bluuebunny/crossref_metadata_2025_split huggingface dataset:
The functional genomics laboratory: functional validation of genetic variants
Authors: Rodenburg Richard J. 
Published: February 2018

AbstractCurrently, one of the main challenges in human molecular genetics is the interpretation of rare genetic variants of unknown clinical significance. A conclusive diagnosis is of importance for the patient to obtain certainty about the cause of the disease, for the clinician to be able to provide optimal care to the patient and to predict the disease course, and for the clinical geneticist for genetic counseling of the patient and family members. Conclusive evidence for pathogenicity of genetic variants is therefore crucial. This review gives an introduction to the problem of the interpretation of genetic variants of unknown clinical significance in view of the recent advances in genetic screening, and gives an overview of the possibilities for functional tests that can be performed to answer questions about the function of genes and the functional consequences of genetic variants (“functional genomics”) in the field of inborn errors of metabolism (IEM), including several examples of functional genomics studies of mitochondrial disorders and several other IEM.
Emergency Management of Priapism in the United Kingdom: A Survey of Current Practice
Authors: Bullock Nicholas , Steggall Martin , Brown Gareth 
Published: February 2018

Abstract

Background
Despite its importance, current practice in the emergency management of priapism in the United Kingdom is unknown.

Aim
To evaluate current practice in the emergency management of priapism in the United Kingdom.

Methods
All “full,” “associate urological specialist,” and “trainee” members of the British Association of Urological Surgeons (BAUS; leading membership-based organization for practitioners of urologic surgery in the United Kingdom) were invited to participate in an online survey. Questions related to the emergency management of priapism, access to tertiary andrology services, and use of guidelines.

Outcomes
Key outcome measures included frequency of encountered cases, access to specialist andrology support, confidence in key management steps, and use of current guidelines.

Results
213 of 1,304 (16.3%) eligible members completed the survey. Most reported managing 1 case annually (median = 1, range = 0–&gt;10). Only 7.0% transferred patients to a tertiary center and 87.8% believed they could access specialist andrology advice if required. Respondents were less confident in performing intracavernosal phenylephrine instillation (88.7%) compared with corporal aspiration (98.1%), with confidence lowest among trainee members. Only 68.5% reported performing the distal shunt procedure. Of the 212 respondents that chose to answer questions relating to guidelines, only 155 (73.1%) were aware of their existence, with those published by the European Association of Urology being most popular (53.8%). 205 (96.2%) respondents expressed an interest in the development of a UK-specific guideline, with 162 of 212 (76.4%) stating they would use this in practice.

Clinical Implications
Urologists in the United Kingdom support the development of UK-specific guidance on the emergency management of priapism for use within the context of the National Health Service.

Strengths and Limitations
This is the first study to assess current practice in the emergency management of priapism in the United Kingdom. Its strength is that most UK urologists were invited to participate through collaboration with the BAUS. Although the response rate of 16.3% is acceptable for a national survey of this nature, responses were self-reported, rendering them susceptible to bias.

Conclusion
This study demonstrates that some UK urologists lack confidence in key steps in the emergency management of priapism and identifies a strong level of support for the development of up-to-date UK-specific guidance.
A strategy to represent impacts of subgrid-scale topography on snow evolution in the Canadian Land Surface Scheme
Authors: Younas Waqar , Hay Rachel W. , MacDonald Matt K. , Islam Siraj ul , Déry Stephen J. 
Published: February 2018

ABSTRACTThis sensitivity study applies the offline Canadian Land Surface Scheme (CLASS) version 3.6 to simulate snowpack evolution in idealized topography using observations at Likely, British Columbia, Canada over 1 July 2008 to 30 June 2009. A strategy for a subgrid-scale snow (SSS) parameterization is developed to incorporate two key features: ten elevation bands at 100 m intervals to capture air temperature lapse rates, and five slope angles on four aspects to resolve solar radiation impacts on the evolution of snow depth and SWE. Simulations reveal strong elevational dependencies of snow depth and SWE when adjusting temperatures using a moist adiabatic lapse rate with elevation, with 26% peak SWE differences between that at the average elevation versus the mean of the remainder of the elevation bands. Differences in peak SWE on north- and south-facing slopes increase from 3.0 mm at 10° slope to 17.9 mm at 50° slope. When applied to elevation, slope and aspect combinations derived from a high-resolution digital elevation model, elevation dominates the control of peak SWE values. Inclusion of the range of SSS effects into a regional climate model will improve snowpack and hydrological simulations of western North America's snow-dominated, mountainous watersheds.
Seed dispersal syndromes in the Madagascan flora: the unusual importance of primates
Authors: Albert-Daviaud Aurélie , Perillo Sarah , Stuppy Wolfgang 
Published: February 2018

AbstractMadagascar is one of the most threatened biodiversity hotspots, and protection of its biodiversity is becoming increasingly urgent as deforestation of the island continues. For the long-term success of conservation efforts it is essential that key ecological processes, such as seed dispersal, are protected and restored. Therefore, the identification of ecological gaps is a vital task. For Madagascar, only little is known about plant–animal interactions, and traditional methods of ecological research are too time-consuming to provide crucial information about breakdowns in these interactions. To identify likely dispersal gaps we therefore used a theoretical approach to analyse plant–disperser interactions in Madagascar. We used data science tools to impute missing data on relevant plant traits to subsequently predict the most likely dispersal agents for each of Madagascar's endemic plant species. We found that 38% of the endemic species (N = 8,784) are endozoochorous, and among these 26–41% display a primate syndrome and 17–19% a bird syndrome (depending on the definition of syndromes). This lower percentage of endozoochorous species and higher percentage of species with a primate syndrome in Madagascar compared to other tropical areas reflects the unusual disperser guild on the island. Only five bird species but 20 lemur species are frugivorous, and 16 of those lemur species are currently threatened with extinction. The disappearance of frugivorous lemurs would significantly change the vegetation dynamics of Madagascar's ecosystems, and a high proportion of Madagascar's endemic plants would enter an extinction vortex.
Are sacred caves still safe havens for the endemic bats of Madagascar?
Authors: Fernández-Llamazares Álvaro , López-Baucells Adrià , Rocha Ricardo , Andriamitandrina Santatra F. M. , Andriatafika Zo Emmanuel , Burgas Daniel , Temba Eric Marcel , Torrent Laura , Cabeza Mar 
Published: February 2018

AbstractDespite conservation discourses in Madagascar increasingly emphasizing the role of customary institutions for wildlife management, we know relatively little about their effectiveness. Here, we used semi-structured interviews with 54 adults in eight villages to investigate whether sacred caves and taboos offer conservation benefits for cave-dwelling bats in and around Tsimanampetsotsa National Park, south-west Madagascar. Although some caves were described as sites of spiritual significance for the local communities, most interviewees (c. 76%) did not recognize their present-day sacred status. Similarly, only 22% of the interviewees recognized taboos inhibiting bat hunting and consumption. Legal protection of bats and caves through protected areas was often more widely acknowledged than customary regulations, although up to 30% of the interviewees reported consumption of bats within their communities. Guano extraction was often tolerated in sacred caves in exchange for economic compensation. This may benefit bat conservation by creating incentives for bat protection, although extraction is often performed through destructive and exploitative practices with little benefit for local communities. In view of these results our study questions the extent to which sacred sites, taboos and protected areas offer protection for bats in Madagascar. These results support previous studies documenting the erosion of customary institutions in Madagascar, including the loss of the spiritual values underpinning sacred sites. Given that many Malagasy bats are cave-dwelling species and that most depend on the customary protection of these sites, it is important to obtain a better understanding of the complex interactions between spiritual practices, taboos and protected areas in sustaining bat diversity.
THE SMALL IMPROVEMENT ARGUMENT, EPISTEMICISM AND INCOMPARABILITY
Authors: Flanigan Edmund Tweedy , Halstead John 
Published: February 2018

Abstract:The Small Improvement Argument (SIA) is the leading argument for value incomparability. All vagueness-based accounts of the SIA have hitherto assumed the truth of supervaluationism, but supervaluationism has some well-known problems. This paper explores the implications of epistemicism, a leading rival theory. We argue that if epistemicism is true, then options are comparable in small improvement cases. Moreover, even if SIAs do not exploit vagueness, if epistemicism is true, then options cannot be on a par. The epistemicist account of the SIA has an advantage over leading existing rival accounts of the SIA because it accounts for higher-order hard cases.
Lenalidomide regulates CNS autoimmunity by promoting M2 macrophages polarization
Authors: Weng Qinjie , Wang Jiaying , Wang Jiajia , Wang Jing , Sattar Fahmida , Zhang Zhikang , Zheng Jiahuan , Xu Zijie , Zhao Mengting , Liu Xuan , Yang Lijun , Hao Guifeng , Fang Liang , Lu Q. Richard , Yang Bo , He Qiaojun 
Published: February 2018

AbstractMultiple sclerosis (MS) is a chronic and debilitating neurological disorder of the central nervous system (CNS), characterized by infiltration of leukocytes into CNS and subsequent demyelination. Emerging evidences have revealed the beneficial roles of M2 macrophages in ameliorating experimental autoimmune encephalomyelitis (EAE), a model for MS. Here, we identify that lenalidomide alone could promote macrophages M2 polarization to prevent the progression of EAE, which is associated with subsequent inhibition of proinflammatory Th1 and Th17 cells both in peripheral lymph system and CNS. Depletion of macrophages by pharmacology treatment of clodronate liposomes or transferring lenalidomide-induced BMDMs in EAE mice completely abolished the therapeutic effect of lenalidomide or prevented EAE development, respectively. The macrophages-derived IL10 was upregulated both in vivo and in vitro after lenalidomide treatment. Moreover, lenalidomide-treated IL10-dificient EAE mice had higher clinical scores and more severe CNS damage, and intravenous injection of lenalidomide-treated IL10−/− BMDMs into mice with EAE at disease onset did not reverse disease severity, implying IL10 may be essential in lenalidomide-ameliorated EAE. Mechanistically, lenalidomide significantly increased expression and autocrine secretion of IL10, subsequently activated STAT3-mediated expression of Ym1. These studies facilitate the development of potential novel therapeutic application of lenalidomide for the treatment of MS.
Mechanism of inhibition of Shiga-toxigenic Escherichia coli SubAB cytotoxicity by steroids and diacylglycerol analogues
Authors: Yahiro Kinnosuke , Nagasawa Sayaka , Ichimura Kimitoshi , Takeuchi Hiroki , Ogura Kohei , Tsutsuki Hiroyasu , Shimizu Takeshi , Iyoda Sunao , Ohnishi Makoto , Iwase Hirotaro , Moss Joel , Noda Masatoshi 
Published: February 2018

AbstractShiga toxigenic Escherichia coli (STEC) are responsible for a worldwide foodborne disease, which is characterized by severe bloody diarrhea and hemolytic uremic syndrome (HUS). Subtilase cytotoxin (SubAB) is a novel AB5 toxin, which is produced by Locus for Enterocyte Effacement (LEE)-negative STEC. Cleavage of the BiP protein by SubAB induces endoplasmic reticulum (ER) stress, followed by induction of cytotoxicity in vitro or lethal severe hemorrhagic inflammation in mice. Here we found that steroids and diacylglycerol (DAG) analogues (e.g., bryostatin 1, Ingenol-3-angelate) inhibited SubAB cytotoxicity. In addition, steroid-induced Bcl-xL expression was a key step in the inhibition of SubAB cytotoxicity. Bcl-xL knockdown increased SubAB-induced apoptosis in steroid-treated HeLa cells, whereas SubAB-induced cytotoxicity was suppressed in Bcl-xL overexpressing cells. In contrast, DAG analogues suppressed SubAB activity independent of Bcl-xL expression at early time points. Addition of Shiga toxin 2 (Stx2) with SubAB to cells enhanced cytotoxicity even in the presence of steroids. In contrast, DAG analogues suppressed cytotoxicity seen in the presence of both toxins. Here, we show the mechanism by which steroids and DAG analogues protect cells against SubAB toxin produced by LEE-negative STEC.
Warm blood cardioplegia versus cold crystalloid cardioplegia for myocardial protection during coronary artery bypass grafting surgery
Authors: Nardi Paolo , Pisano Calogera , Bertoldo Fabio , Vacirca Sara R. , Saitto Guglielmo , Costantino Antonino , Bovio Emanuele , Pellegrino Antonio , Ruvolo Giovanni 
Published: February 2018

AbstractWe retrospectively analyzed early results of coronary artery bypass grafting (CABG) surgery using two different types of cardioplegia for myocardial protection: antegrade intermittent warm blood or cold crystalloid cardioplegia. From January 2015 to October 2016, 330 consecutive patients underwent isolated on-pump CABG. Cardiac arrest was obtained with use of warm blood cardioplegia (WBC group, n = 297) or cold crystalloid cardioplegia (CCC group, n = 33), according to the choice of the surgeon. Euroscore II and preoperative characteristics were similar in both groups, except for the creatinine clearance, slightly lower in WBC group (77.33 ± 27.86 mL/min versus 88.77 ± 51.02 mL/min) (P < 0.05). Complete revascularization was achieved in both groups. In-hospital mortality was 2.0% (n = 6) in WBC group, absent in CCC group. The required mean number of cardioplegia’s doses per patient was higher in WBC group (2.3 ± 0.8) versus CCC group (2.0 ± 0.7) (P = 0.045), despite a lower number of distal coronary artery anastomoses (2.7 ± 0.8 versus 3.2 ± 0.9) (P = 0.0001). Cardiopulmonary and aortic cross-clamp times were similar in both groups. The incidence of perioperative myocardial infarction (WBC group 3.4% versus CCC group 3.0%) and low cardiac output syndrome (4.4% versus 3.0%) were similar in both groups. As compared with WBC group, in CCC group CK-MB/CK ratio >10% was lower during each time points of evaluation, with a statistical significant difference at time 0 (4% ± 1.6% versus 5% ± 2.5%) (P = 0.021). In presence of complete revascularization, despite the value of CK-MB/CK ratio >10% was less in the CCC group, clinical results were not affected by both types of cardioplegia adopted to myocardial protection. As compared with cold crystalloid, warm blood cardioplegia requires a shorter interval of administration to achieve better myocardial protection.
Hardware-efficient fermionic simulation with a cavity–QED system
Authors: Zhu Guanyu , Subaşı Yiğit , Whitfield James D. , Hafezi Mohammad 
Published: February 2018

AbstractIn digital quantum simulation of fermionic models with qubits, non-local maps for encoding are often encountered. Such maps require linear or logarithmic overhead in circuit depth which could render the simulation useless, for a given decoherence time. Here we show how one can use a cavity–QED system to perform digital quantum simulation of fermionic models. In particular, we show that highly nonlocal Jordan–Wigner or Bravyi–Kitaev transformations can be efficiently implemented through a hardware approach. The key idea is using ancilla cavity modes, which are dispersively coupled to a qubit string, to collectively manipulate and measure qubit states. Our scheme reduces the circuit depth in each Trotter step of the Jordan–Wigner encoding by a factor of N2, comparing to the scheme for a device with only local connectivity, where N is the number of orbitals for a generic two-body Hamiltonian. Additional analysis for the Fermi–Hubbard model on an N × N square lattice results in a similar reduction. We also discuss a detailed implementation of our scheme with superconducting qubits and cavities.
Heat transfer across a nanoscale pressurized air gap and its application in magnetic recording
Authors: Zheng Jinglin , Chen Yung-Kan , Zhou Qin 
Published: February 2018

AbstractIn this study, we investigated how a thermally actuated air bearing slider heats up a fast-spinning storage disk through a highly pressurized nanoscale air gap in a magnetic recording system. A Eulerian-description-based computational approach is developed considering heat conduction through a pressurized air film and near-field radiation across the gap. A set of field equations that govern the air bearing dynamics, slider thermo-mechanics and disk heat dissipation are solved simultaneously through an iterative approach. A temperature field on the same order as the hot slider surface itself is found to be established in the disk. The effective local heat transfer coefficient is found to vary substantially with disk materials and linear speeds. This approach quantifies the magnitude of different thermal transport schemes and the accuracy is verified by an excellent agreement with our experiment, which measures the local slider temperature rise with a resistance temperature sensor. It also demonstrates an effective computational approach to treat transient thermal processes in a system of components with fast relative speed and different length scales. Finally, the investigated thermal transport mechanism leads to a substantial spacing change that has a significant impact on the spacing margin of today’s magnetic storage systems.
Passband reconstruction from photometry
Authors: Weiler M. , Jordi C. , Fabricius C. , Carrasco J. M. 
Published: February 2018

Context. Based on an initial expectation from laboratory measurements or instrument simulations, photometric passbands are usually subject to refinements. These refinements use photometric observations of astronomical sources with known spectral energy distribution.
Aims. This work investigates the methods for and limitations in determining passbands from photometric observations. A simple general formalism for passband determinations from photometric measurements is derived. The results are applied to the passbands of HIPPARCOS, Tycho, and Gaia DR1.
Methods. The problem of passband determination is formulated in a basic functional analytic framework. For the solution of the resulting equations, functional principal component analysis is applied.
Results. We find that, given a set of calibration sources, the passband can be described with respect to the set of calibration sources as the sum of two functions, one which is uniquely determined by the set of calibration sources, and one which is entirely unconstrained. The constrained components for the HIPPARCOS, Tycho, and Gaia DR1 passbands are determined, and the unconstrained components are estimated.
Online Event Reconstruction in the CBM Experiment at FAIR
Authors: Akishina Valentina , Kisel Ivan 
Published: February 2018

Targeting for rare observables, the CBM experiment will operate at high interaction rates of up to 10 MHz, which is unprecedented in heavy-ion experiments so far. It requires a novel free-streaming readout system and a new concept of data processing. The huge data rates of the CBM experiment will be reduced online to the recordable rate before saving the data to the mass storage. Full collision reconstruction and selection will be performed online in a dedicated processor farm. In order to make an efficient event selection online a clean sample of particles has to be provided by the reconstruction package called First Level Event Selection (FLES).
The FLES reconstruction and selection package consists of several modules: track finding, track fitting, event building, short-lived particles finding, and event selection. Since detector measurements contain also time information, the event building is done at all stages of the reconstruction process. The input data are distributed within the FLES farm in a form of time-slices. A time-slice is reconstructed in parallel between processor cores. After all tracks of the whole time-slice are found and fitted, they are collected into clusters of tracks originated from common primary vertices, which then are fitted, thus identifying the interaction points. Secondary tracks are associated with primary vertices according to their estimated production time. After that short-lived particles are found and the full event building process is finished. The last stage of the FLES package is a selection of events according to the requested trigger signatures. The event reconstruction procedure and the results of its application to simulated collisions in the CBM detector setup are presented and discussed in detail.
Medical Management of Portal Hypertension and Its Complications
Authors: Singh Tavankit , McCullough Arthur 
Published: February 2018

AbstractPortal hypertension, most commonly caused by cirrhosis, is defined as an elevated hepatic venous pressure gradient that can lead to complications including ascites, hepatic, esophageal/gastric varices, hepatic encephalopathy, and hepatorenal syndrome. While these complications are initially managed by medical and endoscopic treatments, progressive decompensation of liver disease may lead to liver transplantation.