bluuebunny/crossref_metadata_2025 huggingface dataset:
Empirical evaluation of cloud-based testing techniques
Authors: Priyanka  , Chana Inderveer , Rana Ajay
Published: July 2012

Software Testing is a challenging activity for many software engineering projects, especially for large scale systems. The amount of tests cases can range from a few hundred to several thousands, requiring significant computing resources and lengthy execution times. Cloud computing offers the potential to address both of these issues: it offers resources such as virtualized hardware, effectively unlimited storage, and software services that can aid in reducing the execution time of large test suites in a cost-effective manner. In this paper we report on a systematic review of cloud based testing techniques published in major software engineering journals and conferences conducted by other researchers. Research papers were gathered from various scholarly databases using provided search engines within a given period of time. A total of 82 research papers are analyzed in this systematic review and we classified it into four categories according to issues addressed by them. We identified majority of the research papers focused on Cloud based Testing and Issues (38 papers) and 23 papers focused on Cloud based Testing Frameworks. By looking at the areas focused by existing researchers, gaps and untouched areas of cloud based testing can be discovered
PICA
Authors: Lee Jongeun , Shrivastava Aviral
Published: July 2012

Processor Idle Cycle Aggregation (PICA) is a promising approach for low-power execution of processors, in which small memory stalls are aggregated to create large ones, enabling profitable switch of the processor into low-power mode. We extend the previous approach in three dimensions. First we develop static analysis for the PICA technique and present optimal parameters for five common types of loops based on steady-state analysis. Second, to remedy the weakness of software-only control in varying environment, we enhance PICA with minimal hardware extension that ensures correct execution for any loops and parameters, thus greatly facilitating exploration-based parameter tuning. Third, we demonstrate that our PICA technique can be applied to certain types of nested loops with variable bounds, thus enhancing the applicability of PICA. We validate our analytical model against simulation-based optimization and also show, through our experiments on embedded application benchmarks, that our technique can be applied to a wide range of loops with average 20% energy reductions, compared to executions without PICA.
Dynamic Cache Reconfiguration for Soft Real-Time Systems
Authors: Wang Weixun , Mishra Prabhat , Gordon-Ross Ann
Published: July 2012

In recent years, efficient dynamic reconfiguration techniques have been widely employed for system optimization. Dynamic cache reconfiguration is a promising approach for reducing energy consumption as well as for improving overall system performance. It is a major challenge to introduce cache reconfiguration into real-time multitasking systems, since dynamic analysis may adversely affect tasks with timing constraints. This article presents a novel approach for implementing cache reconfiguration in soft real-time systems by efficiently leveraging static analysis during runtime to minimize energy while maintaining the same service level. To the best of our knowledge, this is the first attempt to integrate dynamic cache reconfiguration in real-time scheduling techniques. Our experimental results using a wide variety of applications have demonstrated that our approach can significantly reduce the cache energy consumption in soft real-time systems (up to 74%).
A Variability-Aware Robust Design Space Exploration Methodology for On-Chip Multiprocessors Subject to Application-Specific Constraints
Authors: Palermo Gianluca , Silvano Cristina , Zaccaria Vittorio
Published: July 2012

Manufacturing process variation is dramatically becoming one of the most important challenges related to power and performance optimization for sub-90nm CMOS technologies. Process variability impacts the optimization of the target system metrics, that is, performance and energy consumption by introducing fluctuations and unpredictability. Besides, it impacts the parametric yield of the chip with respect to application level constraints by reducing the number of devices working within normal operating conditions.

The impact of variability on systems with stringent application-specific requirements (such as portable multimedia and critical embedded systems) is much greater than on general-purpose systems given the emphasis on predictability and reduced operating margins. In this market segment, failing to address such a problem within the early design stages of the chip may lead to missing market deadlines and suffering greater economic losses.

In the context of a design space exploration framework for supporting the platform-based design approach, we address the problem of robustness with respect to manufacturing process variations. First, we apply
Response Surface Modeling
(RSM) techniques to enable an efficient evaluation of the statistical measures of execution time and energy consumption for each system configuration. Then, we apply a robust design space exploration framework to afford the problem of the impact of manufacturing process variations onto the system-level metrics and consequently onto the application-level constraints. We finally provide a comparison of our design space exploration technique with conventional approaches on two different case studies.
Generating Invariant-Based Certificates for Embedded Systems
Authors: Blech Jan Olaf , Périn Michaël
Published: July 2012

Automatic verification tools, such as model checkers and tools based on static analysis or on abstract interpretation, have become popular in software and hardware development. They increase confidence and potentially provide rich feedback. However, with increasing complexity, verification tools themselves are more likely to contain errors.

In contrast to automatic verification tools, higher-order theorem provers use mathematically founded proof strategies checked by a small proof checker to guarantee selected properties. Thus, they enjoy a high level of trustability. Properties of software and hardware systems and their justifications can be encapsulated into a certificate, thereby guaranteeing correctness of the systems, with respect to the properties. These results offer a much higher degree of confidence than results achieved by verification tools. However, higher-order theorem provers are usually slow, due to their general and minimalistic nature. Even for small systems, a lot of human interaction is required for establishing a certificate.

In this work, we combine the advantages of automatic verification tools (i.e., speed and automation) with those of higher-order theorem provers (i.e., high level of trustability). The verification tool generates a certificate for each invocation. This is checked by the higher-order theorem prover, thereby guaranteeing the desired property. The generation of certificates is much easier than producing the analysis results of the verification tool in the first place. In our work, we are able to create certificates that come with an algorithmic description of the proof of the desired property as justification. We concentrate on verification tools that generate invariants of systems and certify automatically that these do indeed hold. Our approach is applied to the certification of the verdicts of a deadlock-detection tool for an asynchronous component-based language.
Perspective-oriented generation of football match summaries
Authors: Bouayad-Agha Nadjet , Casamayor Gerard , Mille Simon , Wanner Leo
Published: July 2012

Team sports commentaries call for techniques that are able to select content and generate wordings to reflect the affinity of the targeted reader for one of the teams. The existing works tend to have in common that they either start from knowledge sources of limited size to whose structures then different ways of realization are explicitly assigned, or they work directly with linguistic corpora, without the use of a deep knowledge source. With the increasing availability of large-scale ontologies this is no longer satisfactory: techniques are needed that are applicable to general purpose ontologies, but which still take user preferences into account. We take the best of both worlds in that we use a two-layer ontology. The first layer is composed of raw domain data modelled in an application-independent base OWL ontology. The second layer contains a rich perspective generation-motivated domain communication knowledge ontology, inferred from the base ontology. The two-layer ontology allows us to take into account user perspective-oriented criteria at different stages of generation to generate perspective-oriented commentaries. We show how content selection, discourse structuring, information structure determination, and lexicalization are driven by these criteria and how stage after stage a truly user perspective-tailored summary is generated. The viability of our proposal has been evaluated for the generation of football match summaries of the First Spanish Football League. The reported outcome of the evaluation demonstrates that we are on the right track.
Distributed speech translation technologies for multiparty multilingual communication
Authors: Sakti Sakriani , Paul Michael , Finch Andrew , Hu Xinhui , Ni Jinfu , Kimura Noriyuki , Matsuda Shigeki , Hori Chiori , Ashikari Yutaka , Kawai Hisashi , Kashioka Hideki , Sumita Eiichiro , Nakamura Satoshi
Published: July 2012

Developing a multilingual speech translation system requires efforts in constructing automatic speech recognition (ASR), machine translation (MT), and text-to-speech synthesis (TTS) components for all possible source and target languages. If the numerous ASR, MT, and TTS systems for different language pairs developed independently in different parts of the world could be connected, multilingual speech translation systems for a multitude of language pairs could be achieved. Yet, there is currently no common, flexible framework that can provide an entire speech translation process by bringing together heterogeneous speech translation components. In this article we therefore propose a distributed architecture framework for multilingual speech translation in which all speech translation components are provided on distributed servers and cooperate over a network. This framework can facilitate the connection of different components and functions. To show the overall mechanism, we first present our state-of-the-art technologies for multilingual ASR, MT, and TTS components, and then describe how to combine those systems into the proposed network-based framework. The client applications are implemented on a handheld mobile terminal device, and all data exchanges among client users and spoken language technology servers are managed through a Web protocol. To support multiparty communication, an additional communication server is provided for simultaneously distributing the speech translation results from one user to multiple users. Field testing shows that the system is capable of realizing multiparty multilingual speech translation for real-time and location-independent communication.
Which facial profile do humans expect after seeing a frontal view? a comparison with a linear face model
Authors: Schumacher Matthaeus , Blanz Volker
Published: July 2012

Manipulated versions of three-dimensional faces that have different profiles, but almost the same appearance in frontal views, provide a novel way to investigate if and how humans use class-specific knowledge to infer depth from images of faces. After seeing a frontal view, participants have to select the profile that matches that view. The profiles are original (ground truth), average, random other, and two solutions computed with a linear face model (3D Morphable Model). One solution is based on 2D vertex positions, the other on pixel colors in the frontal view. The human responses demonstrate that humans neither guess nor just choose the average profile. The results also indicate that humans actually use the information from the front view, and not just rely on the plausibility of the profiles per se. All our findings are perfectly consistent with a correlation-based inference in a linear face model. The results also verify that the 3D reconstructions from our computational algorithms (stimuli 4 and 5) are similar to what humans expect, because they are chosen to be the true profile equally often as the ground-truth profiles. Our experiments shed new light on the mechanisms of human face perception and present a new quality measure for 3D reconstruction algorithms.
Querying RDF dictionaries in compressed space
Authors: Martínez-Prieto Miguel A. , Fernández Javier D. , Cánovas Rodrigo
Published: July 2012

The use of dictionaries is a common practice among those applications performing on huge RDF datasets. It allows long terms occurring in the RDF triples to be replaced by short IDs which reference them. This decision greatly compacts the dataset and mitigates the scalability issues underlying to its management. However, the dictionary size is not negligible and the techniques used for its representation also suffer from scalability limitations. This paper focuses on this scenario by adapting compression techniques for string dictionaries to the case of RDF. We propose a novel technique:
D

comp

, which can be tuned to represent the dictionary in compressed space (22--64%) and to perform basic lookup operations in a few microseconds (1--50μ
s
). In addition, we propose
D

comp

as a basis for specific SPARQL query optimizations leveraging its ability for early FILTER resolution.
A Note on the Stability of the Integral‐Differential Equation of the Parabolic Type in a Banach Space
Authors: Ashyraliyev Maksat
Published: July 2012

The integral‐differential equation of the parabolic type in a Banach space is considered. The unique solvability of this equation is established. The stability estimates for the solution of this equation are obtained. The difference scheme approximately solving this equation is presented. The stability estimates for the solution of this difference scheme are obtained.
Periconceptional Folate Deficiency and Implications in Neural Tube Defects
Authors: Safi J. , Joyeux L. , Chalouhi G. E.
Published: July 2012

Nutritional deficiencies are preventable etiological and epigenetic factors causing congenital abnormalities, first cause of infant mortality. Folate deficiency has a well-established teratogenic effect, leading to an increasing risk of neural tube defects. This paper highlights the most recent medical literature about folate deficiency, be it maternal or paternal. It then focuses on associated deficiencies as nutritional deficiencies are multiple and interrelated. Observational and interventional studies have all been consistent with a 50–70% protective effect of adequate women consumption of folates on neural tube defects. Since strategies to modify women’s dietary habits and vitamin use have achieved little progress, scientific as well as political effort is mandatory in order to implement global preventive public health strategies aimed at improving the alimentation of women in reproductive age, especially folic acid supplementation. Even with the recent breakthrough of fetal surgery for myelomeningocele, the emphasis should still be on prevention as the best practice rather than treatment of neural tube defects.
Fine Tuning of Redox Networks on Multiheme Cytochromes fromGeobacter sulfurreducensDrives Physiological Electron/Proton Energy Transduction
Authors: Morgado Leonor , Dantas Joana M. , Bruix Marta , Londer Yuri Y. , Salgueiro Carlos A.
Published: July 2012

The bacteriumGeobacter sulfurreducens (Gs)can grow in the presence of extracellular terminal acceptors, a property that is currently explored to harvest electricity from aquatic sediments and waste organic matter into microbial fuel cells. A family composed of five triheme cytochromes (PpcA-E) was identified inGs. These cytochromes play a crucial role by bridging the electron transfer from oxidation of cytoplasmic donors to the cell exterior and assisting the reduction of extracellular terminal acceptors. The detailed thermodynamic characterization of such proteins showed that PpcA and PpcD have an important redox-Bohr effect that might implicate these proteins in the e−/H+coupling mechanisms to sustain cellular growth. The physiological relevance of the redox-Bohr effect in these proteins was studied by determining the fractional contribution of each individual redox-microstate at different pH values. For both proteins, oxidation progresses from a particular protonated microstate to a particular deprotonated one, over specific pH ranges. The preferred e−/H+transfer pathway established by the selected microstates indicates that both proteins are functionally designed to couple e−/H+transfer at the physiological pH range for cellular growth.
The Lie Brackets on Time Scales
Authors: Kusak H. , Caliskan A.
Published: July 2012

The Lie derivative, which has a wide range of application in physics and geometry, is trying to be examined on time scales. Firstly, nabla Lie bracket is defined on two‐dimensional time scales. Secondly, the nabla Lie multiplication and some properties are given on the time scales. Lastly, for analyzing the differences between the real Lie multiplication and the nabla Lie multiplication, a numerical example is given.
Generalized Fuzzy Soft Expert Set
Authors: Hazaymeh Ayman A. , Abdullah Ismail B. , Balkhi Zaid T. , Ibrahim Rose I.
Published: July 2012

In 2011 Alkhazaleh and Salleh defined the concept of soft expert sets
where the user can know the opinion of all the experts in one model and give an
application of this concept in decision‐making problems. Also, they introduced
the concept of the fuzzy soft expert set as a combination between the soft expert
set and the fuzzy set. In 2010 Majumdar and Samanta presented the concept of
a generalized fuzzy soft sets. The purpose of this paper is to combine the work
of Alkhazaleh and Salleh (2011) and Majumdar and Samanta (2010), from which
we can obtain a new concept: generalized fuzzy soft expert sets (GFSESs). We
also introduce its operations, namely, complement, union intersection, “AND” and
“OR”, and study their properties. The generalized fuzzy soft expert sets are used
to analyze a decision‐making problem. Also in our model the user can know the
opinion of all experts in one model. In this work we also introduce the concept
of a generalized fuzzy soft expert sets with multiopinions (four opinions), which
will be more effective and useful. Finally, we give an application of this concept in
decision‐making problem.
Prevalence of IgG4-Related Disease in Japan Based on Nationwide Survey in 2009
Authors: Uchida Kazushige , Masamune Atsushi , Shimosegawa Tooru , Okazaki Kazuichi
Published: July 2012

The number of patients with autoimmune pancreatitis who visited hospitals in Japan in 2007 was approximately 2709 (95% confidence interval; range 2540–3040). Because IgG4-related disease is a new clinical entity, there are no data with regard to its prevalence. To estimate the number of patients with IgG4-related disease in Japan, we randomly selected hospitals using stratification and asked them how many patients they had with IgG4-related disease in 2009. The number of patients with Mikulicz’s disease, IgG4-related retroperitoneal fibrosis, IgG4-related renal disease, IgG4-related pulmonary disease, and IgG4-related lymphadenopathy who visited hospitals in Japan in 2009 was approximately 4304 (95% confidence interval; range 3360–5048), 272 (95% confidence interval; range 264–306), 57 (95% confidence interval; range 47–66), 354 (95% confidence interval; range 283–424), and 203 (95% confidence interval; range 187–240), respectively. The total number of patients with IgG4-related disease without autoimmune pancreatitis in Japan was approximately 5190 (95% confidence interval; range 4141–6084). The male : female ratio was 1 : 0.77, and the average of age of disease onset was 58.8 years. The total number of patients with IgG4-related disease in Japan in 2009, including autoimmune pancreatitis, was approximately 8000.
The Ecology of Bacterial Genes and the Survival of the New
Authors: Francino M. Pilar
Published: July 2012

Much of the observed variation among closely related bacterial genomes is attributable to gains and losses of genes that are acquired horizontally as well as to gene duplications and larger amplifications. The genomic flexibility that results from these mechanisms certainly contributes to the ability of bacteria to survive and adapt in varying environmental challenges. However, the duplicability and transferability of individual genes imply that natural selection should operate, not only at the organismal level, but also at the level of the gene. Genes can be considered semiautonomous entities that possess specific functional niches and evolutionary dynamics. The evolution of bacterial genes should respond both to selective pressures that favor competition, mostly among orthologs or paralogs that may occupy the same functional niches, and cooperation, with the majority of other genes coexisting in a given genome. The relative importance of either type of selection is likely to vary among different types of genes, based on the functional niches they cover and on the tightness of their association with specific organismal lineages. The frequent availability of new functional niches caused by environmental changes and biotic evolution should enable the constant diversification of gene families and the survival of new lineages of genes.
Hybrid Scaffolds for Tissue Regeneration: Chemotaxis and Physical Confinement as Sources of Biomimesis
Authors: Sprio Simone , Sandri Monica , Panseri Silvia , Cunha Carla , Tampieri Anna
Published: July 2012

Biomineralization is a complex ensemble of concomitant phenomena, driving the development of vertebrate and invertebrate organisms, particularly the formation of human bone tissue. In such a process collagen molecules assemble and organize in a complex 3‐D structure and simultaneously mineralize with nearly amorphous apatite nanoparticles, whose heterogeneous nucleation, growth, and specific orientation are mediated by various chemical, physical, morphological, and structural control mechanisms, activated by the organic matrix at different size levels. The present work investigates on in‐lab biomineralization processes, performed to synthesize hybrid hydroxyapatite/collagen scaffolds for bone and osteochondral regeneration. The synthesis processes are carried out by soft‐chemistry procedures, with the purpose to activate all the different control mechanisms at the basis of new bone formation in vivo, so as to achieve scaffolds with high biomimesis, that is, physical, chemical, morphological, and ultrastructural properties very close to the newly formed human bone. Deep analysis of cell behaviour in contact with such hybrid scaffolds confirms their strong affinity with human bone, which in turn determines high regenerative properties in vivo.
A Rare Case of Retroperitoneal Leiomyoma
Authors: Mahendru Rajiv , Gaba Geetinder , Yadav Shweta , Gaba Gurmeet , Gupta Chinky
Published: July 2012

Introduction. Leiomyoma uteri is one of the most common benign conditions for which women undergo hysterectomy every year. Fibroids found retroperitoneally are a rare entity, especially, primary retroperitoneal fibroid.Case Presentation. We report a case of 42-year-old para 1 who presented to our hospital with recurring retention of urine, lower abdominal and pelvic pain, and dyspareunia . Provisional diagnosis on the basis of examination and imaging was large subserosal fibroid with mild right-sided hydroureteronephrosis, due to pressure effect of the fibroid. Abdominal hysterectomy was done for the patient, and intraoperatively, a bulky uterus was found with multiple small fibroids on anterior and posterior walls, and a large fibroid approx.10×8 cm was found arising from the posterior surface at the level of internal os retroperitoneally, which was confirmed by histopathology as leiomyoma.Conclusion. Retroperitoneal fibroids are rare neoplasms and treatment is surgical removal. Preoperative imaging can only give provisional diagnosis and can be misguiding. Final diagnosis of retroperitoneal fibroid can be made only intraoperatively.
Changes in the Equilibrium of Standing on One Leg at Various Life Stages
Authors: Morioka Shu , Fukumoto Takahiko , Hiyamizu Makoto , Matsuo Atsushi , Takebayashi Hideaki , Miyamoto Kenzo
Published: July 2012

The ability to maintain a one-leg standing position and the relation between plantar two-point discrimination and standing time on one leg were assessed. Participants were 1,241 apparently healthy people aged 2–92 years. Participants were asked to stand on one leg with eyes open (EO group) or closed (EC group) for up to 120 seconds. Coefficients of determination (COD) between subjects’ ages and results for both groups were calculated by quadratic and cubic functions. The slope of the tangent line drawn against the resultant curve was calculated by a differential formula. COD for the quadratic function were 0.65 (EO) and 0.33 (EC); age at maximum values in both groups was 37 years. COD for the cubic function were 0.77 (EO) and 0.52 (EC); maximum values were at ages 30 (EO) and 28 (EC) and minimum values at ages 88 (EO) and 77 (EC). The ability to remain standing on one leg with eyes closed appears to begin deteriorating in the late 20s. Age and plantar two-point discrimination distance had a significant positive correlation, and the two-point discrimination distance and standing time on one leg had a significant negative correlation. Decreased plantar sensation appears to be related to the decline in duration of one-leg standing.
Melatonin: A Novel Indolamine in Oral Health and Disease
Authors: Chava V. K. , Sirisha K.
Published: July 2012

This paper attempts to summarise the findings accumulated within the last few years concerning the hormone of darkness “melatonin.” Based on its origin, from the pineal gland until recently it was portrayed exclusively as a hormone. Due to its lipophilic nature, it is accessible to every cell. Thus, in the classic sense it is a cell protector rather than a hormone. Recent studies, by Claustrat et al. (2005), detected few extrapineal sources of melatonin like retina, gastrointestinal tract, and salivary glands. Due to these sources, research by Cutando et al. (2007), is trying to explore the implications of melatonin in the oral cavity, in addition to its physiologic anti-oxidant, immunomodulatory and oncostatic functions at systemic level that may be receptor dependent or independent. Recently, certain in vivo studies by Shimozuma et al. (2011), detected the secretion of melatonin from salivary glands further emphasising its local activity. Thus, within our confines the effects of melatonin in the mouth are reviewed, adding a note on therapeutic potentials of melatonin both systemically and orally.
Immobilization of Laccase in Alginate-Gelatin Mixed Gel and Decolorization of Synthetic Dyes
Authors: Mogharabi Mehdi , Nassiri-Koopaei Nasser , Bozorgi-Koushalshahi Maryam , Nafissi-Varcheh Nastaran , Bagherzadeh Ghodsieh , Faramarzi Mohammad Ali
Published: July 2012

Alginate-gelatin mixed gel was applied to immobilized laccase for decolorization of some synthetic dyes including crystal violet. The immobilization procedure was accomplished by adding alginate to a gelatin solution containing the enzyme and the subsequent dropwise addition of the mixture into a stirred CaCl2solution. The obtained data showed that both immobilized and free enzymes acted optimally at 50°C for removal of crystal violet, but the entrapped enzyme showed higher thermal stability compared to the free enzyme. The immobilized enzyme represented optimum decolorization at pH 8. Reusability of the entrapped laccase was also studied and the results showed thatca. 85% activity was retained after five successive cycles. The best removal condition was applied for decolorization of seven other synthetic dyes. Results showed that the maximum and minimum dye removal was related to amido black 10B and eosin, respectively.
Isolated Foveal Hypoplasia: Tomographic, Angiographic and Autofluorescence Patterns
Authors: Mota Ágata , Fonseca Sofia , Carneiro Ângela , Magalhães Augusto , Brandão Elisete , Falcão-Reis Fernando
Published: July 2012

Purpose. To report clinical aspects, tomographic, angiographic, and autofluorescence patterns of two cases of isolated foveal hypoplasia.Methods. Foveal hypoplasia was found in a 23-year-old male patient and in a 64-year-old woman with impaired visual acuity of unknown etiology that remained unchanged for years.Results. In the first case, spectral-domain optical coherence tomography (SD-OCT) showed reduced foveal pit and continuity of inner retinal layers in the fovea. Photoreceptor layer had a normal thickness centrally. The foveal avascular zone (FAZ) was absent in the flourescein angiogram (FA). Fundus autofluorescence showed reduced foveal attenuation of autofluorescence. In the second patient, there was the same pattern in SD-OCT, with normal aspect in FA and only a slightly reduced foveal attenuation of autofluorescence.Conclusion. OCT, as a noninvasive and quick method, is helpful in the diagnosis of foveal hypoplasia. FA and fundus autofluorescence were less sensitive.
PKCδ Regulates Death Receptor 5 Expression Induced by PS-341 through ATF4–ATF3/CHOP Axis in Human Lung Cancer Cells
Authors: Xu Linyan , Su Ling , Liu Xiangguo
Published: July 2012

PS-341 (bortezomib), a proteasome inhibitor, has been approved for the treatment of multiple myeloma. Our previous work has shown that PS-341 induces death receptor 5 (DR5)–dependent apoptosis and enhances the TNF-related apoptosis-inducing ligand–induced apoptosis in human non–small cell lung cancer cells. However, the definite mechanism remains undefined. In the present study, we reveal that PKCδ and RSK2 mediate PS-341–induced DR5 upregulation, involving coactivation of endoplasmic reticulum (ER) stress. We discovered that PS-341 activated ER stress through elevating the expression of BiP, p-eIF2α, IRE1α, ATF4, ATF3, and CCAAT/enhancer-binding protein homologous protein (CHOP). Further study showed that DR5 upregulation was dependent on ATF4, ATF3, and CHOP expression. Silencing either one of the ATF4, ATF3, and CHOP expression decreased DR5 upregulation and subsequent apoptosis. We determined that ATF4 regulated ATF3 and CHOP expression. Thereafter, ATF3 and CHOP formed a complex and regulated DR5 expression. In addition, we discovered that the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and RSK2 were elevated after PS-341 treatment and inhibition of their phosphorylation using MAP-ERK kinase 1/2 inhibitor decreased the DR5 level, indicating that ERK/RSK2 signaling is involved in DR5 upregulation. Furthermore, we detected the cleavage of PKCδ, and the blockage of PKCδ expression cut down DR5 upregulation and apoptosis. Importantly, knockdown of PKCδ expression decreased the induction of ER stress and the phosphorylation of ERK1/2 and RSK2, suggesting that PKCδ regulates DR5 expression through ERK/RSK2 signaling and ATF4–CHOP/ATF3 axis. Collectively, we show that PS-341 induces PKCδ-dependent DR5 expression through activation of ERK/RSK2 and ER stress signaling pathway. Mol Cancer Ther; 11(10); 2174–82. ©2012 AACR.
Feasibility of Double-Blind Clinical Trials with Oral Diacetylmorphine: A Randomized Controlled Phase II Study in an Inpatient Setting
Authors: Colom Farran Joan , Casas Miguel , Pérez de los Cobos José , del Río Miquel , Roncero Carlos , Castells Xavier , Valero Sergi , Eiroa-Orosa Francisco José , Batlle Francisca , Trujols Joan ,   on behalf of the Catalan Oral Heroin Study Group
Published: July 2012

The aim of this study was to evaluate the feasibility of conducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the capacity of oral DAM to block opiate withdrawal and clinicians’ ability to distinguish it from morphine and methadone. This was a randomized, phase II, double-blind, multicenter pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone administered twice a day during 10 days. Forty-five heroin-dependent patients were randomly assigned to these three treatment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immediate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments.
Prevalence of Problem Drug Use and Injecting Drug Use in Luxembourg: A Longitudinal and Methodological Perspective
Authors: Origer Alain
Published: July 2012

Background: To estimate the prevalence of problem drug use (PDU) and injecting drug use (IDU) in Luxembourg and analyze trends between 1997 and 2009. To assess the feasibility of prevalence estimations based on drug use surveillance systems. Methods: Serial multi-method PDU/IDU prevalence estimations based upon capture-recapture, Poisson regression, multiplier and back-calculation methods. Comparative analysis of methods and assessment of their robustness to variations of external factors. Results: National PDU and IDU prevalence rates were estimated at 6.16/1,000 (95% CI 4.62/1,000 to 7.81/1,000) and 5.68/1,000 (95% CI 4.53/1,000 to 6.85/1,000) inhabitants aged 15–64 years, respectively. Absolute prevalence and prevalence rates of PDU increased between 1997 and 2000 and declined from 2003 onwards, whereas IDU absolute prevalence and prevalence rates witnessed an increasing trend between 1997 and 2007. Conclusions: Drug use surveillance systems can be valuable instruments for the estimation and trend analysis of drug misuse prevalence given multiple methods are applied that rely on serial and representative data from different sources and different settings, control multiple counts and build upon standardized and sustained data collection routines. The described institutional contact indicator revealed to be a useful tool in the context of PDU/IDU prevalence estimations and thus contributes to enhancing evidence-based drug policy planning.
Maternal Hemodynamics in Normal Pregnancies at 11–13 Weeks’ Gestation
Authors: Khalil Asma , Akolekar Ranjit , Syngelaki Argyro , Elkhouli Mohamed , Nicolaides Kypros H.
Published: July 2012

Objective: In women with established pre-eclampsia and gestational diabetes there is an increase in central aortic systolic blood pressure (SBPAo), pulse wave velocity (PWV) and augmentation index (AIx), which are measures of arterial stiffness. The aim of this study was to establish normal ranges for PWV, AIx and SBPAo at 11–13 weeks’ gestation and to examine the maternal characteristics which affect these parameters. Methods: This was a prospective study in singleton pregnancies at 11+0–13+6 weeks’ gestation. Maternal history and characteristics were recorded and PWV, AIx and SBPAo were measured. Multiple regression analysis was used to examine which of the maternal characteristics provided a significant contribution in the prediction of Alx-75, PWV and SBPAo. Results: In normal pregnancies PWV, AIx-75 and SBPAo were related to certain maternal characteristics, including increase with maternal age for AIx-75 and PWV, decrease with maternal height for AIx-75 and increase with maternal weight for PWV and SBPAo and decrease for AIx (p < 0.0001). The median, 5th, 10th, 90th and 95th percentiles for AIx-75 MoM (multiple of the unaffected median), PWV MoM and SBPAo MoM were 1.00, 0.72, 0.79, 1.34 and 1.48; 1.00, 0.77, 0.82, 1.24 and 1.33; and 1.00, 0.86, 0.88, 1.15 and 1.20, respectively. Conclusions: This study provides normal ranges for PWV, AIx and SBPAo at 11–13 weeks’ gestation and defines the maternal characteristics which affect these vascular parameters.
Microelectrode Recording Duration and Spatial Density Constraints for Automatic Targeting of the Subthalamic Nucleus
Authors: Shamir Reuben R. , Zaidel Adam , Joskowicz Leo , Bergman Hagai , Israel Zvi
Published: July 2012

Background: Accurate detection of the boundaries of the subthalamic nucleus (STN) in deep brain stimulation (DBS) surgery using microelectrode recording (MER) is considered to refine localization and may therefore improve clinical outcome. However, MER tends to extend operation time and its cost-utility balance has been debated. Objectives: To quantify the tradeoff between accuracy of STN localization and the spatial and temporal parameters of MER that effect the operation time using an automated detection method. Methods: We retrospectively estimated the accuracy of STN detection on data from 100 microelectrode trajectories. Our dense (average step = 0.12 mm) and long (average duration = 22.5 s) MER data was downsampled in the spatial and temporal domains. Then, the STN borders were detected automatically on both the downsampled and original data and compared to each other. Results: With a recording duration of 16 s, average accuracy for detecting STN entry ranged from 0.06 mm for a 0.1-mm step to 0.51 mm for a 1.0-mm step. Smaller effects were found along the temporal axis. For example, a 0.1-mm recording step yielded an STN entry average accuracy ranging from 0.06 mm for a 16-second recording duration to 0.16 mm for 0.1 s. Conclusions: STN entry detection error was about half of the step size. Sampling duration of STN activity can be minimized to 1 s/record without compromising accuracy. We conclude that bilateral DBS surgery time utilizing MER may be significantly shortened without compromising targeting accuracy.
Altered Serum Levels of Brain-Derived Neurotrophic Factor in Patients with Pathological Gambling
Authors: Geisel Olga , Banas Roman , Hellweg Rainer , Müller Christian A.
Published: July 2012

Background: Brain-derived neurotrophic factor (BDNF) plays important roles in neurotransmitter release and synaptic plasticity and has been hypothesized to be involved in the development and maintenance of addictive disorders. The objective of this study was to investigate alterations of BDNF expression in a non-substance-related addiction, i.e. pathological gambling (PG). Methods: Serum levels of BDNF were assessed in male patients with PG (n = 14) and healthy control subjects (n = 13) carefully matched for sex, age, body mass index, smoking status and urbanicity. Symptoms and severity of PG were measured by the adapted form of the Yale-Brown Obsessive-Compulsive Scale. Results: BDNF serum levels were significantly increased in patients with PG in comparison to healthy control subjects (p = 0.016). There were no significant correlations between BDNF serum levels and severity of PG or clinical and demographic variables. Conclusions: Our results show alterations of BDNF serum levels in patients suffering from a behavioural addiction and suggest that non-substance-related addictions like PG might be associated with neuroendocrinological changes similar to the changes observed in substance-related addictions.
Prooxidant-Antioxidant Balance and Antioxidized LDL Antibody Level Values and Cardiac Function in Patients with Coronary Artery Disease
Authors: Rahsepar Amir Ali , Mirzaee Asadollah , Moodi Fatemeh , Moohebati Mohsen , Tavallaie Shima , Eshraghi Ali , Alavi Maryam-Sadat , Khorashadizadeh Fatemeh , Pourghadamyari Hossein , Paydar Roghayeh , Amini Maral , Khojasteh Roshanak , Mousavi Somayeh , Sahebi Maryam , Ghayour-Mobarhan Majid , Ferns Gordon A.A.
Published: July 2012

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = –0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.
Direct Recording of Renal Sympathetic Nerve Activity in Unrestrained, Conscious Mice
Authors: Hamza Shereen M. , Hall John E.
Published: July 2012

Renal sympathetic nerve activity (RSNA) has been measured in anesthetized mice. However, anesthesia and acute surgical preparation cause poor cardiovascular stability and unphysiological blood pressures. This compromised physiological state confounds proper interpretation of experimental results considering the inseparable link between cardiovascular status and autonomic nervous tone. We, therefore, developed a surgical and experimental protocol for measuring RSNA in conscious, unrestrained mice. Male C57Bl/6J mice were chronically instrumented with blood pressure radiotelemeters, an indwelling jugular venous catheter and a bipolar electrode for recording RSNA. Mice were placed in a home cage and left to recover for 48 to 72 hours. Survival rate was 100%; all of the mice exhibited normal behavior with no sign of distress 24 hours after surgery. RSNA was successfully recorded in 80% of the mice at 48 and 72 hours postsurgery; viable RSNA was reduced to 70% and 50% at 4 and 5 days postsurgery, respectively. Mean arterial pressure (116±2 mm Hg; n=10) was consistent with values reported previously for conscious mice. RSNA increased with the normal physical activities of eating and grooming and was validated by ganglionic blockade and pharmacological manipulation of blood pressure; reduction in blood pressure to 62±3 mm Hg with nitroprusside increased RSNA by 77±9% above baseline (n=5;
P
<0.05), whereas an increase in blood pressure to 137±6 mm Hg with phenylephrine reduced RSNA by 79±2% compared with baseline (n=5;
P
<0.05). Thus, we demonstrate an accessible and effective method for direct assessment of RSNA in conscious, unrestrained mice.
Associations of Bisphenol A Exposure With Heart Rate Variability and Blood Pressure
Authors: Bae Sanghyuk , Kim Jin Hee , Lim Youn-Hee , Park Hye Yin , Hong Yun-Chul
Published: July 2012

Bisphenol A (BPA) is a high-volume production chemical that has been suspected to have adverse health effects. Recent studies have suggested that cardiovascular diseases are associated with the BPA exposure. The aim of present study was to investigate the associations of urinary BPA with heart rate variability and blood pressure. We recruited 560 noninstitutionalized elderly citizens from August 2008 to August 2010 in Seoul. All of the participants were ≥60 years old. The participants took medical examinations ≤5 times. Urinary BPA concentration, heart rate variability, and blood pressure were measured at each time. A total of 1511 observations from 521 participants were included in the analyses. We observed that urinary BPA was associated negatively with the root mean square of successive differences for heart rate and positively with blood pressure. The odds ratio of showing hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) was 1.27 (95% CI, 0.85–1.88) in the fourth quartile compared with the first quartile of urinary BPA concentration. When the analyses were restricted to participants who did not report previous history of hypertension (n=258), the odds ratio was increased to 2.35 (95% CI, 1.33–4.17).
Stem Cell Antigen 1 Protects Against Cardiac Hypertrophy and Fibrosis After Pressure Overload
Authors: Zhou Heng , Bian Zhou-Yan , Zong Jing , Deng Wei , Yan Ling , Shen Di-Fei , Guo Haipeng , Dai Jia , Yuan Yuan , Zhang Rui , Lin Ya-Fen , Hu Xue , Li Hongliang , Tang Qi-Zhu
Published: July 2012

Stem cell antigen (Sca) 1, a glycosyl phosphatidylinositol-anchored protein localized to lipid rafts, is upregulated in the heart during myocardial infarction and renovascular hypertension-induced cardiac hypertrophy. It has been suggested that Sca-1 plays an important role in myocardial infarction. To investigate the role of Sca-1 in cardiac hypertrophy, we performed aortic banding in Sca-1 cardiac-specific transgenic mice, Sca-1 knockout mice, and their wild-type littermates. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. Sca-1 expression was upregulated and detected in cardiomyocytes after aortic banding surgery in wild-type mice. Sca-1 transgenic mice exhibited significantly attenuated cardiac hypertrophy and fibrosis and preserved cardiac function compared with wild-type mice after 4 weeks of aortic banding. Conversely, Sca-1 knockout dramatically worsened cardiac hypertrophy, fibrosis, and dysfunction after pressure overload. Furthermore, aortic banding–induced activation of Src, mitogen-activated protein kinases, and Akt was blunted by Sca-1 overexpression and enhanced by Sca-1 deficiency. Our results suggest that Sca-1 protects against cardiac hypertrophy and fibrosis via regulation of multiple pathways in cardiomyocytes.
Working Memory Capacity and Visual–Verbal Cognitive Load Modulate Auditory–Sensory Gating in the Brainstem: Toward a Unified View of Attention
Authors: Sörqvist Patrik , Stenfelt Stefan , Rönnberg Jerker
Published: July 2012

Two fundamental research questions have driven attention research in the past: One concerns whether selection of relevant information among competing, irrelevant, information takes place at an early or at a late processing stage; the other concerns whether the capacity of attention is limited by a central, domain-general pool of resources or by independent, modality-specific pools. In this article, we contribute to these debates by showing that the auditory-evoked brainstem response (an early stage of auditory processing) to task-irrelevant sound decreases as a function of central working memory load (manipulated with a visual–verbal version of the n-back task). Furthermore, individual differences in central/domain-general working memory capacity modulated the magnitude of the auditory-evoked brainstem response, but only in the high working memory load condition. The results support a unified view of attention whereby the capacity of a late/central mechanism (working memory) modulates early precortical sensory processing.