bluuebunny/crossref_metadata_2025 huggingface dataset:
Emodin inhibits coxsackievirus B3 replication via multiple signalling cascades leading to suppression of translation
Authors: Zhang Huifang M. , Wang Fengping , Qiu Ye , Ye Xin , Hanson Paul , Shen Hongxing , Yang Decheng
Published: December 2015

CVB3 (coxsackievirus 3) is a primary causal agent of viral myocarditis. Emodin is a natural compound isolated from certain plant roots. In the present study, we found that emodin inhibited CVB3 replication in vitro and in mice, and now we report an unrecognized mechanism by which emodin inhibits CVB3 replication through suppression of viral protein translation via multiple pathways. On one hand, emodin treatment inhibited Akt/mTOR (mammalian target of rapamycin) signalling and activated 4EBP1 (eukaryotic initiation factor 4R-binding protein 1), leading to suppression of translation initiation of ribosomal protein L32 encoded by a 5′-TOP (terminal oligopyrimidine) mRNA. On the other hand, emodin treatment differentially regulated multiple signal cascades, including Akt/mTORC1/p70S6K (p70 S6 kinase), ERK1/2 (extracellular-signal-regulated kinase 1/2)/p90RSK (p90 ribosomal S6 kinase) and Ca2+/calmodulin, leading to activation of eEF2K (eukaryotic elongation factor 2 kinase) and subsequent inactivation of eEF2 (eukaryotic elongation factor 2), resulting in inhibition of CVB3 VP1 (viral protein 1) synthesis. These data imply that eEF2K is a major factor mediating cross-talk of different arms of signalling cascades in this signal network. This notion was verified by either overexpressing eEF2K or treating the cells with siRNAs or eEF2K inhibitor A484954. We showed further that the emodin-induced decrease in p70S6K phosphorylation plays a dominant positive role in activation of eEF2K and in turn in conferring the antiviral effect of emodin. This finding was further solidified by expressing constitutively active and dominant-negative Akt. Collectively, our data reveal that emodin inhibits viral replication through impairing translational machinery and suppression of viral translation elongation.
Direct numerical simulation of Taylor-Couette flow subjected to a radial temperature gradient
Authors: Teng Hao , Liu Nansheng , Lu Xiyun , Khomami Bamin
Published: December 2015

Direct numerical simulations have been performed to study the Taylor-Couette (TC) flow between two rotating, coaxial cylinders in the presence of a radial temperature gradient. Specifically, the influence of the buoyant force and the outer cylinder rotation on the turbulent TC flow system with the radius ratio η = 0.912 was examined. For the co-rotating TC flows with Rei (inner cylinder) =1000 and Reo (outer cylinder) =100, a transition pathway to highly turbulent flows is realized by increasing σ, a parameter signifying the ratio of buoyant to inertial force. This nonlinear flow transition involves four intriguing states that emerge in sequence as chaotic wavy vortex flow for σ = 0, wavy interpenetrating spiral flows for σ = 0.02 and 0.05, intermittent turbulent spirals for σ = 0.1 and 0.2, and turbulent spirals for σ = 0.4. Overall, the fluid motion changes from a centrifugally driven flow regime characterized by large-scale wavy Taylor vortices (TVs) to a buoyancy-dominated flow regime characterized by small-scale turbulent vortices. Commensurate changes in turbulence statistics and heat transfer are seen as a result of the weakening of large-scale TV circulations and enhancement of turbulent motions. Additionally, the influence of variation of the outer cylinder rotation, −500 < Reo < 500 in presence of buoyancy (σ = 0.1) with Rei = 1000, has been considered. Specifically, it is demonstrated that this variation strongly influences the azimuthal and axial mean flows with a weaker influence on the fluctuating fluid motions. Of special interest, here are the turbulent dynamics near the outer wall where a marked decrease of turbulence intensity and a sign inversion of the Reynolds stress Rrz are observed for the strongly counter-rotating regimes (Reo = − 300 and −500). To this end, it has been shown that the underlying flow physics for this drastic modification are associated with the modification of the correlation between the radial and axial fluctuating motions. In turn, the intriguing effects of this modification on the mean axial flow, turbulent statistics, force balance, and dynamic processes such as turbulence production and dissipation are discussed.
Existence and uniqueness of two dimensional Euler-Poisson system and WKB approximation to the nonlinear Schrödinger-Poisson system
Authors: Masaki Satoshi , Ogawa Takayoshi
Published: December 2015

In this paper, we study a dispersive Euler-Poisson system in two dimensional Euclidean space. Our aim is to show unique existence and the zero-dispersion limit of the time-local weak solution. Since one may not use dispersive structure in the zero-dispersion limit, when reducing the regularity, lack of critical embedding H1⊊L∞ becomes a bottleneck. We hence employ an estimate on the best constant of the Gagliardo-Nirenberg inequality. By this argument, a reasonable convergence rate for the zero-dispersion limit is deduced with a slight loss. We also consider the semiclassical limit problem of the Schrödinger-Poisson system in two dimensions.
Local measurement of thermal conductivity and diffusivity
Authors: Hurley David H. , Schley Robert S. , Khafizov Marat , Wendt Brycen L.
Published: December 2015

Simultaneous measurement of local thermal diffusivity and conductivity is demonstrated on a range of ceramic samples. This was accomplished by measuring the temperature field spatial profile of samples excited by an amplitude modulated continuous wave laser beam. A thin gold film is applied to the samples to ensure strong optical absorption and to establish a second boundary condition that introduces an expression containing the substrate thermal conductivity. The diffusivity and conductivity are obtained by comparing the measured phase profile of the temperature field to a continuum based model. A sensitivity analysis is used to identify the optimal film thickness for extracting the both substrate conductivity and diffusivity. Proof of principle studies were conducted on a range of samples having thermal properties that are representatives of current and advanced accident tolerant nuclear fuels. It is shown that by including the Kapitza resistance as an additional fitting parameter, the measured conductivity and diffusivity of all the samples considered agreed closely with the literature values. A distinguishing feature of this technique is that it does not require a priori knowledge of the optical spot size which greatly increases measurement reliability and reproducibility.
Contraction coefficients for noisy quantum channels
Authors: Hiai Fumio , Ruskai Mary Beth
Published: December 2015

Generalized relative entropy, monotone Riemannian metrics, geodesic distance, and trace distance are all known to decrease under the action of quantum channels. We give some new bounds on, and relationships between, the maximal contraction for these quantities.
Plasma lenses for ultrashort multi-petawatt laser pulses
Authors: Palastro J. P. , Gordon D. , Hafizi B. , Johnson L. A. , Peñano J. , Hubbard R. F. , Helle M. , Kaganovich D.
Published: December 2015

An ideal plasma lens can provide the focusing power of a small f-number, solid-state focusing optic at a fraction of the diameter. An ideal plasma lens, however, relies on a steady-state, linear laser pulse-plasma interaction. Ultrashort multi-petawatt (MPW) pulses possess broad bandwidths and extreme intensities, and, as a result, their interaction with the plasma lens is neither steady state nor linear. Here, we examine nonlinear and time-dependent modifications to plasma lens focusing, and show that these result in chromatic and phase aberrations and amplitude distortion. We find that a plasma lens can provide enhanced focusing for 30 fs pulses with peak power up to ∼1 PW. The performance degrades through the MPW regime, until finally a focusing penalty is incurred at ∼10 PW.
Adding 0.2 V to the open circuit voltage of organic solar cells by enhancing the built-in potential
Authors: Tessler Nir
Published: December 2015

We present a systematic device model that reproduces the important features of bulk heterojunction organic solar cells. While examining the model outputs we find that one of the limiting factors in organic solar cells is the reduced built-in potential due to effective pinning of the electrodes relative to the energy gap at the bulk of the device. Having identified this as a problem we suggest a device structure that can enhance the open circuit voltage. Our detailed modeling shows that such a structure can enhance the open circuit voltage as well as the short circuit current leading to above 40% improvement in power conversion efficiency of state of the art organic solar cells.
Model reduction for stochastic chemical systems with abundant species
Authors: Smith Stephen , Cianci Claudia , Grima Ramon
Published: December 2015

Biochemical processes typically involve many chemical species, some in abundance and some in low molecule numbers. We first identify the rate constant limits under which the concentrations of a given set of species will tend to infinity (the abundant species) while the concentrations of all other species remains constant (the non-abundant species). Subsequently, we prove that, in this limit, the fluctuations in the molecule numbers of non-abundant species are accurately described by a hybrid stochastic description consisting of a chemical master equation coupled to deterministic rate equations. This is a reduced description when compared to the conventional chemical master equation which describes the fluctuations in both abundant and non-abundant species. We show that the reduced master equation can be solved exactly for a number of biochemical networks involving gene expression and enzyme catalysis, whose conventional chemical master equation description is analytically impenetrable. We use the linear noise approximation to obtain approximate expressions for the difference between the variance of fluctuations in the non-abundant species as predicted by the hybrid approach and by the conventional chemical master equation. Furthermore, we show that surprisingly, irrespective of any separation in the mean molecule numbers of various species, the conventional and hybrid master equations exactly agree for a class of chemical systems.
Transition probabilities of normal states determine the Jordan structure of a quantum system
Authors: Leung Chi-Wai , Ng Chi-Keung , Wong Ngai-Ching
Published: December 2015

Let Φ : 𝔖(M1) → 𝔖(M2) be a bijection (not assumed affine nor continuous) between the sets of normal states of two quantum systems, modelled on the self-adjoint parts of von Neumann algebras M1 and M2, respectively. This paper concerns with the situation when Φ preserves (or partially preserves) one of the following three notions of “transition probability” on the normal state spaces: the transition probability PU introduced by Uhlmann [Rep. Math. Phys. 9, 273-279 (1976)], the transition probability PR introduced by Raggio [Lett. Math. Phys. 6, 233-236 (1982)], and an “asymmetric transition probability” P0 (as introduced in this article). It is shown that the two systems are isomorphic, i.e., M1 and M2 are Jordan ∗-isomorphic, if Φ preserves all pairs with zero Uhlmann (respectively, Raggio or asymmetric) transition probability, in the sense that for any normal states μ and ν, we have PΦ(μ),Φ(ν)=0 if and only if P(μ, ν) = 0, where P stands for PU (respectively, PR or P0). Furthermore, as an extension of Wigner’s theorem, it is shown that there is a Jordan ∗-isomorphism Θ : M2 → M1 satisfying Φ = Θ∗|𝔖(M1) if and only if Φ preserves the “asymmetric transition probability.” This is also equivalent to Φ preserving the Raggio transition probability. Consequently, if Φ preserves the Raggio transition probability, it will preserve the Uhlmann transition probability as well. As another application, the sets of normal states equipped with either the usual metric, the Bures metric or “the metric induced by the self-dual cone,” are complete Jordan ∗-invariants for the underlying von Neumann algebras.
Growth and characterization of ZnO1−xSx highly mismatched alloys over the entire composition
Authors: Jaquez M. , Yu K. M. , Ting M. , Hettick M. , Sánchez-Royo J. F. , Wełna M. , Javey A. , Dubon O. D. , Walukiewicz W.
Published: December 2015

Alloys from ZnO and ZnS have been synthesized by radio-frequency magnetron sputtering over the entire alloying range. The ZnO1−xSx films are crystalline for all compositions. The optical absorption edge of these alloys decreases rapidly with small amount of added sulfur (x ∼ 0.02) and continues to red shift to a minimum of 2.6 eV at x = 0.45. At higher sulfur concentrations (x > 0.45), the absorption edge shows a continuous blue shift. The strong reduction in the band gap for O-rich alloys is the result of the upward shift of the valence-band edge with x as observed by x-ray photoelectron spectroscopy. As a result, the room temperature bandgap of ZnO1−xSx alloys can be tuned from 3.7 eV to 2.6 eV. The observed large bowing in the composition dependence of the energy bandgap arises from the anticrossing interactions between (1) the valence-band of ZnO and the localized sulfur level at 0.30 eV above the ZnO valence-band maximum for O-rich alloys and (2) the conduction-band of ZnS and the localized oxygen level at 0.20 eV below the ZnS conduction band minimum for the S-rich alloys. The ability to tune the bandgap and knowledge of the location of the valence and conduction-band can be advantageous in applications, such as heterojunction solar cells, where band alignment is crucial.
Ultra-compact and wide-spectrum-range thermo-optic switch based on silicon coupled photonic crystal microcavities
Authors: Zhang Xingyu , Chakravarty Swapnajit , Chung Chi-Jui , Pan Zeyu , Yan Hai , Chen Ray T.
Published: December 2015

We design, fabricate, and experimentally demonstrate a compact thermo-optic gate switch comprising a 3.78 μm-long coupled L0-type photonic crystal microcavities on a silicon-on-insulator substrate. A nanohole is inserted in the center of each individual L0 photonic crystal microcavity. Coupling between identical microcavities gives rise to bonding and anti-bonding states of the coupled photonic molecules. The coupled photonic crystal microcavities are numerically simulated and experimentally verified with a 6 nm-wide flat-bottom resonance in its transmission spectrum, which enables wider operational spectrum range than microring resonators. An integrated micro-heater is in direct contact with the silicon core to efficiently drive the device. The thermo-optic switch is measured with an optical extinction ratio of 20 dB, an on-off switching power of 18.2 mW, a thermo-optic tuning efficiency of 0.63 nm/mW, a rise time of 14.8 μs, and a fall time of 18.5 μs. The measured on-chip loss on the transmission band is as low as 1 dB.
Charge transfer excitons at ZnMgO/P3HT heterojunctions: Relation to photovoltaic performance
Authors: Eyer M. , Sadofev S. , Puls J. , Blumstengel S.
Published: December 2015

Formation of hybrid charge transfer excitons (HCTE), i.e., coulombically bound charge pairs residing at inorganic/organic interfaces is verified in prototypical ZnMgO/poly(3-hexylthiophene) (P3HT) planar heterojunctions. Radiative recombination of HCTE generates electroluminescence (EL) in the near infrared spectral region. Via the Mg content, the energy offset ΔEIO between the ZnMgO conduction band minimum and the P3HT highest occupied molecular orbital is systematically tuned. Both, the EL emission maximum as well as the open circuit voltage VOC, scale linearly with ΔEIO, showing the clear correlation between the HCTE transition energy and the VOC at inorganic/organic semiconductor heterojunctions.
Influence of wetting state on optical reflectance spectra of Si nanopillar arrays
Authors: Gwon Minji , Kim Sujung , Li Jiaqi , Xu Xiumei , Kim Sun-Kyung , Lee Eunsongyi , Kim Dong-Wook , Chen Chang
Published: December 2015

Finite-difference time-domain (FDTD) simulations showed that the reflectance spectra of crystalline Si nanopillar (NP) arrays with diameters of 40, 70, 100, and 130 nm differed depending on wetting state. The observed reflectance dips of the 40-nm-diameter NP array were in good agreement with those estimated from destructive interference conditions at the top and bottom of the NPs: the NP arrays were treated as a homogeneous medium with an effective permittivity according to the effective medium approximation model. In contrast, the dip positions of the FDTD-simulated spectra for 70-, 100-, and 130-nm-diameter NP arrays deviated from the results of interference calculations, particularly for short wavelengths. This suggested that Mie resonances in individual NPs significantly increased the absorption cross-section at the resonant wavelengths, which was sensitive to the refractive index of the surrounding medium (i.e., the wetting state). Optical reflectance measurements provide an easy and efficient means of inspecting the wetting behavior of non-flat surfaces.
Program to characterize US nuclear stockpile declared a success
Authors: Kramer David
Published: December 2015

Officials say their understanding of nuclear systems is now better than it was during the era of underground testing.
Solid-state cooling with caloric materials
Authors: Takeuchi Ichiro , Sandeman Karl
Published: December 2015

The drive to replace volatile liquid refrigerants is gaining steam, with potentially disruptive technologies on the horizon.
HAARP, the most powerful ionosphere heater on Earth
Authors: Pedersen Todd
Published: December 2015

When stimulated with high-intensity radio waves, the ionosphere responds with baffling and beautiful displays.
Nursing staff work patterns in a residential aged care home: a time–motion study
Authors: Qian Siyu , Yu Ping , Hailey David
Published: November 2015

Objective Residential aged care services are challenged by an increasing number of residents and a shortage of nursing staff. Developing strategies to overcome this challenge requires an understanding of nursing staff work patterns. The aim of the present study was to investigate the work processes followed by nursing staff and how nursing time is allocated in a residential aged care home. Methods An observational time–motion study was conducted at two aged care units for 12 morning shifts. Seven nurses were observed, one per shift. Results In all, there were 91 h of observation. The results showed that there was a common work process followed by all nurse participants. Medication administration, documentation and verbal communication were the most time-consuming activities and were conducted most frequently. No significant difference between the two units was found in any category of activities. The average duration of most activities was less than 1 min. There was no difference in time utilisation between the endorsed enrolled nurses and the personal carers in providing nursing care. Conclusion Medication administration, documentation and verbal communication were the major tasks in morning shifts in a residential aged care home. Future research can investigate how verbal communication supports nursing care. What is known about the topic? The aging population will substantially increase the demand for residential aged care services. There is a lack of research on nurses’ work patterns in residential aged care homes. What does this paper add? The present study provides a comprehensive understanding of nurses’ work patterns in a residential aged care home. There is a common work process followed by nurses in providing nursing care. Medication administration, verbal communication and documentation are the most time-consuming activities and they are frequently conducted in the same period of time. Wound care, physical review and documentation on desktop computers are arranged flexibly by the nurses. What are the implications for practitioners? When developing a task reallocation strategy to improve work efficiency, effort can be put into tasks that can be arranged more flexibly.
Cationic Micelles Based on Polyhedral Oligomeric Silsesquioxanes for Enhanced Gene Transfection
Authors: Liu Connie K. , Dou Qingqing , Liow Sing Shy , Kumar Jatin N. , Loh Xian Jun
Published: November 2015

The synthesis and gene transfection efficiency of a series of amphiphilic copolymers, poly(2-(dimethylamino)ethyl methacrylate)-poly (methacrylate isobutyl polyhedral oligomeric silsesquioxane) (PDMAEMA-POSS) copolymers are reported. The hydrophobic POSS interior allows a cell-sensitizing drug such as paclitaxel to be incorporated, whereas the cationic and hydrophilic PDMAEMA corona allows the complexation of anionic DNA to form a nano-sized polyplex. These drug-encapsulated copolymers display excellent gene transfection efficiency compared with polyethylenimine or PDMAEMA homopolymers.
Carbon dioxide fertilisation and supressed respiration induce enhanced spring biomass production in a mixed species temperate meadow exposed to moderate carbon dioxide enrichment
Authors: Haworth Matthew , Moser Gerald , Raschi Antonio , Kammann Claudia , Grünhage Ludger , Müller Christoph
Published: November 2015

The rising concentration of carbon dioxide in the atmosphere ([CO2]) has a direct effect on terrestrial vegetation through shifts in the rates of photosynthetic carbon uptake and transpirational water-loss. Free Air CO2 Enrichment (FACE) experiments aim to predict the likely responses of plants to increased [CO2] under normal climatic conditions. The Giessen FACE system operates a lower [CO2] enrichment regime (480 μmol mol–1) than standard FACE (550–600 μmol mol–1), permitting the analysis of a mixed species temperate meadow under a [CO2] level equivalent to that predicted in 25–30 years. We analysed the physiological and morphological responses of six species to investigate the effect of moderate [CO2] on spring biomass production. Carbon dioxide enrichment stimulated leaf photosynthetic rates and supressed respiration, contributing to enhanced net assimilation and a 23% increase in biomass. The capacity for photosynthetic assimilation was unaffected by [CO2] enrichment, with no downregulation of rates of carboxylation of Rubisco or regeneration of ribulose-1,5-bisphosphate. Foliar N content was also not influenced by increased [CO2]. Enhanced [CO2] reduced stomatal size, but stomatal density and leaf area index remained constant, suggesting that the effect on gas exchange was minimal.
Love moderates the relationship between partner type and condom use among women engaging in transactional vaginal sex
Authors: Roth Alexis M. , Rosenberger Joshua G. , Hensel Devon J. , Wiehe Sarah E. , Fortenberry J. Dennis , Wagner Karla D.
Published: November 2015

Background
Relationship characteristics and day-to-day variation in affective state have been associated with HIV risk behaviour. However, no research has assessed the impact of these factors on event-level condom use among women engaging in transactional sex. Methods: Twenty-six women engaging in transactional sex were enrolled in a prospective study of their sexual health. They completed diaries about multi-level predictors of condom use during vaginal sex twice, daily. Results: Over 4 weeks, 18 participants reported 87 paid/traded vaginal intercourse events. Of these, 51.7% were condom protected. The majority of paid/traded events (81.5%) occurred with a non-romantic partner. After controlling for partner type, feeling in love on a given day was associated with higher odds of condom use during paid/traded sexual events, while having sex on the weekend and at night were associated with lower odds of condom use (all P ≤ 0.05). There was a significant interaction between being in love and using condoms during transactional sex (P < 0.01). In paid/traded sexual events with romantic partners, the frequency of condom use was 71.4% (5/7) when women did not report love and 40% (4/10) when love was reported. In sexual events with non-romantic partners, the frequency of condom use was 43.8% (14/32) when women did not report love and 59.5% (22/37) when love was reported. Conclusions: Women were less likely to report protected sex with romantic partners and more likely to report protected sex with non-romantic partners when they are in love. Interventions focusing on the link between day-to-day variation in affective state on condom use may help women with risk management across partner types.
Procedure to estimate ammonia loss after N fertiliser application to moist soil
Authors: Fillery Ian R. P. , Khimashia Nirav
Published: November 2015

Decision support systems (DSS) that provide advice on best N fertiliser management practice ideally need to assess the effect that fertiliser type, rate and management have on N loss. Currently only nitrate leaching and denitrification losses can be assessed in Australian DSS that use output from the Agriculture Production Simulator (APSIM). This paper describes a simple spreadsheet-based model for estimating NH3 loss from urea, urea ammonium nitrate and ammonium sulfate that can be used in conjunction or independent of current DSS. The use of scaling factors that reduce NH3 emission on the basis of factors known to be key determinants of NH3 loss, including type of fertiliser used, rate of fertiliser applied, management of fertiliser, rainfall and crop development was found to account for 85% of the variance between predicted and observed values when tested against 40 case studies. The model also had good predictive power with a root mean square error (RMSE) equivalent to 4.8% of N applied.
Rudimentary empathy in macaques’ social decision-making
Authors: Ballesta Sebastien , Duhamel Jean-René
Published: December 2015

Significance

We investigated nonhuman primate prosociality within a decision-making behavioral framework. Our results suggest that macaques have a concept of their peers’ well being. The strength and originality of our experimental design is in challenging monkeys with several decisions involving both pleasant and unpleasant outcomes to self and others, thus allowing us to evaluate social motivation in different contexts. Behavioral measures, such as empathic eye blinking and mutual looking, show that the degrees of empathy and of willingness to interact with peers differ among individuals. These differences were mainly consistent with the preexisting social bonds displayed within our group-housed monkeys. Our results thus provide evidence of partner-dependent behavioral mechanisms shaping primates’ social decisions.
Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain
Authors: Forsyth Jennifer K. , Bachman Peter , Mathalon Daniel H. , Roach Brian J. , Asarnow Robert F.
Published: December 2015

Significance

Experience-dependent plasticity is the capacity of the brain to undergo changes following environmental input and use, and is a primary means through which the adult brain enables new behavior. In the current study, we provide evidence that enhancing signaling at the glutamate
N
-methyl-
d
-aspartate receptor (NMDAR) can enhance the mechanism underlying many forms of experience-dependent plasticity (i.e., long-term potentiation of synaptic currents) and also enhance experience-dependent learning in healthy adult humans. This suggests exciting possibilities for manipulating plasticity in adults and has implications for treating neurological and neuropsychiatric disorders in which experience-dependent plasticity is impaired.
How culture gets embrained: Cultural differences in event-related potentials of social norm violations
Authors: Mu Yan , Kitayama Shinobu , Han Shihui , Gelfand Michele J.
Published: December 2015

Significance

Despite the fact that social norms are a fundamental aspect of human nature, there has been little research on how social norm violations are detected at the neurobiological level. Combining a new social norm violation paradigm with cross-cultural electroencephalography, we show consistent negative deflection of event-related potential around 400 ms (N400) over the central and parietal regions for both Americans and Chinese in detecting norm violations. However, the N400 at the frontal and temporal regions was evident only among Chinese, illustrating culture-specific neural substrates underlying detecting norm violations. Moreover, the frontal N400 was associated with greater cultural superiority and self-control, as well as lower creativity. The findings shed new light on the neurobiology of the detection of social norm violations.
Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination
Authors: Zhou Liang , Yang Dong , Wang De-Juan , Xie Ya-Jun , Zhou Jia-Huan , Zhou Lin , Huang Hao , Han Shuo , Shao Chong-Yu , Li Hua-Shun , Zhu J. Julius , Qiu Meng-Sheng , De Zeeuw Chris I. , Shen Ying
Published: December 2015

Significance

Protein Numb controls cell fate by interacting with a number of signaling molecules, critical for maintaining neural stem cells and neuronal development in the central nervous system. However, the function of Numb has not been studied in mature neurons. Here, we found that deletion of Numb in cerebellar Purkinje cells causes deficits in motor learning, which can be ascribed to a reduced level of synaptic metabotropic glutamate 1 receptor (mGlu1). Although Numb deficiency does not alter the expression of mGlu1-associated proteins and activity-dependent plasticity of mGlu1, it inhibits intracellular trafficking of mGlu1. To our knowledge, our work is the first to demonstrate an important function of Numb in mature neurons.
Ventral and dorsal streams for choosing word order during sentence production
Authors: Thothathiri Malathi , Rattinger Michelle
Published: December 2015

Significance

Languages allow multiple word orders for expressing the same meaning. Prior statistical experience with verbs in less-common sentence structures is known to facilitate subsequent use of those structures. To investigate how this is implemented in the brain, we trained participants in an artificial language and examined how they used that language to describe novel scenarios. Different verbs were associated with different word orders during training. Functional activation and connectivity patterns revealed that the choice of word order was supported by a ventral pathway for verbs that appeared in two competing orders, and dorsal pathways for verbs that appeared exclusively in the less-common order. Thus, the brain accomplishes the same language output via different routes, depending on past experience.
Discontinuous shear thickening in Brownian suspensions by dynamic simulation
Authors: Mari Romain , Seto Ryohei , Morris Jeffrey F. , Denn Morton M.
Published: December 2015

Significance

Colloidal shear thickening is a phenomenon by which a dense mixture (or suspension) of sub–micrometer-sized particles in a fluid becomes more viscous when strained. It has important (mostly negative) consequences as dense suspensions are found in many industrial processes. Its origin is a long-standing unsolved problem in soft-matter physics. We perform dynamic simulations that show that the shear thickening may be explained as a stress-induced transition from a flow of lubricated near-contacting particles to a flow of a frictionally contacting network of particles. Our numerical data quantitatively match previous experimental data.
Thirty-year quest for structure–nucleation relationships in oxide glasses
Authors: Zanotto E. D. , Tsuchida J. E. , Schneider J. F. , Eckert H.
Published: December 2015

Over the past three decades, researchers have investigated the existence of possible relationships between crystal nucleation kinetics and the atomic-scale structure of silicate glasses. The main driving force for this quest was the fact that while the vast majority of glass-forming substances only undergo surface (heterogeneous) nucleation when sufficiently heated, a few systems also show the thermodynamically less favourable case of internal (homogeneous) nucleation on laboratory time/length scales. For such glass systems, various macroscopic properties, such as densities, configurational entropies and frozen-in birefringence, have suggested that the structure in the glassy state shows a closer resemblance to the structure of the phase formed upon crystallisation than in the case of glass systems only undergoing heterogeneous nucleation. However, the specific structural features and their length scales have remained uncertain. In this article, we review and discuss the research investigating relationships between the occurrence of internal nucleation and structural parameters related to various different length scales. The latter include (1) short-range order, concerning both network modifier cation-oxygen distances and coordination numbers as well as network former Q n distributions, (2) intermediate range order describing network former connectivities, network former/network modifier correlations, and network modifier distance distributions, and (3) medium range order as reflected by silicate tetrahedral ring-size statistics. Inspection of this data for several stoichiometric oxide glasses and their respective isochemical crystals suggests a positive correlation between homogeneous nucleation ability and structural similarity at the level of short- and intermediate-range order of the network modifier cations. In contrast, no correlation can be found with regard to any structural parameters describing the local structures of the network former species ( Q n distributions). Based on the limited set of data available, we develop concrete recommendations for future experiments to test this hypothesis.
An Asp–CaM complex is required for centrosome–pole cohesion and centrosome inheritance in neural stem cells
Authors: Schoborg Todd , Zajac Allison L. , Fagerstrom Carey J. , Guillen Rodrigo X. , Rusan Nasser M.
Published: December 2015

The interaction between centrosomes and mitotic spindle poles is important for efficient spindle formation, orientation, and cell polarity. However, our understanding of the dynamics of this relationship and implications for tissue homeostasis remains poorly understood. Here we report that Drosophila melanogaster calmodulin (CaM) regulates the ability of the microcephaly-associated protein, abnormal spindle (Asp), to cross-link spindle microtubules. Both proteins colocalize on spindles and move toward spindle poles, suggesting that they form a complex. Our binding and structure–function analysis support this hypothesis. Disruption of the Asp–CaM interaction alone leads to unfocused spindle poles and centrosome detachment. This behavior leads to randomly inherited centrosomes after neuroblast division. We further show that spindle polarity is maintained in neuroblasts despite centrosome detachment, with the poles remaining stably associated with the cell cortex. Finally, we provide evidence that CaM is required for Asp’s spindle function; however, it is completely dispensable for Asp’s role in microcephaly suppression.
Accurate continuous geographic assignment from low- to high-density SNP data
Authors: Guillot Gilles , Jónsson Hákon , Hinge Antoine , Manchih Nabil , Orlando Ludovic
Published: November 2015

Motivation: Large-scale genotype datasets can help track the dispersal patterns of epidemiological outbreaks and predict the geographic origins of individuals. Such genetically-based geographic assignments also show a range of possible applications in forensics for profiling both victims and criminals, and in wildlife management, where poaching hotspot areas can be located. They, however, require fast and accurate statistical methods to handle the growing amount of genetic information made available from genotype arrays and next-generation sequencing technologies.

Results: We introduce a novel statistical method for geopositioning individuals of unknown origin from genotypes. Our method is based on a geostatistical model trained with a dataset of georeferenced genotypes. Statistical inference under this model can be implemented within the theoretical framework of Integrated Nested Laplace Approximation, which represents one of the major recent breakthroughs in statistics, as it does not require Monte Carlo simulations. We compare the performance of our method and an alternative method for geospatial inference, SPA in a simulation framework. We highlight the accuracy and limits of continuous spatial assignment methods at various scales by analyzing genotype datasets from a diversity of species, including Florida Scrub-jay birds Aphelocoma coerulescens, Arabidopsis thaliana and humans, representing 41–197,146 SNPs. Our method appears to be best suited for the analysis of medium-sized datasets (a few tens of thousands of loci), such as reduced-representation sequencing data that become increasingly available in ecology.

Availability and implementation:  http://www2.imm.dtu.dk/∼gigu/Spasiba/

Contact:  gilles.b.guillot@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Comment on: ‘ERGC: an efficient referential genome compression algorithm’
Authors: Deorowicz Sebastian , Grabowski Szymon , Ochoa Idoia , Hernaez Mikel , Weissman Tsachy
Published: November 2015

Motivation: Data compression is crucial in effective handling of genomic data. Among several recently published algorithms, ERGC seems to be surprisingly good, easily beating all of the competitors.

Results: We evaluated ERGC and the previously proposed algorithms GDC and iDoComp, which are the ones used in the original paper for comparison, on a wide data set including 12 assemblies of human genome (instead of only four of them in the original paper). ERGC wins only when one of the genomes (referential or target) contains mixed-cased letters (which is the case for only the two Korean genomes). In all other cases ERGC is on average an order of magnitude worse than GDC and iDoComp.

Contact:  sebastian.deorowicz@polsl.pl, iochoa@stanford.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The impact of real-time alerting on appropriate prescribing in kidney disease: a cluster randomized controlled trial
Authors: Awdishu Linda , Coates Carrie R , Lyddane Adam , Tran Kim , Daniels Charles E , Lee Joshua , El-Kareh Robert
Published: November 2015

Background

Patients with kidney disease are at risk for adverse events due to improper medication prescribing. Few randomized controlled trials of clinical decision support (CDS) utilizing dynamic assessment of patients’ kidney function to improve prescribing for patients with kidney disease have been published.

Methods

We developed a CDS tool for 20 medications within a commercial electronic health record. Our system detected scenarios in which drug discontinuation or dosage adjustment was recommended for adult patients with impaired renal function in the ambulatory and acute settings – both at the time of the initial prescription (“prospective” alerts) and by monitoring changes in renal function for patients already receiving one of the study medications (“look-back” alerts). We performed a prospective, cluster randomized controlled trial of physicians receiving clinical decision support for renal dosage adjustments versus those performing their usual workflow. The primary endpoint was the proportion of study prescriptions that were appropriately adjusted for patients’ kidney function at the time that patients’ conditions warranted a change according to the alert logic. We employed multivariable logistic regression modeling to adjust for glomerular filtration rate, gender, age, hospitalized status, length of stay, type of alert, time from start of study, and clustering within the prescribing physician on the primary endpoint.

Results

A total of 4068 triggering conditions occurred in 1278 unique patients; 1579 of these triggering conditions generated alerts seen by physicians in the intervention arm and 2489 of these triggering conditions were captured but suppressed, so as not to generate alerts for physicians in the control arm. Prescribing orders were appropriate adjusted in 17% of the time vs 5.7% of the time in the intervention and control arms, respectively (odds ratio: 1.89, 95% confidence interval, 1.45-2.47, P < .0001). Prospective alerts had a greater impact than look-back alerts (55.6% vs 10.3%, in the intervention arm).

Conclusions

The rate of appropriate drug prescribing in kidney impairment is low and remains a patient safety concern. Our results suggest that CDS improves drug prescribing, particularly when providing guidance on new prescriptions.
Probabilistic frames for non-Boolean phenomena
Authors: Narens Louis
Published: December 2015

Classical probability theory, as axiomatized in 1933 by Andrey Kolmogorov, has provided a useful and almost universally accepted theory for describing and quantifying uncertainty in scientific applications outside quantum mechanics. Recently, cognitive psychologists and mathematical economists have provided examples where classical probability theory appears inadequate but the probability theory underlying quantum mechanics appears effective. Formally, quantum probability theory is a generalization of classical probability. This article explores relationships between generalized probability theories, in particular quantum-like probability theories and those that do not have full complementation operators (e.g. event spaces based on intuitionistic logic), and discusses how these generalizations bear on important issues in the foundations of probability and the development of non-classical probability theories for the behavioural sciences.
Disease variants alter transcription factor levels and methylation of their binding sites
Authors: Bonder Marc Jan , Luijk René , Zhernakova Daria , Moed Matthijs , Deelen Patrick , Vermaat Martijn , van Iterson Maarten , van Dijk Freerk , van Galen Michiel , Bot Jan , Slieker Roderick C. , Jhamai P. Mila , Verbiest Michael , Suchiman H. Eka D. , Verkerk Marijn , van der Breggen Ruud , van Rooij Jeroen , Lakenberg Nico , Arindrarto Wibowo , Kielbasa Szymon M. , Jonkers Iris , van t Hof Peter , Nooren Irene , Beekman Marian , Deelen Joris , van Heemst Diana , Zhernakova Alexandra , Tigchelaar Ettje F. , Swertz Morris A. , Hofman Albert , Uitterlinden André G. , Pool René , van Dongen Jenny , Hottenga Jouke J. , Stehouwer Coen D.A. , van der Kallen Carla J.H. , Schalkwijk Casper G. , van den Berg Leonard H. , van Zwet Erik. W , Mei Hailiang , Li Yang , Lemire Mathieu , Hudson Thomas J. , Slagboom P. Eline , Wijmenga Cisca , Veldink Jan H. , van Greevenbroek Marleen M.J. , van Duijn Cornelia M. , Boomsma Dorret I. , Isaacs Aaron , Jansen Rick , van Meurs Joyce , t Hoen Peter A.C. , Franke Lude , Heijmans Bastiaan T.
Published: December 2015

Most disease associated genetic risk factors are non-coding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer downstream effects of disease variants but the large majority remains unexplained.. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions. However, a large-scale, combined analysis of methylome and transcriptome data to infer downstream effects of disease variants is lacking. Here, we show that disease variants have wide-spread effects on DNA methylation in trans that likely reflect the downstream effects on binding sites of cis-regulated transcription factors. Using data on 3,841 Dutch samples, we detected 272,037 independent cis-meQTLs (FDR < 0.05) and identified 1,907 trait-associated SNPs that affect methylation levels of 10,141 different CpG sites in trans (FDR < 0.05), an eight-fold increase in the number of downstream effects that was known from trans-eQTL studies. Trans-meQTL CpG sites are enriched for active regulatory regions, being correlated with gene expression and overlap with Hi-C determined interchromosomal contacts. We detected many trans-meQTL SNPs that affect expression levels of nearby transcription factors (including NFKB1, CTCF and NKX2-3), while the corresponding trans-meQTL CpG sites frequently coincide with its respective binding site. Trans-meQTL mapping therefore provides a strategy for identifying and better understanding downstream functional effects of many disease-associated variants.
The role of deleterious substitutions in crop genomes
Authors: Kono Thomas J. Y. , Fu Fengli , Mohammadi Mohsen , Hoffman Paul J. , Liu Chaochih , Stupar Robert M. , Smith Kevin P. , Tiffin Peter , Fay Justin C. , Morrell Peter L.
Published: November 2015

Populations continually incur new mutations with fitness effects ranging from lethal to adaptive. While the distribution of fitness effects (DFE) of new mutations is not directly observable, many mutations likely have either no effect on organismal fitness or are deleterious. Historically, it has been hypothesized that a population may carry many mildly deleterious variants as segregating variation, which reduces the mean absolute fitness of the population. Recent advances in sequencing technology and sequence conservation-based metrics for inferring the functional effect of a variant permit examination of the persistence of deleterious variants in populations. The issue of segregating deleterious variation is particularly important for crop improvement, because the demographic history of domestication and breeding allows deleterious variants to persist and reach moderate frequency, potentially reducing crop productivity. In this study, we use exome resequencing of fifteen barley accessions and genome resequencing of eight soybean accessions to investigate the prevalence of deleterious SNPs in the protein-coding regions of the genomes of two crops. We conclude that individual cultivars carry hundreds of deleterious SNPs on average, and that nonsense variants make up a minority of deleterious SNPs. Our approach annotates known phenotype-altering variants as deleterious more frequently than the genome-wide average, suggesting that putatively deleterious variants are likely to affect phenotypic variation. We also report the implementation of a SNP annotation tool (BAD_Mutations) that makes use of a likelihood ratio test based on alignment of all currently publicly available Angiosperm genomes.