bluuebunny/crossref_metadata_2025 huggingface dataset:
Medicinal chemistry of cannabinoids
Authors: Vemuri V Kiran , Makriyannis A
Published: March 2015

The endocannabinoid system comprises the two well characterized Gi/o‐protein coupled receptors (cannabinoid receptor 1 (CB1) and CB2), their endogenous lipid ligands, and the enzymes involved in their biosynthesis and biotransformation. Drug discovery efforts relating to the endocannabinoid system have been focused mainly on the two cannabinoid receptors and the two endocannabinoid deactivating enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). This review provides an overview of cannabinergic agents used in drug research and those being explored clinically.
Nanotubular Heterostructure of Tin Dioxide/Titanium Dioxide as a Binder‐Free Anode in Lithium‐Ion Batteries
Authors: Kim Myungjun , Lee Joobong , Lee Seonhee , Seo Seongrok , Bae Changdeuck , Shin Hyunjung
Published: March 2015

Titanium dioxide (TiO2), tin dioxide (SnO2), and heterostructured TiO2/SnO2 nanotube (NT) arrays have been fabricated by template‐assisted atomic‐layer deposition (ALD) for use as anodes in a lithium‐ion battery (LIB). TiO2 NT arrays with 8 nm thick walls showed higher capacity (≈250 mA h g−1 after the 50th cycle at a rate of C/10) than the typical theoretical capacity of bulk TiO2 and a radically improved capacity retention property upon cycling. SnO2 NT arrays with different wall thicknesses (8, 10, 13, and 20 nm) were also fabricated and their electrochemical performances were measured. All of the SnO2 NT arrays showed substantially higher initial irreversible capacity and higher reversible capacity than those of bulk TiO2. Thinner walls of the SnO2 NTs result in better capacity retention. Heterotubular structures of TiO2 (5 nm)/SnO2 (10 nm)/TiO2 (5 nm) were successfully fabricated, and displayed a sufficiently high capacity (≈300 mA h g−1 after 50 cycles) with exceptionally improved cycling performance up to the 50th cycle.
CXCR4 antagonist AMD3100 redistributes leukocytes from primary immune organs to secondary immune organs, lung, and blood in mice
Authors: Liu Qian , Li Zhanzhuo , Gao Ji‐Liang , Wan Wuzhou , Ganesan Sundar , McDermott David H. , Murphy Philip M.
Published: March 2015

AMD3100 (plerixafor), is a specific CXCR4 antagonist approved by the FDA for mobilizing hematopoietic stem cells from bone marrow to blood for transplantation in cancer. AMD3100 also mobilizes most mature leukocyte subsets to blood; however, their source and trafficking potential have not been fully delineated. Here, we show that a single injection of AMD3100 10 mg/kg into C57Bl/6 mice rapidly mobilizes (peak ∼ 2.5 h) the same leukocyte subsets to blood as in humans. Using this model, we found that AMD3100 mobilization of neutrophils, lymphocytes, and monocytes to blood is not reduced by splenectomy or by blockade of lymphocyte egress from lymph node with FTY720, but is coupled to (i) reduced content of each of these cell types in the bone marrow; (ii) reduced T‐cell numbers in thymuses; (iii) increased lymphocytes in lymph nodes; and (iv) increased neutrophil and monocyte content in the lung. Direct intrathymic labeling showed that AMD3100 selectively mobilizes naïve thymic CD4+ and CD8+ T cells to blood. Finally, AMD3100‐induced neutrophil mobilization to blood did not reduce neutrophil trafficking to thioglycollate‐inflamed peritoneum. Thus, AMD3100 redistributes lymphocytes, monocytes, and neutrophils from primary immune organs to secondary immune organs, peripheral tissues, and blood, without compromising neutrophil trafficking to inflamed sites.
Flux Crystal Growth of the Ternary Polygermanide LaPtGe2, a p‐Type Metal
Authors: Bugaris Daniel E. , Sturza Mihai , Han Fei , Im Jino , Chung Duck Young , Freeman Arthur J. , Kanatzidis Mercouri G.
Published: March 2015

Large plate crystals of LaPtGe2 have been grown by using an inert indium metal flux. This compound crystallizes in the CeNiSi2‐type structure (orthorhombic space group Cmcm) with lattice parameters a = 4.3770(9) Å, b = 17.186(3) Å, and c = 4.3942(9) Å. The structure of LaPtGe2 is a three‐dimensional framework with alternating PbO‐type layers of PtGe and infinite Ge chains, separated by La atoms. Electrical resistivity and Hall effect measurements characterize LaPtGe2 as a metal with holes that act as the charge carriers. Strong temperature dependence of the Hall coefficient and a violation of Kohler's rule (from magnetoresistance data) both indicate possible multiband effects. The electronic structure calculations suggest the metallic nature of LaPtGe2 and show that the strongest bonding exists between Pt and Ge within the PbO‐type layers.
Room‐Temperature Hydrogenation of Citral Catalyzed by Palladium–Silver Nanocrystals Supported on SnO2
Authors: Wang Shuo , Shen Rongan , Chen Zheng , Wang Jiaxi , Wang Dingsheng , Li Yadong
Published: March 2015

We have developed two strategies to optimize Pd catalysts. On one hand, Ag was introduced into Pd and then they were applied to the selective hydrogenation of citral under mild conditions. The addition of metallic Ag could tune the selectivity of Pd and made it suitable for the selective hydrogenation of the conjugated double bond. The selectivity of citronellal increased from 0 (for Pd/C and Pd0.7Ag0.3/C) to 96 % (for Pd0.4Ag0.6/C) as the Ag content increased. On the other hand, the addition of SnO2 made the Pd catalysts more inclined to activate the C=O bond and gave better performance for the hydrogenation of the conjugated double bond compared with the corresponding Pd–Ag catalysts. The selectivity of citronellal increased from 0 (for Pd0.7Ag0.3/C) to 76 % (for Pd0.7Ag0.3–SnO2/C was used) after the addition of SnO2. On the basis of these results, we developed a catalyst (Pd0.6Ag0.4–SnO2/C) with the best catalytic performance for the selective hydrogenation of citral (the conversion of citral reached 99 %, and the selectivity was up to 96 %).
Diterpenes with Unprecedented Skeletons from the Red Alga Sphaerococcus coronopifolius
Authors: Smyrniotopoulos Vangelis , Kiss Robert , Mathieu Véronique , Vagias Constantinos , Roussis Vassilios
Published: March 2015

Three previously unknown diterpenes – spirosphaerol (1), anthrasphaerol (2) and corfusphaeroxide (3) – have been isolated from the red alga Sphaerococcus coronopifolius. Their structures were elucidated by spectral analysis, including NMR and MS. The isolated metabolites were evaluated for their in vitro antitumour activities against one murine and five human cancer cell lines.
Affiliation‐seeking among the powerless: Lacking power increases social affiliative motivation
Authors: Case Charleen R. , Conlon Kyle E. , Maner Jon K.
Published: March 2015

Although it is well known that many people possess fundamental desires for both social affiliation and power, research has only begun to investigate the interplay between these two core social motives. The current research tested the hypothesis that an individual's level of power would influence that person's level of social affiliative motivation. We predicted that, compared with participants in a control condition, (1) individuals who possess power would exhibit less social affiliative motivation; and (2) individuals who lack power would display greater social affiliative motivation. Although we found little evidence to support the former prediction, we observed consistent evidence across two experiments that supported the latter. In Experiment 1, priming participants with low power (versus control) led them to display greater interest in joining a campus service aimed at fostering new friendships among students. In Experiment 2, placing participants in a position of low power (versus control) led them to seek greater proximity to a partner. Together, these results suggest that lacking power motivates people to seek social affiliation. Copyright © 2015 John Wiley & Sons, Ltd.
Detection of p53 Gene by Using Genomagnetic Assay Combined with Carbon Nanotube Modified Disposable Sensor Technology
Authors: Congur Gulsah , Plucnara Medard , Erdem Arzum , Fojta Miroslav
Published: March 2015

Electrochemical monitoring of DNA hybridization related to p53 gene sequence was investigated using genomagnetic assay combined with single walled carbon nanotube (SWCNT) modified pencil graphite electrodes (PGEs). The hybridization was performed either at magnetic beads (MB) surface or in solution. The enhanced guanine signal was obtained using SWCNT‐PGEs compared to one obtained by unmodified PGEs. The selectivity of genomagnetic assay was tested under optimum conditions. The DLs were calculated as 0.88 µM and 0.11 µM for hybridization performed at MB surface and solution, respectively. This selective, practical and cost effective genomagnetic assay combined with SWCNT‐PGEs is reported herein for the first time.
Bioreactors in tissue engineering: Advances in stem cell culture and three‐dimensional tissue constructs
Authors: Gelinsky Michael , Bernhardt Anne , Milan Falk
Published: March 2015

Bioreactors play an increasing role in tissue engineering—the generation of mammalian tissue equivalents in vitro. They can be applied for effective (stem) cell expansion, which is a crucial step concerning the fabrication of tissue engineering constructs of clinically relevant dimensions for which large cell numbers are needed. Furthermore, bioreactors are necessary for the maintenance of three‐dimensional (3D) tissue engineering constructs during cultivation ex vivo, and can be used to further stimulate the cells with a variety of physical cues. The development of novel bioreactor systems as well as mathematical modeling of their characteristics is a fast‐developing field of research. The present review provides a concise overview about recent developments in bioreactors for stem cell expansion, perfusion bioreactor systems for 3D cultures, and bioreactors for physical stimulation.
Climate change impacts on bedload transport in alpine drainage basins with hydropower exploitation
Authors: Raymond Pralong Mélanie , Turowski Jens Martin , Rickenmann Dieter , Zappa Massimiliano
Published: March 2015

Sediment transport is known to have a significant impact on hydropower infrastructures and changes in sediment transport rates are important for sediment management measures and hydroelectricity production. In this study, we present how climate change may affect bedload transport in 66 high alpine catchments used by hydropower companies in the Valais, Switzerland. Future sediment yield is estimated with a runoff‐based sediment transport model for the two future 30 year time periods 2021–2050 and 2070–2099. The analysis is integrated into a modelling chain in which error‐corrected and downscaled climate scenarios generated in the framework of the ENSEMBLES project are coupled to the hydrological model PREVAH, glacier retreat and bedload transport. To calibrate the sediment transport model, we used the observed sediment volumes in water intakes and reservoirs if such data were available. The results obtained show on average a decrease of sediment yield due to the reduced runoff generation during summer, especially for the scenario period 2070–2099. A shift of the seasonal sediment transport regime with a current maximum during July and August to earlier months in the year is predicted. Projections of future sediment yield rely on the accuracy of the individual modeling chain elements. The different sources of uncertainty are discussed qualitatively. Copyright © 2015 John Wiley & Sons, Ltd.
A self‐limiting bank erosion mechanism? inferring temporal variations in bank form and skin drag from high resolution topographic data
Authors: Leyland Julian , Darby Stephen E. , Teruggi Liliana , Rinaldi Massimo , Ostuni Daniele
Published: March 2015

Fluvial bank erosion rates are often quantified by assuming that the erosion rate is a function of the excess (above a critical threshold) boundary shear stress applied by the flow. Research has shown that the form roughness induced by natural topographic bank features, such as slumps, spurs and embayments, is the dominant component of the spatially‐averaged total shear stress, meaning that form roughness provides an important control on bank erosion rates. However, measuring the relative components of the total shear stress for a natural system is not straightforward. In this work we use the method of Kean and Smith to partition the form and skin drag components of river bank roughness using a time series (2005–2011) of high‐resolution topographic surveys of an eroding bank of the Cecina River in central Italy. This method approximates the form drag component of the roughness along a longitudinal bank profile as a series of user‐defined Gaussian curves. The extracted metrics are used in conjunction with an estimate of the outer region flow velocity to partition the form and skin drag components of the total boundary shear stress according to the Kean and Smith analytical solution. The relative magnitude of the form and skin shear stress at each survey date is analysed alongside DEMs of difference to reveal that intense episodes of erosion are followed by periods of quiescence. We show that this is due to the protection offered by increased form drag roughness following erosion. We conceptualise the dynamic feedbacks that exist between river discharge, bank erosion processes and bank form roughness, into a simple model of the self‐limiting nature of river bank erosion. Copyright © 2015 John Wiley & Sons, Ltd.
Pharmacologic heat shock protein 70 induction confers cytoprotection against inflammation in gliovascular cells
Authors: Kacimi Rachid , Yenari Midori A.
Published: March 2015

The inhibition of the 90‐kDa heat shock protein (HSP90) leads to upregulation of the 70‐kDa‐inducible HSP70. HSP70 has been previously shown to be neuroprotective and anti‐inflammatory. Geldanamycin (GA) and other HSP90 inhibitors have emerged as promising therapeutic agents in cancer, presumably owing to their ability to upregulate HSP70. However, the effects of HSP90 inhibition in brain inflammation are still unclear. We investigate the effect of a panel of HSP90 inhibitors on endotoxin‐activated microglia and eventual protection from brain‐derived endothelial cells. Prior studies have shown that GA protects brain cells from oxidative stress. We show here that when astrocytes or microglial BV2 cells were pretreated with GA or other HSP90 inhibitors, endotoxin‐induced cell death was reduced in cocultures of BV2 microglia and brain‐derived endothelial cells (bEND.3). Endotoxin‐stimulated BV2 cells led to increased nitric oxide (NO) and inducible nitric oxide synthase which was prevented by treatment with all HSP90 inhibitors. HSP90 inhibitors also prevented lipopolysaccharide (LPS)‐induced BV2 cell death. We also found that HSP90 inhibition blocked nuclear translocation of nuclear factor kappa B and attenuated IκBα degradation, and inhibited LPS‐activated JAK‐STAT phosphorylation. We show that pharmacologic inhibition of HSP90 with subsequent HSP70 induction protects cells that comprise the cerebral vasculature against cell death owing to proinflammatory stimuli. This approach may have therapeutic potential in neurological conditions with an inflammatory component. GLIA 2015;63:1200–1212
Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B
Authors: Jiang De‐Ke , Ma Xiao‐Pin , Yu Hongjie , Cao Guangwen , Ding Dong‐Lin , Chen Haitao , Huang Hui‐Xing , Gao Yu‐Zhen , Wu Xiao‐Pan , Long Xi‐Dai , Zhang Hongxing , Zhang Youjie , Gao Yong , Chen Tao‐Yang , Ren Wei‐Hua , Zhang Pengyin , Shi Zhuqing , Jiang Wei , Wan Bo , Saiyin Hexige , Yin Jianhua , Zhou Yuan‐Feng , Zhai Yun , Lu Pei‐Xin , Zhang Hongwei , Gu Xiaoli , Tan Aihua , Wang Jin‐Bing , Zuo Xian‐Bo , Sun Liang‐Dan , Liu Jun O. , Yi Qing , Mo Zengnan , Zhou Gangqiao , Liu Ying , Sun Jielin , Shugart Yin Yao , Zheng S. Lilly , Zhang Xue‐Jun , Xu Jianfeng , Yu Long
Published: March 2015

Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome‐wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two‐stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], P
meta=1.28 × 10−34; and rs422951 [T320A] in NOTCH4, P
meta = 5.33 × 10−16); one synonymous variant (rs378352 in HLA‐DOA corresponding to HLA‐DOA*010101, P
meta = 1.04 × 10−23); and one noncoding variant (rs2853953 near HLA‐C, P
meta = 5.06 × 10−20). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, P
meta = 2.95 × 10−15). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA‐C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA‐DQB1, rs7453920 at HLA‐DQB2, rs3077 at HLA‐DPA1, and rs9277535 at HLA‐DPA2, which are all located in the HLA region, 9.84 × 10−71 ≤ P
meta ≤ 9.92 × 10−7). Conclusion: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease. (Hepatology 2015;62:118‐128)
Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts
Authors: Kogan Natalya M , Melamed Eitan , Wasserman Elad , Raphael Bitya , Breuer Aviva , Stok Kathryn S , Sondergaard Rachel , Escudero Ana VVillarreal , Baraghithy Saja , Attar-Namdar Malka , Friedlander-Barenboim Silvina , Mathavan Neashan , Isaksson Hanna , Mechoulam Raphael , Müller Ralph , Bajayo Alon , Gabet Yankel , Bab Itai
Published: March 2015

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ9-tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro–computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes. © 2015 American Society for Bone and Mineral Research.
Mechanisms Regulating Acquisition of Platelet‐Derived Factor V/Va by Megakaryocytes
Authors: Gertz Jacqueline M. , Bouchard Beth A.
Published: March 2015

Factor Va serves as the nonenzymatic protein cofactor for the prothrombinase complex, which converts prothrombin to thrombin in the events leading to formation of a hemostatic plug. Several observations support the concept that platelet‐derived factor V/Va is physically and functionally distinct and plays a more important role in thrombin generation at sites of vascular injury as compared to its plasma counterpart. Platelet‐derived factor V/Va is generated following endocytosis of the plasma‐derived molecule by the platelet precursor cells, megakaryocytes, via a two receptor system consisting of low density lipoprotein (LDL) receptor‐related protein‐1 (LRP‐1) and an unidentified specific “binding site”. More recently, it was suggested that a cell surface‐expressed β‐galactoside binding protein, galectin‐8, was involved in factor V endocytosis. Endocytosed factor V is trafficked through the cell and retailored prior to its storage in α‐granules. Given the essential role of platelet‐derived factor Va in clot formation, understanding the cellular and molecular mechanisms that regulate how platelets acquire this molecule will be important for the treatment of excessive bleeding or clotting. J. Cell. Biochem. 116: 2121–2126, 2015. © 2015 Wiley Periodicals, Inc.
Deimination level and peptidyl arginine deiminase 2 expression are elevated in astrocytes with increased incubation temperature
Authors: Enriquez‐Algeciras Mabel , Bhattacharya Sanjoy K. , Serra Horacio M.
Published: March 2015

Astrocytes respond to environmental cues, including changes in temperatures. Increased deimination, observed in many progressive neurological diseases, is thought to be contributed by astrocytes. We determined the level of deimination and expression of peptidyl arginine deiminase 2 (PAD2) in isolated primary astrocytes in response to changes on either side (31°C and 41°C) of the optimal temperature (37°C). We investigated changes in the astrocytes by using a number of established markers and accounted for cell death with the CellTiter‐Blue assay. We found increased expression of glial fibrillary acidic protein, ALDH1L1, and J1‐31, resulting from increased incubation temperature and increased expression of TSP1, S100β, and AQP4, resulting from decreased incubation temperature vs. optimal temperature, suggesting activation of different biochemical pathways in astrocytes associated with different incubation temperatures. Mass spectrometric analyses support such trends. The PAD2 level was increased only as a result of increased incubation temperature with a commensurate increased level of deimination. Actin cytoskeleton and iso[4]LGE, a lipid peroxidase modification, also showed an increase with higher incubation temperature. Altogether, these results suggest that temperature, as an environmental cue, activates astrocytes in a different manner on either side of the optimal temperature and that increase in deimination is associated only with the higher temperature side of the spectrum. © 2015 Wiley Periodicals, Inc.
Patterns of structural and sequence variation within isotype lineages of the Neisseria meningitidis transferrin receptor system
Authors: Adamiak Paul , Calmettes Charles , Moraes Trevor F. , Schryvers Anthony B.
Published: March 2015

Neisseria meningitidis inhabits the human upper respiratory tract and is an important cause of sepsis and meningitis. A surface receptor comprised of transferrin‐binding proteins A and B (TbpA and TbpB), is responsible for acquiring iron from host transferrin. Sequence and immunological diversity divides TbpBs into two distinct lineages; isotype I and isotype II. Two representative isotype I and II strains, B16B6 and M982, differ in their dependence on TbpB for in vitro growth on exogenous transferrin. The crystal structure of TbpB and a structural model for TbpA from the representative isotype I N. meningitidis strain B16B6 were obtained. The structures were integrated with a comprehensive analysis of the sequence diversity of these proteins to probe for potential functional differences. A distinct isotype I TbpA was identified that co‐varied with TbpB and lacked sequence in the region for the loop 3 α‐helix that is proposed to be involved in iron removal from transferrin. The tightly associated isotype I TbpBs had a distinct anchor peptide region, a distinct, smaller linker region between the lobes and lacked the large loops in the isotype II C‐lobe. Sequences of the intact TbpB, the TbpB N‐lobe, the TbpB C‐lobe, and TbpA were subjected to phylogenetic analyses. The phylogenetic clustering of TbpA and the TbpB C‐lobe were similar with two main branches comprising the isotype 1 and isotype 2 TbpBs, possibly suggesting an association between TbpA and the TbpB C‐lobe. The intact TbpB and TbpB N‐lobe had 4 main branches, one consisting of the isotype 1 TbpBs. One isotype 2 TbpB cluster appeared to consist of isotype 1 N‐lobe sequences and isotype 2 C‐lobe sequences, indicating the swapping of N‐lobes and C‐lobes. Our findings should inform future studies on the interaction between TbpB and TbpA and the process of iron acquisition.
On the microphysical effects of observed cloud edge charging
Authors: Harrison R. G. , Nicoll K. A. , Ambaum M. H. P.
Published: March 2015

Liquid layer clouds are abundant globally. Lacking strong convection, they do not become electrified by the usual thunderstorm mechanisms of collisional electrification between hydrometeors of different phases. Instead, the background global circuit current flow in fair weather is largely unaffected by the layer cloud's presence, and, if the layer cloud is extensive horizontally, the vertical fair weather conduction current passes through the cloud. A consequence of the vertical current flow is that, at the cloud–air boundary where there is a conductivity transition and droplets form or evaporate, droplet charging occurs. Charge can affect both droplet evaporation and droplet–droplet collisions. Using new radiosonde instrumentation, the charge observed at layer cloud edges is evaluated for both these microphysical droplet processes. This shows that the charging is more likely to affect collision processes than activation, for small droplets. Enhancing the collection efficiency of small droplets modifies their evolution and propagates through the size distribution to shorten the autoconversion time‐scale to rain drops, and the cloud radiative properties. Because the conduction current density is influenced by both external (e.g. solar modulation of high‐energy particles) and internal (e.g. El Niño–Southern Oscillation) factors, current flow leading to layer cloud edge charging provides a possible route for expressing solar influences on the climate system and a teleconnection mechanism for communicating internal climate variability.
Bias in estimating the causal hazard ratio when using two‐stage instrumental variable methods
Authors: Wan Fei , Small Dylan , Bekelman Justin E. , Mitra Nandita
Published: March 2015

Two‐stage instrumental variable methods are commonly used to estimate the causal effects of treatments on survival in the presence of measured and unmeasured confounding. Two‐stage residual inclusion (2SRI) has been the method of choice over two‐stage predictor substitution (2SPS) in clinical studies. We directly compare the bias in the causal hazard ratio estimated by these two methods. Under a principal stratification framework, we derive a closed‐form solution for asymptotic bias of the causal hazard ratio among compliers for both the 2SPS and 2SRI methods when survival time follows the Weibull distribution with random censoring. When there is no unmeasured confounding and no always takers, our analytic results show that 2SRI is generally asymptotically unbiased, but 2SPS is not. However, when there is substantial unmeasured confounding, 2SPS performs better than 2SRI with respect to bias under certain scenarios. We use extensive simulation studies to confirm the analytic results from our closed‐form solutions. We apply these two methods to prostate cancer treatment data from Surveillance, Epidemiology and End Results‐Medicare and compare these 2SRI and 2SPS estimates with results from two published randomized trials. Copyright © 2015 John Wiley & Sons, Ltd.
Deconstruction of DNA Methylation Patterns During Myogenesis Reveals Specific Epigenetic Events in the Establishment of the Skeletal Muscle Lineage
Authors: carrió Elvira , Díez-Villanueva Anna , Lois Sergi , Mallona Izaskun , Cases Ildefonso , Forn Marta , Peinado Miguel A. , Suelves Mònica
Published: March 2015

The progressive restriction of differentiation potential from pluripotent embryonic stem cells (ESCs) to tissue-specific stem cells involves widespread epigenetic reprogramming, including modulation of DNA methylation patterns. Skeletal muscle stem cells are required for the growth, maintenance, and regeneration of skeletal muscle. To investigate the contribution of DNA methylation to the establishment of the myogenic program, we analyzed ESCs, skeletal muscle stem cells in proliferating (myoblasts) and differentiating conditions (myotubes), and mature myofibers. About 1.000 differentially methylated regions were identified during muscle-lineage determination and terminal differentiation, mainly located in gene bodies and intergenic regions. As a whole, myogenic stem cells showed a gain of DNA methylation, while muscle differentiation was accompanied by loss of DNA methylation in CpG-poor regions. Notably, the hypomethylated regions in myogenic stem cells were neighbored by enhancer-type chromatin, suggesting the involvement of DNA methylation in the regulation of cell-type specific enhancers. Interestingly, we demonstrated the hypomethylation of the muscle cell-identity Myf5 super-enhancer only in muscle cells. Furthermore, we observed that upstream stimulatory factor 1 binding to Myf5 super-enhancer occurs upon DNA demethylation in myogenic stem cells. Taken altogether, we characterized the unique DNA methylation signature of skeletal muscle stem cells and highlighted the importance of DNA methylation-mediated regulation of cell identity Myf5 super-enhancer during cellular differentiation. Stem Cells  2015;33:2025–2036
Multipotent Glia-Like Stem Cells Mediate Stress Adaptation
Authors: Rubin de Celis Maria F. , Garcia-Martin Ruben , Wittig Dierk , Valencia Gabriela D. , Enikolopov Grigori , Funk Richard H. , Chavakis Triantafyllos , Bornstein Stefan R. , Androutsellis-Theotokis Andreas , Ehrhart-Bornstein Monika
Published: March 2015

The neural crest-derived adrenal medulla is closely related to the sympathetic nervous system; however, unlike neural tissue, it is characterized by high plasticity which suggests the involvement of stem cells. Here, we show that a defined pool of glia-like nestin–expressing progenitor cells in the adult adrenal medulla contributes to this plasticity. These glia-like cells have features of adrenomedullary sustentacular cells, are multipotent, and are able to differentiate into chromaffin cells and neurons. The adrenal is central to the body's response to stress making its proper adaptation critical to maintaining homeostasis. Our results from stress experiments in vivo show the activation and differentiation of these progenitors into new chromaffin cells. In summary, we demonstrate the involvement of a new glia-like multipotent stem cell population in adrenal tissue adaptation. Our data also suggest the contribution of stem and progenitor cells in the adaptation of neuroendocrine tissue function in general. Stem Cells  2015;33:2037–2051
Assessing and generating test sets in terms of behavioural adequacy
Authors: Fraser Gordon , Walkinshaw Neil
Published: March 2015

Identifying a finite test set that adequately captures the essential behaviour of a program such that all faults are identified is a well‐established problem. This is traditionally addressed with syntactic adequacy metrics (e.g. branch coverage), but these can be impractical and may be misleading even if they are satisfied. One intuitive notion of adequacy, which has been discussed in theoretical terms over the past three decades, is the idea of behavioural coverage: If it is possible to infer an accurate model of a system from its test executions, then the test set can be deemed to be adequate. Despite its intuitive basis, it has remained almost entirely in the theoretical domain because inferred models have been expected to be exact (generally an infeasible task) and have not allowed for any pragmatic interim measures of adequacy to guide test set generation. This paper presents a practical approach to incorporate behavioural coverage. Our BESTEST approach (1) enables the use of machine learning algorithms to augment standard syntactic testing approaches and (2) shows how search‐based testing techniques can be applied to generate test sets with respect to this criterion. An empirical study on a selection of Java units demonstrates that test sets with higher behavioural coverage significantly outperform current baseline test criteria in terms of detected faults. © 2015 The Authors. Software Testing, Verification and Reliability published by John Wiley & Sons, Ltd.
Testing the impact of at‐source stormwater management on urban flooding through a coupling of network and overland flow models
Authors: Burns Matthew J. , Schubert Jochen E. , Fletcher Tim D. , Sanders Brett F.
Published: March 2015

In many urban catchments, stormwater flooding is a serious problem. Low‐impact development and the use of stormwater control measures (SCMs) have the potential to mitigate such flooding, but this potential is highly context specific and remains largely untested. In this study, we tested the potential of SCMs to impact stormwater flooding in a peri‐urban catchment by coupling a one‐dimensional 1D stormwater drainage model with a two‐dimensional (2D) overland flow model. We predicted consequent flood dynamics for a range of storm events and management scenarios. We found that realistically extensive application of rain tanks and infiltration trenches is most effective in mitigating stormwater flooding for common‐to‐rare storm events [5‐ to 20‐year annual recurrence interval (ARI)] with short durations, such that the events have rainfall depths that are similar to the retention (or storage) capacity of commonly used small‐scale SCMs. Retention of stormwater also has the ability to mitigate overland flow intensity, positively impacting pedestrian safety and reducing potential building damage for rare events with ARIs above 20 years. In addition, SCMs also provide benefits to alternative options such as pipe upgrades, through their protection of receiving waters and enhancement of urban landscape amenity. WIREs Water 2015, 2:291–300. doi: 10.1002/wat2.1078

This article is categorized under:

Engineering Water > Sustainable Engineering of Water

Science of Water > Water Extremes
Crystal Structure of a Commercial Product Called Lead Cyanurate
Authors: Dolabdjian Konstantin , Ströbele Markus , Meyer H.‐Jürgen
Published: March 2015

The reaction of PbO with cyanuric acid was reported to give lead cyanurate, described in the literature as Pb3(O3C3N3)2·2H2O. Crystalline powders were prepared and investigated by X‐ray powder diffraction, yielding a monoclinic crystal structure (space group Cc, a = 16.6217(1) Å, b = 6.7161(1) Å, c = 12.4308(1) Å, β = 117.567(1)°). The structure solution and refinement yielded lead oxide isocyanurate corresponding to the formula Pb3O2(O3C3N3H2)2, with a layered arrangement of [Pb3O2]2+ ions and monovalent isocyanurate anions in an alternating fashion.
Ice Hockey Summit II: Zero Tolerance for Head Hits and Fighting
Authors: Smith Aynsley M. , Stuart Michael J. , Dodick David W. , Roberts William O. , Alford Patrick W. , Ashare Alan B. , Aubrey Mark , Benson Brian W. , Burke Chip J. , Dick Randall , Eickhoff Chad , Emery Carolyn A. , Flashman Laura A. , Gaz Daniel V. , Giza Chris C. , Greenwald Richard M. , Herring Stanley A. , Hoshizaki T. Blaine , Hudziak James J. , Huston John , Krause David , LaVoi Nicole , Leaf Matt , Leddy John J. , MacPherson Allison , McKee Ann C. , Mihalik Jason P. , Moessner Anne M. , Montelpare William J. , Putukian Margot , Schneider Kathryn J. , Szalkowski Ron , Tabrum Mark , Whitehead James R. , Wiese‐Bjornstal Diane M.
Published: March 2015

Objective

To present currently known basic science and on‐ice influences of sport related concussion (SRC) in hockey, building upon the Ice Hockey Summit I action plan (2011) to reduce SRC.

Methods

The prior summit proceedings included an action plan intended to reduce SRC. As such, the proceedings from Summit I served as a point of departure, for the science and discussion held during Summit II (Mayo Clinic, Rochester MN, October, 2013). Summit II focused on Basic Science of Concussions in Ice Hockey: Taking Science Forward; (2) Acute and Chronic Concussion Care: Making a Difference; (3) Preventing Concussions via Behavior, Rules, Education and Measuring Effectiveness; (4) Updates in Equipment: their Relationship to Industry Standards and (5) Policies and Plans at State, National and Federal Levels to reduce SRC. Action strategies derived from the presentations and discussion described in these sectors were subsequently voted on for purposes of prioritization. The following proceedings include the knowledge and research shared by invited faculty, many of whom are health care providers and clinical investigators.

Results

The Summit II evidence based action plan emphasizes the rapidly evolving scientific content of hockey SRC. It includes the most highly prioritized strategies voted on for implementation to decrease concussion.

Conclusions

The highest priority action items identified from the Summit include: 1) eliminate head hits from all levels of ice hockey, 2) change body checking policies, and 3) eliminate fighting in all amateur and professional hockey.
“Rule of Law” in a Party-State: A Conceptual Interpretive Framework of the Constitutional Reality of China
Authors: LI Ling
Published: March 2015

This article identifies and conceptualizes the structural features of the Party-state and proposes a “dual normative system” as a framework to interpret the constitutional reality of China. This framework has four components: (1) structural integration of the Chinese Communist Party (CCP or the Party) and the state; (2) reserved delegation of authority to the state; (3) bifurcation of state decision-making processes; and (4) cohabitation of the two normative systems: one of the Party and one of the state. This article demonstrates that the political reforms in China since the 1980s have not separated the power of the Party and the state, but have created an increasingly institutionalized dual normative system that is more complex compared with the previous fused system, yet more pliable to adjustments and more open to different interpretations, including to that of the “Party-state constitutionalism”, which interprets the “rule of law” as compatible with the rule of the Party.
“Johns” in the Spotlight: Anti-prostitution Efforts and the Surveillance of Clients
Authors: Khan Ummni
Published: March 2015

This essay examines surveillant practices that subject sex trade clients (“clients”) to socio-legal control. In particular, I employ the concepts of the gaze, voyeurism, and exhibitionism to unpack the surveillant dynamics, and consider how power and pleasure are harnessed, produced, and thwarted in the increasing scrutiny of the sex trade’s demand side. I further examine my own research of the regulation of clients within this analytical framework. Following David Lyon’s insights on the scopophilic dimensions of surveillance (2006), I argue that the instrumental goals of surveillance are interconnected with a voyeurism that gratifies the pleasures of looking at, categorizing, defining and making sense of, clients. Yet, bearing in mind the multi-directionality of the gaze, I also analyze the controlled exhibition of sex work signifiers, as information is not just gathered, but also displayed and performed.
Early Neolithic Trackways in the Thames Floodplain at Belmarsh, London Borough of Greenwich
Authors: Hart Diccon ,   with contributions by, Allott Lucy , Bamforth Michael , Bates Martin , Jones Sarah , Marshall Peter , Walker Mike , Weisskopf Alison
Published: March 2015

Excavations in 2008 on the site of a proposed new prison at Belmarsh West, London Borough of Greenwich, found the heavily decayed remains of two superimposed Early Neolithic trackways. These structures, which are radiocarbon dated to the first quarter of the 4th millennium calBCcomprise some of the earliest structures yet encountered in the London Basin. The trackways were found towards the base of a peat sequence, immediately above the underlying Devensian gravels. The associated palaeoenvironmental record suggests that they were constructed in response to rising base levels, within a local floodplain environment dominated by alder carr, in order to maintain mobility across an expanding wetland landscape. The archaeological and geomorphological background to the excavations and a description of the results of the excavations are presented, with a particular emphasis on the Neolithic structures. The significance and wider context of the structures are examined through a consideration of their construction, wider palaeoenvironmental context, and the ways in which the structures can shed light on the nature of Early Neolithic subsistence strategies and land-use within the Thames floodplain.
Making Merit: The Indian Institutes of Technology and the Social Life of Caste
Authors: Subramanian Ajantha
Published: March 2015

The politics of meritocracy at the Indian Institutes of Technology illuminates the social life of caste in contemporary India. I argue that the IIT graduate's status depends on the transformation of privilege into merit, or the conversion of caste capital into modern capital. Analysis of this process calls for a relational approach to merit. My ethnographic research on the southeastern state of Tamilnadu, and on IIT Madras located in the state capital of Chennai, illuminates claims to merit, not simply as the transformation of capital but also as responses to subaltern assertion. Analyzing meritocracy in relation to subaltern politics allows us to see the contextual specificity of such claims: at one moment, they are articulated through the disavowal of caste, at another, through caste affiliation. This marking and unmarking of caste suggests a rethinking of meritocracy, typically assumed to be a modernist ideal that disclaims social embeddedness and disdains the particularisms of caste and race. I show instead that claims to collective belonging and to merit are eminently commensurable, and become more so when subaltern assertion forces privilege into the foreground. Rather than the progressive erasure of ascribed identities in favor of putatively universal ones, we are witnessing the re-articulation of caste as an explicit basis for merit and the generation of newly consolidated forms of upper-casteness.
The “Criminal Tribe” in India before the British
Authors: Piliavsky Anastasia
Published: March 2015

This paper challenges the broad consensus in current historiography that holds the Indian stereotype of criminal tribe to be a myth of colonial making. Drawing on a selection of precolonial descriptions of robber castes—ancient legal texts and folktales; Jain, Buddhist and Brahmanic narratives; Mughal sources; and Early Modern European travel accounts—I show that the idea of castes of congenital robbers was not a British import, but instead a label of much older vintage on the subcontinent. Enjoying pride of place in the postcolonial critics' pageant of “colonial stereotypes,” the case of criminal tribes is representative and it bears on broader questions about colonial knowledge and its relation to power. The study contributes to the literature that challenges the still widespread tendency to view colonial social categories, and indeed the bulk of colonial knowledge, as the imaginative residue of imperial politics. I argue that while colonialusesof the idea of a criminal tribe comprises a lurid history of violence against communities branded as born criminals in British law, the stereotype itself has indigenous roots. The case is representative and it bears on larger problems of method and analysis in “post-Orientalist” historiography.
Nationality Medicines in China: Institutional Rationality and Healing Charisma
Authors: Lai Lili , Farquhar Judith
Published: March 2015

This article describes emergent Chinese regimes of knowledge about “minority nationality medicines.” We adopt Weberian terms of rational and charismatic authority to better understand ethnic healing as it is developing among minorities in southwestern China. In the course of uneven development among diverse ethnic groups over recent decades, modern information regimes and institutional models have started to transform the many forms of healing and heritage that can be found “on the ground” in minority areas. We delineate a shifting border between official (or rational) and wild (or charismatic) forms of medicine, and argue that every healing situation results from a dynamic and sometimes destructive relation between these forms of authority. We draw from research conducted among seven minority nationalities scattered in five provinces in China's south and southwest. After an overview of relevant scholarly work that circulates nationally, we discuss views and practices of three healers belonging to Zhuang, Tujia, and Yao groups, respectively. Ultimately we suggest that all healing, including that taking place in biomedical clinics, relies on some contact with “the wild,” and forges a relationship between rationality and charisma.
Low temperature photoionized Ne plasmas induced by laser-plasma EUV sources
Authors: Bartnik A. , Fiedorowicz H. , Fok T. , Jarocki R. , Szczurek M. , Wachulak P.
Published: March 2015

In this work, two laser-produced plasma (LPP) sources – extreme ultraviolet (EUV) and a LPP soft X-ray (SXR) source were used to create Ne photoionized plasmas. A radiation beam was focused onto a gas stream, injected into a vacuum chamber synchronously with the radiation pulse. EUV radiation spanned a wide spectral range with pronounced maximum centered at λ≈11 nm, while in case of the SXR source spectral maximum was at λ≈1.4 nm. Emission spectra of photoionized plasmas created this way were measured in a wide spectral range λ = 10–100 nm. The dominating spectral lines originated from singly charged ions (Ne II) and neutral atoms (Ne I). For the highest radiation fluence, spectral lines originating from Ne III and even Ne IV species were detected. Differences between the experimental spectra, obtained for all irradiation conditions, were analyzed. They were attributed either to different fluence or spectral distribution of driving photons.
Suppression of stimulated rotational Raman scattering over long air paths via controlling the polarization state
Authors: Feng B. , Fan X.M. , Lu Z.W. , Lin D.Y. , Yang F. , Wang Y.L.
Published: March 2015

Stimulated rotational Raman scattering (SRRS) limits the effective transmission distances of the high-energy and high-power laser pulses in laser–fusion systems and other applications. A simple and practical method of suppressing SRRS process by controlling the polarization direction of Stokes light is proposed. For a narrowband, linearly polarized, flat-topped laser pulse of 351 nm with intensity of 2 GW/cm2 and width of 3 ns, the SRRS threshold distance in air is lengthened to 30.0 m from 16.2 m easily using the method. Simulation results demonstrate that the method is also applicable for broadband laser.