bluuebunny/crossref_metadata_2025 huggingface dataset:
Domain-driven technique for functionality identification in source code
Authors: Anwikar Vallabh , Naik Ravindra , Contractor Adnan , Makkapati Hemanth
Published: July 2012

While migrating existing software systems to Software Product Lines, finding out the functionalities in the software is critical. For maintenance activities like deleting or changing existing features, or adding new similar features, identifying and extracting functionalities from the software is significant. This paper describes a technique for creating mapping between the source code and functionalities implemented by it while exploiting the domain knowledge. The technique is based on the notion of function variables that are used by developers for expressing functionality in the source code. By tracking the known values of the function variables and evaluating the conditions that use them, the mapping is identified. Our technique makes use of static data ow analysis and partial evaluation, and is designed with automation perspective. After applying to few samples representing real-life code structure and programming practices, the technique identified precise mapping of the detailed program elements to functions
A unified tabular method for modeling variants of software product line
Authors: Ripon Shamim H.
Published: July 2012

Reuse of software is a promising approach to improving the efficiency of software development regarding time, cost and quality. Reuse requires a systematic approach. The best results are achieved if we focus on systems in a specific domain, so-called product line. The key difference between the conventional software engineering and software product line engineering is variant management. The main idea of software product line is to identify the common core functionality which can be implemented once and reused afterwards for all members of the product line. To facilitate this reuse opportunity the domain engineering phase makes the domain model comprising the common as well as variant requirements. In principle, common requirements among systems in a family are easy to handle. However, problem arises during handling variants. Different variants have dependencies on each other; a single variant can affect several variants of the domain model. These problems become complex when the volume of information grows in a domain and there are a lot of variants with several interdependencies. Hence, a separate model is required for handling the variants. This paper presents a mechanism, which we call, Unified Tabular Method to facilitate the management of variant dependencies in product lines. The tabular method consists of a variant part to model the variants and their dependencies, and a decision table to depict the customization decision regarding each variant while deriving customized products. Tabular method alleviates the problem of possible explosion of variant combinations and facilitates the tracing of variant information in the domain model
Unequal Error Protection Based on DVFS for JSCD in Low-Power Portable Multimedia Systems
Authors: Yang Yoon Seok , Choi Gwan
Published: July 2012

This article presents a low-power decoder design for joint source-channel decoding (JSCD) based on a novel unequal error protection (UEP) scheme over additive white gaussian noise (AWGN) channels. Conventional JSCD schemes, adopting low-density parity check (LDPC) codes for multimedia devices, typically operate at a fixed-time decoding loop, regardless of the quality of data received. We present a JSCD scheme that achieves reduction in power through minimum energy decoding and dynamic voltage and frequency scaling (DVFS). Consequently, up to 39% power reduction is achieved in Foreman, Akiyo, and Mobile video streams without performance degradation in reconstructed video quality.
Integrated Task and Interrupt Management for Real-Time Systems
Authors: Leyva-del-Foyo Luis E. , Mejia-Alvarez Pedro , de Niz Dionisio
Published: July 2012

Real-time scheduling algorithms like RMA or EDF and their corresponding schedulability test have proven to be powerful tools for developing predictable real-time systems. However, the traditional interrupt management model presents multiple inconsistencies that break the assumptions of many of the real-time scheduling tests, diminishing its utility. In this article, we analyze these inconsistencies and present a model that resolves them by integrating interrupts and tasks in a single scheduling model. We then use the RMA theory to calculate the cost of the model and analyze the circumstances under which it can provide the most value. This model was implemented in a kernel module. The portability of the design of our module is discussed in terms of its independence from both the hardware and the kernel. We also discuss the implementation issues of the model over conventional PC hardware, along with its cost and novel optimizations for reducing the overhead. Finally, we present our experimental evaluation to show evidence of its temporal determinism and overhead.
Predicting the Long-Term Behavior of a Micro-Solar Power System
Authors: Jeong Jaein , Culler David
Published: July 2012

Micro-solar power system design is challenging because it must address long-term system behavior under highly variable solar energy conditions and consider a large space of design options. Several micro-solar power systems and models have been made, validating particular points in the whole design space. We provide a general architecture of micro-solar power systems---comprising key components and interconnections among the components---and formalize each component in an analytical or empirical model of its behavior. To model the variability of solar energy, we provide three solar radiation models, depending on the degree of information available: an astronomical model for ideal conditions, an obstructed astronomical model for estimating solar radiation under the presence of shadows and obstructions, and a weather-effect model for estimating solar radiation under weather variation. Our solar radiation models are validated with a concrete design, the HydroWatch node, thus achieving small deviation from the long-term measurement. They can be used in combination with other micro-solar system models to improve the utility of the load and estimate the behavior of micro-solar power systems more accurately. Thus, our solar radiation models provide more accurate estimations of solar radiation and close the loop for micro-solar power system modeling.
Minification affects verbal- and action-based distance judgments differently in head-mounted displays
Authors: Zhang Ruimin , Nordman Anthony , Walker James , Kuhl Scott A.
Published: July 2012

Numerous studies report that people underestimate egocentric distances in Head-Mounted Display (HMD) virtual environments compared to real environments as measured by direct blind walking. Geometric minification, or rendering graphics with a larger field of view than the display's field of view, has been shown to eliminate this underestimation in a virtual hallway environment [Kuhl et al. 2006, 2009]. This study demonstrates that minification affects blind walking in a sparse classroom and does not influence verbal reports of distance. Since verbal reports of distance have been reported to be compressed in real environments, we speculate that minification in an HMD replicates peoples' real-world blind walking and verbal report distance judgments. We also demonstrate a new method for quantifying any unintentional miscalibration in our experiments. This process involves using the HMD in an augmented reality configuration and having each participant indicate where the targets and horizon appeared after each experiment. More work is necessary to understand how and why minification changes verbal- and walking-based egocentric distance judgments differently.
A spatiotemporal extension for dealing with moving objects with extent in Oracle 11g
Authors: Matos Luís , Moreira José , Carvalho Alexandre
Published: July 2012

This paper deals with the design and implementation of a data model and operations for dealing with continuously changing spatial data in Oracle 11g object-relational DBMS. The data model relies on abstract data types but we introduce modifications to the internal structure of the spatiotemporal data representations proposed in the literature, to reduce storage requirements and to enable the reuse of data during the execution of queries. We show how to implement spatiotemporal operations relying on the spatial functions released by the underlying DBMS and how to use the alternative data representations to reduce the volume of temporary data created in the evaluation of spatiotemporal operations. We also demonstrate how to use the proposed data types and operations for storage and manipulation of moving objects data using SQL. Finally, we discuss on the advantages and disadvantages of the proposed solutions.
Transparently increasing RMI fault tolerance
Authors: Reis Diogo , Miranda Hugo
Published: July 2012

Traditional Remote Procedure Call systems (RPCs) have a single point of failure at the server side. To address this issue, a number of approaches extend RPC syntax and semantic to provide fault tolerance. However, these solutions are neither transparent for the application programmer nor for the client. This paper describes FTRMI, a middleware platform that enhances the Java Remote Method Invocation (JRMI) with strong replica consistency, increasing fault tolerance. FTRMI is completely transparent for the client and does not require recoding on the server side.
Isolation of Antidiabetic Principle from Fruit Rinds ofPunica granatum
Authors: Jain Vishal , Viswanatha G. L. , Manohar D. , Shivaprasad H. N.
Published: July 2012

Present study was aimed to isolate and evaluate the antidiabetic activity of phytoconstituents from fruit rinds ofPunica granatum. With the above objectives Valoneic acid dilactone (VAD) was isolated from methanolic fruit rind extracts ofPunica granatum(MEPG) and confirmed by1H-NMR,13C-NMR, and mass spectral data. Antidiabetic activity was evaluated by Aldose reductase,α-amylase and PTP1B inhibition assays inin vitroand Alloxan-induced diabetes in rats was used as anin vivomodel. In bioactivity studies, MEPG and VAD have showed potent antidiabetic activity inα-amylase, aldose reductase, and PTP1B inhibition assays with IC50values of 1.02, 2.050, 26.25 μg/mL and 0.284, 0.788, 12.41 μg/mL, respectively. Furthermore, in alloxan-induced diabetes model MEPG (200 and 400 mg/kg, p.o.) and VAD (10, 25, and 50 mg/kg, p.o.) have showed significant and dose dependent antidiabetic activity by maintaining the blood glucose levels within the normal limits. Inline with the biochemical findings histopathology of MEPG (200 and 400 mg/kg, p.o.), VAD (10, 25, and 50 mg/kg, p.o.), and glibenclamide (10 mg/kg, p.o.) treated animals showed significant protection against alloxan-induced pancreatic tissue damage. These findings suggest that MEPG and VAD possess significant antidiabetic activity in bothin vitroandin vivomodels.
Solution of the First Boundary‐Value Problem for a System of Autonomous Second‐Order Linear Partial Differential Equations of Parabolic Type with a Single Delay
Authors: Diblík Josef , Khusainov Denis , Kukharenko Oleksandra , Svoboda Zdeněk
Published: July 2012

The first boundary‐value problem for an autonomous second‐order system of linear partial differential equations of parabolic type with a single delay is considered. Assuming that a decomposition of the given system into a system of independent scalar second‐order linear partial differential equations of parabolic type with a single delay is possible, an analytical
solution to the problem is given in the form of formal series and the character of their convergence is discussed. A delayed exponential function is used in order to analytically solve auxiliary initial problems (arising when Fourier method is applied) for ordinary linear differential equations of the first order with a single delay.
Subwavelength Plasmonic Waveguides and Plasmonic Materials
Authors: Yang Ruoxi , Lu Zhaolin
Published: July 2012

With the fast development of microfabrication technology and advanced computational tools, nanophotonics has been widely studied for high-speed data transmission, sensitive optical detection, manipulation of ultrasmall objects, and visualization of nanoscale patterns. As an important branch of nanophotonics, plasmonics has enabled light-matter interactions at a deep subwavelength length scale. Plasmonics, or surface plasmon based photonics, focus on how to exploit the optical property of metals with abundant free electrons and hence negative permittivity. The oscillation of free electrons, when properly driven by electromagnetic waves, would form plasmon-polaritons in the vicinity of metal surfaces and potentially result in extreme light confinement. The objective of this article is to review the progress of subwavelength or deep subwavelength plasmonic waveguides, and fabrication techniques of plasmonic materials.
Urbach-Wiethe Syndrome and the Ophthalmologist: Review of the Literature and Introduction of the First Instance of Bilateral Uveitis
Authors: Abtahi Seyed-Mojtaba , Kianersi Farzan , Abtahi Mohammad-Ali , Abtahi Seyed-Hossein , Zahed Arash , Fesharaki Hamid-Reza , Abtahi Zahra-Alsadat , Baradaran Shahzad , Mazloumi Mehdi , Naghiabadi Saeed
Published: July 2012

Patients suffering from Urbach-Wiethe syndrome (UWS), also known as lipoid proteinosis or hyalinosis cutis et mucosae, may have an ophthalmologist involved in the diagnosis and management of their disease. Along with moniliform blepharosis as a pathognomonic feature of the disease, an ophthalmologist may encounter other manifestations of UWS in any part of the eye such as cornea; conjunctiva; sclera; trabecular meshwork; iris/pupil; lens and zonular fibers; retina; nasolacrimal duct. This paper provides a review on the pathogenesis and the diverse ocular manifestations seen in UWS patients. Uncommon complications are discussed in this paper (glaucoma; dry eye and epiphora; complications of lens, retina, cornea; iris/pupil and conjunctiva). Moreover, a 27-year-old male UWS patient is described with bilateral diffuse anterior stromal iris atrophy, diffuse keratic precipitates; posterior subcapsular cataract; 1 + vitreous cell in anterior vitreous examination. This case was thought to be the first instance of bilateral uveitis associated with UWS. Overall, ophthalmologists may encounter diverse ocular complications accompanying this syndrome. They should be familiar with well-established ophthalmologic manifestations leading them to cooperate with other specialists in diagnosis and management of the disease.
Finite Difference Method for the Reverse Parabolic Problem
Authors: Ashyralyyev Charyyar , Dural Ayfer , Sozen Yasar
Published: July 2012

A finite difference method for the approximate solution of the reverse multidimensional parabolic differential equation with a multipoint boundary condition and Dirichlet condition is applied. Stability, almost coercive stability, and coercive stability estimates for the solution of the first and second orders of accuracy difference schemes are obtained. The theoretical statements are supported by the numerical example.
Emerging Putative Biomarkers: The Role of Alpha 2 and 6 Integrins in Susceptibility, Treatment, and Prognosis
Authors: Marthick James R. , Dickinson Joanne L.
Published: July 2012

The genetic architecture underpinning prostate cancer is complex, polygenic and despite recent significant advances many questions remain. Advances in genetic technologies have greatly improved our ability to identify genetic variants associated with complex disease including prostate cancer. Genome-wide association studies (GWASs) and microarray gene expression studies have identified genetic associations with prostate cancer susceptibility and tumour development. The integrins feature prominently in both studies examining the underlying genetic susceptibility and mechanisms driving prostate tumour development. Integrins are cell adhesion molecules involved in extracellular and intracellular signalling and are imperative for tumour development, migration, and angiogenesis. Although several integrins have been implicated in tumour development, the roles of integrinα2and integrinα6are the focus of this paper as evidence is now emerging that these integrins are implicit in prostate cancer susceptibility, cancer stem cell biology, angiogenesis, cell migration, and metastases to bone and represent potential biomarkers and therapeutic targets. There currently exists an urgent need to develop tools that differentiate indolent from aggressive prostate cancers and predict how patients will respond to treatment. This paper outlines the evidence supporting the use ofα2andα6integrins in clinical applications for tailored patient treatment.
Enhancement of Electron Transfer Efficiency in Solar Cells Based on PbS QD/N719 Dye Cosensitizers
Authors: Gao Yanyan , Zou Xiaoping , Sun Zhe , Huang Zongbo , Zhou Hongquan
Published: July 2012

Cosensitized solar cells (CSSCs) have recently become an active subject in the field of sensitized solar cells (SSCs) due to their increasing electronic utilization. However, because of the dye molecules, layer must be single, dye‐SSCs cannot be co‐sensitized with two different dyes to form two different molecules layer. But it is possible to be cosensitized with quantum dots (QDs) and dyes. Here we designed novel photoanode architecture, namely, PbS QDs and N719 dyes are used as co‐sensitizers of the TiO2 mesoporous film. The experimental result shows that PbS QDs/N719 dyes co‐sensitized structure can make PbS QDs and N719 dyes mutual improvement. Taking the advantage of PbS not only achieved higher transfer efficiency of photo‐excited electron, but also achieved obviously wider range and higher intensity of absorption. The PbS QDs which have been deposited on the TiO2 film was coated by N719 dyes, which can effectively prevent PbS QDs from corroding by electrolyte and light. As we expected, the solar energy‐conversion efficiency which is showed by CSSCs fabricated following these photoanodes is relatively higher than the PbS QDs or N719 dyes, single‐sensitized solar cells under the illumination of one sun.
A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges
Authors: di Martino Erica , Tomlinson Darren C. , Knowles Margaret A.
Published: July 2012

Fibroblast growth factors (FGFs) orchestrate a variety of cellular functions by binding to their transmembrane tyrosine-kinase receptors (FGFRs) and activating downstream signalling pathways, including RAS/MAPK, PLCγ1, PI3K, and STATs. In the last ten years, it has become clear that FGF signalling is altered in a high proportion of bladder tumours. Activating mutations and/or overexpression ofFGFR3are common in urothelial tumours with low malignant potential and low-stage and -grade urothelial carcinomas (UCs) and are associated with a lower risk of progression and better survival in some subgroups.FGFR1is not mutated in UC, but overexpression is frequent in all grades and stages and recent data indicate a role in urothelial epithelial-mesenchymal transition.In vitroandin vivostudies have shown that FGFR inhibition has cytotoxic and/or cytostatic effects in FGFR-dependent bladder cancer cells and FGFR-targeted agents are currently being investigated in clinical studies for the treatment of UC. Urine-based tests detecting commonFGFR3mutations are also under development for surveillance of low-grade and -stage tumours and for general population screening. Overall, FGFRs hold promise as therapeutic targets, diagnostic and prognostic markers, and screening tools for early detection and clinical management of UC.
Security Analysis and Enhancements of an Effective Biometric-Based Remote User Authentication Scheme Using Smart Cards
Authors: An Younghwa
Published: July 2012

Recently, many biometrics-based user authentication schemes using smart cards have been proposed to improve the security weaknesses in user authentication system. In 2011, Das proposed an efficient biometric-based remote user authentication scheme using smart cards that can provide strong authentication and mutual authentication. In this paper, we analyze the security of Das’s authentication scheme, and we have shown that Das’s authentication scheme is still insecure against the various attacks. Also, we proposed the enhanced scheme to remove these security problems of Das’s authentication scheme, even if the secret information stored in the smart card is revealed to an attacker. As a result of security analysis, we can see that the enhanced scheme is secure against the user impersonation attack, the server masquerading attack, the password guessing attack, and the insider attack and provides mutual authentication between the user and the server.
On the Rate of Convergence of Kirk‐Type Iterative Schemes
Authors: Hussain Nawab , Chugh Renu , Kumar Vivek , Rafiq Arif
Published: July 2012

The purpose of this paper is to introduce Kirk‐type new iterative schemes called Kirk‐SP and Kirk‐CR schemes and to study the convergence of these iterative schemes by employing certain quasi‐contractive operators. By taking an example, we will compare Kirk‐SP, Kirk‐CR, Kirk‐Mann, Kirk‐Ishikawa, and Kirk‐Noor iterative schemes for aforementioned class of operators. Also, using computer programs in C++, we compare the above‐mentioned iterative schemes through examples of increasing, decreasing, sublinear, superlinear, and oscillatory functions.
Pedestrian Tracking Solution Combining an Impulse Radio Handset Transmitter with an Ankle-Mounted Inertial Measurement Unit
Authors: Youssef Joe , Denis Benoît , Godin Christelle , Lesecq Suzanne
Published: July 2012

We address the indoor tracking problem by combining an Impulse Radio-Ultra-Wideband handset with an ankle-mounted Inertial Measurement Unit embedding an accelerometer and a gyroscope. The latter unit makes possible the detection of the stance phases to overcome velocity drifts. Regarding radiolocation, a time-of-arrival estimator adapted to energy-based receivers is applied to mitigate the effects of dense multipath profiles. A novel quality factor associated with this estimator is also provided as a function of the received signal-to-noise ratio, enabling us to identify outliers corresponding to obstructed radio links and to scale the covariance matrix of radiolocation measurements. Finally, both radio and inertial subsystems are loosely-coupled into one single navigation solution relying on a specific extended Kalman filter. In the proposed fusion strategy, processed inertial data control the filter state prediction whereas Combined Time Differences Of Arrival are formed as input observations. These combinations offer low computational complexity as well as a unique filter structure over time, even after removing outliers. Experimental results obtained in a representatively harsh indoor environment emphasize the complementarity of the two technologies and the relevance of the chosen fusion method while operating with low-cost, noncollocated, asynchronous, and heterogeneous sensors.
Quasi-Analytical Solutions of DKP Equation under the Deng-Fan Interaction
Authors: Hassanabadi S. , Rajabi A. A. , Yazarloo B. H. , Zarrinkamar S. , Hassanabadi H.
Published: July 2012

Quasianalytical solutions of Duffin-Kemmer-Petiau equation under scalar and vector Deng-Fan potentials are reported via a novel ansatz.
On Some Properties of New Paranormed Sequence Space of Nonabsolute Type
Authors: Karakaya Vatan , Şimşek Necip
Published: July 2012

We introduce some new generalized sequence space
related to the space ℓ(p). Furthermore we investigate some topological properties
as the completeness, the isomorphism, and also we give some inclusion
relations between this sequence space and some of the other sequence spaces.
In addition, we compute α‐, β‐, and γ‐duals of this space and characterize
certain matrix transformations on this sequence space.
Synchronization of Coupled Networks with Mixed Delays by Intermittent Control
Authors: Yuan Kun , Cao Jinde , Fei Shumin
Published: July 2012

The synchronization of coupled networks with mixed delays is investigated by employing Lyapunov functional method and intermittent control. A sufficient condition is derived to ensure the global synchronization of coupled networks, which is controlled by the designed intermittent controller. Finally, a numerical simulation is constructed to justify the theoretical analysis.
Caudate Nucleus Volume Mediates the Link between Cardiorespiratory Fitness and Cognitive Flexibility in Older Adults
Authors: Verstynen Timothy D. , Lynch Brighid , Miller Destiny L. , Voss Michelle W. , Prakash Ruchika Shaurya , Chaddock Laura , Basak Chandramallika , Szabo Amanda , Olson Erin A. , Wojcicki Thomas R. , Fanning Jason , Gothe Neha P. , McAuley Edward , Kramer Arthur F. , Erickson Kirk I.
Published: July 2012

The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years,N=179). Measures of cardiorespiratory fitness (VO2max), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum.
Validity and Reliability of Accelerometer-Based Gait Assessment in Patients with Diabetes on Challenging Surfaces
Authors: de Bruin Eling D. , Hubli Michèle , Hofer Pamela , Wolf Peter , Murer Kurt , Zijlstra Wiebren
Published: July 2012

Walking on irregular terrain influences gait of diabetic patients. We investigate the test-retest reliability and construct validity of gait measured with the DynaPort MiniMod under single and dual task conditions in diabetic patients walking on irregular terrain to identify the measurement error (precision) and minimal clinical detectable change. 29 patients with Type 2 diabetes were measured once, and 25 repeated the measurement within 7 days. Patients walked on a therapy garden walkway. Differences between three groups of diabetics with various levels of lower extremity neuropathy were analyzed with planned contrasts. ICC was excellent for intervisit measurements with ICC's . Bland and Altman Plots, SEM, and SDD showed precise values, distributed around zero for both test conditions. A significant effect of grouping on step length performance hints at possible construct validity of the device. Good reliability of DynaPort MiniMod measurements on a therapy garden walkway and an indication for discriminatory capability suggests that DynaPort MiniMod could facilitate the study of gait in diabetic patients in conditions close to real-life situations. Good reliability, small measurement error, and values of minimal clinical detectable change recommend the further utilization of DynaPort MiniMod for the evaluation of gait parameters in diabetic patients.
Genetic Variants in miRNAs Predict Bladder Cancer Risk and Recurrence
Authors: Wang Meilin , Chu Haiyan , Li Pu , Yuan Lin , Fu Guangbo , Ma Lan , Shi Danni , Zhong Dongyan , Tong Na , Qin Chao , Yin Changjun , Zhang Zhengdong
Published: July 2012

miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA–disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71–0.90, P = 2.92 × 10−4]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings. Cancer Res; 72(23); 6173–82. ©2012 AACR.
REST Is a Novel Prognostic Factor and Therapeutic Target for Medulloblastoma
Authors: Taylor Pete , Fangusaro Jason , Rajaram Veena , Goldman Stewart , Helenowski Irene B. , MacDonald Tobey , Hasselblatt Martin , Riedemann Lars , Laureano Alvaro , Cooper Laurence , Gopalakrishnan Vidya
Published: July 2012

Medulloblastoma is a malignant pediatric brain tumor. Current treatment following patient stratification into standard and high-risk groups using clinical features has improved survival. However, a subset of patients with standard risk features have unanticipated aggressive disease, underscoring the need for a better understanding of tumor biology and the development of novel treatments. Poor differentiation, a hallmark of medulloblastomas is associated with elevated expression levels of the repressor of neuronal differentiation called repressor element 1-silencing transcription factor (REST). Here, we assessed whether elevated REST expression levels had prognostic significance and whether its pharmacologic manipulation would promote neurogenesis and block tumor cell growth. REST levels in patient tumors were measured by immunohistochemistry and stratified into negative, low/moderate- (+/++/+++), and high-REST (+++++) groups. Kaplan–Meier curves revealed that patients with high-REST tumors had worse overall and event-free survival compared with patients with REST-negative or REST-low tumors. Because histone deacetylases (HDAC) are required for REST-dependent repression of neurogenesis, we evaluated a panel of HDAC inhibitors (HDACI) for their effects on growth and differentiation of established and primary REST-positive cell lines. MS-275, trichostatin-A (TSA), valproic acid (VPA), and suberoylanilide hydroxamic acid (SAHA) upregulated expression of the REST-target neuronal differentiation gene, Syn1, suggesting a potential effect of these HDACIs on REST function. Interestingly, VPA and TSA substantially increased histone acetylation at the REST promoter and activated its transcription, whereas SAHA unexpectedly promoted its proteasomal degradation. A REST-dependent decrease in cell growth was also observed following SAHA treatment. Thus, our studies suggest that HDACIs may have therapeutic potential for patients with REST-positive tumors. This warrants further investigation. Mol Cancer Ther; 11(8); 1713–23. ©2012 AACR.
Targeting the PI3K/mTOR Axis, Alone and in Combination with Autophagy Blockade, for the Treatment of Malignant Peripheral Nerve Sheath Tumors
Authors: Ghadimi Markus P. , Lopez Gonzalo , Torres Keila E. , Belousov Roman , Young Eric D. , Liu Jeffery , Brewer Kari J. , Hoffman Aviad , Lusby Kristelle , Lazar Alexander J. , Pollock Raphael E. , Lev Dina
Published: July 2012

There is a critical need for efficacious therapeutic strategies to improve the outcome of patients afflicted by malignant peripheral nerve sheath tumors (MPNST). Multiple lines of evidence suggest a role for deregulated phosphoinositide 3-kinase (PI3K)/mTOR signaling in MPNST, making this axis an attractive target for therapeutic manipulation. On the basis of previous observations obtained from in vitro experimentation, here we aimed to assess the effects of PI3K/mTOR blockade on MPNST growth in vivo. The anti-MPNST impact of XL765, a dual PI3K/mTOR inhibitor currently being evaluated in human cancer clinical trials, was tested in two human MPNST xenograft models (STS26T and MPNST724) and an experimental model of pulmonary metastasis (STS26T). XL765 abrogated human MPNST local and metastatic growth in severe combined immunodeficient mice. Notably, this therapeutic approach failed to induce apoptosis in MPNST cells but rather resulted in marked productive autophagy. Importantly, genetic and pharmacologic autophagy blockade reversed apoptotic resistance and resulted in significant PI3K/mTOR inhibition-induced MPNST cell death. The addition of the autophagy inhibitor, chloroquine, to the therapeutic regimen of MPNST xenografts after pretreatment with XL765 resulted in superior antitumor effects as compared with either agent alone. Together, preclinical studies described here expand our previous findings and suggest that PI3K/mTOR inhibition alone and (most importantly) in combination with autophagy blockade may comprise a novel and efficacious therapy for patients harboring MPNST. Mol Cancer Ther; 11(8); 1758–69. ©2012 AACR.
Deregulation of XPC and CypA by Cyclosporin A: An Immunosuppression-Independent Mechanism of Skin Carcinogenesis
Authors: Han Weinong , Soltani Keyoumars , Ming Mei , He Yu-Ying
Published: July 2012

Skin cancer is the most common malignancy in organ transplant recipients, causing serious morbidity and mortality. Preventing and treating skin cancer in these individuals has been extraordinarily challenging. Following organ transplantation, cyclosporin A (CsA) has been used as an effective immunosuppressive to prevent rejection. Therefore immunosuppression has been widely assumed to be the major cause for increased skin carcinogenesis. However, the mechanism of skin carcinogenesis in organ transplant recipients has not been understood to date; specifically, it remains unknown whether these cancers are immunosuppression dependent or independent. Here, using both immunocompromised nude mice which are defective in mature T lymphocytes as an in vivo model and human keratinocytes as an in vitro model, we showed that CsA impairs genomic integrity in the response of keratinocytes to ultra violet B (UVB). Following UVB radiation, CsA inhibited UVB-induced DNA damage repair by suppressing the transcription of the DNA repair factor xeroderma pigmentosum C (XPC). In addition, CsA compromised the UVB-induced checkpoint function by upregulating the molecular chaperone protein cyclophilin A (CypA). XPC mRNA levels were lower, whereas CypA mRNA and protein levels were higher in human skin cancers than in normal skin. CsA-induced phosphoinositide 3-kinase(PI3K)/AKT activation was required for both XPC suppression and CypA upregulation. Blocking UVB damage or inhibiting the PI3K/AKT pathway prevented CsA-sensitized skin tumorigenesis. Our findings identified deregulation of XPC and CypA as key targets of CsA, and UVB damage and PI3K/AKT activation as two principal drivers for CsA-sensitized skin tumorigenesis, further supporting an immunosuppression-independent mechanism of CsA action on skin tumorigenesis. Cancer Prev Res; 5(9); 1155–62. ©2012 AACR.
The Phosphorylated Sodium Chloride Cotransporter in Urinary Exosomes Is Superior to Prostasin as a Marker for Aldosteronism
Authors: van der Lubbe Nils , Jansen Pieter M. , Salih Mahdi , Fenton Robert A. , van den Meiracker Anton H. , Danser A.H. Jan , Zietse Robert , Hoorn Ewout J.
Published: July 2012

Urinary exosomes are vesicles derived from renal tubular epithelial cells. Exosomes often contain several disease-associated proteins and are thus useful targets for identifying biomarkers of disease. Here, we hypothesized that the phosphorylated (active) form of the sodium chloride cotransporter (pNCC) or prostasin could serve as biomarkers for aldosteronism. We tested this in 2 animal models of aldosteronism (aldosterone infusion or low-sodium diet) and in patients with primary aldosteronism. Urinary exosomes were isolated from 24-hour urine or spot urine using ultracentrifugation. In rats, a normal or a high dose of aldosterone for 2, 3, or 8 days increased pNCC 3-fold in urinary exosomes (
P
<0.05 for all). A low-sodium diet also increased pNCC in urinary exosomes approximately 1.5-fold after 4 and after 8 days of treatment. The effects of these maneuvers on prostasin in urinary exosomes were less clear, showing a significant 1.5-fold increase only after 2 and 3 days of high-aldosterone infusion. In urinary exosomes of patients with primary aldosteronism, pNCC was 2.6-fold higher (
P
<0.05) while prostasin was 1.5-fold higher (
P
=0.07) than in patients with essential hypertension. Urinary exosomal pNCC and, to a lesser extent, prostasin are promising markers for aldosteronism in experimental animals and patients. These markers may be used to assess the biological activity of aldosterone and, potentially, as clinical biomarkers for primary aldosteronism.
Neurodynamics of Cognitive Set Shifting in Monkey Frontal Cortex and Its Causal Impact on Behavioral Flexibility
Authors: Kamigaki Tsukasa , Fukushima Tetsuya , Tamura Keita , Miyashita Yasushi
Published: July 2012

Flexible behavior depends on the ability to shift an internal cognitive set as soon as external demand changes. According to neuropsychological studies in human and nonhuman primates, selective lesion to the PFC impairs flexible behavioral shifting. Our previous fMRI study demonstrated that the prefrontal regions showed transient activation related to set shifting in humans and monkeys. To investigate the underlying neural processing, we recorded single-unit activities while monkeys performed a cognitive-set-shifting task, which required shifting between shape-matching and color-matching behaviors. We identified a group of neurons in the inferior arcuate region that exhibited selective activity when the monkeys were required to shift their cognitive set. These shift-related neurons were localized in the focal area along the posterior bank of the inferior arcuate sulcus. Reversible inactivation of this area ipsilateral to the response hand with a small volume of muscimol (even with 0.5 μl) selectively impaired the performance of behavioral shifting. Moreover, this selective behavioral impairment strongly correlated with the dose of muscimol. These results demonstrated localized neural processing for cognitive set shifting and its causal role for behavioral flexibility in primates.
The Structure and Argument of 1 John
Authors: Jensen Matthew
Published: July 2012

This article proposes a structure and argument for 1 John based on the locations of both the verb γράϕω and the vocative forms. It argues that 1 John has two parts: an extended introduction that orientates the reader to the themes of sin and love (1.1–2.11), and a body in which the historical situation is addressed (2.15–5.21). It divides 1 John into units based on vocabulary associated with each theme and then appeals to literary devices to verify each unit. The relationship between each unit is investigated in order to ascertain the structure.
Experiences of adult stroke survivors and their parent carers: a qualitative study
Authors: Jones Lisa , Morris Reg
Published: July 2012

Objective:

To explore the experiences of adult stroke survivors and their parent carers.

Design:

Qualitative methodology: interpretative phenomenological analysis.

Setting:

Six residential areas across England and south Wales.

Participants:

Six adult stroke survivors (aged 27–46), six mothers (aged 59–76) and five fathers (aged 55–76).

Method:

Semi-structured interviews to explore the relationship and interactions between parent and survivor prior to and after a stroke, with opportunities to explore both positive and negative changes. All interviews were transcribed and analysed by a six step interpretative phenomenological analysis process. Survivors, mothers and fathers were analysed as three separate groups and the results were synthesised.

Results:

Identical and interconnected themes emerged from the three groups, permitting synthesis into a single organising framework with four superordinate themes capturing the key issues for all three groups. The four superordinate themes were: ‘emotional turmoil’; ‘significance of parents’; ‘negotiating independence versus dependence’ and ‘changed relationships’.

Conclusions:

Parents reported adjusting to caring with relative ease. Survivors did not adjust to being cared for with such ease and felt positioned in a child role. Balancing independence and dependence was a challenge for survivors and parents and is considered within a systemic theory framework. Implications for service developments and guidelines are considered.
The effect of exposure to chlorine on pulmonary function tests and respiratory and allergic symptoms in Iranian lifeguards
Authors: Boskabady MH , Esmaeilizadeh M , Boskabady M
Published: July 2012

Lifeguards are frequently exposed to various irritant chemicals including chlorine during work, which can induce respiratory and allergic disorders. In this study, pulmonary function tests (PFTs) and self-reported respiratory and allergic symptoms in lifeguards were compared with matched control subjects. The frequency of respiratory and allergic symptoms was evaluated in a sample of 38 Iranian male lifeguards and 38 control subjects with similar age, having other jobs from the general population, using a questionnaire including questions on work-related respiratory and allergic symptoms in the past year, smoking habits, and duration of working as a lifeguard. PFTs were also measured in lifeguard subjects before and 15 min after 200 µg inhaled salbutamol and baseline PFT in controls. A total of 22 (55%) participants reported work-related respiratory symptoms. Sputum (39.4%) and cough (18.4%) were the most common symptoms and only 7.9% and 15.8% of lifeguards reported wheezing and shortness of breath, respectively. Both sputum and breathlessness were significantly higher in lifeguards than control group ( p < 0.05 and p < 0.005, respectively). Most allergic symptoms (sneezing and runny nose) in lifeguards were also significantly greater than control group ( p < 0.05 for both cases). In addition, all respiratory (except sputum and wheezing) and allergic symptoms were significantly higher in lifeguards during work compared with rest period ( p < 0.05 to p < 0.005). Most PFT values were also significantly lower in lifeguards than control subjects ( p < 0.05 to p < 0.001). In addition, most (all) PFT values were significantly improved after 200 µg inhaled salbutamol ( p < 0.05 to p < 0.001). These results showed that lifeguards have higher frequencies of work related respiratory symptoms and allergic symptoms particularly during the work period. PFT values were also significantly reduced among lifeguards.
A controlled before and after study to evaluate a patient and health professional partnership model towards effective medication reconciliation
Authors: Lingaratnam Senthil , Aranda Sanchia , Pearce Tracy , Kirsa Sue
Published: July 2012

Preventable medication errors impact substantially on the Australian healthcare system. Where ‘poor communication of medical information at transition points is responsible for as many as 50% of all medication errors’, a leading contributor for this type of medication error is lack of consumer knowledge about medicines information. This study was aimed at designing and testing the effectiveness of a consumer–healthcare professional partnership model towards effective medication reconciliation. This model aims to empower consumers about their medicines information, so that they would contribute more effectively to medication reconciliation and thereby minimise medication errors occurring at transition points. Components of this model were informed by qualitative data gleaned from patient opinion surveys, focus group sessions involving nurses, doctors and pharmacists working at the hospital and results of a literature search of medication safety tools. Programme development was informed by health improvement approaches centred on a Plan-Do-Study-Act cycle. Evaluation for effectiveness was conducted within a framework of a controlled before and after study. Results revealed that there was a 1.4-fold increase in the reporting rate of pharmacists intervention. The study could not demonstrate that the designed intervention was effective in minimising near-misses. However, there is statistically insignificant reduction in errors for patients that were correctly exposed to the intervention. Anecdotal evidence suggests there is utility for a patient population keen to claim greater ownership of their medicines information. Further, we advocate that patient education about medicines and the establishment of a consumer–healthcare professional model occur prior to ward admission.
Ulnar Collateral Ligament Reconstruction Revisited
Authors: Dodson Christopher C. , Altchek David W.
Published: July 2012

Context:

Ulnar collateral ligament (UCL) insufficiency of the elbow can be a debilitating injury that often prevents athletes from competing effectively. The overhead athlete is particularly susceptible to this injury because the anterior bundle of the UCL is the primary restraint to the valgus stress that is created during the throwing motion. Repetitive trauma from constant overhead or throwing activity can ultimately render the ligament incompetent and cause recurrent pain and instability.

Results:

The authors currently use a “docking” technique that provides excellent graft fixation and reduces ulnar nerve related complications.

Conclusions:

This article details the assessment of the throwing athlete with valgus instability secondary to UCL insufficiency and highlights the technical aspects for reconstruction. The majority of athletes who undergo UCL reconstruction of the elbow can successfully return to their preinjury function.

Strength-of-Recommendation Taxonomy (SORT):

A