bluuebunny/crossref_metadata_2025 huggingface dataset:
Disrupting metabolism to treat autoimmunity
Authors: Matsushita Mai , Pearce Edward J.
Published: April 2018

Dimethyl fumarate, a treatment for multiple sclerosis, inhibits Warburg metabolism
Development and Evaluation of a Novel Loop-Mediated Isothermal Amplification Assay for Diagnosis of Cutaneous and Visceral Leishmaniasis
Authors: Adams Emily Rebecca , Schoone Gerard , Versteeg Inge , Gomez Maria Adelaida , Diro Ermias , Mori Yasuyoshi , Perlee Desiree , Downing Tim , Saravia Nancy , Assaye Ashenafi , Hailu Asrat , Albertini Audrey , Ndung'u Joseph Mathu , Schallig Henk
Published: April 2018

A novel pan-
Leishmania
loop-mediated isothermal amplification (LAMP) assay for the diagnosis of cutaneous and visceral leishmaniasis (CL and VL) that can be used in near-patient settings was developed. Primers were designed based on the 18S ribosomal DNA (rDNA) and the conserved region of minicircle kinetoplast DNA (kDNA), selected on the basis of high copy number. LAMP assays were evaluated for CL diagnosis in a prospective cohort trial of 105 patients in southwest Colombia. Lesion swab samples from CL suspects were collected and were tested using the LAMP assay, and the results were compared to those of a composite reference of microscopy and/or culture in order to calculate diagnostic accuracy. LAMP assays were tested on samples (including whole blood, peripheral blood mononuclear cells, and buffy coat) from 50 suspected VL patients from Ethiopia. Diagnostic accuracy was calculated against a reference standard of microscopy of splenic or bone marrow aspirates. To calculate analytical specificity, 100 clinical samples and isolates from fever-causing pathogens, including malaria parasites, arboviruses, and bacteria, were tested. We found that the LAMP assay had a sensitivity of 95% (95% confidence interval [CI], 87.2% to 98.5%) and a specificity of 86% (95% CI, 67.3% to 95.9%) for the diagnosis of CL. With VL suspects, the sensitivity of the LAMP assay was 92% (95% CI, 74.9% to 99.1%) and its specificity was 100% (95% CI, 85.8% to 100%) in whole blood. For CL, the LAMP assay is a sensitive tool for diagnosis and requires less equipment, time, and expertise than alternative CL diagnostics. For VL, the LAMP assay using a minimally invasive sample is more sensitive than the gold standard. Analytical specificity was 100%.
A Chikungunya Virus
trans
-Replicase System Reveals the Importance of Delayed Nonstructural Polyprotein Processing for Efficient Replication Complex Formation in Mosquito Cells
Authors: Bartholomeeusen Koen , Utt Age , Coppens Sandra , Rausalu Kai , Vereecken Katleen , Ariën Kevin K. , Merits Andres
Published: April 2018

Chikungunya virus (CHIKV) is a medically important alphavirus that is transmitted by
Aedes aegypti
and
Aedes albopictus
mosquitoes. The viral replicase complex consists of four nonstructural proteins (nsPs) expressed as a polyprotein precursor and encompasses all enzymatic activities required for viral RNA replication. nsPs interact with host components of which most are still poorly understood, especially in mosquitos. A CHIKV
trans
-replicase system that allows the uncoupling of RNA replication and nsP expression was adapted to mosquito cells and subsequently used for analysis of universal and host-specific effects of 17 different nonstructural polyprotein (ns-polyprotein) mutations. It was found that mutations blocking nsP enzymatic activities as well as insertions of enhanced green fluorescent protein (EGFP) into different nsPs had similar effects on
trans
-replicase activity regardless of the host (i.e., mammalian or mosquito). Mutations that slow down or accelerate ns-polyprotein processing generally had no effect or reduced
trans
-replicase activity in mammalian cells, while in mosquito cells most of them increased
trans
-replicase activity prominently. Increased RNA replication in mosquito cells was counteracted by an antiviral RNA interference (RNAi) response. Substitution of the W258 residue in the membrane binding peptide of nsP1 resulted in a temperature-sensitive defect, in the context of both the
trans
-replicase and infectious CHIKV. The defect was compensated for by secondary mutations selected during passaging of mutant CHIKV. These findings demonstrate the value of alphavirus
trans
-replicase systems for studies of viral RNA replication and virus-host interactions.

IMPORTANCE
Chikungunya virus is an important mosquito-transmitted human pathogen. This virus actively replicates in mosquitoes, but the underlying molecular mechanisms and interactions of viral and host components are poorly understood. This is partly due to the lack of reliable systems for functional analysis of viral nonstructural polyproteins (ns-polyproteins) and nonstructural proteins (nsPs) in mosquito cells. Adaption of a CHIKV
trans
-replicase system allowed study of the effects of mutations in the ns-polyprotein on RNA replication in cells derived from mammalian and mosquito hosts. We found that a slowdown of ns-polyprotein processing facilitates replication complex formation and/or functioning in mosquito cells and that this process is antagonized by the natural RNAi defense system present in mosquito cells. The mosquito-adapted CHIKV
trans
-replicase system represents a valuable tool to study alphavirus-mosquito interactions at the molecular level and to develop advanced antiviral strategies.
Critical Role of the Human T-Cell Leukemia Virus Type 1 Capsid N-Terminal Domain for Gag-Gag Interactions and Virus Particle Assembly
Authors: Martin Jessica L. , Mendonça Luiza M. , Marusinec Rachel , Zuczek Jennifer , Angert Isaac , Blower Ruth J. , Mueller Joachim D. , Perilla Juan R. , Zhang Wei , Mansky Louis M.
Published: April 2018

Retrovirus particle assembly and release from infected cells is driven by the Gag structural protein. Gag-Gag interactions, which form an oligomeric lattice structure at a particle budding site, are essential to the biogenesis of an infectious virus particle. The CA domain of Gag is generally thought to possess the key determinants for Gag-Gag interactions, and the present study has discovered several critical amino acid residues in the CA domain of HTLV-1 Gag, an important cancer-causing human retrovirus, which are distinct from that of HIV-1 as well as other retroviruses studied to date. Altogether, our results provide important new insights into a poorly understood aspect of HTLV-1 replication that significantly enhances our understanding of the molecular nature of Gag-Gag interaction determinants crucial for virus particle assembly.
Neuro-ophthalmological manifestations of Behçet’s disease
Authors: Alghamdi Ammr , Bodaghi Bahram , Comarmond Chloé , Desbois Anne Claire , Domont Fanny , Wechsler Bertrand , Depaz Raphael , Le Hoang Phuc , Cacoub Patrice , Touitou Valérie , Saadoun David
Published: April 2018

Background

The neuro-ophthalmological manifestations of Behcet’s disease (BD) are rare, and data regarding their characteristics and outcome are lacking.

Objective

To report prevalence, main characteristics and outcome of neuro-ophthalmological manifestations in BD.

Patients and methods

This is a retrospective monocentric study of 217 patients diagnosed with neuro-Behçet’s disease (NBD), of whom 29 (13.3%) patients presented with neuro-ophthalmological manifestations (55% of men and mean±SD age of 26±8 years). All patients underwent a detailed ophthalmological examination and were followed up in the internal medicine and the ophthalmology departments.

Results

Neuro-ophthalmological manifestations were the first presentation of BD in 45% of patients and developed later in the course of the disease in 55% of patients. They are divided into parenchymal (PM) and non-parenchymal (NPM)-related manifestations in, respectively, 13 patients (45%) and 16 patients (55%). PM included papillitis in seven patients (53.8%), retrobulbar optic neuritis in four patients (30.8%) and third cranial nerve palsy in two patients (15.4%). NPM included papilloedema related to cerebral venous thrombosis in all 16 patients, of whom 6 patients (37.5%) had sixth cranial nerve palsy. At initial examination, 93.1% of patients had visual alterations, including mainly decreased visual acuity visual field defects and/or diplopia. All patients were treated with corticosteroids and 79% of patients received immunosuppressive agents. After treatment, the visual outcome improved or stabilised in 66.7% of patients while it worsened in 33.3. The mean±SD logarithm of the minimum angle of resolution visual acuity improved from 0.4±0.3 at diagnosis to 0.2±0.3 after therapy. 10.3% and 3.4% of patients were legally blind at diagnosis and after therapy, respectively.

Conclusion

Neuro-ophthalmological manifestations of BD represented 13% of NBD. They could be potentially severe and disabling. Prompt treatment is the key factor in improving visual outcome.
Prevalence of glaucoma in the Australian National Eye Health Survey
Authors: Keel Stuart , Xie Jing , Foreman Joshua , Lee Pei Ying , Alwan Mostafa , Fahy Eamonn T , van Wijngaarden Peter , Fan Gaskin Jennifer C , Ang Ghee Soon , Crowston Jonathan G , Taylor Hugh R , Dirani Mohamed
Published: April 2018

Aim

To estimate the prevalence of glaucoma in Australia.

Methods

This was a population-based study of 3098 non-Indigenous Australians (50–98 years) and 1738 Indigenous Australians (40–92 years) stratified by remoteness. Each participant underwent a standard examination that included visual field assessment, tonometry and non-mydriatic fundus photography. Two fellowship-trained glaucoma specialists independently assessed relevant case notes (past ocular history, best-corrected visual acuity, frequency doubling technology visual fields, Van Herick grade, intraocular pressure and optic disc-centred photographs) and assigned a diagnosis ranked on a scale of certainty: none, possible, probable or definite glaucoma.

Results

A total of 4792 (99.1%, 3062 non-Indigenous and 1730 Indigenous) participants had retinal photographs in at least one eye that were gradable for glaucoma. The weighted prevalence of glaucoma (definite) in non-Indigenous Australians and Indigenous Australians was 1.5% (95% CI 1.0 to 2.2) and 0.6% (95% CI 0.4 to 1.1), respectively. When definite and probable cases of glaucoma were combined, rates were 3.4% (95% CI 2.7 to 4.3) among non-Indigenous and 1.6% (95% CI 1.1 to 2.3) in Indigenous Australians. Only 52.4% of non-Indigenous Australians and 28.0% of Indigenous Australians with glaucoma self-reported a known history of glaucoma.

Conclusion

We estimate that 198 923 non-Indigenous Australians aged 50 years and over and 2139 Indigenous Australians aged 40 years and over have glaucoma. Given the high rates of undiagnosed glaucoma coupled with a significant ageing of the Australian population, improvements in case detection and access to low vision rehabilitation services may be required to cope with the growing burden of glaucoma.
Resting nailfold capillary blood flow in primary open-angle glaucoma
Authors: Cousins Clara C , Chou Jonathan C , Greenstein Scott H , Brauner Stacey C , Shen Lucy Q , Turalba Angela V , Houlihan Patricia , Ritch Robert , Wiggs Janey L , Knepper Paul A , Pasquale Louis R
Published: April 2018

Background/Aims

An altered haemodynamic profile for various ocular posterior segment capillary beds has been documented in primary open-angle glaucoma (POAG). POAG may also involve abnormal non-ocular blood flow, and the nailfold capillaries, which are not affected by elevated intraocular pressure (IOP), are readily assessable.

Methods

We measured resting nailfold capillary blood flow in 67 POAG and 63 control subjects using video capillaroscopy. Masked readers tracked blood column voids between consecutive, registered image sequence frames, measured vessel diameter and calculated blood flow. We used multiple logistic regression to investigate the relation between nailfold capillary blood flow and POAG. In secondary analyses, we stratified cases by maximum IOP and concurrent topical beta-blocker use.

Results

Mean (±SD) blood flow in picolitres per second was 26.8±17.6 for POAG cases and 50.1±24.2 for controls (p<0.0001). After adjustment for demographic and clinical factors including blood pressure and pulse, every picolitre per second increase in resting nailfold blood flow was associated with a 6% (95% CI 0.92 to 0.96) reduced odds of POAG (p<0.0001). Similar relations between nailfold capillary blood flow and POAG were found for cases stratified by maximum known IOP and for cases stratified by concurrent topical beta-blocker use.

Conclusion

Reduced resting nailfold capillary blood flow is present in POAG independent of covariates such as blood pressure, pulse and IOP.
Nonclassical properties of the squeezing and rotating coherent state
Authors: Ren Gang , Du Jian-ming , Yu Hai-jun
Published: April 2018

In this paper, we construct and investigate the nonclassical properties of the squeezing and rotating coherent state (SRCS) via a generalized squeezed operator by introducing a novel parameter r. In a particular case r = 0, SRCS reduces to the normal squeezed coherent state (SCS). The influence of r is studied in terms of squeezing and quantum statistical properties. Our results show that in the SCS not only is squeezing enhanced but also is rotated by the parameter r. Our discussion about the fidelity between SRCS and SCS shows that the fidelity values decrease with increasing parameter r. The experimental scheme for producing SRCS is also given via a self-Kerr medium and non-degenerate parametric amplifier.
Numerical simulations of MHD forced convection flow of micropolar fluid inside a right-angled triangular cavity saturated with porous medium: Effects of vertical moving wall
Authors: Nazeer Mubbashar , Ali N. , Javed Tariq
Published: April 2018

The present article explores the effects of moving lid on the forced convection flow of micropolar fluid inside a right-angle triangular cavity saturated with porous medium. The base and hypotenuse or inclined sides of the cavity are maintained at constant temperatures, while the vertical side of the enclosure is adiabatic and moving with constant velocity in upward or downward direction. The flow equations are simulated by using the robust finite element numerical technique. The pressure term from the momentum equations is eliminated by using the penalty parameter. For a consistent solution, the value of the penalty parameter is selected as 107. The simulations are performed for the cases based on the direction of moving lid. The numerical outcomes are shown in terms of streamlines, temperature contours, and local and average Nusselt numbers for sundry parameters, such as micropolar parameter, Reynolds number, Richardson number, Darcy number, Hartmann number, and Prandtl number. It is observed that the shape of the inner circulating cell is elliptic when the lid is moving in the upward direction and fluid is clear (Newtonian fluid). It is also found that average Nusselt number in both cases increases with increasing Prandtl number, Richardson number, micropolar parameter, and Darcy number, whereas it decreases with increasing Hartmann number. Further, it achieves a maximum when the lid is moving in the downward direction, regardless of the choice of involved parameters. The numerical code is also validated with previous published results. The investigation of the current study is beneficial in porous heat exchangers, construction of triangular-shaped solar collectors, rigid crystal, polymeric fluid transport, etc.
A study for hydrogen-like lawrencium
Authors: Ürer Güldem
Published: April 2018

Studying hydrogenic ions with high Z is an occasion to understand atomic structure. It also provides a reliable test of methods used to determine atomic structures. Many fields and applications require precise atomic data. For this reason, a hydrogen-like study is performed for lawrencium (Lr102+, Z = 103). The energy levels of hydrogen-like lawrencium are calculated with both multiconfiguration Hartree–Fock (MCHF) and multiconfiguration Dirac–Fock (MCDF) methods. The calculations contain Breit–Pauli relativistic corrections in MCHF calculation and the transverse photon and quantum electrodynamics (QED) effects in MCDF calculation along with electron correlations. In addition, some transition parameters (wavelengths, λ, logarithmic weighted oscillator strengths, log(gf) value, and transition probabilities, Aki) for allowed (E1) and forbidden (E2 and M1) transitions are investigated. The results from this study are compared with only a few theoretical works, but there is no available experimental data yet for Lr102+.
Punishing the redundant influence improves the accuracy of link prediction
Authors: Yang Yujie , Zhang Jianhua , Zhu Xuzhen
Published: April 2018

The influence of traditionally composing node degree ignores the fact that effective transmission determines the similarity between endpoints in link prediction. Due to effective transmission, the degrees connected to the common neighbor and the short-path can be regarded as efficient influence, whereas the degrees connected to the noncommon neighbor and the long-path represent redundant influence because of their inefficiency, not to mention the paths disconnected to the target node. Therefore, in this paper, we propose a new method based on punishing the redundant influence (PRI) to improve the accuracy of the link prediction by emphasizing the effective influence and increasing the similarity between node pairs. From the results of extensive experiments in twelve real-world networks, PRI achieves superior performance compared to the traditional methods.
The evolutionary mechanism of high-speed railway system based on hypernetwork theory
Authors: Suo Qi , Guo JinLi
Published: April 2018

Railway system as an important transportation pattern can improve regional economic growth and accelerate the development of transportation structure. In this paper, we propose an evolving model to describe the evolutionary mechanism of high-speed railway system by using hypernetwork theory. The stations are represented as nodes while the lines are represented as hyperedges. The evolving process includes two ingredients: growing and linking which is driven by both random and preferential attachment. We analytically deduce the node hyperdegree distribution which is shown to follow a shifted power-law distribution. Furthermore, we test the impact of parameters on the model. Then the empirical investigations of China Railway High-speed (CRH) are demonstrated which can be explained by the proposed model. The model can reveal the macro characteristics of railway system and provide reference for the further development of high-speed railway.
Density functional theory study on CO adsorption on the PdnAl (n= 1–5) clusters
Authors: Li Zhi , Zhou Zhonghao , Zhao Zhen , Wang Qi
Published: April 2018

The configurations, stability, electronic properties and CO adsorption of the ground state Pd[Formula: see text]Al (n = 1–5) clusters are calculated by the density functional theory (DFT). The results reveal that the lowest-energy configurations of Pd[Formula: see text]Al clusters inherit the geometries of the host Pd[Formula: see text] clusters to a larger extent. The C atom in CO molecule prefers to approach more Pd atoms rather than Al atoms in small Pd[Formula: see text]Al clusters. Pd[Formula: see text]AlCO clusters have higher average binding energies than the corresponding small Pd[Formula: see text]CO clusters except for PdCO. AlCO and Pd3AlCO clusters possess better kinetic stability than their neighbors by the HOMO–LUMO gaps. Except for Pd6clusters, CO molecule prefers to adsorb on small Pd[Formula: see text] clusters rather than Pd[Formula: see text]Al clusters. Both the Al–Pd bonding in Pd[Formula: see text]Al clusters and C–Pd bonding in Pd[Formula: see text]AlCO clusters have certain covalent characters.
A Recognition Model of Driving Risk Based on Belief Rule-Base Methodology
Authors: Sun Chuan , Wu Chaozhong , Chu Duanfeng , Lu Zhenji , Tan Jian , Wang Jianyu
Published: April 2018

This paper aims to recognize driving risks in individual vehicles online based on a data-driven methodology. Existing advanced driver assistance systems (ADAS) have difficulties in effectively processing multi-source heterogeneous driving data. Furthermore, parameters adopted for evaluating the driving risk are limited in these systems. The approach of data-driven modeling is investigated in this study for utilizing the accumulation of on-road driving data. A recognition model of driving risk based on belief rule-base (BRB) methodology is built, predicting driving safety as a function of driver characteristics, vehicle state and road environment conditions. The BRB model was calibrated and validated using on-road data from 30 drivers. The test results show that the recognition accuracy of our proposed model can reach about 90% in all situations with three levels (none, medium, large) of driving risks. Furthermore, the proposed simplified model, which provides real-time operation, is implemented in a vehicle driving simulator as a reference for future ADAS and belongs to research on artificial intelligence (AI) in the automotive field.
Real-Time Pedestrian Detection Using Convolutional Neural Networks
Authors: Kuang Ping , Ma Tingsong , Li Fan , Chen Ziwei
Published: April 2018

Pedestrian detection provides manager of a smart city with a great opportunity to manage their city effectively and automatically. Specifically, pedestrian detection technology can improve our secure environment and make our traffic more efficient. In this paper, all of our work both modification and improvement are made based on YOLO, which is a real-time Convolutional Neural Network detector. In our work, we extend YOLO’s original network structure, and also give a new definition of loss function to boost the performance for pedestrian detection, especially when the targets are small, and that is exactly what YOLO is not good at. In our experiment, the proposed model is tested on INRIA, UCF YouTube Action Data Set and Caltech Pedestrian Detection Benchmark. Experimental results indicate that after our modification and improvement, the revised YOLO network outperforms the original version and also is better than other solutions.
COMPARISON PRINCIPLES FOR HADAMARD-TYPE FRACTIONAL DIFFERENTIAL EQUATIONS
Authors: YIN CHUNTAO , MA LI , LI CHANGPIN
Published: April 2018

The aim of this paper is to establish the comparison principles for differential equations involving Hadamard-type fractional derivatives. First, the continuous dependence of solutions on the right-hand side functions of Hadamard-type fractional differential equations (HTFDEs) is proposed. Then, we state and prove the first and second comparison principles for HTFDEs, respectively. The corresponding examples are provided as well.
SELF-SIMILARITY AND LIPSCHITZ EQUIVALENCE OF UNIONS OF CANTOR SETS
Authors: LIU CHUNTAI
Published: April 2018

Self-similarity and Lipschitz equivalence are two basic and important properties of fractal sets. In this paper, we consider those properties of the union of Cantor set and its translate. We give a necessary and sufficient condition that the union is a self-similar set. Moreover, we show that the union satisfies the strong separation condition if it is of the self-similarity. By using the augment tree, we characterize the Lipschitz equivalence between Cantor set and the union of Cantor set and its translate.
Algorithm for Searching an Equilibrium in a Routing Game with Piecewise Constant Cost Functions
Authors: Parfenov Andrey
Published: April 2018

We consider nonatomic routing games which are used to model transportation systems with a large number of agents and suggest an algorithm to search for the user equilibrium in such games, which is a generalization of the notion of Nash equilibrium. In general, finding a user equilibrium in routing games is computationally a hard problem. We consider the following subclass of routing games: games with piecewise constant cost functions, and construct an algorithm finding equilibrium in such games. This algorithm is based on the potential function method and the method of piecewise linear (PWL) costs enumeration which finds min-cost flow in a network with PWL cost functions. If each cost function increases, then the complexity of our algorithm is polynomial in the parameters of the network. But if some cost functions have decreasing points, then the complexity is exponential by the number of such points.
ProBAPred: Inferring protein–protein binding affinity by incorporating protein sequence and structural features
Authors: Lu Bangli , Li Chen , Chen Qingfeng , Song Jiangning
Published: April 2018

Protein-protein binding interaction is the most prevalent biological activity that mediates a great variety of biological processes. The increasing availability of experimental data of protein–protein interaction allows a systematic construction of protein–protein interaction networks, significantly contributing to a better understanding of protein functions and their roles in cellular pathways and human diseases. Compared to well-established classification for protein–protein interactions (PPIs), limited work has been conducted for estimating protein–protein binding free energy, which can provide informative real-value regression models for characterizing the protein–protein binding affinity. In this study, we propose a novel ensemble computational framework, termed ProBAPred (Protein–protein Binding Affinity Predictor), for quantitative estimation of protein–protein binding affinity. A large number of sequence and structural features, including physical–chemical properties, binding energy and conformation annotations, were collected and calculated from currently available protein binding complex datasets and the literature. Feature selection based on the WEKA package was performed to identify and characterize the most informative and contributing feature subsets. Experiments on the independent test showed that our ensemble method achieved the lowest Mean Absolute Error (MAE; 1.657[Formula: see text]kcal/mol) and the second highest correlation coefficient ([Formula: see text]), compared with the existing methods. The datasets and source codes of ProBAPred, and the supplementary materials in this study can be downloaded at http://lightning.med.monash.edu/probapred/ for academic use. We anticipate that the developed ProBAPred regression models can facilitate computational characterization and experimental studies of protein–protein binding affinity.
SUBSTITUTES OR COMPLEMENTS? THE ROLE OF CORPORATE INCUBATOR SUPPORT AND INNOVATION CLIMATE FOR INNOVATIVE BEHAVIOR IN THE HOSTING FIRM
Authors: KRUFT TOBIAS , GAMBER MICHAEL , KOCK ALEXANDER
Published: April 2018

Incubation of organisations by corporate incubators is currently regaining attention as a key way to foster innovation. However, understanding of how corporate incubators affect employee’s innovative behaviour in the host company is still limited. This study aims to fill this gap by examining the relationship between corporate incubator influence and innovative work behaviour and how this is moderated by innovation climate. Using a multi-level regression with 1,202 participants nested in 100 organisational units of a large, international company, the study shows that corporate incubators and innovation climate significantly affect innovative work behaviour. Further, we found that shared and individual perceptions of innovation climate moderate incubator influence differently. In order to improve innovative work behaviour, corporate incubators can compensate a weak innovation climate while strengthening the impact of individual perceptions of innovation climate on innovative behaviour, which introduces new ways of how companies are able to improve their innovativeness.
Differential associations between plasma concentrations of insulin and glucose and intestinal expression of key genes involved in chylomicron metabolism
Authors: Drouin-Chartier Jean-Philippe , Tremblay André J , Lemelin Valéry , Lamarche Benoît , Couture Patrick
Published: April 2018

The mechanisms underlying the oversecretion of apolipoprotein (apo)B-48-containing triglyceride-rich lipoproteins (TRL) in insulin-resistance (IR) states in humans remain to be fully understood. The objective of this study was to evaluate the association between the plasma levels of insulin and glucose and the intestinal expression of key genes involved in chylomicron metabolism in a large sample of nondiabetic men displaying various degrees of IR. Duodenal biopsies were obtained by gastroduodenoscopy in 127 men free of intestinal disease. Gene expression was measured using quantitative PCR in duodenal samples. Plasma insulin and glucose concentrations were measured in the fasting state. Postprandial TRL apoB-48 kinetics were measured using a primed-constant infusion of l-[5,5,5-D3]leucine for 12 h in a subgroup of 75 subjects maintained in a constant fed state. Plasma insulin levels were negatively associated with intestinal expression of ACS1 (standard β = −0.20, P = 0.007), DGAT1 (β = −0.18, P = 0.001), DGAT2 (β = −0.20, P = 0.02), and MTP (β = −0.27, P = 0.0005), whereas glucose levels were positively associated with MTP expression (β = 0.15, P = 0.04) independent of age, BMI, waist circumference, dietary intake, and duodenal expression of SREBP1c. Insulin levels, but not glucose concentrations, were positively correlated with postprandial TRL apoB-48 production rate ( r = 0.24, P = 0.04) and pool size ( r = 0.27, P = 0.03). In conclusion, plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism. These results suggest that alterations in intestinal lipoprotein metabolism associated with IR may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency.

NEW & NOTEWORTHY We demonstrate that plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism in men. For instance, intestinal expression of MTP is negatively associated with plasma insulin concentrations and positively associated with plasma glucose concentrations. Alterations in intestinal lipoprotein metabolism associated with insulin resistance may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency.
Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis
Authors: Waters David W. , Blokland Kaj E. C. , Pathinayake Prabuddha S. , Burgess Janette K. , Mutsaers Steven E. , Prele Cecilia M. , Schuliga Michael , Grainge Christopher L. , Knight Darryl A.
Published: April 2018

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause with a median survival of only three years. Little is known about the mechanisms that precede the excessive collagen deposition seen in IPF, but cellular senescence has been strongly implicated in disease pathology. Senescence is a state of irreversible cell-cycle arrest accompanied by an abnormal secretory profile and is thought to play a critical role in both development and wound repair. Normally, once a senescent cell has contributed to wound repair, it is promptly removed from the environment via infiltrating immune cells. However, if immune clearance fails, the persistence of senescent cells is thought to drive disease pathology through their altered secretory profile. One of the major cell types involved in wound healing is fibroblasts, and senescent fibroblasts have been identified in the lungs of patients with IPF and in fibroblast cultures from IPF lungs. The question of what is driving abnormally high numbers of fibroblasts into senescence remains unanswered. The transcription factor signal transducer and activator of transcription 3 (STAT3) plays a role in a myriad of processes, including cell-cycle progression, gene transcription, as well as mitochondrial respiration, all of which are dysregulated during senescence. Activation of STAT3 has previously been shown to correlate with IPF progression and therefore is a potential molecular target to modify early-stage senescence and restore normal fibroblast function. This review summarizes what is presently known about fibroblast senescence in IPF and how STAT3 may contribute to this phenotype.
Effects of morphine on respiratory load detection, load magnitude perception, and tactile sensation in obstructive sleep apnea
Authors: Tomazini Martins Rodrigo , Carberry Jayne C. , Gandevia Simon C. , Butler Jane E. , Eckert Danny J.
Published: April 2018

Pharyngeal and respiratory sensation is impaired in obstructive sleep apnea (OSA). Opioids may further diminish respiratory sensation. Thus protective pharyngeal neuromuscular and arousal responses to airway occlusion that rely on respiratory sensation could be impaired with opioids to worsen OSA severity. However, little is known about the effects of opioids on upper airway and respiratory sensation in people with OSA. This study was designed to determine the effects of 40 mg of MS-Contin on tactile sensation, respiratory load detection, and respiratory magnitude perception in people with OSA during wakefulness. A double-blind, randomized, crossover design (1 wk washout) was used. Twenty-one men with untreated OSA (apnea/hypopnea index = 26 ± 17 events/h) recruited from a larger clinical study completed the protocol. Tactile sensation using von Frey filaments on the back of the hand, internal mucosa of the cheek, uvula, and posterior pharyngeal wall were not different between placebo and morphine [e.g., median (interquartile range) posterior wall = 0.16 (0.16, 0.4) vs. 0.4 (0.14, 1.8) g, P = 0.261]. Similarly, compared with placebo, morphine did not alter respiratory load detection thresholds for nadir mask pressure detected = −2.05 (−3.37, −1.55) vs. −2.19 (−3.36, −1.41) cmH2O, P = 0.767], or respiratory load magnitude perception [mean ± SD Borg scores during a 5 resistive load (range: 5–126 cmH2O·l−1·s−1) protocol = 4.5 ± 1.6 vs. 4.2 ± 1.2, P = 0.347] but did reduce minute ventilation during quiet breathing (11.4 ± 3.3 vs. 10.7 ± 2.6 l/min, P < 0.01). These findings indicate that 40 mg of MS-Contin does not systematically impair tactile or respiratory sensation in men with mild to moderate, untreated OSA. This suggests that altered respiratory sensation to acute mechanical stimuli is not likely to be a mechanism that contributes to worsening of OSA with a moderate dose of morphine.

NEW & NOTEWORTHY Forty milligrams of MS-Contin does not alter upper airway tactile sensation, respiratory load detection thresholds, or respiratory load magnitude perception in people with obstructive sleep apnea but does decrease breathing compared with placebo during wakefulness. Despite increasing concerns of harm with opioids, the current findings suggest that impaired respiratory sensation to acute mechanical stimuli with this dose of MS-Contin is unlikely to be a direct mechanism contributing to worsening sleep apnea severity in people with mild-to-moderate disease.
Arachidonic acid supplementation transiently augments the acute inflammatory response to resistance exercise in trained men
Authors: Markworth James F. , D'Souza Randall F. , Aasen Kirsten M. M. , Mitchell Sarah M. , Durainayagam Brenan R. , Sinclair Andrew J. , Peake Jonathan M. , Egner Ingrid M. , Raastad Truls , Cameron-Smith David , Mitchell Cameron J.
Published: April 2018

Strenuous exercise can result in skeletal muscle damage, leading to the systemic mobilization, activation, and intramuscular accumulation of blood leukocytes. Eicosanoid metabolites of arachidonic acid (ARA) are potent inflammatory mediators, but whether changes in dietary ARA intake influence exercise-induced inflammation is not known. This study investigated the effect of 4 wk of dietary supplementation with 1.5 g/day ARA ( n = 9, 24 ± 1.5 yr) or corn-soy oil placebo ( n = 10, 26 ± 1.3 yr) on systemic and intramuscular inflammatory responses to an acute bout of resistance exercise (8 sets each of leg press and extension at 80% one-repetition maximum) in previously trained men. Whole EDTA blood, serum, peripheral blood mononuclear cells (PMBCs), and skeletal muscle biopsies were collected before exercise, immediately postexercise, and at 2, 4, and 48 h of recovery. ARA supplementation resulted in higher exercise-stimulated serum creatine kinase activity [incremental area under the curve (iAUC) P = 0.046] and blood leukocyte counts (iAUC for total white cells, P < 0.001; neutrophils: P = 0.007; monocytes: P = 0.015). The exercise-induced fold change in peripheral blood mononuclear cell mRNA expression of interleukin-1β ( IL1B), CD11b ( ITGAM), and neutrophil elastase ( ELANE), as well as muscle mRNA expression of the chemokines interleukin-8 ( CXCL8) and monocyte chemoattractant protein 1 ( CCL2) was also greater in the ARA group than placebo. Despite this, ARA supplementation did not influence the histological presence of leukocytes within muscle, perceived muscle soreness, or the extent and duration of muscle force loss. These data show that ARA supplementation transiently increased the inflammatory response to acute resistance exercise but did not impair recovery.

NEW & NOTEWORTHY Daily arachidonic acid supplementation for 4 wk in trained men augmented the acute systemic and intramuscular inflammatory response to a subsequent bout of resistance exercise. Greater exercise-induced inflammatory responses in men receiving arachidonic acid supplementation were not accompanied by increased symptoms of exercise-induced muscle damage. Although increased dietary arachidonic acid intake does not appear to influence basal inflammation in humans, the acute inflammatory response to exercise stress is transiently increased following arachidonic acid supplementation.
Power reserve following ramp-incremental cycling to exhaustion: implications for muscle fatigue and function
Authors: Hodgson Michael D. , Keir Daniel A. , Copithorne David B. , Rice Charles L. , Kowalchuk John M.
Published: April 2018

In ramp-incremental cycling exercise, some individuals are capable of producing power output (PO) in excess of that produced at their limit of tolerance (LoT) whereas others cannot. This study sought to describe the 1) prevalence of a “power reserve” within a group of young men ( n = 21; mean ± SD: age 25 ± 4 yr; V̇o2max 45 ± 8 ml·kg−1·min−1); and 2) muscle fatigue characteristics of those with and without a power reserve. “Power reserve” (ΔPReserve) was determined as the difference between peak PO achieved during a ramp-incremental test to exhaustion and maximal, single-leg isokinetic dynamometer power determined within 45 s of completing the ramp-incremental test. Between-group differences in pre- vs. postexercise changes in voluntary and electrically stimulated single-leg muscle force production measures (maximal voluntary contraction torque, voluntary activation, maximal isotonic velocity and isokinetic power; 1-, 10-, 50-Hz torque; and 10/50-Hz ratio), V̇o2max, and constant-PO cycling time-to-exhaustion also were assessed. Frequency distribution analysis revealed a dichotomy in the prevalence of a power reserve within the sample resulting in two groups: 1) “No Reserve” (NRES: power reserve <5%; n = 10) and 2) “Reserve” (RES: power reserve >15%; n = 11). At the LoT, all participants had achieved V̇o2max. Muscle fatigue was evident in both groups, although the NRES group had greater reductions ( P < 0.05) in 10-Hz peak torque (PT), 10/50 Hz ratio, and maximal velocity. Time to the LoT during the constant PO test was 22 ± 16% greater ( P < 0.05) in RES (116 ± 19 s; PO = 317 ± 52 W) than in NRES (90 ± 23 s; PO = 337 ± 71 W), despite similar ramp-incremental exercise durations and V̇o2max between groups. Compared with the RES group, the NRES group accrued greater peripheral muscle fatigue at the LoT, suggesting that the mechanisms contributing to exhaustion in a ramp-incremental protocol are not uniform.

NEW & NOTEWORTHY This study demonstrates that the mechanisms associated with the limit of tolerance during ramp-incremental cycling exercise differ between those who are capable of generating power output in excess of that at exercise termination vs. those who are not. Those without a “power reserve” exhibit greater peripheral muscle fatigue and reduced muscle endurance, supporting the hypothesis that exhaustion occurs at a specific level of neuromuscular fatigue. In contrast, those with a power reserve likely are limited by other mechanisms.
Kinematic patterns while walking on a slope at different speeds
Authors: Dewolf A. H. , Ivanenko Y. , Zelik K. E. , Lacquaniti F. , Willems P. A.
Published: April 2018

During walking, the elevation angles of the thigh, shank, and foot (i.e., the angle between the segment and the vertical) covary along a characteristic loop constrained on a plane. Here, we investigate how the shape of the loop and the orientation of the plane, which reflect the intersegmental coordination, change with the slope of the terrain and the speed of progression. Ten subjects walked on an inclined treadmill at different slopes (between −9° and +9°) and speeds (from 0.56 to 2.22 m/s). A principal component analysis was performed on the covariance matrix of the thigh, shank, and foot elevation angles. At each slope and speed, the variance accounted for by the two principal components was >99%, indicating that the planar covariation is maintained. The two principal components can be associated to the limb orientation (PC1*) and the limb length (PC2*). At low walking speeds, changes in the intersegmental coordination across slopes are characterized mainly by a change in the orientation of the covariation plane and in PC2* and to a lesser extent, by a change in PC1*. As speed increases, changes in the intersegmental coordination across slopes are more related to a change in PC1 *, with limited changes in the orientation of the plane and in PC 2*. Our results show that the kinematic patterns highly depend on both slope and speed.

NEW & NOTEWORTHY In this paper, changes in the lower-limb intersegmental coordination during walking with slope and speed are linked to changes in the trajectory of the body center of mass. Modifications in the kinematic pattern with slope depend on speed: at slow speeds, the net vertical displacement of the body during each step is related to changes in limb length and orientation. When speed increases, the vertical displacement is mostly related to a change in limb orientation.
Decreased Retinal Thickness in Type 1 Diabetic Children with Signs of Nonproliferative Diabetic Retinopathy
Authors: Ruiz-Ocaña P. , Espinoza Requena P. , Alonso-Ojembarrena A. , Alemany Márquez P. , Jiménez Carmona S. , Lechuga-Sancho A. M.
Published: April 2018

The retina functions as a neurovascular unit. How early vascular alterations affect neuronal layers remains controversial; early vascular failure could lead to edema increasing retinal thicknesses, but alternatively neuronal loss could lead to reduced retinal thickness. Objective. To evaluate retinal thickness in a cohort of pediatric patients with type 1 diabetes mellitus (PwT1DM) and to analyze differences according to the presence or absence of nonproliferative diabetic retinopathy (NPDR), poor metabolic control, and diabetes duration. Patients and Methods. We performed retinographies and optical coherence tomography (OCT) (TOPCON 3D1000®) to PwT1DM followed at our center and healthy controls. Measurements of the control group served to calculate reference values. Results. 59 PwT1DM (age 12.51 ± 2.59) and 22 healthy controls (age 10.66 ± 2.51) volunteered. Only two PwT1DM, both adolescents with poor metabolic control, presented NPRD. Both showed decreased thicknesses and retinal volumes. The odds ratio of having decreased retinal thickness when signs of NPDR were present was 11.72 (95% IC 1.16–118.28; p=0.036). Conclusions. PwT1DM with NPDR have increased odds of decreased retinal thicknesses and volumes. Whether these changes are reversible by improving metabolic control or not remains to be elucidated.
Characterization of Transcription Termination-Associated RNAs: New Insights into their Biogenesis, Tailing, and Expression in Primary Tumors
Authors: Laudadio Ilaria , Formichetti Sara , Gioiosa Silvia , Klironomos Filippos , Rajewsky Nikolaus , Macino Giuseppe , Carissimi Claudia , Fulci Valerio
Published: April 2018

Next-generation sequencing has uncovered novel classes of small RNAs (sRNAs) in eukaryotes, in addition to the well-known miRNAs, siRNAs, and piRNAs. In particular, sRNA species arise from transcription start sites (TSSs) and the transcription termination sites (TTSs) of genes. However, a detailed characterization of these new classes of sRNAs is still lacking. Here, we present a comprehensive study of sRNAs derived from TTSs of expressed genes (TTSa-RNAs) in human cell lines and primary tissues. Taking advantage of sRNA-sequencing, we show that TTSa-RNAs are present in the nuclei of human cells, are loaded onto both AGO1 and AGO2, and their biogenesis does not require DICER and AGO2 endonucleolytic activity. TTSa-RNAs display a strong bias against a G residue in the first position at 5′ end, a known feature of AGO-bound sRNAs, and a peculiar oligoA tail at 3′ end. AGO-bound TTSa-RNAs derive from genes involved in cell cycle progression regulation and DNA integrity checkpoints. Finally, we provide evidence that TTSa-RNAs can be detected by sRNA-Seq in primary human tissue, and their expression increases in tumor samples as compared to nontumor tissues, suggesting that in the future, TTSa-RNAs might be explored as biomarker for diagnosis or prognosis of human malignancies.
Network Coding for Backhaul Offloading in D2D Cooperative Fog Data Networks
Authors: Quinton Ben , Aboutorab Neda
Published: April 2018

Future distributed data networks are expected to be assisted by users cooperation and coding schemes. Given the explosive increase in the end‐users’ demand for download of the content from the servers, in this paper, the implementation of instantly decodable network coding (IDNC) is considered in full‐duplex device‐to‐device (D2D) cooperative fog data networks. In particular, this paper is concerned with designing efficient transmission schemes to offload traffic from the expensive backhaul of network servers by employing IDNC and users cooperation. The generalized framework where users send request for multiple packets and the transmissions are subject to erasure is considered. The optimal problem formulation is presented using the stochastic shortest path (SSP) technique over the IDNC graph with induced subgraphs. However, as the optimal solution suffers from the intractability of being NP‐hard, it is not suitable for real‐time communications. The complexity of the problem is addressed by presenting a greedy heuristic algorithm used over the proposed graph model. The paper shows that by implementing IDNC in a full‐duplex cooperative D2D network model significant reduction in the number of downloads required from the servers can be achieved, which will result in offloading of the backhaul servers and thus saving valuable servers’ resources. It is also shown that the performance of the proposed heuristic algorithm is very close to the optimal solution with much lower computational complexity.