bluuebunny/crossref_metadata_2025 huggingface dataset:
Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia
Authors: Vaillant Fanny , Lauzier Benjamin , Ruiz Matthieu , Shi Yanfen , Lachance Dominic , Rivard Marie-Eve , Bolduc Virginie , Thorin Eric , Tardif Jean-Claude , Des Rosiers Christine
Published: August 2016

While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR−/−). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired ( P < 0.001) contractile function (aortic flow: −45%; cardiac output: −34%; stroke volume: −35%) and glycolysis (−24%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine ( O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression.
CCSPG38A polymorphism environment interactions regulate CCSP levels differentially in COPD
Authors: Knabe Lucie , Varilh Jessica , Bergougnoux Anne , Gamez Anne-Sophie , Bonini Jennifer , Pommier Alexandra , Petit Aurélie , Molinari Nicolas , Vachier Isabelle , Taulan-Cadars Magali , Bourdin Arnaud
Published: August 2016

Impaired airway homeostasis in chronic obstructive pulmonary disease (COPD) could be partly related to club cell secretory protein (CCSP) deficiency. We hypothesize that CCSP G38A polymorphism is involved and aim to examine the influence of the CCSP G38A polymorphism on CCSP transcription levels and its regulatory mechanisms. CCSP genotype and CCSP levels in serum and sputum were assessed in 66 subjects with stable COPD included in a 1-yr observational study. Forty-nine of them had an exacerbation. In an in vitro study, the impact on the CCSP promoter of 38G wild-type or 38A variant was assessed. BEAS-2B cells were transfected by either the 38G or 38A construct, in the presence/absence of cigarette smoke extract (CSE) or lipopolysaccharides (LPS). Cotransfections with modulating transcription factors, p53 and Nkx2.1, identified by in silico analysis by using ConSite and TFSEARCH were conducted. A allele carrier COPD patients had lower serum and sputum CCSP levels, especially among active smokers, and a decreased body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) score. In vitro, baseline CCSP transcription levels were similar between the wild and variant constructs. CSE decreased more profoundly the CCSP transcription level of 38A transfected cells. The opposite effect was observed with p53 cotransfection. LPS stimulation induced CCSP repression in 38A promoter transfected cells. Cotransfection with Nkx2.1 significantly activated the CCSP promoters irrespective of the polymorphism. Circulating CCSP levels are associated with smoking and the CCSP G38A polymorphism. CSE, LPS, and the Nkx2.1 and p53 transcription factors modulated the CCSP promoter efficiency. The 38A polymorphism exaggerated the CCSP repression in response to p53 and CSE.
Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma
Authors: Nakano Satoko , Nakamuro Takako , Yokoyama Katsuhiko , Kiyosaki Kunihiro , Kubota Toshiaki
Published: August 2016

Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections.Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration.Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP.Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP.
A Simple Method of Preparation of High Silica Zeolite Y and Its Performance in the Catalytic Cracking of Cumene
Authors: Liu Zhanjun , Shi Chenxi , Wu Dan , He Shixuan , Ren Bo
Published: August 2016

A series of high silicon zeolites Y were prepared through direct synthetic method by using silica sol as the silicon source and sodium aluminate as the aluminum source. The effects of alkalinity and crystallization time of the process of synthesis were investigated. To separately reveal the crystalline structure, element content, morphology, and surface areas, the as-synthesized zeolite Y was characterized by powder X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy (SEM), and N2adsorption-desorption isotherms (BET). The results show the as-synthesized zeolite Y with high relative crystallization and uniform morphology; the SiO2/Al2O3ratio was about 4.54~6.46. For an application, the zeolite cracking activity was studied with cumene as the probe molecules.
Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients withPneumocystisPneumonia
Authors: Sun Jia , Su Junwei , Xie Yirui , Yin Michael T. , Huang Ying , Xu Lijun , Zhou Qihui , Zhu Biao
Published: August 2016

Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients.Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients withPneumocystispneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve.Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P=0.008,R2=0.258), HBDH (P=0.001,R2=0.335), and Ferritin (P=0.005,R2=0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2> 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56,P<0.001; 1.11 ± 0.72,P=0.043), larger AUC (95% CI 0.781–1.000,P<0.001; 95% CI 0.592–0.917,P=0.043), and more significantly inverse correlation with the oxygenation index.Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.
Membrane Stabilization and Detoxification of Acetaminophen‐Mediated Oxidative Onslaughts in the Kidneys of Wistar Rats by Standardized Fraction of Zea mays L. (Poaceae), Stigma maydis
Authors: Sabiu S. , O’Neill F. H. , Ashafa A. O. T.
Published: August 2016

This study evaluated membrane stabilization and detoxification potential of ethyl acetate fraction of Zea mays L., Stigma maydis in acetaminophen‐induced oxidative onslaughts in the kidneys of Wistar rats. Nephrotoxic rats were orally pre‐ and posttreated with the fraction and vitamin C for 14 days. Kidney function, antioxidative and histological analyses were thereafter evaluated. The acetaminophen‐mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium, and tissue levels of oxidized glutathione, protein‐oxidized products, lipid peroxidized products, and fragmented DNA were dose‐dependently assuaged in the fraction‐treated animals. The fraction also markedly improved creatinine clearance rate, glutathione, and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the fraction. The observed effects compared favorably with that of vitamin C and are informative of the fraction’s ability to prevent progression of renal pathological conditions and preserve kidney functions as evidently supported by the histological analysis. Although the effects were prominently exhibited in the fraction‐pretreated groups, the overall data from the present findings suggest that the fraction could prevent or extenuate acetaminophen‐mediated oxidative renal damage via fortification of antioxidant defense mechanisms.
Hyperemesis Gravidarum in Undiagnosed Gitelman’s Syndrome
Authors: Acelajado Maria Czarina , Culpepper R. Michael , Bolton III Wilburn D.
Published: August 2016

Introduction. Gitelman’s syndrome (GS) is an autosomal recessive inherited defect in the thiazide-sensitive sodium-chloride cotransporter (NCCT) in the renal distal convoluted tubule. Physiologic changes of pregnancy promote renal potassium wasting, but serum potassium levels are kept in the physiologic range by increased levels of progesterone, which resist kaliuresis. In the presence of GS, this compensatory mechanism is easily overwhelmed, resulting in profound hypokalemia. We present a case of an 18-year-old primigravida with undiagnosed GS who presented with hyperemesis gravidarum in her 7th week of pregnancy. This report adds to the limited experience with GS in pregnancy as reported in literature and provides additional information on medical management that leads to successful maternal and fetal outcomes.
Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus
Authors: Reyes-Haro Daniel , Labrada-Moncada Francisco Emmanuel , Varman Durairaj Ragu , Krüger Janina , Morales Teresa , Miledi Ricardo , Martínez-Torres Ataúlfo
Published: August 2016

Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (−23%) and dentate gyrus (−48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression.
Design of Blast-Loaded Glazing Windows and Facades: A Review of Essential Requirements towards Standardization
Authors: Larcher Martin , Arrigoni Michel , Bedon Chiara , van Doormaal J. C. A. M. , Haberacker Christof , Hüsken Götz , Millon Oliver , Saarenheimo Arja , Solomos George , Thamie Laurent , Valsamos Georgios , Williams Andy , Stolz Alexander
Published: August 2016

The determination of the blast protection level of laminated glass windows and facades is of crucial importance, and it is normally done by using experimental investigations. In recent years numerical methods have become much more powerful also with respect to this kind of application. This paper attempts to give a first idea of a possible standardization concerning such numerical simulations. Attention is drawn to the representation of the blast loading and to the proper description of the behaviour of the material of the mentioned products, to the geometrical meshing, and to the modelling of the connections of the glass components to the main structure. The need to validate the numerical models against reliable experimental data, some of which are indicated, is underlined.
Adaptive Tracking Control of Second-Order Multiagent Systems with Jointly Connected Topologies
Authors: Chen Lei , Qin Kaiyu , Hu Jiangping
Published: August 2016

This paper considers a consensus problem of leader-following multiagent system with unknown dynamics and jointly connected topologies. The multiagent system includes a self-active leader with an unknown acceleration and a group of autonomous followers with unknown time-varying disturbances; the network topology associated with the multiagent system is time varying and not strongly connected during each time interval. By using linearly parameterized models to describe the unknown dynamics of the leader and all followers, we propose a decentralized adaptive tracking control protocol by using only the relative position measurements and analyze the stability of the tracking error and convergence of the adaptive parameter estimators with the help of Lyapunov theory. Finally, some simulation results are presented to demonstrate the proposed adaptive tracking control.
The Effect of Calcination Temperature on Structure and Photocatalytic Properties of WO3/TiO2Nanocomposites
Authors: Mioduska Joanna , Zielińska-Jurek Anna , Janczarek Marcin , Hupka Jan
Published: August 2016

Series of WO3/TiO2nanocomposites were obtained by hydrothermal method followed by calcination in the temperature range from 400°C to 900°C. The characteristics of photocatalysts by X-ray diffractometry (XRD), scanning electron microscope (SEM), and diffuse reflectance spectroscopy (DRS) showed that increasing the calcination temperature from 400 to 900°C resulted in change of photocatalytic activity under UV-Vis light. Moreover, the amount of WO3crystalline phase and amorphous phase in WO3/TiO2aggregates, as revealed by XRD analysis, was dependent on the calcination temperature. The WO3/TiO2samples with 8 mol% load of WO3in respect to TiO2calcinated at 500 and 800°C possess the highest photocatalytic activity in reaction of phenol degradation, which is about 1.2 and 1.5 times that with calcination at 400°C. The increase in calcination temperature above 400°C resulted in increase of WO3crystallinity and reduction of the amount of amorphous phase in the nanocomposite structure. Moreover, the annealing of nanocomposites above 700°C decreases the value of optical band gap energies of obtained WO3/TiO2nanomaterials.
A Survey of the DVB-T Spectrum: Opportunities for Cognitive Mobile Users
Authors: Csurgai-Horváth László , Rieger István , Kertész József
Published: August 2016

Cognitive radio (CR) systems are designed to utilize the available radio spectrum in an efficient and intelligent manner. Terrestrial Digital Video Broadcasting (DVB-T) frequency bands are one of the future candidates for cognitive radio applications especially because after digital television transition the TV white spaces (TVWS) became available for radio communication. This paper deals with the survey of the DVB-T spectrum; wideband measurements were performed on mobile platform in order to study the variation of the radio signal power in city area aboard a moving vehicle. The measurement environment was a densely built-in region where the proper DVB-T receiving was guaranteed by three TV transmitters, utilizing three central channel frequencies using 610, 746, and 770 MHz. In our paper the methods, the applied antenna, and measurement devices will be presented together with simulated and measured fading statistics. The final result is an estimation of the cognitive DVB-T spectrum utilization opportunity; furthermore a scenario is also proposed for secondary channel usage.
Clinical Outcomes of Endoscopic Submucosal Dissection for Early Esophageal Squamous Cell Neoplasms: A Retrospective Single-Center Study in China
Authors: Chen Yanfang , Zhao Ye , Zhao Xiaojing , Shi Ruihua
Published: August 2016

Aims. To retrospectively analyze the clinical outcomes for a large number of endoscopic submucosal dissections (ESDs) in early esophageal squamous cell neoplasms (ESCNs) at the First Affiliated Hospital of Nanjing Medical University.Patients and Methods. From January 2010 to February 2014, 296 patients (mean age 61.4 years, range 31–85 years; 202 men) with 307 early ESCNs (79 intramucosal invasive esophageal squamous cell carcinomas (ESCCs) and 228 high-grade intraepithelial neoplasia (HGIN) cases) were included from a total of 519 consecutive patients who were treated by esophageal ESD at our hospital. The primary end points of the study were rates of en bloc resection and complete resection. Secondary end points were complications, residual and recurrence rates, and mortality during follow-up.Results. The en bloc resection rate and complete resection rate were 93.5% and 78.2%, respectively. Complications included strictures (8.4%), perforations (1.0%), and bleedings (0.7%). Twenty-seven (9.1%) patients experienced residual and 18 (6.1%) patients experienced recurrence during a mean follow-up period of 30 months. Thirteen patients died from causes unrelated to ESCC, and no cancer-related death was observed.Conclusions. Our study showed that ESD is a successful and relatively safe treatment for intramucosal invasive ESCC and HGIN, fulfilling the criteria of lymph node negative tumors. This should encourage clinicians to select ESD performed by experienced operators as a potential or even preferred treatment option for lesions amenable to endoscopic treatment.
A Rare Complication of Trimethoprim-Sulfamethoxazole: Drug Induced Aseptic Meningitis
Authors: Jha Pinky , Stromich Jeremiah , Cohen Mallory , Wainaina Jane Njeri
Published: August 2016

Drug induced aseptic meningitis is a rare but challenging diagnosis, most commonly reported with nonsteroidal anti-inflammatory drugs and antibiotics. Trimethoprim/sulfamethoxazole is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. Drug induced aseptic meningitis, when seen with trimethoprim/sulfamethoxazole, occurs predominantly in patients with some degree of immune compromise and is less commonly seen in immune competent individuals. The patient often exhibits the classic symptoms of meningitis. Early diagnosis is important, since the cessation of the antibiotic leads to rapid clinical improvement. Trimethoprim/sulfamethoxazole induced aseptic meningitis has been underreported to FDA/MED-WATCH program. Here we report two cases of trimethoprim/sulfamethoxazole: an immune competent individual and immune compromised individual, both of which presented with signs of meningitis and a negative infectious workup. Trimethoprim/sulfamethoxazole is an uncommon and mysterious adverse reaction to a commonly used antibiotic. It should be considered in the differential diagnosis of patients presenting with acute signs and symptoms of meningitis especially after infectious causes have been ruled out.
The Influence of Heating Time and Temperature on the Properties of CIGSSe Solar Cells
Authors: Flammini Marco Giacomo , Debernardi Nicola , Le Ster Maxime , Dunne Brendan , Bosman Johan , Theelen Mirjam
Published: August 2016

Nonencapsulated CIGSSe solar cells, with a silver grid, were exposed to different temperatures for various periods in order to measure the effect of the heat exposure in CIGSSe modules. The heat treatment time and temperature were varied during the experiments, which were executed at atmospheric conditions. In all the cases, after reaching a temperature of about 300°C, theIVmeasurement showed a reduction of 2-3% in terms ofVOCandJSC. This is confirmed, respectively, by Raman and EQE measurements as well. The efficiency drop was −7%, −29%, and −48%, respectively, for 30 seconds, 300 seconds, and 600 seconds of exposure time. With temperatures larger than 225°C, the series resistance starts to increase exponentially and a secondary barrier becomes visible in theIVcurve. This barrier prevents the extraction of electrons and consequently reducing the solar cells efficiency. Lock-in thermography demonstrated the formation of shunts on the mechanical scribes only for 300 and 600 seconds exposure times. The shunt resistance reduction is in the range of 5% for all time periods.
Atraumatic Restoration of Vertical Food Impaction with an Open Contact Using Flowable Composite Resin Aided by Cerclage Wire under Tension
Authors: Li Quan-Li , Ying Cao Chris , Xu Qiang-Jian , Xu Xiao-Hua , Yin Jia-Li
Published: August 2016

To date, treating vertical food impaction with open contact effectively, especially with an atraumatic therapy, remains a challenge. In this study, we developed a simple, atraumatic, and economic therapeutic measure to treat vertical food impaction. The scientific rationale of our therapeutic technique is to restore an intact and firm proximal contact with proper location and form relationships to prevent forceful interproximal wedging of food, which in turn protects interdental papilla. We performed the procedure using flowable composite resin or composite resin cement with the aid of a cerclage wire under tension to rebuild the contact area. The reported method is especially useful for some challenging clinical cases, such as food impaction after crown and inlay on onlay restoration, and some conventional treatment methods, such as contouring the marginal ridge and developmental grooves, are ineffective.
Disjoint Key Establishment Protocol for Wireless Sensor and Actor Networks
Authors: Ghafoor AtaUllah , Sher Muhammad , Imran Muhammad , Baig Imran
Published: August 2016

Key distribution is essential for providing secure communication between commercial and sensitive applications of wireless sensor and actor networks (WSANs). It becomes more challenging when any of the intermediate sensor nodes is compromised by the adversaries as the messages carrying secure keys will be exposed and links will be unreliable. This paper presents a Disjoint Key Establishment Protocol (DKEP) that does not require transmitting keys across the nodes. In DKEP, each node is preloaded with one row and one column from a matrix. After the deployment, indices for row and column are exchanged between the two nodes and values at intersection of row and column index will be used to calculate the key on each node. DKEP is verified by performing formal analysis using Rubin Logic and validated using simulations in NS-2. Simulation results demonstrate the effectiveness and efficiency of DKEP compared to contemporary schemes in terms of reducing storage and communication cost and improving resilience against node compromise attacks. Moreover, the proposed scheme is implemented in a group-based mobile application scenario for secure message exchange.
Behavior of Hollow Thin Welded Tubes Filled with Sand Slag Concrete
Authors: Ferhoune Noureddine , Senani Meriem , Guettala Abdelhamid
Published: August 2016

This paper presents the axial bearing capacity of thin welded rectangular steel stubs filled with concrete sand. A series of tests was conducted to study the behavior of short composite columns under axial compressive load; the cross section dimensions were 100 × 70 × 2 mm. A total of 20 stubs have been tested, as follows: 4 hollow thin welded tubes were tested to axial and eccentric load compression, 4 were filled with ordinary concrete appointed by BO columns, 6 were filled with concrete whose natural sand was completely substituted by a crystallized sand slag designated in this paper by BSI, and 6 were tucked in concrete whose natural sand was partially replaced by a crystallized sand slag called BSII. The main parameters studied are the height of the specimen (300 mm–500 mm), eccentricity of load and type of filling concrete. Based on test results obtained, it is confirmed that the length of the tubes has a considerable effect on the bearing capacity and the failure mode. In all test tubes, fracture occurred by the convex local buckling of steel section due to the outward thrust of the concrete; it was observed that the sand concrete improves the bearing capacity of tubes compounds compared to those filled with ordinary concrete.
Automated Search-Based Robustness Testing for Autonomous Vehicle Software
Authors: Betts Kevin M. , Petty Mikel D.
Published: August 2016

Autonomous systems must successfully operate in complex time-varying spatial environments even when dealing with system faults that may occur during a mission. Consequently, evaluating the robustness, or ability to operate correctly under unexpected conditions, of autonomous vehicle control software is an increasingly important issue in software testing. New methods to automatically generate test cases for robustness testing of autonomous vehicle control software in closed-loop simulation are needed. Search-based testing techniques were used to automatically generate test cases, consisting of initial conditions and fault sequences, intended to challenge the control software more than test cases generated using current methods. Two different search-based testing methods, genetic algorithms and surrogate-based optimization, were used to generate test cases for a simulated unmanned aerial vehicle attempting to fly through an entryway. The effectiveness of the search-based methods in generating challenging test cases was compared to both a truth reference (full combinatorial testing) and the method most commonly used today (Monte Carlo testing). The search-based testing techniques demonstrated better performance than Monte Carlo testing for both of the test case generation performance metrics: (1) finding the single most challenging test case and (2) finding the set of fifty test cases with the highest mean degree of challenge.
Ultrasonographic Diagnosis ofSchistosoma mansoniEggs in Rectum
Authors: Rodrigues Fabio G. , Campos Joao Batista , Toppa Nivaldo Hartung , Wexner Steven D. , Dasilva Giovanna
Published: August 2016

Schistosomiasis is a trematode infection endemic in more than 70 countries that affects an estimated 250 million people. We report the case of a 60-year-old healthy female referred for endoscopic ultrasound after rectal examination revealed granular lesions. Ultrasound revealed the presence of deep mucosal nodular lesions with calcified/hyperechoic inclusions. Histologic evaluation has confirmed the final diagnosis of chronic schistosomal colitis. In patients with nonspecific intestinal lesions without a suspected diagnosis of schistosomiasis, endoscopic ultrasound can be enlightening. Schistosomiasis is still an endemic infection in some parts of Brazil and other tropical regions, causing colorectal lesions with unspecific presentation.
A Review on Compliant Joint Mechanisms for Lower Limb Exoskeletons
Authors: Gálvez-Zúñiga Miguel A. , Aceves-López Alejandro
Published: August 2016

Lower limb exoskeletons are experiencing a rapid development that may suggest a prompt introduction to the market. These devices have an inherent close interaction with the human body; therefore, it is necessary to ensure user’s safety and comfort. The first exoskeletal designs used to represent the human joints as simple revolute joints. This approximation introduces an axial misalignment issue, which generates uncontrollable internal forces. A mathematical description of the said misalignments is provided to better understand the concept and its consequences. This review will only focus on mechanisms aiming to comply with its user.
Kinetics of Free Radical Polymerization of N-Substituted Amides and Their Structural Implications
Authors: Aldea Anca , Albu Ana-Maria , Nicolescu Alina , Tecuceanu Victorita
Published: August 2016

Two N-substituted amides (N-acryloyl morpholine and N-methyl-N-vinylacetamide) were polymerized in different solvents using radical initiator. The tacticity of obtained polymers was determined by 400 MHz1H-NMR and13C-NMR. At a given temperature, the syndiotacticity increased with increasing the solvent polarity. This solvent effect may be related to the hydrogen bonding interaction among solvent, monomer, and/or growing species. A peculiar aspect regards the steric hindrance at the nitrogen atom.
Stereocontrol of Methyl Methacrylate during Photoinduced Nitroxide-Mediated Polymerization in the Presence of Photosensitive Alkoxyamine
Authors: Su Juahui , Liu Xiaoxuan , Li Maijun , Zhang Ting , Cui Yanyan
Published: August 2016

Photosensitive alkoxyamine 2,2,6,6-tetramethyl-1-(1-phenylethoxy)piperidin-4-yl quinoline-2-carboxylate (PE-TEMPO-Q) was synthesized. Photochemical properties of PE-TEMPO-Q were studied to develop photoinduced nitroxide-mediated polymerization of methyl methacrylate (MMA). Rapid and facile polymerization at ambient temperature with PE-TEMPO-Q as an initiator was confirmed to proceed in a controlled mechanism based on the linear growth in molecular weight combined with relative narrow polydispersity index (1.4–1.8) of the resulting polymers. The stereochemistry of obtained polymers was also investigated, and the syndiotacticity slightly increased compared with the typical photopolymerization. Dual-controlled photopolymerization of MMA was achieved in the presence of synthesized alkoxyamine.
Numerical Analysis of Hydrodynamics for Bionic Oscillating Hydrofoil Based on Panel Method
Authors: Xue Gang , Liu Yanjun , Zhang Muqun , Ding Hongpeng
Published: August 2016

The kinematics model based on the Slender-Body theory is proposed from the bionic movement of real fish. The Panel method is applied to the hydrodynamic performance analysis innovatively, with the Gauss-Seidel method to solve the Navier-Stokes equations additionally, to evaluate the flexible deformation of fish in swimming accurately when satisfying the boundary conditions. A physical prototype to mimic the shape of tuna is developed with the revolutionized technology of rapid prototyping manufacturing. The hydrodynamic performance for rigid oscillating hydrofoil is analyzed with the proposed method, and it shows good coherence with the cases analyzed by the commercial softwareFluentand the experimental data from robofish. Furthermore, the hydrodynamic performance of coupled hydrofoil, which consisted of flexible fish body and rigid caudal fin, is analyzed with the proposed method. It shows that the caudal fin has great influence on trailing vortex shedding and the phase angle is the key factor on hydrodynamic performance. It is verified that the shape of trailing vortex is similar to the image of the motion curve at the trailing edge as the assumption of linear vortex plane under the condition of small downwash velocity. The numerical analysis of hydrodynamics for bionic movement based on the Panel method has certain value to reveal the fish swimming mechanism.
Study on Power Switching Process of a Hybrid Electric Vehicle with In-Wheel Motors
Authors: Wang Shaohua , He Chunrong , Ren Hao , Chen Long , Shi Dehua
Published: August 2016

Hybrid electric vehicles with in-wheel motors (IWM) achieve a variety of driving modes by two power sources—the engine and the IWM. One of the critical problems that exists in such vehicle is the different transient characteristics between the engine and the IWM. Therefore, switching processes between the power sources have noteworthy impacts on vehicle dynamics and driving performance. For the particular switching process of the pure electric mode to the engine driving mode, a specific control strategy coordinating clutch torque, motor torque, and engine torque was proposed to solve drivability issues caused by inconsistent responses of different power sources during the mode transition. The specific switching process could be described as follows: the engine was started by IWM with the clutch serving as a key enabling actuator, dynamic torque compensation through IWM was implemented after engine started, and, meanwhile, engine speed was controlled to track the target speed through the closed loop PID control strategy. The bench tests results showed that the vehicle jerk caused during mode switching was reduced and fast and smooth mode switching was realized, which leads to the improvement of vehicle’s riding comfort.
Chemomics‐Integrated Proteomics Analysis of Jie‐Geng‐Tang to Ameliorate Lipopolysaccharide‐Induced Acute Lung Injury in Mice
Authors: Tao Jin , Nie Yan , Hou Yuanyuan , Ma Xiaoyao , Ding Guoyu , Gao Jie , Jiang Min , Bai Gang
Published: August 2016

Jie‐Geng‐Tang (JGT), a classic and famous traditional Chinese medicine (TCM) prescription composed of Platycodon grandiflorum (Jacq.) A. DC. (PG) and Glycyrrhiza uralensis Fisch. (GU), is well known for “clearing heat and relieving toxicity” and its ability to “diffuse the lung and relieve sore throat.” However, the mechanism underlying its action remains unclear. In this study, potential anti‐inflammatory ingredients were screened and submitted to PharmMapper and the KEGG bioinformatics website to predict the target proteins and related pathways, respectively. Differentially expressed candidate proteins from acute lung injury (ALI) mice treated with JGT were identified by isobaric tags for relative and absolute quantitation (iTRAQ) and LC Triple‐TOF. Eleven potential anti‐inflammatory ingredients were found, including the derivatives of glycyrrhizic acid, licorice‐saponin, liquiritin, and platycodigenin. A total of sixty‐seven differentially expressed proteins were confirmed after JGT treatment with four therapeutic functions, including immunoregulation, anti‐inflammation, ribosome, and muscle contraction. PG and GU comediate PI3K/Akt signal pathway inhibition of NF‐κB, VCAM1, and ICAM1 release which primarily act on PI3K, PDK1, AKT, and GSK3β. GU markedly inhibits the ERK/MAPK signaling pathways and primarily acts on LCK, RAS, and MEK. A network was constructed using bioactive ingredients, targets, and pathways to determine the mechanism underlying JGT treatment of ALI.
Cloning, Expression, and Characterization of a Novel Thermophilic Monofunctional Catalase fromGeobacillussp. CHB1
Authors: Jia Xianbo , Chen Jichen , Lin Chenqiang , Lin Xinjian
Published: August 2016

Catalases are widely used in many scientific areas. A catalase gene (Kat) fromGeobacillussp. CHB1 encoding a monofunctional catalase was cloned and recombinant expressed inEscherichia coli(E. coli), which was the first time to clone and express this type of catalase ofgenus Geobacillusstrains as far as we know. ThisKatgene was 1,467 bp in length and encoded a catalase with 488 amino acid residuals, which is only 81% similar to the previously studiedBacillussp. catalase in terms of amino acid sequence. Recombinant catalase was highly soluble inE. coliand made up 30% of the totalE. coliprotein. Fermentation broth of the recombinantE. colishowed a high catalase activity level up to 35,831 U/mL which was only lower than recombinantBacillussp. WSHDZ-01 among the reported catalase production strains. The purified recombinant catalase had a specific activity of 40,526 U/mg andKmof 51.1 mM. The optimal reaction temperature of this recombinant enzyme was 60°C to 70°C, and it exhibited high activity over a wide range of reaction temperatures, ranging from 10°C to 90°C. The enzyme retained 94.7% of its residual activity after incubation at 60°C for 1 hour. High yield and excellent thermophilic properties are valuable features for this catalase in industrial applications.
Accelerated Life Test for Photovoltaic Cells Using Concentrated Light
Authors: Cotfas Daniel Tudor , Cotfas Petru Adrian , Floroian Dan Ion , Floroian Laura
Published: August 2016

This paper presents a new method developed to significantly reduce the necessary time for the ageing tests for different types of photovoltaic cells. Two ageing factors have been applied to the photovoltaic cells: the concentrated light and the temperature. The maximum power of the photovoltaic cells was monitored during the ageing process. The electrical dc and ac parameters of the photovoltaic cells were measured and analyzed at 1 sun irradiance, before and after the test stress. During the test, two photovoltaic cells are kept at maximum power point and the other two are kept at open circuit voltage point. The method is validated through the results obtained for the monocrystalline silicon solar cell.
Androgen and Estrogen Receptors in Breast Cancer Coregulate Human UDP-Glucuronosyltransferases 2B15 and 2B17
Authors: Hu Dong G. , Selth Luke A. , Tarulli Gerard A. , Meech Robyn , Wijayakumara Dhilushi , Chanawong Apichaya , Russell Roslin , Caldas Carlos , Robinson Jessica L.L. , Carroll Jason S. , Tilley Wayne D. , Mackenzie Peter I. , Hickey Theresa E.
Published: August 2016

Glucuronidation is an enzymatic process that terminally inactivates steroid hormones, including estrogens and androgens, thereby influencing carcinogenesis in hormone-dependent cancers. While estrogens drive breast carcinogenesis via the estrogen receptor alpha (ERα), androgens play a critical role as prohormones for estrogen biosynthesis and ligands for the androgen receptor (AR). In this study, the expression and regulation of two androgen-inactivating enzymes, the UDP-glucuronosyltransferases UGT2B15 and UGT2B17, was assessed in breast cancer. In large clinical cohorts, high UGT2B15 and UGT2B17 levels positively influenced disease-specific survival in distinct molecular subgroups. Expression of these genes was highest in cases positive for ERα. In cell line models, ERα, AR, and the transcription factor FOXA1 cooperated to increase transcription via tandem binding events at their proximal promoters. ERα activity was dependent on FOXA1, facilitated by AR activation, and potently stimulated by estradiol as well as estrogenic metabolites of 5α-dihydrotestosterone. AR activity was mediated via binding to an estrogen receptor half-site 3′ to the FOXA1 and ERα-binding sites. Although AR and FOXA1 bound the UGT promoters in AR-positive/ERα-negative breast cancer cell lines, androgen treatment did not influence basal transcription levels. Ex vivo culture of human breast tissue and ERα+ tumors provided evidence for upregulation of UGT2B15 and UGT2B17 by estrogen or androgen treatment. ERα binding was evident at the promoters of these genes in a small cohort of primary tumors and distant metastases. Collectively, these data provide insight into sex steroid receptor-mediated regulation of androgen-inactivating enzymes in ERα+ breast cancer, which may have subtype-specific consequences for disease progression and outcomes. Cancer Res; 76(19); 5881–93. ©2016 AACR.
PAK4 Phosphorylates p53 at Serine 215 to Promote Liver Cancer Metastasis
Authors: Xu Hai-Tao , Lai Wai-Lung , Liu Heong-Fai , Wong Leo Lap-Yan , Ng Irene Oi-Lin , Ching Yick Pang
Published: August 2016

PAK4 kinase contributes to signaling pathways controlling cancer cell transformation, invasion, and survival, but its clinicopathological impact has begun to emerge only recently. Here we report that PAK4 overexpression in hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of our studies. By stably overexpressing or silencing PAK4 in HCC cells, we showed that it was critical for their migration. Mechanistic investigations in this setting revealed that PAK4 directly phosphorylated p53 at S215, which not only attenuated transcriptional transactivation activity but also inhibited p53-mediated suppression of HCC cell invasion. Taken together, our results showed how PAK4 overexpression in HCC promotes metastatic invasion by regulating p53 phosphorylation. Cancer Res; 76(19); 5732–42. ©2016 AACR.
Nestin Mediates Hedgehog Pathway Tumorigenesis
Authors: Li Peng , Lee Eric H. , Du Fang , Gordon Renata E. , Yuelling Larra W. , Liu Yongqiang , Ng Jessica M.Y. , Zhang Hao , Wu Jinhua , Korshunov Andrey , Pfister Stefan M. , Curran Tom , Yang Zeng-jie
Published: August 2016

The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem–like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation, resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway–driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies. Cancer Res; 76(18); 5573–83. ©2016 AACR.
A BRCA1/2 Mutational Signature and Survival in Ovarian High-Grade Serous Carcinoma
Authors: Dong Fei , Davineni Phani K. , Howitt Brooke E. , Beck Andrew H.
Published: August 2016

Background: Mutational signatures have been identified by the broad sequencing of cancer genomes and reflect underlying processes of mutagenesis. The clinical application of mutational signatures is not well defined. Here we aim to assess the prognostic utility of mutational signatures in ovarian high-grade serous carcinoma.

Methods: Open access data of 15,439 somatic mutations of 310 ovarian high-grade serous carcinomas from The Cancer Genome Atlas (TCGA) are used to construct a Bayesian model to classify each cancer as either having or lacking a BRCA1/2 mutational signature. We evaluate the association of the BRCA1/2 signature with overall survival on the TCGA dataset and on an independent cohort of 92 ovarian high-grade serous carcinomas from the Australian Ovarian Cancer Study (AOCS).

Results: Patients from TCGA with tumors harboring the BRCA1/2 mutational signature have improved survival (55.2 months vs. 38.0 months), which is independent of BRCA1/2 gene mutation status, age, stage, and grade (HR = 0.64; P = 0.02). In the AOCS dataset, the BRCA1/2 mutational signature is also associated with improved overall survival (46.3 months vs. 23.6 months) independent of age and stage (HR = 0.52; P = 0.007).

Conclusions: A BRCA1/2 mutational signature is a prognostic marker in ovarian high-grade serous carcinoma. Mutational signature analysis of ovarian cancer genomes may be useful in addition to testing for BRCA1/2 mutations.

Impact: This study identifies the use of mutational signatures as a biomarker for survival outcome in ovarian high-grade serous carcinoma. Cancer Epidemiol Biomarkers Prev; 25(11); 1511–6. ©2016 AACR.
Progression of EGFR-Mutant Lung Adenocarcinoma is Driven By Alveolar Macrophages
Authors: Wang Don-Hong , Lee Hyun-Sung , Yoon David , Berry Gerald , Wheeler Thomas M. , Sugarbaker David J. , Kheradmand Farrah , Engleman Edgar , Burt Bryan M.
Published: August 2016

Purpose: Lung adenocarcinomas with mutations in the EGFR have unprecedented initial responses to targeted therapy against the EGFR. Over time, however, these tumors invariably develop resistance to these drugs. We set out to investigate alternative treatment approaches for these tumors.

Experimental Design: To investigate the immunologic underpinnings of EGFR-mutant lung adenocarcinoma, we utilized a bitransgenic mouse model in which a mutant human EGFR gene is selectively expressed in the lungs.

Results: EGFR oncogene–dependent progression and remission of lung adenocarcinoma was respectively dependent upon the expansion and contraction of alveolar macrophages, and the mechanism underlying macrophage expansion was local proliferation. In tumor-bearing mice, alveolar macrophages downregulated surface expression of MHC-II and costimulatory molecules; increased production of CXCL1, CXCL2, IL1 receptor antagonist; and increased phagocytosis. Depletion of alveolar macrophages in tumor-bearing mice resulted in reduction of tumor burden, indicating a critical role for these cells in the development of EGFR-mutant adenocarcinoma. Treatment of mice with EGFR-targeting clinical drugs (erlotinib and cetuximab) resulted in a significant decrease in alveolar macrophages in these mice. An activated alveolar macrophage mRNA signature was dominant in human EGFR-mutant lung adenocarcinomas, and the presence of this alveolar macrophage activation signature was associated with unfavorable survival among patients undergoing resection for EGFR-mutant lung adenocarcinoma.

Conclusions: Because of the inevitability of failure of targeted therapy in EGFR-mutant non-small cell lung cancer (NSCLC), these data suggest that therapeutic strategies targeting alveolar macrophages in EGFR-mutant NSCLC have the potential to mitigate progression and survival in this disease. Clin Cancer Res; 23(3); 778–88. ©2016 AACR.