bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilevel resistive switching in TiO2/Al2O3 bilayers at low temperature
Authors: Andreeva N. , Ivanov A. , Petrov A.
Published: February 2018

We report an approach to design a metal-insulator-metal (MIM) structure exhibiting multilevel resistive switching. Toward this end, two oxide layers (TiO2 and Al2O3) were combined to form a bilayer structure. MIM structures demonstrate stable bipolar switching relative to the resistive state determined by the bias voltage. The resistive state of such bilayer structures can be electrically tuned over seven orders of magnitude. The resistance is determined by the concentration of oxygen vacancies in the active layer of Al2O3. To elucidate a possible mechanism for resistive switching, structural studies and measurements have been made in the temperature range 50–295 K. Resistive switching occurs over the entire temperature range, which assumes the electronic character of the process in the Al2O3 layer. The experimental results indicate that hopping transport with variable-length jumps is the most probable transport mechanism in these MIM structures.
The effect of energy accumulation and boundary slip on laminar flow between rotating plates
Authors: Wu Zhenpeng , Zeng Liangcai , Chen Keying , Jin Xiaohong , Wu Shiqian
Published: February 2018

The poor operating conditions of fluid lubrication equipment during the start-up process are due to the resistance of the high-viscosity lubricating liquid. Moreover, the excessive reduction in fluid viscosity due to the elevated temperature resulting from power consumption during prolonged operation is not conducive to the generation of dynamic pressure. In this study, we examine the effect of energy accumulation and boundary slip on the laminar flow of a liquid between a pair of rotating plates. The experiments are conducted using a rotary rheometer, with polymethyl methacrylate (PMMA) as the thermal insulation material and polytetrafluoroethylene (PTFE) as the slip drag reduction material, and a three-dimensional simulation model is established. This model is derived by combining the energy equation including the slip length and the heat conduction equation. Thus, the temperature changes over time are predicted by this model, and the model accuracy is verified by experiments. The results reveal the following points: 1) boundary slips function as a drag reduction mechanism for short-time continuous operation; 2) under prolonged operation, the slip reduces the extent of the oil viscosity decrease and clear control of the elevated temperature by the boundary slip is observed.
MeBIK1, a novel cassava receptor-like cytoplasmic kinase, regulates PTI response of transgenic Arabidopsis
Authors: Li Ke , Xiong Xi , Zhu Shousong , Liao Hualan , Xiao Xiaorong , Tang Zhijuan , Hong Yuhui , Li Chunxia , Luo Lijuan , Zheng Linlin , Niu Xiaolei , Chen Yinhua
Published: February 2018

Cassava bacterial blight is the most destructive disease in cassava, causing a significant reduction in its production. The innate immunity response, which has a broad spectrum and a persistent effect, is the basal defence of plants in response to pathogens. Isolation and identification of innate immune-related genes in cassava will contribute to understanding the disease resistance mechanism. In Arabidopsis, the receptor-like cytoplasmic kinase (RLCK) AtBIK1 is known to be an important signal mediator in pathogen-associated molecular pattern-triggered immunity (PTI) response, forming a signal complex from various receptors including the flagellin receptor FLS2, the chitin receptor CERK1 and the receptor for bacterial EF-Tu EFR (Zhang et al. 2010). In the present study, we selected a candidate receptor-like cytoplasmic kinase gene, MeBIK1, from the cassava genome. MeBIK1 encodes a 409 amino acid polypeptide comprising a typical serine/threonine protein kinase domain, and is located on the cell membrane. MeBIK1 gene expression was significantly increased upon stimulation with flagellin (flg22) and peaked at 1 h. In vitro genetic complementation experiment showed that MeBIK1 complemented the reduced pathogen-associated molecular pattern-triggered immunity (PTI) response in Arabidopsis bik1 mutant. Arabidopsis MeBIK1 overexpression lines OX1 demonstrated a strong resistance to Xanthomonas axonopodis pv. manihotis HN01, whereas its sensitivity to Pseudomonas syringae pv. tomato DC3000 was enhanced. The peak level of reactive oxygen species (ROS) burst was reached in different Arabidopsis plants (bik1, OX1 and wild type) at 12 min after induction with flg22. However, the OX1 showed significantly higher ROS levels than the control and mutant, whereas the lowest level of ROS burst was found in the bik1 mutant. These results indicate that cassava MeBIK1 has a similar function as Arabidopsis AtBIK1 and improves disease resistance in transgenic Arabidopsis by regulating the PTI response.
In and out of glacial extremes by way of dust−climate feedbacks
Authors: Shaffer Gary , Lambert Fabrice
Published: February 2018

Significance

In observational data, we find striking and globally coherent increases of atmospheric dust concentrations and deposition during the coldest phases of glacial−interglacial climate cycles. As shown by our simulations with a climate−carbon cycle model, such a relationship between dust and climate implies that dust-induced cooling is responsible for the final step from intermediate to extreme glacial cooling and drawdown of atmospheric CO
2
concentrations. These results also increase our overall understanding of glacial−interglacial cycles by putting further constraints on the timing and strength of other processes involved in these cycles, like changes in sea ice and ice sheet extents or changes in ocean circulation and deep water formation.
Windowed Granger causal inference strategy improves discovery of gene regulatory networks
Authors: Finkle Justin D. , Wu Jia J. , Bagheri Neda
Published: February 2018

Significance

Discovery of gene regulatory networks (GRNs) is crucial for gaining insights into biological processes involved in development or disease. Although time-resolved, high-throughput data are increasingly available, many algorithms do not account for temporal delays underlying regulatory systems—such as protein synthesis and posttranslational modifications—leading to inaccurate network inference. To overcome this challenge, we introduce Sliding Window Inference for Network Generation (SWING), which uniquely accounts for temporal information. We validate SWING in both in silico and in vitro experimental systems, highlighting improved performance in identifying time-delayed edges and illuminating network structure. SWING performance is robust to user-defined parameters, enabling identification of regulatory mechanisms from time-series gene expression data.
Divergent biodiversity change within ecosystems
Authors: Magurran Anne E. , Deacon Amy E. , Moyes Faye , Shimadzu Hideyasu , Dornelas Maria , Phillip Dawn A. T. , Ramnarine Indar W.
Published: February 2018

The Earth’s ecosystems are under unprecedented pressure, yet the nature of contemporary biodiversity change is not well understood. Growing evidence that community size is regulated highlights the need for improved understanding of community dynamics. As stability in community size could be underpinned by marked temporal turnover, a key question is the extent to which changes in both biodiversity dimensions (temporal α- and temporal β-diversity) covary within and among the assemblages that comprise natural communities. Here, we draw on a multiassemblage dataset (encompassing vertebrates, invertebrates, and unicellular plants) from a tropical freshwater ecosystem and employ a cyclic shift randomization to assess whether any directional change in temporal α-diversity and temporal β-diversity exceeds baseline levels. In the majority of cases, α-diversity remains stable over the 5-y time frame of our analysis, with little evidence for systematic change at the community level. In contrast, temporal β-diversity changes are more prevalent, and the two diversity dimensions are decoupled at both the within- and among-assemblage level. Consequently, a pressing research challenge is to establish how turnover supports regulation and when elevated temporal β-diversity jeopardizes community integrity.
POSH regulates Hippo signaling through ubiquitin-mediated expanded degradation
Authors: Ma Xianjue , Guo Xiaowei , Richardson Helena E. , Xu Tian , Xue Lei
Published: February 2018

Significance

Here we performed a genetic screen in
Drosophila
and identified POSH (Plenty of SH3s), an E3 ubiquitin ligase, as a regulator of Hippo pathway. We found POSH ubiquitinates and degrades Ex (Expanded) to inactivate Hippo signaling. Intriguingly, POSH is particularly crucial for damage-induced intestinal stem cell renewal in a Yorki-dependent manner, highlighting the essential physiological role of POSH as a stress sensor in gut epithelia. Given the conservation of the Hippo signaling pathway between
Drosophila
and human, our findings here suggest that POSH might play a similar role in mammalian growth control.
Sex bias in MHC I-associated shaping of the adaptive immune system
Authors: Schneider-Hohendorf Tilman , Görlich Dennis , Savola Paula , Kelkka Tiina , Mustjoki Satu , Gross Catharina C. , Owens Geoffrey C. , Klotz Luisa , Dornmair Klaus , Wiendl Heinz , Schwab Nicholas
Published: February 2018

Significance

Our analysis shows that sex can be associated with the degree to which HLA molecules propagate selection and expansion of T cells as characterized by their T cell receptor variable beta chain (TCRBV). Furthermore, CD8 T cells, especially in men with autoimmune diseases such as multiple sclerosis or rheumatoid arthritis, are capable of expanding in unison with other CD8 T cells, even without expressing TCRBVs with biochemical similarity in pivotal HLA-binding regions. Our findings add to the understanding of sex bias in diseases with immune system involvement: autoimmunity, infection, and cancer. These results also reveal pathology-associated TCRBVs of interest for future studies and support the argument for sex-separated analysis of HLA disease associations in general.
Light color acclimation is a key process in the global ocean distribution ofSynechococcus cyanobacteria
Authors: Grébert Théophile , Doré Hugo , Partensky Frédéric , Farrant Gregory K. , Boss Emmanuel S. , Picheral Marc , Guidi Lionel , Pesant Stéphane , Scanlan David J. , Wincker Patrick , Acinas Silvia G. , Kehoe David M. , Garczarek Laurence
Published: February 2018

MarineSynechococcuscyanobacteria are major contributors to global oceanic primary production and exhibit a unique diversity of photosynthetic pigments, allowing them to exploit a wide range of light niches. However, the relationship between pigment content and niche partitioning has remained largely undetermined due to the lack of a single-genetic marker resolving all pigment types (PTs). Here, we developed and employed a robust method based on three distinct marker genes (cpcBA,mpeBA, andmpeW) to estimate the relative abundance of all knownSynechococcusPTs from metagenomes. Analysis of theTaraOceans dataset allowed us to reveal the global distribution ofSynechococcusPTs and to define their environmental niches. Green-light specialists (PT 3a) dominated in warm, green equatorial waters, whereas blue-light specialists (PT 3c) were particularly abundant in oligotrophic areas. Type IV chromatic acclimaters (CA4-A/B), which are able to dynamically modify their light absorption properties to maximally absorb green or blue light, were unexpectedly the most abundant PT in our dataset and predominated at depth and high latitudes. We also identified populations in which CA4 might be nonfunctional due to the lack of specific CA4 genes, notably in warm high-nutrient low-chlorophyll areas. Major ecotypes within clades I–IV and CRD1 were preferentially associated with a particular PT, while others exhibited a wide range of PTs. Altogether, this study provides important insights into the ecology ofSynechococcusand highlights the complex interactions between vertical phylogeny, pigmentation, and environmental parameters that shapeSynechococcuscommunity structure and evolution.
Monoterpenes are the largest source of summertime organic aerosol in the southeastern United States
Authors: Zhang Haofei , Yee Lindsay D. , Lee Ben H. , Curtis Michael P. , Worton David R. , Isaacman-VanWertz Gabriel , Offenberg John H. , Lewandowski Michael , Kleindienst Tadeusz E. , Beaver Melinda R. , Holder Amara L. , Lonneman William A. , Docherty Kenneth S. , Jaoui Mohammed , Pye Havala O. T. , Hu Weiwei , Day Douglas A. , Campuzano-Jost Pedro , Jimenez Jose L. , Guo Hongyu , Weber Rodney J. , de Gouw Joost , Koss Abigail R. , Edgerton Eric S. , Brune William , Mohr Claudia , Lopez-Hilfiker Felipe D. , Lutz Anna , Kreisberg Nathan M. , Spielman Steve R. , Hering Susanne V. , Wilson Kevin R. , Thornton Joel A. , Goldstein Allen H.
Published: February 2018

Significance

Atmospheric fine organic aerosol impacts air quality, climate, and human health. Speciating and quantifying the sources of organic aerosol on the molecular level improves understanding of their formation chemistry and hence the resulting impacts. Such study, however, has not been possible due to the chemical complexity of atmospheric organic aerosol. Here, we provide comprehensive molecular characterization of atmospheric organic aerosol samples from the southeastern United States by combining state-of-the-art high-resolution mass spectrometry techniques. We find that monoterpene secondary organic aerosol accounts for approximately half of total fine organic aerosol. More importantly, the monoterpene secondary organic aerosol mass increases with enhanced nitrogen oxide processing, indicating anthropogenic influence on biogenic secondary organic aerosol formation.
T cell receptors for the HIV KK10 epitope from patients with differential immunologic control are functionally indistinguishable
Authors: Joglekar Alok V. , Liu Zhe , Weber Jeffrey K. , Ouyang Yong , Jeppson John D. , Noh Won Jun , Lamothe-Molina Pedro A. , Chen Huabiao , Kang Seung-gu , Bethune Michael T. , Zhou Ruhong , Walker Bruce D. , Baltimore David
Published: February 2018

Significance

Success or failure of CD8+ T cell responses dictates whether an infected patient can control HIV durably. HIV-specific CD8+ T cells from HIV controllers and chronic progressors were shown to differ in their antiviral function. Here, we investigated whether HIV-specific T cell receptors (TCRs) can explain functional differences in CD8+ T cells from patients with differential immunologic control. Through in vitro, in vivo, and in silico studies, we found that HIV-specific TCRs were functionally equivalent. These results suggest that the factors that modulate the CD8+ T cell response to HIV are independent of their TCRs.
Structural studies of
Acidianus
tailed spindle virus reveal a structural paradigm used in the assembly of spindle-shaped viruses
Authors: Hochstein Rebecca , Bollschweiler Daniel , Dharmavaram Sanjay , Lintner Nathanael G. , Plitzko Jürgen M. , Bruinsma Robijn , Engelhardt Harald , Young Mark J. , Klug William S. , Lawrence C. Martin
Published: February 2018

The spindle-shaped virion morphology is common among archaeal viruses, where it is a defining characteristic of many viral families. However, structural heterogeneity intrinsic to spindle-shaped viruses has seriously hindered efforts to elucidate the molecular architecture of these lemon-shaped capsids. We have utilized a combination of cryo-electron microscopy and X-ray crystallography to study
Acidianus
tailed spindle virus (ATSV). These studies reveal the architectural principles that underlie assembly of a spindle-shaped virus. Cryo-electron tomography shows a smooth transition from the spindle-shaped capsid into the tubular-shaped tail and allows low-resolution structural modeling of individual virions. Remarkably, higher-dose 2D micrographs reveal a helical surface lattice in the spindle-shaped capsid. Consistent with this, crystallographic studies of the major capsid protein reveal a decorated four-helix bundle that packs within the crystal to form a four-start helical assembly with structural similarity to the tube-shaped tail structure of ATSV and other tailed, spindle-shaped viruses. Combined, this suggests that the spindle-shaped morphology of the ATSV capsid is formed by a multistart helical assembly with a smoothly varying radius and allows construction of a pseudoatomic model for the lemon-shaped capsid that extends into a tubular tail. The potential advantages that this novel architecture conveys to the life cycle of spindle-shaped viruses, including a role in DNA ejection, are discussed.
National trends in drinking water quality violations
Authors: Allaire Maura , Wu Haowei , Lall Upmanu
Published: February 2018

Ensuring safe water supply for communities across the United States is a growing challenge in the face of aging infrastructure, impaired source water, and strained community finances. In the aftermath of the Flint lead crisis, there is an urgent need to assess the current state of US drinking water. However, no nationwide assessment has yet been conducted on trends in drinking water quality violations across several decades. Efforts to reduce violations are of national concern given that, in 2015, nearly 21 million people relied on community water systems that violated health-based quality standards. In this paper, we evaluate spatial and temporal patterns in health-related violations of the Safe Drinking Water Act using a panel dataset of 17,900 community water systems over the period 1982–2015. We also identify vulnerability factors of communities and water systems through probit regression. Increasing time trends and violation hot spots are detected in several states, particularly in the Southwest region. Repeat violations are prevalent in locations of violation hot spots, indicating that water systems in these regions struggle with recurring issues. In terms of vulnerability factors, we find that violation incidence in rural areas is substantially higher than in urbanized areas. Meanwhile, private ownership and purchased water source are associated with compliance. These findings indicate the types of underperforming systems that might benefit from assistance in achieving consistent compliance. We discuss why certain violations might be clustered in some regions and strategies for improving national drinking water quality.
Female migration and its impact on language choice and use among Afro-Costa Rican women
Authors: Philip Lisbeth A.
Published: February 2018

This chapter examines the socio-historical and linguistic impact of two separate historical migratory experiences on a group of 127 Afro-Costa Rican women whose ancestors were, in the vast majority of cases, Black West Indian Immigrants who settled in the province of Limón, Costa Rica. It provides a description of two female migrations, to Costa Rica and later to the United States, to understand their impact on the participants’ choice of language within the family and in the affective domains. These domains of language are used as variables for the sociolinguistic analysis of Language maintenance and language shift (LMLS) among the sample in question in Puerto Limón and Siquirres, the two main economic areas of the province of Limón.
Features of some ergative languages that impact on acquisition
Authors: Bavin Edith L.
Published: February 2018

Bybee’s (e.g., 2006, 2010, 2013) view is that grammar is the cognitive
organisation of one’s experience with the language. Evidence from the
language acquisition field supports this approach. A major task for the
child in acquiring a language is detecting distributional properties of the
language and the co-occurrence of features, that is, identifying the
form-function units in the language input. In this chapter, I briefly
discuss ergative alignment and present examples from research on the
acquisition of ergative languages to show that different cues to ergativity
are provided. The examples illustrate that children quickly attune to
contexts for ergative marking, identifying regularity and recurring patterns
as they construct a grammar.
know and understand in ASL
Authors: Janzen Terry
Published: February 2018

Topic constructions in ASL are understood to be composed of information
identifiable to the addressee that serves as the reference point from which
to view the comment or comments immediately following it. This study
compares the instances of use in a corpus of conversational ASL of KNOW and
UNDERSTAND as lexical verbs and their grammaticalized form and function when
they appear as topic markers, and with know as a discourse marker.
Topic phrases introduced by know tend to have a wider domain as an
identifiable reference point rather than a specific entity or event within
the signer’s and addressee’s shared knowledge. Topic phrases introduced by
understand tend to introduce an idea that the signer wishes to
set as a reference point.
The company that word-boundary sounds keep
Authors: Brown Earl K.
Published: February 2018

This paper analyzes the frequency with which words occur in phonological
contexts favorable to reduction, referred to here as “contextual ratio
frequency.” Duration and center of gravity of word-final /s/ are measured in
the speech of ten speakers of Mexican Spanish living in Salinas, California.
The 1,028 tokens are subjected to mixed effects linear regression, with
speaker and lexical item entered as random effects. The results suggest that
contextual ratio frequency is a better predictor of word-boundary sound
reduction than lexical frequency, and support the idea that words that occur
frequently in phonological contexts conducive to reduction are reduced more
often because words are represented mentally as malleable cognitive entities
that respond to usage-based factors.
Gradient conventionalization of the Spanish expression of ‘becoming’
quedar(se) + ADJ in seven centuries
Authors: Wilson Damián Vergara
Published: February 2018

The present chapter focuses on the evolution of semantic categories in the
Spanish expression of ‘becoming’ quedar(se) + ADJ and
examines how this analogical extension is affected by the
conventionalization of prominent category members. To this end, this study
operationalizes conventionalization through examining factors such as
previous usage, widespread usage, and frequency in developing a gradient
index of conventionalization of specific verb + adjective combinations in a
diachronic corpus. Through developing an index that can be used to compare
the conventionalization of a specific combination from one century to the
next, we see that a robust centralized member will contribute to the ongoing
maintenance and productivity of a semantic category even in the face of
overall frequency reduction of the construction.
The evidence add ups
Authors: Beckner Clay
Published: February 2018

In a usage-based model of the lexicon, linguistic elements that repeatedly
co-occur in sequence come to form a processing unit (Bybee 2002b). The present study supplements
previous psycholinguistic research finding that multiword sequences may form
a ‘prefabricated’ sequence. I describe a new experiment designed to elicit
‘affix shift’ speech errors (e.g., adds up →
add ups), which give evidence of holistic processing of
a multiword sequence. Analysis of the data indicates that affix positioning
errors are predicted by a confluence of factors – a high-frequency
stimulus sequence (settle down) in tandem with
low-frequency component words (settle,
down). These findings provide support for a usage-based
account, in which linguistic units are not fixed, but gradient and
changeable with experience.
Observations of dynamic transformation products in a commercially hot-rolled steel
Authors: Hutchinson Bevis , Komenda Jacek
Published: February 2018

Sufficient evidence has now accumulated to show that dynamic transformation (DT) is a real phenomenon in steels and can take place over a wide range of temperatures in the austenite regime. During plastic deformation, some of the austenite is transformed to ferrite despite austenite being the chemically more stable equilibrium phase. Occurrence of DT has been demonstrated in various laboratory tests but apparently not in commercially hot-rolled steels. In this note, we review some old results on high strength low alloy strip steel that contained microstructural features that appear to have been caused by DT. We deduce that DT occurred early in the rolling schedule, leading to thin-pancaked sheets of ferrite in the final product. The presence of these pre-existing ferrite nuclei frequently gave rise to adjacent regions of coarse polygonal ferrite grains during cooling.
An Opioid Overdose Curriculum for Medical Residents: Impact on Naloxone Prescribing, Knowledge, and Attitudes
Authors: Taylor Jessica L. , Rapoport Alison B. , Rowley Christopher F. , Mukamal Kenneth J. , Stead Wendy
Published: February 2018

Background: Despite escalating opioid overdose death rates, addiction medicine is underrepresented in residency curricula. Providing naloxone to at-risk patients, relatives, and first responders reduces overdose deaths, but rates of naloxone prescribing remain low. The goal of this study is to examine the impact of a brief curricular intervention for internal medicine residents on naloxone prescribing rates, knowledge, and attitudes. Methods: Internal medicine residents ( N = 160) at an urban, tertiary care medical center received two 1-hour didactic sessions addressing overdose prevention, including intranasal naloxone. The number of naloxone prescriptions generated by residents was compared to faculty, who received no similar intervention, in the 3-month periods before and after the curriculum. Resident knowledge and attitudes, as assessed by pre- and post-intervention surveys, were compared. Results: The resident naloxone prescribing rate increased from 420 to 1270 per 100,000 inpatient discharges ( P = .01) and from 0 to 370 per 100,000 ambulatory visits ( P < .001) post-intervention. Similar increases were not observed among inpatient faculty, whose prescribing rate decreased from 1150 to 880 per 100,000 discharges ( P = .08), or among outpatient faculty, whose rate increased from 30 to 180 per 100,000 ambulatory visits ( P < .001) but was lower than the post-intervention resident rate ( P = .01). Residents demonstrated high baseline knowledge about naloxone, but just 13% agreed that they were adequately trained to prescribe pre-intervention. Post-intervention, residents were more likely to agree that they were adequately trained to prescribe (Likert mean 2.5 vs. 3.9, P < .001), to agree that treating addiction is rewarding (Likert mean 2.9 vs. 3.3, P = .03), and to attain a perfect score on the knowledge composite (57% vs. 33%, P = .05). Conclusions: A brief curricular intervention improved resident knowledge and attitudes regarding intranasal naloxone for opioid overdose reversal and significantly increased prescribing rates.
The Relationship between Drug use Settings, Roles in the Drug Economy, and Witnessing a Drug Overdose in Baltimore, Maryland
Authors: Latkin Carl A. , Edwards Catie , Davey-Rothwell Melissa A. , Yang Cui , Tobin Karin E.
Published: February 2018

Background: There has been a dramatic increase in drug overdose deaths in the United States. In the current study, the authors examined factors associated with witnessing a drug overdose. Methods: A sample of 450 substance users in Baltimore, Maryland, were recruited for a behavioral intervention and were administered a survey. Multinomial logistic regression models were used to compare participants who never witnessed a drug overdose with those who witnessed one in the prior 6 months and those who witnessed an overdose over 6 months ago. Results: Most (58%) participants were male, 40% experienced homelessness in the prior 6 months, 63% reported a history of heroin injecting, 84% had snorted heroin, 75% reported witnessing a drug overdose, and 38% experienced an overdose. In multinomial logistic regression models, witnessing an overdose in the past 6 months was associated with number of different types of places where drugs were used (adjusted odds ratio [aOR] = 1.34), history of experiencing an overdose (aOR = 1.80), injecting heroin and/or speedball (aOR = 1.78), and snorting heroin (aOR = 1.54). Witnessing an overdose more than 6 months ago was associated with number of different places where drugs were used (aOR = 1.25), history of experiencing an overdose (aOR = 1.61), snorting heroin (aOR = 1.42), and injecting heroin or speedball (aOR = 1.47). Conclusions: These data suggest that people who engage in more public and frequent drug use, and hence are more likely to witness an overdose, should be targeted for interventions to prevent and treat drug overdose.
Caffeine use in a Super Rugby game and its relationship to post‐game sleep
Authors: Dunican Ian C. , Higgins Charles C. , Jones Maddison J. , Clarke Michael W. , Murray Kevin , Dawson Brian , Caldwell John A. , Halson Shona L. , Eastwood Peter R.
Published: February 2018

Objective: To examine the relationship between regular game‐related caffeine consumption on sleep after an evening Super Rugby game. Methods: Twenty elite rugby union players wore a wrist‐activity monitor to measure sleep for three days before, three days after and on the night of an evening Super Rugby game (19:00–21:00). Players ingested caffeine as they would normally (i.e. before and sometimes during a game) and saliva samples were collected before (17:00) and after (21:30) the game for caffeine concentration. Results: Compared to the nights leading up to the game, on the night of the game, players went to bed 3 h later (23:08 ± 66 min vs 02:11 ± 114 min; p < .001) and had 1:30 hh:mm less sleep (5:54 ± 2:59 vs 8:02 ± 1:24 hh:mm; p < .05) and four players did not sleep after the game. Post‐game caffeine saliva concentrations were greater than pre‐game levels in 17 players (Pre‐game 0.40 µg/mL vs Post‐game 2.77 µg/mL; p < .001). The increase in caffeine saliva concentrations was moderately associated with an increase in sleep latency (p < .05), a decrease in sleep efficiency (p < .05), and a trend for a decrease in sleep duration (p = .06) on game night. Conclusion: Caffeine consumption before a Super Rugby game markedly increases post‐game saliva caffeine levels. This may contribute to the observed 3.5 h delay in time at sleep onset and the 1.5 h reduction in sleep duration on the night of the game. This study highlights the need for a strategic approach to the use of caffeine within a Super Rugby team considering the potential effect on post‐game sleep.
Effect of movement velocity during resistance training on muscle‐specific hypertrophy: A systematic review
Authors: Hackett Daniel A. , Davies Timothy B. , Orr Rhonda , Kuang Kenny , Halaki Mark
Published: February 2018

Currently, it is unclear whether manipulation of movement velocity during resistance exercise has an effect on hypertrophy of specific muscles. The purpose of this systematic review of literature was to investigate the effect of movement velocity during resistance training on muscle hypertrophy. Five electronic databases were searched using terms related to movement velocity and resistance training. Inclusion criteria were randomised and non‐randomised comparative studies; published in English; included healthy adults; used dynamic resistance exercise interventions directly comparing fast training to slower movement velocity training; matched in prescribed intensity and volume; duration ≥4 weeks; and measured muscle hypertrophy. A total of six studies were included involving 119 untrained participants. Hypertrophy of the quadriceps was examined in five studies and of the biceps brachii in two studies. Three studies found significantly greater increases in hypertrophy of the quadriceps for moderate‐slow compared to fast training. For the remaining studies examining the quadriceps, significant within‐group increase in hypertrophy was found for only moderate‐slow training in one study and for only fast training in the other study. The two studies that examined hypertrophy of the biceps brachii found greater increases for fast compared to moderate‐slow training. Caution is required when interpreting the findings from this review due to the low number of studies, hence insufficient data. Future longitudinal randomised controlled studies in cohorts of healthy adults are required to confirm and extend our findings.
Rab6-dependent retrograde traffic of LAT controls immune synapse formation and T cell activation
Authors: Carpier Jean-Marie , Zucchetti Andres E. , Bataille Laurence , Dogniaux Stéphanie , Shafaq-Zadah Massiullah , Bardin Sabine , Lucchino Marco , Maurin Mathieu , Joannas Leonel D. , Magalhaes Joao Gamelas , Johannes Ludger , Galli Thierry , Goud Bruno , Hivroz Claire
Published: February 2018

The adapter molecule linker for activation of T cells (LAT) orchestrates the formation of signalosomes upon T cell receptor (TCR) stimulation. LAT is present in different intracellular pools and is dynamically recruited to the immune synapse upon stimulation. However, the intracellular traffic of LAT and its function in T lymphocyte activation are ill defined. We show herein that LAT, once internalized, transits through the Golgi–trans-Golgi network (TGN), where it is repolarized to the immune synapse. This retrograde transport of LAT depends on the small GTPase Rab6 and the target soluble N-ethylmaleimide-sensitive factor attachment protein receptor (t-SNARE) Syntaxin-16, two regulators of the endosome-to-Golgi/TGN retrograde transport. We also show in vitro in Syntaxin-16– or Rab6-silenced human cells and in vivo in CD4+ T lymphocytes of the Rab6 knockout mouse that this retrograde traffic controls TCR stimulation. These results establish that the retrograde traffic of LAT from the plasma membrane to the Golgi-TGN controls the polarized delivery of LAT at the immune synapse and T lymphocyte activation.
Metaplastic Cdx2-depleted cells can be very disruptive neighbors
Authors: Lourenço Filipe C. , Winton Douglas J.
Published: February 2018

In this issue of JEM, Balbinot et al. (https://doi.org/10.1084/jem.20170934) describe an original mechanism where Cdx2 inactivation regulates intestinal metaplastic to neoplastic transition in a paracrine fashion. Surprisingly, the target cells are neighboring “normal” Cdx2-positive cells.
Biofortification, Crop Adoption and Health Information: Impact Pathways in Mozambique and Uganda
Authors: de Brauw Alan , Eozenou Patrick , Gilligan Daniel O. , Hotz Christine , Kumar Neha , Meenakshi J.V.
Published: February 2018

Biofortification is a promising strategy to combat micronutrient malnutrition by promoting the adoption of staple food crops bred to be dense sources of specific micronutrients. Research on biofortified orange‐fleshed sweet potato (OFSP) has shown that the crop improves the vitamin A status of children who consume as little as 100 grams per day, and intensive promotion strategies improve dietary intakes of vitamin A in field experiments. However, little is known about OFSP adoption behavior, or about the role that nutrition information plays in promoting adoption and changing diet. We report evidence from similar randomized field experiments conducted in Mozambique and Uganda to promote OFSP. We further use causal mediation analysis to study impact pathways for adoption and dietary intakes. Despite different agronomic conditions and sweet potato cropping patterns across the two countries, the project had similar impacts, leading to adoption by 61% to 68% of farmers exposed to the project, and doubling vitamin A intakes in children. In both countries, two intervention models that differed in training intensity and cost had comparable impacts relative to the control group. The project increased the knowledge of key nutrition messages; however, added knowledge of nutrition messages appears to have minimally affected adoption, conditional on assumptions required for causal mediation analysis. Increased vitamin A intakes were largely explained by adoption and not by nutrition knowledge gained, though in Uganda a large share of impacts on vitamin A intakes cannot be explained by mediating variables. Similar impacts could likely have been achieved by reducing the scope of nutrition trainings.
pBRIT: gene prioritization by correlating functional and phenotypic annotations through integrative data fusion
Authors: Kumar Ajay Anand , Van Laer Lut , Alaerts Maaike , Ardeshirdavani Amin , Moreau Yves , Laukens Kris , Loeys Bart , Vandeweyer Geert
Published: February 2018

Motivation

Computational gene prioritization can aid in disease gene identification. Here, we propose pBRIT (prioritization using Bayesian Ridge regression and Information Theoretic model), a novel adaptive and scalable prioritization tool, integrating Pubmed abstracts, Gene Ontology, Sequence similarities, Mammalian and Human Phenotype Ontology, Pathway, Interactions, Disease Ontology, Gene Association database and Human Genome Epidemiology database, into the prediction model. We explore and address effects of sparsity and inter-feature dependencies within annotation sources, and the impact of bias towards specific annotations.

Results

pBRIT models feature dependencies and sparsity by an Information-Theoretic (data driven) approach and applies intermediate integration based data fusion. Following the hypothesis that genes underlying similar diseases will share functional and phenotype characteristics, it incorporates Bayesian Ridge regression to learn a linear mapping between functional and phenotype annotations. Genes are prioritized on phenotypic concordance to the training genes. We evaluated pBRIT against nine existing methods, and on over 2000 HPO-gene associations retrieved after construction of pBRIT data sources. We achieve maximum AUC scores ranging from 0.92 to 0.96 against benchmark datasets and of 0.80 against the time-stamped HPO entries, indicating good performance with high sensitivity and specificity. Our model shows stable performance with regard to changes in the underlying annotation data, is fast and scalable for implementation in routine pipelines.

Availability and implementation

http://biomina.be/apps/pbrit/; https://bitbucket.org/medgenua/pbrit.

Supplementary information

Supplementary data are available at Bioinformatics online.
Clinical pathways for primary care: current use, interest and perceived usability
Authors: Toy Jennifer M , Drechsler Adam , Waters Richard C
Published: February 2018

Objective

Translating clinical evidence to daily practice remains a challenge and may improve with clinical pathways. We assessed interest in and usability of clinical pathways by primary care professionals.

Methods

An online survey was created. Interest in pathways for patient care and learning was assessed at start and finish. Participants completed baseline questions then pathway-associated question sets related to management of 2 chronic diseases. Perceived pathway usability was assessed using the system usability scale. Accuracy and confidence of answers was compared for baseline and pathway-assisted questions.

Results

Of 115 participants, 17.4% had used clinical pathways, the lowest of decision support tool types surveyed. Accuracy and confidence in answers significantly improved for all pathways. Interest in using pathways daily or weekly was above 75% for the respondents.

Conclusion

There is low utilization of, but high interest in, clinical pathways by primary care clinicians. Pathways improve accuracy and confidence in answering written clinical questions.
NeuroForm Atlas Stent-Assisted Coiling: Preliminary Results
Authors: ten Brinck Michelle F M , de Vries Joost , Bartels Ronald H M A , Grotenhuis J André , Boogaarts Hieronymus D
Published: February 2018

BACKGROUND

Stent-assisted coiling (SAC) is increasingly being performed as intervention for wide-neck intracranial aneurysms. The NeuroForm Atlas Stent (CE-marked; Stryker, Kalamazoo, Michigan) is relatively new.

OBJECTIVE

To evaluate the effectiveness and safety of NeuroForm Atlas SAC for intracranial aneurysms in the first such study.

METHODS

 We retrospectively analyzed data from all patients treated with the NeuroForm Atlas SAC of an intracranial aneurysm, both ruptured and unruptured, between June 2015 and December 2016. Primary end-points were favorable clinical outcomes (modified Rankin scale score 0-2) and successful aneurysm occlusion (Raymond-Roy class I/II), both at 6-mo follow-up. Secondary end-points were the occurrence of intervention-related complications leading to permanent neurological deficit, the occurrence of intervention-related stroke and neurological death, immediate aneurysm occlusion, rupture (or rerupture) of the aneurysm, and recanalization.

RESULTS

Twenty-seven consecutive patients, 10 with ruptured saccular wide-neck aneurysms, were treated with NeuroForm Atlas SAC. At 6-mo follow-up, 18/26 (69.2%) survivors had successful aneurysm occlusion and 22/26 (84.6%) had favorable clinical outcome. One patient had died of a cause unrelated to treatment. No intervention-related complications leading to permanent neurological deficit occurred. However, intraprocedural thromboembolic complications occurred in 4/27 patients (14.8%), and ischemic stroke related to treatment occurred in 4/26 (15.4%). No hemorrhagic complications were observed.

CONCLUSION

NeuroForm Atlas SAC is a feasible way to treat ruptured and unruptured wide-neck aneurysms that are not amenable to conventional coiling or clipping. Aneurysm occlusion and favorable clinical outcome are consistent with previously reported rates for SAC of wide-neck aneurysms with other devices.
First Report of Cucurbit yellow stunting disorder virus in Cucurbits in Georgia, United States
Authors: Gadhave Kiran R. , Dutta Bhabesh , Coolong Timothy , Sparks Alton N. , Adkins Scott , Srinivasan Rajagopalbabu
Published: February 2018

This study for the first time provides evidence for the presence of Cucurbit yellow stunting disorder virus (CYSDV) in Georgia. Thus, three whitefly-transmitted cucurbit-infecting viruses are now known in the state. Future research is required to evaluate the host range of CYSDV and its economic impact on cucurbit production in Georgia.
Incidence of Viruses in Two Large-Scale Plantings of Blackberry in South Carolina as Detected Through the Use of Sentinel Plants and RT-PCR
Authors: Poudel Bindu , Rollins Philip , Bishop David T. , Scott Simon W.
Published: February 2018

Some plants in two large-scale blackberry plantings established from virus-indexed planting material displayed symptoms typical of virus infection in the early days of the growing season immediately after planting. Groups of sentinel plants exposed within the plantings for 30-day periods over additional growing seasons, and subsequently screened for the presence of five viruses by reverse transcription PCR, detected Blackberry yellow vein-associated virus (BYVaV), Blackberry virus Y (BVY), Blackberry chlorotic ringspot virus (BCRV), Blackberry virus E (BVE), and Blackberry leaf mottle-associated virus (BLMaV). Because these viruses are thought to be transmitted through the actions of arthropods, and bearing in mind that the plantings had been established with virus-indexed material, it seems that the viruses must be moving into the new crops from adjacent native vegetation and once established moving freely within the crops. BYVaV has been reported from South Carolina previously. A recent publication reports the detection of BLMaV in samples originating from South Carolina and demonstrates transmission of the virus by mites. This is the first report of the detection of BCRV, BVY, and BVE within the state and provides support for the movement of the latter two viruses (BVY and BVE) within established plantings of blackberry as a result of vector activity.
Bayesian detection of convergent rate changes of conserved noncoding elements on phylogenetic trees
Authors: Hu Zhirui , Sackton Timothy B. , Edwards Scott V. , Liu Jun S.
Published: February 2018

Conservation of DNA sequence over evolutionary time is a strong indicator of function, and gain or loss of sequence conservation can be used to infer changes in function across a phylogeny. Changes in evolutionary rates on particular lineages in a phylogeny can indicate shared functional shifts, and thus can be used to detect genomic correlates of phenotypic convergence. However, existing methods do not allow easy detection of patterns of rate variation, which causes challenges for detecting convergent rate shifts or other complex evolutionary scenarios. Here we introduce PhyloAcc, a new Bayesian method to model substitution rate changes in conserved elements across a phylogeny. The method assumes several categories of substitution rate for each branch on the phylogenetic tree, estimates substitution rates per category, and detects changes of substitution rate as the posterior probability of a category switch. Simulations show that PhyloAcc can detect genomic regions with rate shifts in multiple target species better than previous methods and has a higher accuracy of reconstructing complex patterns of substitution rate changes than prevalent Bayesian relaxed clock models. We demonstrate the utility of PhyloAcc in two classic examples of convergent phenotypes: loss of flight in birds and the transition to marine life in mammals. In each case, our approach reveals numerous examples of conserved non-exonic elements with accelerations specific to the phenotypically convergent lineages. Our method is widely applicable to any set of conserved elements where multiple rate changes are expected on a phylogeny.
Single day construction of multi-gene circuits with 3G assembly
Authors: Halleran Andrew D. , Swaminathan Anandh , Murray Richard M.
Published: February 2018

The ability to rapidly design, build, and test prototypes is of key importance to every engineering discipline. DNA assembly often serves as a rate limiting step of the prototyping cycle for synthetic biology. Recently developed DNA assembly methods such as isothermal assembly and type IIS restriction enzyme systems take different approaches to accelerate DNA construction. We introduce a hybrid method, Golden Gate-Gibson (3G), that takes advantage of modular part libraries introduced by type IIS restriction enzyme systems and isothermal assembly‘s ability to build large DNA constructs in single pot reactions. Our method is highly efficient and rapid, facilitating construction of entire multi-gene circuits in a single day. Additionally, 3G allows generation of variant libraries enabling efficient screening of different possible circuit constructions. We characterize the efficiency and accuracy of 3G assembly for various construct sizes, and demonstrate 3G by characterizing variants of an inducible cell-lysis circuit.