bluuebunny/crossref_metadata_2025 huggingface dataset:
Unbuilt Anxieties: Infrastructure Projects, Transnational Conflict in the South China/East Sea, and Vietnamese Statehood
Authors: MacLean Ken
Published: June 2016

The conflicts shaping territorial claims and counter-claims to overlapping areas of the South China Sea threatens to significantly damage Sino-Vietnamese relations, destabilize regional security arrangements, and alter the geopolitical status quo. The governments of both countries routinely invoke historical documents, commission scientific studies, and cite legal principles to justify their competing claims in the maritime region and the resources contained therein. The role different types of energy infrastructure play in the state-level disputes have received little attention, however. This essay addresses this oversight. In it, I foreground the complex ways not yet built infrastructure affect Sino-Vietnamese relations as well as our theoretical understanding of “the state”, especially with regard to Vietnam. Not yet built infrastructure refers to more than the assemblage of things that will be built in the future to power the economy, such as oil rigs, natural gas pipelines, and refineries. The concept also includes the ideological positions that presuppose the materialization of blueprint plans in physical form, i.e., the broader goals such infrastructure is meant to achieve. Towards this end, the article focuses on how state actors and their proxies conceptualize the likely impacts not yet built infrastructure will have upon their respective interests once construction is completed. The case study highlights how the need for energy security strengthens national security at some moments, weakens it at others, and both at still others.
Influenza
Authors: Vernazza Pietro
Published: June 2016

Zusammenfassung. Die Grippe gehört zu den durch Impfungen verhütbaren Erkrankungen, doch die Bereitschaft, sich gegen diese alljährlich Auftretende Grippe zu schützen ist in der Allgemeinbevölkerung minimal. Dabei handelt es sich in keiner Weise um eine immer harmlos verlaufende Erkrankung, wie unser authentischer Fallbericht zeigt. Personen mit abgeschwächter Immunantwort, insbesondere Schwangere Frauen und ältere Menschen sind besonders gefährdet für einen komplizierten Verlauf bei einer Influenza-Infektion. Doch gerade bei diesen Menschen ist auch die Immun­antwort auf die Grippeimpfung naturgemäss limitiert, sodass gerade in dieser Zielgruppe die Wirksamkeit der Impfung eingeschränkt ist. Die eingeschränkte Wirksamkeit in dieser Zielgruppe ist ein potentieller „Imageschaden“ für die Grippe-Impfung. Es stellt sich die Frage, ob wir nicht stärker die Impfung der gesunden Personen in der Umgebung von gefährdeten Menschen propagieren sollten. Ältere Daten aber auch moderne Modellrechnungen weisen zudem darauf hin, dass eine konsequente Impfung von (Schul-)Kindern bezüglich Mortalität am wirksamsten wäre.
Humans Misread Wind Speeds, Skewing a Major Hazards Database
Authors: Deatrick Elizabeth
Published: June 2016

Weather spotters who report storm measurements and observations to a U.S. national compendium of storm data often exaggerate winds speeds—by about one third, on average.
Interferon‐β therapy specifically reduces pathogenic memory B cells in multiple sclerosis patients by inducing a FAS‐mediated apoptosis
Authors: Rizzo Fabiana , Giacomini Elena , Mechelli Rosella , Buscarinu Maria Chiara , Salvetti Marco , Severa Martina , Coccia Eliana Marina
Published: June 2016

Growing evidences put B lymphocytes on a central stage in multiple sclerosis (MS) immunopathology. While investigating the effects of interferon‐β (IFN‐β) therapy, one of the most used first‐line disease‐modifying drugs for the treatment of relapsing‐remitting MS, in circulating B‐cell sub‐populations, we found a specific and marked decrease of CD27+ memory B cells. Interestingly, memory B cells are considered a population with a great disease‐driving relevance in MS and resulted to be also target of B‐cell depleting therapies. In addition, Epstein–Barr virus (EBV), associated with MS etiopathogenesis, harbors in this cell type and an IFN‐β‐induced reduction of the memory B‐cell compartment, in turn, resulted in a decreased expression of the EBV gene latent membrane protein 2A in treated patients. We found that in vivo IFN‐β therapy specifically and highly induced apoptosis in memory B cells, in accordance with a strong increase of the apoptotic markers Annexin‐V and active caspase‐3, via a mechanism requiring the FAS‐receptor/TACI (transmembrane activator and CAML interactor) signaling. Thus, efficacy of IFN‐β therapy in MS may rely not only on its recognized anti‐inflammatory activities but also on the specific depletion of memory B cells, considered to be a pathogenic cell subset, reducing their inflammatory impact in target organs.
The Arabidopsis acetylated histone-binding protein BRAT1 forms a complex with BRP1 and prevents transcriptional silencing
Authors: Zhang Cui-Jun , Hou Xiao-Mei , Tan Lian-Mei , Shao Chang-Rong , Huang Huan-Wei , Li Yong-Qiang , Li Lin , Cai Tao , Chen She , He Xin-Jian
Published: June 2016

Transposable elements and other repetitive DNA sequences are usually subject to DNA methylation and transcriptional silencing. However, anti-silencing mechanisms that promote transcription in these regions are not well understood. Here, we describe an anti-silencing factor, Bromodomain and ATPase domain-containing protein 1 (BRAT1), which we identified by a genetic screen in Arabidopsis thaliana. BRAT1 interacts with an ATPase domain-containing protein, BRP1 (BRAT1 Partner 1), and both prevent transcriptional silencing at methylated genomic regions. Although BRAT1 mediates DNA demethylation at a small set of loci targeted by the 5-methylcytosine DNA glycosylase ROS1, the involvement of BRAT1 in anti-silencing is largely independent of DNA demethylation. We also demonstrate that the bromodomain of BRAT1 binds to acetylated histone, which may facilitate the prevention of transcriptional silencing. Thus, BRAT1 represents a potential link between histone acetylation and transcriptional anti-silencing at methylated genomic regions, which may be conserved in eukaryotes.
A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels
Authors: Martínez-Martínez Maria Ángeles , De Juan Romero Camino , Fernández Virginia , Cárdenas Adrián , Götz Magdalena , Borrell Víctor
Published: June 2016

The outer subventricular zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species such as human and ferret, where it contains abundant basal radial glia cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident downregulation of Cdh1 and Trnp1, and their upregulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease.
Critical length scale controls adhesive wear mechanisms
Authors: Aghababaei Ramin , Warner Derek H. , Molinari Jean-Francois
Published: June 2016

The adhesive wear process remains one of the least understood areas of mechanics. While it has long been established that adhesive wear is a direct result of contacting surface asperities, an agreed upon understanding of how contacting asperities lead to wear debris particle has remained elusive. This has restricted adhesive wear prediction to empirical models with limited transferability. Here we show that discrepant observations and predictions of two distinct adhesive wear mechanisms can be reconciled into a unified framework. Using atomistic simulations with model interatomic potentials, we reveal a transition in the asperity wear mechanism when contact junctions fall below a critical length scale. A simple analytic model is formulated to predict the transition in both the simulation results and experiments. This new understanding may help expand use of computer modelling to explore adhesive wear processes and to advance physics-based wear laws without empirical coefficients.
Extensive sequencing of seven human genomes to characterize benchmark reference materials
Authors: Zook Justin M. , Catoe David , McDaniel Jennifer , Vang Lindsay , Spies Noah , Sidow Arend , Weng Ziming , Liu Yuling , Mason Christopher E. , Alexander Noah , Henaff Elizabeth , McIntyre Alexa B.R. , Chandramohan Dhruva , Chen Feng , Jaeger Erich , Moshrefi Ali , Pham Khoa , Stedman William , Liang Tiffany , Saghbini Michael , Dzakula Zeljko , Hastie Alex , Cao Han , Deikus Gintaras , Schadt Eric , Sebra Robert , Bashir Ali , Truty Rebecca M. , Chang Christopher C. , Gulbahce Natali , Zhao Keyan , Ghosh Srinka , Hyland Fiona , Fu Yutao , Chaisson Mark , Xiao Chunlin , Trow Jonathan , Sherry Stephen T. , Zaranek Alexander W. , Ball Madeleine , Bobe Jason , Estep Preston , Church George M. , Marks Patrick , Kyriazopoulou-Panagiotopoulou Sofia , Zheng Grace X.Y. , Schnall-Levin Michael , Ordonez Heather S. , Mudivarti Patrice A. , Giorda Kristina , Sheng Ying , Rypdal Karoline Bjarnesdatter , Salit Marc
Published: June 2016

The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry. The data come from 12 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCode WGS, and Illumina exome and WGS paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly.
Horizontal gene transfer events reshape the global landscape of arm race between viruses and homo sapiens
Authors: Chen Dong-Sheng , Wu Yi-Quan , Zhang Wei , Jiang San-Jie , Chen Shan-Ze
Published: June 2016

Horizontal gene transfer (HGT) drives the evolution of recipient organism particularly if it provides a novel function which enhances the fitness or its adaption to the environment. Virus-host co-evolution is attractive for studying co-evolutionary processes, since viruses strictly replicate inside of the host cells and thus their evolution is inexorably tangled with host biology. HGT, as a mechanism of co-evolution between human and viruses, has been widely documented, however, the roles HGT play during the interaction between human and viruses are still in their infancy. In this study, we performed a comprehensive analysis on the genes horizontally transferred between viruses and their corresponding human hosts. Our study suggests that the HGT genes in human are predominantly enriched in immune related GO terms while viral HGT genes are tend to be encoded by viruses which promote the invasion of immune system of hosts. Based on our results, it gives us a hint about the evolution trajectory of HGT events. Overall, our study suggests that the HGT between human and viruses are highly relevant to immune interaction and probably reshaped the arm race between hosts and viruses.
Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model
Authors: Mishra Vikas , Skotak Maciej , Schuetz Heather , Heller Abi , Haorah James , Chandra Namas
Published: June 2016

Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa.
Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury
Authors: Cocchiaro Pasquale , Fox Christopher , Tregidgo Nicholas W. , Howarth Rachel , Wood Katrina M. , Situmorang Gerhard R. , Pavone Luigi M. , Sheerin Neil S. , Moles Anna
Published: June 2016

Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases.
The second will be first: competition on directed networks
Authors: Cencetti Giulia , Bagnoli Franco , Di Patti Francesca , Fanelli Duccio
Published: June 2016

Multiple sinks competition is investigated for a walker diffusing on directed complex networks. The asymmetry of the imposed spatial support makes the system non transitive. As a consequence, it is always possible to identify a suitable location for the second absorbing sink that screens at most the flux of agents directed against the first trap, whose position has been preliminarily assigned. The degree of mutual competition between pairs of nodes is analytically quantified through apt indicators that build on the topological characteristics of the hosting graph. Moreover, the positioning of the second trap can be chosen so as to minimize, at the same time, the probability of being in turn shaded by a thirdly added trap. Supervised placing of absorbing traps on a asymmetric disordered and complex graph is hence possible, as follows a robust optimization protocol. This latter is here discussed and successfully tested against synthetic data.
IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy
Authors: Millar Neal L. , Akbar Moeed , Campbell Abigail L. , Reilly James H. , Kerr Shauna C. , McLean Michael , Frleta-Gilchrist Marina , Fazzi Umberto G. , Leach William J. , Rooney Brian P. , Crowe Lindsay A. N. , Murrell George A. C. , McInnes Iain B.
Published: June 2016

Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction.In vitroeffects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in ‘early tendinopathy’ compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders.
Sesterterpene ophiobolin biosynthesis involving multiple gene clusters in Aspergillus ustus
Authors: Chai Hangzhen , Yin Ru , Liu Yongfeng , Meng Huiying , Zhou Xianqiang , Zhou Guolin , Bi Xupeng , Yang Xue , Zhu Tonghan , Zhu Weiming , Deng Zixin , Hong Kui
Published: June 2016

Terpenoids are the most diverse and abundant natural products among which sesterterpenes account for less than 2%, with very few reports on their biosynthesis. Ophiobolins are tricyclic 5–8–5 ring sesterterpenes with potential pharmaceutical application. Aspergillus ustus 094102 from mangrove rizhosphere produces ophiobolin and other terpenes. We obtained five gene cluster knockout mutants, with altered ophiobolin yield using genome sequencing and in silico analysis, combined with in vivo genetic manipulation. Involvement of the five gene clusters in ophiobolin synthesis was confirmed by investigation of the five key terpene synthesis relevant enzymes in each gene cluster, either by gene deletion and complementation or in vitro verification of protein function. The results demonstrate that ophiobolin skeleton biosynthesis involves five gene clusters, which are responsible for C15, C20, C25, and C30 terpenoid biosynthesis.
Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure
Authors: Ohno Shoko , Yokoi Hideki , Mori Kiyoshi , Kasahara Masato , Kuwahara Koichiro , Fujikura Junji , Naito Masaki , Kuwabara Takashige , Imamaki Hirotaka , Ishii Akira , Saleem Moin A. , Numata Tomohiro , Mori Yasuo , Nakao Kazuwa , Yanagita Motoko , Mukoyama Masashi
Published: June 2016

Pharmacological blockade of the N- and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of α1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2−/− mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2−/− mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2+/+ mice. Interestingly, diabetic heterozygous Cav2.2+/− mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2+/+ mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by ω-conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-β (TGF-β) in podocytes was abolished with ω-conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes.
Mesoscopic bar magnet based on ε-Fe2O3 hard ferrite
Authors: Ohkoshi Shin-ichi , Namai Asuka , Yamaoka Takehiro , Yoshikiyo Marie , Imoto Kenta , Nasu Tomomichi , Anan Shizuka , Umeta Yoshikazu , Nakagawa Kosuke , Tokoro Hiroko
Published: June 2016

Ferrite magnets have a long history. They are used in motors, magnetic fluids, drug delivery systems, etc. Herein we report a mesoscopic ferrite bar magnet based on rod-shaped ε-Fe2O3with a large coercive field (>25 kOe). The ε-Fe2O3–based bar magnet is a single crystal with a single magnetic domain along the longitudinal direction. A wide frequency range spectroscopic study shows that the crystallographica-axis of ε-Fe2O3, which corresponds to the longitudinal direction of the bar magnet, plays an important role in linear and non-linear magneto-optical transitions, phonon modes and the magnon (Kittel mode). Due to its multiferroic property, a magnetic-responsive non-linear optical sheet is manufactured as an application using an ε-Fe2O3–based bar magnet, resin and polyethylene terephthalate. Furthermore, from the viewpoint of the large coercive field property, we demonstrate that a mesoscopic ε-Fe2O3bar magnet can be used as a magnetic force microscopy probe.
Germ cell specific overactivation of WNT/βcatenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development
Authors: Kumar Manish , Camlin Nicole J. , Holt Janet E. , Teixeira Jose M. , McLaughlin Eileen A. , Tanwar Pradeep S.
Published: June 2016

All the major components of the WNT signalling pathway are expressed in female germ cells and embryos. However, their functional relevance in oocyte biology is currently unclear. We examined ovaries collected from TCFGFP mice, a well-known Wnt reporter mouse model, and found dynamic changes in the Wnt/βcatenin signalling activity during different stages of oocyte development and maturation. To understand the functional importance of Wnt signalling in oocytes, we developed a mouse model with the germ cell-specific constitutive activation of βcatenin using cre recombinase driven by the DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1ex3cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1ex3cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/βcatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth.
Chromatographic analysis of Polygalae Radix by online hyphenating pressurized liquid extraction
Authors: Song Yuelin , Song Qingqing , Li Jun , Shi Shepo , Guo Liping , Zhao Yunfang , Jiang Yong , Tu Pengfei
Published: June 2016

Practicing “green analytical chemistry” is of great importance when profiling the chemical composition of complex matrices. Herein, a novel hybrid analytical platform was developed for direct chemical analysis of complex matrices by online hyphenating pressurized warm water extraction followed by turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry (PWWE-TFC-LC-MS/MS). Two parallel hollow guard columns acted as extraction vessels connected to a long narrow polyether ether ketone tube, while warm water served as extraction solvent and was delivered at a flow rate of 2.5 mL/min to generate considerable back pressure at either vessel. A column oven heated both the solvent and crude materials. A TFC column, which is advantageous for the comprehensive trapping of small molecular substances from fluids under turbulent flow conditions, was employed to transfer analytes from the PWWE module to LC-MS/MS. Two electronic valves alternated each vessel between extraction and elution phases. As a proof-of-concept, a famous herbal medicine for the treatment of neurodegenerative disorders, namely Polygalae Radix, was selected for the qualitative and quantitative analyses. The results suggest that the hybrid platform is advantageous in terms of decreasing time, material, and solvent consumption and in its automation, versatility, and environmental friendliness.
Universal amorphous-amorphous transition in GexSe100−x glasses under pressure
Authors: Yildirim Can , Micoulaut Matthieu , Boolchand Punit , Kantor Innokenty , Mathon Olivier , Gaspard Jean-Pierre , Irifune Tetsuo , Raty Jean-Yves
Published: June 2016

Pressure induced structural modifications in vitreous GexSe100−x (where 10 ≤ x ≤ 25) are investigated using X-ray absorption spectroscopy (XAS) along with supplementary X-ray diffraction (XRD) experiments and ab initio molecular dynamics (AIMD) simulations. Universal changes in distances and angle distributions are observed when scaled to reduced densities. All compositions are observed to remain amorphous under pressure values up to 42 GPa. The Ge-Se interatomic distances extracted from XAS data show a two-step response to the applied pressure; a gradual decrease followed by an increase at around 15–20 GPa, depending on the composition. This increase is attributed to the metallization event that can be traced with the red shift in Ge K edge energy which is also identified by the principal peak position of the structure factor. The densification mechanisms are studied in details by means of AIMD simulations and compared to the experimental results. The evolution of bond angle distributions, interatomic distances and coordination numbers are examined and lead to similar pressure-induced structural changes for any composition.
Novel Proton Conducting Solid Bio-polymer Electrolytes Based on Carboxymethyl Cellulose Doped with Oleic Acid and Plasticized with Glycerol
Authors: Chai M. N. , Isa M. I. N.
Published: June 2016

The plasticized solid bio-polymer electrolytes (SBEs) system has been formed by introducing glycerol (Gly) as the plasticizer into the carboxymethyl cellulose (CMC) doped with oleic acid (OA) via solution casting techniques. The ionic conductivity of the plasticized SBEs has been studied using Electrical Impedance Spectroscopy. The highest conductivity achieved is 1.64 × 10−4S cm−1for system containing 40 wt. % of glycerol. FTIR deconvolution technique had shown that the conductivity of CMC-OA-Gly SBEs is primarily influenced by the number density of mobile ions. Transference number measurement has shown that the cation diffusion coefficient and ionic mobility is higher than anion which proved the plasticized polymer system is a proton conductor.
Suppressing epileptic activity in a neural mass model using a closed-loop proportional-integral controller
Authors: Wang Junsong , Niebur Ernst , Hu Jinyu , Li Xiaoli
Published: June 2016

Closed-loop control is a promising deep brain stimulation (DBS) strategy that could be used to suppress high-amplitude epileptic activity. However, there are currently no analytical approaches to determine the stimulation parameters for effective and safe treatment protocols. Proportional-integral (PI) control is the most extensively used closed-loop control scheme in the field of control engineering because of its simple implementation and perfect performance. In this study, we took Jansen’s neural mass model (NMM) as a test bed to develop a PI-type closed-loop controller for suppressing epileptic activity. A graphical stability analysis method was employed to determine the stabilizing region of the PI controller in the control parameter space, which provided a theoretical guideline for the choice of the PI control parameters. Furthermore, we established the relationship between the parameters of the PI controller and the parameters of the NMM in the form of a stabilizing region, which provided insights into the mechanisms that may suppress epileptic activity in the NMM. The simulation results demonstrated the validity and effectiveness of the proposed closed-loop PI control scheme.
Optimal hash arrangement of tentacles in jellyfish
Authors: Okabe Takuya , Yoshimura Jin
Published: June 2016

At first glance, the trailing tentacles of a jellyfish appear to be randomly arranged. However, close examination of medusae has revealed that the arrangement and developmental order of the tentacles obey a mathematical rule. Here, we show that medusa jellyfish adopt the best strategy to achieve the most uniform distribution of a variable number of tentacles. The observed order of tentacles is a real-world example of an optimal hashing algorithm known as Fibonacci hashing in computer science.
Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study
Authors: Seo Hyeon , Kim Donghyeon , Jun Sung Chan
Published: June 2016

Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.
Identification and characterization of DcUCGalT1, a galactosyltransferase responsible for anthocyanin galactosylation in purple carrot (Daucus carota L.) taproots
Authors: Xu Zhi-Sheng , Ma Jing , Wang Feng , Ma Hong-Yu , Wang Qiu-Xia , Xiong Ai-Sheng
Published: June 2016

Purple carrots (Daucus carota ssp. sativus var. atrorubens Alef.) accumulate large amounts of cyanidin-based anthocyanins in their taproots. Cyanidin can be glycosylated with galactose, xylose and glucose in sequence by glycosyltransferases resulting in cyanidin 3-xylosyl (glucosyl) galactosides in purple carrots. The first step in the glycosylation of cyanidin is catalysis by UDP-galactose: cyanidin galactosyltransferase (UCGalT) transferring the galactosyl moiety from UDP-galactose to cyanidin. In the present study, a gene from ‘Deep purple’ carrot, DcUCGalT1, was cloned and heterologously expressed in E. coli BL21 (DE3). The recombinant DcUCGalT1 galactosylated cyanidin to produce cyanidin-3-O-galactoside and showed optimal activity for cyanidin at 30 °C and pH 8.6. It showed lower galactosylation activity for peonidin, pelargonidin, kaempferol and quercetin. It accepted only UDP-galactose as a glycosyl donor when cyanidin was used as an aglycone. The expression level of DcUCGalT1 was positively correlated with anthocyanin biosynthesis in carrots. The enzyme extractions from ‘Deep purple’ exhibited galactosylation activity for cyanidin, peonidin and pelargonidin, while those from ‘Kuroda’ (a non-purple cultivar) did not.
Tailoring the Microstructure of a Solid Oxide Fuel Cell Anode Support by Calcination and Milling of YSZ
Authors: Hanifi Amir Reza , Laguna-Bercero Miguel A. , Sandhu Navjot Kaur , Etsell Thomas H. , Sarkar Partha
Published: June 2016

In this study, the effects of calcination and milling of 8YSZ (8 mol% yttria stabilized zirconia) used in the nickel-YSZ anode on the performance of anode supported tubular fuel cells were investigated. For this purpose, two different types of cells were prepared based on a Ni-YSZ/YSZ/Nd2NiO4+δ-YSZ configuration. For the anode preparation, a suspension was prepared by mixing NiO and YSZ in a ratio of 65:35 wt% (Ni:YSZ 50:50 vol.%) with 30 vol.% graphite as the pore former. As received Tosoh YSZ or its calcined form (heated at 1500 °C for 3 hours) was used in the anode support as the YSZ source. Electrochemical results showed that optimization of the fuel electrode microstructure is essential for the optimal distribution of gas within the support of the cell, especially under electrolysis operation where the performance for an optimized cell (calcined YSZ) was enhanced by a factor of two. In comparison with a standard cell (containing as received YSZ), at 1.5 V and 800 °C the measured current density was −1380 mA cm−2 and −690 mA cm−2 for the cells containing calcined and as received YSZ, respectively. The present study suggests that the anode porosity for improved cell performance under SOEC is more critical than SOFC mode due to more complex gas diffusion under electrolysis mode where large amount of steam needs to be transfered into the cell.
Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China
Authors: Cui Hongrui , Shi Ying , Ruan Tao , Li Xuesong , Teng Qiaoyang , Chen Hongjun , Yang Jianmei , Liu Qinfang , Li Zejun
Published: June 2016

H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross-reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China.
Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells
Authors: Gaudreau Marie-Claude , Grapton Damien , Helness Anne , Vadnais Charles , Fraszczak Jennifer , Shooshtarizadeh Peiman , Wilhelm Brian , Robert François , Heyd Florian , Möröy Tarik
Published: June 2016

The proliferation and survival of hematopoietic stem cells (HSCs) has to be strictly coordinated to ensure the timely production of all blood cells. Here we report that the splice factor and RNA binding protein hnRNP L (heterogeneous nuclear ribonucleoprotein L) is required for hematopoiesis, since its genetic ablation in mice reduces almost all blood cell lineages and causes premature death of the animals. In agreement with this, we observed that hnRNP L deficient HSCs lack both the ability to self-renew and foster hematopoietic differentiation in transplanted hosts. They also display mitochondrial dysfunction, elevated levels of γH2AX, are Annexin V positive and incorporate propidium iodide indicating that they undergo cell death. Lin-c-Kit+ fetal liver cells from hnRNP L deficient mice show high p53 protein levels and up-regulation of p53 target genes. In addition, cells lacking hnRNP L up-regulated the expression of the death receptors TrailR2 and CD95/Fas and show Caspase-3, Caspase-8 and Parp cleavage. Treatment with the pan-caspase inhibitor Z-VAD-fmk, but not the deletion of p53, restored cell survival in hnRNP L deficient cells. Our data suggest that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways.
Virtual Planning, Control, and Machining for a Modular-Based Automated Factory Operation in an Augmented Reality Environment
Authors: Pai Yun Suen , Yap Hwa Jen , Md Dawal Siti Zawiah , Ramesh S. , Phoon Sin Ye
Published: June 2016

This study presents a modular-based implementation of augmented reality to provide an immersive experience in learning or teaching the planning phase, control system, and machining parameters of a fully automated work cell. The architecture of the system consists of three code modules that can operate independently or combined to create a complete system that is able to guide engineers from the layout planning phase to the prototyping of the final product. The layout planning module determines the best possible arrangement in a layout for the placement of various machines, in this case a conveyor belt for transportation, a robot arm for pick-and-place operations, and a computer numerical control milling machine to generate the final prototype. The robotic arm module simulates the pick-and-place operation offline from the conveyor belt to a computer numerical control (CNC) machine utilising collision detection and inverse kinematics. Finally, the CNC module performs virtual machining based on the Uniform Space Decomposition method and axis aligned bounding box collision detection. The conducted case study revealed that given the situation, a semi-circle shaped arrangement is desirable, whereas the pick-and-place system and the final generated G-code produced the highest deviation of 3.83 mm and 5.8 mm respectively.
Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1
Authors: Drmota Prebil Sara , Slapšak Urška , Pavšič Miha , Ilc Gregor , Puž Vid , de Almeida Ribeiro Euripedes , Anrather Dorothea , Hartl Markus , Backman Lars , Plavec Janez , Lenarčič Brigita , Djinović-Carugo Kristina
Published: June 2016

The activity of several cytosolic proteins critically depends on the concentration of calcium ions. One important intracellular calcium-sensing protein is α-actinin-1, the major actin crosslinking protein in focal adhesions and stress fibers. The actin crosslinking activity of α-actinin-1 has been proposed to be negatively regulated by calcium, but the underlying molecular mechanisms are poorly understood. To address this, we determined the first high-resolution NMR structure of its functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form. These structures reveal that in the absence of calcium, CaMD displays a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Mutagenesis experiments, coupled with mass-spectrometry and isothermal calorimetry data designed to validate the calcium binding stoichiometry and binding site, showed that human non-muscle α-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally, based on our structural data and analogy with other α-actinins, we provide a structural model of regulation of the actin crosslinking activity of α-actinin-1 where calcium induced structural stabilisation causes fastening of the juxtaposed actin binding domain, leading to impaired capacity to crosslink actin.
Transcriptional reprogramming and phenotypic switching associated with the adaptation of Lactobacillus plantarum C2 to plant niches
Authors: Filannino Pasquale , Di Cagno Raffaella , Crecchio Carmine , De Virgilio Caterina , De Angelis Maria , Gobbetti Marco
Published: June 2016

Lactobacillus plantarum has been isolated from a large variety of ecological niches, thus highlighting its remarkable environmental adaptability as a generalist. Plant fermentation conditions markedly affect the functional features of L. plantarum strains. We investigated the plant niche-specific traits of L. plantarum through whole-transcriptome and phenotypic microarray profiles. Carrot (CJ) and pineapple (PJ) juices were chosen as model systems and MRS broth was used as a control. A set of 3,122 genes was expressed and 21 to 31% of genes were differentially expressed depending on the plant niche and cell physiological state. L. plantarum C2 seemed to specifically respond to plant media conditions. When L. plantarum was cultured in CJ, useful pathways were activated, which were aimed to sense the environment, save energy and adopt alternative routes for NAD+ regeneration. In PJ the acidic environment caused a transcriptional switching, which was network-linked to an acid tolerance response involving carbohydrate flow, amino acid and protein metabolism, pH homeostasis and membrane fluidity. The most prominent phenotypic dissimilarities observed in cells grown in CJ and PJ were related to carbon and nitrogen metabolism, respectively. Summarising, a snapshot of a carrot and pineapple sensing and adaptive regulation model for L. plantarum C2 was proposed.
The alterations in the extracellular matrix composition guide the repair of damaged liver tissue
Authors: Klaas Mariliis , Kangur Triin , Viil Janeli , Mäemets-Allas Kristina , Minajeva Ave , Vadi Krista , Antsov Mikk , Lapidus Natalia , Järvekülg Martin , Jaks Viljar
Published: June 2016

While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue.
Photodynamic therapy inhibit Fibroblast Growth Factor-10 induced keratinocyte differentiation and proliferation through ROS in Fibroblast Growth Factor Receptor-2b pathway
Authors: Gozali Maya Valeska , Yi Fei , Zhang Jia-an , Liu Juan , Wu Hong-jin , Xu Yang , Luo Dan , Zhou Bing-rong
Published: June 2016

5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is known to be effective in several skin diseases such as acne, actinic keratoses, condyloma acuminata. However, some detailed mechanisms of ALA-PDT to treat these skin diseases still remain elusive. In this study, we aimed to investigate mechanism of ALA-PDT in in-vitro and in-vivo models. For in vitro, we use human keratinocyte cell line (HaCaT) cells. CCK-8 was used to detect cell proliferation activity, immunofluorescence and western blotting method to detect the content of keratin (K)1, K6, K16, protein kinase C (PKC), fibroblast growth factor receptor-2b (FGFR2b) protein, ELISA and RT-PCR to detect expression of interleukin (IL) 1α in the cell supernatant and detect reactive oxygen species (ROS). For in vivo, we use 20 rabbits to induce hyperkeratosis acne model in their ear. Dermatoscope was used to see follicle hyperkeratosis and skin biopsy to analyze histology and immunohistochemical of PKC, FGFR2b, K1, K6 and K16. Results from this study suggest that ROS stimulated by ALA-PDT lead to inhibition of FGFR2b pathway in PKC downstream to cause reduction of IL1α expression and eventually, keratinocytes differentiation and proliferation. Our data thus reveal a treatment mechanism of ALA-PDT underlying hyperkeratosis related dermatoses.
Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet α/β cell ratio and subsequent insulin secretion
Authors: Ramaswamy S. , Grace C. , Mattei A. A. , Siemienowicz K. , Brownlee W. , MacCallum J. , McNeilly A. S. , Duncan W. C. , Rae M. T.
Published: June 2016

Exogenous androgenic steroids applied to pregnant sheep programmes a PCOS-like phenotype in female offspring. Via ultrasound guidance we applied steroids directly to ovine fetuses at d62 and d82 of gestation and examined fetal (day 90 gestation) and postnatal (11 months old) pancreatic structure and function. Of three classes of steroid agonists applied (androgen - Testosterone propionate (TP), estrogen - Diethystilbesterol (DES) and glucocorticoid - Dexamethasone (DEX)), only androgens (TP) caused altered pancreatic development. Beta cell numbers were significantly elevated in prenatally androgenised female fetuses (P = 0.03) (to approximately the higher numbers found in male fetuses), whereas alpha cell counts were unaffected, precipitating decreased alpha:beta cell ratios in the developing fetal pancreas (P = 0.001), sustained into adolescence (P = 0.0004). In adolescence basal insulin secretion was significantly higher in female offspring from androgen-excess pregnancies (P = 0.045) and an exaggerated, hyperinsulinaemic response to glucose challenge (P = 0.0007) observed, whereas prenatal DES or DEX treatment had no effects upon insulin secretion. Postnatal insulin secretion correlated with beta cell numbers (P = 0.03). We conclude that the pancreas is a primary locus of androgenic stimulation during development, giving rise to postnatal offspring whose pancreas secreted excess insulin due to excess beta cells in the presence of a normal number of alpha cells.