bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and Characterization ofParacoccussp. GSM2 Capable of Degrading Textile Azo Dye Reactive Violet 5
Authors: Bheemaraddi Mallikarjun C. , Patil Santosh , Shivannavar Channappa T. , Gaddad Subhashchandra M.
Published: April 2014

A potential bacterial strain GSM2, capable of degrading an azo dye Reactive Violet 5 as a sole source of carbon, was isolated from textile mill effluent from Solapur, India. The 16S rDNA sequence and phenotypic characteristics indicated an isolated organism asParacoccussp. GSM2. This strain exhibited complete decolorization of Reactive Violet 5 (100 mg/L) within 16 h, while maximally it could decolorize 800 mg/L of dye within 38 h with 73% decolorization under static condition. For color removal, the most suitable pH and temperature were pH 6.0–9.0 and 25–40°C, respectively. The isolate was able to decolorize more than 70% of five structurally different azo dyes within 38 h. The isolate is salt tolerant as it can bring out more than 90% decolorization up to a salt concentration of 2% (w/v). UV-Visible absorption spectra before and after decolorization suggested that decolorization was due to biodegradation and was further confirmed by FT-IR spectroscopy. Overall results indicate the effectiveness of the strain GSM2 explored for the treatment of textile industry effluents containing various azo dyes. To our knowledge, this could be the first report on biodegradation of Reactive Violet 5 byParacoccussp. GSM2.
The Pathology of T Cells in Systemic Lupus Erythematosus
Authors: Mak Anselm , Kow Nien Yee
Published: April 2014

Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies. Thus, the condition was traditionally classified as a “B-cell disease”. Compelling evidence has however shown that without the assistance of the helper T lymphocytes, it is indeed difficult for the “helpless” B cells to become functional enough to trigger SLE-related inflammation. T cells have been recognized to be crucial in the pathogenicity of SLE through their capabilities to communicate with and offer enormous help to B cells for driving autoantibody production. Recently, a number of phenotypic and functional alterations which increase the propensity to trigger lupus-related inflammation have been identified in lupus T cells. Here, potential mechanisms involving alterations in T-cell receptor expressions, postreceptor downstream signalling, epigenetics, and oxidative stress which favour activation of lupus T cells will be discussed. Additionally, how regulatory CD4+, CD8+, andγδT cells tune down lupus-related inflammation will be highlighted. Lastly, while currently available outcomes of clinical trials evaluating therapeutic agents which manipulate the T cells such as calcineurin inhibitors indicate that they are at least as efficacious and safe as conventional immunosuppressants in treating lupus glomerulonephritis, larger clinical trials are undoubtedly required to validate these as-yet favourable findings.
Leczyme: A New Candidate Drug for Cancer Therapy
Authors: Tatsuta Takeo , Sugawara Shigeki , Takahashi Kohta , Ogawa Yukiko , Hosono Masahiro , Nitta Kazuo
Published: April 2014

Sialic acid-binding lectin (SBL), isolated from oocytes ofRana catesbeiana, is leczyme and has both lectin and ribonuclease (RNase) activities. A remarkable antitumor effect of SBL has also been reported. SBL agglutinates various kinds of tumor cells but not normal cells. SBL agglutination activity is not affected by mono- or oligosaccharides. However, SBL-induced agglutination and antitumor effects are inhibited by sialomucin but not asialomucin. In addition, SBL has very little effect on sialidase-treated cells. SBL causes cancer-selective induction of apoptosis by multiple signaling pathways, which target RNA. Synergistic antitumor effects with other molecules, such as tumor necrosis factor-related apoptosis ligand (TRAIL) and interferon-γ(IFN-γ), have been reported. Thus, SBL may be a novel candidate molecule for anticancer drug development. Sialoglycoconjugates on the tumor cell surface may be associated with lectin activity and antitumor effects of SBL. We review the properties of SBL, particularly its lectin, RNase, and antitumor activities, and comprehensively examine the potential application of SBL for clinical purposes.
Leaf Anatomy and Photochemical Behaviour ofSolanum lycopersicumL. Plants from Seeds Irradiated with Low-LET Ionising Radiation
Authors: De Micco V. , Paradiso R. , Aronne G. , De Pascale S. , Quarto M. , Arena C.
Published: April 2014

Plants can be exposed to ionising radiation not only in Space but also on Earth, due to specific technological applications or after nuclear disasters. The response of plants to ionising radiation depends on radiation quality/quantity and/or plant characteristics. In this paper, we analyse some growth traits, leaf anatomy, and ecophysiological features of plants ofSolanum lycopersicumL. “Microtom” grown from seeds irradiated with increasing doses of X-rays (0.3, 10, 20, 50, and 100 Gy). Both juvenile and compound leaves from plants developed from irradiated and control seeds were analysed through light and epifluorescence microscopy. Digital image analysis allowed quantifying anatomical parameters to detect the occurrence of signs of structural damage. Fluorescence parameters and total photosynthetic pigment content were analysed to evaluate the functioning of the photosynthetic machinery. Radiation did not affect percentage and rate of seed germination. Plants from irradiated seeds accomplished the crop cycle and showed a more compacthabitus. Dose-depended tendencies of variations occurred in phenolic content, while other leaf anatomical parameters did not show distinct trends after irradiation. The sporadic perturbations of leaf structure, observed during the vegetative phase, after high levels of radiation were not so severe as to induce any significant alterations in photosynthetic efficiency.
A Doping Bits Based BP Decoding for Rateless Distributed Source Coding Applications
Authors: Masoodhu Banu N. M. , Sasikumar S.
Published: April 2014

A novel doping bits based belief propagation decoding algorithm, for rate-adaptive LDPC codes based on fixed bipartite graph code, is proposed. The proposed work modifies the decoding algorithm, by converting the puncturing nodes to regular source nodes and by following the encoding rule at the decoder. The transmitted doping bits in place of punctured bits, with the modified decoding algorithm at the decoder, feed all the punctured nodes with reliable log likelihood ratios. This enables the proposed decoding algorithm to recover all punctured nodes in the early iteration. The fast convergence leads to decoder complexity reduction while providing considerable improvement in performance.
Thermal Transport between Graphene Sheets and SiC Substrate by Molecular-Dynamical Calculation
Authors: Wang Zan , Bi Kedong , Guan Huawei , Wang Jiong
Published: April 2014

Using nonequilibrium molecular dynamics, we investigate the mechanisms of thermal transport across SiC/graphene sheets. In simulations, 3C-, 4H-, and 6H-SiC are considered separately. Interfacial thermal resistances between Bernal stacking graphene sheets and SiC (Si- or C-terminated) are calculated at the ranges of 100 K~700 K. The results indicate, whether Si-terminated or C-terminated interface, the interfacial thermal resistances of 4H- and 6H-SiC have similar trends over temperatures. Si-terminated interfacial thermal resistances of 3C-SiC are higher than those of 4H- and 6H-SiC in a wide temperature range from 100 K to 600 K. But, for C-rich interface, this range is reduced from 350 K to 500 K.
Dynamics of an Information Spreading Model with Isolation
Authors: Zhao Xia-Xia , Wang Jian-Zhong
Published: April 2014

Information plays an important role in modern society. In this paper, we presented a mathematical model of information spreading with isolation. It was found that such a model has rich dynamics including Hopf bifurcation. The results showed that, for a wide range of parameters, there is a bistable phenomenon in the process of information spreading and thus the information cannot be well controlled. Moreover, the model has a limit cycle which implies that the information exhibits periodic outbreak which is consistent with the observations in the real world.
The Clinical Significance of PR, ER, NF-κB, and TNF-αin Breast Cancer
Authors: Zhou Xian-Long , Fan Wei , Yang Gui , Yu Ming-Xia
Published: April 2014

Objectives. To investigate the expression of estrogen (ER), progesterone receptors (PR), nuclear factor-κB (NF-κB), and tumor necrosis factor-α(TNF-α) in human breast cancer (BC), and the correlation of these four parameters with clinicopathological features of BC.Methods and Results. We performed an immunohistochemical SABC method for the identification of ER, PR, NF-κB, and TNF-αexpression in 112 patients with primary BC. The total positive expression rate of ER, PR, NF-κB, and TNF-αwas 67%, 76%, 84%, and 94%, respectively. The expressions of ER and PR were correlated with tumor grade, TNM stage, and lymph node metastasis (P<0.01, resp.), but not with age, tumor size, histological subtype, age at menarche, menopause status, number of pregnancies, number of deliveries, and family history of cancer. Expressions of ER and PR were both correlated with NF-κB and TNF-αexpression (P<0.05, resp.). Moreover, there was significant correlation between ER and PR(P<0.0001)as well as between NF-κB and TNF-αexpression(P<0.05).Conclusion. PR and ER are highly expressed, with significant correlation with NF-κB and TNF-αexpression in breast cancer. The important roles of ER and PR in invasion and metastasis of breast cancer are probably associated with NF-κB and TNF-αexpression.
Endocannabinoid Receptors Gene Expression in Morbidly Obese Women with Nonalcoholic Fatty Liver Disease
Authors: Auguet Teresa , Berlanga Alba , Guiu-Jurado Esther , Terra Ximena , Martinez Salomé , Aguilar Carmen , Filiu Elisa , Alibalic Ajla , Sabench Fàtima , Hernández Mercé , Del Castillo Daniel , Richart Cristóbal
Published: April 2014

Background. Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD.Methods. We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL,n=16), simple steatosis (SS,n=28), and nonalcoholic steatohepatitis (NASH,n=28) by enzyme-linked immunosorbent assay and RT-PCR.Results. We found that CB1 mRNA expression was significantly higher in NASH compared with SS and correlated negatively with PPARα. Regarding CB2, CB2 mRNA expression correlated positively with ACC1, PPARγ, IL6, TNFα, resistin, and adiponectin.Conclusions. The increased expression of CB1 in NASH and the negative correlation with PPARαsuggest a deleterious role of CB1 in NAFLD. Regarding CB2, its positive correlation with the anti-inflammatory molecule adiponectin and, paradoxically, with inflammatory genes suggests that this receptor has a dual role. Taken together, our results suggest that endocannabinoid receptors might be involved in the pathogenesis of NAFLD, a finding which justifies further study.
A Hybrid GRASP+VND Heuristic for the Two‐Echelon Vehicle Routing Problem Arising in City Logistics
Authors: Zeng Zheng-yang , Xu Wei-sheng , Xu Zhi-yu , Shao Wei-hui
Published: April 2014

The two‐echelon vehicle routing problem (2E‐VRP) is a variant of the classical vehicle routing problem (VRP) arising in
two‐level transportation systems such as those encountered in the context of city logistics. In the 2E‐VRP, freight from a depot is
compulsorily delivered through intermediate depots, named satellites. The first echelons are routes that distribute freight from depot
to satellites, and the second are those from satellites to customers. This problem is solved by a hybrid heuristic which is composed
of a greedy randomized adaptive search procedure (GRASP) with a route‐first cluster‐second procedure embedded and a variable
neighborhood descent (VND), called GRASP+VND hereafter. Firstly, an extended split algorithm in the GRASP continuously
splits randomly generated permutations of all customers and assigns customers to satellites reasonably until a feasible assignment
appears, and a complete 2E‐VRP feasible solution is obtained by solving the first echelon problem subsequently and, secondly,
a VND phase attempts to improve this solution until no more improvements can be found. The process above is iterated until the
maximum number of iterations is reached. Computational tests conducted on three sets of benchmark instances from the literature
show that our algorithm is both effective and efficient and outperforms the best existing heuristics for the 2E‐VRP.
rs744166 Polymorphism of theSTAT3Gene Is Associated with Risk of Gastric Cancer in a Chinese Population
Authors: Yuan Kexin , Liu Huimin , Huang Lina , Ren Xiyun , Liu Jingjing , Dong Xiaoqun , Tian Wenjing , Jia Yunhe
Published: April 2014

The aim of this study was to explore the association between polymorphisms in signal transducer and activator of transcription protein 3 (STAT3) and the risk of gastric cancer. In the present study, a case-control study was conducted in which rs2293152 and rs744166 polymorphisms inSTAT3were analyzed in 209 Chinese patients with gastric cancer and 294 cancer-free controls. The genotypes were determined by polymerase chain reaction restriction fragment length polymorphism method. For the rs744166 polymorphism, the TC genotype (adjustedOR=0.60, 95% CI = 0.39–0.92, andP=0.020) and CC genotype (adjustedOR=0.41, 95%CI=0.21–0.80, andP=0.009) were associated with a decreased risk of gastric cancer compared to the TT genotype. However, rs2293152 did not show any difference in gastric cancer risk between patients and controls in the CG/CC genotype compared to the GG genotype. Besides, the SNP effects were additive to the effects of environmental factors without any interaction between them in the susceptibility to gastric cancer. Collectively, rs744166 polymorphism might be significantly associated with a decreased risk of gastric cancer in a Chinese population. Additionally, polymorphisms inSTAT3, along with environmental factors, might be associated with the development of gastric cancer.
Modified Projective Outer Synchronization between Two Fractional Order Complex Networks via Adaptive Control
Authors: Liu Hong-juan , Liu Guo-qi , Yu Hai , Zhu Zhi-liang
Published: April 2014

The modified projective outer synchronization between two different fractional order complex dynamical networks with different node dynamics and different topological structures is investigated in this paper. Based on the stability theorem of fractional order systems, the adaptive controllers and sufficient criteria for achieving the synchronization are given by applying the nonlinear control. The proposed method is also applicable to modified projective outer synchronization between two fractional order complex networks with identical topological structures. In addition, there are fewer restrictions on the coupling configuration matrix and inner-coupling matrix. The corresponding numerical results coincide with theoretical analysis, which also show that feedback strength and fractional order can effectively affect the synchronization performance.
Prevalence of HIV and Syphilis Infection among Men Who Have Sex with Men in China: A Meta-Analysis
Authors: Zhou Yunhua , Li Dongliang , Lu Dabing , Ruan Yuhua , Qi Xiao , Gao Ge
Published: April 2014

Objectives.To figure out the most current prevalence of HIV and syphilis in MSM in China.Methods.A meta-analysis was conducted on the studies searched through PubMed, CNKI, and Wanfang published between 1 January 2009 and 11 April 2013.Results.Eighty-four eligible studies, either in Chinese or in English, were included in this review. The pooled prevalence of HIV and syphilis infection in MSM in China was 6.5% and 11.2%, respectively. The subgroup analyses indicated that the prevalence of HIV infection was higher in the economically less developed cities than that in the developed cities (7.5% versus 6.1%,P<0.05). In contrast, the prevalence of syphilis infection was lower in less developed cities than in developed cities (8.6% versus 15.1%). Studies with a sample size smaller than 500 had a lower prevalence of HIV and syphilis infection than those with a sample size greater than 500 (5.9% versus 7.2% for HIV; 11.0% versus 11.5% for syphilis, respectively).Conclusions.HIV and syphilis infection are prevalent in MSM in China. The different prevalence of HIV and syphilis infection between developing and developed cities underscores the need to target prevention strategies based on economic conditions.
Analysis of the Associations between Vitamin D and Albuminuria orβ-Cell Function in Chinese Type 2 Diabetes
Authors: Cai Xiaoling , Hu Zhaoheng , Chen Ling , Han Xueyao , Ji Linong
Published: April 2014

Objective. To investigate the associations of 25-(OH)D andβ-cell function or insulin resistance or albuminuria in Chinese type 2 diabetic patients.Methods. In total, 1408 type 2 diabetic patients without vitamin D supplement were included in this retrospective study.Results. Comparison between patients with and without 25-(OH)D deficiency indicated that, compared with patients with 25-(OH)D ≥ 50 nmol/L, patients with 25-(OH)D < 50 nmol/L showed a higher level of urine albumin-creatinine ratio (ACR) (90.15±10.30 mg/g versus52.79±14.97 mg/g). Multiple regression analysis indicated that 25-(OH)D was independently and negatively correlated with urine ACR (OR=0.985, 95%CI 0.972–0.999,P=0.03), adjusted by age, diabetic duration, HBP duration, SBP, HbA1c, creatinine, LDL-C, triglyceride, total cholesterol, and HDL-C. Compared with patients with normal level of urine ACR, patients with higher level of urine ACR showed a significant lower level of 25-(OH)D (34.49±13.52 nmol/L versus37.46±13.6 nmol/L,P=0.00). Analysis of the associations of 25-(OH)D andβ-cell function or insulin resistance showed that 25-(OH)D may not correlate withβ-cell function or insulin resistance.Conclusion. 25-(OH)D was independently associated with albuminuria in Chinese type 2 diabetic patients but was not associated withβ-cell function or insulin resistance.
Exergoeconomic and Enviroeconomic Analysis of Photovoltaic Modules of Different Solar Cells
Authors: Gaur Ankita , Tiwari G. N.
Published: April 2014

The exergoeconomic and enviroeconomic analysis of semitransparent and opaque photovoltaic (PV) modules based on different kinds of solar cells are presented. Annual electricity and net present values have also been computed for the composite climatic conditions of New Delhi, India. Irrespective of the solar cell type, the semitransparent PV modules have shown higher net energy loss rate (Len) and net exergy loss rate (Lex) compared to the opaque ones. Among all types of solar modules, the one based on c-Si, exhibited the minimum Len and Lex. Compared to the opaque ones, the semitransparent PV modules have shown higher CO2 reduction giving higher environmental cost reduction per annum and the highest environmental cost reduction per annum was found for a-Si PV module.
Stabilization and Tracking Control of Inverted Pendulum Using Fractional Order PID Controllers
Authors: Mishra Sunil Kumar , Chandra Dinesh
Published: April 2014

This work focuses on the use of fractional calculus to design robust fractional-order PID (PIλDμ) controller for stabilization and tracking control of inverted pendulum (IP) system. A particle swarm optimisation (PSO) based direct tuning technique is used to design two PIλDμcontrollers for IP system without linearizing the actual nonlinear model. The fitness function is minimized by running the SIMULINK model of IP system according to the PSO program in MATLAB. The performance of proposed PIλDμcontrollers is compared with two PID controllers. Simulation results are also obtained by adding disturbances to the model to show the robustness of the proposed controllers.
Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus
Authors: Li Jing , Leng Xiaomei , Li Zhijun , Ye Zhizhong , Li Caifeng , Li Xiaofeng , Zhu Ping , Wang Zhengang , Zheng Yi , Li Xiangpei , Zhang Miaojia , Tian Xin-Ping , Li Mengtao , Zhao Jiuliang , Zhang Feng-Chun , Zhao Yan , Zeng Xiaofeng
Published: April 2014

We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P<0.05) associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P<0.05). Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P<0.05). Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.
Different Bleeding Patterns with the Use of Levonorgestrel Intrauterine System: Are They Associated with Changes in Uterine Artery Blood Flow?
Authors: Bastianelli Carlo , Farris Manuela , Rapiti Stefania , Bruno Vecchio Roberta , Benagiano Giuseppe
Published: April 2014

Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis.Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated.Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion.Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates.
Morphological Characterisation of Some Important Indian Garcinia Species
Authors: Parthasarathy Utpala , Nandakishore O. P.
Published: April 2014

The genus Garcinia has over 200 species distributed in the tropics of the world. About 35 species occur in India, many of which are endemic and economically important with immense medicinal properties. However, lack of awareness, coupled with habitat destruction, leads to genetic erosion of this forest resource and many species are threatened. The Indian Institute of Spices Research (IISR), Calicut, has Garcinia genetic resources’ collection of 15 species of Western Ghats and Eastern Himalaya species. The morphological characterisation of the species of these two different eco systems indicates that there are variations within the species of the same ecosystem while there are similarities in the species of two different ecosystems.
Physiological Constants of the Entomopathogenic Bacterium Xenorhabdus nematophila Determined by Microbial Growth Kinetics
Authors: Kooliyottil Rinu , Inman Floyd , Mandjiny Sivanadane , Holmes Len
Published: April 2014

Xenorhabdus nematophila, an entomopathogenic bacterium that symbiotically associates with the entomoparasitic nematode Steinernema carpocapsae, was studied to determine its physiological parameters of glucose utilization. X. nematophila was cultured in chemically defined media containing various concentrations of glucose under optimal conditions utilizing a two-liter fermentation system. Specific growth rates were obtained from each glucose batch. Specific growth rates and their associated glucose concentrations were used to determine physiological parameters. These parameters include the bacterium’s substrate utilization constant (Ks) and its maximum specific growth rate (μmax). The bacteria exhibited a Ks value of 2.02 mg/L suggesting that X. nematophila has a high affinity for glucose. The μmax of Xenorhabdus was determined to be 1.03 h−1. Further research is needed to determine if microbial affinities to different substrates have any influence on biological relationships (symbiosis, pathogenicity, parasitism, etc.) between prokaryotes and higher organisms.
Incidence and Survival Analysis of Gastrointestinal Stromal Tumors in Shanghai: A Population-Based Study from 2001 to 2010
Authors: Lv Minzhi , Wu Chunxiao , Zheng Ying , Zhao Naiqing
Published: April 2014

Objectives.A population-based study was undertaken to investigate the epidemiological features of gastrointestinal stromal tumors (GISTs) in Shanghai, especially the incidence and the preliminary exploration of survival.Methods.A total of 1923 patients with GISTs diagnosed from 2001 to 2010 in Shanghai were reviewed. The annual incidence and overall survival of GISTs were calculated; Cox proportional hazards’ regression was used to analyze several prognostic factors.Results.The average crude incidence of GISTs was 2.11 per 100,000 between 2004 and 2008, and the age-standardized incidence was 1.28 per 100,000. The incidence increased gradually from 2004 to 2008. In addition, 57% of cases had GIST in the stomach and 33% in the intestine. The 5-year overall survival of GISTs was 86.98%. The Cox regression analysis showed older age (≥65 yr versus <40 yr, HR = 5.085; (40, 65) yr versus <40 yr, HR = 1.975), male gender (HR = 1.474), and tumor locations (intestinal versus stomach, HR = 1.609) were predictors of its mortality.Conclusion.GISTs, mainly occurring in the stomach, are more common in elderly population, with an increasing incidence from 2004 to 2008. Older age, male gender, and tumor locations are risk factors for its mortality.
The Multifaceted Functions of CXCL10 in Cardiovascular Disease
Authors: van den Borne Pleunie , Quax Paul H. A. , Hoefer Imo E. , Pasterkamp Gerard
Published: April 2014

C-X-C motif ligand 10 (CXCL10), or interferon-inducible protein-10, is a small chemokine belonging to the CXC chemokine family. Its members are responsible for leukocyte trafficking and act on tissue cells, like endothelial and vascular smooth muscle cells. CXCL10 is secreted by leukocytes and tissue cells and functions as a chemoattractant, mainly for lymphocytes. After binding to its receptor CXCR3, CXCL10 evokes a range of inflammatory responses: key features in cardiovascular disease (CVD). The role of CXCL10 in CVD has been extensively described, for example for atherosclerosis, aneurysm formation, and myocardial infarction. However, there seems to be a discrepancy between experimental and clinical settings. This discrepancy occurs from differences in biological actions between species (e.g. mice and human), which is dependent on CXCL10 signaling via different CXCR3 isoforms or CXCR3-independent signaling. This makes translation from experimental to clinical settings challenging. Furthermore, the overall consensus on the actions of CXCL10 in specific CVD models is not yet reached. The purpose of this review is to describe the functions of CXCL10 in different CVDs in both experimental and clinical settings and to highlight and discuss the possible discrepancies and translational difficulties. Furthermore, CXCL10 as a possible biomarker in CVD will be discussed.
The Use of Quick Response (QR) Codes in Landmark-Based Pedestrian Navigation
Authors: Basiri Anahid , Amirian Pouria , Winstanley Adam
Published: April 2014

Vehicle navigation systems usually simply function by calculating the shortest fastest route over a road network. In contrast, pedestrian navigation can have more diverse concerns. Pedestrians are not constrained to road/path networks; their route may involve going into buildings (where accurate satellite locational signals are not available) and they have different priorities, for example, preferring routes that are quieter or more sheltered from the weather. In addition, there are differences in how people are best directed: pedestrians noticing landmarks such as buildings, doors, and steps rather than junctions and sign posts. Landmarks exist both indoors and outdoors. A system has been developed that uses quick response (QR) codes affixed to registered landmarks allowing users to localise themselves with respect to their route and with navigational instructions given in terms of these landmarks. In addition, the system includes images of each landmark helping users to navigate visually in addition to through textual instructions and route maps. The system runs on a mobile device; the users use the device’s camera to register each landmark’s QR code and so update their position (particularly indoors) and progress through the route itinerary.
Road Rage: Prevalence Pattern and Web Based Survey Feasibility
Authors: Mina Shaily , Verma Rohit , Balhara Yatan Pal Singh , Ul-Hasan Shiraz
Published: April 2014

Introduction.Incidents of road rage are on a rise in India, but the literature is lacking in the aspect. There is an increasing realization of possibility of effective web based interventions to deliver public health related messages.Objective.The aim was to quantitatively evaluate risk factors among motor vehicle drivers using an internet based survey.Methods. Facebook users were evaluated using Life Orientation Test-Revised (LOT-R) and Driving Anger Scale (DAS).Results.An adequate response rate of 65.9% and satisfactory reliability with sizable correlation were obtained for both scales. Age was found to be positively correlated to LOT-R scores (r=0.21;P=0.02) and negatively correlated to DAS scores (r=-0.19;P=0.03). Years of education were correlated to LOT-R scores (r=0.26;P=0.005) but not DAS scores (r=-0.14;P=0.11). LOT-R scores did not correlate to DAS scores.Conclusion.There is high prevalence of anger amongst drivers in India particularly among younger males. A short web survey formatted in easy to use question language can result in a feasible conduction of an online survey.
Biomarkers of Type II Synthetic Pyrethroid Pesticides in Freshwater Fish
Authors: Kaviraj Anilava , Gupta Abhik
Published: April 2014

Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions.
A Heuristic for Disassembly Planning in Remanufacturing System
Authors: Sung Jinmo , Jeong Bongju
Published: April 2014

This study aims to improve the efficiency of disassembly planning in remanufacturing environment. Even though disassembly processes are considered as the reverse of the corresponding assembly processes, under some technological and management constraints the feasible and efficient disassembly planning can be achieved by only well-designed algorithms. In this paper, we propose a heuristic for disassembly planning with the existence of disassembled part/subassembly demands. A mathematical model is formulated for solving this problem to determine the sequence and quantity of disassembly operations to minimize the disassembly costs under sequence-dependent setup and capacity constraints. The disassembly costs consist of the setup cost, part inventory holding cost, disassembly processing cost, and purchasing cost that resulted from unsatisfied demand. A simple but efficient heuristic algorithm is proposed to improve the quality of solution and computational efficiency. The main idea of heuristic is to divide the planning horizon into the smaller planning windows and improve the computational efficiency without much loss of solution quality. Performances of the heuristic are investigated through the computational experiments.
G Protein–Coupled Receptor Kinase GRK5 Phosphorylates Moesin and Regulates Metastasis in Prostate Cancer
Authors: Chakraborty Prabir Kumar , Zhang Yushan , Coomes Alexandra S. , Kim Wan-Ju , Stupay Rachel , Lynch Lauren D. , Atkinson Tamieka , Kim Jae I. , Nie Zhongzhen , Daaka Yehia
Published: April 2014

G protein–coupled receptor kinases (GRK) regulate diverse cellular functions ranging from metabolism to growth and locomotion. Here, we report an important contributory role for GRK5 in human prostate cancer. Inhibition of GRK5 kinase activity attenuated the migration and invasion of prostate cancer cells and, concordantly, increased cell attachment and focal adhesion formation. Mass spectrometric analysis of the phosphoproteome revealed the cytoskeletal-membrane attachment protein moesin as a putative GRK5 substrate. GRK5 regulated the subcellular distribution of moesin and colocalized with moesin at the cell periphery. We identified amino acid T66 of moesin as a principal GRK5 phosphorylation site and showed that enforcing the expression of a T66-mutated moesin reduced cell spreading. In a xenograft model of human prostate cancer, GRK5 silencing reduced tumor growth, invasion, and metastasis. Taken together, our results established GRK5 as a key contributor to the growth and metastasis of prostate cancer. Cancer Res; 74(13); 3489–500. ©2014 AACR.
NADPH Oxidase NOX4 Supports Renal Tumorigenesis by Promoting the Expression and Nuclear Accumulation of HIF2α
Authors: Gregg Jennifer L. , Turner Robert M. , Chang Guimin , Joshi Disha , Zhan Ye , Chen Li , Maranchie Jodi K.
Published: April 2014

Most sporadically occurring renal tumors include a functional loss of the tumor suppressor von Hippel Lindau (VHL). Development of VHL-deficient renal cell carcinoma (RCC) relies upon activation of the hypoxia-inducible factor-2α (HIF2α), a master transcriptional regulator of genes that drive diverse processes, including angiogenesis, proliferation, and anaerobic metabolism. In determining the critical functions for HIF2α expression in RCC cells, the NADPH oxidase NOX4 has been identified, but the pathogenic contributions of NOX4 to RCC have not been evaluated directly. Here, we report that NOX4 silencing in VHL-deficient RCC cells abrogates cell branching, invasion, colony formation, and growth in a murine xenograft model RCC. These alterations were phenocopied by treatment of the superoxide scavenger, TEMPOL, or by overexpression of manganese superoxide dismutase or catalase. Notably, NOX4 silencing or superoxide scavenging was sufficient to block nuclear accumulation of HIF2α in RCC cells. Our results offer direct evidence that NOX4 is critical for renal tumorigenesis and they show how NOX4 suppression and VHL re-expression in VHL-deficient RCC cells are genetically synonymous, supporting development of therapeutic regimens aimed at NOX4 blockade. Cancer Res; 74(13); 3501–11. ©2014 AACR.
Genetic and Pharmacological Strategies to Refunctionalize the von Hippel Lindau R167Q Mutant Protein
Authors: Ding Zhiyong , German Peter , Bai Shanshan , Reddy A. Srinivas , Liu Xian-De , Sun Mianen , Zhou Lijun , Chen Xiaohua , Zhao Xiaobei , Wu Chengbiao , Zhang Shuxing , Mills Gordon B. , Jonasch Eric
Published: April 2014

Aberrant von Hippel Lindau (VHL) protein function is the underlying driver of VHL-related diseases, including both sporadic and inherited clear cell renal cell carcinoma (ccRCC). About one third of VHL mutations are missense point mutations, with R167Q being the most common VHL point mutation in hereditary VHL disease. Although it has been studied extensively, the ability of VHL-R167Q to downregulate hypoxia-inducible factor 2α (HIF2α) is still controversial. In addition, the manner in which the mutation contributes to tumorigenesis is not fully understood. No therapeutic approach is available to target VHL-R167Q and similar missense point mutations. We analyzed VHL-R167Q proteostasis and function at normoxia, at hypoxia with different oxygen pressure, and in a xenograft mouse model. We showed that the protein levels of VHL-R167Q dictate its ability to downregulate HIF2α and suppress tumor growth. Strikingly, the proteasome inhibitors bortezomib and carfilzomib, which are currently in clinical use, stabilize VHL-R167Q and increase its ability to downregulate HIF2α. VHL-R167Q binds elongin C and elongin B with considerably less avidity than wild-type VHL does but retains residual capacity to generate a VHL-elongin C-elongin B complex, downregulate HIF2α, and suppress tumorigenesis, which could be rescued by increase of VHL-R167Q levels. Finally, we used in silico approaches and identified other missense VHL mutants in addition to VHL-R167Q that might be rescued by similar strategies. Thus, our studies revealed detailed information describing how VHL-R167Q contributes to tumorigenesis and identified a potential targeted therapy for ccRCC and other VHL-related disease in patients carrying VHL-R167Q or similar missense mutations. Cancer Res; 74(11); 3127–36. ©2014 AACR.
Colorectal Cancer Cell Lines Are Representative Models of the Main Molecular Subtypes of Primary Cancer
Authors: Mouradov Dmitri , Sloggett Clare , Jorissen Robert N. , Love Christopher G. , Li Shan , Burgess Antony W. , Arango Diego , Strausberg Robert L. , Buchanan Daniel , Wormald Samuel , O'Connor Liam , Wilding Jennifer L. , Bicknell David , Tomlinson Ian P.M. , Bodmer Walter F. , Mariadason John M. , Sieber Oliver M.
Published: April 2014

Human colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, to what extent these established cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 colorectal cancer cell lines for mutations and DNA copy number by whole-exome sequencing and SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published for primary colorectal cancers in The Cancer Genome Atlas. Notably, we found that exome mutation and DNA copy-number spectra in colorectal cancer cell lines closely resembled those seen in primary colorectal tumors. Similarities included the presence of two hypermutation phenotypes, as defined by signatures for defective DNA mismatch repair and DNA polymerase ϵ proofreading deficiency, along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGFβ, and p53 pathways. Furthermore, we documented mutations enriched in genes involved in chromatin remodeling (ARID1A, CHD6, and SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, and TRRAP). Chromosomal instability was prevalent in nonhypermutated cases, with similar patterns of chromosomal gains and losses. Although paired cell lines derived from the same tumor exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differences mainly reflected a preexisting heterogeneity in the tumor cells. In conclusion, our results establish that human colorectal cancer lines are representative of the main subtypes of primary tumors at the genomic level, further validating their utility as tools to investigate colorectal cancer biology and drug responses. Cancer Res; 74(12); 3238–47. ©2014 AACR.
New Strategies in Ewing Sarcoma: Lost in Translation?
Authors: Arnaldez Fernanda I. , Helman Lee J.
Published: April 2014

Ewing sarcoma is the second most common pediatric malignant bone tumor. Aggressive multimodality therapy has led to an improvement in outcomes, particularly in patients with localized disease. However, therapy-related toxicities are not trivial, and the prognosis for patients with relapsed and/or metastatic disease continues to be poor. In this article, we outline some of the promising therapies that have the potential to change the Ewing sarcoma therapeutic paradigm in the not-too-distant future: insulin-like growth factor receptor inhibitors, targeting of the fusion protein, epigenetic manipulation, PARP inhibitors, and immunotherapy. Clin Cancer Res; 20(12); 3050–6. ©2014 AACR.
A Meta-analysis of Somatic Mutations from Next Generation Sequencing of 241 Melanomas: A Road Map for the Study of Genes with Potential Clinical Relevance
Authors: Xia Junfeng , Jia Peilin , Hutchinson Katherine E. , Dahlman Kimberly B. , Johnson Douglas , Sosman Jeffrey , Pao William , Zhao Zhongming
Published: April 2014

Next generation sequencing (NGS) has been used to characterize the overall genomic landscape of melanomas. Here, we systematically examined mutations from recently published melanoma NGS data involving 241 paired tumor-normal samples to identify potentially clinically relevant mutations. Melanomas were characterized according to an in-house clinical assay that identifies well-known specific recurrent mutations in five driver genes: BRAF (affecting V600), NRAS (G12, G13, and Q61), KIT (W557, V559, L576, K642, and D816), GNAQ (Q209), and GNA11 (Q209). Tumors with none of these mutations are termed “pan negative.” We then mined the driver mutation-positive and pan-negative melanoma NGS data for mutations in 632 cancer genes that could influence existing or emerging targeted therapies. First, we uncovered several genes whose mutations were more likely associated with BRAF- or NRAS-driven melanomas, including TP53 and COL1A1 with BRAF, and PPP6C, KALRN, PIK3R4, TRPM6, GUCY2C, and PRKAA2 with NRAS. Second, we found that the 69 “pan-negative” melanoma genomes harbored alternate infrequent mutations in the five known driver genes along with many mutations in genes encoding guanine nucleotide binding protein α-subunits. Third, we identified 12 significantly mutated genes in “pan-negative” samples (ALK, STK31, DGKI, RAC1, EPHA4, ADAMTS18, EPHA7, ERBB4, TAF1L, NF1, SYK, and KDR), including five genes (RAC1, ADAMTS18, EPHA7, TAF1L, and NF1) with a recurrent mutation in at least two “pan-negative” tumor samples. This meta-analysis provides a road map for the study of additional potentially actionable genes in both driver mutation-positive and pan-negative melanomas. Mol Cancer Ther; 13(7); 1918–28. ©2014 AACR.
PI3K and Bcl-2 Inhibition Primes Glioblastoma Cells to Apoptosis through Downregulation of Mcl-1 and Phospho-BAD
Authors: Pareja Fresia , Macleod David , Shu Chang , Crary John F. , Canoll Peter D. , Ross Alonzo H. , Siegelin Markus D.
Published: April 2014

Glioblastoma multiforme (GBM) is a highly malignant human brain neoplasm with limited therapeutic options. GBMs display a deregulated apoptotic pathway with high levels of the antiapoptotic Bcl-2 family of proteins and overt activity of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Therefore, combined interference of the PI3K pathway and the Bcl-2 family of proteins is a reasonable therapeutic strategy. ABT-263 (Navitoclax), an orally available small-molecule Bcl-2 inhibitor, and GDC-0941, a PI3K inhibitor, were used to treat established glioblastoma and glioblastoma neurosphere cells, alone or in combination. Although GDC-0941 alone had a modest effect on cell viability, treatment with ABT-263 displayed a marked reduction of cell viability and induction of apoptotic cell death. Moreover, combinatorial therapy using ABT-263 and GDC-0941 showed an enhanced effect, with a further decrease in cellular viability. Furthermore, combination treatment abrogated the ability of stem cell–like glioma cells to form neurospheres. ABT-263 and GDC-0941, in combination, resulted in a consistent and significant increase of Annexin V positive cells and loss of mitochondrial membrane potential compared with either monotherapy. The combination treatment led to enhanced cleavage of both initiator and effector caspases. Mechanistically, GDC-0941 depleted pAKT (Serine 473) levels and suppressed Mcl-1 protein levels, lowering the threshold for the cytotoxic actions of ABT-263. GDC-0941 decreased Mcl-1 in a posttranslational manner and significantly decreased the half-life of Mcl-1 protein. Ectopic expression of human Mcl-1 mitigated apoptotic cell death induced by the drug combination. Furthermore, GDC-0941 modulated the phosphorylation status of BAD, thereby further enhancing ABT-263–mediated cell death.

Implications: Combination therapy with ABT-263 and GDC-0941 has novel therapeutic potential by specifically targeting aberrantly active, deregulated pathways in GBM, overcoming endogenous resistance to apoptosis. Mol Cancer Res; 12(7); 987–1001. ©2014 AACR.
Prevalence of Surgical Site Infection at the Stoma Site following Four Skin Closure Techniques: A Retrospective Cohort Study
Authors: Li Linda T. , Brahmbhatt Reshma , Hicks Stephanie C. , Davila Jessica A. , Berger David H. , Liang Mike K.
Published: April 2014

Background/Aims: Surgical site infection (SSI) is a common complication of stoma reversal. Studies have suggested that different skin closures affect SSI rates. Our aim was to determine which skin closure technique following stoma reversal leads to the lowest rate of SSI. Methods: We conducted a retrospective review of all adult patients undergoing stoma reversal at a single institution (2005-2011) and compared the rate of SSI following four skin closure techniques: primary closure (PC), secondary closure (SC), loose PC (LPC), and circular closure (CC). Univariate analysis included χ2 or Fisher's exact test and ANOVA or Kruskal-Wallis H test for categorical and continuous data, respectively. A multivariate logistic regression model was created to identify predictors of SSI. Results: One hundred and forty-six patients were identified: 40 (27%) PC, 68 (47%) SC, 20 (14%) LPC, and 18 (12%) CC. CC was less likely to have SSI (6%) compared to PC (43%), SC (16%), and LPC (15%; p < 0.01). Increasing body mass index was a predictor of SSI (odds ratio 1.11, 95% confidence interval 1.04-1.12, p < 0.01). CC was associated with the lowest odds of developing SSI [0.07 (0.01-0.63), p = 0.02]. Conclusions: SSI rate was the lowest for stomas that were closed with CC.