bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack
Authors: Brookes Rebecca L. , Crichton Siobhan , Wolfe Charles D.A. , Yi Qilong , Li Linxin , Hankey Graeme J. , Rothwell Peter M. , Markus Hugh S. 
Published: December 2017

Background and Purpose—

A variant in the histone deacetylase 9 (
HDAC9
) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate.

Methods—
Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression.

Results—

A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis
P
=0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3–0.7;
P
=0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29–0.77;
P
=0.003).

Conclusions—
These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke.
BATAL: The Balloon Measurement Campaigns of the Asian Tropopause Aerosol Layer
Authors: Vernier J.-P. , Fairlie T. D. , Deshler T. , Venkat Ratnam M. , Gadhavi H. , Kumar B. S. , Natarajan M. , Pandit A. K. , Akhil Raj S. T. , Hemanth Kumar A. , Jayaraman A. , Singh A. K. , Rastogi N. , Sinha P. R. , Kumar S. , Tiwari S. , Wegner T. , Baker N. , Vignelles D. , Stenchikov G. , Shevchenko I. , Smith J. , Bedka K. , Kesarkar A. , Singh V. , Bhate J. , Ravikiran V. , Durga Rao M. , Ravindrababu S. , Patel A. , Vernier H. , Wienhold F. G. , Liu H. , Knepp T. N. , Thomason L. , Crawford J. , Ziemba L. , Moore J. , Crumeyrolle S. , Williamson M. , Berthet G. , Jégou F. , Renard J.-B. 
Published: December 2017

AbstractWe describe and show results from a series of field campaigns that used balloonborne instruments launched from India and Saudi Arabia during the summers 2014–17 to study the nature, formation, and impacts of the Asian Tropopause Aerosol Layer (ATAL). The campaign goals were to i) characterize the optical, physical, and chemical properties of the ATAL; ii) assess its impacts on water vapor and ozone; and iii) understand the role of convection in its formation. To address these objectives, we launched 68 balloons from four locations, one in Saudi Arabia and three in India, with payload weights ranging from 1.5 to 50 kg. We measured meteorological parameters; ozone; water vapor; and aerosol backscatter, concentration, volatility, and composition in the upper troposphere and lower stratosphere (UTLS) region. We found peaks in aerosol concentrations of up to 25 cm–3 for radii > 94 nm, associated with a scattering ratio at 940 nm of ∼1.9 near the cold-point tropopause. During medium-duration balloon flights near the tropopause, we collected aerosols and found, after offline ion chromatography analysis, the dominant presence of nitrate ions with a concentration of about 100 ng m–3. Deep convection was found to influence aerosol loadings 1 km above the cold-point tropopause. The Balloon Measurements of the Asian Tropopause Aerosol Layer (BATAL) project will continue for the next 3–4 years, and the results gathered will be used to formulate a future National Aeronautics and Space Administration–Indian Space Research Organisation (NASA–ISRO) airborne campaign with NASA high-altitude aircraft.
Climate Impacts on Density Altitude and Aviation Operations
Authors: Goodman Christopher J. , Small Griswold Jennifer D. 
Published: December 2017

AbstractA critical determinant of aircraft performance is density altitude, or the density given as a height above mean sea level, which is dependent on air temperature, pressure, and humidity. These meteorological variables change on various time scales (e.g., hourly, seasonal, and decadal) and are regionally impacted by large-scale climate variability as the result of phenomena such as El Niño–Southern Oscillation or the Arctic Oscillation. Here a statistical analysis is performed to determine the impacts of climate variability on seasonally averaged density altitude, a key metric used by pilots to determine aircraft performance and efficiency, as a function of El Niño–Southern Oscillation and the Arctic Oscillation using NCEP–NCAR reanalysis data and historical aviation meteorological records. Regressions show regional dependencies and impacts to density altitudes that vary as a function of season for both El Niño–Southern Oscillation and Arctic Oscillation cases. The results highlight the importance of understanding the regional nature of the impact of climate variability on density altitude and the potential impacts on aviation operations.
A Global Climatology of Tropospheric Inertial Instability
Authors: Thompson Callum F. , Schultz David M. , Vaughan Geraint 
Published: December 2017

Abstract
A climatology of tropospheric inertial instability is constructed using the European Centre for Medium-Range Weather Forecasts interim reanalysis (ERA-Interim) at 250, 500, and 850 hPa. For each level, two criteria are used. The first criterion is the traditional criterion of absolute vorticity that is opposite in sign to the local Coriolis parameter. The second criterion, referred to as the gradient criterion, is the traditional criterion with an added term incorporating flow curvature. Both criteria show that instability, on all pressure levels, occurs most frequently in the tropics and decreases toward the poles. Compared to the traditional criterion, the gradient criterion diagnoses instability much more frequently outside the tropics and less frequently near the equator. The global distribution of inertial instability also shows many local maxima in the occurrence of instability. A sample of these local maxima is investigated further by constructing composites of the synoptic-scale flow associated with instability. The composites show that instability occurs in association with cross-equatorial flow in the North Atlantic Ocean, the Somali jet, tip jets off northern Madagascar, the western Pacific subtropical high, gap winds across Central America, upper-level ridging over western North America, and the North Atlantic polar jet. Furthermore, relatively long-lived synoptic-scale regions of instability are found within the midlatitude jet streams.
Are Peak Summer Sultry Heat Wave Days over the Yangtze–Huaihe River Basin Predictable?
Authors: Gao Miaoni , Wang Bin , Yang Jing , Dong Wenjie 
Published: December 2017

AbstractThe Yangtze–Huaihe River basin (YHRB) is the core region of sultry heat wave occurrence over China during peak summer [July and August (JA)]. The extremely hot and muggy weather is locally controlled by a descending high pressure anomaly connected to the western Pacific subtropical high. During 1961–2015, the heat wave days (HWDs) in JA over the YHRB exhibit large year-to-year and decadal variations. Prediction of the total number of HWDs in JA is of great societal and scientific importance. The summer HWDs are preceded by a zonal dipole SST tendency pattern in the tropical Pacific and a meridional tripole SST anomaly pattern over the North Atlantic. The former signifies a rapid transition from a decaying central Pacific El Niño in early spring to a developing eastern Pacific La Niña in summer, which enhances the western Pacific subtropical high and increases pressure over the YHRB by altering the Walker circulation. The North Atlantic tripole SST anomalies persist from the preceding winter to JA and excite a circumglobal teleconnection pattern placing a high pressure anomaly over the YHRB. To predict the JA HWDs, a 1-month lead prediction model is established with the above two predictors. The forward-rolling hindcast achieves a significant correlation skill of 0.66 for 1981–2015, and the independent forecast skill made for 1996–2015 reaches 0.73. These results indicate the source of predictability of summer HWDs and provide an estimate for the potential predictability, suggesting about 55% of the total variance may be potentially predictable. This study also reveals greater possibilities for dynamical models to improve their prediction skills.
Origins of Coupled Model Biases in the Arabian Sea Climatological State
Authors: Nagura Motoki , McCreary J. P. , Annamalai H. 
Published: December 2017

This study investigates biases of the climatological mean state of the northern Arabian Sea (NAS) in 31 coupled ocean–atmosphere models. The focus is to understand the cause of the large biases in the depth of the 20°C isotherm [Formula: see text] that occur in many of them. Other prominent biases are the depth [Formula: see text] and temperature [Formula: see text] of Persian Gulf water (PGW) and the wintertime mixed-layer thickness (MLT) along the northern boundary.For models that lack a Persian Gulf (group 1), [Formula: see text] is determined by the wintertime MLT bias [Formula: see text] through the formation of an Arabian Sea high-salinity water mass (ASHSW) that is too deep. For models with a Persian Gulf (group 2), if [Formula: see text] > MLT (group 2B), PGW remains mostly trapped to the western boundary and, again, [Formula: see text] directly controls [Formula: see text]. If [Formula: see text] MLT (group 2A), PGW spreads into the NAS and impacts [Formula: see text] because [Formula: see text] > 20°C; nevertheless [Formula: see text] still influences [Formula: see text] indirectly through its impact on [Formula: see text].The thick wintertime mixed layer is driven primarily by surface cooling [Formula: see text] during the fall. Nevertheless, variations in ΔMLT among the models are more strongly linked to biases in the density stratification (jump) across the bottom of the mixed layer than to [Formula: see text] biases. The jump is in turn determined primarily by sea surface salinity biases (ΔSSS) advected into the NAS by the West India Coastal Current, and the source of ΔSSS is the rainfall deficit associated with the models’ weak summer monsoon. Ultimately, then, ΔD20 is linked to this deficit.
Role of Equatorial Basin-Mode Resonance for the Seasonal Variability of the Angola Current at 11°S
Authors: Kopte Robert , Brandt Peter , Claus Martin , Greatbatch Richard J. , Dengler Marcus 
Published: December 2017

AbstractMultiyear moored velocity observations of the Angola Current near 11°S reveal a weak southward mean flow superimposed by substantial intraseasonal to seasonal variability, including annual and semiannual cycles with distinct baroclinic structures. In the equatorial Atlantic these oscillations are associated with basin-mode resonances of the fourth and second baroclinic modes, respectively. Here, the role of basin-mode resonance and local forcing for the Angola Current seasonality is investigated. A suite of linear shallow-water models for the tropical Atlantic is employed, each model representing a single baroclinic mode forced at a specific period. The annually and semiannually oscillating forcing is given by 1) an idealized zonally uniform zonal forcing restricted to the equatorial band corresponding to a remote equatorial forcing or 2) realistic, spatially varying Fourier components of wind stress data that include local forcing off Angola, particularly alongshore winds. Model-computed modal amplitudes are scaled to match moored velocity observations from the equatorial Atlantic. The observed annual cycle of alongshore velocity at 11°S is well reproduced by the remote equatorial forcing. Including local forcing slightly improves the agreement between observed and simulated semiannual oscillations at 11°S compared to the purely equatorial forcing. However, the model-computed semiannual cycle lacks amplitude at middepth. This could be the result of either underestimating the strength of the second equatorial basin mode of the fourth baroclinic mode or other processes not accounted for in the shallow-water models. Overall, the findings underline the importance of large-scale linear equatorial wave dynamics for the seasonal variability of the boundary circulation off Angola.
Observing Finescale Oceanic Velocity Structure with an Autonomous Nortek Acoustic Doppler Current Profiler
Authors: Shcherbina Andrey Y. , D’Asaro Eric A. , Nylund Sven 
Published: December 2017

AbstractThis paper describes the instrumentation and techniques for long-term targeted observation of the centimeter-scale velocity structure within the oceanic surface boundary layer, made possible by the recent developments in capabilities of autonomous platforms and self-contained pulse-coherent acoustic Doppler current profilers (ADCPs). Particular attention is paid to the algorithms of ambiguity resolution (“unwrapping”) of pulse-coherent Doppler velocity measurements. The techniques are demonstrated using the new Nortek Signature1000 ADCP mounted on a Lagrangian float, a combination shown to be capable of observing ocean turbulence in a number of recent studies. Statistical uncertainty of the measured velocities in relation to the ADCP setup is also evaluated. Described techniques and analyses should be broadly applicable to other autonomous and towed applications of pulse-coherent ADCPs.
AtopobiumandFusobacteriumas novel candidates for sarcoidosis-associated microbiota
Authors: Zimmermann Alexandra , Knecht Henrik , Häsler Robert , Zissel Gernot , Gaede Karoline I. , Hofmann Sylvia , Nebel Almut , Müller-Quernheim Joachim , Schreiber Stefan , Fischer Annegret 
Published: December 2017

Sarcoidosis is a granulomatous disease that mainly affects the lung. A role of microbial factors in disease pathogenesis is assumed, but has not been investigated systematically in a large cohort.This cross-sectional study compared the lung microbiota of 71 patients with sarcoidosis, 15 patients with idiopathic pulmonary fibrosis (non-infectious controls) and 10 healthy controls (HCs). Next-generation sequencing of 16S DNA was used on bronchoalveolar lavage samples to characterise the microbial composition, which was analysed for diversity and indicator species. Host genotypes for 13 known sarcoidosis risk variants were determined and correlated with microbial parameters.The microbial composition differed significantly between sarcoidosis and HC samples (redundancy analysis ANOVA, p=0.025) and between radiographic Scadding types.Atopobiumspp. was detected in 68% of sarcoidosis samples, but not in HC samples.Fusobacteriumspp. was significantly more abundant in sarcoidosis samples compared with those from HCs. Mycobacteria were found in two of 71 sarcoidosis samples. Host-genotype analysis revealed an association of the rs2076530 (BTNL2) risk allele with a decrease in bacterial burden (p=0.002).Our results indicate Scadding type-dependent microbiota in sarcoidosis BAL samples.Atopobiumspp. andFusobacteriumspp. were identified as sarcoidosis-associated bacteria, which may enable new insights into the pathogenesis and treatment of the disease.
Identifying the primary outcome for a randomised controlled trial in rheumatoid arthritis: the role of a discrete choice experiment
Authors: Stamuli Eugena , Torgerson David , Northgraves Matthew , Ronaldson Sarah , Cherry Lindsey 
Published: December 2017

AbstractBackgroundThis study sought to establish the preferences of people with Rheumatoid Arthritis (RA) about the best outcome measure for a health and fitness intervention randomised controlled trial (RCT). The results of this study were used to inform the choice of the trial primary and secondary outcome measure.MethodsA discrete choice experiment (DCE) was used to assess people's preferences regarding a number of outcomes (foot and ankle pain, fatigue, mobility, ability to perform daily activities, choice of footwear) as well as different schedules and frequency of delivery for the health and fitness intervention. The outcomes were chosen based on literature review, clinician recommendation and patients' focus groups. The DCE was constructed in SAS software using the D‐efficiency criteria. It compared hypothetical scenarios with varying levels of outcomes severity and intervention schedule. Preference weights were estimated using appropriate econometric models. The partial log‐likelihood method was used to assess the attribute importance.ResultsOne hundred people with RA completed 18 choice sets. Overall, people selected foot and ankle pain as the most important outcome, with mobility being nearly as important. There was no evidence of differential preference between intervention schedules or frequency of delivery.ConclusionsFoot and ankle pain can be considered the patient choice for primary outcome of an RCT relating to a health and fitness intervention. This study demonstrated that, by using the DCE method, it is possible to incorporate patients' preferences at the design stage of a RCT. This approach ensures patient involvement at early stages of health care design.
Bax-inhibiting peptide attenuates bleomycin-induced lung injury in mice
Authors: Suzuki Kunihiro , Yanagihara Toyoshi , Yokoyama Tetsuya , Maeyama Takashige , Ogata-Suetsugu Saiko , Arimura-Omori Masako , Mikumo Hironori , Hamada Naoki , Harada Eiji , Kuwano Kazuyoshi , Harada Taishi , Nakanishi Yoichi 
Published: December 2017

Rationale: Bax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits the activation of Bax.
Objective: The purpose of this study was to investigate whether the control of Bax activity by BIP-V5 reduces the degree of bleomycin-induced lung injury.
Methods: C57BL/6J mice were administered bleomycin and BIP-V5 intratracheally on day 0. Bronchoalveolar lavage fluid and lung tissue were obtained on day 7. Human pulmonary alveolar epithelial cells (A549 cells) and mouse pulmonary alveolar epithelial cells (LA-4 cells ) were stimulated with bleomycin to induce apoptosis.
Results: Administration of BIP-V5 improved the survival rate and degree of bleomycin-induced lung injury by suppressing Bax activation in mice. BIP-V5 treatment decreased bleomycin-induced apoptosis of alveolar epithelial cell lines (A549 cells and LA-4 cells) by suppressing Bax activation.
Conclusions: The administration of BIP-V5 may constitute a novel therapeutic strategy against lung injury.
Real-time observation of light-controlled transcription in living cells
Authors: Rademacher Anne , Erdel Fabian , Trojanowski Jorge , Schumacher Sabrina , Rippe Karsten 
Published: December 2017

ABSTRACT
Gene expression is tightly regulated in space and time. To dissect this process with high temporal resolution, we introduce an optogenetic tool termed blue light-induced chromatin recruitment (BLInCR) that combines rapid and reversible light-dependent recruitment of effector proteins with a real-time readout for transcription. We used BLInCR to control the activity of a cluster of reporter genes in the human osteosarcoma cell line U2OS by reversibly recruiting the viral transactivator VP16. RNA production was detectable ∼2 min after VP16 recruitment and readily decreased when VP16 dissociated from the cluster in the absence of light. Quantitative assessment of the activation process revealed biphasic activation kinetics with a pronounced early phase in cells treated with the histone deacetylase inhibitor SAHA. Comparison with kinetic models of transcription activation suggests that the gene cluster undergoes a maturation process when activated. We anticipate that BLInCR will facilitate the study of transcription dynamics in living cells.
This article has an associated First Person interview with the first author of the paper.
Phosphorylation of the RNA-binding protein Zfs1 modulates sexual differentiation in fission yeast
Authors: Navarro Francisco J. , Chakravarty Probir , Nurse Paul 
Published: December 2017

ABSTRACT
Sexual differentiation in the fission yeast Schizosaccharomyces pombe promotes cell cycle arrest and extensive changes in gene expression, resulting in cell-to-cell fusion, the exchange of hereditary material and specialized cell division. These events are detrimental to the cell if they are triggered in inappropriate conditions, and therefore the decision to differentiate must be precisely controlled. Here, we investigated the role of the RNA-binding protein Zfs1 in this process by identifying its targets and characterizing novel post-translational regulatory mechanisms. We found that Zfs1 negatively regulates the G1 cyclin Puc1, and deregulated Puc1 levels inhibit differentiation in the zfs1Δ mutant. We also found that Zfs1 undergoes phosphorylation, which is stimulated upon nitrogen depletion or inhibition of the TOR pathway. Phosphorylation of Zfs1 modulates accumulation of Puc1 and plays an important role in the response of the cell to sexual differentiation signals. We propose that Zfs1 functions as an integrator of nutrient information to modulate sexual differentiation, contributing to the establishment of the differentiation-activating threshold.
Effects of mutating α-tubulin lysine 40 on sensory dendrite development
Authors: Jenkins Brian V. , Saunders Harriet A. J. , Record Helena L. , Johnson-Schlitz Dena M. , Wildonger Jill 
Published: December 2017

ABSTRACT
Microtubules are essential for neuronal structure and function. Axonal and dendritic microtubules are enriched in post-translational modifications that impact microtubule dynamics, transport and microtubule-associated proteins. Acetylation of α-tubulin lysine 40 (K40) is a prominent and conserved modification of neuronal microtubules. However, the cellular role of microtubule acetylation remains controversial. To resolve how microtubule acetylation might affect neuronal morphogenesis, we mutated endogenous α-tubulin in vivo using a new Drosophila strain that facilitates the rapid knock-in of designer αTub84B alleles (the predominant α-tubulin-encoding gene in flies). Leveraging our new strain, we found that microtubule acetylation, as well as polyglutamylation and (de)tyrosination, is not essential for survival. However, we found that dendrite branch refinement in sensory neurons relies on α-tubulin K40. Mutagenesis of K40 reveals moderate yet significant changes in dendritic lysosome transport, microtubule polymerization and Futsch protein distribution in dendrites but not in axons. Our studies point to an unappreciated role for α-tubulin K40 and acetylation in dendrite morphogenesis. While our results are consistent with the idea that acetylation tunes microtubule function within neurons, they also suggest there may be an acetylation-independent requirement for α-tubulin K40.
This article has an associated First Person interview with the first author of the paper.