bluuebunny/crossref_metadata_2025 huggingface dataset:
The Liuyuan Volcanic Belt in NW China revisited: evidence for Permian rifting associated with the assembly of continental blocks in the Central Asian Orogenic Belt
Authors: WANG YU , LUO ZHAOHUA , SANTOSH M. , WANG SHUZHI , WANG NA
Published: February 2016

The basaltic pillow lavas in the Liuyuan region of NW China, considered to be part of an ophiolitic suite, have been central to the models on tectonic setting, evolution and timing of the final closure of the Palaeo-Asian Ocean. New field evidence on the sedimentary units associated with the basalts reveals comparable sequences in the northern and southern flanks of the Liuyuan Volcanic Belt with coarse to fine sediments from periphery to the centre. The dacites and rhyolites formed coevally with the pillow basalts. The pillow basalts are interlayered with lacustrine sandstone, claystone and clayey lake deposits. Detrital zircons from these sediments yield zircon U–Pb ages of 291–285 Ma. Andesites, dacites and rhyolites from the basaltic sequence yield U–Pb ages of 280–277 Ma, similar to the 282–280 Ma ages of gabbros that intrude the pillow lavas. All these rocks cover the 460–440 Ma granite and greenschist basement and have been intruded by gabbros ofc.272 Ma age, with subsequent (230–227 Ma) north–south contractional thrusting and folding. The data from our study are incompatible with the existing models that consider the basalts as part of an ophiolitic suite. Along the northern continental margin of China from west to east, the Tarim, Dunhuang-Alxa and North China cratonic areas all show evidence for regional extension through rifting during early–middle Permian time. These rift features and basaltic eruptions occurred coevally with the assembly of various microcontinental blocks against the Siberian craton atc.300–250 Ma, synchronous with amalgamation of the Central Asian Orogenic Belt (CAOB) on the northern side of the Liuyuan Rift. These events were also broadly synchronous with formation of the global supercontinent Pangea.
Vietnam War slang, as used by Rambo, desk jockeys and tail-end Charlies
Authors: Coleman Julie
Published: February 2016

In many ways, Dalzell's is an exemplary slang dictionary, as one might expect from so experienced a slang lexicographer. Slang dictionaries do not usually explain the principles underlying inclusion, the selection of headword forms, the ordering of senses and the designation of country of origin, although this information is vital to any careful user.
The reform of the National Matriculation English Test and its impact on the future of English in China
Authors: Zhao Junhai
Published: February 2016

With more and more importance being attached to English since China's economic reform and opening up to the outside world in the late 1970s, the entire Chinese society has placed such high importance to the learning of English that at times it even plays a vital role for a person who plans to pursue further education and seek a better career (China Daily, 5 August, 2010). However, the end of 2013 saw an ‘unanticipated’ reform of policy on the National Matriculation English Test (henceforth, NMET) instituted by the Chinese Ministry of Education (henceforth, MOE). It was ‘unanticipated’ because in the past few years the Chinese government has invested heavily in English language teaching. As reported by ABC News (15 November, 2010), ‘China is pushing its people to learn English’, and English has thus occupied a prominent place in the life of the Chinese people because it is the ‘key’ to success (Chen, 2008: 16-37). According to this new policy, the once favorite ‘son’, i.e. English, may lose its predominance in the Chinese foreign language landscape and its importance may be diminished in exams. These changes are likely to cause a series of chain reactions since the dominant position of English largely lies in its weight in various levels of exams, with the NMET having the greatest impact. Given the determining factor of the NMET in Chinese people's attitudes towards English, NMET reform would almost undoubtedly change the current situation of English in China and it would be no exaggeration to say that it will have a foreseeable impact on various aspects of Chinese social life as well. In this article, I briefly review the causes for the ‘focus shift’ and attempt an analysis of the impact of the role of English in China in the future.
Modelling the epidemiology of Escherichia coli ST131 and the impact of interventions on the community and healthcare centres
Authors: TALAMINOS A. , LÓPEZ-CERERO L. , CALVILLO J. , PASCUAL A. , ROA L. M. , RODRÍGUEZ-BAÑO J.
Published: February 2016

ST131 Escherichia coli is an emergent clonal group that has achieved successful worldwide spread through a combination of virulence and antimicrobial resistance. Our aim was to develop a mathematical model, based on current knowledge of the epidemiology of ESBL-producing and non-ESBL-producing ST131 E. coli, to provide a framework enabling a better understanding of its spread within the community, in hospitals and long-term care facilities, and the potential impact of specific interventions on the rates of infection. A model belonging to the SEIS (Susceptible–Exposed–Infected–Susceptible) class of compartmental models, with specific modifications, was developed. Quantification of the model is based on the law of mass preservation, which helps determine the relationships between flows of individuals and different compartments. Quantification is deterministic or probabilistic depending on subpopulation size. The assumptions for the model are based on several developed epidemiological studies. Based on the assumptions of the model, an intervention capable of sustaining a 25% reduction in person-to-person transmission shows a significant reduction in the rate of infections caused by ST131; the impact is higher for non-ESBL-producing ST131 isolates than for ESBL producers. On the other hand, an isolated intervention reducing exposure to antimicrobial agents has much more limited impact on the rate of ST131 infection. Our results suggest that interventions achieving a continuous reduction in the transmission of ST131 in households, nursing homes and hospitals offer the best chance of reducing the burden of the infections caused by these isolates.
Biomarkers detect involvement of acute myocardial injury in a paediatric haemolytic–uraemic syndrome patient
Authors: Palanca Arias Daniel , López Ramón Marta , Jiménez Montañés Lorenzo
Published: February 2016

Although extrarenal manifestations of haemolytic–uraemic syndrome are not frequent, myocardial dysfunction should be given special consideration because of the importance of proper early haemodynamic management and potential complications. We report the case of a 21-month-old child with haemolytic–uraemic syndrome who developed clinical signs of poor myocardial function with depressed myocardial function noted by bedside echocardiography and significant elevation of biomarkers. Early intervention and supportive treatment for the patient were crucial during the acute phase of cardiac failure, and repeated monitoring of biomarkers and ecocardiography were useful diagnostic tools that provided relevant information throughout the patient’s evolution.
An Assessment of Collaboration and Disasters: A Hospital Perspective
Authors: Adelaine Sabrina A. , Shoaf Kimberly , Harvey Caitlin
Published: February 2016

Introduction

There is no standard guidance for strategies for hospitals to use to coordinate with other agencies during a disaster.

Hypothesis/Problem

This study analyzes successful strategies and barriers encountered by hospitals across the nation in coordinating and collaborating with other response agencies.

Methods

Quantitative and qualitative data were collected from a web-based study from 577 acute care hospitals sampled from the 2013 American Hospital Association (AHA) database. The results were analyzed using descriptive statistics.

Results

The most common barriers to collaboration are related to finances, ability to communicate, and personnel.

AdelaineSA, ShoafK, HarveyC. An assessment of collaboration and disasters: a hospital perspective. Prehosp Disaster Med. 2016;31(2):121–125.
Constraints on variation, reduplication of semantics, and degrees of freedom: some notes on the computational account of code mixing
Authors: HARTSUIKER ROBERT J.
Published: February 2016

Goldrick, Putnam and Schwarz (2016) propose a very explicit account of code mixing, which nicely draws implications from the well-established findings of coactivation during bilingual language production, and that code mixing is constrained by grammatical principles. This precise characterization will undoubtedly serve as a useful basis for further research on code mixing, second language sentence production, and syntactic learning. However, there are three issues with the account that require further elaboration.
Spatially structured morphological and molecular diversity amongDioscorea cayenensisandD. rotundatayam accessions
Authors: Silva L. R. G. , Mezette T. F. , Nascimento W. F. , Silva E. F. , Veasey E. A.
Published: February 2016

Yams (Dioscoreaspp.) are one of the main root and tuber crops in the world, especially within the species complexDioscorea cayenensis/D. rotundata. Few studies have been conducted in Brazil with these species, including genetic diversity. The objective of this study was to characterize the genetic diversity of local varieties ofD. cayenensisandD. rotundatausing morphological and molecular markers, and provide information on the management and use of the crop by family farmers from different regions in Brazil. Thus, yam tubers were sampled from several municipalities in the South, Southeast and Northeast regions. Eighteen morphological traits and ten microsatellite loci were used to analyse 47 yam accessions (23D. cayenensisand 24D. rotundata). Species identification was carried out after field morphological evaluation. Spatial genetic analysis indicated significant structure among the local varieties, mostly between regions and species. Both cluster and Bayesian analyses showed a separation of the accessions into two distinct groups: group I with accessions originated from the Southeast region and group II with accessions originated from the Northeast region, while accessions from the South region were intermediate or included in either group. The results showed a separation betweenD. cayenensisandD. rotundataaccessions in Brazil, and thatD. cayenensisoccurs predominantly in the Southeast region, whileD. rotundataoccurs in the Northeast region. Further studies with larger sampling would be welcome in order to confirm these findings. Also, this study highlights the importance of family farmers in the genetic diversity conservation of these species in Brazil.
Cognitive behavioural therapy in the treatment of social skills deficits and social phobia in a man with an autism spectrum disorder: a single-case study
Authors: Turner Mark A. , Hammond Neil
Published: February 2016

Autism spectrum disorders (ASD) including high-functioning types such as Asperger's syndrome (AS) are diagnosed when there is evidence of a triad of qualitative impairments in social interaction, communication, and stereotyped/repetitive behaviours. It is not uncommon for these impairments to be accompanied by social anxiety. The present single-case study investigates the use of cognitive behavioural therapy (CBT) to treat a 47-year-old man who was assessed as having difficulties with social skills and social phobia in the context of a late diagnosis of AS. He received 20 h of CBT adapted for his AS in 15 sessions including a 1-month follow-up. Following a highly individualized formulation, treatment included modelling, role-playing, reinforcement, thought challenging, and behavioural experimentation. Results from five self-report measures showed continued improvements from the start of therapy to follow-up in social anxiety, global distress, depression and self-esteem. The client gave positive feedback about his experience of treatment. The case study is discussed with reference to limitations and some reflections for CBT in ASD.
Wundballistik – eine Kurzübersicht
Authors: Bolliger Stephan A. , Eggert Sebastian , Thali Michael J.
Published: February 2016

Zusammenfassung. Mittels experimentellem Beschiessen von synthetischen Modellen aus Gelatine, Glyzerinseife und Kunstknochen, validiert mit realen Befunden aus dem (kriegs-) chirurgischen und rechtsmedizinischen Fallgut untersucht die Wundballistik die munitionsspezifische Wirkung, also das Wundprofil, von Geschossen auf den Körper. Unter «Wundprofil» versteht man die Eindringtiefe, die Geschossdeformation/Fragmentation, den Durchmesser der temporären Wundhöhle und den Durchmesser der permanenten Wundhöhle. In Kenntnis dieser Merkmale und der verwendeten Munition kann ein Chirurg rasch abschätzen, wie gross die Verletzung im Inneren des Patienten sein wird. Der Rechtsmediziner kann aufgrund des Wundprofils Rückschlüsse auf die verwendete Munition ziehen. Des Weiteren erlaubt die Wundballistik eine Messung der Zerstörungskraft von verschiedenen Munitionstypen, was die Grundlage von Richtlinien zur Wirkungsbegrenzung von Kriegsmunition darstellt.
Männliches Mammakarzinom: Was ist anders?
Authors: Niederberger Philipp , Bucher Susanne , Aebi Stefan
Published: February 2016

Zusammenfassung. Brustkrebs ist beim Mann eine seltene Krankheit. Die Symptome sind ähnlich wie bei der Frau: Bei palpablem Tumor in der Brust, vergrösserten axillären Lymphknoten oder verdächtigen Hautveränderungen der Brust (Ulzeration, Sekretion, peau d'orange) empfehlen sich Mammografie, Mammasonografie mit Beurteilung der regionären Lymphknoten und präoperativer histologischer Bestätigung. Die Therapie des männlichen Mammakarzinoms erfolgt wie bei der Frau: Resektion gefolgt von Pharmakotherapie und Bestrahlung. Anders als bei Frauen kommt in der adjuvanten Therapie Tamoxifen und nicht ein Aromatasehemmer zum Einsatz. Die Behandlungsprinzipien in der metastasierten Situation gleichen dem Vorgehen bei Frauen.
Die Schulter des Überkopfsportlers
Authors: Wieser Karl , Gerber Christian , Meyer Dominik C.
Published: February 2016

Zusammenfassung. Repetitive sportliche Höchstleistungen der Überkopfsportler stellen eine enorme Belastung für das Schultergelenk dar. Werfer erlangen Wurfarmrotationsgeschwindigkeiten von über 7000°/s, wobei hierbei Gelenkskompressions- und Distraktionskräfte von über 1000 N entstehen. Dies ist nur durch eine Adaptation der Schultermuskulatur und des Schultergelenkes mit bis zu 29° vermehrter Humeruskopfretrotorsion möglich. Diese, bei Werfern besonders ausgeprägten Anpassungen, führen zu zwei typischen Problemen: 1. Das hintere Einklemmen der Rotatorenmanschette und des glenoidalen Labrums zwischen Gelenkspfanne und Humeruskopf («inneres Impingement») bei der Ausholbewegung; 2. Störende Innenrotationseinschränkung (GIRD) mit kompensatorischen Beschwerden der Scapula-stabilisierenden Muskulatur. Die präzise Analyse von Kinematik und Pathomechanik der Werferschulter hat zum Ziel, diese Überlastungsschäden zu verstehen und einer kausalen Therapie zuzuführen.
Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin
Authors: Long K. , Moss L. , Laursen L. , Boulter L. , ffrench-Constant C.
Published: February 2016

Development of the cerebral cortex requires regulation of proliferation and differentiation of neural stem cells and a diverse range of progenitors. Recent work suggests a role for extracellular matrix (ECM) and the major family of ECM receptors, the integrins. Here we show that enhancing integrin beta-1 signalling, by expressing a constitutively active integrin beta-1 (CA*β1) in the embryonic chick mesencephalon, enhances neurogenesis and increases the number of mitotic cells dividing away from the ventricular surface, analogous to sub-apical progenitors in mouse. Only non-integrin-expressing neighbouring cells (lacking CA*β1) contributed to the increased neurogenesis. Transcriptome analysis reveals upregulation of Wnt7a within the CA*β1 cells and upregulation of the ECM protein Decorin in the neighbouring non-expressing cells. Experiments using inhibitors in explant models and genetic knock-downs in vivo reveal an integrin-Wnt7a-Decorin pathway that promotes proliferation and differentiation of neuroepithelial cells, and identify Decorin as a novel neurogenic factor in the central nervous system.
Autophagy regulates Notch degradation and modulates stem cell development and neurogenesis
Authors: Wu Xiaoting , Fleming Angeleen , Ricketts Thomas , Pavel Mariana , Virgin Herbert , Menzies Fiona M. , Rubinsztein David C.
Published: February 2016

Autophagy is a conserved, intracellular, lysosomal degradation pathway. While mechanistic aspects of this pathway are increasingly well defined, it remains unclear how autophagy modulation impacts normal physiology. It is, however, becoming clear that autophagy may play a key role in regulating developmental pathways. Here we describe for the first time how autophagy impacts stem cell differentiation by degrading Notch1. We define a novel route whereby this plasma membrane-resident receptor is degraded by autophagy, via uptake into ATG16L1-positive autophagosome-precursor vesicles. We extend our findings using a physiologically relevant mouse model with a hypomorphic mutation in Atg16L1, a crucial autophagy gene, which shows developmental retention of early-stage cells in various tissues where the differentiation of stem cells is retarded and thus reveal how modest changes in autophagy can impact stem cell fate. This may have relevance for diverse disease conditions, like Alzheimer’s Disease or Crohn’s Disease, associated with altered autophagy.
Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase
Authors: Kristjansson Ragnar P. , Oddsson Asmundur , Helgason Hannes , Sveinbjornsson Gardar , Arnadottir Gudny A. , Jensson Brynjar O. , Jonasdottir Aslaug , Jonasdottir Adalbjorg , Bragi Walters G. , Sulem Gerald , Oskarsdottir Arna , Benonisdottir Stefania , Davidsson Olafur B. , Masson Gisli , Th Magnusson Olafur , Holm Hilma , Sigurdardottir Olof , Jonsdottir Ingileif , Eyjolfsson Gudmundur I. , Olafsson Isleifur , Gudbjartsson Daniel F. , Thorsteinsdottir Unnur , Sulem Patrick , Stefansson Kari
Published: February 2016

Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH measurements, respectively. Here we describe 13 variants associating with serum CK and 16 with LDH levels, including four that associate with both. Among those, 15 are non-synonymous variants and 12 have a minor allele frequency below 5%. We report sequence variants in genes encoding the enzymes being measured (CKM and LDHA), as well as in genes linked to muscular (ANO5) and immune/inflammatory function (CD163/CD163L1, CSF1, CFH, HLA-DQB1, LILRB5, NINJ1 and STAB1). A number of the genes are linked to the mononuclear/phagocyte system and clearance of enzymes from the serum. This highlights the variety in the sources of normal diversity in serum levels of enzymes.
NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force
Authors: Li Chenyu , Xue Chenyi , Yang Qiaoyun , Low Boon Chuan , Liou Yih-Cherng
Published: February 2016

In vertebrate cells, chromosomes oscillate to align precisely during metaphase. NuSAP, a microtubule-associated protein, plays a critical role in stabilizing spindle microtubules. In this study, we utilize 3D time-lapse live-cell imaging to monitor the role of NuSAP in chromosome oscillation and identify NuSAP as a novel regulator of the chromokinesin, Kid. Depletion of NuSAP significantly suppresses the amplitude and velocity of chromosome oscillation. We analyse the effects of NuSAP and Kid depletion in monopolar and bipolar cells with or without kinetochore microtubule depletion. Twelve postulated conditions are deciphered to reveal the contribution of NuSAP to the polar force generated at kinetochore microtubules and to the regulation of the polar ejection force generated by Kid, thus revealing a pivotal role of NuSAP in chromosome oscillation.
Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions
Authors: Brown Maxwell W. , Kim Yoori , Williams Gregory M. , Huck John D. , Surtees Jennifer A. , Finkelstein Ilya J.
Published: February 2016

DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2–Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2–Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2–Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2–Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2–Msh3 and Msh2–Msh6 navigate on a crowded genome and suggest how Msh2–Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin.
PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications
Authors: Lancaster G. I. , Kammoun H. L. , Kraakman M. J. , Kowalski G. M. , Bruce C. R. , Febbraio M. A.
Published: February 2016

Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation.
Ferroelastic switching in a layered-perovskite thin film
Authors: Wang Chuanshou , Ke Xiaoxing , Wang Jianjun , Liang Renrong , Luo Zhenlin , Tian Yu , Yi Di , Zhang Qintong , Wang Jing , Han Xiu-Feng , Van Tendeloo Gustaaf , Chen Long-Qing , Nan Ce-Wen , Ramesh Ramamoorthy , Zhang Jinxing
Published: February 2016

A controllable ferroelastic switching in ferroelectric/multiferroic oxides is highly desirable due to the non-volatile strain and possible coupling between lattice and other order parameter in heterostructures. However, a substrate clamping usually inhibits their elastic deformation in thin films without micro/nano-patterned structure so that the integration of the non-volatile strain with thin film devices is challenging. Here, we report that reversible in-plane elastic switching with a non-volatile strain of approximately 0.4% can be achieved in layered-perovskite Bi2WO6 thin films, where the ferroelectric polarization rotates by 90° within four in-plane preferred orientations. Phase-field simulation indicates that the energy barrier of ferroelastic switching in orthorhombic Bi2WO6 film is ten times lower than the one in PbTiO3 films, revealing the origin of the switching with negligible substrate constraint. The reversible control of the in-plane strain in this layered-perovskite thin film demonstrates a new pathway to integrate mechanical deformation with nanoscale electronic and/or magnetoelectronic applications.
A prognostic signature based on three-genes expression in triple-negative breast tumours with residual disease
Authors: Pinto Joseph A , Araujo Jhajaira , Cardenas Nadezhda K , Morante Zaida , Doimi Franco , Vidaurre Tatiana , Balko Justin M , Gomez Henry L
Published: February 2016

Residual disease after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is related with poor prognosis; however, the risk of recurrence after 3 years from surgery, becomes similar to other breast cancer subtypes indicating that TNBC is composed of tumours of different prognosis. To evaluate genes related to TNBC aggressiveness in the outcome of TNBC resistant to NAC, we profiled 82 samples of residual tumours whose expression for 449 genes was quantified with NanoString. The validation set (GSE25066) consisted of 113 TNBC cases with residual disease. The stepwise multivariate survival analysis performed by the Cox proportional hazards mode selected CCL5, DDIT4 and POLR1C as independent prognostic factors for distant recurrence-free survival (DRFS). We developed a three-genes signature using the regression coefficients for each gene (−0.393×CCL5+0.443×DDIT4+0.490×POLR1C). The median score in the discovery set (0.1494) identified two subgroups with different DRFS (P<0.001). The median score in the validation set was 0.0024 and was able to discriminate patients with different DRFS (P=0.002). In addition, the three-genes signature was a prognostic factor in TNBC patients regardless their response to NAC (data set GSE58812; P=0.001) and in patients with oestrogen-receptor-negative tumours (data set GSE16446; P=0.041). Here we describe a prognostic signature based on expression levels of CCL5, DDIT4 and POLR1C. The knowledge about the involvement of these genes in chemotherapy resistance could improve the therapeutic strategies in TNBC.
Allelopathic Polyketides from an Endolichenic Fungus Myxotrichum SP. by Using OSMAC Strategy
Authors: Yuan Chao , Guo Yu-Hua , Wang Hai-Ying , Ma Xiao-Jun , Jiang Tao , Zhao Jun-Ling , Zou Zhong-Mei , Ding Gang
Published: February 2016

Three new polyketides myxotritones A-C (2–4), together with a new natural product 7,8-dihydro-7R,8S-dihydroxy-3,7-dimethyl-2-benzopyran-6-one (1) were obtained from the endolichenic fungus Myxotrichum sp. by using OMSAC (One Strain, Many Compounds) method. The planar structures of these new compounds were determined by NMR experiment and HRESIMS data and the absolute configuration of 1 was established by X-ray diffraction and the stereochemistry of the new compounds 2-4 were determined by same biosynthesis origin and similar CD spectra with 1. Allelopathic test showed that compound 4 significantly retarded root elongation of Arabidopsis thaliana seed, indicating that this fungus might contribute to the defense of its host lichen. From the view of biosynthetic pathway, all four compounds 1-4 might be originated from Non-Reduced Polyketide synthase (NR-PKS).
Fluid leakage near the percolation threshold
Authors: Dapp Wolf B. , Müser Martin H.
Published: February 2016

Percolation is a concept widely used in many fields of research and refers to the propagation of substances through porous media (e.g., coffee filtering), or the behaviour of complex networks (e.g., spreading of diseases). Percolation theory asserts that most percolative processes are universal, that is, the emergent powerlaws only depend on the general, statistical features of the macroscopic system, but not on specific details of the random realisation. In contrast, our computer simulations of the leakage through a seal—applying common assumptions of elasticity, contact mechanics and fluid dynamics—show that the critical behaviour (how the flow ceases near the sealing point) solely depends on the microscopic details of the last constriction. It appears fundamentally impossible to accurately predict from statistical properties of the surfaces alone how strongly we have to tighten a water tap to make it stop dripping and also how it starts dripping once we loosen it again.
Regulating wave front dynamics from the strongly discrete to the continuum limit in magnetically driven colloidal systems
Authors: Martinez-Pedrero Fernando , Tierno Pietro , Johansen Tom H. , Straube Arthur V.
Published: February 2016

The emergence of wave fronts in dissipative driven systems is a fascinating phenomenon which can be found in a broad range of physical and biological disciplines. Here we report the direct experimental observation of discrete fronts propagating along chains of paramagnetic colloidal particles, the latter propelled above a traveling wave potential generated by a structured magnetic substrate. We develop a rigorously reduced theoretical framework and describe the dynamics of the system in terms of a generalized one-dimensional dissipative Frenkel-Kontorova model. The front dynamics is explored in a wide range of field parameters close to and far from depinning, where the discrete and continuum limits apply. We show how symmetry breaking and finite size of chains are used to control the direction of front propagation, a universal feature relevant to different systems and important for real applications.
Towards a Physarum learning chip
Authors: Whiting James G. H. , Jones Jeff , Bull Larry , Levin Michael , Adamatzky Andrew
Published: February 2016

Networks of protoplasmic tubes of organism Physarum polycehpalum are macro-scale structures which optimally span multiple food sources to avoid repellents yet maximize coverage of attractants. When data are presented by configurations of attractants and behaviour of the slime mould is tuned by a range of repellents, the organism preforms computation. It maps given data configuration into a protoplasmic network. To discover physical means of programming the slime mould computers we explore conductivity of the protoplasmic tubes; proposing that the network connectivity of protoplasmic tubes shows pathway-dependent plasticity. To demonstrate this we encourage the slime mould to span a grid of electrodes and apply AC stimuli to the network. Learning and weighted connections within a grid of electrodes is produced using negative and positive voltage stimulation of the network at desired nodes; low frequency (10 Hz) sinusoidal (0.5 V peak-to-peak) voltage increases connectivity between stimulated electrodes while decreasing connectivity elsewhere, high frequency (1000 Hz) sinusoidal (2.5 V peak-to-peak) voltage stimulation decreases network connectivity between stimulated electrodes. We corroborate in a particle model. This phenomenon may be used for computation in the same way that neural networks process information and has the potential to shed light on the dynamics of learning and information processing in non-neural metazoan somatic cell networks.
Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs
Authors: Oleaga Carlota , Bernabini Catia , Smith Alec S.T. , Srinivasan Balaji , Jackson Max , McLamb William , Platt Vivien , Bridges Richard , Cai Yunqing , Santhanam Navaneetha , Berry Bonnie , Najjar Sarah , Akanda Nesar , Guo Xiufang , Martin Candace , Ekman Gail , Esch Mandy B. , Langer Jessica , Ouedraogo Gladys , Cotovio Jose , Breton Lionel , Shuler Michael L. , Hickman James J.
Published: February 2016

We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems and constitutes a step towards an in vitro “human-on-a-chip” assay for systemic toxicity screening.
5-HT2 receptors mediate functional modulation of GABAa receptors and inhibitory synaptic transmissions in human iPS-derived neurons
Authors: Wang Haitao , Hu Lingli , Liu Chunhua , Su Zhenghui , Wang Lihui , Pan Guangjin , Guo Yiping , He Jufang
Published: February 2016

Neural progenitors differentiated from induced pluripotent stem cells (iPS) hold potentials for treating neurological diseases. Serotonin has potent effects on neuronal functions through multiple receptors, underlying a variety of neural disorders. Glutamate and GABA receptors have been proven functional in neurons differentiated from iPS, however, little is known about 5-HT receptor-mediated modulation in such neuronal networks. In the present study, human iPS were differentiated into cells possessing featured physiological properties of cortical neurons. Whole-cell patch-clamp recording was used to examine the involvement of 5-HT2 receptors in functional modulation of GABAergic synaptic transmission. We found that serotonin and DOI (a selective agonist of 5-HT2A/C receptor) reversibly reduced GABA-activated currents and this 5-HT2A/C receptor mediated inhibition required G protein, PLC, PKC and Ca2+ signaling. Serotonin increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs), which could be mimicked by α-methylserotonin, a 5-HT2 receptor agonist. In contrast, DOI reduced both frequency and amplitude of mIPSCs. These findings suggested that in iPS-derived human neurons serotonin postsynaptically reduced GABAa receptor function through 5-HT2A/C receptors, but presynaptically other 5-HT2 receptors counteracted the action of 5-HT2A/C receptors. Functional expression of serotonin receptors in human iPS-derived neurons provides a pre-requisite for their normal behaviors after grafting.
Active layers of high-performance lead zirconate titanate at temperatures compatible with silicon nano- and microelectronic devices
Authors: Bretos Iñigo , Jiménez Ricardo , Tomczyk Monika , Rodríguez-Castellón Enrique , Vilarinho Paula M. , Calzada M. Lourdes
Published: February 2016

Applications of ferroelectric materials in modern microelectronics will be greatly encouraged if the thermal incompatibility between inorganic ferroelectrics and semiconductor devices is overcome. Here, solution-processable layers of the most commercial ferroelectric compound ─ morphotrophic phase boundary lead zirconate titanate, namely Pb(Zr0.52Ti0.48)O3 (PZT) ─ are grown on silicon substrates at temperatures well below the standard CMOS process of semiconductor technology. The method, potentially transferable to a broader range of Zr:Ti ratios, is based on the addition of crystalline nanoseeds to photosensitive solutions of PZT resulting in perovskite crystallization from only 350 °C after the enhanced decomposition of metal precursors in the films by UV irradiation. A remanent polarization of 10.0 μC cm−2 is obtained for these films that is in the order of the switching charge densities demanded for FeRAM devices. Also, a dielectric constant of ~90 is measured at zero voltage which exceeds that of current single-oxide candidates for capacitance applications. The multifunctionality of the films is additionally demonstrated by their pyroelectric and piezoelectric performance. The potential integration of PZT layers at such low fabrication temperatures may redefine the concept design of classical microelectronic devices, besides allowing inorganic ferroelectrics to enter the scene of the emerging large-area, flexible electronics.
Should adrenaline be used in patients with hemodynamically stable anaphylaxis? Incident case control study nested within a retrospective cohort study
Authors: Ko Byuk Sung , Kim Ji Yeon , Seo Dong-Woo , Kim Won Young , Lee Jae Ho , Sheikh Aziz , Bates David W.
Published: February 2016

Although adrenaline (epinephrine) is a cornerstone of initial anaphylaxis treatment, it is not often used. We sought to assess whether use of adrenaline in hemodynamically stable patients with anaphylaxis could prevent the development of hypotension. We conducted a retrospective cohort study of 761 adult patients with anaphylaxis presenting to the emergency department (ED) of a tertiary care hospital over a 10-year period. We divided the patients into two groups according to the occurrence of hypotension and compared demographic characteristics, clinical features, treatments and outcomes. Of the 340 patients with anaphylaxis who were normotensive at first presentation, 40 patients experienced hypotension during their ED stay. The ED stay of the hypotension group was significantly longer than that of patients who did not experience hypotension (496 min vs 253 min, P = 0.000). Adrenaline use in hemodynamically stable anaphylaxis patient was independently associated with a lower risk of developing in-hospital occurrence of hypotension: OR, 0.254 [95% CI, 0.091–0.706]. Adrenaline use in hemodynamically stable anaphylaxis patients was associated with a reduced risk of developing in-hospital occurrence of hypotension. Adverse events induced by adrenaline were rare when the intramuscular route was used.
GSK-3β downregulates Nrf2 in cultured cortical neurons and in a rat model of cerebral ischemia-reperfusion
Authors: Chen Xi , Liu Yuanling , Zhu Jin , Lei Shipeng , Dong Yuan , Li Lingyu , Jiang Beibei , Tan Li , Wu Jingxian , Yu Shanshan , Zhao Yong
Published: February 2016

The NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays a critical role in protecting against oxidative stress in brain ischemia and reperfusion injury. Glycogen synthase kinase 3β (GSK-3β) may play a critical role in regulating Nrf2 in a Kelch-like ECH-associated protein 1 (Keap1)-independent manner. However, the relationship between GSK-3β and Nrf2 in brain ischemia and reperfusion injury is not clear. In this study, we explored the mechanisms through which GSK-3β regulates Nrf2 and Nrf-2/ARE pathways in vitro and in vivo. We used oxygen and glucose deprivation/reoxygenation (OGD/R) in primary cultured cortical neurons and a middle cerebral artery occlusion-reperfusion (MCAO/R) rat model to mimic ischemic insult. In this study, GSK-3β siRNA and inhibitors (SB216763 and LiCl) were used to inhibit GSK-3β in vitro and in vivo. After inhibiting GSK-3β, expression of total and nuclear Nrf2, Nrf2-ARE binding activity and expression of Nrf2/ARE pathway-driven genes HO-1 and NQO-1 increased. Overexpression of GSK-3β yielded opposite results. These results suggest that GSK-3β downregulates Nrf2 and the Nrf2/ARE pathway in brain ischemia and reperfusion injury. GSK-3β may be an endogenous antioxidant relevant protein and may represent a new therapeutic target in treatment of ischemia and reperfusion injury.
Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats
Authors: Ingberg Edvin , Theodorsson Elvar , Theodorsson Annette , Ström Jakob O.
Published: February 2016

The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se and not the route and method of administration, that determines the effect and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.
Powder metallurgy inspired low-temperature fabrication of high-performance stereocomplexed polylactide products with good optical transparency
Authors: Bai Dongyu , Liu Huili , Bai Hongwei , Zhang Qin , Fu Qiang
Published: February 2016

Stereocomplexation between enantiomeric poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) provides an avenue to greatly enhance performance of eco-friendly polylactide (PLA). Unfortunately, although the manufacturing of semicrystalline polymers generally involves melt processing, it is still hugely challenging to create high-performance stereocomplexed polylactide (sc-PLA) products from melt-processed high-molecular-weight PLLA/PDLA blends due to the weak crystallization memory effect of stereocomplex (sc) crystallites after complete melting as well as the substantial degradation of PLA chains at elevated melt-processing temperatures of ca. 240–260 °C. Inspired by the concept of powder metallurgy, here we report a new facile route to address these obstacles by sintering of sc-PLA powder at temperatures as low as 180–210 °C, which is distinctly different from traditional sintering of polymer powders performed at temperatures far exceeding their melting temperatures. The enantiomeric PLA chain segments from adjacent powder particles can interdiffuse across particle interfaces and co-crystallize into new sc crystallites capable of tightly welding the interfaces during the low-temperature sintering process and thus highly transparent sc-PLA products with outstanding heat resistance, mechanical strength and hydrolytic stability have been successfully fabricated for the first time.
Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells
Authors: Kumari Bharti , Jain Pratistha , Das Shaoli , Ghosal Suman , Hazra Bibhabasu , Trivedi Ashish Chandra , Basu Anirban , Chakrabarti Jayprokas , Vrati Sudhanshu , Banerjee Arup
Published: February 2016

Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation.
Atomic structures and oxygen dynamics of CeO2 grain boundaries
Authors: Feng Bin , Sugiyama Issei , Hojo Hajime , Ohta Hiromichi , Shibata Naoya , Ikuhara Yuichi
Published: February 2016

Material performance is significantly governed by grain boundaries (GBs), a typical crystal defects inside, which often exhibit unique properties due to the structural and chemical inhomogeneity. Here, it is reported direct atomic scale evidence that oxygen vacancies formed in the GBs can modify the local surface oxygen dynamics in CeO2, a key material for fuel cells. The atomic structures and oxygen vacancy concentrations in individual GBs are obtained by electron microscopy and theoretical calculations at atomic scale. Meanwhile, local GB oxygen reduction reactivity is measured by electrochemical strain microscopy. By combining these techniques, it is demonstrated that the GB electrochemical activities are affected by the oxygen vacancy concentrations, which is, on the other hand, determined by the local structural distortions at the GB core region. These results provide critical understanding of GB properties down to atomic scale and new perspectives on the development strategies of high performance electrochemical devices for solid oxide fuel cells.
A novel nitro-dexamethasone inhibits agr system activity and improves therapeutic effects in MRSA sepsis models without antibiotics
Authors: Yang Yun , Li Haibo , Sun Hongwu , Gong Li , Guo Ling , Shi Yun , Cai Changzhi , Gu Hao , Song Zhen , Yang Liuyang , Tong Yanan , Wei Chao , Zou Quanming , Zeng Hao
Published: February 2016

Methicillin-resistant Staphylococcus aureus (MRSA) sepsis is a life-threatening medical condition that involves systemic inflammation throughout the body. Glucocorticoids are widely used in combination with antibiotics in the treatment of MRSA sepsis to fight the overwhelming inflammation. Here, we describe the improved anti-inflammatory properties of a nitric oxide (NO)-releasing derivative of dexamethasone, ND8008. ND8008 affected MRSA biofilm formation, caused biofilm cell death and reduced the effects of virulence factors, such as α-toxin, by inhibiting the activity of the Staphylococcus aureus accessory gene regulator (agr) system. Dosing of mice with ND8008 (127.4 nmol/kg, i.p.) alone greatly reduced the inflammatory response caused by MRSA blood stream infection and considerably increased the survival rate of septic mice. These findings suggest that this novel NO-releasing derivative of dexamethasone ND8008 could be helpful in the treatment of MRSA sepsis.
Conformational dynamics is key to understanding loss-of-function of NQO1 cancer-associated polymorphisms and its correction by pharmacological ligands
Authors: Medina-Carmona Encarnación , Palomino-Morales Rogelio J. , Fuchs Julian E. , Padín-Gonzalez Esperanza , Mesa-Torres Noel , Salido Eduardo , Timson David J. , Pey Angel L.
Published: February 2016

Protein dynamics is essential to understand protein function and stability, even though is rarely investigated as the origin of loss-of-function due to genetic variations. Here, we use biochemical, biophysical, cell and computational biology tools to study two loss-of-function and cancer-associated polymorphisms (p.R139W and p.P187S) in human NAD(P)H quinone oxidoreductase 1 (NQO1), a FAD-dependent enzyme which activates cancer pro-drugs and stabilizes several oncosuppressors. We show that p.P187S strongly destabilizes the NQO1 dimer in vitro and increases the flexibility of the C-terminal domain, while a combination of FAD and the inhibitor dicoumarol overcome these alterations. Additionally, changes in global stability due to polymorphisms and ligand binding are linked to the dynamics of the dimer interface, whereas the low activity and affinity for FAD in p.P187S is caused by increased fluctuations at the FAD binding site. Importantly, NQO1 steady-state protein levels in cell cultures correlate primarily with the dynamics of the C-terminal domain, supporting a directional preference in NQO1 proteasomal degradation and the use of ligands binding to this domain to stabilize p.P187S in vivo. In conclusion, protein dynamics are fundamental to understanding loss-of-function in p.P187S and to develop new pharmacological therapies to rescue this function.