microwave applications, thus an industrially viable means to stabilize its oscillation has been strongly sought. Here we demonstrate implementation of a phase locked loop using a STO as a voltage controlled oscillator (VCO) that generates a 7.344 GHz microwave signal stabilized by a 153 MHz reference signal. Spectrum measurement showed successful phase locking of the microwave signal to the reference signal, characterized by an extremely narrow oscillation peak with a linewidth of less than the measurement limit of 1 Hz. This demonstration should be a major breakthrough toward various practical applications of STOs.
IFN-γ modulates Ly-49 receptors on NK cells in IFN-γ-induced pregnancy failure
Authors: Li Zhong-Yin , Song Zhi-Hui , Meng Chao-Yang , Yang Dan-Dan , Yang Ying , Peng Jing-Pian
Published: December 2015

We have previously shown that interferon gamma (IFN-γ) induces aberrant CD49b+ natural killer (NK) cell recruitment by regulating CX3CL1 and eventually provokes foetal loss. In this study, we show that IFN-γ also modulates Ly-49 receptors on NK cells during pregnancy failure. The percentages of Ly-49A+ and Ly-49G2+ NK cells in the uteri of the IFN-γ-treated group were significantly lower than those observed in the control group. Moreover, the median fluorescence intensity (MFI) values of Ly-49A and Ly-49G2 expression on NK cells in the uteri of the IFN-γ-treated group were significantly lower than those of the control group. Using isolated spleen leucocytes, we further found that IFN-γ significantly reduced the percentage of Ly-49A+ NK cells in vitro. However, CX3CL1 was not involved in the modulation of Ly-49 receptors and the expression of CX3CR1 was not regulated by IFN-γ in spleen leucocytes. Collectively, our data indicate that IFN-γ can modulate Ly-49 receptors on NK cells and this process may play a role in IFN-γ-induced pregnancy failure. Thus, we provide a new line of evidence correlating the deleterious effects of IFN-γ with its role in regulating NK cell Ly-49 receptors during pregnancy failure.
Different soil respiration responses to litter manipulation in three subtropical successional forests
Authors: Han Tianfeng , Huang Wenjuan , Liu Juxiu , Zhou Guoyi , Xiao Yin
Published: December 2015

Aboveground litter inputs have been greatly altered by human disturbances and climate change, which have important effects on soil respiration. However, the knowledge of how soil respiration responds to altered litter inputs is limited in tropical and subtropical forests. We conducted an aboveground litterfall manipulation experiment in three successional forests in the subtropics to examine the soil respiration responses to different litter inputs from January 2010 to July 2012. The soil respiration decreased by 35% in the litter exclusion treatments and increased by 77% in the doubled litter additions across all three forests. The reduction in soil respiration induced by the litter exclusion was greatest in the early successional forest, which may be related to a decrease in the soil moisture and shifts in the microbial community. The increase in soil respiration produced by the doubled litter addition was largest in the mature forest, which was most probably due to its relatively high quantity and quality of litterfall. Our results suggest that the effect of reduced litter inputs on the soil respiration lessened with forest succession but that the doubled litter inputs resulted in a stronger priming effect in the mature forest than in the other two forests.
Treatment of snoring with positional therapy in patients with positional obstructive sleep apnea syndrome
Authors: Chen Wen-Chyuan , Lee Li-Ang , Chen Ning-Hung , Fang Tuan-Jen , Huang Chung-Guei , Cheng Wen-Nuan , Li Hsueh-Yu
Published: December 2015

Position therapy plays a role in treating snoring and obstructive sleep apnea syndrome (OSAS). The purpose of this study was to investigate whether position therapy using a head-positioning pillow (HPP) could reduce snoring sounds in patients with mild-to-moderate positional OSAS, taking into account the potential confounding effects of body weight. A total of 25 adults with positional OSAS (apnea-hypopnea index [AHI]supine:AHInon-supine ≥ 2) were prospectively enrolled. Patients were asked to use their own pillows at home during the first night (N0) and the HPP during the second (N1) and third (N2) nights. The primary outcome measures included the subjective snoring severity (SS, measured on a visual analogue scale ranging from 0 to 10) and the objective snoring index (SI, expressed as the number of snoring events per hour measured on an acoustic analytical program). Both endpoints were recorded over three consecutive nights. From N0 to N2, the median SS and SI values in the entire study cohort decreased significantly from 5.0 to 4.0 and from 218.0 events/h to 115.0 events/h, respectively. In the subgroup of overweight patients, SS showed a significant improvement, whereas SI did not. Both SS and SI were found to be significantly improved in normal-weight patients.
Internal fixation treatments for intertrochanteric fracture: a systematic review and meta-analysis of randomized evidence
Authors: Yu Jiajie , Zhang Chao , Li Ling , Kwong Joey S. W. , Xue Li , Zeng Xiantao , Tang Li , Li Youping , Sun Xin
Published: December 2015

The relative effects of internal fixation strategies for intertrochanteric fracture after operation remain uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to address this important issue. We searched PubMed, EMBASE and CENTRAL for RCTs that compared different internal fixation implants in patients with intertrochanteric fracture at 6-month follow-up or longer. We ultimately included 43 trials enrolling 6911 patients; most trials were small in sample sizes and events. Their risk of bias was generally unclear due to insufficient reporting. Because of these, no statistically significant differences were present from most of the comparisons across all the outcomes and no definitive conclusions can be made. However, a number of trials compared two commonly used internal fixation strategies, gamma nail (GN) and sliding hip screw (SHS). There is good evidence suggesting that, compared to SHS, GN may increase the risk of cut out (OR = 1.87, 95% CI, 1.08 to 3.21), re-operation (OR = 1.61, 95% CI, 1.02 to 2.53), intra-operative (OR = 3.14, 95% CI, 1.34 to 7.35) and later fractures (OR = 3.67, 95% CI, 1.37 to 9.83). Future randomized trials or observational studies that are carefully designed and conducted are warranted to establish the effects of alternative internal fixation strategies for intertrochanteric fracture.
Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling
Authors: Samoshkin Alexander , Convertino Marino , Viet Chi T. , Wieskopf Jeffrey S. , Kambur Oleg , Marcovitz Jaclyn , Patel Pinkal , Stone Laura S. , Kalso Eija , Mogil Jeffrey S. , Schmidt Brian L. , Maixner William , Dokholyan Nikolay V. , Diatchenko Luda
Published: December 2015

The primary molecular target for clinically used opioids is the μ-opioid receptor (MOR). Besides the major seven-transmembrane (7TM) receptors, the MOR gene codes for alternatively spliced six-transmembrane (6TM) isoforms, the biological and clinical significance of which remains unclear. Here, we show that the otherwise exclusively intracellular localized 6TM-MOR translocates to the plasma membrane upon coexpression with β2-adrenergic receptors (β2-ARs) through an interaction with the fifth and sixth helices of β2-AR. Coexpression of the two receptors in BE(2)-C neuroblastoma cells potentiates calcium responses to a 6TM-MOR ligand and this calcium response is completely blocked by a selective β2-antagonist in BE(2)-C cells and in trigeminal and dorsal root ganglia. Co-administration of 6TM-MOR and β2-AR ligands leads to substantial analgesic synergy and completely reverses opioid-induced hyperalgesia in rodent behavioral models. Together, our results provide evidence that the heterodimerization of 6TM-MOR with β2-AR underlies a molecular mechanism for 6TM cellular signaling, presenting a unique functional responses to opioids. This signaling pathway may contribute to the hyperalgesic effects of opioids that can be efficiently blocked by β2-AR antagonists, providing a new avenue for opioid therapy.
Electrophysiological effects of non-invasive Radio Electric Asymmetric Conveyor (REAC) on thalamocortical neural activities and perturbed experimental conditions
Authors: Zippo Antonio G. , Rinaldi Salvatore , Pellegata Giulio , Caramenti Gian Carlo , Valente Maurizio , Fontani Vania , Biella Gabriele E. M.
Published: December 2015

The microwave emitting Radio Electric Asymmetric Conveyor (REAC) is a technology able to interact with biological tissues at low emission intensity (2 mW at the emitter and 2.4 or 5.8 GHz) by inducing radiofrequency generated microcurrents. It shows remarkable biological effects at many scales from gene modulations up to functional global remodeling even in human subjects. Previous REAC experiments by functional Magnetic Resonance Imaging (fMRI) on healthy human subjects have shown deep modulations of cortical BOLD signals. In this paper we studied the effects of REAC application on spontaneous and evoked neuronal activities simultaneously recorded by microelectrode matrices from the somatosensory thalamo-cortical axis in control and chronic pain experimental animal models. We analyzed the spontaneous spiking activity and the Local Field Potentials (LFPs) before and after REAC applied with a different protocol. The single neuron spiking activities, the neuronal responses to peripheral light mechanical stimuli, the population discharge synchronies as well as the correlations and the network dynamic connectivity characteristics have been analyzed. Modulations of the neuronal frequency associated with changes of functional correlations and significant LFP temporal realignments have been diffusely observed. Analyses by topological methods have shown changes in functional connectivity with significant modifications of the network features.