bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex
Authors: Qi Xiaofeng , Schmiege Philip , Coutavas Elias , Li Xiaochun
Published: August 2018

It takes two to signal

The Hedgehog (HH) signaling pathway is important in development, and excessive HH signaling is associated with cancer. Signaling occurs through the G protein–coupled receptor Smoothened. The pathway is repressed by the membrane receptor Patched-1 (PTCH1), and this inhibition is relieved when PTCH1 binds the secreted protein HH. Two recent papers have described structures of HH bound to PTCH1, but surprisingly, each described a different binding epitope on HH. Qi
et al.
present a cryo–electron microscopy structure that explains this apparent contradiction by showing that a single HH protein uses both of these interfaces to engage two PTCH1 receptors (see the Perspective by Sommer and Lemmon). Functional assays suggest that both interfaces must be bound for efficient signaling.

Science
, this issue p.
eaas8843
; see also p.
26
Observation of Dicke cooperativity in magnetic interactions
Authors: Li Xinwei , Bamba Motoaki , Yuan Ning , Zhang Qi , Zhao Yage , Xiang Maolin , Xu Kai , Jin Zuanming , Ren Wei , Ma Guohong , Cao Shixun , Turchinovich Dmitry , Kono Junichiro
Published: August 2018

Cooperative quantum magnetism

One of the earliest and most intensively studied problems in quantum optics is the interaction of a two-level system (an atom) with a single photon. This simple system provides a rich platform for exploring exotic light-matter interactions and the emergence of more complex phenomena such as superradiance, which is a cooperative effect that emerges when the density of atoms is increased and coupling between them is enhanced. Going beyond the light-matter system, Li
et al.
observed analogous cooperative effects for coupled magnetic systems. The results suggest that ideas in quantum optics could be carried over and used to control and predict exotic phases in condensed matter systems.

Science
, this issue p.
794
How AI can be a force for good
Authors: Taddeo Mariarosaria , Floridi Luciano
Published: August 2018

An ethical framework will help to harness the potential of AI while keeping humans in control
High-affinity adsorption leads to molecularly ordered interfaces on TiO
2
in air and solution
Authors: Balajka Jan , Hines Melissa A. , DeBenedetti William J. I. , Komora Mojmir , Pavelec Jiri , Schmid Michael , Diebold Ulrike
Published: August 2018

A preference for acids

When titanium dioxide surfaces are exposed to water under ambient conditions, an ordered overlayer forms. Balajka
et al.
studied this process with scanning tunneling microscopy and x-ray photoelectron spectroscopy for water adsorption under vacuum conditions and in air (see the Perspective by Park). The ordered overlayer was only formed in air, the result of the adsorption of organic acids (formic and acetic acids). Although other species such as alcohols were present in much higher concentrations in air, the bidentate adsorption and entropic effects favored acid adsorption.

Science
, this issue p.
786
; see also p.
753
The paradox of irrigation efficiency
Authors: Grafton R. Q. , Williams J. , Perry C. J. , Molle F. , Ringler C. , Steduto P. , Udall B. , Wheeler S. A. , Wang Y. , Garrick D. , Allen R. G.
Published: August 2018

Higher efficiency rarely reduces water consumption
Orchestrating cortical brain development
Authors: Thomas Jean-Leon
Published: August 2018

Signaling in the developing vasculature coordinates central nervous system morphology
In Vitro
Antiviral Profile of Ruzasvir, a Potent and Pangenotype Inhibitor of Hepatitis C Virus NS5A
Authors: Asante-Appiah Ernest , Liu Rong , Curry Stephanie , McMonagle Patricia , Agrawal Sony , Carr Donna , Rokosz Laura , Lahser Frederick , Bystol Karin , Chase Robert , Black Stuart , Ferrari Eric , Ingravallo Paul , Tong Ling , Yu Wensheng , Kozlowski Joseph
Published: August 2018

Inhibition of NS5A has emerged as an attractive strategy to intervene in hepatitis C virus (HCV) replication. Ruzasvir (formerly MK-8408) was developed as a novel NS5A inhibitor to improve upon the potency and barrier to resistance of early compounds.
A Putative Acetylation System in Vibrio cholerae Modulates Virulence in Arthropod Hosts
Authors: Liimatta Kalle , Flaherty Emily , Ro Gabby , Nguyen Duy K. , Prado Cecilia , Purdy Alexandra E.
Published: August 2018

The bacterium
Vibrio cholerae
causes severe disease in humans, and strains can persist in the environment in association with a wide diversity of host species. By investigating the molecular mechanisms that underlie these interactions, we can better understand constraints affecting the ecology and evolution of this global pathogen. The
Drosophila
model of
Vibrio cholerae
infection has revealed that bacterial regulation of acetate and other small metabolites from within the fly gastrointestinal tract is crucial for its virulence. Here, we demonstrate that genes that may modify the proteome of
V. cholerae
affect virulence toward
Drosophila
, most likely by modulating central metabolic pathways that control the consumption of acetate as well as other small molecules. These findings further highlight the many layers of regulation that tune bacterial metabolism to alter the trajectory of interactions between bacteria and their hosts.
Diagnostic Approach to Health Care- and Device-Associated Central Nervous System Infections
Authors: Martin Ryan M. , Zimmermann Lara L. , Huynh Mindy , Polage Christopher R.
Published: August 2018

Health care- and device-associated central nervous system (CNS) infections have a distinct epidemiology, pathophysiology, and microbiology that require a unique diagnostic approach. Most clinical signs, symptoms, and tests used to diagnose community-acquired CNS infections are insensitive and nonspecific in neurosurgical patients due to postsurgical changes, invasive devices, prior antimicrobial exposure, and underlying CNS disease.
Are
In Vitro
Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?
Authors: Patel Twisha S. , Carver Peggy L. , Eschenauer Gregory A.
Published: August 2018

The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and
Candida
species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for
Candida
species.
The Human Bocavirus 1 NP1 Protein Is a Multifunctional Regulator of Viral RNA Processing
Authors: Dong Yanming , Fasina Olufemi O. , Pintel David J.
Published: August 2018

The
Parvovirinae
are small nonenveloped icosahedral viruses that are important pathogens in many animal species, including humans. The NP1 protein of human bocavirus 1 (HBoV1), similar to NP1 of the bocavirus minute virus of canine (MVC), regulates viral alternative RNA processing by both suppressing polyadenylation at an internal site, (pA)p, and facilitating splicing of an upstream adjacent intron. These effects allow both extension into the capsid gene and splicing of the viral pre-mRNA that correctly registers the capsid gene open reading frame. Characterization of HBoV1 NP1 generalizes this central mode of parvovirus gene regulation to another member of the bocavirus genus and uncovers both important similarities and differences in function compared to MVC NP1 that will be important for future comparative studies.
Strengthening health security: an intuitive and user-friendly tool to estimate country-level costs
Authors: Katz Rebecca , Graeden Ellie , Eaneff Stephanie , Kerr Justin
Published: August 2018

Member States of the WHO working to build capacity under the International Health Regulations (IHR) are advised to develop prioritised, costed plans to implement improvements based on the results of voluntary external assessments. Defining the costs associated with capacity building under the IHR, however, has challenged nations, funders and supporting organisations. Most current efforts to develop costed national action plans involve long-term engagements that may take weeks or months to complete. While these efforts have value in and of themselves, there is an urgent need for a rapid-use tool to provide cost estimates regardless of the level of expertise of the personnel assigned to the task. In this paper, we describe a tool that can—in a matter of hours—provide country-level cost estimates for capacity building under the IHR. This paper also describes how the tool can be used in countries, as well as the challenges inherent in any costing process.
Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis
Authors: Jiang Weixi , Huang Sirun , Teng Hua , Wang Peipei , Wu Meng , Zhou Xia , Ran Haitao
Published: August 2018

Objective

This study aimed to assess the accuracy of staging liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) usingpoint shear wave elastography (pSWE) and transient elastography (TE).

Setting

Relevant records on NAFLD were retrieved from PubMed, Embase, Web of Science and the China National Knowledge Infrastructure databases up to 20 December 2017. A bivariate mixed-effects model was conducted to combine sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the summary receiver operating characteristic curve (AUC) between pSWE and TE. A sensitivity analysis was implemented to explore the source of heterogeneity.

Participants

Patients with NAFLD who had a liver stiffness measurement using pSWE and TE before liver biopsy were enrolled according to the following criteria: 2×2 contingency tables can be calculated via the reported number of cases; sensitivity and specificity were excluded according to the following criteria: history of other hepatic damage, such as chronic hepatitis C, concurrent active hepatitis B infection, autoimmune hepatitis, suspicious drug usage and alcohol abuse.

Results

Nine pSWE studies comprising a total of 982 patients and 11 TE studies comprising a total of 1753 patients were included. For detection of significant fibrosis, advanced fibrosis and cirrhosis, the summary AUC was 0.86 (95% CI 0.83 to 0.89), 0.94 (95% CI 0.91 to 0.95) and 0.95 (95% CI 0.93 to 0.97) for pSWE, and the summary AUC was 0.85 (95% CI 0.82 to 0.88), 0.92 (95% CI 0.89 to 0.94) and 0.94 (95% CI 0.93 to 0.97) for TE, respectively. The proportion of failure measurement was over tenfold as common with TE using an M probe compared with pSWE.

Conclusion

pSWE and TE, providing precise non-invasive staging of liver fibrosis in NAFLD, are promising techniques, particularly for advanced fibrosis and cirrhosis.
Effects of menaquinone-7 supplementation in patients with aortic valve calcification: study protocol for a randomised controlled trial
Authors: Lindholt Jes Sanddal , Frandsen Niels Erik , Fredgart Maise Høigaard , Øvrehus Kristian A , Dahl Jordi Sanchez , Møller Jacob Eifer , Folkestad Lars , Urbonaviciene Grazina , Becker Søren Warberg , Lambrechtsen Jess , Auscher Søren , Hosbond Susanne , Alan Dilek Hunerel , Rasmussen Lars Melholt , Gerke Oke , Mickley Hans , Diederichsen Axel
Published: August 2018

Introduction

Aortic stenosis is a common heart valve disease, and due to the growing elderly population, the prevalence is increasing. The disease is progressive with increasing calcification of the valve cusps. A few attempts with medical preventive treatment have failed; thus, presently, the only effective treatment of aortic stenosis is surgery. This study will examine the effect of menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). We hypothesise that MK-7 supplementation will slow down the calcification process.

Methods and analysis

In this multicenter and double-blinded, placebo-controlled study, 400 men aged 65–74 years with substantial AVC are randomised (1:1) to treatment with MK-7 (720 µg/day) supplemented by the recommended daily dose of vitamin D (25 µg/day) or placebo treatment (no active treatment) for 2 years. Exclusion criteria are treatment with vitamin K antagonist or coagulation disorders. To evaluate AVC score, a non-contrast CT scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is difference in AVC score from baseline to follow-up at 2 years. Intention-to-treat principle is used for all analyses.

Ethics and dissemination

There are no reported adverse effects associated with the use of MK-7. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20170059) and the Data Protection Agency (17/19010). It is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported.

Trial registration number

NCT03243890.
FLUID trial: a protocol for a hospital-wide open-label cluster crossover pragmatic comparative effectiveness randomised pilot trial
Authors: McIntyre Lauralyn , Taljaard Monica , McArdle Tracy , Fox-Robichaud Alison , English Shane W , Martin Claudio , Marshall John , Menon Kusum , Muscedere John , Cook Deborah J , Weijer Charles , Saginur Raphael , Maybee Alies , Iyengar Akshai , Forster Alan , Graham Ian D , Hawken Steven , McCartney Colin , Seely Andrew JE , Stiell Ian G , Thavorn Kednapa , Fergusson Dean A
Published: August 2018

Introduction

0.9% saline and Ringer’s lactate are the two most common resuscitation crystalloid fluids. 0.9% saline may lead to hyperchloraemic metabolic acidosis and may be associated with impaired kidney function and death. Few large multicentre randomised trials have been conducted to evaluate the effect of these two fluids on clinically important outcomes.

Methods

FLUID is a pragmatic pilot cluster randomised crossover trial in which four hospitals will be randomised to normal saline or Ringer’s lactate for 14 weeks, then crossover to the alternative fluid for the subsequent 14 weeks after 1 to 3 week transition. With waiver of informed consent, all adult and paediatric patients admitted to participating sites will be included in the FLUID trial except for neonates. Primary feasibility outcome is study fluid protocol adherence (target:≥80%). Secondary feasibility outcomes include time to research ethics board (REB) approval and readiness to trial initiation (≤3 months from REB submission and approval). Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes for the future large FLUID trial will be described. Protocol adherence will be collected by site at specified time points. All clinical data will be obtained at patient level through provincial health administrative data held at the Institute for Clinical Evaluative Sciences (ICES). Event rates for the primary and secondary outcomes will be described using frequencies and proportions with 95% CIs. Intracluster and interperiod correlation coefficients will be calculated from population-level data available at ICES.

Ethics and dissemination

The study protocol has been approved by the Ottawa Health Science Research Ethics Board. The FLUID pilot will determine feasibility, and ICES data across all potential sites in Ontario will allow calculation of sample size parameter estimates to inform the design and implementation of the large trial.

Trial registration number

NCT02721485; Pre-results.
Emergency Preparedness, Resilience and Response (EPRR)
Authors: Quantick Oliver
Published: August 2018

As an organisation, locality or nation, there is a growing need to respond to a wide range of incidents and emergencies that could affect health and the care of patients. Responses to both domestic and international incidents have shown that collaboration, understanding and joint responses across organisations have improved the outcome of those affected by incidents which impact on health. Emergency response is something that is of increasing importance and has been tested on multiple occasions during recent events in the UK. Regarding health, the aim is to respond rapidly and efficiently, reducing potential morbidity and mortality to the lowest possible level in a given circumstance. This paper discusses what is meant by EPRR (Emergency, Preparedness, Resilience and Response), types of potential incidents, how we collectively prepare for responding and what has been learnt during recent events. It concludes with an outline of some selected current activity and highlights the likelihood of increased cross-sector working in EPRR.
Reprocessing legacy three-dimensional seismic data from the Halfmile Lake and Brunswick No. 6 volcanogenic massive sulphide deposits, New Brunswick, Canada
Authors: Bellefleur Gilles , Cheraghi Saeid , Malehmir Alireza
Published: August 2018

We reprocessed legacy three-dimensional (3D) seismic data from the Halfmile Lake and Brunswick areas, both of which were acquired for mineral exploration in the Bathurst Mining Camp, New Brunswick. Each 3D seismic survey was acquired over known volcanogenic massive sulphide deposits and covered areas with strong mineral potential. Most improvements resulted from a reduction of coherent and random noise on prestack gathers and from an improved velocity model, combined with re-imaging with dip moveout corrections and poststack migration or prestack time migration. At Halfmile Lake, the new imaging results show the Deep zone and a possible extension of the sulphide mineralization at greater depth. True amplitude processing has shown that this anomaly has strong amplitudes and is offset from the Deep zone by a shallowly dipping fault (<15°). With the clearer geological context provided by our results, this anomaly, which appears as a stand-alone anomaly on an original image obtained by Noranda Exploration Ltd., becomes a defendable exploration target. Nonorthogonal acquisition geometry and receiver patches of the Brunswick No. 6 3D seismic survey generated artefacts after dip moveout processing that reduced the overall quality of the seismic volumes. By using a filtering approach based on the application of a weighted Laplacian-Gaussian filter in the Kx–Ky domain, we reduced the noise and improved the continuity of reflections. We also imaged the short and flat reflections observed previously only in the shallow part of prestack time migrated data. These short reflections appear as diffractions on the filtered stacked section with dip moveout corrections, indicating that they originate from small geological bodies or discontinuities in the subsurface.
The gluon condensation in high energy cosmic rays
Authors: Zhu Wei , Lan Jiangshan , Ruan Jianhong
Published: August 2018

The gluon condensation (GC)-effects in high energy cosmic rays are investigated. After a brief review of the GC, several examples including gamma-, electron- and positron-spectra in a broad [Formula: see text] region can be explained by the GC-effects. We find that the GC may break the power-law of the cosmic ray spectra if the energy of accelerated protons exceeds the GC-threshold. The GC is a new phenomenon that is not yet known, it provides a new window to understand the high energy cosmic ray spectra.
An overview of deterministic database systems
Authors: Abadi Daniel J. , Faleiro Jose M.
Published: August 2018

Deterministic database systems show great promise, but their deployment may require changes in the way developers interact with the database.
Guiding Formal Verification Orchestration Using Machine Learning Methods
Authors: Elmandouh Eman M. , Wassal Amr G.
Published: August 2018

Typical modern HW designs include many blocks associated with thousands of design properties. Having today's commercial formal verifiers utilize a complementary set of state-of-art formal algorithms is a key in enabling the formal verification tools to successfully cope with verification problems of different sizes, types, and complexities. Formal engines orchestration is the methodology used to pick the most appropriate formal engine for a specific verification problem. It assures proper scheduling of the formal engines to minimize the time consumed to solve individual design verification problems, hence highly impacts the time required to verify the overall design properties. This work proposes the utilization of supervised machine learning classification techniques to guide the orchestration step by predicting the formal engines that should be assigned to a design property. Up to 16,500 formal verification runs on RTL designs and their properties are used to train the classifier to create a prediction model. The classifier assigns any new verification problem to an appropriate list of formal engines associated with a probability distribution over the set of engines classes. Our results indicate how the proposed model is able to improve the formal suite total run-time by up to 59% of its maximum allowable time improvement using multi-classification-based orchestration and to nominate with 88% accuracy the appropriate formal engines for new-to-verify HW designs.
When machine learning is facially invalid
Authors: Pasquale Frank
Published: August 2018

Observations on the use of machine learning and facial inferences to classify people using inexplicable data.
Reflecting on the design-culture connection in HCI and HCI4D
Authors: Abdelnour-Nocera José , Rangaswamy Nimmi
Published: August 2018

The
Interactions
website (interactions.acm.org) hosts a stable of bloggers who share insights and observations on HCI, often challenging current practices. Each issue we'll publish selected posts from some of the leading and emerging voices in the field.
Luminal Na+ homeostasis has an important role in intestinal peptide absorption in vivo
Authors: Ishizuka Noriko , Nakayama Michiko , Watanabe Miki , Tajima Haruna , Yamauchi Yuri , Ikari Akira , Hayashi Hisayoshi
Published: August 2018

Intestinal cell line studies indicated luminal Na+ homeostasis is essential for proton-coupled peptide absorption, because the driving force of PepT1 activity is supported by the apical Na+/H+ exchanger NHE3. However, there is no direct evidence demonstrating the importance of in vivo luminal Na+ for peptide absorption in animal experiments. To investigate the relationship between luminal Na+ homeostasis and peptide absorption, we took advantage of claudin 15-deficient (cldn15−/−) mice, whereby Na+ homeostasis is disrupted. We quantitatively assessed the intestinal segment responsible for peptide absorption using radiolabeled nonhydrolyzable dipeptide (glycylsarcosine, Gly-Sar) and nonabsorbable fluid phase marker polyethylene glycol (PEG) 4000 in vivo. In wild-type (WT) mice, the concentration ratio of Gly-Sar to PEG 4000 decreased in the upper jejunum, suggesting the upper jejunum is responsible for peptide absorption. Gly-Sar absorption was decreased in the jejunum of cldn15−/− mice. To elucidate the mechanism underlining these impairments, a Gly-Sar-induced short-circuit ( Isc) current was measured. In WT mice, increments of Gly-Sar-induced Isc were inhibited by the luminal application of a NHE3-specific inhibitor S3226 in a dose-dependent fashion. In contrast to in vivo experiments, robust Gly-Sar-induced Isc increments were observed in the jejunal mucosa of cldn15−/− mice. Gly-Sar-induced Isc was inhibited by S3226 or a reduction of luminal Na+ concentration, which mimics low luminal Na+ concentrations in vivo . Our study demonstrates that luminal Na+ homeostasis is important for peptide absorption in native epithelia and that there is a cooperative functional relationship between PepT1 and NHE3.

NEW & NOTEWORTHY Our study is the first to demonstrate that luminal Na+ homeostasis is important for proton-coupled peptide absorption in in vivo animal experiments.
HIV transgene expression impairs K+ channel function in the pulmonary vasculature
Authors: Mondejar-Parreño Gema , Morales-Cano Daniel , Barreira Bianca , Callejo María , Ruiz-Cabello Jesús , Moreno Laura , Esquivel-Ruiz Sergio , Mathie Alistair , Butrous Ghazwan , Perez-Vizcaino Francisco , Cogolludo Angel
Published: August 2018

Human immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH); however, the pathogenesis of HIV-related PAH remains unclear. Since K+ channel dysfunction is a common marker in most forms of PAH, our aim was to analyze whether the expression of HIV proteins is associated with impairment of K+ channel function in the pulmonary vascular bed. HIV transgenic mice (Tg26) expressing seven of the nine HIV viral proteins and wild-type (WT) mice were used. Hemodynamic assessment was performed by echocardiography and catheterization. Vascular reactivity was studied in endothelium-intact pulmonary arteries. K+ currents were recorded in freshly isolated pulmonary artery smooth muscle cells (PASMC) using the patch-clamp technique. Gene expression was assessed using quantitative RT-PCR. PASMC from Tg26 mice had reduced K+ currents and were more depolarized than those from WT. Whereas voltage-gated K+ channel 1.5 (Kv1.5) currents were preserved, pH-sensitive noninactivating background currents ( IKN) were nearly abolished in PASMC from Tg26 mice. Tg26 mice had reduced lung expression of Kv7.1 and Kv7.4 channels and decreased responses to the Kv7.1 channel activator L-364,373 assessed by vascular reactivity and patch-clamp experimental approaches. Although we found pulmonary vascular remodeling and endothelial dysfunction in Tg26 mice, this was not accompanied by changes in hemodynamic parameters. In conclusion, the expression of HIV proteins in vivo impairs pH-sensitive IKN and Kv7 currents. This negative impact of HIV proteins in K+ channels was not sufficient to induce PAH, at least in mice, but may play a permissive or accessory role in the pathophysiology of HIV-associated PAH.
Julius H. Comroe Distinguished Lecture: Interdependence of neuromodulators in the control of breathing
Authors: Forster Hubert V.
Published: August 2018

In vitro and in vivo anesthetized studies led to the conclusion that “deficiencies in one neuromodulator are immediately compensated by the action of other neuromodulators,” which suggests an interdependence among neuromodulators. This concept was the focus of the 2018 Julius H. Comroe Lecture to the American Physiological Society in which I summarized our published studies testing the hypothesis that if modulatory interdependence was robust, breathing would not decrease during dialysis of antagonists to G protein-coupled excitatory receptors or agonists to inhibitory receptors into the ventral respiratory column (VRC) or the hypoglossal motor nuclei (HMN). We found breathing was not decreased during unilateral VRC dialyses of antagonists to excitatory muscarinic, serotonergic, and neurokinin-1 receptors alone or in combinations nor was breathing decreased with unilateral VRC dialysis of a µ-opioid receptor agonist. Analyses of the effluent dialysate revealed locally increased serotonin (excitatory) during muscarinic receptor blockade and decreased γ-aminobutyric acid (inhibitory) during dialysis of opioid agonists, suggesting an interdependence of neuromodulators through release of compensatory neuromodulators. Bilateral dialysis of receptor antagonists or agonist in the VRC increased breathing, which does not support the concept that unchanged breathing with unilateral dialyses was due to contralateral compensation. In contrast, in the HMN neither unilateral nor bilateral dialysis of the excitatory receptor antagonists altered breathing, but unilateral dialysis of the opioid receptor agonist decreased breathing. We conclude: 1) there is site-dependent interdependence of neuromodulators during physiologic conditions, and 2) attributing physiologic effects to a specific receptor perturbation is complicated by local compensatory mechanisms.
Effect of localized microclimate heating on peripheral skin temperatures and manual dexterity during cold exposure
Authors: Castellani John W. , Yurkevicius Beau R. , Jones Myra L. , Driscoll Timothy J. , Cowell Courtney M. , Smith Laurel , Xu Xiaojiang , O’Brien Catherine
Published: August 2018

Reduced dexterity is a major problem in cold weather, with a need for a countermeasure that increases hand (Thand) and finger (Tfing) temperatures and improves dexterity. The purpose of this study was to determine whether electric heat (set point, 42°C) applied to the forearm (ARM, 82 W), face (FACE, 9.2 W), or combination of both (COMB, 91.2 W), either at the beginning of cold exposure (COLD; 0.5°C, 120 min; 2 clo insulation, seated, bare-handed) or after Tfing fell to 10.5°C [delayed trials (D)], improves Thand, Tfing, dexterity, and finger key pinch strength (Sfing). Volunteers ( n = 8; 26 ± 9 yr) completed 7 experimental trials in COLD: ARM, ARM-D, FACE, FACE-D, COMB, COMB-D, and no heating (CON). Temperatures were measured before (BASE) and throughout COLD. Tests of dexterity [Purdue Pegboard assembly (PP) and magazine loading (MAGLOAD)] and Sfing were measured at BASE and after 45 and 90 min of COLD. Data presented are at minute 90. Thand was warmer ( P < 0.001) during ARM (18.0 ± 2.6°C) and COMB (18.9 ± 2.0°C) versus CON (15.3 ± 1.5°C) and FACE (15.8 ± 1.5°C) for heating that was initiated at the beginning of COLD. Tfing was higher ( P < 0.04) during COMB (12.7 ± 5.1°C) versus CON (9.7 ± 2.1°C) and FACE (8.9 ± 2.2°C). The change from BASE for PP (no. of pieces) was less ( P < 0.005) in COMB (−4.5 ± 3.3) and ARM (−5.0 ± 6.0) versus CON (−13.0 ± 7.3) and FACE (−10.0 ± 8.3), and for MAGLOAD, it tended ( P = 0.06) to be less in COMB (−8.9 ± 6.2 cartridges) versus CON (−14.8 ± 3.7 cartridges). There was no change in Sfing from BASE (10.5 kg) to minute 90 in ARM or COMB (0.7 ± 1.4 and −0.2 ± 1.7 kg, respectively) but a decrease ( P < 0.01) in CON and FACE (−2.1 ± 2.0 and −1.6 ± 1.9 kg, respectively). There were no differences in Thand, Tfing, dexterity, and Sfing at minute 90 when comparing heating that was initiated at the beginning of COLD versus delayed heating. In conclusion, heating using either COMB or ARM, compared with CON and FACE, improved Thand and Tfing and reduced the decline in dexterity by 20%–50% and Sfing by 90%. Furthermore, delayed heating had no deleterious effect on Thand, Tfing, dexterity, and Sfing compared with heating that started at the beginning of cold exposure.

NEW & NOTEWORTHY The present study demonstrated that, during sedentary cold air exposure, localized heating that was applied from the beginning of cold exposure on the forearm increases hand and finger temperatures and finger strength, leading to subsequent improvements in manual dexterity. In addition, localized heating that was delayed until finger temperatures cooled significantly also caused higher peripheral temperatures, leading to better strength and manual dexterity, compared with no heating.
Kernel Neighborhood Rough Sets Model and Its Application
Authors: Zeng Kai , Jing Siyuan
Published: August 2018

Rough set theory has been successfully applied to many fields, such as data mining, pattern recognition, and machine learning. Kernel rough sets and neighborhood rough sets are two important models that differ in terms of granulation. The kernel rough sets model, which has fuzziness, is susceptible to noise in the decision system. The neighborhood rough sets model can handle noisy data well but cannot describe the fuzziness of the samples. In this study, we define a novel model called kernel neighborhood rough sets, which integrates the advantages of the neighborhood and kernel models. Moreover, the model is used in the problem of feature selection. The proposed method is tested on the UCI datasets. The results show that our model outperforms classic models.
Cryptanalysis and Improvement of Three Certificateless Aggregate Signature Schemes
Authors: Yang Xiaodong , Li Yutong , Chen Chunlin , Xiao Likun , Wang Caifen
Published: August 2018

The certificateless aggregate signature (CLAS) scheme is a very important data aggregation technique that compresses a large number of signatures from different users into a short signature. CLAS can reduce the total length of a signature and the computational overhead of signature verification and is therefore highly suitable for resource-constrained network environments. Many CLAS schemes have been proposed in recent years, but the construction of a secure and efficient CLAS scheme remains important. In 2018, Li et al. found that the CLAS scheme proposed by He et al. could not resist malicious-but-passive KGC attacks, and they presented an improved CLAS scheme. Du et al. proposed a CLAS scheme with the constant aggregate signature length and claimed that their scheme was resistant to forgery attacks. Chen et al.designed a CLAS scheme with efficient verification and proved that their CLAS scheme was secure in the random oracle model. In this paper, we demonstrate that Li et al.’s CLAS scheme, Du et al.’s CLAS scheme, and Chen et al.’s CLAS scheme are insecure against coalition attacks and present concrete examples. That is, an attacker can forge a valid aggregate signature using some illegal single signatures. To withstand suck attacks, we propose an improved CLAS scheme based on Chen et al.’s CLAS scheme.
Spark Sensing: A Cloud Computing Framework to Unfold Processing Efficiencies for Large and Multiscale Remotely Sensed Data, with Examples on Landsat 8 and MODIS Data
Authors: Lan Hai , Zheng Xinshi , Torrens Paul M.
Published: August 2018

Inquiry using data from remote Earth-observing platforms often confronts a straightforward but particularly thorny problem: huge amounts of data, in ever-replenishing supplies, are available to support inquiry, but scientists’ agility in converting data into actionable information often struggles to keep pace with rapidly incoming streams of data that amass in expanding archival silos. Abstraction of those data is a convenient response, and many studies informed purely by remotely sensed data are by necessity limited to a small study area with a relatively few scenes of imagery, or they rely on larger mosaics of images at low resolution. As a result, it is often challenging to thread explanations across scales from the local to the global, even though doing so is often critical to the science under pursuit. Here, a solution is proposed, by exploiting Apache Spark, to implement parallel, in-memory image processing with ability to rapidly classify large volumes of multiscale remotely sensed images and to perform necessary analysis to detect changes on the time series. It shows that processing on three different scales of Landsat 8 data (up to ~107.4 GB, five-scene, time series image sets) can be accomplished in 1018 seconds on local cloud environment. Applying the same framework with slight parameter adjustments, it processed same coverage MODIS data in 54 seconds on commercial cloud platform. Theoretically, the proposed scheme can handle all forms of remote sensing imagery commonly used in the Earth and environmental sciences, requiring only minor adjustments in parameterization of the computing jobs to adjust to the data. The authors suggest that the “Spark sensing” approach could provide the flexibility, extensibility, and accessibility necessary to keep inquiry in the Earth and environmental sciences at pace with developments in data provision.
Ranking Spreaders in Complex Networks Based on the Most Influential Neighbors
Authors: Yi Zelong , Wu Xiaokun , Li Fan
Published: August 2018

Identifying influential spreaders in complex networks is crucial for containing virus spread, accelerating information diffusion, and promoting new products. In this paper, inspired by the effect of leaders on social ties, we propose the most influential neighbors’ k-shell index that is the weighted sum of the products between k-core values of itself and the node with the maximum k-shell values. We apply the classical Susceptible-Infected-Recovered (SIR) model to verify the performance of our method. The experimental results on both real and artificial networks show that the proposed method can quantify the node influence more accurately than degree centrality, betweenness centrality, closeness centrality, and k-shell decomposition method.
Optimization of Fluorescent Labeling for In Vivo Nanoimaging of Sarcomeres in the Mouse Heart
Authors: Kobirumaki-Shimozawa Fuyu , Shimozawa Togo , Oyama Kotaro , Kushida Yasuharu , Terui Takako , Ishiwata Shin’ichi , Fukuda Norio
Published: August 2018

The present study was conducted to systematically investigate the optimal viral titer as well as the volume of the adenovirus vector (ADV) that expresses α-actinin-AcGFP in the Z-disks of myocytes in the left ventricle (LV) of mice. An injection of 10 μL ADV at viral titers of 2 to 4 × 1011 viral particles per mL (VP/mL) into the LV epicardial surface consistently expressed α-actinin-AcGFP in myocytes in vivo, with the fraction of AcGFP-expressing myocytes at ~10%. Our analysis revealed that SL was ~1.90-2.15 μm upon heart arrest via deep anesthesia. Likewise, we developed a novel fluorescence labeling method of the T-tubular system by treating the LV surface with CellMask Orange (CellMask). We found that the T-tubular distance was ~2.10-2.25 μm, similar to SL, in the healthy heart in vivo. Therefore, the present high-precision visualization method for the Z-disks or the T-tubules is beneficial to unveiling the mechanisms of myocyte contraction in health and disease in vivo.
His-Bundle Pacing in a Patient with Transcatheter Aortic Valve Implantation-Induced Left Bundle Branch Block
Authors: Sen Jonathan , Mok Michael , Perrin Mark
Published: August 2018

Transcatheter aortic valve implantation (TAVI) is an effective intervention for severe aortic stenosis in patients at intermediate or high surgical risk, but damage to the native conduction system such as left bundle branch block (LBBB) may offset its benefits. New onset LBBB is associated with a higher risk of cardiovascular morbidity and mortality. His-bundle pacing (HBP) may be useful to treat TAVI-induced LBBB but has yet to be reported. We present the case of a 76-year-old man with severe symptomatic aortic stenosis treated with TAVI. His preoperative electrocardiogram showed sinus rhythm with a narrow QRS complex. Insertion of a CoreValve Evolut R transcatheter aortic valve was uneventful apart from the development of LBBB with a long PR interval. A dual-lead DDD pacemaker was implanted via the left cephalic vein on the following day. HV was mildly prolonged at 60 ms. Capture of the proximal His restored AV synchrony without correction of LBBB. Repositioning of the lead with capture of the left bundle branch enabled complete ventricular resynchronisation with a single lead. Our case demonstrates that LBBB in the setting of TAVI may be corrected by HBP.
Artemisinin-Based Combination Therapy Depressed Mitosis and Induced Chromosome Aberration in Onion Root Cells
Authors: Raji J. I. , Onwuamah C. K. , Odeigah P. G. C.
Published: August 2018

Artemisinin-based combination therapy is used to treat uncomplicated malaria disease in most endemic countries. Although most antimalarial drugs are effective in killing the parasite, there is a concern of induced toxicity to the cell. Here, the cytogenotoxicity of dihydroartemisinin-piperaquine phosphate (DHAP), a coformulation for artemisinin-based combination therapy, was evaluated usingAllium cepamodel. The toxicity on the mitotic index varies with the duration of exposure and dose tested. Chromosome aberrations observed include chromosome fragments, chromosome bridges, binucleated cells, and micronucleated cells. This study showed that DHAP can depress mitosis and induce chromosome abnormalities. Their accumulation in cells may be inhibitory to cell division and growth. This calls for caution in the administration of artemisinin combination therapy for the treatment of malaria ailment. Wide spacing of dosage is therefore suggested in order to avoid the risk of genetic damage.
GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells
Authors: Bergante Sonia , Creo Pasquale , Piccoli Marco , Ghiroldi Andrea , Menon Alessandra , Cirillo Federica , Rota Paola , Monasky Michelle M. , Ciconte Giuseppe , Pappone Carlo , Randelli Pietro , Anastasia Luigi
Published: August 2018

Gangliosides, the sialic acid-conjugated glycosphingolipids present in the lipid rafts, have been recognized as important regulators of cell proliferation, migration, and apoptosis. Due to their peculiar localization in the cell membrane, they modulate the activity of several key cell receptors, and increasing evidence supports their involvement also in stem cell differentiation. In this context, herein we report the role played by the ganglioside GM1 in the osteogenic differentiation of human tendon stem cells (hTSCs). In particular, we found an increase of GM1 levels during osteogenesis that is instrumental for driving the process. In fact, supplementation of the ganglioside in the medium significantly increased the osteogenic differentiation capability of hTSCs. Mechanistically, we found that GM1 supplementation caused a reduction in the phosphorylation of the platelet-derived growth factor receptor-β(PDGFR-β), which is a known inhibitor of osteogenic commitment. These results were further corroborated by the observation that GM1 supplementation was able to revert the inhibitory effects on osteogenesis when the process was inhibited with exogenous PDGF.
Synergistic Effect of Bupleuri Radix and Scutellariae Radix on Adipogenesis and AMP‐Activated Protein Kinase: A Network Pharmacological Approach
Authors: Lee Jueun , Park Jinbong , Park Hyewon , Youn Dong-Hyun , Lee Jaehoon , Hong Seokbeom , Um Jae-Young
Published: August 2018

Obesity has become a major health threat in developed countries. However, current medications for obesity are limited because of their adverse effects. Interest in natural products for the treatment of obesity is thus rapidly growing. Korean medicine is characterized by the wide use of herbal formulas. However, the combination rule of herbal formulas in Korean medicine lacks experimental evidence. According to Shennong’s Classic of Materia Medica, the earliest book of herbal medicine, Bupleuri Radix (BR) and Scutellariae Radix (SR) possess the Sangsoo relationship, which means they have synergistic features when used together. Therefore these two are frequently used together in prescriptions such as Sosiho‐Tang. In this study, we used the network pharmacological method to predict the interaction between these two herbs and then investigated the effects of BR, SR, and their combination on obesity in 3T3‐L1 adipocytes. BR, SR, and BR‐SR mixture significantly decreased lipid accumulation and the expressions of two major adipogenic factors, peroxisome proliferator‐activated receptor‐gamma (PPARγ) and CCAAT/enhancer‐binding protein‐alpha (C/EBPα), and their downstream genes, Adipoq, aP2, and Lipin1 in 3T3‐L1 cells. In addition, the BR‐SR mixture had synergistic effects compared with BR or SR on inhibition of adipogenic‐gene expressions. BR and SR also inhibited the protein expressions of PPARγ and C/EBPα. Furthermore, the two extracts successfully activated AMP‐activated protein kinase alpha (AMPK α), the key regulator of energy metabolism. When compared to those of BR or SR, the BR‐SR mixture showed higher inhibition rates of PPARγ and C/EBPα, along with higher activation rate of AMPK. These results indicate a new potential antiobese pharmacotherapy and also provide scientific evidence supporting the usage of herbal combinations instead of mixtures in Korean medicine.
Organic Extract of Justicia pectoralis Jacq. Leaf Inhibits Interferon‐γ Secretion and Has Bacteriostatic Activity against Acinetobacter baumannii and Klebsiella pneumoniae
Authors: Nunes Tiago Rafael de Sousa , Cordeiro Marina Ferraz , Beserra Fernanda Gomes , Souza Matheus Landim de , Silva Wliana Alves Viturino da , Ferreira Magda Rhayanny Assunção , Soares Luiz Alberto Lira , Costa-Junior Sérgio Dias , Cavalcanti Isabella Macário Ferro , Pitta Maira Galdino da Rocha , Pitta Ivan da Rocha , Rêgo Moacyr Jesus Barreto de Melo
Published: August 2018

Justicia pectoralis Jacq. (Acanthaceae) leaves currently found in the Brazilian north‐east are widely used to treat diabetes, menstrual pains, asthma, and other disorders. This work aimed to identify the phytochemical characterization and biological activities of J. pectoralis leaf extracts. The plant material was ground and the crude extracts were obtained with water or acetone: water (7:3 v/v), yielding aqueous (JPA), and organic (JPO) extracts. Phytochemical characterization was performed by thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC). Cytotoxicity was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) (MTT) assay and trypan blue (TB) exclusion assay in peripheral blood mononuclear cells (PBMCs), BALB/c splenocytes, and neoplastic cells (TOLEDO, K562, DU‐145, and PANC‐1) at 1, 10, and 100 μg/mL. Antibacterial activity was evaluated using the microdilution test to obtain the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Cytokines, IFN‐γ, and IL‐17A from culture supernatants of BALB/c mice splenocytes were measured by sandwich ELISA. In the TLC analysis, both JPA and JPO extracts presented coumarin and flavonoids. In addition, HPLC was able to identify coumarin, apigenin, and ellagic acid in both extracts. JPO IC50 was 57.59 ± 1.03 μg/mL (MTT) and 69.44 ± 8.08 μg/mL (TB) in TOLEDO. MIC value of JPO against Acinetobacter baumannii and Klebsiella pneumoniae was 500 μg/mL. JPO (100 μg/mL) significantly inhibited IFN‐γ levels (p=0.03). J. pectoralis is a potential candidate to be further investigated as an IFN‐γ inhibitory agent and against Acinetobacter baumannii and Klebsiella pneumoniae.
The Spiraling Case of a Yellow Chef: Isolated Hyperbilirubinemia
Authors: Jiang Karen , Bazarbashi Ahmad Najdat , Dahdal Sami , Voiculescu Adina , Khalaf Natalia
Published: August 2018

Leptospirosis is a common bacterial disease in tropical regions of the world due to greater exposure to rodents and domestic animals; however, this condition can also occur in US urban areas, though it often goes unrecognized. Gastrointestinal symptoms are very commonly seen, and icteric leptospirosis is often confused for other conditions resulting in delayed diagnosis and worse outcomes. As mortality increases with more extensive hepatic involvement, gastroenterologists should be aware of the constellation of gastrointestinal symptoms related to leptospirosis, as it can occur in the absence of classic exposure history.
Biological Activities, Health Benefits, and Therapeutic Properties of Avenanthramides: From Skin Protection to Prevention and Treatment of Cerebrovascular Diseases
Authors: Perrelli Andrea , Goitre Luca , Salzano Anna Maria , Moglia Andrea , Scaloni Andrea , Retta Saverio Francesco
Published: August 2018

Oat (Avena sativa) is a cereal known since antiquity as a useful grain with abundant nutritional and health benefits. It contains distinct molecular components with high antioxidant activity, such as tocopherols, tocotrienols, and flavanoids. In addition, it is a unique source of avenanthramides, phenolic amides containing anthranilic acid and hydroxycinnamic acid moieties, and endowed with major beneficial health properties because of their antioxidant, anti‐inflammatory, and antiproliferative effects. In this review, we report on the biological activities of avenanthramides and their derivatives, including analogs produced in recombinant yeast, with a major focus on the therapeutic potential of these secondary metabolites in the treatment of aging‐related human diseases. Moreover, we also present recent advances pointing to avenanthramides as interesting therapeutic candidates for the treatment of cerebral cavernous malformation (CCM) disease, a major cerebrovascular disorder affecting up to 0.5% of the human population. Finally, we highlight the potential of foodomics and redox proteomics approaches in outlining distinctive molecular pathways and redox protein modifications associated with avenanthramide bioactivities in promoting human health and contrasting the onset and progression of various pathologies.