bluuebunny/crossref_metadata_2025 huggingface dataset:
Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy
Authors: Tsutsui Yuko , Deredge Daniel , Wintrode Patrick L. , Hays Franklin A.
Published: August 2016

Imatinib (Gleevec), a non-receptor tyrosine kinase inhibitor (nRTKI), is one of the most successful anti-neoplastic drugs in clinical use. However, imatinib-resistant mutations are increasingly prevalent in patient tissues and driving development of novel imatinib analogs. We present a detailed study of the conformational dynamics, in the presence and absence of bound imatinib, for full-length human c-Src using hydrogen-deuterium exchange and mass spectrometry. Our results demonstrate that imatinib binding to the kinase domain effects dynamics of proline-rich or phosphorylated peptide ligand binding sites in distal c-Src SH3 and SH2 domains. These dynamic changes in functional regulatory sites, distal to the imatinib binding pocket, show similarities to structural transitions involved in kinase activation. These data also identify imatinib-sensitive and imatinib-resistant, mutation sites. Thus, the current study identifies novel c-Src allosteric sites associated with imatinib binding and kinase activation and provide a framework for follow-on development of TKI binding modulators.
Small Molecular-Sized Artesunate Attenuates Ocular Neovascularization via VEGFR2, PKCα and PDGFR Targets
Authors: Zong Yao , Yuan Yongguang , Qian Xiaobing , Huang Zhen , Yang Wei , Lin Leilei , Zheng Qishan , Li Yujie , He Huining , Gao Qianying
Published: August 2016

Ocular neovascularization (NV) is the primary cause of blindness in many ocular diseases. Large molecular weight anti- vascular endothelial growth factor (VEGF) protein drugs, such as Avastin and Lucentis, have saved the vision of millions. However, approximately 20–30% of patients respond poorly to anti-VEGF treatment. We found that artesunate (ART), a small molecular derivative of artemisinin, had a significant inhibitory effect on ocular NV by downregulating the expression of VEGFR2, PKCα and PDGFR. ART significantly inhibited retinal NV in rabbits and macular edema in monkeys with greater anterior chamber penetrability and more durable efficacy than Avastin. Our pilot study showed that intravitreal injection of 80 μg ART significantly inhibited iris and corneal NV in a severe retinal detachment case. Our results suggest that ART might be a potential persistent small-molecule drug to manage ocular NV via multi-targets.
Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy
Authors: López-Ozuna Vanessa M. , Hachim Ibrahim Y. , Hachim Mahmood Y. , Lebrun Jean-Jacques , Ali Suhad
Published: August 2016

Triple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) and its signaling pathway serve as a sub-classifier and predictor of pro-differentiation therapy in TNBC. Using immunohistochemistry and various gene expression in silica analyses we observed that prolactin receptor (PRLR) protein and mRNA levels are down regulated in TNBC cases. In addition, examining correlation of PRLR gene expression with metagenes of TNBC subtypes (580 cases), we found that PRLR gene expression sub-classifies TNBC patients into a new subgroup (TNBC-PRLR) characterized by epithelial-luminal differentiation. Importantly, gene expression of PRL signaling pathway components individually (PRL, PRLR, Jak2 and Stat5a), or as a gene signature is able to predict TNBC patients with significantly better survival outcomes. As PRL hormone is a druggable target we determined the biological role of PRL in TNBC biology. Significantly, restoration/activation of PRL pathway in TNBC cells representative of mesenchymal or TNBC-PRLR subgroups led to induction of epithelial phenotype and suppression of tumorigenesis. Altogether, these results offer potential new modalities for TNBC stratification and development of personalized therapy based on PRL pathway activation.
Metabolomics Profiling for Obstructive Sleep Apnea and Simple Snorers
Authors: Xu Huajun , Zheng Xiaojiao , Qian Yingjun , Guan Jian , Yi Hongliang , Zou Jianyin , Wang Yuyu , Meng Lili , Zhao Aihua , Yin Shankai , Jia Wei
Published: August 2016

Few clinical studies have explored altered urinary metabolite levels in patients with obstructive sleep apnea (OSA). Thus, we applied a metabolomics approach to analyze urinary metabolites in three groups of participants: patients with polysomnography (PSG)-confirmed OSA, simple snorers (SS) and normal subjects. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and gas chromatography coupled with time-of-flight mass spectrometry were used. A total of 21 and 31 metabolites were differentially expressed in the SS and OSA groups, respectively. Patients with OSA had 18 metabolites different from those with SS. Of the 56 metabolites detected among the 3 groups, 24 were consistently higher or lower. A receiver operator curve analysis revealed that the combination of 4-hydroxypentenoic acid, arabinose, glycochenodeoxycholate-3-sulfate, isoleucine, serine and xanthine produced a moderate diagnostic score with a sensitivity (specificity) of 75% (78%) for distinguishing OSA from those without OSA. The combination of 4-hydroxypentenoic acid, 5-dihydrotestosterone sulfate, serine, spermine and xanthine distinguished OSA from SS with a sensitivity of 85% and specificity of 80%. Multiple metabolites and metabolic pathways associated with SS and OSA were identified using the metabolomics approach and the altered metabolite signatures could potentially serve as an alternative diagnostic method to PSG.
Microbial metabolism mediates interactions between dissolved organic matter and clay minerals in streamwater
Authors: Hunter W. R. , Battin T. J.
Published: August 2016

Sorption of organic molecules to mineral surfaces is an important control upon the aquatic carbon (C) cycle. Organo-mineral interactions are known to regulate the transport and burial of C within inland waters, yet the mechanisms that underlie these processes are poorly constrained. Streamwater contains a complex and dynamic mix of dissolved organic compounds that coexists with a range of organic and inorganic particles and microorganisms. To test how microbial metabolism and organo-mineral complexation alter amino acid and organic carbon fluxes we experimented with 13C-labelled amino acids and two common clay minerals (kaolinite and montmorillonite). The addition of 13C-labelled amino acids stimulated increased microbial activity. Amino acids were preferentially mineralized by the microbial community, concomitant with the leaching of other (non-labelled) dissolved organic molecules that were removed from solution by clay-mediated processes. We propose that microbial processes mediate the formation of organo-mineral particles in streamwater, with potential implications for the biochemical composition of organic matter transported through and buried within fluvial environments.
Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders
Authors: Chiocchetti A G , Haslinger D , Stein J L , de la Torre-Ubieta L , Cocchi E , Rothämel T , Lindlar S , Waltes R , Fulda S , Geschwind D H , Freitag C M
Published: August 2016

Genes for autism spectrum disorders (ASDs) are also implicated in fragile X syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell line, the most widely used system to study neurodevelopment, is currently discussed for its applicability to model cortical development. We implemented an optimal neuronal differentiation protocol of this system and evaluated neurodevelopment at the transcriptomic level using the CoNTeXT framework, a machine-learning algorithm based on human post-mortem brain data estimating developmental stage and regional identity of transcriptomic signatures. Our improved model in contrast to currently used SH-SY5Y models does capture early neurodevelopmental processes with high fidelity. We applied regression modelling, dynamic time warping analysis, parallel independent component analysis and weighted gene co-expression network analysis to identify activated gene sets and networks. Finally, we tested and compared these sets for enrichment of risk genes for neuropsychiatric disorders. We confirm a significant overlap of genes implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this observation, we report that risk genes affect pathways specific for each disorder during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were enriched among the positive regulators, but only ID-implicated genes were also negative regulators of neuronal differentiation. ASD and ID genes were involved in dendritic branching modules, but only ASD risk genes were implicated in histone modification or axonal guidance. Only ID genes were over-represented among cell cycle modules. We conclude that the underlying signatures are disorder-specific and that the shared genetic architecture results in overlaps across disorders such as ID in ASD. Thus, adding developmental network context to genetic analyses will aid differentiating the pathophysiology of neuropsychiatric disorders.
An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
Authors: Brundin L , Sellgren C M , Lim C K , Grit J , Pålsson E , Landén M , Samuelsson M , Lundgren K , Brundin P , Fuchs D , Postolache T T , Traskman-Bendz L , Guillemin G J , Erhardt S
Published: August 2016

Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Åsberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
ZSM-5 with controllable acidity as an efficient catalyst for a highly adjustable propene/ethene ratio in the 1-butene cracking
Authors: Zhao Shufang , Yang Di , Zhang Xiaowei , Yao Xuting , Liu Yueming , He Mingyuan
Published: August 2016

A facile strategy was proposed for the control of zeolitic acidity by selective cracking of a silane with an acid site.
Second-generation probes for biosynthetic intermediate capture: towards a comprehensive profiling of polyketide assembly
Authors: Wilkening Ina , Gazzola Silvia , Riva Elena , Parascandolo James S. , Song Lijiang , Tosin Manuela
Published: August 2016

Novel chemical probes provide kinetic insights into polyketide assembly.
Catalyst-free dehydrocoupling of amines, alcohols, and thiols with pinacol borane and 9-borabicyclononane (9-BBN)
Authors: Romero Erik A. , Peltier Jesse L. , Jazzar Rodolphe , Bertrand Guy
Published: August 2016

The dehydrocoupling of pinacol borane and 9-borabicyclononane with amines, alcohols and thiols can be achieved under mild conditions without catalyst.
Excitonic and vibrational coherence in artificial photosynthetic systems studied by negative-time ultrafast laser spectroscopy
Authors: Han Dongjia , Xue Bing , Du Juan , Kobayashi Takayoshi , Miyatake Tomohiro , Tamiaki Hitoshi , Xing Xin , Yuan Wei , Li Yanyan , Leng Yuxin
Published: August 2016

Two dimensional display of ΔA(ω,t) in artificial photosynthetic systems by negative-time ultrafast laser spectroscopy.
Mechanochemical synthesis in the Li–Mg–N–D system under deuterium gas: a neutron diffraction study
Authors: Li Z. , Zhang J. , Latroche M. , Wang S. , Jiang L. , Du J. , Cuevas F.
Published: August 2016

This article unveils the synthesis of a novel Li3MgN2D compound in the Li–Mg–N–D system using mechanochemistry, and its structural and sorption properties.
A carboxylate-bridged NiII8 cluster with a distorted cubane topology: structure, magnetism and density functional studies
Authors: Arora Himanshu , Cano Joan , Lloret Francesc , Mukherjee Rabindranath
Published: August 2016

An octanickel(ii) cluster supported solely by carboxylate-bridges has been achieved by a (2-pyridyl)ethylamine-appended dicarboxylate ligand. A study of magnetostructural analysis has been carried out and substantiated by theoretical calculations.
A structurally flexible triazolate-based metal–organic framework featuring coordinatively unsaturated copper(i) sites
Authors: Schmieder P. , Denysenko D. , Grzywa M. , Magdysyuk O. , Volkmer D.
Published: August 2016

A novel CuI-bistriazolate MOF showing reversible breathing behaviour is able to form a weak complex with carbon monoxide.
Two sequential enhancements of laser-induced Cu plasma with cylindrical cavity confinement
Authors: Wang Ying , Chen Anmin , Sui Laizhi , Li Suyu , Wang Xiaowei , Jiang Yuanfei , Huang Xuri , Jin Mingxing
Published: August 2016

This study was conducted to investigate spatial confinement effects in laser-induced Cu plasma via optical emission spectroscopy.
Gold nanoparticles supported on layered TiO2–RGO hybrid as an enhanced and recyclable catalyst for microwave-assisted hydration reaction
Authors: Cheng Yunfeng , Zhao Qingshan , Li Yang , Peng Wenchao , Zhang Guoliang , Zhang Fengbao , Fan Xiaobin
Published: August 2016

A novel composite (Au–SO42−/TiO2–RGO) is synthesized and serves as an enhanced catalyst for alkyne hydration.
Trifluoromethylation of (hetero)aryl iodides and bromides with copper(i) chlorodifluoroacetate complexes
Authors: Lin Xiaoxi , Li Zhengyu , Han Xiaoyan , Weng Zhiqiang
Published: August 2016

A new copper-mediated trifluoromethylation of aryl halides using copper(i) chlorodifluoroacetate complexes as reagent has been developed.
Correction: A versatile glycosylation strategy via Au(iii) catalyzed activation of thioglycoside donors
Authors: Vibhute Amol M. , Dhaka Arun , Athiyarath Vignesh , Sureshan Kana M.
Published: August 2016

Correction for ‘A versatile glycosylation strategy via Au(iii) catalyzed activation of thioglycoside donors’ by Amol M. Vibhute et al., Chem. Sci., 2016, 7, 4259–4263.
Melatonin in functionalized biomimetic constructs promotes rapid tissue regeneration in Wistar albino rats
Authors: Murali Ragothaman , Thanikaivelan Palanisamy , Cheirmadurai Kalirajan
Published: August 2016

Biomimetic collagen–poly(dialdehyde) gum acacia based hybrid scaffolds with a synergistic combination of melatonin were prepared to regenerate tissue formation in wound-healing applications.
An AlAs/germanene heterostructure with tunable electronic and optical properties via external electric field and strain
Authors: Tan Chunjian , Yang Qun , Meng Ruishen , Liang Qiuhua , Jiang Junke , Sun Xiang , Ye Huaiyu , Chen X. P.
Published: August 2016

By means of comprehensive first-principles calculations, we investigate the stability, electronic and optical properties of an AlAs/germanene heterostructure.
Structural basis of arginine asymmetrical dimethylation by PRMT6
Authors: Wu Hong , Zheng Weihong , Eram Mohammad S. , Vhuiyan Mynol , Dong Aiping , Zeng Hong , He Hao , Brown Peter , Frankel Adam , Vedadi Masoud , Luo Minkui , Min Jinrong
Published: August 2016

PRMT6 is a type I protein arginine methyltransferase, generating the asymmetric dimethylarginine mark on proteins such as histone H3R2. Asymmetric dimethylation of histone H3R2 by PRMT6 acts as a repressive mark that antagonizes trimethylation of H3 lysine 4 by the MLL histone H3K4 methyltransferase. PRMT6 is overexpressed in several cancer types, including prostate, bladder and lung cancers; therefore, it is of great interest to develop potent and selective inhibitors for PRMT6. Here, we report the synthesis of a potent bisubstrate inhibitor GMS [6′-methyleneamine sinefungin, an analog of sinefungin (SNF)], and the crystal structures of human PRMT6 in complex, respectively, with S-adenosyl-L-homocysteine (SAH) and the bisubstrate inhibitor GMS that shed light on the significantly improved inhibition effect of GMS on methylation activity of PRMT6 compared with SAH and an S-adenosyl-L-methionine competitive methyltransferase inhibitor SNF. In addition, we also crystallized PRMT6 in complex with SAH and a short arginine-containing peptide. Based on the structural information here and available in the PDB database, we proposed a mechanism that can rationalize the distinctive arginine methylation product specificity of different types of arginine methyltransferases and pinpoint the structural determinant of such a specificity.
N-linked glycosylation of N48 is required for equilibrative nucleoside transporter 1 (ENT1) function
Authors: Bicket Alex , Coe Imogen R.
Published: August 2016

Human equilibrative nucleoside transporter 1 (hENT1) transports nucleosides and nucleoside analogue drugs across cellular membranes and is necessary for the uptake of many anti-cancer, anti-parasitic and anti-viral drugs. Previous work, and in silico prediction, suggest that hENT1 is glycosylated at Asn48 in the first extracellular loop of the protein and that glycosylation plays a role in correct localization and function of hENT1. Site-directed mutagenesis of wild-type (wt) hENT1 removed potential glycosylation sites. Constructs (wt 3xFLAG-hENT1, N48Q-3xFLAG-hENT1 or N288Q-3xFLAG-hENT2) were transiently transfected into HEK293 cells and cell lysates were treated with or without peptide–N-glycosidase F (PNGase-F), followed by immunoblotting analysis. Substitution of N48 prevents hENT1 glycosylation, confirming a single N-linked glycosylation site. N48Q-hENT1 protein is found at the plasma membrane in HEK293 cells but at lower levels compared with wt hENT1 based on S-(4-nitrobenzyl)-6-thioinosine (NBTI) binding analysis (wt 3xFLAG-ENT1 Bmax, 41.5±2.9 pmol/mg protein; N48Q-3xFLAG-ENT1 Bmax, 13.5±0.45 pmol/mg protein) and immunofluorescence microscopy. Although present at the membrane, chloroadenosine transport assays suggest that N48Q-hENT1 is non-functional (wt 3xFLAG-ENT1, 170.80±44.01 pmol/mg protein; N48Q-3xFLAG-ENT1, 57.91±17.06 pmol/mg protein; mock-transfected 74.31±19.65 pmol/mg protein). Co-immunoprecipitation analyses suggest that N48Q ENT1 is unable to interact with self or with wt hENT1. Based on these data we propose that glycosylation at N48 is critical for the localization, function and oligomerization of hENT1.
Theoretical investigations on equilateral triangular dielectric resonator antenna
Authors: Maity Sudipta , Gupta Bhaskar
Published: August 2016

Equilateral triangular dielectric resonator antenna (ETDRA) is investigated here analytically for TMz mode. For theoretical analysis, the triangular surfaces on the top and bottom of the isolated ETDRA are modelled either as perfect magnetic conductors (PMC) or imperfect magnetic conductors (IPMC), whereas the side walls having rectangular cross‐section are modelled as PMC only. The concept of reduction in effective size due to the avoidance of any corner by the electric field lines is used for the first time to predict the resonant frequency for different TMzmnp modes with an accuracy of 4%. Consequently, an expression is also given here for efficient evaluation of effective dimensions of the ETDRA for various TMzmnp modes. Closed form expressions for the far‐field radiation patterns of dominant TMz101 mode are also presented using both (PMC and IPMC) models. Theoretical results are compared with published data as found in the open literature. One antenna prototype is also fabricated, tested and measured for further verification. It is found that the authors’ theoretical results are in close agreement with measured data.
Channel models for capacity evaluation of MIMO handsets in data mode
Authors: Nielsen Jesper Ødum , Yanakiev Boyan , Caporal Del Barrio Samantha , Pedersen Gert Frølund
Published: August 2016

This study investigates different correlation based models useful for evaluation of outage capacity (OC) of mobile multiple‐input and multiple‐output (MIMO) handsets. The work is based on a large measurement campaign in a micro‐cellular setup involving two dual‐band base stations (BSs), 10 different handsets in an indoor environment for different use cases and test users. Several models are evaluated statistically, comparing the OC values estimated from the model and measurement data, respectively, for about 2700 measurement routes. The models are based on either estimates of the full correlation matrices or simplifications. Among other results, it is shown that the OC can be predicted accurately (median error typically within 2.6%) with a model assuming knowledge only of the Tx‐correlation coefficient and the mean power gain.
Independence of events, and errors in understanding it
Authors: Roney Chris
Published: August 2016

This article outlines errors that may occur when people predict event outcomes. The focus is on how our tendency to perceive independent events as connected, consistent with tenets of Gestalt Psychology, biases our expectations. Two well-documented phenomena that occur when people make predictions after a run of a particular outcome—the “gambler’s fallacy” and the “hot hand”—are used to illustrate the issue, and research is presented that highlights the importance of misperceptions of independence. Novel implications and hypotheses are presented that are generated from use of this gestalt approach.
Influence of emitter ring manufacturing tolerances on electron beam quality of high power gyrotrons
Authors: Pagonakis Ioannis Gr. , Illy Stefan , Thumm Manfred
Published: August 2016

A sensitivity analysis of manufacturing imperfections and possible misalignments of the emitter ring in the gyrotron cathode structure on the electron beam quality has been performed. It has been shown that a possible radial displacement of the emitter ring of the order of few tens of microns can cause dramatic effects on the beam quality and therefore the gyrotron operation. Two different design approaches are proposed in order to achieve an electron beam which is less sensitive to manufacturing imperfections.
The magnetic recoil spectrometer (MRSt) for time-resolved measurements of the neutron spectrum at the National Ignition Facility (NIF)
Authors: Frenje J. A. , Hilsabeck T. J. , Wink C. W. , Bell P. , Bionta R. , Cerjan C. , Gatu Johnson M. , Kilkenny J. D. , Li C. K. , Séguin F. H. , Petrasso R. D.
Published: August 2016

The next-generation magnetic recoil spectrometer for time-resolved measurements of the neutron spectrum has been conceptually designed for the National Ignition Facility. This spectrometer, called MRSt, represents a paradigm shift in our thinking about neutron spectrometry for inertial confinement fusion applications, as it will provide simultaneously information about the burn history and time evolution of areal density (ρR), apparent ion temperature (Ti), yield (Yn), and macroscopic flows during burn. From this type of data, an assessment of the evolution of the fuel assembly, hotspot, and alpha heating can be made. According to simulations, the MRSt will provide accurate data with a time resolution of ∼20 ps and energy resolution of ∼100 keV for total neutron yields above ∼1016. At lower yields, the diagnostic will be operated at a higher-efficiency, lower-energy-resolution mode to provide a time resolution of ∼20 ps.
Microscopic molecular dynamics characterization of the second-order non-Navier-Fourier constitutive laws in the Poiseuille gas flow
Authors: Rana A. , Ravichandran R. , Park J. H. , Myong R. S.
Published: August 2016

The second-order non-Navier-Fourier constitutive laws, expressed in a compact algebraic mathematical form, were validated for the force-driven Poiseuille gas flow by the deterministic atomic-level microscopic molecular dynamics (MD). Emphasis is placed on how completely different methods (a second-order continuum macroscopic theory based on the kinetic Boltzmann equation, the probabilistic mesoscopic direct simulation Monte Carlo, and, in particular, the deterministic microscopic MD) describe the non-classical physics, and whether the second-order non-Navier-Fourier constitutive laws derived from the continuum theory can be validated using MD solutions for the viscous stress and heat flux calculated directly from the molecular data using the statistical method. Peculiar behaviors (non-uniform tangent pressure profile and exotic instantaneous heat conduction from cold to hot [R. S. Myong, “A full analytical solution for the force-driven compressible Poiseuille gas flow based on a nonlinear coupled constitutive relation,” Phys. Fluids 23(1), 012002 (2011)]) were re-examined using atomic-level MD results. It was shown that all three results were in strong qualitative agreement with each other, implying that the second-order non-Navier-Fourier laws are indeed physically legitimate in the transition regime. Furthermore, it was shown that the non-Navier-Fourier constitutive laws are essential for describing non-zero normal stress and tangential heat flux, while the classical and non-classical laws remain similar for shear stress and normal heat flux.
Up-down asymmetry measurement of tungsten distribution in large helical device using two extreme ultraviolet (EUV) spectrometers
Authors: Liu Y. , Morita S. , Huang X. L. , Oishi T. , Goto M. , Zhang H. M.
Published: August 2016

Two space-resolved extreme ultraviolet spectrometers working in wavelength ranges of 10-130 Å and 30-500 Å have been utilized to observe the full vertical profile of tungsten line emissions by simultaneously measuring upper- and lower-half plasmas of LHD, respectively. The radial profile of local emissivity is reconstructed from the measured vertical profile in the overlapped wavelength range of 30-130 Å and the up-down asymmetry is examined against the local emissivity profiles of WXXVIII in the unresolved transition array spectrum. The result shows a nearly symmetric profile, suggesting a good availability in the present diagnostic method for the impurity asymmetry study.
Radial direct bandgap p-i-n GaNP microwire solar cells with enhanced short circuit current
Authors: Sukrittanon Supanee , Liu Ren , Breeden Michael C. , Pan Janet L. , Jungjohann K. L. , Tu Charles W. , Dayeh Shadi A.
Published: August 2016

We report the demonstration of dilute nitride heterostructure core/shell microwire solar cells utilizing the combination of top-down reactive-ion etching to create the cores (GaP) and molecular beam epitaxy to create the shells (GaNP). Systematic studies of cell performance over a series of microwire lengths, array periods, and microwire sidewall morphologies examined by transmission electron microscopy were conducted to shed light on performance-limiting factors and to optimize the cell efficiency. We show by microscopy and correlated external quantum efficiency characterization that the open circuit voltage is degraded primarily due to the presence of defects at the GaP/GaNP interface and in the GaNP shells, and is not limited by surface recombination. Compared to thin film solar cells in the same growth run, the microwire solar cells exhibit greater short circuit current but poorer open circuit voltage due to greater light absorption and number of defects in the microwire structure, respectively. The comprehensive understanding presented in this work suggests that performance benefits of dilute nitride microwire solar cells can be achieved by further tuning of the epitaxial quality of the underlying materials.
Mixed quantum-classical simulations of the vibrational relaxation of photolyzed carbon monoxide in a hemoprotein
Authors: Schubert Alexander , Falvo Cyril , Meier Christoph
Published: August 2016

We present mixed quantum-classical simulations on relaxation and dephasing of vibrationally excited carbon monoxide within a protein environment. The methodology is based on a vibrational surface hopping approach treating the vibrational states of CO quantum mechanically, while all remaining degrees of freedom are described by means of classical molecular dynamics. The CO vibrational states form the “surfaces” for the classical trajectories of protein and solvent atoms. In return, environmentally induced non-adiabatic couplings between these states cause transitions describing the vibrational relaxation from first principles. The molecular dynamics simulation yields a detailed atomistic picture of the energy relaxation pathways, taking the molecular structure and dynamics of the protein and its solvent fully into account. Using the ultrafast photolysis of CO in the hemoprotein FixL as an example, we study the relaxation of vibrationally excited CO and evaluate the role of each of the FixL residues forming the heme pocket.
Global and local curvature in density functional theory
Authors: Zhao Qing , Ioannidis Efthymios I. , Kulik Heather J.
Published: August 2016

Piecewise linearity of the energy with respect to fractional electron removal or addition is a requirement of an electronic structure method that necessitates the presence of a derivative discontinuity at integer electron occupation. Semi-local exchange-correlation (xc) approximations within density functional theory (DFT) fail to reproduce this behavior, giving rise to deviations from linearity with a convex global curvature that is evidence of many-electron, self-interaction error and electron delocalization. Popular functional tuning strategies focus on reproducing piecewise linearity, especially to improve predictions of optical properties. In a divergent approach, Hubbard U-augmented DFT (i.e., DFT+U) treats self-interaction errors by reducing the local curvature of the energy with respect to electron removal or addition from one localized subshell to the surrounding system. Although it has been suggested that DFT+U should simultaneously alleviate global and local curvature in the atomic limit, no detailed study on real systems has been carried out to probe the validity of this statement. In this work, we show when DFT+U should minimize deviations from linearity and demonstrate that a “+U” correction will never worsen the deviation from linearity of the underlying xc approximation. However, we explain varying degrees of efficiency of the approach over 27 octahedral transition metal complexes with respect to transition metal (Sc–Cu) and ligand strength (CO, NH3, and H2O) and investigate select pathological cases where the delocalization error is invisible to DFT+U within an atomic projection framework. Finally, we demonstrate that the global and local curvatures represent different quantities that show opposing behavior with increasing ligand field strength, and we identify where these two may still coincide.
Bifurcation analysis of the behavior of partially wetting liquids on a rotating cylinder
Authors: Lin Te-Sheng , Rogers Steven , Tseluiko Dmitri , Thiele Uwe
Published: August 2016

We discuss the behavior of partially wetting liquids on a rotating cylinder using a model that takes into account the effects of gravity, viscosity, rotation, surface tension, and wettability. Such a system can be considered as a prototype for many other systems where the interplay of spatial heterogeneity and a lateral driving force in the proximity of a first- or second-order phase transition results in intricate behavior. So does a partially wetting drop on a rotating cylinder undergo a depinning transition as the rotation speed is increased, whereas for ideally wetting liquids, the behavior only changes quantitatively. We analyze the bifurcations that occur when the rotation speed is increased for several values of the equilibrium contact angle of the partially wetting liquids. This allows us to discuss how the entire bifurcation structure and the flow behavior it encodes change with changing wettability. We employ various numerical continuation techniques that allow us to track stable/unstable steady and time-periodic film and drop thickness profiles. We support our findings by time-dependent numerical simulations and asymptotic analyses of steady and time-periodic profiles for large rotation numbers.
Non-viscous regularization of the Davey-Stewartson equations: Analysis and modulation theory
Authors: Guo Yanqiu , Hacinliyan Irma , Titi Edriss S.
Published: August 2016

In the present study, we are interested in the Davey-Stewartson equations (DSE) that model packets of surface and capillary-gravity waves. We focus on the elliptic-elliptic case, for which it is known that DSE may develop a finite-time singularity. We propose three systems of non-viscous regularization to the DSE in a variety of parameter regimes under which the finite-time blow-up of solutions to the DSE occurs. We establish the global well-posedness of the regularized systems for all initial data. The regularized systems, which are inspired by the α-models of turbulence and therefore are called the α-regularized DSE, are also viewed as unbounded, singularly perturbed DSE. Therefore, we also derive reduced systems of ordinary differential equations for the α-regularized DSE by using the modulation theory to investigate the mechanism with which the proposed non-viscous regularization prevents the formation of the singularities in the regularized DSE. This is a follow-up of the work [Cao et al., Nonlinearity 21, 879–898 (2008); Cao et al., Numer. Funct. Anal. Optim. 30, 46–69 (2009)] on the non-viscous α-regularization of the nonlinear Schrödinger equation.
Two-dimensional boron: Lightest catalyst for hydrogen and oxygen evolution reaction
Authors: Mir Showkat H. , Chakraborty Sudip , Jha Prakash C. , Wärnå John , Soni Himadri , Jha Prafulla K. , Ahuja Rajeev
Published: August 2016

The hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) have been envisaged on a two-dimensional (2D) boron sheet through electronic structure calculations based on a density functional theory framework. To date, boron sheets are the lightest 2D material and, therefore, exploring the catalytic activity of such a monolayer system would be quite intuitive both from fundamental and application perspectives. We have functionalized the boron sheet (BS) with different elemental dopants like carbon, nitrogen, phosphorous, sulphur, and lithium and determined the adsorption energy for each case while hydrogen and oxygen are on top of the doping site of the boron sheet. The free energy calculated from the individual adsorption energy for each functionalized BS subsequently guides us to predict which case of functionalization serves better for the HER or the OER.
Do quantum spin liquids exist?
Authors: Imai Takashi , Lee Young S.
Published: August 2016

The search for the hypothetical state has been a 43-year-long slog, one whose end may now be in sight.
Larger lizards live longer in the group-living Egernia stokesii
Authors: Pearson S. K. , Godfrey S. S. , Bull C. M. , Gardner M. G.
Published: August 2016

Animal space use has implications for gene flow, disease dynamics, mating systems and the evolution of sociality. Given recent attention to sociality in reptiles, lizards are an important group for expanding our understanding of animal space use. Lizard space use is commonly investigated within one population over a short period and limited attention has been given to potential predictors of site fidelity. This study evaluated site fidelity in three populations of group-living Egernia stokesii (gidgee skink) between two field surveys separated by almost a decade. Of 43 recaptured lizards, 28 (65%) occupied their original space, and 15 (36%) of those shared their space with the same other lizard or lizards in both surveys. This confirmed long-term site and social bond fidelity in E. stokesii. We found that larger lizards were more likely to be recaptured. Neither body size, individual genetic heterozygosity, nor the availability of refuges strongly predicted whether lizards were recaptured in the same or a different place. The reasons why some lizards stayed in the same space while others moved are yet to be resolved.
Trading experience modulates anterior insula to reduce the endowment effect
Authors: Tong Lester C. P. , Ye Karen J. , Asai Kentaro , Ertac Seda , List John A. , Nusbaum Howard C. , Hortaçsu Ali
Published: August 2016

Significance

Trading experience has been shown to reduce the endowment effect, a decision-making bias that distorts market prices and reduces trade. Understanding the mechanisms underlying how experience changes this bias will provide important insights for developing interventions to improve market efficiency. Using functional magnetic resonance imaging, we show that market experience causes a reduction in right anterior insula activation during selling, which mediates a decrease in the endowment effect. These findings suggest that trading mitigates negative affective responses in the context of selling.
CCN1/CYR61-mediated meticulous patrolling by Ly6C
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monocytes fuels vascular inflammation
Authors: Imhof Beat A. , Jemelin Stephane , Ballet Romain , Vesin Christian , Schapira Marc , Karaca Melis , Emre Yalin
Published: August 2016

Significance

Upon infection, circulating leukocytes leave the bloodstream and migrate into the inflammatory site. Neutrophils are the first leukocytes to be recruited within a few hours, followed by inflammatory lymphocyte antigen 6 complex (Ly6C)-positive monocytes. This study refines the model of the leukocyte recruitment cascade. We demonstrate that upon Toll-like receptor 7/8-mediated vascular inflammation, platelet activation drives the rapid mobilization of Ly6C
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monocytes to the luminal side of the endothelium. Accumulated Ly6C
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monocytes do not extravasate into the tissue. Instead, they meticulously patrol the endothelium and control the subsequent recruitment of neutrophils. Moreover, we show that endothelium-bound cyteine-rich protein 61 (CYR61)/CYR61 connective tissue growth factor nephroblastoma overexpressed 1 (CCN1) protein provides a molecular support for adequate patrolling of Ly6C
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monocytes in the steady state and under inflammatory conditions.
Water-soluble cavitands promote hydrolyses of long-chain diesters
Authors: Shi Qixun , Mower Matthew P. , Blackmond Donna G. , Rebek Julius
Published: August 2016

Significance

Molecules in confined spaces behave differently from those in bulk solution and a number of container (host) compounds have been developed to exploit the differences. In aqueous media, hydrophobic forces can drive binding of guests into the limited space of container hosts, and flexible guests assume shapes congruent with the container’s space. Long-chain hydrocarbons take on folded conformations, which bring the guest’s ends closer together. Sites that are remote in bulk solution are no longer so in the complex; the sites become “entangled” and affect each other’s reactivity. Product distributions that are statistically determined in solution are significantly altered in cavitands and lead to enhanced yields of desired reaction products.
Increased incidence of infective endocarditis after the 2009 European Society of Cardiology guideline update: a nationwide study in the Netherlands
Authors: van den Brink Floris S. , Swaans Martin J. , Hoogendijk Mark G. , Alipour Arash , Kelder Johannes C. , Jaarsma Wybren , Eefting Frank D. , Groenmeijer Bjorn , Kupper A. Jon Funke , ten Berg Jurrien M.
Published: August 2016

Aims

After the introduction of the European Society of Cardiology (ESC) guidelines on prevention, diagnosis, and treatment of infective endocarditis (IE) in 2009, prophylaxis for patients at risk became less strict. We hypothesize that there will be a rise in IE after the introduction of the guideline update.

Methods and Results

We performed a nationwide retrospective trend study using segmented regression analysis of the interrupted time series. The patient data were obtained via the national healthcare insurance database, which collects all the diagnoses nationwide. We compared the data before and after the introduction of the 2009 ESC guideline. Between 2005 and 2011, a total of 5213 patients were hospitalized with IE in the Netherlands. During this period, there was a significant increase in IE from 30.2 new cases per 1 000 000 in 2005 to 62.9 cases per 1 000 000 in 2011 (P < 0.001). In 2009, the incidence of IE increased significantly above the projected historical trend (rate ratio: 1.327, 95% CI: 1.205–1.462; P < 0.001). This coincides with the introduction of the 2009 ESC guideline. After the introduction of the ESC guideline, the streptococci-positive cultures increased significantly in the following years 2010–11 from 31.1 to 53.2% (P = 0.0031).

Conclusion

This observational study shows that there has been a steady increase in the IE incidence between 2005 and 2011. After the introduction of the 2009 ESC guidelines, the incidence increased more than expected from previous historical trends. Furthermore, there was a significant increase in streptococci-related IE cases.
Colonization and Intrusive Invasion of Potato Psyllid by ‘Candidatus Liberibacter solanacearum’
Authors: Cicero Joseph M. , Fisher Tonja W. , Qureshi Jawwad A. , Stansly Philip A. , Brown Judith K.
Published: August 2016

Previous studies have shown that the fastidious bacterial plant pathogen ‘Candidatus Liberibacter solanacearum’ (CLso) is transmitted circulatively and propagatively by the potato psyllid (PoP) Bactericera cockerelli. In this study, the temporal and spatial interrelationships between CLso PoP were investigated by scanning electron microscopy of the digestive system of PoP immature and adult instars and salivary glands of adults post CLso ingestion. CLso biofilms were not detectable on the outer midgut surface of the first and second instars; however, for third to fifth instars and teneral and mature adults, biofilms were observed in increasing numbers in each successive developmental stage. In adult PoP midguts, CLso cells were observed between the basal lamina and basal epithelial cell membranes; in basal laminar perforations, on the outer basal laminar surface, and in the ventricular lumen, epithelial cytosol, and filter chamber periventricular space. CLso were also abundantly visible in the salivary gland pericellular spaces and in the epidermal cell cytosol of the head. Collectively, these results point to an intrusive, systemic invasion of PoP by CLso that employs an endo/exocytosis-like mechanism, in the context of a propagative, circulative mode of transmission.
Accelerated selection of a viral RNA polymerase variant during gene copy number amplification promotes rapid evolution of vaccinia virus
Authors: Cone Kelsey R. , Kronenberg Zev N. , Yandell Mark , Elde Nels C.
Published: August 2016

Viruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial infections of vaccinia virus in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution in A24R conferred fitness tradeoffs, including increased activation of the antiviral factor Protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We show that the sweep of this variant can be accelerated by the presence of copy number variation (CNV) at the K3L locus, which with multiple copies strongly reduces PKR activation. Therefore, adaptive cases of CNV can also facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses.

Importance

Viruses can quickly evolve to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations might concurrently emerge in populations. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R, and show that these mutations can affect the activation of host nucleic acid sensing pathways through different mechanisms. We also found that structural variants within viral genomes in the form of gene copy number variation (CNV) provide dual benefits to evolving populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accommodate the accumulation of mutations conferring modest benefits, or even fitness tradeoffs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect action.
Literature mining supports a next-generation modeling approach to predict cellular byproduct secretion
Authors: King Zachary A. , O’Brien Edward J. , Feist Adam M. , Palsson Bernhard O.
Published: August 2016

The metabolic byproducts secreted by growing cells can be easily measured and provide a window into the state of a cell; they have been essential to the development of microbiology1, cancer biology2, and biotechnology3. Progress in computational modeling of cells has made it possible to predict metabolic byproduct secretion with bottom-up reconstructions of metabolic networks. However, owing to a lack of data, it has not been possible to validate these predictions across a wide range of strains and conditions. Through literature mining, we were able to generate a database ofEscherichia colistrains and their experimentally measured byproduct secretions. We simulated these strains in six historical genome-scale models ofE. coli, and we report that the predictive power of the models has increased as they have expanded in size and scope. Next-generation models of metabolism and gene expression are even more capable than previous models, but parameterization poses new challenges.