bluuebunny/crossref_metadata_2025 huggingface dataset:
Error/Erasure-Resilient and Complexity-Constrained Zero-Delay Distributed Coding for Large-Scale Sensor Networks
Authors: Viswanatha Kumar , Ramaswamy Sharadh , Saxena Ankur , Rose Kenneth
Published: December 2014

There has been considerable interest in distributed source coding (DSC) in recent years, primarily due to its potential contributions to low-power sensor networks. However, two major obstacles pose an existential threat to practical deployment of such techniques: the exponential growth of decoding complexity with network size and coding rates and the critical requirement of resilience to bit errors and erasures, given the severe channel conditions in many wireless sensor network applications. This article proposes a novel, unified approach for large-scale, error/erasure-resilient DSC that incorporates an optimally designed, nearest neighbor classifier-based decoding framework, where the design explicitly controls performance versus decoding complexity. Motivated by the highly nonconvex nature of the cost function, we present a deterministic annealing-based optimization algorithm for the joint design of the system parameters, which further enhances the performance over the greedy iterative descent technique. Simulation results on both synthetic and real sensor network data provide strong evidence for performance gains compared to other state-of-the-art techniques and may open the door to practical deployment of DSC in large sensor networks. Moreover, the framework provides a principled way to naturally scale to large networks while constraining decoder complexity, thereby enabling performance gains that increase with network size.
A Distributed Load-balancing Scheme Based on a Complex Network Model of Cloud Servers
Authors: Kumar Narander , Agarwal Shalini , Zaidi Taskeen , Saxena Vipin
Published: December 2014

Efficient management of resources in a federation of interacting computing servers and devices, for example, in a cloud computing environment, requires a load-balancing system that is self-regulatory and oblivious in nature. Due to the increasing size of data centers and their distribution across the globe, centralized load-balancing approaches suffer significant deficiencies in terms of communication overhead caused by the need to collect state dependent information. The technology of the cloud in its current state runs as many as 200 virtual machines on a single server, which clearly shows the importance of studying distributed load-balancing systems in the cloud. In the present paper, the federation of cloud servers is modeled as a complex network. In a complex network the structure and dynamics of the underlying system are encoded in the network topology itself. A method using random walks on complex networks for discovering free resources in a Cloud Server Network is given. The given method is used to balance the overall load on the network by equalising loads on overloaded and underloaded nodes without the need of a global load balancer. Simulation results are obtained through Network Simulator Version 2, which show that the proposed load-balancing scheme performs well for a large network by uniformly distributing the workload among the servers in polynomial time.
Measurement of the Reliability of a Component-Based Development using a Path-Based Approach
Authors: Nautiyal Lata , Gupta Neena , Dimri Sushil Chandra
Published: December 2014

Component-based systems are based on the idea of assembling lots of independent and pre-defined components based on discriminating designs. Component-based systems provide a better reuse of software components along with flexibility, scalability and better quality of services to fulfill the requirements of the end user. We can consider component-based software engineering successful only if it has the ability to select and integrate reliable components. In this paper we propose an innovative reliability model in terms of multiple execution paths and the usage percentage of each and every component.
Identifying Interactions for Combinatorial Testing using Data Flow Techniques
Authors: Sabharwal Sangeeta , Aggarwal Manuj
Published: December 2014

Combinatorial (t-way) testing has been proved to be an effective technique that identifies faults caused by interactions among a small number of input parameters. However, the degree of interaction to be considered for testing is still an open issue. Although higher strength t-way testing improves fault detection, it leads to a considerable increase in number of interactions to be tested and hence the test set size. In this paper, an approach is proposed that attempts to reduce the number of interactions to be tested. The source code is transformed into a flow graph and data flow analysis is applied to it to identify the interactions that exist in the system. The initial results suggest that the approach is able to achieve a considerable reduction in the number of interactions to be tested.
How to Develop a General Theory of Software Engineering
Authors: Ralph Paul , Exman Iaakov , Ng Pan-Wei , Johnson Pontus , Goedicke Michael , Kocata Alper Tolga , Yan Kate Liu
Published: December 2014

Many academic disciplines have general theories, which apply across the discipline and explain diverse phenomena. General theories facilitate developing a cumulative body of knowledge, increase a field's resistance to fads and pseudoscience, and help us respond to novel situations where old heuristics break down. The goal of the SEMAT General Theory of Software Engineering (GTSE) workshop is therefore to promote developing and testing general theories for software engineering. The Third GTSE workshop was co-located with the International Conference on Software Engineering (ICSE) in 2014. Participants explored different types of theories and how to assemble them into a framework. Participants debated how to make theories practical to practitioners and agreed that different types of practitioners (e.g. developers) have different needs for theories.
FLOSS Research Track at the 10th International Symposium on Open Collaboration (OpenSym 2014)
Authors: Robles Gregorio , González-Barahona Jesús M. , Riehle Dirk
Published: December 2014

This is a report from the Free/Libre/Open Source (FLOSS) research track at the 10th International Symposium on Open Collaboration (OpenSym 2014), which took place in Berlin, Germany, August 27-29. As part of a broader community interested in "everything open", including open access, open data, open educational resources, Wikipedia, wikis and open collaboration, this research track was a place to discuss software engineering related issues from various points of view, based on a selection of research papers that was considered by the programme committee. As such, we had contributions on technical (such as the usefulness of automatic bug reporting tools, the implementation of standards, or linking various data sources), community-related (integration, congruence), economic (business models, or the impact of FLOSS in the growth of businesses), and fundamental (such as software forks) matters. We look forward to next year's OpenSym, which will take place 19-21 August 2015 in San Francisco, California, see http://opensym.org.
legaSCi
Authors: Schumacher Christoph , Weinstock Jan Henrik , Leupers Rainer , Ascheid Gerd , Tosoratto Laura , Lonardo Alessandro , Petras Dietmar , Hoffmann Andreas
Published: December 2014

Architects and developers use virtual prototypes of computer systems to receive early feedback on hardware design decisions as well as to develop and debug system software. This is facilitated by the comprehensive inspection capabilities virtual prototypes offer. For virtual prototypes, execution speed is crucial to support the users' productivity. Parallel simulation techniques are employed to offset the speed impact of the increasing number of cores that need to be simulated in virtual prototypes of parallel and embedded systems.

SystemC is the de facto industry standard library for virtual platform modeling. Since currently no parallel SystemC library is commonly available, typical SystemC models are coded for execution in sequential simulation environments. Simply putting such models into parallel simulators may lead to thread-safety issues and may additionally cause nondeterministic simulator behavior.

This article proposes a methodology to support simulation creators to face the challenge of integrating such legacy models into parallel SystemC environments. The feasibility of the proposed method is evaluated by parallelizing the latest instance of the EU FP7 project EURETILE embedded platform simulator. Using
legaSCi
, on four host processor cores a speedup of 2.13× is demonstrated, without having to change the individual models of the simulator.
Now what?
Authors: Stout Jane , Camp Tracy
Published: December 2014

Our culture is currently paying a great deal of attention to issues of diversity in computing and technology. More specifically, society wonders why there are not more women involved in computing. Statistics on women's representation in all levels of the postsecondary academic pipeline, and in professions outside of the academy, have been bleak for decades. In response to this, social scientists have taken great interest in understanding why this cultural phenomenon exists. Although women's underrepresentation may seem intractable due to many years of stagnancy, we urge readers to take heart, and capitalize on the cultural climate, which places great emphasis on promoting gender equity and diversity in computing.

In this article, we review a number of factors that explain women's low participation in and attrition from computing, which have been developed through empirical research. We then articulate actionable items that can be implemented "on the ground" in classrooms and professional settings, as well as "on the books" at the administrative and public policy level. We conclude by urging readers to consider this a "people's issue" rather than a "women's issue", because all people can benefit from environments, cultural beliefs and policies that espouse inclusivity and equity.
Much ado about salary
Authors: Barr Valerie
Published: December 2014

This paper is a response to the interview between Maria Klawe and Satya Nadella at the 2014 Grace Hopper Celebration of Women in Computing conference in a context of the history of the conference since 1994. Maria Klawe is president of Harvey Mudd College and member of the Microsoft board of directors. Satya Nadella is the CEO of Microsoft.
Reflections on GHC2014
Authors: Weikle Dee A. B.
Published: December 2014

In this paper, we describe the formatting guidelines for ACM SIG Proceedings.
Computational Geometry Column 60
Authors: Dumitrescu Adrian , Jiang Minghui
Published: December 2014

This column is devoted to maximal empty axis-parallel rectangles amidst a point set. In particular, among these, maximum-area rectangles are of interest.
Some Function Spaces via Orthonormal Bases on Spaces of Homogeneous Type
Authors: Chen Chuang , Li Ji , Liao Fanghui
Published: December 2014

Let(X,d,μ)be a space of homogeneous type in the sense of Coifman and Weiss, where the quasi-metricdmay have no regularity and the measureμsatisfies only the doubling property. Adapting the recently developed randomized dyadic structures ofXand applying orthonormal bases ofL2(X)constructed recently by Auscher and Hytönen, we develop the Besov and Triebel-Lizorkin spaces on such a general setting. In this paper, we establish the wavelet characterizations and provide the dualities for these spaces. The results in this paper extend earlier related results with additional assumptions on the quasi-metricdand the measureμto the full generality of the theory of these function spaces.
A Comparative Study on Visual Choice Reaction Time for Different Colors in Females
Authors: Balakrishnan Grrishma , Uppinakudru Gurunandan , Girwar Singh Gaur , Bangera Shobith , Dutt Raghavendra Aswini , Thangavel Dinesh
Published: December 2014

Reaction time is one of the important methods to study a person’s central information processing speed and coordinated peripheral movement response. Visual choice reaction time is a type of reaction time and is very important for drivers, pilots, security guards, and so forth. Previous studies were mainly on simple reaction time and there are very few studies on visual choice reaction time. The aim of our study was to compare the visual choice reaction time for red, green, and yellow colors of 60 healthy undergraduate female volunteers. After giving adequate practice, visual choice reaction time was recorded for red, green, and yellow colors using reaction time machine (RTM 608, Medicaid, Chandigarh). Repeated measures of ANOVA and Bonferroni multiple comparison were used for analysis andP<0.05was considered statistically significant. The results showed that both red and green had significantly less choice visual choice reaction (Pvalues<0.0001and 0.0002) when compared with yellow. This could be because individual color mental processing time for yellow color is more than red and green.
Synthesis of a Biglucoside and Its Application as Montmorillonite Hydration Inhibitor
Authors: Zhang Xin-chun , Wang Xing-zhi , Chen Gang , Deng Qiang , Hao Huarui
Published: December 2014

A biglucoside (BG) was synthesized with glucose and epichlorohydrin as raw materials. The inhibition of BG against montmorillonite swelling was investigated by various methods including montmorillonite linear expansion test, mud ball immersing test, thermogravimetric analysis, and scanning electron microscopy. The results show that the BG has good inhibition ability to the hydration swelling and dispersion of montmorillonite. Under the same condition, the linear expansion ratio of montmorillonite in BG solution is much lower than that of MEG. The particle distribution measurement, thermogravimetric analysis, FT-IR, and scanning electron microscopy results all prove the efficient inhibition of BG.
The Secretion of IL-22 from Mucosal NKp44+NK Cells Is Associated with Microbial Translocation and Virus Infection in SIV/SHIV-Infected Chinese Macaques
Authors: Wang Wei , Wu Fangxin , Cong Zhe , Liu Kejian , Qin Chuan , Wei Qiang
Published: December 2014

Microbial translocation (MT) causes systemic immune activation in chronic human immunodeficiency virus (HIV) infection. The role of a novel subtype of innate lymphoid cells, the NKp44+NK cells, in HIV/simian immunodeficiency virus- (SIV-) induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV-) infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44+NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44+NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44+NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44+NK cells and interleukin-22 (IL-22) secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44+NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.
Consolidation by Prefabricated Vertical Drains with a Threshold Gradient
Authors: Guo Xiao , Xie Kang-He , Deng Yue-Bao
Published: December 2014

This paper shows the development of an approximate analytical solution of radial consolidation by prefabricated vertical drains with a threshold gradient. To understand the effect of the threshold gradient on consolidation, a parametric analysis was performed using the present solution. The applicability of the present solution was demonstrated in two cases, wherein the comparisons with Hansbo’s results and observed data were conducted. It was found that (1) the flow with the threshold gradient would not occur instantaneously throughout the whole unit cell. Rather, it gradually occurs from the vertical drain to the outside; (2) the moving boundary would never reach the outer radius of influence if R + 1 < n, whereas it will reach the outer radius of influence at some time; (3) the excess pore pressure will not be dissipated completely, but it will maintain a long‐term stable value at the end of consolidation; (4) the larger the threshold gradient is, the greater the long‐term excess pore pressure will be; and (5) the present solution could predict the consolidation behavior in soft clay better than previous methods.
Rate of Nonadherence to Antipsychotic Medications and Factors Leading to Nonadherence among Psychiatric Patients in Gondar University Hospital, Northwest Ethiopia
Authors: Endale Gurmu Abyot , Abdela Esileman , Allele Bashir , Cheru Ermias , Amogne Bemnet
Published: December 2014

Objective. The main aim of this study was to assess the rate of medication nonadherence among psychiatry patients at University of Gondar Hospital. Materials and Methods. Cross-sectional, descriptive method was conducted over a period of one month in May, 2013, at University of Gondar Hospital. Rate of nonadherence was computed using Medication Adherence Rating Scale questionnaire and self-reporting via a structured patient interview. Chi-square was used to determine the statistical significance of the association of variables with adherence. Result. Out of 209 respondents, 105 (50.2%) were found to be nonadherent. Patients who were forced to take their medication against their will (P<0.001), those who did not believe they require medication (P=0.026), and those who discontinued their medication without consulting their prescriber (P<0.001) had significant association with nonadherence. Adherence among schizophrenia was 75.7%; psychotic was 46.7%; bipolar disorder was 37.5%; and psychosis with depression was 52.6%. Reasons for nonadherence included recovery from the illness (26.7%), seeking alternative therapy and unavailability of drugs (18.1% each), adverse drug reaction (12.7%), forgetfulness (10.6%), and being busy (8.6%). Conclusion. The observed rate of antipsychotic medication nonadherence in this study was high. Interventions to increase adherence are therefore crucial.
A Middleware for the Integration of Smart Grid Elements with WSN Based Solutions
Authors: de Araújo Paulo Régis C. , Holanda Raimir , Rodrigues Antonio Wendell de Oliveira , de Araújo André Luiz Carneiro , Moraes Filho José de Aguiar , Oliveira João Paolo C. M.
Published: December 2014

Currently, electricity distributors make use of various types of equipment divided into levels of automation. This automation enables the integration of elements such as Intelligent Electronic Devices (IEDs) to the supervision of the distribution electrical system, but there is not an appropriate environment to increase the scale of these elements. In this context, the smart grid comes with specifications that allow adding new elements to the intelligence of the power grid operation. However, the cost of communication is still an impediment to the scalability of the integration of these elements into the current structure. In this paper, we propose a middleware that optimizes the communication of this integration using wireless sensor networks (WSN). The goal is to ensure a gradual integration of new elements taking advantage of the increase in the number of sensor nodes in the network due to the scalability of the system itself. The conversion solutions have been used to allow easy communication between the WSN and the smart grid system, and we also have used data aggregation and compression techniques to increase the lifetime of the wireless sensor network.
A Case of Apparent Contact Dermatitis Caused byToxocaraInfection
Authors: Qualizza Rosanna , Makrì Eleni , Losappio Laura , Incorvaia Cristoforo
Published: December 2014

Infection fromToxocaraspecies may give rise to a large array of clinical symptoms, including apparent manifestations of allergy such as asthma, urticaria/angioedema, and dermatitis. We report a case, thus far not described, of contact dermatitis attributed to nickel allergy but caused byToxocarainfection. The patient was a 53-year-old woman presenting from 10 years a dermatitis affecting head, neck, and thorax. Patch tests initially performed gave a positive result to nickel, but avoidance of contact with nickel did not result in recovery. The patient referred to our Allergy Service in 2010 because of dermatitis to feet. Patch testing confirmed the positive result for nickel, but expanding the investigation a positive result for IgG antibodies toToxocarawas detected by Western blotting and ELISA. Treatment with mebendazole achieved immediate efficacy on feet dermatitis. Then, two courses of treatment with albendazole resulted in complete regression of dermatitis accompanied by development of negative ELISA and Western blotting forToxocaraantibodies. This report adds another misleading presentation ofToxocarainfection as apparent contact dermatitis caused by nickel and suggests bearing in mind, in cases of contact dermatitis not responding to avoidance of the responsible hapten and to medical treatment, the possible causative role ofToxocara.
Practical Implication of Chromatographic Method for Estimation of Aceclofenac and Pregabalin in Bulk and Pharmaceutical Dosage Forms
Authors: Gelani Hitendrakumar D. , Chauhan Payal P. , Shah Samir K.
Published: December 2014

Background. Aceclofenac and Pregabalin in combination significantly reduce pain as compared to individual drug in chronic low back pain. Literature reveals that all the reported spectrophotometric methods either need tedious extraction procedures, do not offer high sensitivity, use nonspecific reagent, or recommend the measurement of absorbance in the near UV region where interference most probably occurs that does not offer suitable linearity range. Result. A selective, sensitive, accurate, and precise, high performance liquid chromatographic method with UV detector analysis of Aceclofenac and Pregabalin was investigated. Good chromatographic separation was achieved using an ODS-BP hypersil C18 column (250 mm × 4.6 mm, i.d., 5 μm) and a mobile phase consisting of 0.05 M phosphate buffer (KH2PO4) (pH 6.0) : methanol (60 : 40, v/v) at a flow rate 1 mL/min. The ultraviolet detector was set at wavelength 218 nm. Retention time for Aceclofenac and Pregabalin was found to be 3.220 and 5.910 min, respectively. Rectilinear relationship with good regression coefficients 0.999 and 0.999 was found over the concentration ranges of 5–25 μg/mL and 3.75–18.75 μg/mL for ACF and PGB, respectively, with detection limits 0.64 and 0.35 μg/mL and quantitation limits 1.95 and 1.06 μg/mL. Conclusion. The mean percentage recoveries were in the range of 98.45–100.08 and 99.69–100.48 for ACF and PGB, respectively. The developed method was successfully applied to the analysis of the drugs in their commercial tablets.
Prevalence and Associated Factors of Pressure Ulcer among Hospitalized Patients at Felegehiwot Referral Hospital, Bahir Dar, Ethiopia
Authors: Gedamu Haileyesus , Hailu Mignote , Amano Abdella
Published: December 2014

Introduction. Pressure ulcers, also known as decubitus ulcers (bed sores), are localized skin injuries that remain a major health problem affecting approximately 3 million adults. Objective. The aim of this study was to assess the prevalence and associated factors of pressure ulcer among hospitalized patients in Felegehiwot referral hospital. Methods. This cross-sectional study used systematic sampling on a sample of 422 patients. The data was collected by trained data collectors through pretested checklist. Bivariate analysis was used principally and variables were then entered into multiple logistic regressions model for controlling the possible effect of confounders and the variables which have significant association were identified on the basis of OR with 95% CI and P value. Results. The finding of this study revealed that 71 (16.8%) of them had pressure ulcer. Prolonged length of stay in hospital, slight limit of sensory perception, and friction and shearing forces were significantly associated with the presence of pressure ulcer. Conclusions and Recommendations. The prevalence of pressure ulcer was high among hospitalized patients. Researches of prospective (follow-up) study required investigating the incidence and associated factors of pressure ulcer for hospitalized patients.
Prediction of Neutron Yield of IR-IECF Facility in High Voltages Using Artificial Neural Network
Authors: Sadighzadeh A. , Salehizadeh A. , Mohammadzadeh M. , Shama F. , Setayeshi S. , Feghhi S. A. H. , Sadati S. M. , Rezaei M. , Haji Ebrahimi E. , Roshani G. H.
Published: December 2014

Artificial neural network (ANN) is applied to predict the number of produced neutrons from IR-IECF device in wide discharge current and voltage ranges. Experimentally, discharge current from 20 to 100 mA had been tuned by deuterium gas pressure and cathode voltage had been changed from −20 to −82 kV (maximum voltage of the used supply). The maximum neutron production rate (NPR) of 1.46 × 107 n/s had occurred when the voltage was −82 kV and the discharge current was 48 mA. The back-propagation algorithm is used for training of the proposed multilayer perceptron (MLP) neural network structure. The obtained results show that the proposed ANN model has achieved good agreement with the experimental data. Results show that NPR of 1.855 × 108 n/s can be achieved in voltage and current of 125 kV and 45 mA, respectively. This prediction shows 52% increment in maximum voltage of power supply. Also, the optimum discharge current can increase 1270% NPR.
On the Torsion Units of Integral Adjacency Algebras of Finite Association Schemes
Authors: Herman Allen , Singh Gurmail
Published: December 2014

Torsion units of group rings have been studied extensively since the 1960s. As association schemes are generalization of groups, it is natural to ask about torsion units of association scheme rings. In this paper we establish some results about torsion units of association scheme rings analogous to basic results for torsion units of group rings.
Red Cell Distribution Width Is Associated with Presence, Stage, and Grade in Patients with Renal Cell Carcinoma
Authors: Wang Fang-Ming , Xu Gongjun , Zhang Yan , Ma Lu-Lin
Published: December 2014

It has been reported that red blood cell width (RDW) is a marker associated with the presence and adverse outcomes of various diseases. However, no data are available on the correlation of RDW with presence, stage, and grade in patients with renal cell carcinoma (RCC) yet. By retrospectively analyzing clinical and laboratory data at baseline of histologically confirmed RCC cases and controls, the present study demonstrated that the RDW values were significantly higher in patients with RCC than those in controls, and the baseline RDW value was independently associated with the presence of RCC. Besides, the data revealed a positive association between RCC stage and grade and the level of RDW. These findings may have important clinical implications due to future application using a RDW value in predicting RCC.
EOQ Model for Deteriorating Items with Stock‐Level‐Dependent Demand Rate and Order‐Quantity‐Dependent Trade Credit
Authors: Min Jie , Ou Jian , Zhong Yuan-Guang , Liu Xin-Bao
Published: December 2014

This paper develops a generalized inventory model for exponentially deteriorating items with current‐stock‐dependent demand rate and permissible delay in payments. In the model, the payment for the item must be made immediately if the order quantity is less than the predetermined quantity; otherwise, a fixed trade credit period is permitted. The maximization of the average profit per unit of time is taken as the inventory system’s objective. The necessary and sufficient conditions and some properties of the optimal solution to the model are developed. Simple solution procedures are proposed to efficiently determine the optimal ordering policies of the considered problem. Numerical example is also presented to illustrate the solution procedures obtained.
DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling
Authors: Liu Ronghua , Gu Jie , Jiang Pei , Zheng Yijie , Liu Xiaoming , Jiang Xuechao , Huang Enyu , Xiong Shudao , Xu Fengkai , Liu Guangwei , Ge Di , Chu Yiwei
Published: December 2014

Purpose: MicroRNAs (miRNA) are involved in and are controlled by epigenetic regulation, and thereby form a reciprocal regulatory circuit. Using next-generation sequencing (NGS)–based miRNA profiling, this study aimed to discover esophageal squamous cell carcinoma (ESCC)–specific miRNAs and miRNA-related epigenetic modulations.

Experimental Design: NGS-based miRNA profiles were generated for four pairs of ESCC tissues and adjacent normal tissues. In situ hybridization was used to assess miRNA expression and its correlation with prognosis. miRNA-related DNA methylations were identified using bisulfite genomic sequencing, and the role of DNA methyltransferase 1 (DNMT1) was investigated using RNA interference. miRNA targets were screened by mRNA sequencing, and functional validation was performed in vitro and in vivo.

Results: NGS-based miRNA profiling identified 78 differentially expressed miRNAs in ESCC. Among them, microRNA126-3p (miR-126) was significantly downregulated, and its downregulation correlated with poor ESCC prognosis. Downregulation of miR-126 was due to promoter hypermethylation of its host gene, Egfl7. DNMT1 was aberrantly upregulated in ESCC and responsible for the hypermethylation of Egfl7. Intriguingly, DNMT1 was suppressed by overexpression of miR-126, indicating the existence of a regulatory feedback circuit. ADAM9 was identified as a key target of miR-126. Ectopic expression of miR-126 or silencing of ADAM9 reduced ESCC cell proliferation and migration by inhibiting epidermal growth factor receptor–AKT signaling.

Conclusions: Our results indicate that miR-126 is a potential prognostic indicator for ESCC and suggest that a novel “DNMT1–miR-126 epigenetic circuit” is involved in ESCC progression. Consequently, miR-126–based epigenetic modulations may provide a basic rationale for new approaches to antitumor therapeutics. Clin Cancer Res; 21(4); 854–63. ©2014 AACR.
Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors
Authors: Goglia Alexander G. , Delsite Robert , Luz Antonio N. , Shahbazian David , Salem Ahmed F. , Sundaram Ranjini K. , Chiaravalli Jeanne , Hendrikx Petrus J. , Wilshire Jennifer A. , Jasin Maria , Kluger Harriet M. , Glickman J. Fraser , Powell Simon N. , Bindra Ranjit S.
Published: December 2014

Most cancer therapies involve a component of treatment that inflicts DNA damage in tumor cells, such as double-strand breaks (DSBs), which are considered the most serious threat to genomic integrity. Complex systems have evolved to repair these lesions, and successful DSB repair is essential for tumor cell survival after exposure to ionizing radiation (IR) and other DNA-damaging agents. As such, inhibition of DNA repair is a potentially efficacious strategy for chemo- and radiosensitization. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) represent the two major pathways by which DSBs are repaired in mammalian cells. Here, we report the design and execution of a high-throughput, cell-based small molecule screen for novel DSB repair inhibitors. We miniaturized our recently developed dual NHEJ and HR reporter system into a 384-well plate-based format and interrogated a diverse library of 20,000 compounds for molecules that selectively modulate NHEJ and HR repair in tumor cells. We identified a collection of novel hits that potently inhibit DSB repair, and we have validated their functional activity in a comprehensive panel of orthogonal secondary assays. A selection of these inhibitors was found to radiosensitize cancer cell lines in vitro, which suggests that they may be useful as novel chemo- and radio sensitizers. Surprisingly, we identified several FDA-approved drugs, including the calcium channel blocker mibefradil dihydrochloride, that demonstrated activity as DSB repair inhibitors and radiosensitizers. These findings suggest the possibility for repurposing them as tumor cell radiosensitizers in the future. Accordingly, we recently initiated a phase I clinical trial testing mibefradil as a glioma radiosensitizer. Mol Cancer Ther; 14(2); 326–42. ©2014 AACR.
p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma
Authors: Li Zhen , Sun Yin , Chen Xufeng , Squires Jill , Nowroozizadeh Behdokht , Liang Chaozhao , Huang Jiaoti
Published: December 2014

Prostatic small cell neuroendocrine carcinoma (SCNC) is a rare but aggressive form of prostate cancer that is negative for androgen receptor (AR) and not responsive to hormonal therapy. The molecular etiology of this prostate cancer variant is not well understood; however, mutation of the p53 (TP53) tumor suppressor in prostate neuroendocrine cells inactivates the IL8–CXCR2–p53 pathway that normally inhibits cellular proliferation, leading to the development of SCNC. SCNC also overexpresses Aurora kinase A (AURKA) which is considered to be a viable therapeutic target. Therefore, the relationship of these two molecular events was studied, and we show that p53 mutation leads to increased expression of miR-25 and downregulation of the E3 ubiquitin ligase FBXW7, resulting in elevated levels of Aurora kinase A. This study demonstrates an intracellular pathway by which p53 mutation leads to Aurora kinase A expression, which is critically important for the rapid proliferation and aggressive behavior of prostatic SCNC.

Implications: The pathogenesis of prostatic SCNC involves a p53 and Aurora Kinase A signaling mechanism, both potentially targetable pathways. Mol Cancer Res; 13(3); 584–91. ©2014 AACR.
A Simple and Feasible Method to Determine Absolute Blood Volume in Hemodialysis Patients in Clinical Practice
Authors: Kron Joachim , Schneditz Daniel , Leimbach Til , Aign Sabine , Kron Susanne
Published: December 2014

Background: We developed a simple method to determine the absolute blood volume (V) during hemodialysis in everyday clinical practice and examined its relationship with volume overload, clinical relevance, and accuracy. Methods: The increase in relative blood volume (RBVpost - RBVpre) measured before and after infusion of 240 ml of ultra-pure dialysate using the bolus function of a commercial online hemodiafiltration machine incorporating a relative blood volume monitor was applied to determine absolute blood volume. The specific blood volume (Vs, blood volume per kg body mass at dry weight, in ml/kg) was compared to volume status as assessed by bioimpedance analysis and clinical criteria. Results: The blood volume measured in 30 stable hemodialysis patients was 6.51 ± 1.70 l at the beginning, corresponding to a specific blood volume of 80.1 ± 12.8 ml/kg, and dropped to 5.84 ± 1.61 l or 72.0 ± 12.1 ml/kg at the end of the dialysis session, respectively. Specific blood volume correlated with volume status assessed both clinically and by bioimpedance analysis. Intradialytic morbid events occurred only in treatments where specific blood volume fell below 65 ml/kg. The reproducibility of the technique was better than 4% and the in vitro accuracy corresponds to a resolution in Vs of better than 1 ml/kg. Conclusion: Absolute blood volume can be easily measured at the beginning of the dialysis session using the current dialysis technology. Information about V and Vs could be a promising tool to avoid intradialytic morbid events. This technique could be completely automated without altering the hardware of currently available online dialysis devices. Therefore, it is recommended that this technique be integrated into all hemodiafiltration machines.
Correlation of Lower Concentrations of Hydrogen Sulfide with Atherosclerosis in Chronic Hemodialysis Patients with Diabetic Nephropathy
Authors: Li Han , Feng Su-Juan , Zhang Gui-Zhi , Wang Shi-Xiang
Published: December 2014

Background/Aims: To explore the relationship between hydrogen sulfide (H2S) and uremic accelerated atherosclerosis (UAAS) in chronic hemodialysis patients with diabetic nephropathy (CHD/DN). Methods: A total of 36 CHD/DN and 32 chronic hemodialyzed non-diabetic patients with chronic glomerulonephritis (CHD/non-DN) were studied. Plasma H2S was measured with a sulfide sensitive electrode. Results: Plasma H2S in CHD/DN was significantly lower than that in CHD/non-DN patients. Plasma H2S was positively correlated with plasma TGF-β1, and negatively correlated with MMP-12 in CHD/DN patients. CHD/DN patients exhibited higher CCA-IMT, hsCRP, and lower H2S levels than in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was negatively correlated with plasma H2S, and positively correlated with hsCRP and LDL. On multiple regression analysis, H2S levels exhibited independent association with IMT in CHD/DN patients. Conclusions: These findings suggest possible linkage between H2S metabolism and TGF-β/Smad signaling pathway modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients.
Prevalence of Muscular Dystrophies: A Systematic Literature Review
Authors: Theadom Alice , Rodrigues Miriam , Roxburgh Richard , Balalla Shiavnthi , Higgins Chris , Bhattacharjee Rohit , Jones Kelly , Krishnamurthi Rita , Feigin Valery
Published: December 2014

Background: Determining the prevalence of neuromuscular disorders for the general population is important to identify the scope of burden on society and enable comparisons with other health conditions. This systematic review aims to identify and collate the findings of studies published between 1960 and 2013 on the prevalence of all types of muscular dystrophies. Summary: Relevant articles were identified through electronic database searches and manual searches of reference lists. There were 38 articles from across 19 countries that met the inclusion criteria. The total combined prevalence for all muscular dystrophies for studies classified as having a low risk of bias ranged between 19.8 and 25.1 per 100,000 person-years. Myotonic dystrophy (0.5-18.1 per 100,000), Duchenne muscular dystrophy (1.7-4.2) and facioscapulohumeral muscular dystrophy (3.2-4.6 per 100,000) were found to be the most common types of disorder. There was wide variation in study methodology, case ascertainment, and verification procedures and populations studied, all of which may contribute to the wide prevalence range, in addition to the likely variation in prevalence by country. Key Messages: Greater consistency in the conduct and reporting of neuroepidemiological studies is urgently needed to enable comparisons to be made between studies, countries, and over time.
Association of Red Blood Cell Distribution Width Levels with Severity of Coronary Artery Disease in Patients with Non-ST Elevation Myocardial Infarction
Authors: Sahin Omer , Akpek Mahmut , Sarli Bahadir , Baktir Ahmet Oguz , Savas Goktug , Karadavut Serhat , Elcik Deniz , Saglam Hayrettin , Kaya Mehmet Gungor , Arinc Huseyin
Published: December 2014

Objectives: The aim of this study was to evaluate the association of the levels of red blood cell distribution width (RDW) with the severity of atherosclerosis and to determine whether or not the RDW level on admission is an independent predictor of all-cause mortality in patients with non-ST elevation myocardial infarction (NSTEMI). Materials and Methods: A total of 335 consecutive patients with NSTEMI were enrolled in this study. The patients were divided into high (n = 105) and low (n = 230) SYNTAX groups. The high SYNTAX group was defined as patients with a value in the third tertile (SYNTAX score, SXscore ≥12), while the low SYNTAX group was defined as those with a value in the lower 2 tertiles (SXscore <12). The high RDW group (n = 152) was defined as patients with RDW >14.25% and the low RDW group (n = 183) as those with RDW ≤14.25%. All-cause mortality was followed up to 38 months. Results: The mean follow-up period was 18 ± 11 months. The RDW levels of patients were significantly higher in the high SYNTAX group than in the low SYNTAX group (15.2 ± 1.8 vs. 14.2 ± 1.2, p < 0.001). Pearson's coefficients were used to determine the degree of association between RDW levels and SXscore and also between RDW levels and high-sensitivity C-reactive protein. There was a significant correlation between RDW levels and SXscore (r = 0.460, p < 0.001). Also, there was a significant correlation between RDW levels and high-sensitivity C-reactive protein (r = 0.180, p = 0.001). All-cause mortality rate was not significantly different between the high and low RDW groups (log-rank, p = 0.621). Conclusion: RDW levels were independently associated with high SXscore but were not associated with long-term mortality in NSTEMI patients.
Randomized Phase 2 Trial of Intracoronary Nitrite During Acute Myocardial Infarction
Authors: Jones Daniel A. , Pellaton Cyril , Velmurugan Shanti , Rathod Krishnaraj Sinha , Andiapen Mervyn , Antoniou Sotiris , van Eijl Sven , Webb Andrew J. , Westwood Mark A. , Parmar Mahesh K. , Mathur Anthony , Ahluwalia Amrita
Published: December 2014

Rationale:

Preclinical evidence demonstrates that inorganic nitrite, after its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury.

Objective:

We investigated whether intracoronary injection of nitrite during primary percutaneous coronary intervention might improve infarct size in ST-elevated myocardial infarction.

Methods and Results:

Patients undergoing primary percutaneous coronary intervention (n=80) were randomized to receive intracoronary (10 mL) sodium nitrite (1.8 μmol) or NaCl (placebo) before balloon inflation. The primary end point was infarct size assessed by measuring creatine kinase release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac MRI on day 2. Baseline characteristics were similar between the groups. No evidence of differences in creatine kinase release (
P
=0.92), troponin T (
P
=0.85), or cardiac MRI–assessed infarct size (
P
=0.254) were evident. In contrast, there was an improvement in myocardial salvage index (
P
=0.05) and reduction in major adverse cardiac event at 1 year (2.6% versus 15.8%;
P
=0.04) in the nitrite group. In a 66-patient subgroup with thrombolysis in myocardial infarction ≤1 flow, there was reduced serum creatine kinase (
P
=0.030) and a 19% reduction in cardiac MRI–determined infarct size (
P
=0.034) with nitrite. No adverse effects of nitrite were detected.

Conclusions:

In this phase II study, intracoronary nitrite infusion did not alter infarct size, although a trend to improved myocardial salvage index and a significant reduction in major adverse cardiac event was evident. In a subgroup of patients with thrombolysis in myocardial infarction flow ≤1, nitrite reduced infarct size and major adverse cardiac event and improved myocardial salvage index, indicating that a phase III clinical trial assessing intracoronary nitrite administration as an adjunct to percutaneous coronary intervention in ST-elevated myocardial infarction patients is warranted.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01584453.
Sexual Activity and Counseling in the First Month After Acute Myocardial Infarction Among Younger Adults in the United States and Spain
Authors: Lindau Stacy Tessler , Abramsohn Emily M. , Bueno Héctor , D’Onofrio Gail , Lichtman Judith H. , Lorenze Nancy P. , Mehta Sanghani Rupa , Spatz Erica S. , Spertus John A. , Strait Kelly , Wroblewski Kristen , Zhou Shengfan , Krumholz Harlan M.
Published: December 2014

Background—

United States and European cardiovascular society guidelines recommend physicians counsel patients about resuming sexual activity after acute myocardial infarction (AMI), but little is known about patients’ experience with counseling about sexual activity after AMI.

Methods and Results—

The prospective, longitudinal Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study, conducted at 127 hospitals in the United States and Spain, was designed, in part, to evaluate gender differences in baseline sexual activity, function, and patient experience with physician counseling about sexual activity after an AMI. This study used baseline and 1-month data collected from the 2:1 sample of women (N=2349) and men (N=1152) ages 18 to 55 years with AMI. Median age was 48 years. Among those who reported discussing sexual activity with a physician in the month after AMI (12% of women, 19% of men), 68% were given restrictions: limit sex (35%), take a more passive role (26%), and/or keep the heart rate down (23%). In risk-adjusted analyses, factors associated with not discussing sexual activity with a physician included female gender (relative risk, 1.07; 95% confidence interval, 1.03–1.11), age (relative risk, 1.05 per 10 years; 95% confidence interval, 1.02–1.08), and sexual inactivity at baseline (relative risk, 1.11; 95% confidence interval, 1.08–1.15). Among patients who received counseling, women in Spain were significantly more likely to be given restrictions than U.S. women (relative risk; 1.36, 95% confidence interval, 1.11–1.66).

Conclusions—

Very few patients reported counseling for sexual activity after AMI. Those who did were commonly given restrictions not supported by evidence or guidelines.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00597922.
Oscillatory Cerebral Blood Flow Is Associated With Impaired Neurocognition and Functional Hyperemia in Postural Tachycardia Syndrome During Graded Tilt
Authors: Stewart Julian M. , Del Pozzi Andrew T. , Pandey Akash , Messer Zachary R. , Terilli Courtney , Medow Marvin S.
Published: December 2014

We hypothesize that upright cognitive impairment in patients with postural tachycardia syndrome (POTS) is caused by reduced cerebral blood flow (CBF). The CBF velocity (CBF
v
) measured by transcranial Doppler ultrasound decreased excessively during 70° tilt in a minority of patients with intermittent hyperpnea/hypocapnia. Incremental tilt showed no difference in mean CBF
v
. But N-back memory tasking indicated progressive compromised memory, reduced functional hyperemia, and reduced neurovascular coupling. Orthostasis caused slow oscillations in CBF
v
linked to oscillations in arterial pressure in patients with POTS. We also hypothesize that oscillatory CBF
v
degrades neurovascular coupling. We performed 2-back testing when subjects were in supine position and during incremental tilts to 15°, 30°, 45°, and 60° in 11 patients with POTS and 9 controls. Oscillatory arterial pressure, oscillatory CBF
v
, and neurovascular coupling were similar in supine position. The oscillatory arterial pressure increased by 31%, 45%, 67%, and 93% in patients with POTS during tilt and remained unchanged in the controls. Oscillatory CBF
v
increased by 61%, 82%, 161%, and 264% in patients with POTS during tilt and remained unchanged in the controls. Functional hyperemia decreased from 4.1% to 3.0%, 1.1%, 0.2%, and to 0.04% in patients with POTS, but it was unchanged at 4% in the controls. Percent correct N-back responses decreased from 78% to 33% in patients with POTS, whereas they remained at 89% in the controls. In patients with POTS, oscillatory CBF
v
was linearly correlated with functional hyperemia (
r
2
=0.76). Increased oscillatory CBF is associated with reduced neurovascular coupling and diminished cognitive perf ormance in patients with POTS.