bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Beak and Feather Disease Virus Genomes from Wild Musk Lorikeets (
Glossopsitta concinna
)
Authors: Das Shubhagata , Subir Sarker , Adriaanse Katherine , Forwood Jade K. , Ghorashi Seyed A. , Raidal Shane R.
Published: October 2016

Three complete genomes of beak and feather disease virus (BFDV) were recovered from wild musk lorikeets (
Glossopsitta concinna
). The genomes consisted of 2,008 to 2,010 nucleotides (nt) and encode two major proteins transcribing in opposing directions. This is the first report of BFDV complete genome sequences obtained from this host species.
Unusual case of globe perforation: the brittle cornea without systemic manifestations
Authors: Joshi Shilpa Ajit , Uppapalli Shalomith , More Pranav , Deshpande Madan
Published: October 2016

Brittle cornea syndrome is a rare generalised connective tissue disorder with ocular features like keratoglobus or keratoconus, severe corneal thinning and a high risk of perforation. Various authors in different case reports and case series have brought out the fact that brittle cornea is a disorder with characteristic systemic manifestations such as deafness, joint hypermobility, hyperelasticity of skin, kyphoscoliosis and dental abnormalities alongwith ophthalmic features. We report a case of globe perforation following trivial trauma, in an individual with brittle cornea without any extraocular manifestations, posing a challenge in the diagnosis and dilemma in surgical repair of cornea, restoration of globe integrity and visual rehabilitation. The absence of systemic manifestations decreased the index of suspicion and led to a surprise in the theatre—a point this case emphasised.
Experimentation with e-cigarettes as a smoking cessation aid: a cross-sectional study in 28 European Union member states
Authors: Filippidis Filippos T , Laverty Anthony A , Vardavas Constantine I
Published: October 2016

Objectives

To describe patterns of experimentation with electronic cigarettes as a smoking cessation aid, their self-reported impact on smoking cessation and to identify factors associated with self-reported successful quit attempts within the European Union (EU).

Design

A cross-sectional study.

Setting

28 European Union member states.

Methods

We analysed data from wave 82.4 of the Special Eurobarometer survey, collected in December 2014 from all 28 EU member states. The total sample size was n=27 801 individuals aged ≥15 years; however, our analyses were conducted in different subgroups with sample sizes ranging from n=470 to n=9363. Data on e-cigarette experimentation and its self-reported impact on smoking cessation were collected. Logistic regression models were used to assess factors associated with experimentation of e-cigarettes as cessation aids and with successful quitting. Logistic regression was also used to assess changes in the use of e-cigarettes as cessation aids between 2012 (using data from wave 77.1 of the Eurobarometer) and 2014 in each member state.

Results

E-cigarettes were often experimented with as a cessation aid, especially among younger smokers (OR=5.29) and those who reported financial difficulties (OR=1.33). In total, 10.6% of those who had ever attempted to quit smoking and 27.4% of those who did so using a cessation aid had experimented with e-cigarettes as a cessation aid. Among those who had used e-cigarettes as a cessation aid, those with higher education were more likely to have been successful in quitting (OR=2.23). There was great variation in trends of use of e-cigarette as a cessation aid between member states.

Conclusions

Experimentation with e-cigarettes as a potential cessation aid at a population level has increased throughout the EU in recent years, and certain population groups are more likely to experiment with them as cessation aids. Research on the potential population impact of these trends is imperatively needed.
Bathing adaptations in the homes of older adults (BATH-OUT): protocol for a feasibility randomised controlled trial (RCT)
Authors: Whitehead Phillip J , James Marilyn , Belshaw Stuart , Dawson Tony , Day Miriam R , Walker Marion F
Published: October 2016

Introduction

The Care Act 2014 has placed a responsibility on local authorities in England to provide services that prevent deterioration and minimise the use of other health and social care services. Housing adaptations have been identified as 1 of the 10 most promising prevention services for older adults, with bathing adaptations being the most requested. However, many local authorities have lengthy waiting times which may increase costs, reduce effectiveness and reduce the preventive effect. There is no robust evidence of the effect of these adaptations on: health, well-being and functional ability.

Methods and analysis

This is a feasibility randomised controlled trial (RCT) with nested qualitative interview study. The RCT will recruit between 40 and 60 people who have been referred for an accessible showering facility, and their carers, from 1 local authority in England. They will be randomised to either usual adaptations (∼3-month wait) or immediate adaptations (no wait). The primary outcome is the feasibility of conducting a powered study. The outcomes assessed will be: health and social care-related quality of life, independence in activities of daily living and bathing, falls and use of health and social care services. Outcomes will be assessed at 3 and 6 months. Preliminary health economic feasibility will be established.

Ethics and dissemination

Favourable ethical opinion was provided by the Social Care Research Ethics Committee (reference number 16/IEC08/0017). The results of this study will lay the foundations for a further powered study. This would investigate the effect of bathing adaptations on quality of life and whether increased waiting times are associated with poorer outcomes and increased costs. The results have further potential to inform trials of other housing or social care interventions using the novel waiting list control method. Dissemination will include peer-reviewed publications and presentations at national and international conferences.

Trial registration number

ISRCTN14876332; Pre-results.
The scientific agreement on firearm issues
Authors: Hemenway David , Nolan Elizabeth P
Published: October 2016

Introduction

No one has systematically collected the views of firearm researchers to determine if and where agreement exists on the scientific evidence about firearms and firearm violence.

Methods

We send a short monthly on-line survey to firearm researchers. Each survey asks respondents their level of agreement with a statement about firearms, their rating of the quality of the scientific evidence on the specific issue, their familiarity with that literature and their area of expertise. Survey participants are first-authors of a firearms article published in a peer-reviewed journal since 2011. For the first 15 surveys, on average, surveys were sent to 322 researchers, and 109 researchers responded (34% response rate).

Results

Among respondents, approximately 46% were public health researchers and 32% were sociologists/criminologists. Agreement exists among firearm researchers that more guns and weaker gun laws cause serious public health problems, that the costs of gun availability are typically greater than the benefits and that stronger gun laws may improve public safety and health. 84% of researchers agreed, and only 8% disagreed with the statement ‘in the United States, having a gun in the home increases the risk of suicide’. For only three statements did most respondents rate the quality of the scientific evidence as strong or very strong. Overall, there was a higher level of agreement among public health/medicine researchers than among researchers in the other disciplines.

Discussion

Surveys of researchers can provide useful information about agreement on specific issues and about the quality of the scientific evidence.
Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study
Authors: Firbank M J , Yarnall A J , Lawson R A , Duncan G W , Khoo T K , Petrides G S , O'Brien J T , Barker R A , Maxwell R J , Brooks D J , Burn D J
Published: October 2016

Objective

To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline.

Methods

FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA.

Results

PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score.

Conclusions

Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.
Research and development on lactoferrin and its derivatives in China from 2011–2015
Authors: Wang Xiao , Wang Xiumin , Hao Ya , Teng Da , Wang Jianhua
Published: October 2016

Lactoferrin (Lf), a multifunctional glycoprotein, is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. Lactoferricin (Lfcin) is located in the N-terminal region of this protein. In this review, the current state of research into Lf and Lfcin in China is described. Searching with HistCite software in Web Sci located 118 papers published by Chinese researchers from 2011–2015, making China one of the top 3 producers of Lf research and development in the world. The biological functions of Lf and Lfcin are discussed, including antibacterial, antiviral, antifungal, anticarcinogenic, and anti-inflammatory activities; targeted drug delivery, induction of neurocyte, osteoblast, and tenocyte growth, and possible mechanisms of action. The preparation and heterologous expression of Lf in animals, bacteria, and yeast are discussed in detail. Five Lf-related food additive factories and 9 Lf-related health food production companies are certified by the China Food and Drug Administration (CFDA). The latest progress in the generation of transgenic livestock in China, the safety of the use of transgenic animals, and future prospects for the uses of Lf and Lfcin are also covered.
An efficient local cascade defense method in complex networks
Authors: Jiang Zhong-Yuan , Ma Jian-Feng
Published: October 2016

Cascading failures in networked systems often lead to catastrophic consequence. Defending cascading failure propagation by employing local load redistribution method is an efficient way. Given initial load of every node, the key of improving network robustness against cascading failures is to maximally defend cascade propagation with minimum total extra capacity of all nodes. With finite total extra capacity of all nodes, we first discuss three general extra capacity distributions including degree-based distribution (DD), average distribution (AD) and random distribution (RD). To sufficiently use the total spare capacity (SC) of all neighboring nodes of a failed node, then we propose a novel SC-based local load redistribution mechanism to improve the cascade defense ability of network. We investigate the network robustness against cascading failures induced by a single node failure under the three extra capacity distributions in both scale-free networks and random networks. Compared with the degree-based (DB) local load redistribution method, our SC method achieves higher robustness under all of the three extra capacity distributions. The extensive simulation results can well confirm the effectiveness of the SC local load redistribution method.
B̄ → Xsγ in the CP violating MSSM
Authors: Yang Xiu-Yi , Nie Jing , Gao Tie-Jun , Yin Hong-Jie
Published: October 2016

Complete expressions of the [Formula: see text] and [Formula: see text] vertices are derived in the framework of minimal supersymmetric extension of the standard model. With some assumptions on parameters of the model, a numerical analysis of the supersymmetric contributions to the branching ratio and CP-asymmetry of [Formula: see text] is presented.
Efficient Realization of Fixed-Point Binary and Ternary Adders on FPGAs
Authors: Khurshid Burhan , Naaz Roohie
Published: October 2016

Binary and ternary adders are frequently used to speed-up many digital signal processing (DSP) operations like multiplication, compression, filtering, convolution, etc. FPGA realization of these circuits uses a combination of look-up tables (LUTs) and carry-chains. Alternatively, inbuilt operators and parameterizable IP cores provide an efficient means of implementing these circuits. However, the realization is not optimal in the sense that the full potential of the underlying resources is not utilized. In this paper, we use technology-dependent approaches to restructure the Boolean networks corresponding to these circuits. The restructured networks are then mapped optimally onto the FPGA fabric using minimum possible resources. Our analysis shows a subsequent speed-up in the performance of these circuits when compared to different conventional and existing approaches.
Entropy corrected holographic dark energy models in modified gravity
Authors: Jawad Abdul , Azhar Nadeem , Rani Shamaila
Published: October 2016

We consider the power law and the entropy corrected holographic dark energy (HDE) models with Hubble horizon in the dynamical Chern–Simons modified gravity. We explore various cosmological parameters and planes in this framework. The Hubble parameter lies within the consistent range at the present and later epoch for both entropy corrected models. The deceleration parameter explains the accelerated expansion of the universe. The equation of state (EoS) parameter corresponds to quintessence and cold dark matter ([Formula: see text]CDM) limit. The [Formula: see text] approaches to [Formula: see text]CDM limit and freezing region in both entropy corrected models. The statefinder parameters are consistent with [Formula: see text]CDM limit and dark energy (DE) models. The generalized second law of thermodynamics remain valid in all cases of interacting parameter. It is interesting to mention here that our results of Hubble, EoS parameter and [Formula: see text] plane show consistency with the present observations like Planck, WP, BAO, [Formula: see text], SNLS and nine-year WMAP.
Viscosity to entropy ratio of QGP in relativistic heavy ion collisions: The second-order viscose hydrodynamics
Authors: Mehrabi Pari Sharareh , Taghavi Shahri Fatemeh , Javidan Kurosh
Published: October 2016

The nuclear suppression factor [Formula: see text] and elliptic flow [Formula: see text] are calculated by considering the effects of shear viscosity to the entropy density ratio [Formula: see text], using the viscose hydrodynamics at the first- and second-orders of approximation and considering temperature dependent coupling [Formula: see text]. It is shown that the second-order viscose hydrodynamics (varying shear viscosity to entropy ratio) with averaged value of [Formula: see text] gives the best results of [Formula: see text] and [Formula: see text] in comparison to the experimental data.
Strongly 2-nil-clean rings
Authors: Chen Huanyin , Sheibani Marjan
Published: October 2016

A ring [Formula: see text] is strongly 2-nil-clean if every element in [Formula: see text] is the sum of two idempotents and a nilpotent that commute. Fundamental properties of such rings are obtained. We prove that a ring [Formula: see text] is strongly 2-nil-clean if and only if for all [Formula: see text], [Formula: see text] is nilpotent, if and only if for all [Formula: see text], [Formula: see text] is strongly nil-clean, if and only if every element in [Formula: see text] is the sum of a tripotent and a nilpotent that commute. Furthermore, we prove that a ring [Formula: see text] is strongly 2-nil-clean if and only if [Formula: see text] is tripotent and [Formula: see text] is nil, if and only if [Formula: see text] or [Formula: see text], where [Formula: see text] is a Boolean ring and [Formula: see text] is nil; [Formula: see text] is a Yaqub ring and [Formula: see text] is nil. Strongly 2-nil-clean group algebras are investigated as well.
Invariants of finite-dimensional algebras recognized by the semigroup of conjugacy classes of left ideals
Authors: Mȩcel Arkadiusz , Okniński Jan
Published: October 2016

We study the semigroup structure on the set [Formula: see text] of conjugacy classes of left ideals of a finite-dimensional algebra [Formula: see text] over an algebraically closed field [Formula: see text], equipped with the natural multiplication inherited from [Formula: see text], and the structure of the contracted semigroup algebra [Formula: see text]. It is shown that [Formula: see text] has a finite chain of ideals with either nilpotent or completely [Formula: see text]-simple factors with trivial maximal subgroups, so in particular it is locally finite. The ordinary quiver [Formula: see text] of [Formula: see text] is proved to be a subquiver of [Formula: see text], if [Formula: see text] is finite. Moreover, in this case, the structure of [Formula: see text] determines, up to isomorphism, the structure of the algebra [Formula: see text] modulo its Jacobson radical. Combining these results we show that if the semigroup [Formula: see text] is finite, then it determines the structure of any (not necessarily basic) triangular algebra [Formula: see text] which admits a normed presentation.
Rings whose cyclics are D3-modules
Authors: Nguyen Xuan Hau , Yousif Mohamed F. , Zhou Yiqiang
Published: October 2016

This is a study of rings whose cyclic modules are [Formula: see text]-modules with applications to rings whose cyclics are quasi-discrete and, respectively, discrete.
A special chain theorem in the set of intermediate rings
Authors: Nasr Mabrouk Ben , Zeidi Nabil
Published: October 2016

Let [Formula: see text] be an extension of integral domains, and let [Formula: see text] be the integral closure of [Formula: see text] in [Formula: see text]. The main purpose of this paper is to study [Formula: see text], the set of intermediate rings between [Formula: see text] and [Formula: see text]. As a main tool, we establish an explicit description of any intermediate ring in terms of localizations of [Formula: see text] (or [Formula: see text]). This study effectively enables us to characterize the minimal extensions in [Formula: see text]. We also prove a special chain theorem concerning the length of an arbitrary maximal chain in [Formula: see text].
PHYSICAL SYMMETRY AND VIRTUAL PLANE-BASED REDUCTION REFERENCE: A PRELIMINARY STUDY FOR ROBOT-ASSISTED PELVIC FRACTURE REDUCTION
Authors: WANG LIFENG , WANG TIANMIAO , LI CHANGSHENG , TANG PEIFU , XU YING , ZHANG LIHAI , GUO NA , ZHAO YANPENG , ZHAO LU , HU LEI
Published: October 2016

Traditional pelvis fracture reduction suffers from some disadvantages. Robot-assisted pelvis fracture reduction offers some promise in solving these problems. However, the reduction reference to guide robot motion is a key issue that must be resolved. In this paper, we propose a physical symmetry and virtual plane-based reduction reference and adopt the method of registration to calculate the virtual plane for the reference, which were verified via experiments. The results of the position symmetry experiments of the original pelvis and virtual plane-based position symmetry experiments were similar; both showed that the symmetry errors of the pelvis were less than 4[Formula: see text]mm and 2.5[Formula: see text]. The results indicated that the proposed method could be used as a reference for robot-assisted pelvis fracture reduction.
A NEW PARAMETER ESTIMATION METHOD FOR ONLINE SOFT TISSUE CHARACTERIZATION
Authors: SHIN JAEHYUN , ZHONG YONGMIN , SMITH JULIAN , GU CHENGFAN
Published: October 2016

Dynamic soft tissue characterization is of importance to robotic-assisted minimally invasive surgery. The traditional linear regression method is unsuited to handle the non-linear Hunt–Crossley (HC) model and its linearization process involves a linearization error. This paper presents a new non-linear estimation method for dynamic characterization of mechanical properties of soft tissues. In order to deal with non-linear and dynamic conditions involved in soft tissue characterization, this method improves the non-linearity and dynamics of the HC model by treating parameter [Formula: see text] as independent variable. Based on this, an unscented Kalman filter is developed for online estimation of soft tissue parameters. Simulations and comparison analysis demonstrate that the proposed method is able to estimate mechanical parameters for both homogeneous tissues and heterogeneous and multi-layer tissues, and the achieved performance is much better than that of the linear regression method.
DIRECT CORONARY COUPLING APPROACH FOR COMPUTING FFRCT
Authors: XIE XINZHOU , ZHENG MINWEN , DUAN XU , XIE SONGYUN , WANG YUANYUAN
Published: October 2016

With the advances in computational fluid dynamics (CFD) and image-based modeling techniques, fractional flow reserve (FFR) can be computed from coronary computed tomography angiography (CTA) scans (FFRCT). However, this non-invasive approach requires large-scale computational resources, which limits its application in routine clinical setting. A 3D–0D coupling approach is proposed to improve the coupling efficiency of FFRCT. Aortic–root is modeled by a lumped parameter model and connected with the models of left ventricle and systemic circulation. With this approach, the interested coronary regions can be directly coupled to the lumped parameter model, resulting in a significant reduction (up to 20 times reduction) in the volume of the CFD computing domain. The proposed approach is applied to a patient-specific model and compared with previous non-reduced approach. Results show that the computed coronary flow rates, pressure waveforms and FFRCT contours by the proposed approach are consistent well with that of the non-reduced approach. These results demonstrate that the proposed approach can reduce the CFD computing domain of FFRCT significantly while maintaining the similar accuracy as compared with the non-reduced approach, and it can be further employed to promote FFRCT in routine clinical setting.
ANALYSIS OF CAVITATION CHARACTERISTICS IN THROTTLE VALVE WITH DIFFERENT STRUCTURE PARAMETERS
Authors: LI BEIBEI , LI WENHUA , JIAO MINGLI , WANG BINGYANG , LIU XIUMEI
Published: October 2016

The pressure and cavitation characteristics of fluid through throttle valves with different structure parameters were investigated numerically using computational fluid dynamics. The mass flow rate, pressure drop, and the volume fraction of the vapor in the single and two-step throttle valve were computed. The cavitation regions were mainly distributed on the top of the valve rod and the corner of the valve seat in both of the different throttle valves. The size of cavitation region at the corner of the channel grows firstly, and then decrease with the decreasing opening degree. Furthermore, the lowest pressure region, as well as the area and strength of cavitation region, in the two-step throttle valve were smaller than a single one at the same opening degree. The formula for equivalent orifice area of throttle valve was derived, in order to explain the effect of opening degree. The results indicated that the two-step throttle has high anti-cavitation capability.
NONRESTRAINT MASTER SYSTEM FOR SURGICAL ROBOTS
Authors: JANG IK GYU , PARK SAMUEL BYEONGJUN , PARK HONG SEONG , JO YUNG-HO
Published: October 2016

Purpose: To overcome the anisotropic characteristics caused by nonuniform friction and singularity in mechanical master interfaces in minimally invasive surgical robot systems, we developed a nonrestraint optical master interface. Materials and Methods: The interface was developed using high-resolution infrared cameras and small reflection markers attached on handheld tongs. We derived 7-degrees of freedom (DOF) motion of the tongs from the kinematic solution of three markers. The accuracy of 3-DOF rotational motion was examined to verify the spatial resolution. The manipulability of the developed nonrestraint master system was evaluated by comparing it with a mechanical master interface (Phantom Premium, SensAble Inc.). Results: The rotational discrepancies were less than 1.72[Formula: see text], 0.39[Formula: see text], and 0.87[Formula: see text] for roll, pitch, and yaw, respectively. The motion comparisons, including straight line, circle, and eight-shape motions, indicated that the nonrestraint master could achieve movements that are more natural. Discussion: In vitro tests showed the feasibility of the proposed nonrestraint optical master interface for use with surgical robots. Because the proposed interface allows natural motion capability, more intuitive surgical motions are possible. In addition, the motion range are expected to increase and the problems associated with master–slave coupling are expected to reduce by our nonrestraint master interface.
Studies on Magnetron Sputtered ZnO–Ag Films: Adhesion Activity of S. aureus
Authors: Geetha S. R. , Dhivya P. , Raj P. Deepak , Sridharan M. , Princy S. Adline
Published: October 2016

Zinc oxide (ZnO) thin films have been deposited onto thoroughly cleaned stainless steel (AISI SS 304) substrates by reactive direct current (dc) magnetron sputtering and the films were doped with silver (Ag). The prepared thin films were analyzed using X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM) to investigate the structural and morphological properties. The thickness values of the films were in the range of 194 to 256[Formula: see text]nm. XRD results revealed that the films were crystalline with preferred (002) orientation. Grain size values of pure ZnO films were found to be 19.82–23.72[Formula: see text]nm. On introducing Ag into ZnO film, the micro-structural properties varied. Adhesion test was carried out with Staphylococcus aureus (S. aureus) in order to know the adherence property of the deposited films. Colony formation units (CFU) were counted manually and bacterial adhesion inhibition (BAI) was calculated. We observed a decrease in the CFU on doping Ag in the ZnO films. BAI of the film deposited at – 100 V substrate bias was found to be increased on Ag doping from 69 to 88%.
Global stability results for models of commensalism
Authors: Georgescu Paul , Maxin Daniel , Zhang Hong
Published: October 2016

We analyze the global stability of the coexisting equilibria for several models of commensalism, first by devising a procedure to modify several Lyapunov functionals which were introduced earlier for corresponding models of mutualism, further confirming their usefulness. It is seen that commensalism promotes global stability, in connection with higher-order self-limiting terms which prevent unboundedness. We then use the theory of asymptotically autonomous systems to prove global stability results for models of commensalism which are subject to Allee effects, finding that commensalisms of appropriate strength can overcome the influence of strong Allee effects.
TCR Signal Strength and T Cell Development
Authors: Gascoigne Nicholas R.J. , Rybakin Vasily , Acuto Oreste , Brzostek Joanna
Published: October 2016

Thymocyte selection involves the positive and negative selection of the repertoire of T cell receptors (TCRs) such that the organism does not suffer autoimmunity, yet has the benefit of the ability to recognize any invading pathogen. The signal transduced through the TCR is translated into a number of different signaling cascades that result in transcription factor activity in the nucleus and changes to the cytoskeleton and motility. Negative selection involves inducing apoptosis in thymocytes that express strongly self-reactive TCRs, whereas positive selection must induce survival and differentiation programs in cells that are more weakly self-reactive. The TCR recognition event is analog by nature, but the outcome of signaling is not. A large number of molecules regulate the strength of the TCR-derived signal at various points in the cascades. This review discusses the various factors that can regulate the strength of the TCR signal during thymocyte development.
Hydrogen sulfide-induced vasodilation mediated by endothelial TRPV4 channels
Authors: Naik Jay S. , Osmond Jessica M. , Walker Benjimen R. , Kanagy Nancy L.
Published: October 2016

Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large-conductance Ca2+-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium. Calcium influx through TRPV4 may activate these endothelial BK channels (eBK). We hypothesized that H2S-mediated vasodilation involves activation of TRPV4 within the endothelium. In pressurized, phenylephrine-constricted mesenteric arteries, H2S elicited a dose-dependent vasodilation blocked by inhibition of TRPV4 channels (GSK2193874A, 300 nM). H2S (1 μM) increased TRPV4-dependent (1.8-fold) localized calcium events in EC of pressurized arteries loaded with fluo-4 and Oregon Green. In pressurized EC tubes, H2S (1 μM) and the TRPV4 activator, GSK101679A (30 nM), increased calcium events 1.8- and 1.5-fold, respectively. H2S-induced an iberiotoxin-sensitive outward current measured using whole cell patch-clamp techniques in freshly dispersed EC. H2S increased K+ currents from 10 to 30 pA/pF at +150 mV. Treatment with Na2S increased the level of sulfhydration of TRPV4 channels in aortic ECs. These results demonstrate that H2S-mediated vasodilation involves activation of TRPV4-dependent Ca2+ influx and BK channel activation within EC. Activation of TRPV4 channels appears to cause calcium events that result in the opening of eBK channels, endothelial hyperpolarization, and subsequent vasodilation.
Modulation of respiratory output by cervical epidural stimulation in the anesthetized mouse
Authors: Huang Ruyi , Baca Serapio M. , Worrell Jason W. , Liu Xingquan , Seo Yeji , Leiter James C. , Lu Daniel C.
Published: October 2016

Respiration is produced and controlled by well-characterized brain stem nuclei, but the contributions of spinal circuits to respiratory control and modulation remain under investigation. Many respiratory studies are conducted in in vitro preparations (e.g., brain stem slice) obtained from neonatal rodents. While informative, these studies do not fully recapitulate the complex afferent and efferent neural circuits that are likely to be involved in eupnea (i.e., quiet breathing). To begin to investigate spinal contributions to respiration, we electrically stimulated the cervical spinal cord during unassisted respiration in anesthetized, intact mice. Specifically, we used epidermal electrical stimulation at 20 Hz and varied current intensity to map changes in respiration. Stimulating at 1.5 mA at cervical level 3 (C3) consistently caused a significant increase in respiratory frequency compared with prestimulation baseline and when compared with sham stimulations. The increase in respiratory frequency persisted for several minutes after epidural stimulation ceased. There was no change in tidal volume, and the estimated minute ventilation was increased as a consequence of the increase in respiratory frequency. Sigh frequency also increased during epidural stimulation at C3. Neither the increase in respiratory frequency nor the increase in sighing were observed after stimulation at other dorsal cervical levels. These findings suggest that the spinal circuits involved in the modulation of eupnea and sighing may be preferentially activated by specific endogenous inputs. Moreover, the cervical spinal cord may play a role in respiratory modulation that affects both eupneic respiration and sigh production in intact, adult mice.
The effect of body mass and sex on the accuracy of respiratory magnetometers for measurement of end-expiratory lung volumes
Authors: Avraam Joanne , Bourke Rosie , Trinder John , Nicholas Christian L. , Brazzale Danny , O’Donoghue Fergal J. , Rochford Peter D. , Jordan Amy S.
Published: October 2016

Respiratory magnetometers are increasingly being used in sleep studies to measure changes in end-expiratory lung volume (EELV), including in obese obstructive sleep apnea patients. Despite this, the accuracy of magnetometers has not been confirmed in obese patients nor compared between sexes. Thus we compared spirometer-measured and magnetometer-estimated lung volume and tidal volume changes during voluntary end-expiratory lung volume changes of 1.5, 1, and 0.5 l above and 0.5 l below functional respiratory capacity in supine normal-weight [body mass index (BMI) < 25 kg/m] and healthy obese (BMI > 30 kg/m) men and women. Two different magnetometer calibration techniques proposed by Banzett et al. [Banzett RB, Mahan ST, Garner DM, Brughera A, Loring SH. J Appl Physiol (1985) 79: 2169–2176, 1995] and Sackner et al. [Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky F, Krieger B. J Appl Physiol (1985) 66: 410–420, 1989] were assessed. Across all groups and target volumes, magnetometers overestimated spirometer-measured EELV by ~65 ml (<0.001) with no difference between techniques (0.07). The Banzett method overestimated the spirometer EELV change in normal-weight women for all target volumes except +0.5 l, whereas no differences between mass or sex groups were observed for the Sackner technique. The variability of breath-to-breath measures of EELV was significantly higher for obese compared with nonobese subjects and was higher for the Sackner than Banzett technique. On the other hand, for tidal volume, both calibration techniques underestimated spirometer measurements (<0.001), with the underestimation being more marked for the Banzett than Sackner technique (0.03), in obese than normal weight (<0.001) and in men than in women (0.003). These results indicate that both body mass and sex affect the accuracy of respiratory magnetometers in measuring EELV and tidal volume.
Hybrid Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Modulating Tumor Hypoxia
Authors: Abbasi Azhar Z. , Gordijo Claudia R. , Amini Mohammad Ali , Maeda Azusa , Rauth Andrew M. , DaCosta Ralph S. , Wu Xiao Yu
Published: October 2016

Hypoxia in the tumor microenvironment (TME) mediates resistance to radiotherapy and contributes to poor prognosis in patients receiving radiotherapy. Here we report the design of clinically suitable formulations of hybrid manganese dioxide (MnO2) nanoparticles (MDNP) using biocompatible materials to reoxygenate the TME by reacting with endogenous H2O2. MDNP containing hydrophilic terpolymer-protein-MnO2 or hydrophobic polymer-lipid-MnO2 provided different oxygen generation rates in the TME relevant to different clinical settings. In highly hypoxic murine or human xenograft breast tumor models, we found that administering either MDNP formulation before radiotherapy modulated tumor hypoxia and increased radiotherapy efficacy, acting to reduce tumor growth, VEGF expression, and vascular density. MDNP treatment also increased apoptosis and DNA double strand breaks, increasing median host survival 3- to 5-fold. Notably, in the murine model, approximately 40% of tumor-bearing mice were tumor-free after a single treatment with MDNPs plus radiotherapy at a 2.5-fold lower dose than required to achieve the same curative treatment without MDNPs. Overall, our findings offer a preclinical proof of concept for the use of MDNP formulations as effective radiotherapy adjuvants. Cancer Res; 76(22); 6643–56. ©2016 AACR.
HA1-2-fljB Vaccine Induces Immune Responses against Pandemic Swine-Origin H1N1 Influenza Virus in Mice
Authors: Kang Xilong , Yang Yun , Jiao Yang , Song Hongqin , Song Li , Xiong Dan , Wu Lili , Pan Zhiming , Jiao Xinan
Published: October 2016

In 2009, a novel pandemic swine-origin influenza A (H1N1) virus caused a public emergency of international concern. Vaccination is the primary strategy for the control of influenza epidemics. However, the poor immunopotency of many vaccine antigens is a major barrier to the development of effective vaccines against influenza. Flagellin, a Toll-like receptor 5 (TLR5) ligand, has been used as an adjuvant to enhance the immunopotency of vaccines in preclinical studies. Here, we developed a recombinant candidate vaccine, HA1-2-fljB, in which the globular head of the hemagglutinin (HA) antigen (residues 62-284) from H1N1 virus was fused genetically to the N-terminus of Salmonella typhimurium ﬂjB. The recombinant HA1-2-fljB protein was expressed efficiently in Escherichia coli, and the immunogenicity and protective efficacy of recombinant HA1-2-fljB were evaluated in a mouse model. Immunization with HA1-2-fljB elicited robust IgG antibodies and neutralizing antibodies and completely protected the mice against infection by swine-origin influenza A/swine/Jangsu/38/2010 (H1N1). These results suggest that HA antigen placed at the N-terminus of flagellin is also an excellent starting point for creating a fusion HA1-2-fljB protein as a candidate vaccine, and the recombinant HA1-2-fljB protein will contribute to the development of a more effective vaccine against swine-origin influenza virus infection.
AMP-Activated Protein Kinase and Sirtuin 1 Coregulation of Cortactin Contributes to Endothelial Function
Authors: Shentu Tzu-Pin , He Ming , Sun Xiaoli , Zhang Jianlin , Zhang Fan , Gongol Brendan , Marin Traci L. , Zhang Jiao , Wen Liang , Wang Yinsheng , Geary Gregory G. , Zhu Yi , Johnson David A. , Shyy John Y.-J.
Published: October 2016

Objective—

Cortactin translocates to the cell periphery in vascular endothelial cells (ECs) on cortical–actin assembly in response to pulsatile shear stress. Because cortactin has putative sites for AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) deacetylation, we examined the hypothesis that AMPK and SIRT1 coregulate cortactin dynamics in response to shear stress.

Approach and Results—

Analysis of the ability of AMPK to phosphorylate recombinant cortactin and oligopeptides whose sequences matched AMPK consensus sequences in cortactin pointed to Thr-401 as the site of AMPK phosphorylation. Mass spectrometry confirmed Thr-401 as the site of AMPK phosphorylation. Immunoblot analysis with AMPK siRNA and SIRT1 siRNA in human umbilical vein ECs and EC-specific AMPKα2 knockout mice showed that AMPK phosphorylation of cortactin primes SIRT1 deacetylation in response to shear stress. Immunoblot analyses with cortactin siRNA in human umbilical vein ECs, phospho-deficient T401A and phospho-mimetic T401D mutant, or aceto-deficient (9K/R) and aceto-mimetic (9K/Q) showed that cortactin regulates endothelial nitric oxide synthase activity. Confocal imaging and sucrose-density gradient analyses revealed that the phosphorylated/deacetylated cortactin translocates to the EC periphery facilitating endothelial nitric oxide synthase translocation from lipid to nonlipid raft domains. Knockdown of cortactin in vitro or genetic reduction of cortactin expression in vivo in mice substantially decreased the endothelial nitric oxide synthase–derived NO bioavailability. In vivo, atherosclerotic lesions increase in ApoE
–
/–
/cortactin
+/–
mice, when compared with ApoE
–/–
/cortactin
+/+
littermates.

Conclusions—

AMPK phosphorylation of cortactin followed by SIRT1 deacetylation modulates the interaction of cortactin and cortical–actin in response to shear stress. Functionally, this AMPK/SIRT1 coregulated cortactin–F-actin dynamics is required for endothelial nitric oxide synthase subcellular translocation/activation and is atheroprotective.
Farnesoid X Receptor and Its Ligands Inhibit the Function of Platelets
Authors: Moraes Leonardo A. , Unsworth Amanda J. , Vaiyapuri Sakthivel , Ali Marfoua S. , Sasikumar Parvathy , Sage Tanya , Flora Gagan D. , Bye Alex P. , Kriek Neline , Dorchies Emilie , Molendi-Coste Olivier , Dombrowicz David , Staels Bart , Bishop-Bailey David , Gibbins Jonathan M.
Published: October 2016

Objective—

Although initially seemingly paradoxical because of the lack of nucleus, platelets possess many transcription factors that regulate their function through DNA-independent mechanisms. These include the farnesoid X receptor (FXR), a member of the superfamily of ligand-activated transcription factors, that has been identified as a bile acid receptor. In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6α-ethyl-chenodeoxycholic acid, modulate platelet activation nongenomically.

Approach and Results—

FXR ligands inhibited the activation of platelets in response to stimulation of collagen or thrombin receptors, resulting in diminished intracellular calcium mobilization, secretion, fibrinogen binding, and aggregation. Exposure to FXR ligands also reduced integrin α
IIb
β
3
outside-in signaling and thereby reduced the ability of platelets to spread and to stimulate clot retraction. FXR function in platelets was found to be associated with the modulation of cyclic guanosine monophosphate levels in platelets and associated downstream inhibitory signaling. Platelets from FXR-deficient mice were refractory to the actions of FXR agonists on platelet function and cyclic nucleotide signaling, firmly linking the nongenomic actions of these ligands to the FXR.

Conclusions—

This study provides support for the ability of FXR ligands to modulate platelet activation. The atheroprotective effects of GW4064, with its novel antiplatelet effects, indicate FXR as a potential target for the prevention of atherothrombotic disease.
Dying With a Left Ventricular Assist Device as Destination Therapy
Authors: Dunlay Shannon M. , Strand Jacob J. , Wordingham Sara E. , Stulak John M. , Luckhardt Angela J. , Swetz Keith M.
Published: October 2016

Background—

Despite the ability of left ventricular assist device as destination therapy (DT-LVAD) to prolong survival for many patients with advanced heart failure, little is known about the eventual end-of-life care that patients with DT-LVAD receive.

Methods and Results—

All patients undergoing DT-LVAD at the Mayo Clinic in Rochester, Minnesota, from January 1, 2007, to September 30, 2014, who subsequently died before July 1, 2015, were included. Information about end-of-life care was obtained from documentation in the electronic medical record. Of 89 patients who died with a DT-LVAD, the median (25th–75th percentile) time from left ventricular assist device implantation to death was 14 (4–31) months. The most common causes of death were multiorgan failure (26%), hemorrhagic stroke (24%), and progressive heart failure (21%). Nearly half (46%) of the patients saw palliative care within 1 month before death; however, only 13 (15%) patients enrolled in hospice a median 11 (range 1–315) days before death. Most patients (78%) died in the hospital, of which 88% died in the intensive care unit. In total, 49 patients had their left ventricular assist device deactivated before death, with all but 3 undergoing deactivation in the hospital. Most patients died within an hour of left ventricular assist device deactivation and all within 26 hours.

Conclusions—

In contrast to the general heart failure population, most patients with DT-LVAD die in the hospital and few use hospice. Further work is needed to understand these differences and to determine whether patients with DT-LVAD are receiving optimal end-of-life care.
Influence of Ethnicity, Age, and Time on Sex Disparities in Long‐Term Cause‐Specific Mortality After Acute Myocardial Infarction
Authors: Gao Fei , Lam Carolyn S.P. , Yeo Khung Keong , Machin David , de Carvalho Leonardo P. , Sim Ling Ling , Koh Tian Hai , Foo David , Ong Hean Yee , Tong Khim Leng , Tan Huay Cheem , Earnest Arul , Chua Terrance , Chan Mark Yan Yee
Published: October 2016

Background

We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort.

Methods and Results

For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22–101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age‐adjusted hazard ratio [
HR
] 1.3, 95% CI 1.2–1.4) but a similar risk of noncardiovascular death (
HR
0.9, 95%
CI
0.8–1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (
HR
1.4, 95%
CI
1.2–1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (
HR
3.4 [95%
CI
1.9–6.0] versus
HR
1.5 [95%
CI
0.6–3.6] for Indian women). Compared with same‐age Malay men, Malay women aged 22 to 49 years had a 2.5‐fold (95%
CI
1.6–3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the
HR
comparing cardiovascular death of Indian women and men decreased from 1.9 (95%
CI
1.5–2.4) at 30 days to 0.9 (95%
CI
0.5–1.6) at 10 years.

Conclusion

Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.