bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis
Authors: Neel Jean-Charles , Humbert Laure , Lebrun Jean-Jacques
Published: December 2012

The transforming growth factor-beta (TGFβ) superfamily encompasses widespread and evolutionarily conserved polypeptide growth factors that regulate and orchestrate growth and differentiation in all cell types and tissues. While they regulate asymmetric cell division and cell fate determination during early development and embryogenesis, TGFβfamily members play a major regulatory role in hormonal and immune responses, cell growth, cell death and cell immortalization, bone formation, tissue remodeling and repair, and erythropoiesis throughout adult life. The biological and physiological functions of TGFβ, the founding member of this family, and its receptors are of central importance to human diseases, particularly cancer. By regulating cell growth, death, and immortalization, TGFβsignaling pathways exert tumor suppressor effects in normal cells and early carcinomas. Thus, it is not surprising that a high number of human tumors arise due to mutations or deletions in the genes coding for the various TGFβsignaling components. As tumors develop and progress, these protective and cytostatic effects of TGFβare often lost. TGFβsignaling then switches to promote cancer progression, invasion, and tumor metastasis. The molecular mechanisms underlying this dual role of TGFβin human cancer will be discussed in depth in this paper, and it will highlight the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGFβsignaling pathway without affecting its tumor suppressive effects.
Price Regulation in Oligopolistic Markets
Authors: Corchón Luis C. , Marcos Félix
Published: December 2012

We consider price regulation in oligopolistic markets when firms are quantity setters. We consider a market for a homogeneous good with a demand function of special form (-linearity), constant returns to scale, and identical firms. Marginal costs can take two values only: low or high. Values of all parameters except the marginal costs are known to the regulator. Assuming that the regulator is risk-neutral and maximizes expected social welfare (defined as the sum of consumer surplus and profits), we characterize the optimal policy and show how this policy depends on the basic parameters of demand and costs.
Dimensional Accuracy of Stone Casts Obtained with Multiple Pours into the Same Mold
Authors: Valente Valdimar da Silva , Zanetti Artêmio Luiz , Feltrin Pedro Paulo , Inoue Ricardo Tatsuo , de Moura Carmem Dolores Vilarinho Soares , Pádua Luiz Evaldo de Moura
Published: December 2012

Aim. The aim of the present study was to compare the dimensional accuracy of stone casts obtained with vinyl polysiloxane molds through the double-impression technique with three pours into the same mold. Methods. A stainless steel master model was constructed simulating a three-unit fixed prosthesis. Twelve impressions were taken of this master model with addition silicone, using the double-impression technique. Three pours of type IV gypsum were then made into each mold, thus producing 36 casts. The pours were made 1 hour, 6 hours and 24 hours after the impression procedure. Next, intra- and interabutment measurements were made in a coordinate measuring machine. Results. Comparative analysis of the dimensional accuracy of stone casts resulting from multiple pours was not statistically significant in pours first and second (P>0.05). These values, however, were statistically significant at third pour in the height in abutment 1 and upper distance interabutment. Conclusion. The wait time (1 hour, and 6 hours) observed before pouring the stone into the same molds did not cause significant dimensional accuracy of the casts.
Rehabilitation Considerations for Children Dependent on Long-Term Mechanical Ventilation
Authors: Dumas Helene M.
Published: December 2012

The purposes of this paper are as follows (1) to describe the prevalence, etiology, and care settings for children dependent on long-term mechanical ventilation (MV); (2) to provide a brief introduction to MV and weaning; (3) to explore health care utilization and cost of care; and, primarily, (4) to discuss the rehabilitation needs of children dependent on long-term MV including activities of daily living, mobility, communication, psychosocial needs, and recreation and leisure. Children with ventilator dependence are a growing segment of the population of children with special health care needs and often require rehabilitation services. MV is a form of life-saving technology that substitutes for or assists a child’s respiratory efforts. Goals for use of MV vary and there are many combinations of MV elements that can obtain desirable results. No standards of care exist for the rehabilitation examination or interventions utilized for children with long-term MV dependence and it remains unclear what effect MV has on the achievement of developmental milestones, daily activities, and participation in daily life.
Design and Development of Degradable Polyethylenimines for Delivery of DNA and Small Interfering RNA: An Updated Review
Authors: Cho Chong-Su
Published: December 2012

Polyethylenimine (PEI), considered as the most potent and promising alternative carrier to viral vectors, has been studied as the “state of the art” among various polymers for nonviral gene delivery applications for many years. Although PEI-based carrier minimizes the bottlenecks associated with viral vectors such as unwanted immunogenicity and production problems, the toxic side effects of PEI prevent its rapid advancements due to nondegradable nature. In this regard, various degradable cross-linking and/or grafting agents have been linked to synthesize degradable PEIs in order to minimize the toxicity and improve the efficacy of PEI-mediated gene carriers. This paper describes an update on various cross-linkers and grafting agents in the design and development of degradable PEI derivatives and their potential applications for effective delivery of DNAin vitroandin vivo. The molecular weight (MW) of PEI and the structural relationship to its cellular toxicity and transfection ability were also discussed. Finally, the potential applications of various degradable PEIs for small interfering RNA (siRNA)-mediated gene silencing were also covered.
Food versus Fuel: Toward a New Paradigm—The Need for a Holistic Approach
Authors: Rosillo-Calle Frank
Published: December 2012

A key objective of this paper is to provide an assessment of the current and future situation on the “food versus fuel” debate and to contribute to possible alternatives to minimise or avoid future conflict. The debate has centred on three main areas: (i) food versus biofuel production, (ii) their positive and negative effects (i.e., GHG, climate change, and the broader environment), and (iii) a socioeconomic impact. The debate has been controversial because it has largely been driven by politics, ethical/moral considerations, and vested interests rather than by science. The paper focuses on food prices, land competition, GHG, energy balance, and energy subsidies and concerns with the rapid expansion of bioenergy for electricity and heat, climatic changes, the role of agriculture as a key factor, the potential of biomass energy resources, and the various alternatives to minimize or avoid conflict between food and fuel production. Biomass for energy is both “part of the problem and part of the solution.” It proposes a holistic approach: a new paradigm that takes full account of the diverse and complex nature of biomass energy sources and states that the fundamental underlying causes are social injustice, inequality, waste, and so forth, rather than land competition for food and fuel.
Residual Renal Function in Hemodialysis Patients: The Role of Angiotensin-Converting Enzyme Inhibitor in Its Preservation
Authors: Xydakis Dimitris , Papadogiannakis Apostolos , Sfakianaki Maria , Kostakis Konstantinos , Stylianou Konstantinos , Petrakis Ioannis , Ergini Antonaki , Voskarides Konstantinos , Dafnis Eugeneios
Published: December 2012

Residual Renal function (RRF) has an important role in the overall morbidity and mortality in hemodialysis patients. The role of angiotensin-converting enzyme inhibitor (ACEi) in preserving renal function in chronic proteinuric nephropathies is well documented. We test the hypothesis that enalapril (an ACEi) slows the rate of decline of RRF in patients starting hemodialysis. A prospective, randomized open-label study was carried out. 42 patients were randomized in two groups either in treatment with enalapril or no treatment at all. Our study has proven that enalapril has a significant effect on preserving residual renal function in patients starting dialysis at least during the first 12 months from the initiation of the hemodialysis. Further studies are necessary in order to investigate the potential long-term effect of ACEi on residual renal function and on morbidity and mortality in patients starting hemodialysis.
Sexual Practices and HIV Prevalence amongst Men Who Have Sex with Men at a Community-Based Voluntary Counseling and Testing Centre in Malaysia
Authors: Koh K. C. , Kanagalingam K. , Tai F. T. , Kamarulzaman A.
Published: December 2012

We describe the sexual practices and condom usage of men who have sex with men (MSM) at a community-based anonymous voluntary counseling and testing centre in Kuala Lumpur, Malaysia. This study is a first for Malaysia in this context. 433 MSM clients disclosed their sexual practices and condom use in the preceding 6 months using a self-reported questionnaire during pre-HIV test counseling at the centre. The mean age was 29.7 years, and 356 were homosexuals while 77 were bisexuals. Forty tested HIV positive (9.2%). 387 (94.9%) of 408 clients had anal sex, 395 (97.8%) of 404 clients had oral sex, while 43 (18.4%) of 233 clients had vaginal sex which revealed that even men who identified themselves as homosexuals do practice vaginal sex. Having multiple sexual partners is common (mean 11.6 partners per client). 259 (59.8%) had unprotected sex within the last 6 months. Consistent condom use rates during vaginal, anal, and oral sex were 20%, 23.5%, and 1.3%, respectively. The odds ratio of testing HIV positive with inconsistent condom use during anal sex was 3.7 (). Clients who used condoms inconsistently during anal sex are more likely to be HIV positive.
Nonlinear Analysis of Guillain Barré Time Series to Elucidate Its Epidemiology
Authors: Lestayo O'Farrill Zurina , Hernández Cáceres José Luís , O'Farrill Mons Esperanza
Published: December 2012

The etiology of Guillain Barré Syndrome (GBS) is not fully clarified, and there is a lack of agreement concerning its putative epidemic character. The low incidence rate of this disease is a disadvantage for employing the traditional statistical methods used in the analysis of epidemics. The objective of this paper is to clarify the GBS epidemic behavior applying a nonlinear time series identification approach. The authors obtained one time series of GBS and nine series of classical infectious epidemics (5 national and 4 international). These data were processed with advanced techniques of statistical time series analysis. This paper shows that GBS behaves similar to the other time series of classical epidemic studied. It corresponds to a nonlinear dynamics, with a point attractor. The spectral analysis pointed to an annual periodicity, and preference for the warmest month of the year was found. These results might suggest that Guillain Barré Syndrome has an epidemic behavior. The adequacy of nonlinear methods for analyzing the dynamics of epidemics, particularly those with low incidence rate, such as GBS was revealed.
Finite-Element-Based Multiple Normal Loading-Unloading of an Elastic-Plastic Spherical Stick Contact
Authors: Chatterjee Biplab , Sahoo Prasanta
Published: December 2012

The repeated normal elastic plastic contact problem of a deformable sphere against a rigid flat under full stick contact condition is investigated with a commercial finite element software ANSYS. Emphasis is placed on the effect of strain hardening and hardening model with the maximum interference of load ranging from elastic to fully plastic, which has not yet been reported. Different values of tangent modulus coupled with isotropic and kinematic hardening models are considered to study their influence on contact parameters. Up to ten normal loading-unloading cycles are applied with a maximum interference of 200 times the interference required to initiate yielding. Results for the variation of mean contact pressure, contact load, residual interference, and contact area with the increasing number of loading unloading cycles at high hardening parameter as well as for low tangent modulus with two different hardening models are presented. Results are compared with available finite element simulations and in situ results reported in the literature. It is found that small variation of tangent modulus results in same shakedown behavior and similar interfacial parameters in repeated loading-unloading with both the hardening rules. However at high tangent modulus, the strain hardening and hardening rules have strong influence on contact parameters.
Branching Pattern of Inferior Mesenteric Artery in a Black African Population: A Dissection Study
Authors: Sinkeet Simeon , Mwachaka Philip , Muthoka Johnstone , Saidi Hassan
Published: December 2012

Background. Branching pattern of inferior mesenteric artery (IMA) and pattern of vascular supply to the left colon and rectosigmoid areas, though important during colorectal surgery, display interethnic variations. Further, these regions have notable vascular “weak points” reported to be highly susceptible to ischemic colitis. This study aimed at evaluating the branching pattern of IMA in a black African population. Materials and Methods. Fifty-seven formalin-embalmed cadavers (28 Male, 27 Female) were studied. The length, branching pattern, and diameter of IMA at its origin were recorded. Results. IMA mean length and diameter at origin were  mm and  mm, respectively. IMA most frequently branched into left colic artery and a common sigmoid trunk in 23 cases while the classical branching pattern was observed in only 7 cases. Colic marginal artery was absent at the splenic flexure and sigmoid colon in 7 and 5 cases, respectively. Arc of Riolan was observed in 9 cases. Conclusion. Branching pattern of IMA shows variations from the previously reported cases which might help account for some of the untoward outcomes observed following colon surgery. An angiographic study to further delineate functionality of the arterial anastomoses in this region is recommended.
The Clinical Area Safety Assessment, a Peer Review of Safety across an Acute Trust
Authors: Robinson Susan , Ward James , Baglin Trevor , Broster Susan , Heesom-Duff Carol , Pascoe Glenn , Ahluwalia Jag
Published: December 2012

Background Most hospitals have developed processes to manage risk in a reactive manner. Few, however, have instituted proactive systems for the identification of latent risk that has the potential to cause harm. Objective To develop a process for the identification of potential risks to safety across all clinical areas of a hospital. Methods Every clinical department in Cambridge University Hospitals Foundation Trust (CUHFT) underwent peer assessment to confirm that the Trust’s processes for safety were in place and identify possible threats to the safety of patients. This assessment consisted of a number of elements that included review of routinely collected data, observed clinical care and a safety questionnaire. The methodology used to apply this process is described. Results The outcomes of 33 clinical area safety assessments (CASA) are reported. No department was awarded unconditional accreditation nor have any had their service suspended. A number of recurrent issues emerged, the most common being that 31% of departments failed to fully comply with Trust requirements for governance and 12% needed to improve compliance with patient safety standards. Concerns related to documentation were identified in 11% of assessments. To date the programme has cost approximately £111,000 with each review requiring approximately 130 hrs to complete. Conclusions The CASA programme has offered an opportunity to improve standardisation in governance and optimise safety processes across our hospital. It has facilitated the dissemination of good practice amongst teams to resolve common problems. Suggestions as to how we plan to further refine this peer review process are offered.
Climate Change how does Weather Affect Surface Water Quality?
Authors: Wright Ben , Stanford Ben , Weiss Josh , Debroux Jean , Routt Jan , Khan Stuart
Published: December 2012

A better understanding of relationships among weather patterns and water quality will allow utilities to more effectively plan for the effects of climate change. Best practice requires understanding as much as possible about changes that can occur and their implications for utility operations and management. This article provides information compiled from published literature on weather and water quality to help utilities develop a series of event‐outcome relationships to describe specific changes to surface water quality relative to climate change.
Microflocculation Reduces Membrane Fouling
Authors: Bryant Tommy , Bradford Wesley L. , Rivera Susan B.
Published: December 2012

A pilot study at the Dekalb‐Jackson Water Treatment Plant in Ider, Alabama, confirmed that pretreatment dosing of a mixed‐oxidant solution improved settled turbidity in its clarifiers prior to membrane filtration.
Consider Aeration and Chemical Alternatives for Copper Corrosion Control
Authors: Ryder Robert A.
Published: December 2012

Several factors drive the need to reduce copper in water systems. However, because those drivers aren't the same for all systems, several options for reducing copper and resulting corrosion are available.
Can a Small System Develop an Effective Asset Management Program?
Authors: Copeland Ari
Published: December 2012

One thing all water and wastewater utilities need, regardless of size or location, is an effective asset management program. Information in this column highlights asset management program benefits and will help small systems start or refine a program.
Regulatory Update: Be Prepared for Changes
Authors: Roberson Alan
Published: December 2012

The regulatory development process in the Office of Groundwater and Drinking Water (OGWDW) of the US Environmental Protection Agency (USEPA) continues to chug along. In addition, it will take some time to sort out how recent election results will affect the US Congress, federal agencies, and the budget. OGWDW has several upcoming regulatory actions that will significantly affect water systems during the next few years.
The Becoming of the Complex Socium: New Causes of Deviance and Crime
Authors: Kravchenko Sergey A.
Published: December 2012

This article focuses on the factors that influence the becoming of the complex socium. The author considers, in his opinion, the most characteristic parameters of the complex socium that is developing in the context of the ‘arrow of time’. He asserts that the becoming of the complex socium brings unintended consequences producing new causes of deviance and crime. Under these conditions he argues for the humanistic turn in sociology, based on non-linear and humanistic sociological imagination, and humanistic praxis.
Contemporaneous Severity of Symptoms and Functioning Reflected by Variations in Reporting Doctor‐Diagnosed Osteoarthritis
Authors: Peeters Geeske , Parkinson Lynne , Badley Elizabeth , Jones Mark , Brown Wendy J. , Dobson Annette J. , Mishra Gita D.
Published: December 2012

Objective

Osteoarthritis (OA) is acknowledged as an enduring condition; however, in epidemiologic studies, half of the participants who report having OA at one time may report not having it at a subsequent time. The aim of this study was to examine whether variations in reporting doctor‐diagnosed OA reflected concurrent fluctuations in indicators of disease severity in middle‐aged women.

Methods

Data were from 7,623 participants (ages 50–55 years in 2001) in the Australian Longitudinal Study on Women's Health. Based on self‐report of doctor‐diagnosed OA at surveys in 2001, 2004, 2007, and 2010, the participants were classified according to pattern of OA reporting (e.g., 0‐0‐0‐0 = “no” on all surveys, 0‐1‐0‐1 = “no‐yes‐no‐yes”). Indicators of disease severity included frequency of joint pain/stiffness, use of antiinflammatory medications, and physical functioning assessed with the Short Form 36. Bar graphs were used to show concurrent variations in OA and markers, and associations were examined using log‐linear models.

Results

In this sample, 46% reported having OA on at least one survey, with half of these cases reporting not having OA at a later survey. The odds of reporting joint pain/stiffness often (odds ratio [OR] 7.26, 95% confidence interval [95% CI] 7.06–7.47) and taking antiinflammatory drugs (OR 4.44, 95% CI 2.37–8.33) were higher and physical functioning scores were lower (OR 3.75, 95% CI 3.56–3.95) when participants reported having OA.

Conclusion

Variations in reporting OA coincided with episodic fluctuations in symptoms and functioning. Inconsistent reporting of OA could therefore reflect the presence of symptoms rather than reporting error and should be considered in longitudinal studies.
Association of Diabetes Mellitus With the Risk of Developing Adhesive Capsulitis of the Shoulder: A Longitudinal Population‐Based Followup Study
Authors: Huang Ya‐Ping , Fann Ching‐Yuan , Chiu Yueh‐Hsia , Yen Ming‐Fang , Chen Li‐Sheng , Chen Hsiu‐Hsi , Pan Shin‐Liang
Published: December 2012

Objective

Although it has been suggested that diabetes mellitus (DM) is a risk factor for developing adhesive capsulitis of the shoulder (ACS), data on the temporal association between these 2 conditions are sparse. The purpose of this population‐based age‐ and sex‐matched cohort study was to investigate the risk of developing ACS in patients with newly diagnosed DM.

Methods

A total of 78,827 subjects with at least 2 ambulatory care visits with a principal diagnosis of DM in 2001 were recruited for the DM group. The non‐DM group comprised 236,481 age‐ and sex‐matched randomly sampled subjects without DM. The 3‐year cumulative risk of ACS was calculated using the Kaplan‐Meier method. A Cox proportional hazards regression model was used to estimate the crude and adjusted hazard ratio (HR) of developing ACS.

Results

During a 3‐year followup period, 946 subjects (1.20%) in the DM group and 2,254 subjects (0.95%) in the non‐DM group developed ACS. The crude HR of developing ACS for the DM group compared to the non‐DM group was 1.333 (95% confidence interval [95% CI] 1.236–1.439, P < 0.0001), whereas the adjusted HR was 1.321 (95% CI 1.224–1.425, P < 0.0001) after adjustment for age, sex, and dyslipidemia.

Conclusion

This longitudinal population‐based followup study showed that there is a significantly increased risk of developing ACS after developing DM.
Development of optically transparent ZnS/poly(vinylpyrrolidone) nanocomposite films with high refractive indices and high Abbe numbers
Authors: Zhang Quanyuan , Goh Eunice Shing Mei , Beuerman Roger , Judeh Zaher , Chan‐Park Mary B. , Chen Tupei , Xu Rong
Published: December 2012

A series of optically transparent ZnS‐poly(vinylpyrrolidone) (PVP) nanocomposite films with high refractive indices and high Abbe numbers have been prepared. Mercaptoethanol (ME) capped ZnS nanoparticles (NPs) were introduced into the PVP polymer matrix via simple blending with high nanophase contents. ME‐ZnS NPs of around 3 nm were prepared from zinc acetate and thiourea precursors in N,N‐dimethylformamide using ME as a capping agent. Transparent nanocomposite films with high refractive indices and high Abbe numbers can be easily prepared by a conventional film casting method. TGA results indicated that the ZnS/PVP nanocomposite films exhibit good thermal stability and the measured contents of ZnS NPs in the films agree well with the theoretical values. The refractive indices and the Abbe numbers of the ZnS/PVP nanocomposite films range from 1.5061 to 1.7523 and 55.6 to 20.4 with the content of ME‐ZnS NPs varied between 0 and 80 wt %, respectively. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Development of a Hypersensitive Periodate‐Cleavable Amino Acid that is Methionine‐ and Disulfide‐Compatible and its Application in MHC Exchange Reagents for T Cell Characterisation
Authors: Amore Alessia , Wals Kim , Koekoek Evelyn , Hoppes Rieuwert , Toebes Mireille , Schumacher Ton N. M. , Rodenko Boris , Ovaa Huib
Published: December 2012

Incorporation of cleavable linkers into peptides and proteins is of particular value in the study of biological processes. Here we describe the synthesis of a cleavable linker that is hypersensitive to oxidative cleavage as the result of the periodate reactivity of a vicinal amino alcohol moiety. Two strategies directed towards the synthesis of a building block suitable for solid‐phase peptide synthesis were developed: a chemoenzymatic route, involving L‐threonine aldolase, and an enantioselective chemical route; these led to α,γ‐diamino‐β‐hydroxybutanoic acids in diastereoisomerically mixed and enantiopure forms, respectively. Incorporation of the 1,2‐amino alcohol linker into the backbone of a peptide generated a conditional peptide that was rapidly cleaved at very low concentrations of sodium periodate. This cleavable peptide ligand was applied in the generation of MHC exchange reagents for the detection of antigen‐specific T cells in peripheral blood cells. The extremely low concentration of periodate required to trigger MHC peptide exchange allowed the co‐oxidation of methionine and disulfide residues to be avoided. Conditional MHC reagents hypersensitive to periodate can now be applied without limitations when UV irradiation is undesired or less practical.
Diagnostic assays for identification of anaplastic lymphoma kinase‐positive non–small cell lung cancer
Authors: Weickhardt Andrew J. , Aisner Dara L. , Franklin Wilbur A. , Varella‐Garcia Marileila , Doebele Robert C. , Camidge D. Ross
Published: December 2012

In series dominated by adenocarcinoma histology, approximately 5% of non–small cell lung cancers (NSCLCs) harbor an anaplastic lymphoma kinase (ALK) gene rearrangement. Crizotinib, a tyrosine kinase inhibitor with significant activity against ALK, has demonstrated high response rates and prolonged progression‐free survival in ALK‐positive patients enrolled in phase 1/2 clinical trials. In 2011, crizotinib received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of proven ALK‐positive NSCLC using an FDA‐approved diagnostic test. Currently, only break‐apart fluorescence in situ hybridization testing is FDA approved as a companion diagnostic for crizotinib; however, many other assays are available or in development. In the current review, the authors summarize the diagnostic tests available, or likely to become available, that could be used to identify patients with ALK‐positive NSCLC, highlighting the pros and cons of each. Cancer 2013. © 2012 American Cancer Society.
Finding near‐perfect parameters for hardware and code optimizations with automatic multi‐objective design space explorations
Authors: Jahr Ralf , Calborean Horia , Vintan Lucian , Ungerer Theo
Published: December 2012

In the design process of computer systems or processor architectures, typically many different parameters are exposed to configure, tune, and optimize every component of a system. For evaluations and before production, it is desirable to know the best setting for all parameters. Processing speed is no longer the only objective that needs to be optimized; power consumption, area, and so on have become very important. Thus, the best configurations have to be found in respect to multiple objectives. In this article, we use a multi‐objective design space exploration tool called Framework for Automatic Design Space Exploration (FADSE) to automatically find near‐optimal configurations in the vast design space of a processor architecture together with a tool for code optimizations and hence evaluate both automatically. As example, we use the Grid ALU Processor (GAP) and its postlink optimizer called GAPtimize, which can apply feedback‐directed and platform‐specific code optimizations. Our results show that FADSE is able to cope with both design spaces. Less than 25% of the maximal reasonable hardware effort for the scalable elements of the GAP is enough to achieve the processor's performance maximum. With a performance reduction tolerance of 10%, the necessary hardware complexity can be further reduced by about two‐thirds. The found high‐quality configurations are analyzed, exhibiting strong relationships between the parameters of the GAP, the distribution of complexity, and the total performance. These performance numbers can be improved by applying code optimizations concurrently to optimizing the hardware parameters. FADSE can find near‐optimal configurations by effectively combining and selecting parameters for hardware and code optimizations in a short time. The maximum observed speedup is 15%. With the use of code optimizations, the maximum possible reduction of the hardware resources, while sustaining the same performance level, is 50%.Copyright © 2012 John Wiley & Sons, Ltd.
ND++ – an extended IPv6 Neighbor Discovery protocol for enhanced stateless address autoconfiguration in MANETs
Authors: Grajzer Monika , Żernicki Tomasz , Głąbowski Mariusz
Published: December 2012

Recent trends in information and communications technologies are oriented toward the design of the Future Internet and the Internet of Things. While IPv6‐based mobile ad hoc networks (MANETs) are emerging as an important building block of these new technologies, it is necessary to come up with adequate self‐configuration capabilities allowing for seamless and automated configuration of addresses in mobile environment. The mechanisms of stateless address autoconfiguration proposed for IPv6 networks are supposed to automate some configuration steps; however, they would need to be aligned with the requirements imposed by MANET networks. Therefore, in this article, we present Neighbor Discovery ++ – an extended IPv6 Neighbor Discovery protocol for enhanced duplicate address detection in MANETs, which provides increased coverage of network nodes, while minimizing protocol overhead. It exploits efficient flooding mechanism on the basis of the multipoint relay concept, which makes it an interesting approach also for large‐scale networks. Trials performed on the designated real‐world testbed platform indicate that ND++ is a promising solution to support efficient address autoconfiguration in MANETs. Copyright © 2012 John Wiley & Sons, Ltd.
Spin Crossover and Thermochromism of Iron(II) Coordination Compounds with 1,2,4‐Triazoles and Tris(pyrazol‐1‐yl)methanes
Authors: Lavrenova Ludmila G. , Shakirova Olga G.
Published: December 2012

We review herein the synthesis and investigation of iron(II) coordination compounds with 1,2,4‐triazoles or tris(pyrazol‐1‐yl)methanes as ligands. Both groups of complexes demonstrate thermally induced spin crossover accompanied by thermochromism [pink (magenta) ↔ white color change]. Factors that influence the nature and temperature of the spin crossover are discussed.
Glutamate dehydrogenase 1 and SIRT4 regulate glial development
Authors: Komlos Daniel , Mann Kara D. , Zhuo Yue , Ricupero Christopher L. , Hart Ronald P. , Liu Alice Y. ‐C. , Firestein Bonnie L.
Published: December 2012

Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by an activation mutation of glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme responsible for the reversible interconversion between glutamate and α‐ketoglutarate. The syndrome presents clinically with hyperammonemia, significant episodic hypoglycemia, seizures, and frequent incidences of developmental and learning defects. Clinical research has implicated that although some of the developmental and neurological defects may be attributed to hypoglycemia, some characteristics cannot be ascribed to low glucose and as hyperammonemia is generally mild and asymptomatic, there exists the possibility that altered GDH1 activity within the brain leads to some clinical changes. GDH1 is allosterically regulated by many factors, and has been shown to be inhibited by the ADP‐ribosyltransferase sirtuin 4 (SIRT4), a mitochondrially localized sirtuin. Here we show that SIRT4 is localized to mitochondria within the brain. SIRT4 is highly expressed in glial cells, specifically astrocytes, in the postnatal brain and in radial glia during embryogenesis. Furthermore, SIRT4 protein decreases in expression during development. We show that factors known to allosterically regulate GDH1 alter gliogenesis in CTX8 cells, a novel radial glial cell line. We find that SIRT4 and GDH1 overexpression play antagonistic roles in regulating gliogenesis and that a mutant variant of GDH1 found in HI/HA patients accelerates the development of glia from cultured radial glia cells. © 2012 Wiley Periodicals, Inc.
Incenting managers toward the triple bottom line: An agency and social norm perspective
Authors: Merriman Kimberly K. , Sen Sagnika
Published: December 2012

Research to date has identified CEO pay structure as an important factor in the environmental and social performance of the organization but has not considered how pay may influence these sustainability efforts at the middle‐management level. We address this void with an experimental manipulation of direct and indirect pay incentives for an environmental sustainability project and production cost savings project. Counter to our predictions, investment in sustainability versus cost savings is significantly lower when incentives for both projects are equivalent, and investment is only comparable when incentives for the sustainability project are superior. Further investigation using qualitative data attributes this to differences in the salient social norms that individuals hold and an apparent undervaluing of the indirect incentive derived through sustainability's contribution to cost savings. The results shed light on primary ways in which human resource management practices may be used to embed support for sustainability initiatives throughout the organization.
Poly‐(L‐lactic acid) and citric acid‐crosslinked gelatin composite matrices as a drug‐eluting stent coating material with endothelialization, antithrombogenic, and drug release properties
Authors: Inoue Motoki , Sasaki Makoto , Katada Yasuyuki , Fujiu Katsuhito , Manabe Ichiro , Nagai Ryozo , Taguchi Tetsushi
Published: December 2012

Biodegradable composite matrices comprising poly‐(L‐lactic acid) (PLLA) and citric acid‐crosslinked alkali‐treated gelatin (AlGelatin) with endothelialization, antithrombogenic, and drug release properties were prepared. The characterization of composite matrices with various mixing ratios was performed by evaluating their swelling ratio, endothelial cell culture, antithrombogenic tests, and drug release behavior. Tamibarotene (Am80), which specifically inhibits smooth muscle cell proliferation, was employed as the drug. The swelling ratio of composite matrices decreased as the PLLA content decreased. The number of endothelial cells cultured on the surfaces of composite matrices was maximal at the PLLA/AlGelatin‐TSC ratio of 80/20. Antithrombogenic tests revealed that the levels of platelets and fibrin network formation decreased as the AlGelatin‐TSC content increased. The Am80 release test indicated that the release rate decreased as PLLA content increased. Using the resulting composite matrix, Am80‐eluting stents possessing a smooth surface and a coating thickness of ∼15 μm were successfully obtained. Am80 was continuously released from the resulting stent at ∼40%, up to 28 days without burst release. Therefore, Am80‐eluting stent with its antithrombogenic and endothelialization properties has great potential for clinical use. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Effect of femoral head size on the wear of metal on metal bearings in total hip replacements under adverse edge‐loading conditions
Authors: Al‐Hajjar Mazen , Fisher John , Williams Sophie , Tipper Joanne L. , Jennings Louise M.
Published: December 2012

Metal‐on‐metal (MoM) bearings have shown low‐wear rates under standard hip simulator conditions; however, retrieval studies have shown large variations in wear rates and mechanisms. High‐wear in vivo has caused catastrophic complications and has been associated with steep cup‐inclination angle (rotational malpositioning). However, increasing the cup‐inclination angle in vitro has not replicated the increases in wear to the same extent as those observed in retrievals. Clinically relevant wear rates, patterns, and particles were observed in vitro for ceramic‐on‐ceramic bearings when microseparation (translational malpositioning) conditions were introduced into the gait cycle. In the present study, 28 and 36‐mm MoM bearings were investigated under adverse conditions. Increasing the cup angle from 45° to 65° resulted in a significant increase in the wear rate of the 28 mm bearings. However, for the 36 mm bearings, head‐rim contact did not occur under the steep cup‐angle condition, and the wear rate did not increase. The introduction of microseparation to the gait cycle significantly increased the wear rate of the MoM bearings. Cup angle and head size did not influence the wear rate under microseparation conditions. This study indicated that high‐in vivo wear rates were associated with edge loading due to rotational malpositioning such as high‐cup‐inclination angle and translational malpositioning that could occur due to several surgical factors. Translational malpositioning had a more dominant effect on the wear rate. Preclinical simulation testing should be undertaken with translational and rotational malpositioning conditions as well as standard walking cycle conditions defined by the ISO standard. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Bone blood flow and metabolism in humans: Effect of muscular exercise and other physiological perturbations
Authors: Heinonen Ilkka , Kemppainen Jukka , Kaskinoro Kimmo , Langberg Henning , Knuuti Juhani , Boushel Robert , Kjaer Michael , Kalliokoski Kari K
Published: December 2012

Human bone blood flow and metabolism during physical exercise remains poorly characterized. In the present study we measured femoral bone blood flow and glucose uptake in young healthy subjects by positron emission tomography in three separate protocols. In 6 women, blood flow was measured in femoral bone at rest and during one-leg intermittent isometric exercise with increasing exercise intensities. In 9 men, blood flow in the femur was determined at rest and during dynamic one-leg exercise and two other physiological perturbations: moderate systemic hypoxia (14 O2) at rest and during exercise, and during intrafemoral infusion of high-dose adenosine. Bone glucose uptake was measured at rest and during dynamic one-leg exercise in 5 men. The results indicate that isometric exercise increased femoral bone blood flow from rest (1.8 ± 0.6 mL/100 g/min) to low intensity exercise (4.1 ± 1.5 mL/100 g/min, p = 0.01), but blood flow did not increase further with increasing intensity. Resting femoral bone blood flow in men was similar to that of women and dynamic one-leg exercise increased it to 4.2 ± 1.2 mL/100 g/min, p < 0.001. Breathing of hypoxic air did not change femoral bone blood flow at rest or during exercise, but intra-arterial infusion of adenosine during resting conditions increased bone blood flow to 5.7 ± 2.4 mL/100 g/min, to the level of moderate-intensity dynamic exercise. Dynamic one-leg exercise increased femoral bone glucose uptake 4.7-fold compared to resting contralateral leg. In conclusion, resting femoral bone blood flow increases by physical exercise, but appears to level off with increasing exercise intensities. Moreover, although moderate systemic hypoxia does not change bone blood flow at rest or during exercise, intra-arterially administered adenosine during resting conditions is capable of markedly enhancing bone blood flow in humans. Finally, bone glucose uptake also increases substantially in response to exercise. © 2013 American Society for Bone and Mineral Research.
Storytelling as a vehicle for self‐awareness: Establishing a foundation for intercultural competency development
Authors: Andenoro Anthony C. , Popa Adrian B. , Bletscher Caitlin G. , Albert Joseph
Published: December 2012

Intercultural competence and the ability to work with diverse populations are critical for successful experiences abroad. Immersion has been identified as a strong preparatory and developmental opportunity for learners engaging in these experiences. However the increasing cost of higher education and the depletion of federal support for these programs have forced educators to employ innovative means to prepare students for international experiences. The authors address this charge via theoretical perspectives suggesting the inclusion of storytelling and narrative as a means of developing self‐awareness and a pathway towards intercultural competence. This perspective provides the foundation for global competency development in non‐immersive contexts with respect to the underlying financial limitations in the current higher education landscape. The authors provide an educational framework that has the potential for a renewed emphasis on self‐development and ultimately, the creation of more globally conscious study abroad learners.
Characterization of oseltamivir‐resistant influenza A(H1N1)pdm09 viruses in Taiwan in 2009–2011
Authors: Yang Ji‐Rong , Huang Yuan‐Pin , Chang Feng‐Yee , Hsu Li‐Ching , Huang Hsiang‐Yi , Pan Yi‐Tsan , Lin Yu‐Cheng , Wu Ho‐Sheng , Liu Ming‐Tsan
Published: December 2012

The early isolated swine‐origin influenza A(H1N1)pdm09 viruses were susceptible to oseltamivir; however, there is a concern about whether oseltamivir‐resistant influenza A(H1N1)pdm09 viruses will spread worldwide as did the oseltamivir‐resistant seasonal influenza A(H1N1) viruses in 2007–2008. In this study, the frequency of oseltamivir resistance in influenza A(H1N1)pdm09 viruses was determined in Taiwan. From May 2009 to April 2011, 1,335 A(H1N1)pdm09‐positive cases in Taiwan were tested for the H275Y mutation in the neuraminidase (NA) gene that confers resistance to oseltamivir. Among these, 15 patients (1.1%) were found to be infected with H275Y virus. All the resistant viruses were detected after the patients have received the oseltamivir. The overall monthly ratio of H275Y‐harboring viruses ranged between 0% and 2.88%, and the peak was correlated with influenza epidemics. The genetic analysis revealed that the oseltamivir‐resistant A(H1N1)pdm09 viruses can emerged from different variants with a great diversity under drug pressure. The ratio of NA/HA activities in different clades of oseltamivir‐resistant viruses was reduced compared to those in the wild‐type viruses, indicating that the balance of NA/HA in the current oseltamivir‐resistant influenza A(H1N1)pdm09 viruses was interfered. It is possible that H275Y‐bearing A(H1N1)pdm09 virus has not yet spread globally because it lacks the essential permissive mutations that can compensate for the negative impact on fitness by the H275Y amino acid substitution in NA. Continuous monitoring the evolution patterns of sensitive and resistant viruses is required to respond to possible emergence of resistant viruses with permissive genetic background which enable the wide spread of resistance. J. Med. Virol. 85:379–387, 2013. © 2012 Wiley Periodicals, Inc.
Characterization of ELISA detection of broad‐spectrum anti‐Epstein–Barr virus antibodies associated with nasopharyngeal carcinoma
Authors: Chang Cindy , Middeldorp Jaap , Yu Kelly J. , Juwana Hedy , Hsu Wan‐Lun , Lou Pei‐Jen , Wang Cheng‐Ping , Chen Jen‐Yang , Liu Mei‐Ying , Pfeiffer Ruth M. , Chen Chien‐Jen , Hildesheim Allan
Published: December 2012

Epstein–Barr virus (EBV) infection is associated with undifferentiated nasopharyngeal carcinomas (NPC). A distinct seroreactivity pattern to EBV is predictive of subsequent risk of sporadic and familial nasopharyngeal carcinomas. There are currently no accepted screening tools for guiding the clinical management of individuals at high‐risk for nasopharyngeal carcinomas, particularly unaffected relatives from nasopharyngeal carcinoma multiplex families. Therefore, the reproducibility of a panel of largely synthetic peptide‐based anti‐EBV antibody ELISAs was evaluated and their ability to distinguish nasopharyngeal carcinoma cases from controls was explored. IgG and IgA antibodies against 6 different EBV antigens (10 assays, total) were tested on sera from 97 individuals representing the full spectrum of anti‐EBV seroprevalence (i.e., healthy individuals with no known EBV seroreactivity, healthy individuals with known EBV seroreactivity, and nasopharyngeal carcinoma cases). Each specimen was tested in triplicate to assess within‐batch and across‐batch variation, and the triplicate testing was repeated on two separate days. Reproducibility was assessed by the coefficients of variation (CVs) and intraclass correlation coefficients (ICCs). All markers were detectable in 17% or more of samples. For all but one marker, the overall, within‐batch, and across‐batch CVs were below 15%, and the ICCs were above 70% for all but three markers. Sensitivity of these markers to detect prevalent nasopharyngeal carcinomas ranged from 22% to 100%, and among unaffected controls, most distinguished those with and without known seropositivity. In conclusion, a large number of EBV markers can be measured reliably in serum samples using peptide‐based anti‐EBV ELISAs. J. Med. Virol. 85:524–529, 2013. Puiblished 2012. This is a US government work, and, as such, is in the public domain of The United States of America.
Intra‐arterial cisplatin with concomitant radiation for advanced hypopharyngeal cancer
Authors: Nomura Kenichiro , Takahara Miki , Katayama Akihiro , Kishibe Kan , Kunibe Isamu , Katada Akihiro , Hayashi Tatsuya , Harabuchi Yasuaki
Published: December 2012

Objectives/Hypothesis:

The current study evaluated the efficacy of radiation and concomitant high‐dose superselective intra‐arterial cisplatin infusion (RADPLAT) for patients with advanced hypopharyngeal cancer.

Study Design:

Retrospective, single‐institutional study.

Methods:

Between February 2004 and October 2010, 43 patients with T2N0 or worse cancer were given superselective intra‐arterial infusions of cisplatin (100‐mg/m2 or 75‐mg flat dose per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional external beam radiotherapy (60–66 Gy).

Results:

In total, three, seven, 21, and 12 patients were diagnosed with stage II, III, IVA, and IVB cancer, respectively. During the median follow‐up period of 34 months, the 3‐year overall survival, disease‐specific survival, and progression‐free survival rates for all patients were 52.2%, 68.2%, and 56.1%, respectively. The 3‐year local control and laryngoesophageal dysfunction‐free survival rates were 81.6% and 49.4%, respectively. No patient died because of treatment toxicity. Among grade IV toxicity, cerebral infarction (n = 1) and laryngeal necrosis (n = 1) resulting in laryngectomy were observed.

Conclusions:

Despite being a single‐institution experience, the results of the current study suggest that RADPLAT can achieve favorable survival rates and high rates of laryngeal preservation for patients with advanced hypopharyngeal cancers. Laryngoscope, 2012