bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Digital Interventions: A Methodological Guide
Authors: Bradbury Katherine , Watts Sam , Arden-Close Emily , Yardley Lucy , Lewith George
Published: February 2014

Digital interventions are becoming an increasingly popular method of delivering healthcare as they enable and promote patient self‐management. This paper provides a methodological guide to the processes involved in developing effective digital interventions, detailing how to plan and develop such interventions to avoid common pitfalls. It demonstrates the need for mixed qualitative and quantitative methods in order to develop digital interventions which are effective, feasible, and acceptable to users and stakeholders.
Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT
Authors: Ponnan Prija , Kumar Ajit , Singh Prabhjot , Gupta Prachi , Joshi Rini , Gaspari Marco , Saso Luciano , Prasad Ashok K. , Rastogi Ramesh C. , Parmar Virinder S. , Raj Hanumantharao G.
Published: February 2014

Our laboratory is credited for the discovery of enzymatic acetylation of protein, a phenomenon unknown till we identified an enzyme termed acetoxy drug: protein transacetylase (TAase), catalyzing the transfer of acetyl group from polyphenolic acetates to receptor proteins (RP). Later, TAase was identified as calreticulin (CR), an endoplasmic reticulum luminal protein. CR was termed calreticulin transacetylase (CRTAase). Our persistent study revealed that CR like other families of histone acetyltransferases (HATs) such as p300, Rtt109, PCAF, and ESA1, undergoes autoacetylation. The autoacetylated CR was characterized as a stable intermediate in CRTAase catalyzed protein acetylation, and similar was the case with ESA1. The autoacetylation of CR like that of HATs was found to enhance protein-protein interaction. CR like HAT-1, CBP, and p300 mediated the acylation of RP utilizing acetyl CoA and propionyl CoA as the substrates. The similarities between CRTAase and HATs in mediating protein acylation are highlighted in this review.
Effects of the Kampo Formula Tokishakuyakusan on Headaches and Concomitant Depression in Middle‐Aged Women
Authors: Terauchi Masakazu , Hiramitsu Shiro , Akiyoshi Mihoko , Owa Yoko , Kato Kiyoko , Obayashi Satoshi , Matsushima Eisuke , Kubota Toshiro
Published: February 2014

Objectives. To identify the correlates of headaches in middle‐aged women and investigate the effects of Tokishakuyakusan (TJ‐23), a formula of traditional Japanese herbal therapy Kampo, on headache and concomitant depression. Methods. We examined cross‐sectionally the baseline records of 345 women aged 40–59 years who visited our menopause clinic. Among them, 37 women with headaches were treated with either hormone therapy (HT) or TJ‐23; the data of these women were retrospectively analyzed to compare the effects of the treatment. Results. The women were classified into 4 groups on the basis of their headache frequency, and no significant intergroup differences were noted in the physical or lifestyle factors, except age. Multiple logistic regression analysis revealed that the significant contributors to the women’s headaches were their age (adjusted OR 0.92 (95% CI 0.88–0.97)) and their depressive symptoms (adjusted OR 1.73 (95% CI 1.39–2.16)). Compared to women treated with HT, women treated with TJ‐23 reported relief from headaches (65% versus 29%) and concomitant depression (60% versus 24%) more frequently. Improvement in the scores of headaches and depression correlated significantly with TJ‐23 treatment. Conclusions. Headache in middle‐aged women is significantly associated with depression; TJ‐23 could be effective for treating both of these symptoms.
Interaction of Bradykinin and B2Bradykinin Receptor Antagonists with Colloidal Au Surface Explored by Surface-Enhanced Raman Scattering
Authors: Skołuba Dominika , Sobolewski Dariusz , Prahl Adam , Proniewicz Edyta
Published: February 2014

Bradykinin (BK), an endogenous peptide hormone, which is involved in a number of physiological and pathophysiological processes, and the potent B2bradykinin receptor antagonists, [D-Arg0,Hyp3,Thi5,8,L-Pip7]BK, Aaa[D-Arg0,Hyp3,Thi5,8,L-Pip7]BK, [D-Arg0,Hyp3,Thi5,D-Phe7,L-Pip8]BK, and Aaa[D-Arg0,Hyp3,Thi5,D-Phe7,L-Pip8]BK, were deposited onto colloidal Au particles of 20 nm size. Interaction of these molecules with colloidal Au surface was explored by surface-enhanced Raman scattering (SERS). Briefly, it was shown that BK adsorbs on the Au surface mainly through the Phe5/Phe8residues. In case of the BK specifically modified analogues mainly the Pip and Thi rings are involved in the interaction process; however, Pip and Thi adopt slightly different orientation with respect to Au for each of the analogues. In addition, the lack of the Aaa vibrations, together with the enhancement of the Thi, Pip, or Phe modes, emphasizes the importance of theC-terminus in the interaction with the Au surface.
Effects of Preventive Acupuncture and Moxibustion on Fat Accumulation, Blood Lipid, and Uterus E2 of Menopause Rats
Authors: Zhu Shi-Peng , He Yu-wei , Chen Huan , Sun Zhi-Fang , Ding Na , Mo Jie , Cao Bing-Yan , Luo Li , Zhang Qing-Qing , Wang Yang , Zhang Lu-Fen , Ren Xiao-Xuan , Guo Meng-Wei , Zhao Ya-Fang , Ma Liang-Xiao , Li Xiao-Hong
Published: February 2014

Objective. To observe the effect of preventive acupuncture and moxibustion on blood lipid of menopause rats. Methods. Seventy 10‐month‐old SD rats with estrous cycle disorders were divided into three control groups and four treatment groups (n = 10/group) and another ten 3.5‐month‐old female SD rats were chosen as young control group. Preventive acupuncture and moxibustion were applied at Guanyuan (CV 4). Body weight growth rate has been recorded. Plasma total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels and uterus E2 level were measured. Results. Compared to young control group, plasma TC and LDL increased and uterus E2 reduced significantly in 12‐month‐old control group. Compared to 12‐month‐old control group, plasma TC and LDL level and body weight growth rate decreased while HDL level increased remarkably in preventive acupuncture 12‐month‐old group. Compared to 14‐month‐old control group, plasma TC level and body weight growth rate decreased remarkably in preventive moxibustion 14‐month‐old group. Conclusions. Preventive acupuncture and moxibustion can significantly decrease the plasma TG and LDL, increase the plasma HDL, and prevent fat accumulation. Our finding suggests that preventive acupuncture and moxibustion have beneficial effects on blood lipid. Different treatment effects were found between preventive acupuncture and preventive moxibustion.
Sonographic Wrist Measurements and Detection of Anatomical Features in Carpal Tunnel Syndrome
Authors: Vögelin Esther , Mészàros Thomas , Schöni Franziska , Constantinescu Mihai A.
Published: February 2014

Introduction. This study compares anatomical findings at wrist level in patients with known carpal tunnel syndrome (CTS) and controls by ultrasonography (US).Material and Methods. Wrist-US investigations of 28 consecutive patients with 38 diagnosed, idiopathic CTS were compared to 49 healthy volunteers without history of CTS. Internal wrists dimensions, the presence of flexor muscle bellies in the carpal tunnel, and cross-sectional area of the median nerve were analyzed. The findings were correlated to gender, age, and BMI.Results. US demonstrated a square internal carpal tunnel configuration in CTS patients compared to controls (P<0.001). Patients with CTS showed a trend towards the presence of flexor muscles bellies in the carpal tunnel (odds ratio 1.77, 95% CI 0.337–8.33). CTS was present in women with higher BMI (P=0.015).Conclusion. US allowed detection of specific anatomical features at wrist level in CTS patients. This observation may enable—following confirmation in larger prospective studies—risk evaluation for CTS development.
Applications and Therapeutic Actions of Complementary and Alternative Medicine for Women with Genital Infection
Authors: Liu Chenfang , Zhang Yuehui , Kong Sai , Tsui Ilene , Yu Yang , Han Fengjuan
Published: February 2014

Genital infection is a common worldwide disease among females with clinical features such as bilateral lower abdominal tenderness, abnormal vaginal or cervical discharge, fever, abnormal vaginal bleeding, dyspareunia, vaginal itching, and adnexal tenderness, which can significantly impair women’s health and quality of life. Genital infection is commonly treated with antibiotics, leading to an imbalance in gut flora due to prolonged use of antibiotics. Therefore, it is necessary to discover safe and efficacious alternative treatment strategies for patients with genital infection. Complementary and alternative medicine (CAM) is becoming increasingly prevalent among women with genital infection. CAM has interested the western mainstream medical community because of its less invasive, safe, effective, economical, and convenient therapies. CAM focuses on the prevention and treatment of disease and has become an important force in treating chronic disease. During the last few decades, the popularity of CAM has gradually increased. To further understand the efficacy of CAM in treating genital infection, our paper will review the current progress of treating genital infection including vulvitis, vaginitis, cervicitis, and pelvic inflammatory disease (PID) with CAM therapies. Several CAM strategies including traditional Chinese medicine (TCM), acupuncture, Psychology interference, and physical therapy are introduced in this review.
Exact Solution of Thermoelastic Problem for a One-Dimensional Bar without Energy Dissipation
Authors: Abd El-Latief A. M. , Khader S. E.
Published: February 2014

We consider a homogeneous isotropic thermoelastic half-space in the context of the theory of thermoelasticity without energy dissipation. There are no body forces or heat source acting on the half-space. The surface of the half-space is affected by a time dependent thermal shock and is traction free. The Laplace transform with respect to time is used. The inverse transforms are obtained in an exact manner for the temperature, thermal stress, and displacement distributions. These solutions are represented graphically and discussed for several cases of the applied heating. Comparison is made between the predictions here and those of the theory of thermoelasticity with one relaxation time.
Double-Diffusive Convection in Presence of Compressible Rivlin-Ericksen Fluid with Fine Dust
Authors: Singh Mahinder , Gupta Rajesh Kumar
Published: February 2014

An investigation is made on the effect of suspended particles (fine dust) on double-diffusive convection of a compressible Rivlin-Ericksen elastico-viscous fluid. The perturbation equations are analyzed in terms of normal modes after linearizing the relevant set of equations. A dispersion relation governing the effects of viscoelasticity, compressibility, stable solute gradient, and suspended particles is derived. For stationary convection, Rivlin-Ericksen fluid behaves like an ordinary Newtonian fluid due to the vanishing of the viscoelastic parameter. The stable solute gradient compressibility has a stabilizing effect on the system whereas suspended particles hasten the onset of thermosolutal instability. The Rayleigh numbers and the wave numbers of the associated disturbances for the onset of instability as stationary convection are obtained and the behaviour of various parameters on Rayleigh numbers has been depicted graphically. It has been observed that oscillatory modes are introduced due to the presence of viscoelasticity, suspended particles, and stable solute gradient which were not existing in the absence of these parameters.
2-Cys Peroxiredoxins: Emerging Hubs Determining Redox Dependency of Mammalian Signaling Networks
Authors: Park Jinah , Lee Sunmi , Lee Sanghyuk , Kang Sang Won
Published: February 2014

Mammalian cells have a well-defined set of antioxidant enzymes, which includes superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins. Peroxiredoxins are the most recently identified family of antioxidant enzymes that catalyze the reduction reaction of peroxides, such as H2O2. In particular, typical 2-Cys peroxiredoxins are the featured peroxidase enzymes that receive the electrons from NADPH by coupling with thioredoxin and thioredoxin reductase. These enzymes distribute throughout the cellular compartments and, therefore, are thought to be broad-range antioxidant defenders. However, recent evidence demonstrates that typical 2-Cys peroxiredoxins play key signal regulatory roles in the various signaling networks by interacting with or residing near a specific redox-sensitive molecule. These discoveries help reveal the redox signaling landscape in mammalian cells and may further provide a new paradigm of therapeutic approaches based on redox signaling.
STAT4Gene Polymorphisms Are Associated with Susceptibility and ANA Status in Primary Biliary Cirrhosis
Authors: Joshita Satoru , Umemura Takeji , Nakamura Minoru , Katsuyama Yoshihiko , Shibata Soichiro , Kimura Takefumi , Morita Susumu , Komatsu Michiharu , Matsumoto Akihiro , Yoshizawa Kaname , Ishibashi Hiromi , Tanaka Eiji , Ota Masao
Published: February 2014

Recent genome-wide association studies suggest that genetic factors contribute to primary biliary cirrhosis (PBC) susceptibility. Although several reports have demonstrated that the interleukin (IL) 12 signaling pathway is involved in PBC pathogenesis, its precise genetic factors have not been fully clarified. Here, we performed an association analysis betweenIL12A,IL12RB, andsignal transducer and activator of transcription 4 (STAT4)genetic variations and susceptibility to PBC. Single nucleotide polymorphisms (SNPs) were genotyped in 395 PBC patients and 458 healthy subjects of Japanese ethnicity and evaluated for associations with PBC susceptibility, anti-nuclear antibody (ANA) status, and anti-mitochondrial antibody (AMA) status. We detected significant associations with PBC susceptibility for severalSTAT4SNPs (rs10168266;P=9.4×10-3, rs11889341;P=1.2×10-3, rs7574865;P=4.0×10-4, rs8179673;P=2.0×10-4, and rs10181656;P=4.2×10-5). Three risk alleles (rs7574865;P=0.040, rs8179673;P=0.032, and rs10181656;P=0.031) were associated with ANA status, but not with AMA positivity. Our findings confirm thatSTAT4is involved in PBC susceptibility and may play a role in ANA status in the Japanese population.
Estimating the Pollution Risk of Cadmium in Soil Using a Composite Soil Environmental Quality Standard
Authors: Qu Mingkai , Li Weidong , Zhang Chuanrong , Huang Biao , Zhao Yongcun
Published: February 2014

Estimating standard-exceeding probabilities of toxic metals in soil is crucial for environmental evaluation. Because soil pH and land use types have strong effects on the bioavailability of trace metals in soil, they were taken into account by some environmental protection agencies in making composite soil environmental quality standards (SEQSs) that contain multiple metal thresholds under different pH and land use conditions. This study proposed a method for estimating the standard-exceeding probability map of soil cadmium using a composite SEQS. The spatial variability and uncertainty of soil pH and site-specific land use type were incorporated through simulated realizations by sequential Gaussian simulation. A case study was conducted using a sample data set from a 150 km2area in Wuhan City and the composite SEQS for cadmium, recently set by the State Environmental Protection Administration of China. The method may be useful for evaluating the pollution risks of trace metals in soil with composite SEQSs.
Control of Yaw Disturbance Using Fuzzy Logic Based Yaw Stability Controller
Authors: Krishna S. , Narayanan S. , Ashok S. Denis
Published: February 2014

Yaw stability is an important consideration for the vehicle directional stability and handling behavior during emergency maneuvers. In order to maintain the desired path of the vehicle, in presence of disturbances due to cross wind, different road conditions, and tire deflections, a fuzzy logic based yaw stability controller is proposed in this paper. Proposed control system receives yaw rate error, steering angle given by the driver, and side slip angle as inputs, for calculating the additional steering angle as output, for maintaining the yaw stability of the vehicle. As the side slip angle cannot be measured directly in a vehicle, it was estimated using a model based Kalman observer. A two-degrees-of-freedom vehicle model is considered in the present work. The effect of disturbance on yaw rate and yaw rate error of the vehicle is simulated for sinusoidal, step maneuver and compared with the existing fuzzy control system which uses two inputs such as steering angle and yaw rate. The simulation results show better performance of the proposed fuzzy based yaw controller as compared with existing control system. Proposed fuzzy based yaw stability controller can be implemented in steer-by-wire system for an active front steering of a road vehicle.
Coefficient Inequalities for a Subclass ofp-Valent Analytic Functions
Authors: Arif Muhammad , Sokół Janusz , Ayaz Muhammad
Published: February 2014

The aim of this paper is to study the problem of coefficient bounds for a newly defined subclass ofp-valent analytic functions. Many known results appear as special consequences of our work.
Variable Selection Method in Prediction Models: Application in Periodontology
Authors: Tramini Paul , Chazel Jean-Christophe , Calas-Bennasar Isabelle , Gibert Philippe , Molinari Nicolas
Published: February 2014

The aim of this study, applied in the field of periodontal diseases, was first to analyze the fatty acid levels in two groups of patients and then to propose a method for selecting the most relevant predictors. Two groups of patients, 29 with moderate or severe periodontitis and 27 who served as controls, were clinically examined, and their fatty acids in serum were measured by gas chromatography. The levels of these 12 fatty acids were the variables of the analysis. Logistic regression, together with the area under the receiver operating characteristic (ROC) curves, allowed determining a composite score which led to a subset of the most relevant covariables. The fatty acid levels differed significantly between the 2 groups in multivariate analysis (P=0.03) and the best logistic model was obtained with only 3 predictive variables: arachidonic acid, linoleic acid, and DHA. Fatty acid levels in serum of patients were significantly different according to the presence of moderate or severe periodontitis. By taking into account the comparison of ROC curves, our approach could optimize the choice of variables in multivariate analyses and could better fit it with diagnosis and prognosis of oral diseases in dental research.
Statistical Analysis of Traffic Accidents in Shanghai River Crossing Tunnels and Safety Countermeasures
Authors: Lu Linjun , Lu Jian , Xing Yingying , Wang Chen , Pan Fuquan
Published: February 2014

A large number of traffic tunnel accidents have been reported in China since the 21th century. However, few studies have been reported to analyze traffic accidents that have occurred in urban road tunnels. This study aims to examine the characteristics of the temporal, spatial, and modality distributions of traffic in Shanghai river crossing tunnels using statistical analysis and comparative analysis. Employing these techniques tunnel accident data obtained from Shanghai center 110 was analyzed to determine temporal and spatial distribution characteristics of traffic accidents in river crossing tunnels in Shanghai. The results of this analysis are discussed and summarized in this paper. Identification of the characteristics of tunnel traffic accidents can provide valuable information for development of effective countermeasures to improve tunnel safety in China.
Techniques for Performance Improvement of Integer Multiplication in Cryptographic Applications
Authors: Brumnik Robert , Kovtun Vladislav , Okhrimenko Andrew , Kavun Sergii
Published: February 2014

The problem of arithmetic operations performance in number fields is actively researched by many scientists, as evidenced by significant publications in this field. In this work, we offer some techniques to increase performance of software implementation of finite field multiplication algorithm, for both 32‐bit and 64‐bit platforms. The developed technique, called “delayed carry mechanism,” allows to preventing necessity to consider a significant bit carry at each iteration of the sum accumulation loop. This mechanism enables reducing the total number of additions and applies the modern parallelization technologies effectively.
Aquaporin-1 Expression in Proliferative Vitreoretinopathy and in Epiretinal Membranes
Authors: Motulsky Elie , Salik Dany , Janssens Xavier , Pion Bart , Dufrane Rebecca , Chaput Florence , Bolaky Nargis , Gregoire Françoise , Caspers Laure , Perret Jason , Willermain François , Delporte Christine
Published: February 2014

Purpose. Aquaporin-1 (AQP1) is involved in cell migration and proliferation; therefore, the purpose of the study was to investigate its expression in proliferative vitreoretinopathy (PVR) and epiretinal membranes (ERM).Methods. 19 membranes from PVR and ERM were collected following eye surgery. AQP1 mRNA and protein expressions were determined by RT-qPCR and immunofluorescence in the membranes from PVR and ERM.Results. AQP1 mRNA and protein were expressed in both PVR and ERM as shown by RT-qPCR and immunofluorescence. AQP1 protein expression was heterogeneous among and between PVR and ERM and colocalized with alpha-smooth muscle actin (αSMA) and with glial fibrillary acidic protein (GFAP). There were a higher percentage of cells coexpressing AQP1 andαSMA than AQP1 and GFAP. GFAP andαSMA did not colocalize.Conclusion. Our data show for the first time AQP1 expression in both PVR and ERM. AQP1 is expressed mostly by theαSMA-positive cells, presumably myofibroblasts, but also by GFAP-positive cells, assumed to be glial cells. These original findings warrant further functional investigations aiming at studying the potential role of AQP1 in cell migration and proliferation occurring during the development of PVR and ERM.
Hydrogenated Silicon Carbide Thin Films Prepared with High Deposition Rate by Hot Wire Chemical Vapor Deposition Method
Authors: Kamble M. M. , Waman V. S. , Mayabadi A. H. , Ghosh S. S. , Gabhale B. B. , Rondiya S. R. , Rokade A. V. , Khadtare S. S. , Sathe V. G. , Shripathi T. , Pathan H. M. , Gosavi S. W. , Jadkar S. R.
Published: February 2014

Structural, optical, and electrical properties of hydrogenated silicon carbide (SiC:H) films, deposited from silane (SiH4) and methane (CH4) gas mixture by HW-CVD method, were investigated. Film properties are carefully and systematically studied as function of deposition pressure which is varied between 200 mTorr and 500 mTorr. The deposition rate is found to be reasonably high (9.4 nm/s <rd< 15.54 nm/s). Formation of SiC:H films is confirmed by FTIR, Raman, and XPS analysis. XRD and Raman analysis revealed that with increasing deposition pressure amorphization occurs in SiC:H films. FTIR spectroscopy analysis shows that bond density of C–H decreases while Si–C and Si–H bond densities increase with increasing deposition pressure. Total hydrogen content increases with increasing deposition pressure and was found to be <20 at.%. The absence of band ~1300–1600 cm−1 in the Raman spectra implies negligible C–C bond concentration and formation of nearly stoichiometric SiC:H films. The band gap shows increasing trend with increasing deposition pressure. The high value of Urbach energy suggests increased structural disorder in SiC:H films. Finally, it has been concluded that CH4 can be used as effective carbon source in HW-CVD method to prepare stoichiometric SiC:H films.
Cervical Cancer: Community Perception and Preventive Practices in an Urban Neighborhood of Lagos (Nigeria)
Authors: Wright K. O. , Aiyedehin O. , Akinyinka M. R. , Ilozumba O.
Published: February 2014

Background. Cervical cancer prevention in developing countries is suboptimal compared with the developed world where there are fewer deaths and improved survival rates. This study describes the perception and preventive practices on cervical cancer by residents of an urban neighborhood of Lagos, Nigeria. Methods. A descriptive cross-sectional study was conducted on 317 consecutively recruited consenting participants at a medical outreach using a pretested, interviewer-administered, semistructured questionnaire. Data analysis was done using statistical package for social sciences version 19. Tests of significance were performed using 95% confidence interval with level of significance set at P<0.05. Results. The majority of respondents were within 30–49 years of age (46.7%) and female (62.1%) and 70.3% had secondary level education and above. About 37.2% of respondents had heard about cervical cancer with 84.5% of the participants willing to attend a cervical cancer health education program. Among the female respondents, 4.1% had received the HPV vaccine, while 5.1% had undergone a Pap test. Awareness about cervical cancer was significantly higher with increasing age in the total population (P<0.05). Conclusion. There is a need to improve awareness of at-risk groups and the menfolk about cervical cancer based on the immense benefit of male involvement in reproductive health matters.
Hepatoprotective Effect of Pretreatment with Thymus vulgaris Essential Oil in Experimental Model of Acetaminophen‐Induced Injury
Authors: Grespan Renata , Aguiar Rafael Pazinatto , Giubilei Frederico Nunes , Fuso Rafael Rocco , Damião Marcio José , Silva Expedito Leite , Mikcha Jane Graton , Hernandes Luzmarina , Bersani Amado Ciomar , Cuman Roberto Kenji Nakamura
Published: February 2014

Acute liver damage caused by acetaminophen overdose is a significant clinical problem and could benefit from new therapeutic strategies. Objective. This study investigated the hepatoprotective effect of Thymus vulgaris essential oil (TEO), which is used popularly for various beneficial effects, such as its antiseptic, carminative, and antimicrobial effects. The hepatoprotective activity of TEO was determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity and subjected to histological analysis. In vitro antioxidant activity was evaluated by assessing the free radical 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH•)‐scavenging effects of TEO and TEO‐induced lipid peroxidation. TEO reduced the levels of the serum marker enzymes AST, ALT, and ALP and MPO activity. The histopathological analysis indicated that TEO prevented acetaminophen‐induced necrosis. The essential oil also exhibited antioxidant activity, reflected by its DPPH radical‐scavenging effects and in the lipid peroxidation assay. These results suggest that TEO has hepatoprotective effects on acetaminophen‐induced hepatic damage in mice.
Potential Uses, Limitations, and Basic Procedures of Micronuclei and Nuclear Abnormalities in Buccal Cells
Authors: Torres-Bugarín Olivia , Zavala-Cerna María Guadalupe , Nava Arnulfo , Flores-García Aurelio , Ramos-Ibarra María Luisa
Published: February 2014

The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN) and nuclear abnormalities (NA) technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique.
An Adaptive Metamodel‐Based Optimization Approach for Vehicle Suspension System Design
Authors: Yang Qinwen , Huang Jin , Wang Gang , Karimi Hamid Reza
Published: February 2014

The performance index of a suspension system is a function of the maximum and minimum values over the parameter interval. Thus metamodel‐based techniques can be used for designing suspension system hardpoints locations. In this study, an adaptive metamodel‐based optimization approach is used to find the proper locations of the hardpoints, with the objectives considering the kinematic performance of the suspension. The adaptive optimization method helps to find the optimum locations of the hardpoints efficiently as it may be unachievable through manually adjusting. For each iteration in the process of adaptive optimization, prediction uncertainty is considered and the multiobjective optimization method is applied to optimize all the performance indexes simultaneously. It is shown that the proposed optimization method is effective while being applied in the kinematic performance optimization of a McPherson suspension system.
An Improved Feature Selection Based on Effective Range for Classification
Authors: Wang Jianzhong , Zhou Shuang , Yi Yugen , Kong Jun
Published: February 2014

Feature selection is a key issue in the domain of machine learning and related fields. The results of feature selection can directly affect the classifier’s classification accuracy and generalization performance. Recently, a statistical feature selection method named effective range based gene selection (ERGS) is proposed. However, ERGS only considers the overlapping area (OA) among effective ranges of each class for every feature; it fails to handle the problem of the inclusion relation of effective ranges. In order to overcome this limitation, a novel efficient statistical feature selection approach called improved feature selection based on effective range (IFSER) is proposed in this paper. In IFSER, an including area (IA) is introduced to characterize the inclusion relation of effective ranges. Moreover, the samples’ proportion for each feature of every class in both OA and IA is also taken into consideration. Therefore, IFSER outperforms the original ERGS and some other state-of-the-art algorithms. Experiments on several well-known databases are performed to demonstrate the effectiveness of the proposed method.
Product Characterization and Kinetics of Biomass Pyrolysis in a Three-Zone Free-Fall Reactor
Authors: Punsuwan Natthaya , Tangsathitkulchai Chaiyot
Published: February 2014

Pyrolysis of biomass including palm shell, palm kernel, and cassava pulp residue was studied in a laboratory free-fall reactor with three separated hot zones. The effects of pyrolysis temperature (250–1050°C) and particle size (0.18–1.55 mm) on the distribution and properties of pyrolysis products were investigated. A higher pyrolysis temperature and smaller particle size increased the gas yield but decreased the char yield. Cassava pulp residue gave more volatiles and less char than those of palm kernel and palm shell. The derived solid product (char) gave a high calorific value of 29.87 MJ/kg and a reasonably high BET surface area of 200 m2/g. The biooil from palm shell is less attractive to use as a direct fuel, due to its high water contents, low calorific value, and high acidity. On gas composition, carbon monoxide was the dominant component in the gas product. A pyrolysis model for biomass pyrolysis in the free-fall reactor was developed, based on solving the proposed two-parallel reactions kinetic model and equations of particle motion, which gave excellent prediction of char yields for all biomass precursors under all pyrolysis conditions studied.
UTX and MLL4 Coordinately Regulate Transcriptional Programs for Cell Proliferation and Invasiveness in Breast Cancer Cells
Authors: Kim Jae-Hwan , Sharma Amrish , Dhar Shilpa S. , Lee Sung-Hun , Gu Bingnan , Chan Chia-Hsin , Lin Hui-Kuan , Lee Min Gyu
Published: February 2014

Histone methyltransferases and demethylases reversibly modulate histone lysine methylation, which is considered a key epigenetic mark associated with gene regulation. Recently, aberrant regulation of gene expression by histone methylation modifiers has emerged as an important mechanism for tumorigenesis. However, it remains largely unknown how histone methyltransferases and demethylases coregulate transcriptional profiles for cancer cell characteristics. Here, we show that in breast cancer cells, the histone H3 lysine 27 (H3K27) demethylase UTX (also known as KDM6A) positively regulates gene expression programs associated with cell proliferation and invasion. The majority of UTX-controlled genes, including a cohort of oncogenes and prometastatic genes, are coregulated by the H3K4 methyltransferase mixed lineage leukemia 4 (MLL4, also called ALR, KMT2D, and MLL2). UTX interacted with a C-terminal region of MLL4. UTX knockdown resulted in significant decreases in the proliferation and invasiveness of breast cancer cells in vitro and in a mouse xenograft model. Such defective cellular characteristics of UTX-depleted cells were phenocopied by MLL4 knockdown cells. UTX-catalyzed demethylation of trimethylated H3K27 and MLL4-mediated trimethylation at H3K4 occurred interdependently at cotarget genes of UTX and MLL4. Clinically, high levels of UTX or MLL4 were associated with poor prognosis in patients with breast cancer. Taken together, these findings uncover that coordinated regulation of gene expression programs by a histone methyltransferase and a histone demethylase is coupled to the proliferation and invasion of breast cancer cells. Cancer Res; 74(6); 1705–17. ©2014 AACR.
Positron Emission Tomography Imaging with 18F-Labeled ZHER2:2891 Affibody for Detection of HER2 Expression and Pharmacodynamic Response to HER2-Modulating Therapies
Authors: Trousil Sebastian , Hoppmann Susan , Nguyen Quang-Dé , Kaliszczak Maciej , Tomasi Giampaolo , Iveson Peter , Hiscock Duncan , Aboagye Eric O.
Published: February 2014

Purpose: Expression of HER2 has profound implications on treatment strategies in various types of cancer. We investigated the specificity of radiolabeled HER2-targeting ZHER2:2891 Affibody, [18F]GE-226, for positron emission tomography (PET) imaging.

Experimental Design: Intrinsic cellular [18F]GE-226 uptake and tumor-specific tracer binding were assessed in cells and xenografts with and without drug treatment. Specificity was further determined by comparing tumor localization of a fluorescently labeled analogue with DAKO HercepTest.

Results: [18F]GE-226 uptake was 11- to 67-fold higher in 10 HER2-positive versus HER2-negative cell lines in vitro independent of lineage. Uptake in HER2-positive xenografts was rapid with net irreversible binding kinetics making possible the distinction of HER2-negative [MCF7 and MCF7-p95HER2: NUV60 (%ID/mL) 6.1 ± 0.7; Ki (mL/cm3/min) 0.0069 ± 0.0014] from HER2-positive tumors (NUV60 and Ki: MCF7-HER2, 10.9 ± 1.5 and 0.015 ± 0.0035; MDA-MB-361, 18.2 ± 3.4 and 0.025 ± 0.0052; SKOV-3, 18.7 ± 2.4 and 0.036 ± 0.0065) within 1 hour. Tumor uptake correlated with HER2 expression determined by ELISA (r2 = 0.78), and a fluorophore-labeled tracer analogue colocalized with HER2 expression. Tracer uptake was not influenced by short-term or continuous treatment with trastuzumab in keeping with differential epitope binding, but reflected HER2 degradation by short-term NVP-AUY922 treatment in SKOV-3 xenografts (NUV60: 13.5 ± 2.1 %ID/mL vs. 9.0 ± 0.9 %ID/mL for vehicle or drug, respectively).

Conclusions: [18F]GE-226 binds with high specificity to HER2 independent of cell lineage. The tracer has potential utility for HER2 detection, irrespective of prior trastuzumab treatment, and to discern HSP90 inhibitor-mediated HER2 degradation. Clin Cancer Res; 20(6); 1632–43. ©2014 AACR.
Phase I Study of Oral Rigosertib (ON 01910.Na), a Dual Inhibitor of the PI3K and Plk1 Pathways, in Adult Patients with Advanced Solid Malignancies
Authors: Bowles Daniel W. , Diamond Jennifer R. , Lam Elaine T. , Weekes Colin D. , Astling David P. , Anderson Ryan T. , Leong Stephen , Gore Lia , Varella-Garcia Marileila , Vogler Brian W. , Keysar Stephen B. , Freas Elizabeth , Aisner Dara L. , Ren Chen , Tan Aik-Chook , Wilhelm Francois , Maniar Manoj , Eckhardt S. Gail , Messersmith Wells A. , Jimeno Antonio
Published: February 2014

Purpose: To determine the pharmacokinetics (PK), maximum tolerated dose (MTD), safety, and antitumor activity of an oral formulation of rigosertib, a dual phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (Plk1) pathway inhibitor, in patients with advanced solid malignancies.

Experimental Design: Patients with advanced solid malignancies received rigosertib twice daily continuously in 21-day cycles. Doses were escalated until intolerable grade ≥2 toxicities, at which point the previous dose level was expanded to define the MTD. All patients were assessed for safety, PK, and response. Urinary PK were performed at the MTD. Archival tumors were assessed for potential molecular biomarkers with multiplex mutation testing. A subset of squamous cell carcinomas (SCC) underwent exome sequencing.

Results: Forty-eight patients received a median of 2 cycles of therapy at 5 dose levels. Rigosertib exposure increased with escalating doses. Dose-limiting toxicities were hematuria and dysuria. The most common grade ≥2 drug-related toxicities involved urothelial irritation. The MTD is 560 mg twice daily. Activity was seen in head and neck SCCs (1 complete response, 1 partial response) and stable disease for ≥12 weeks was observed in 8 additional patients. Tumors experiencing ≥partial response had PI3K pathway activation, inactivated p53, and unique variants in ROBO3 and FAT1, two genes interacting with the Wnt/β-catenin pathway.

Conclusions: The recommended phase II dose of oral rigosertib is 560 mg twice daily given continuously. Urinary toxicity is the dose-limiting and most common toxicity. Alterations in PI3K, p53, and Wnt/β-catenin pathway signaling should be investigated as potential biomarkers of response in future trials. Clin Cancer Res; 20(6); 1656–65. ©2014 AACR.
Gramicidin A Blocks Tumor Growth and Angiogenesis through Inhibition of Hypoxia-Inducible Factor in Renal Cell Carcinoma
Authors: David Justin M. , Owens Tori A. , Inge Landon J. , Bremner Ross M. , Rajasekaran Ayyappan K.
Published: February 2014

Ionophores are hydrophobic organic molecules that disrupt cellular transmembrane potential by permeabilizing membranes to specific ions. Gramicidin A is a channel-forming ionophore that forms a hydrophilic membrane pore that permits the rapid passage of monovalent cations. Previously, we found that gramicidin A induces cellular energy stress and cell death in renal cell carcinoma (RCC) cell lines. RCC is a therapy-resistant cancer that is characterized by constitutive activation of the transcription factor hypoxia-inducible factor (HIF). Here, we demonstrate that gramicidin A inhibits HIF in RCC cells. We found that gramicidin A destabilized HIF-1α and HIF-2α proteins in both normoxic and hypoxic conditions, which in turn diminished HIF transcriptional activity and the expression of various hypoxia-response genes. Mechanistic examination revealed that gramicidin A accelerates O2-dependent downregulation of HIF by upregulating the expression of the von Hippel–Lindau (VHL) tumor suppressor protein, which targets hydroxylated HIF for proteasomal degradation. Furthermore, gramicidin A reduced the growth of human RCC xenograft tumors without causing significant toxicity in mice. Gramicidin A–treated tumors also displayed physiologic and molecular features consistent with the inhibition of HIF-dependent angiogenesis. Taken together, these results demonstrate a new role for gramicidin A as a potent inhibitor of HIF that reduces tumor growth and angiogenesis in VHL-expressing RCC. Mol Cancer Ther; 13(4); 788–99. ©2014 AACR.
Acid-Labile Subunit Levels and the Association with Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age
Authors: Renes J.S. , van Doorn J. , Breukhoven P.E. , Lem A.J. , de Ridder M.A.J. , Hokken-Koelega A.C.S.
Published: February 2014

Aims: To determine acid-labile subunit (ALS) levels in short small for gestational age (SGA) children and to assess the relationship between ALS levels and several clinical and laboratory characteristics. Also, to assess whether adding ALS levels to a growth prediction model might improve the long-term growth prediction. Design/Methods: ALS levels were measured in 312 short SGA children at the start of growth hormone (GH) treatment. Results: Median (interquartile range) ALS of all subjects was -0.5 SDS, significantly below the 0 SDS (p < 0.001). In 34 children (11%), ALS levels were ≤-2 SDS. ALS SDS correlated significantly with height SDS (r = 0.24, p < 0.001), weight SDS (r = 0.30, p < 0.001), BMI SDS (r = 0.20, p = 0.001), IGF-I SDS (r = 0.56, p < 0.001) and IGFBP-3 SDS (r = 0.67, p < 0.001). ALS SDS was also positively correlated with fasting insulin (r = 0.41, p < 0.001) and glucose levels (r = 0.33, p < 0.001), and HOMA-IR (r = 0.35, p < 0.001). Baseline ALS levels contributed to the long-term growth prediction of GH treatment (5%, p < 0.001). Conclusion: Short SGA children tend to have lower ALS levels compared to controls, albeit less reduced than IGF-I and IGFBP-3 levels. Our data suggest that ALS may be involved in glucose homeostasis. Determination of ALS levels before the start of GH treatment in short SGA children contributes moderately to a more accurate prediction of the growth response to GH treatment.
Reintroduced Sumatran Orangutans (Pongo abelii): Using Major Food Tree Species as Indicators of Habitat Suitability
Authors: Kelle Doris , Gärtner Stefanie , Pratje Peter H. , Storch Ilse
Published: February 2014

Reintroducing orangutans (Pongo spp.) into the wild requires a suitable, secure habitat. To identify acceptable areas for their reintroduction and define priority conservation sites, we analysed the tree species composition in the Bukit Tigapuluh ecosystem in Jambi, Sumatra. We used this information to determine the distribution patterns of those species that represent an essential part of the diet of reintroduced orangutans. Important orangutan food tree species showed significant differences in composition, frequency and abundance among topographic forest types and recovered selectively logged and unlogged forests. Riparian forests and recovered selectively logged areas offered a vegetation composition and forest structure most suitable for the reintroduction of orangutans and showed numerous important tree species that serve as indicator species, i.e. species growing predominantly or exclusively in a specific forest type.
Case Report: Guillain-Barré Syndrome following Renal Transplantation - A Diagnostic Dilemma
Authors: Jakes Adam D. , Jani Poonam , Bhandari Sunil
Published: February 2014

Background: Guillain-Barré syndrome (GBS) is an acute polyneuropathy caused by an autoimmune response towards a foreign antigen, notably viral infections. It is characterised by a symmetrical ascending paralysis with treatment remaining largely supportive; however, plasma exchange or intravenous immunoglobulins can be used to shorten recovery time. Case Report: We describe a case of severe acute GBS in a patient post-renal transplantation. The 44-year-old gentleman's induction therapy consisted of methyl prednisolone and basiliximab, with subsequent tacrolimus and mycophenolate mofetil as immunosuppressive agents. Tacrolimus was discontinued immediately on suspicion of a temporal relationship with the patient's condition, and substituted with a combination of ciclosporin, mycophenolate mofetil and prednisolone. Due to extensive patient screening prior to transplant, negative virology/immunology and normal nerve biopsy findings, both tacrolimus and basiliximab may be indicated as causative agents. Conclusion: Immunosuppressive-induced GBS should be considered a differential diagnosis in patients on tacrolimus or basiliximab with acute-onset limb weakness, especially if recently commenced. Discontinuation of tacrolimus and initiation of plasma exchange for the treatment for tacrolimus-associated GBS may be beneficial.
Aspirin Use in Heart Failure
Authors: Bermingham Margaret , Shanahan Mary Katherine , O’Connell Eoin , Dawkins Ian , Miwa Saki , O’Hanlon Rory , Gilmer John , McDonald Kenneth , Ledwidge Mark
Published: February 2014

Background—

Aspirin use in heart failure (HF) is controversial. The drug has proven benefit in comorbidities associated with HF; however, retrospective analysis of angiotensin-converting enzyme inhibitor trials and prospective comparisons with warfarin have shown increased risk of morbidity with aspirin use. This study aims to evaluate the association of low-dose aspirin with mortality and morbidity risk in a large community-based cohort.

Methods and Results—

This was a retrospective cohort study of patients attending an HF disease management program. Aspirin use at baseline and its association with mortality and HF hospitalization in the population was examined. Of 1476 patients (mean age, 70.4±12.4 years; 63% men), 892 (60.4%) were prescribed aspirin. Low-dose aspirin (75 mg/d) was prescribed to 828 (92.8%) patients. Median follow-up time was 2.6 (0.8–4.5) years. During the follow-up period, 464 (31.4%) patients died. In adjusted analysis, low-dose aspirin use was associated with reduced mortality risk compared with nonaspirin use (hazard ratio=0.58; 95% confidence interval, 0.46–0.74), and this was confirmed by a propensity-matched subgroup analysis. Low-dose aspirin use was associated with reduced risk of HF hospitalization compared with nonaspirin use in the total population (adjusted hazard ratio=0.70; 95% confidence interval, 0.54–0.90). In adjusted analysis, there was no difference in mortality or HF hospitalization between high-dose aspirin users (>75 mg/d) and nonaspirin users.

Conclusions—

In this study, low-dose aspirin therapy was associated with a significant reduction in mortality and morbidity risk during long-term follow-up. These results suggest that low-dose aspirin may have a continuing role in secondary prevention in HF and underline the need for more trials of low-dose aspirin use in HF.