bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA06: Serum contains enough information for early detection of pancreatic cancer
Authors: Borrebaeck Carl A. K.
Published: December 2016

One of the driving forces in personalized medicine is the search for protein patterns that can be utilized for improved diagnosis, assessing the risk for tumor relapse and disease progression. Affinity proteomics, a high-throughput technology for protein expression profiling, is now generating data for improved diagnosis and patient stratification, which has been demonstrated in several clinical studies. Pancreatic ductal adenocarcinoma (PDAC) is such a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. Based on multiparametric microarray analysis of over 2500 patient samples, serum protein signatures have for the first time been identified that could discriminate between pancreatic cancer patients with stage I, II, III and IV, which indicates a possibility for early diagnosis and an increased detection rate of surgically resectable tumors, which significantly would increase the life expectancy of pancreatic cancer patients.

Citation Format: Carl A. K. Borrebaeck.{Authors}. Serum contains enough information for early detection of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA06.
Abstract PR05: Genome-scale CRISPR-Cas9 screening to identify essential genes and pathways in pancreatic cancer
Authors: Aguirre Andrew J. , Shao Wei , Xu Han , Weir Barbara , Vazquez Francisca , Meyers Robin , Zhang Cheng-Zhong , Doshi Mihir , Cowley Glenn S. , Ewachiw Theodore , Rasheed Zeshaan , Golub Todd R. , Stegmaier Kimberly , Roberts Charles W. , Garraway Levi A. , Meyerson Matthew , Tsherniak Aviad , Root David E. , Espenshade Peter J. , Hahn William C.
Published: December 2016

Loss-of-function genetic screens in cancer cell lines permit the systematic interrogation of genes and pathways involved in cell proliferation and viability. The CRISPR-Cas9 system enables effective genome editing for perturbation of gene function. To identify genes that are essential for cancer cell proliferation and survival, we have optimized an approach for efficient genome-scale CRISPR-Cas9 pooled screening and performed negative-selection knock-out screens in 43 human cancer cell lines with diverse genetic and phenotypic features, including 8 pancreatic cancer cell lines. We report that CRISPR-Cas9 efficacy varies depending on the cell context and propose methods to effectively identify differential cancer dependencies across cell lines. Additionally, we identify a strong correlation between genomic copy number and perceived gene dependency, and further elucidate a gene-independent effect of CRISPR-Cas9 cutting. Using these screening data, we performed a detailed interrogation of gene and pathway dependencies in pancreatic cancer. Through integrative analysis of CRISPR-Cas9 screening results with RNA-interference and small molecule screening data, as well as DNA and RNA sequencing, we identified a high-confidence set of recurrently essential genes in pancreatic cancer, including several with associated biomarkers. Moreover, through pathway analyses of CRISPR-Cas9 screening data, we have identified a number of essential biologic processes including key metabolic and cell signaling pathways that may represent potential therapeutic avenues. In particular, we characterize the sterol regulatory element binding protein (SREBP) signaling pathway as a recurrent vulnerability in pancreatic cancer and credential this pathway as a potential therapeutic target.

This abstract is also being presented as Poster A13

Citation Format: Andrew J. Aguirre, Wei Shao, Han Xu, Barbara Weir, Francisca Vazquez, Robin Meyers, Cheng-Zhong Zhang, Mihir Doshi, Glenn S. Cowley, Theodore Ewachiw, Zeshaan Rasheed, Todd R. Golub, Kimberly Stegmaier, Charles W. Roberts, Levi A. Garraway, Matthew Meyerson, Aviad Tsherniak, David E. Root, Peter J. Espenshade, William C. Hahn.{Authors}. Genome-scale CRISPR-Cas9 screening to identify essential genes and pathways in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr PR05.
Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia
Authors: Obi Andrea T. , Andraska Elizabeth , Kanthi Yogendra , Kessinger Chase W. , Elfline Megan , Luke Cathy , Siahaan Teruna J. , Jaffer Farouc A. , Wakefield Thomas W. , Henke Peter K.
Published: December 2016

Venous thromboembolism is a major cause of death during and immediately post-sepsis. Venous thrombosis (VT) is mediated by cell adhesion molecules and leukocytes, including neutrophil extracellular traps (NETs). Sepsis, or experimentally, endotoxaemia, shares similar characteristics and is modulated via toll like receptor 4 (TLR4). This study was undertaken to determine if endotoxaemia potentiates early stasis thrombogenesis, and secondarily to determine the role of VT TLR4, ICAM-1 and neutrophils (PMNs). Wild-type (WT), ICAM-1-/- and TLR4-/- mice underwent treatment with saline or LPS (10 mg/kg i.p.) alone, or followed by inferior vena cava (IVC) ligation to generate stasis VT. In vivo microscopy of leukocyte trafficking was performed in non-thrombosed mice, and tissue and plasma were harvested during early VT formation. Pre-thrombosis, circulating ICAM-1 was elevated and increased leukocyte adhesion and rolling occurred on the IVC of LPS-treated mice. Post-thrombosis, endotoxaemic mice formed larger, platelet-poor thrombi. Endotoxaemic TLR4-/- mice did not have an augmented thrombotic response and exhibited significantly decreased circulating ICAM-1 compared to endotoxaemic WT controls. Endotoxaemic ICAM-1-/- mice had significantly smaller thrombi compared to controls. Hypothesising that PMNs localised to the inflamed endothelium were promoting thrombosis, PMN depletion using anti-Ly6G antibody was performed. Paradoxically, VT formed without PMNs was amplified, potentially related to endotoxaemia induced elevation of PAI-1 and circulating FXIII, and decreased uPA. Endotoxaemia enhanced early VT occurs in a TLR-4 and ICAM-1 dependent fashion, and is potentiated by neutropenia. ICAM-1 and/or TLR-4 inhibition may be a unique strategy to prevent sepsis-associated VT.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Prognostic significance of tPA/PAI-1 complex in patients with heart failure and preserved ejection fraction
Authors: Koller Lorenz , Sulzgruber Patrick , Scharnagl Hubert , Delgado Graciela , Goliasch Georg , März Winfried , Winter Max-Paul , Kleber Marcus E. , Niessner Alexander
Published: December 2016

Heart failure with preserved ejection fraction (HFpEF) represents a major epidemic, clinical and public health problem with rising patient numbers every year. Traditional markers for heart failure have been shown to be of limited sensitivity in patients with HFpEF, as those do not reflect pathophysiology of the disease properly. Dysregulation of haemostasis is thought to be central for the initiation and progression of HFpEF. For this reason, we aimed to assess markers of fibrinolytic activity as potential biomarkers for risk assessment in patients with HFpEF. We evaluated blood coagulation parameters in 370 patients with HFpEF included in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. Within an observation period of 9.7 years, 40 percent of these patients died from any cause. tPA/PAI-1 complex significantly predicted all-cause mortality with a hazard ratio (HR) of 1.24 (95 % confidence interval [CI] 1.04–1.47) per increase of 1 SD and cardiovascular mortality with a HR 1.26 (95 % CI 1.02–1.56) per increase of 1 SD. Both associations remained significant after adjustment for cardiovascular risk factors, N-terminal pro–B-type natriuretic peptide (NT-proBNP) and frequent HFpEF- related comorbidities. Importantly, tPA/PAI-1 complex had additional prognostic value above and beyond NT-proBNP as indicated by integrated discrimination improvement (0.0157, p=0.017). In conclusion, the concentration of tPA/ PAI-1 complex is an independent predictor of mortality from all causes and from cardiovascular causes in patients with HFpEF. The concomitant measurement of tPA/PAI-1 complex might be useful in clinical practice to add prognostic value to traditional markers of heart failure.
Atherosclerosis revisited from a clinical perspective: still an inflammatory disease?
Authors: Santovito Donato , Weber Christian
Published: December 2016

Compelling experimental results have substantiated the immune-driven inflammatory nature of atherosclerosis. Most of the scientific advances over the past decades have been achieved by relying on transgenic animal models that have been employed with increasing levels of sophistication. However, recent failures in translating various anti-inflammatory therapeutic strategies for use in humans might raise some skepticism with regards to an inflammatory causality underlying human atherosclerosis. By applying a dialectical approach, this Perspective aims to challenge and deduce the nature of atherosclerosis by reviewing results exclusively derived from human studies and recent clinical trials, as “things may not always be, what they appear”.

Note: The review process for this manuscript was fully handled by Gregory Y. H. Lip, Editor in Chief.
State-of-the-Art Review of Echocardiographic Imaging in the Evaluation and Treatment of Functional Tricuspid Regurgitation
Authors: Hahn Rebecca T.
Published: December 2016

Functional or secondary tricuspid regurgitation (TR) is the most common cause of severe TR in the Western world. The presence of functional TR, either isolated or in combination with left heart disease, is associated with unfavorable natural history. Surgical mortality for isolated tricuspid valve interventions remains higher than for any other single valve surgery, and surgical options for repair do not have consistent long-term durability. In addition, as more patients undergo transcatheter left valve interventions, developing transcatheter solutions for functional TR has gained greater momentum. Numerous transcatheter devices are currently in early clinical trials. All patients require an assessment of valve morphology and function, and transcatheter devices typically require intraprocedural guidance by echocardiography. The following review will describe tricuspid anatomy, define echocardiographic views for evaluating tricuspid valve morphology and function, and discuss imaging requirements for the current transcatheter devices under development for the treatment of functional TR.
Marital History and Survival After Stroke
Authors: Dupre Matthew E. , Lopes Renato D.
Published: December 2016

Background

Stroke is among the leading causes of disability and death in the United States, and nearly 7 million adults are currently alive after experiencing a stroke. Although the risks associated with having a stroke are well established, we know surprisingly little about how marital status influences survival in adults with this condition. This study is the first prospective investigation of how marital history is related to survival after stroke in the United States.

Methods and Results

Data from a nationally representative sample of older adults who experienced a stroke (n=2351) were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among the never married (hazard ratio [
HR
], 1.71; 95%
CI
, 1.31–2.24), remarried (
HR
, 1.23; 95%
CI
, 1.06–1.44), divorced (
HR
, 1.23; 95%
CI
, 1.01–1.49), and widowed (
HR
, 1.25; 95%
CI
, 1.10–1.43) relative to those who remained continuously married. We also found that having multiple marital losses was especially detrimental to survival—regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiological risk factors.

Conclusions

Marital history is significantly associated with survival after stroke. Additional studies are needed to further examine the mechanisms contributing to the associations and to better understand how this information can be used to personalize care and aggressively treat vulnerable segments of the population.
Boundaries and Rights after 2014
Authors: Grant Thomas D.
Published: December 2016

In its Decalogue, the Final Act of the Conference on Security and Co-operation in Europe reflects the centrality of the territorial settlement to public order in Europe. It also reflects the hope that human rights will become more deeply entrenched across all state parties to the Act. The intertwining of territorial provisions and human rights was no mere coincidence: it was at the heart of the compromise that enabled the parties to agree to the text as adopted. The events of 2014—in particular the forcible seizure of Ukrainian territory—raise questions as to the continuing vitality of the compromise that was reached in 1975 and long maintained. The new foreign policy of the Russian Federation, by embracing a potentially far-ranging irredentism, places the territorial idea of the Final Act under stress. Simultaneously, a new domestic policy rejects not only the enforceability of human rights at the international level but also the applicability of human-rights obligations in the national legal order. The new foreign and domestic policies in Russia have emerged in tandem. Their relation to each other must be considered if their effect on public order is to be understood.
Human Rights and National Security Post 9/11
Authors: Schofer Morgan
Published: December 2016

This article seeks to examine the relationship between human rights and national security within the context of counter-terrorism legislation in the United States following 11 September 2001. Working from a constructivist point of view and using discourse analysis and public-opinion data, I aim to determine whether changes have been made to the right to privacy and the anti-torture norm under the administrations of presidents George W. Bush and Barack Obama.
osce vs Transnational Threats
Authors: Lyzhenkov Alexey L.
Published: December 2016

Transnational threats, such as terrorism, illegal trafficking, organized crime, including cyber-crime, remain among the most significant threats to peace, security and stability worldwide and to the osce participating States. Such threats undermine the social and economic development of people who live in the osce region, their fundamental freedoms, their safety, stability and enjoyment of human rights. Are there any tools to address these threats in such a way that people in the osce region would feel secure and safe to fly, to enjoy meeting friends in cafes and restaurants, to attend masses and sporting events, to have usual human life without anxiety for their children, their families and friends, and for themselves? The author tries to answer this question, he provides an overview of the osce toolbox in this area and makes some suggestions on the way forward.
odihr hcnm Handbook on Observing and Promoting the Participation of National Minorities in the Electoral Process
Authors: Nurumov Dmitry
Published: December 2016

This article provides an overview of the
odihr hcnm Handbook on Observing and Promoting the Participation of National Minorities in the Electoral Process. It includes a brief but important discussion of some recurrent issues that have been identified in election observation across the osce region with respect to national minority participation. These findings informed the drafting of the Handbook, which, however, due to its format, does not provide illustrations of particular situations. Thus, this article complements the Handbook by providing references to the concrete examples from the osce area.
A new species of Amyris (Rutaceae, Toddalioideae, Amyridinae) from Mexico
Authors: HERNÁNDEZ-BARÓN LIZETTH JIMENA , ESPEJO-SERNA ADOLFO , PÉREZ-GARCÍA EDUARDO A. , CERROS-TLATILPA ROSA , LÓPEZ-FERRARI ANA ROSA
Published: December 2016

Amyris jorgemeavei from the state of Oaxaca, Mexico, is described and illustrated. The new taxon is compared with A. carterae and A. madrensis, species with similar morphological characteristics. It is however easily differentiated from these two by having glabrous leaves and floral parts, a lobed nectar disc, and it is known only from southwestern Mexico. A comparative table and a distribution map of the three species are included.
Hotspots of mite new species discovery: Sarcoptiformes (2013–2015)
Authors: LI GUANG-YUN , ZHANG ZHI-QIANG
Published: December 2016

A list of of type localities and depositories of new species of the mite order Sarciptiformes published in two journals (Zootaxa and Systematic & Applied Acarology) during 2013–2015 is presented in this paper, and trends and patterns of new species are summarised. The 242 new species are distributed unevenly among 50 families, with 62% of the total from the top 10 families. Geographically, these species are distributed unevenly among 39 countries. Most new species (72%) are from the top 10 countries, whereas 61% of the countries have only 1–3 new species each.  Four of the top 10 countries are from Asia (Vietnam, China, India and The Philippines).
A new species of crayfish in the genus Orconectes (Decapoda: Cambaridae) from the Tennessee River Drainage with comments on and key to members of the O. juvenilis Species Complex
Authors: TAYLOR CHRISTOPHER A. , RHODEN CODY M. , SCHUSTER GUENTER A.
Published: December 2016

The crayfish subgenus Procericambarus (genus Orconectes) found in the Eastern Highlands of the United States represents a rich assemblage of stream-dwelling macroinvertebrates. While the taxonomic status and distribution of its members were clarified in a previous study, newly diagnosed characters and newly collected specimens warranted a revision to previous hypotheses of Procericambarus membership in the southeastern United States. Using morphological characters, we describe herein a new species of crayfish occurring in the Tennessee River drainage of northern Alabama and southwestern Tennessee. We also provide a revised key for the identification of members of O. juvenilis Species Complex.
Gradients of Atmospheric Temperature and Humidity Controlled by Local Urban Land-Use Intensity in Boston
Authors: Wang J. A. , Hutyra L. R. , Li D. , Friedl M. A.
Published: December 2016

Cities are home to the majority of humanity. Therefore, understanding the mechanisms that control urban climates has substantial societal importance to a variety of sectors, including public health and energy management. In this study, data from an urban sensor network (25 stations) and moderate-resolution remote sensing were used to explore how spatial variation in near-surface air temperature Ta, vapor pressure deficit (VPD), and land surface temperature (LST) depend on local variations in urban land use, both diurnally and seasonally, in the Boston, Massachusetts, metropolitan area. Positive correlations were observed between the amount of local impervious surface area (ISA) and both Ta and VPD. Heat-island effects peaked during the growing-season nighttime, when mean Ta and VPD increased by up to 0.02°C and 0.008 kPa, respectively, per unit ISA. Air temperature and VPD were strongly coupled, but their relationship exhibited significant diurnal hysteresis during the growing season, with changes in VPD generally preceding changes in Ta. Over 79% of the urban–rural difference in VPD was explained by differences in near-surface atmospheric water content, which the authors attribute to reduced evapotranspiration from lower canopy cover in Boston’s urban core. Changes in daytime heat-island intensity were mediated by seasonal feedbacks between vegetation transpiration and VPD forcing. Differences between LST and Ta showed weaker coupling in highly urbanized areas than in rural areas, with summertime surface-urban-heat-island intensity (based on LST) being up to 14°C higher than corresponding urban–rural differences in Ta.
Variability of Soil Moisture and Sea Surface Temperatures Similarly Important for Warm-Season Land Climate in the Community Earth System Model
Authors: Orth Rene , Seneviratne Sonia I.
Published: December 2016

Both sea surface temperatures (SSTs) and soil moisture (SM) can influence climate over land. This paper presents a comprehensive comparison of SM versus SST impacts on land climate in the warm season. The authors perform fully coupled ensemble experiments with the Community Earth System Model in which they prescribe SM or SSTs to the long-term median seasonal cycles. It is found that SM variability overall impacts warm-season land climate to a similar extent as SST variability, in the midlatitudes, tropics, and subtropics. Removing SM or SST variability impacts land climate means and reduces land climate variability at different time scales by 10%–50% (temperature) and 0%–10% (precipitation). Both SM- and SST-induced changes are strongest for hot temperatures (up to 50%) and for extreme precipitation (up to 20%). These results are qualitatively similar for the present day and the end of the twenty-first century. Removed SM variability affects surface climate through corresponding variations in surface energy fluxes, and this is controlled to first order by the land–atmosphere coupling strength and the natural SM variability. SST-related changes are partly controlled by the relation of local temperature or precipitation with the El Niño–Southern Oscillation. In addition, in specific regions SST-induced SM changes alter the “direct” SST-induced climate changes; on the other hand, SM variability is found to slightly affect SSTs in some regions. Nevertheless a large level of independence is found between SM–climate and SST–climate coupling. This highlights the fact that SM conditions can influence land climate variables independently of any SST effects and that (initial) soil moisture anomalies can provide valuable information in (sub)seasonal weather forecasts.
Global and Full-Depth Ocean Temperature Trends during the Early Twenty-First Century from Argo and Repeat Hydrography
Authors: Desbruyères Damien , McDonagh Elaine L. , King Brian A. , Thierry Virginie
Published: December 2016

The early twenty-first century’s warming trend of the full-depth global ocean is calculated by combining the analysis of Argo (top 2000 m) and repeat hydrography into a blended full-depth observing system. The surface-to-bottom temperature change over the last decade of sustained observation is equivalent to a heat uptake of 0.71 ± 0.09 W m−2 applied over the surface of Earth, 90% of it being found above 2000-m depth. The authors decompose the temperature trend pointwise into changes in isopycnal depth (heave) and temperature changes along an isopycnal (spiciness) to describe the mechanisms controlling the variability. The heave component dominates the global heat content increase, with the largest trends found in the Southern Hemisphere’s extratropics (0–2000 m) highlighting a volumetric increase of subtropical mode waters. Significant heave-related warming is also found in the deep North Atlantic and Southern Oceans (2000–4000 m), reflecting a potential decrease in deep water mass renewal rates. The spiciness component shows its strongest contribution at intermediate levels (700–2000 m), with striking localized warming signals in regions of intense vertical mixing (North Atlantic and Southern Oceans). Finally, the agreement between the independent Argo and repeat hydrography temperature changes at 2000 m provides an overall good confidence in the blended heat content evaluation on global and ocean scales but also highlights basin-scale discrepancies between the two independent estimates. Those mismatches are largest in those basins with the largest heave signature (Southern Ocean) and reflect both the temporal and spatial sparseness of the hydrography sampling.
The Influence of the Indian Ocean on ENSO Stability and Flavor
Authors: Wieners Claudia E. , Dijkstra Henk A. , de Ruijter Will P. M.
Published: December 2016

The effect of long-term trends and interannual, ENSO-driven variability in the Indian Ocean (IO) on the stability and spatial pattern of ENSO is investigated with an intermediate-complexity two-basin model. The Pacific basin is modeled using a fully coupled (i.e., generating its own background state) Zebiak–Cane model. IO sea surface temperature (SST) is represented by a basinwide warming pattern whose strength is constant or varies at a prescribed lag to ENSO. Both basins are coupled through an atmosphere transferring information between them. For the covarying IO SST, a warm IO during the peak of El Niño (La Niña) dampens (destabilizes) ENSO, and a warm IO during the transition from El Niño to La Niña (La Niña to El Niño) shortens (lengthens) the period. The influence of the IO on the spatial pattern of ENSO is small. For constant IO warming, the ENSO cycle is destabilized because stronger easterlies induce more background upwelling, more thermocline steepening, and a stronger Bjerknes feedback. The SST signal at the east coast weakens or reverses sign with respect to the main ENSO signal [i.e., ENSO resembles central Pacific (CP) El Niños]. This is due to a reduced sensitivity of the SST to thermocline variations in case of a shallow background thermocline, as found near the east coast for a warm IO. With these results, the recent increase in CP El Niño can possibly be explained by the substantial IO (and west Pacific) warming over the last decades.
Impacts of Anthropogenic Heat on Summertime Rainfall in Beijing
Authors: Nie Wanshu , Zaitchik Benjamin F. , Ni Guangheng , Sun Ting
Published: December 2016

Anthropogenic heat is an important component of the urban energy budgets that can affect land surface and atmospheric boundary layer processes. Representation of anthropogenic heat in numerical climate modeling systems is therefore important when simulating urban meteorology and climate and has the potential to improve weather forecasts, climate process studies, and energy demand analysis. Here, spatiotemporally dynamic anthropogenic heat data estimated by the Building Effects Parameterization and Building Energy Model (BEP-BEM) are incorporated into the Weather Research and Forecasting (WRF) Model system to investigate its impact on simulation of summertime rainfall in Beijing, China. Simulations of four local rainfall events with and without anthropogenic heat indicate that anthropogenic heat leads to increased rainfall over the urban area. For all four events, anthropogenic heat emission increases sensible heat flux, enhances mixing and turbulent energy transport, lifts PBL height, increases dry static energy, and destabilizes the atmosphere in urban areas through thermal perturbation and strong upward motion during the prestorm period, resulting in enhanced convergence during the major rainfall period. Intensified rainfall leads to greater atmospheric dry-down during the storm and a higher poststorm LCL.
Surface Relative Dispersion in the Southwestern Gulf of Mexico
Authors: Sansón Luis Zavala , Pérez-Brunius Paula , Sheinbaum Julio
Published: December 2016

Surface dispersion properties in the southwestern Gulf of Mexico are studied by using a set of 441 drifters released during a 7-yr period and tracked for 2 months on average. The drifters have a drogue below the surface Ekman layer, so they approximately follow oceanic currents. This study follows two different approaches: First, two-particle (or pair) statistics are calculated [relative dispersion and finite-scale Lyapunov exponents (FSLEs)]. Relative dispersion estimates are consistent with theoretical dispersion regimes of two-dimensional turbulence: an exponential growth during the first 3 days, a Richardson-like regime between 3 and 20 days (in which relative dispersion grows as a power law in time), and standard dispersion (linear growth) for longer times. The FSLEs yield a power-law regime for scales between 10 and 150 km but do not detect an exponential regime for short separations (less than 10 km). Robust estimates of diffusivities based on both relative dispersion and FSLEs are provided. Second, two different dispersion scenarios are revealed by drifter trajectories and altimetric data and supported by two-particle statistics: (i) a south-to-north advection of drifters, predominantly along the western shelf of the region, and (ii) a retention of drifters during several weeks at the Bay of Campeche, the southernmost part of the Gulf of Mexico. Dominant processes that control the dispersion are the arrival of anticyclonic Loop Current eddies to the western shelf and their interaction with the semipermanent cyclonic structure in the Bay of Campeche.
Observations of Surface Wave–Current Interaction
Authors: Romero Leonel , Lenain Luc , Melville W. Kendall
Published: December 2016

Wave–current interaction can result in significant inhomogeneities of the ocean surface wave field, including modulation of the spectrum, wave breaking rates, and wave statistics. This study presents novel airborne observations from two experiments: 1) the High-Resolution Air–Sea Interaction (HiRes) experiment, with measurements across an upwelling jet off the coast of Northern California, and 2) an experiment in the Gulf of Mexico with measurements of waves interacting with the Loop Current and associated eddies. The significant wave height and slope varies by up to 30% because of these interactions at both sites, whereas whitecap coverage varies by more than an order of magnitude. Whitecap coverage is well correlated with spectral moments, negatively correlated with the directional spreading, and positively correlated with the saturation. Surface wave statistics measured in the Gulf of Mexico, including wave crest heights and lengths of crests per unit surface area, show good agreement with second-order nonlinear approximations, except over a focal area. Similarly, distributions of wave heights are generally bounded by the generalized Boccotti distribution, except at focal regions where the wave height distribution reaches the Rayleigh distribution with a maximum wave height of 2.55 times the significant wave height, which is much larger than the standard classification for extreme waves. However, theoretical distributions of spatial statistics that account for second-order nonlinearities approximately bound the observed statistics of extreme wave elevations. The results are discussed in the context of improved models of breaking and related air–sea fluxes.
Interactions of North Pacific Tropical, Midlatitude, and Polar Disturbances Resulting in Linked Extreme Weather Events over North America in October 2007
Authors: Bosart Lance F. , Moore Benjamin J. , Cordeira Jason M. , Archambault Heather M.
Published: December 2016

This study uses observations and model reanalyses to examine the multiscale processes associated with four high-impact extreme weather events (EWEs) over North America during late October 2007. The EWEs consisted of wind-driven wildfires in California, prolonged anomalous cold conditions in Mexico linked to two cold surges, heavy rainfall in the eastern United States, and severe flood-producing heavy rainfall in southern Mexico. The EWEs involved a pronounced large-scale flow reconfiguration across the North Pacific and North America in conjunction with the formation of a high-amplitude Rossby wave train. The flow reconfiguration involved perturbations to the North Pacific jet stream linked to polar, midlatitude, and tropical disturbances, including three tropopause-level polar disturbances originating over northeastern Asia, transient extratropical cyclones, a diabatic Rossby vortex, and western North Pacific Tropical Cyclone Kajiki. Eulerian and Lagrangian diagnostics indicate that ridge amplification within the wave train was enhanced in connection with latent heat release along warm conveyor belts rooted in the tropics and subtropics over the North Pacific. Two anticyclonic Rossby wave breaking events over North America established synoptic-scale conditions that supported the EWEs. The results highlight how the large- and synoptic-scale flow can evolve to facilitate multiple geographically separated but dynamically linked EWEs. Based on the results, it is posited that during autumn the North Pacific jet stream may be particularly conducive to large-scale flow amplification, possibly resulting in EWEs, in response to perturbations associated with tropical, midlatitude, and polar disturbances.
Where’s all the ‘good’ sports journalism? Sports media research, the sociology of sport, and the question of quality sports reporting
Authors: Weedon Gavin , Wilson Brian , Yoon Liv , Lawson Shawna
Published: December 2016

Across newsrooms and journalism schools, questions as to what constitutes or ‘counts’ as excellent reporting are currently inciting much debate. Among the various frameworks being put forward to describe and encourage ‘excellent’ journalism in its various forms, sport is seldom mentioned – a legacy perhaps of its perennial dismissal as trivial subject matter. This essay grew from our curiosity as to whether the reverse was also true: that is, whether and what those who study sports journalism and sports media – in particular sociologists of sport – have contributed to understandings of ‘best’ and even excellent journalistic practice. We identified and analysed 376 articles from eight leading scholarly journals that feature sports media research with the aim of examining instances where ‘excellent’ sports reporting was either highlighted, described or advocated. After outlining the major themes that emerged from this analysis, we reflect on why so few of the sampled articles explicitly advise on what best practice sports journalism might look like – especially when it comes to coverage of the sport-related social issues that sociologists of sport tend to focus on – and why so little theoretical attention has been afforded to the question of excellent sports journalism more generally. While there are good sociological reasons for focusing on problematic sports reporting, on structural and systemic issues in which media are implicated, and on producing alternatives to hegemonic sports media, we conclude that it is high time for instances of excellent sports journalism to be afforded the theoretical and empirical attention long granted to their ‘bad’ journalistic counterparts.
Understanding the convergence of markets in online sports betting
Authors: Lopez-Gonzalez Hibai , Griffiths Mark D
Published: December 2016

Betting on sports via online platforms has rapidly become a popular form of gambling in many countries. Despite the growing body of research investigating the psychosocial and individual psychological factors determining gambling behaviour, much less attention has been devoted to understanding the market characteristics of online sports betting and its intersection with products from adjacent industries. From an economic convergence perspective, the present paper explores the integration of online sports betting within the digital, sporting and gambling sectors, examining how data markets, eSports, virtual sports, social gaming, immersive reality tools, sports media, sport sponsorship, fantasy sports, in-venue and in-stadium betting, poker and trading are all converging around betting activity. Through this convergence process, it is argued that internet-based sports gambling is colonizing different forms of entertainment, and expanding marketing opportunities, as well as raising psychosocial concerns about the influence of such an integration process.
Neutrophils and the S100A9 protein critically regulate granuloma formation
Authors: Yoshioka Yuya , Mizutani Tatsuaki , Mizuta Satoshi , Miyamoto Ayumi , Murata Satoru , Ano Toshiaki , Ichise Hiroshi , Morita Daisuke , Yamada Hiroyuki , Hoshino Yoshihiko , Tsuruyama Tatsuaki , Sugita Masahiko
Published: December 2016

Key Points

S100A9+ neutrophils accumulated prominently in the central area of granulomas in humans and guinea pigs. Granuloma formation was markedly impaired by a treatment with the S100A9 inhibitor, tasquinimod.
COUSCOus: improved protein contact prediction using an empirical Bayes covariance estimator
Authors: Rawi Reda , Mall Raghvendra , Kunji Khalid , El Anbari Mohammed , Aupetit Michael , Ullah Ehsan , Bensmail Halima
Published: December 2016

Background

The post-genomic era with its wealth of sequences gave rise to a broad range of protein residue-residue contact detecting methods. Although various coevolution methods such as PSICOV, DCA and plmDCA provide correct contact predictions, they do not completely overlap. Hence, new approaches and improvements of existing methods are needed to motivate further development and progress in the field. We present a new contact detecting method, COUSCOus, by combining the best shrinkage approach, the empirical Bayes covariance estimator and GLasso.

Results

Using the original PSICOV benchmark dataset, COUSCOus achieves mean accuracies of 0.74, 0.62 and 0.55 for the top L/10 predicted long, medium and short range contacts, respectively. In addition, COUSCOus attains mean areas under the precision-recall curves of 0.25, 0.29 and 0.30 for long, medium and short contacts and outperforms PSICOV. We also observed that COUSCOus outperforms PSICOV w.r.t. Matthew’s correlation coefficient criterion on full list of residue contacts. Furthermore, COUSCOus achieves on average 10% more gain in prediction accuracy compared to PSICOV on an independent test set composed of CASP11 protein targets. Finally, we showed that when using a simple random forest meta-classifier, by combining contact detecting techniques and sequence derived features, PSICOV predictions should be replaced by the more accurate COUSCOus predictions.

Conclusion

We conclude that the consideration of superior covariance shrinkage approaches will boost several research fields that apply the GLasso procedure, amongst the presented one of residue-residue contact prediction as well as fields such as gene network reconstruction.
A digital enzyme-linked immunosorbent assay for ultrasensitive measurement of amyloid-β 1–42 peptide in human plasma with utility for studies of Alzheimer’s disease therapeutics
Authors: Song Linan , Lachno D. Richard , Hanlon David , Shepro Adam , Jeromin Andreas , Gemani Dipika , Talbot Jayne A. , Racke Margaret M. , Dage Jeffrey L. , Dean Robert A.
Published: December 2016

Background

Amyloid-β 1–42 peptide (Aβ1–42) is associated with plaque formation in the brain of patients with Alzheimer’s disease (AD). Pharmacodynamic studies of AD therapeutics that lower the concentrations of Aβ1–42 in peripheral blood require highly sensitive assays for its measurement. A digital enzyme-linked immunosorbent assay (ELISA) using single molecule array (Simoa) technology has been developed that provides improved sensitivity compared with conventional ELISA methods using the same antibody reagents.

Methods

A sensitive digital ELISA for measurement of Aβ1–42 using antibodies 3D6 and 21F12 was developed. Assay performance was evaluated by repeated testing of pooled human plasma and buffer diluent quality control samples to determine relative accuracy, intra- and inter-assay precision, limit of detection (LOD), lower limit of quantification (LLOQ), dilutional linearity, and spike recovery. The optimized assay was used to quantify Aβ1–42 in clinical samples from patients treated with the β-site amyloid precursor protein cleaving enzyme 1 inhibitor LY2886721.

Results

The prototype assay measured Aβ1–42 with an LOD of 0.3 pg/ml and an LLOQ of 2.8 pg/ml in plasma, calibrated using an Aβ1–42 peptide standard from Fujirebio. Assay precision was acceptable with intra- and inter-assay coefficients of variation both being ≤10%. Dilutional linearity was demonstrated in sample diluent and immunodepleted human plasma. Analyte spike recovery ranged from 51% to 93% with a mean of 80%. This assay was able to quantify Aβ1–42 in all of the 84 clinical samples tested. A rapid reduction in levels of Aβ1–42 was detected within 1 h after drug treatment, and a dose-dependent decrease of Aβ1–42 levels was also observed over the time course of sample collection.

Conclusions

This digital ELISA has potential utility in clinical applications for quantification of Aβ1–42 in plasma where high sensitivity and precision are required.
NK cells require antigen-specific memory CD4+ T cells to mediate superior effector functions during HSV-2 recall responses in vitro
Authors: Chen Branson , Lee Amanda J , Chew Marianne V , Ashkar Ali A
Published: December 2016

Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV-2) infections. However their role as effectors in adaptive immune responses against HSV-2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN-γ) upon re-exposure to HSV-2 antigens in a mouse model of genital HSV-2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN-γ. Our results demonstrate that HSV-2–experienced CD4+ T cells have a crucial role in coordinating NK cell activation and that their presence during HSV-2 antigen presentation is required to activate NK cells in this model of secondary immune response. We also examined the requirement of cell-to-cell contacts for both CD4+ T cells and NK cells. NK cells are dependent on direct interactions with other HSV-2–experienced splenocytes, and CD4+ T cells need to be in close proximity to NK cells to activate them. This study revealed that NK cells do not exhibit any memory toward HSV-2 antigens and, in fact, require specific interactions with HSV-2–experienced CD4+ T cells to produce IFN-γ
Low-frequency rotational isolator for airborne exploration
Authors: Sunderland Andrew , Lockwood Ray , Ju Li , Blair David G.
Published: December 2016

We have determined the performance of a passive rotational vibration isolator for a time-domain airborne electromagnetic (TDEM) receiver. The isolator uses neutrally buoyant flotation to provide very soft suspension and a very low resonant frequency of 0.065 Hz ± 0.005 Hz. One of the limitations of mapping deeper targets in areas of conductive overburden with TDEM systems is that low-frequency coil-vibration noise provides a lower bound to the transmitter base frequency (typically limited to 25 Hz). The purpose of this new isolator is to improve coil vibration related noise between 5 and 20 Hz to allow the transmitter base frequency to be reduced. A fixed-wing flight test determined that a receiver inside the new isolator had five times less rotational noise at 10 Hz than a current commercial system.
Characterization of a TUTase/RNase complex required for Drosophila gametogenesis
Authors: Lin Ching-Jung , Wen Jiayu , Bejarano Fernando , Hu Fuqu , Bortolamiol-Becet Diane , Kan Lijuan , Sanfilippo Piero , Kondo Shu , Lai Eric C.
Published: December 2016

Post-transcriptional regulatory strategies that involve coupling between terminal uridyltransferase (TUTase) and exoribonuclease enzymes have recently been characterized in diverse species. Of note, the 3′ exoribonuclease Dis3L2 has received substantial attention as a factor that metabolizes uridylated substrates in contexts such as general mRNA degradation, turnover of specific miRNAs, and quality control of noncoding RNAs. To date, most studies of Dis3L2 have focused on fungi and mammalian cells. Here, we introduce Drosophila as a system that permits analysis of molecular mechanisms as well as the ability to interrogate organismal phenotypes. We started with a structure–function analysis of the Drosophila TUTase Tailor, which we recently identified to inhibit biogenesis of splicing-derived miRNA hairpins. Next, we show that Tailor/Dis3L2 form a complex via N-terminal domains in the respective proteins that are distinct from their catalytic domains. In vitro, Dis3L2 has nuclease activity, but substrate oligouridylation by Tailor stimulates their degradation by Dis3L2, especially for structured substrates. We analyzed mutants of Tailor and Dis3L2, which are viable and lack overt morphological defects. Instead, these mutants exhibit defects in female and male fertility, implying specific requirements in the germline. Dis3L2 defects are more severe than Tailor, and their requirements appear stronger in males than in females. In particular, loss of Dis3L2 completely blocks productive spermatogenesis, causing male sterility. RNA-seq analysis from single- and double-mutant testes reveals aberrant gene expression programs and suggests that noncoding RNAs may be preferentially affected by Dis3L2. Overall, our studies of a new tailing/trimming complex reveal unexpectedly specific requirements during gametogenesis.
Statistical analysis plan for the WOMAN-ETAPlaT study: Effect of tranexamic acid on platelet function and thrombin generation
Authors: Dallaku Kastriot , Shakur Haleema , Edwards Phil , Beaumont Danielle , Roberts Ian , Huque Sumaya , Delius Maria , Mansmann Ulrich
Published: December 2016

Background. Postpartum haemorrhage (PPH) is a potentially life-threatening complication for women, and the leading cause of maternal mortality. Tranexamic acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and to reduce blood loss in general surgery. TXA may have effects on thrombin generation, platelet function and coagulation factors as a result of its inhibition on the plasmin.

Methods. WOMAN ETAPlaT is a sub-study of the World Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically diagnosed with PPH after a vaginal delivery or caesarean section, are eligible for inclusion in the study. Blood samples will be collected at the baseline and 30 minutes after the first dose of study treatment is given. Platelet function will be evaluated in whole blood immediately after sampling with Multiplate® tests (ADPtest and TRAPtest). Thrombin generation, fibrinogen, D-dimer, and coagulation factors vW, V and VIII will be analysed using platelet poor plasma.

Results. Recruitment to WOMAN ETAPlaT started on 04 November 2013 and closed on 13 January 2015, during this time  188 patients were recruited. The final participant follow-up was completed on 04 March 2015. This article introduces the statistical analysis plan for the study, without reference to unblinded data.  

Conclusion. The data from this study will provide evidence for the effect of TXA on thrombin generation, platelet function and coagulation factors in women with PPH.

Trial registration: ClinicalTrials.gov Identifier: NCT00872469; ISRCTN76912190
The concept of the balanced management of the housing fund´s formation in full accordance with the multy-storeyed house´s life cycle stage
Authors: Кравченко Анастасия , Kravchenko Anastasiya
Published: December 2016

The general directions necessary for the concept of the balanced management of the housing fund formation have been taken under consideration. The characteristics of the multy-storeyed building´s lifetime stages have been illustrated the arrangements affecting the efficiency of the housing fund management are given accordance with the corresponding stages of this procedure. The necessity of making a list of the annuary plans for the process of management and taking under control the execution of these measures have been proved. The methodical approach concerning the elaboration of the effective system of management including life cycle stage of this object has been formulated as well as the probable results of the usage of such a concept.