bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise and Muscular Dystrophy: Implications and Analysis of Effects on Musculoskeletal and Cardiovascular Systems
Authors: Barnabei Matthew S. , Martindale Joshua M. , Townsend DeWayne , Metzger Joseph M.
Published: July 2011

The muscular dystrophies are a heterogeneous collection of progressive, inherited diseases of muscle weakness and degeneration. Although these diseases can vary widely in their etiology and presentation, nearly all muscular dystrophies cause exercise intolerance to some degree. Here, we focus on Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, as a paradigm for the effects of muscle disease on exercise capacity. First described in the mid‐1800s, DMD is a rapidly progressive and lethal muscular dystrophy caused by mutations in the dystrophin gene. Dystrophin is a membrane‐associated cytoskeletal protein, the loss of which causes numerous cellular defects including mechanical instability of the sarcolemma, increased influx of extracellular calcium, and cell signaling defects. Here, we discuss the physiological basis for exercise intolerance in DMD, focusing on the molecular and cellular defects caused by loss of dystrophin and how these manifest as organ‐level dysfunction and reduced exercise capacity. The main focus of this article is the defects present in dystrophin‐deficient striated muscle. However, discussion regarding the effects of dystrophin loss on other tissues, including vascular smooth muscle is also included. Collectively, the goal of this article is to summarize the current state of knowledge regarding the mechanistic basis for exercise intolerance in DMD, which may serve as an archetype for other muscular dystrophies and diseases of muscle wasting. © 2011 American Physiological Society.Compr Physiol1:1353‐1363, 2011.
Oxidants and Redox Signaling in Acute Lung Injury
Authors: Sarma J. Vidya , Ward Peter A.
Published: July 2011

Acute lung injury (ALI) and its more severe form of clinical manifestation, the acute respiratory distress syndrome is associated with significant dysfunction in air exchange due to inflammation of the lung parenchyma. Several factors contribute to the inflammatory process, including hypoxia (inadequate oxygen), hyperoxia (higher than normal partial pressure of oxygen), inflammatory mediators (such as cytokines), infections (viral and bacterial), and environmental conditions (such as cigarette smoke or noxious gases). However, studies over the past several decades suggest that oxidants formed in the various cells of the lung including endothelial, alveolar, and epithelial cells as well as lung macrophages and neutrophils in response to the factors mentioned above mediate the pathogenesis of ALI. Oxidants modify cellular proteins, lipids, carbohydrates, and DNA to cause their aberrant function. For example, oxidation of lipids changes membrane permeability. Interestingly, recent studies also suggest that spatially and temporally regulated production of oxidants plays an important role antimicrobial defense and immunomodulatory function (such as transcription factor activation). To counteract the oxidants an arsenal of antioxidants exists in the lung to maintain the redox status, but when overwhelmed tissue injury and exacerbation of inflammation occurs. We present below the current understanding of the pathogenesis of oxidant‐mediated ALI. © 2011 American Physiological Society.Compr Physiol1:1365‐1381, 2011.
Mechanisms of Exercise‐Induced Mitochondrial Biogenesis in Skeletal Muscle: Implications for Health and Disease
Authors: Hood David A. , Uguccioni Giulia , Vainshtein Anna , D'souza Donna
Published: July 2011

Mitochondria have paradoxical functions within cells. Essential providers of energy for cellular survival, they are also harbingers of cell death (apoptosis). Mitochondria exhibit remarkable dynamics, undergoing fission, fusion, and reticular expansion. Both nuclear and mitochondrial DNA (mtDNA) encode vital sets of proteins which, when incorporated into the inner mitochondrial membrane, provide electron transport capacity for ATP production, and when mutated lead to a broad spectrum of diseases. Acute exercise can activate a set of signaling cascades in skeletal muscle, leading to the activation of the gene expression pathway, from transcription, to post‐translational modifications. Research has begun to unravel the important signals and their protein targets that trigger the onset of mitochondrial adaptations to exercise. Exercise training leads to an accumulation of nuclear‐ and mtDNA‐encoded proteins that assemble into functional complexes devoted to mitochondrial respiration, reactive oxygen species (ROS) production, the import of proteins and metabolites, or apoptosis. This process of biogenesis has important consequences for metabolic health, the oxidative capacity of muscle, and whole body fitness. In contrast, the chronic muscle disuse that accompanies aging or muscle wasting diseases provokes a decline in mitochondrial content and function, which elicits excessive ROS formation and apoptotic signaling. Research continues to seek the molecular underpinnings of how regular exercise can be used to attenuate these decrements in organelle function, maintain skeletal muscle health, and improve quality of life. © 2011 American Physiological Society.Compr Physiol1:1119‐1134, 2011.
Where East not always meets West: Comparing the Sulha process to Western‐style mediation and arbitration
Authors: Pely Doron
Published: July 2011

The author uses literature and interviews to compare elements of the Muslim inter‐clan, mixed‐mode mediation and arbitration tradition of Sulha in Israel's Arab community with comparable elements of Western‐style mediation and arbitration practices. The author uncovers and analyzes the similarities and differences between specific Western‐style and Sulha mediation and arbitration elements, such as confidentiality, venting, and neutrality. Such insights may be helpful when considering possible synergies and points of divergence between Muslim and Western dispute‐resolution practices.
Examining structural components of peace agreements and their durability
Authors: Hoffman Evan , Bercovitch Jacob
Published: July 2011

The authors address a question that is central to many ADR studies; namely, are some peace agreements really better designed than others, and, if so, will these agreements last longer? It is argued that peace ultimately rests on the parties choosing to cooperate with one another to uphold the terms of the agreement. Peace is thus framed as an ongoing, dynamic process involving constant renegotiation. Mediators, therefore, need to be forward‐looking and mindful of how to craft an agreement that has features that recognize the high likelihood that problems will arise after the formal signing.
High‐throughput quantitative analysis of HIV‐1 and SIV‐specific ADCC‐mediating antibody responses
Authors: Pollara Justin , Hart Lydia , Brewer Faraha , Pickeral Joy , Packard Beverly Z. , Hoxie James A. , Komoriya Akira , Ochsenbauer Christina , Kappes John C. , Roederer Mario , Huang Ying , Weinhold Kent J. , Tomaras Georgia D. , Haynes Barton F. , Montefiori David C. , Ferrari Guido
Published: July 2011

We have developed a high‐throughput platform to detect the presence of HIV‐1 and SIV‐specific ADCC‐mediating antibody responses. The assay is based on the hydrolysis of a cell‐permeable fluorogenic peptide substrate containing a sequence recognized by the serine protease, Granzyme B (GzB). GzB is delivered into target cells by cytotoxic effector cells as a result of antigen (Ag)‐specific Ab‐Fcγ receptor interactions. Within the target cells, effector cell‐derived GzB hydrolyzes the substrate, generating a fluorescent signal that allows individual target cells that have received a lethal hit to be identified by flow cytometry. Results are reported as the percentage of target cells with GzB activity (%GzB). Freshly isolated or cryopreserved PBMC and/or NK cells can be used as effector cells. CEM.NKR cells expressing the CCR5 co‐receptor are used as a target cells following: (i) coating with recombinant envelope glycoprotein, (ii) infection with infectious molecular clones expressing the Env antigens of primary and lab adapted viruses, or (iii) chronic infection with a variant of HIV‐1/IIIB, termed A1953. In addition, primary CD4+ T cells infected with HIV‐1 in vitro can also be used as targets. The assay is highly reproducible with a coefficient of variation of less than 25%. Target and effector cell populations, in the absence of serum/plasma, were used to calculate background (8.6 ± 2.3%). We determined that an initial dilution of 1:50 and 1:100 is required for testing of human and non‐human primate samples, respectively. This assay allows for rapid quantification of HIV‐1 or SIV‐specific ADCC‐mediating antibodies that develop in response to vaccination, or in the natural course of infection, thus providing researchers with a new methodology for investigating the role of ADCC‐mediating antibodies as correlates of control or prevention of HIV‐1 and SIV infection. © 2011 International Society for Advancement of Cytometry
Electrochemical Design of Ultrathin Palladium Coated Gold Nanoparticles as Nanostructured Catalyst for Amperometric Detection of Formaldehyde
Authors: Safavi Afsaneh , Farjami Fatemeh
Published: July 2011

An underpotential deposition (UPD) replacement tactic was employed to design a Pd overlayer on gold (Au) nanoparticles electrodeposited on a carbon ionic liquid electrode (CILE). Pd/Au/CILE was applied as an amperometric sensor for the determination of formaldehyde in aqueous solutions. The sensor displayed two linear ranges from 15 µM–1.4 mM and 1.4–56.7 mM of formaldehyde. The limit of detection was 3 µM of formaldehyde and the sensitivity of the sensor was 2.35 µA mM−1, using the calibration graph in the lower range. The presence of 20 mM of formic acid and methanol and 10 mM ethanol did not interfere with the determination of formaldehyde solution.
Electrochemical Determination of Tetracycline Using Molecularly Imprinted Polymer Modified Carbon Nanotube‐Gold Nanoparticles Electrode
Authors: Wang Hongtao , Zhao Huimin , Quan Xie , Chen Shuo
Published: July 2011

This paper reports the use of a tetracycline (TC) sensor constructed from a combination of molecularly imprinted polymer (MIP) and gold nanoparticles modified multiwall carbon nanotubes (MWNTs‐GNPs). The results demonstrated that the amount of recognition sites in the polymer was significantly increased and the electron transfer ability of the sensor was improved. The relationship between the peak current and the TC concentration was linear in the range from 0.1 to 40 mg L−1, and the detection limit was 0.04 mg L−1 (S/N=3). The peak current to TC was 4.3, 6.2 and 6.8 times larger than that of oxytetracycline, chloramphenicol and nafcillin, respectively. Thus, the combination of MIP and MWNTs‐GNPs provides a sensitive and selective electrochemical detection method for tetracycline.
Carbon Nanotube‐Adsorbed Electrospun Nanofibrous Membranes as Coating for Electrochemical Sensors for Sulfhydryl Compounds
Authors: Li Fei , Scampicchio Matteo , Mannino Saverio
Published: July 2011

A new method to modify electrodes with carbon nanotubes (CNT) was developed. Multiwalled carbon nanotubes (MWNT) were adsorbed on the electrospun nylon‐6 nanofibrous membranes (Ny‐6‐NFM) and used as a coating to modify conventional glassy carbon electrodes. The modified electrode was designed for the amperometric detection of sulfhydryl compounds with the potential held at +0.3 V vs. Ag/AgCl. The modified electrode showed a linear response for cysteine up to 0.4 mM (R2=0.997), with a sensitivity of 5.1 µA/mM and a detection limit of 15 µM. Other sulfhydryl compounds showed similar results. After use, the Ny‐6‐NFM was easily peeled off, leaving the bare electrode surface back to its original electrochemical behaviour. This is the first attempt to use a disposable membrane functionalized with MWNT for electroanalytical purposes.
Bile UPLC‐MS fingerprinting and bile acid fluxes during human liver transplantation
Authors: Legido‐Quigley Cristina , McDermott Lindsay , Vilca‐Melendez Hector , Murphy Gerard M. , Heaton Nigel , Lindon John C. , Nicholson Jeremy K. , Holmes Elaine
Published: July 2011

Bile flow restoration is a crucial step in the recovery process post transplantation of the liver. Here, metabolic trajectories based on changes in bile secretion – a known marker of functionality – have been utilised as an approach for discovering bile fluxes during transplantation. A total of ten liver transplants were monitored and from these 68 bile samples from both donors and recipients were collected and analysed using ultra‐performance LC‐MS in combination with multivariate statistical analysis. Based on the principal component scores constructed from the total bile fingerprint, differentiation of the bile acid concentrations before and after transplantation was detected. A trend was also observed, by constructing metabolic trajectories, whereby the post‐transplant profiles approached the position of pre‐transplant profiles within 30–60 min of the restoration of bile secretion function. The ten major conjugated bile acid salts were measured and a significant increase in concentrations of taurocholic acid and taurochenodeoxycholic acid were seen after transplantation. In addition, the ratios of secondary bile acids detected in gall bladder and hepatic bile were measured before and after transplantation. This study suggests that bile acid ratios in the donor liver at the pre‐transplant and post‐transplant stage may be important and that profiling of secreted bile after transplantation may aid clinical assessment and progress post‐transplantation.
Plasma biomarker identification in S‐adenosylhomocysteine hydrolase deficiency
Authors: Sedic Mirela , Kraljevic Pavelic Sandra , Cindric Mario , Vissers Johannes P. C. , Peronja Marija , Josic Djuro , Cuk Mario , Fumic Ksenija , Pavelic Krešimir , Baric Ivo
Published: July 2011

S‐Adenosylhomocysteine hydrolase (AHCY) deficiency is a rare congenital disorder in methionine metabolism clinically characterized by white matter atrophy, delayed myelination, slowly progressive myopathy, retarded psychomotor development and mildly active chronic hepatitis. In the present study, we utilized a comparative proteomics strategy based on 2‐DE/MALDI‐MS and LC/ESI‐MS to analyze plasma proteins from three AHCY‐deficient patients prior to and after receiving dietary treatment designed to alleviate disease symptoms. Obtained results revealed candidate biomarkers for the detection of myopathy specifically associated with AHCY deficiency, such as carbonic anhydrase 3, creatine kinase, and thrombospondin 4. Several proteins mediating T‐cell activation and function were identified as well, including attractin and diacylglycerol kinase α. Further validation and functional analysis of identified proteins with clinical value would ensure that these biomarkers make their way into routine diagnosis and management of AHCY deficiency.
Fractionation of the human plasma proteome for monoclonal antibody proteomics‐based biomarker discovery
Authors: Kovács András , Sperling Edit , Lázár József , Balogh Attila , Kádas János , Szekrényes Ákos , Takács László , Kurucz István , Guttman András
Published: July 2011

mAb proteomics, a reversed biomarker discovery approach, is a novel methodology to recognize the proteins of biomarker potential, but requires subsequent antigen identification steps. While in case of high‐abundant proteins, it generally does not represent a problem, for medium or lower abundant proteins, the identification step requires a large amount of sample to assure the proper amount of antigen for the ID process. In this article, we report on the use of combined chromatographic and precipitation techniques to generate a large set of fractions representing the human plasma proteome, referred to as the Analyte Library, with the goal to use the relevant library fractions for antigen identification in conjunction with mAb proteomics. Starting from 500 mL normal pooled human plasma, this process resulted in 783 fractions with the average protein concentration of 1 mg/mL. First, the serum albumin and immunoglobulins were depleted followed by prefractionation by ammonium sulfate precipitation steps. Each precipitate was then separated by size exclusion chromatography, followed by cation and anion exchange chromatography. The 20 most concentrated ion exchange chromatography fractions were further separated by hydrophobic interaction chromatography. All chromatography and precipitation steps were carefully designed aiming to maintain the native forms of the intact proteins throughout the fractionation process. The separation route of vitamin D‐binding protein (an antibody proteomics lead) was followed in all major fractionation levels by dot blot assay in order to identify the library fraction it accumulated in and the identity of the antigen was verified by Western blot.
A nonparametric characterization of vertical ground motion effects
Authors: Tezcan Jale , Cheng Qiang
Published: July 2011

Design guidelines have traditionally oversimplified the vertical ground motion effects by defining a constant vertical‐to‐horizontal response spectral ratio (V/H). With the recognition that such practice is not always conservative, recent studies have proposed improvements to the representation of vertical seismic effects in design codes, based on empirical ground motion relations.

Conventional empirical modeling requires selecting the functional form of the predictive model. Because of the complicated nature of ground motions, identification of the underlying function is a challenge. A related drawback to this approach is its high susceptibility to overfitting, especially with today's highly complex models.

To address these issues, this paper proposes a nonparametric approach to characterize the vertical seismic effects. Using support vector machines, the V/H ratio is determined without an assumed functional form. The accuracy of the model is measured by adopting an epsilon‐insensitive residual function with a regularization term added to prevent overfitting.

An example application using ground motion records from strike‐slip and normal faulting earthquakes is presented, and the results are compared with a current empirical model, for different magnitude, distance, and local soil conditions. The median V/H estimates from the two models are shown to be in good general agreement. The standard deviation estimates from the proposed model are consistently larger than the estimates from the empirical model.

The results from this study show that the proposed method is a viable alternative and offers the opportunity to characterize vertical seismic effects without an assumed functional form. Copyright © 2011 John Wiley & Sons, Ltd.
Frequency domain substructural identification for arbitrary excitations
Authors: Zhang Z. , Koh C. G. , Perry M. J.
Published: July 2011

Structural identification based on analysis of vibration signals is usually formulated as an optimization problem. Nevertheless, identifying a structural system as a whole often involves a great number of unknowns and degrees of freedom, resulting in considerable convergence difficulty and expensive evaluation of objective function. To handle these issues, this paper aims to propose a frequency domain substructural identification method applicable to arbitrary excitations. This is done by introducing the exponential window method in the formulation so that the effect caused by initial condition is alleviated without using zero padding. The proposed identification method is verified through both numerical and experimental studies. It is shown that significant reduction in computer time can be achieved in addition to remarkable identification accuracy. The experimental study also indicates that the proposed strategy is effective in identifying small structural changes. Copyright © 2011 John Wiley & Sons, Ltd.
Representing egress data
Authors: Gwynne S. M. V.
Published: July 2011

Data are essential to the understanding of human behaviour in fire. Human egress data‐sets are scarce, and those currently available are relatively narrow in scope, from varied sources, inconsistently described and frequently several decades old. This paper describes a framework for the storage and presentation of human egress data. This work has been conducted as part of a project funded by the National Institute of Standards and Technology and, as a result, a central repository of data will be created that provides tools to facilitate the storage, representation and access to the data needed for researchers and engineers alike. When fully implemented, this framework (in the form of a Data Portal) will better inform the use of the data available and make accessing this data more convenient. Copyright © 2011 John Wiley & Sons, Ltd.
Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating Kupffer cell polarization in mice
Authors: Louvet Alexandre , Teixeira-Clerc Fatima , Chobert Marie-Noële , Deveaux Vanessa , Pavoine Catherine , Zimmer Andreas , Pecker Françoise , Mallat Ariane , Lotersztajn Sophie
Published: July 2011

Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic liver disease. Because cannabinoid CB2 receptors (CB2) display potent anti-inflammatory properties, we investigated their role in the pathogenesis of alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell polarization and the consequences on liver steatosis. Wild-type (WT) mice fed an alcohol diet showed an induction of hepatic classical (M1) and alternative (M2) markers. Cotreatment of alcohol-fed mice with the CB2 agonist, JWH-133, decreased hepatic M1 gene expression without affecting the M2 profile. In keeping with this, genetic ablation of CB2 enhanced hepatic induction of M1 gene signature and blunted the induction of M2 markers. CB2 also modulated alcohol-induced fatty liver, as shown by the reduction of hepatocyte steatosis in JWH-133-treated mice and its enhancement in CB2−/− animals. Studies in isolated Kupffer cells and cultured macrophages further demonstrated that CB2 inhibits M1 polarization and favors the transition to an M2 phenotype. In addition, conditioned-medium experiments showed that preventing M1 polarization in CB2-activated macrophages protects from lipid accumulation in hepatocytes. Heme oxygenase-1 (HO-1) mediated the anti-inflammatory effects of CB2 receptors. Indeed, alcohol-fed mice treated with JWH-133 showed increased hepatic expression of macrophage HO-1, as compared to vehicle-treated counterparts. In keeping with this, JWH-133 induced HO-1 expression in cultured macrophages, and the HO-1 inhibitor, zinc protoporphyrin, blunted the inhibitory effect of JWH-133 on lipopolysaccharide-induced nuclear factor-kappa B activation and M1 polarization. Altogether, these findings demonstrate that CB2 receptors display beneficial effects on alcohol-induced inflammation by regulating M1/M2 balance in Kupffer cells, thereby reducing hepatocyte steatosis via paracrine interactions between Kupffer cells and hepatocytes. These data identify CB2 agonists as potential therapeutic agents for the management of alcoholic liver disease. (Hepatology 2011;)
Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis
Authors: Tsuda Masanobu , Ambrosini Yoko M. , Zhang Weici , Yang Guo-Xiang , Ando Yugo , Rong Guanghua , Tsuneyama Koichi , Sumida Kosuke , Shimoda Shinji , Bowlus Christopher L. , Leung Patrick S.C. , He Xiao-Song , Coppel Ross L. , Ansari Aftab A. , Lian Zhe-Xiong , Eric Gershwin M.
Published: July 2011

In primary biliary cirrhosis (PBC), patients develop a multilineage response to a highly restricted peptide of the E2 component of pyruvate dehydrogenase (PDC-E2) involving autoantibody and autoreactive cluster of differentiation (CD)4+ and CD8+ T-cell responses. Recent data from murine models have suggested that liver-infiltrating CD8+ cells play a critical role in biliary destruction in PBC. We hypothesized that chronic antigen stimulation of CD8+ T cells alters effector memory T cell (TEM) frequency and function similar to that seen with chronic viral infections, including failure to terminally differentiate and relative resistance to apoptosis. We have rigorously phenotyped CD8+ T-cell subpopulations from 132 subjects, including 76 patients with PBC and 56 controls, and report a higher frequency of TEM cells characterized as CD45ROhighCD57+CD8high, but expressing the gut homing integrin, α4β7, in peripheral blood mononuclear cells of PBC. These CD8high TEM cells have reduced expression of Annexin V after TCR stimulation. Consistent with a TEM phenotype, CD45ROhighCD57+CD8high T cells express higher levels of granzyme A, granzyme B, perforin, CCR5 and α4β7, and lower levels of CCR7 and CD28 than other CD8high T cells. Furthermore, interleukin (IL)-5 produced by CD8+CD57+ T lymphocytes upon

in vitro

T-cell receptor stimulation are increased in PBC. Histologically, CD8+CD57+ T cells accumulate around the portal area in PBC. Moreover, CD8+CD57+ T cells respond specifically to the major histocompatibility class I epitope of PDC-E2.

Conclusion:

In conclusion, our data demonstrate that CD45ROhighCD57+CD8high T cells are a subset of terminally differentiated cytotoxic TEM cells, which could play a critical role in the progressive destruction of biliary epithelial cells. (Hepatology 2011;54:1293–1302)
Novel feedback inhibition of surface antigen synthesis by mammalian target of rapamycin (mTOR) signal and its implication for hepatitis B virus tumorigenesis and therapy
Authors: Teng Chiao-Fang , Wu Han-Chieh , Tsai Hung-Wen , Shiah Her-Shyong , Huang Wenya , Su Ih-Jen
Published: July 2011

Ground glass hepatocytes (GGHs) harboring hepatitis B virus (HBV) pre-S mutants have been recognized as precursor lesions of hepatocellular carcinoma (HCC). Previously, we observed the activation of mammalian target of rapamycin (mTOR) in GGHs and HCCs, together with a decreased expression of HBV surface antigen (HBsAg) in HCC tissues. It is, therefore, hypothesized that the activation of mTOR during HBV tumorigenesis may potentially down-regulate HBsAg expression. In this study, we verified an inverse relationship between the expression of HBsAg and phosphorylated mTOR (p-mTOR) in 13 of 20 paired nontumorous liver and HCC tissues.

In vitro

, wild-type or mutant pre-S proteins could activate mTOR in the HuH-7 cell line. Interestingly, the up-regulated mTOR, in turn, suppressed HBsAg synthesis at the transcriptional level via the transcription factor, Yin Yang 1 (YY1), which bound to nucleotide 2812-2816 of the pre-S1 promoter. This inhibitory effect by the mTOR signal could be abolished by the knockdown of histone deacetylase 1 (HDAC1). Furthermore, YY1 was physically associated with HDAC1 in a manner dependent on mTOR activation. Collectively, pre-S protein-induced mTOR activation may recruit the YY1-HDAC1 complex to feedback suppress transcription from the pre-S1 promoter.

Conclusion:

The activation of mTOR signal in GGHs may feedback suppress HBsAg synthesis during HBV tumorigenesis and explain the observed decrease or absence of HBsAg in HCC tissues. Therapy using mTOR inhibitors for HCCs may potentially activate HBV replication in patients with chronic HBV infection. (Hepatology 2011 )
Unsteady boundary layer flow of a Casson fluid due to an impulsively started moving flat plate
Authors: Mustafa M. , Hayat T. , Pop I. , Aziz A.
Published: July 2011

This paper discusses the unsteady flow and heat transfer of a Casson fluid over a moving flat plate with a parallel free stream. The analytic solutions of the system of nonlinear partial differential equations valid for all times in the whole spatial domain are constructed in the series form by a homotopic approach. The influences of the governing parameters on the velocity, temperature, skin friction coefficient, and local Nusselt number are thoroughly investigated. It is revealed that an increase in the dimensionless time decreases the velocity and enhances the temperature. The surface shear stress and surface heat transfer are enhanced by increasing the Casson fluid parameter (β) and Eckert number (Ec), respectively. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20358
Heat transfer from a vertical fin array by laminar natural convection and radiation—A quasi‐3D approach
Authors: Govinda Rao B. , Dharma Rao V. , Naidu S.V. , Sharma K.V. , Sreenivasulu B.
Published: July 2011

A quasi‐3D numerical model is developed to study the problem of laminar natural convection and radiation heat transfer from a vertical fin array. An enclosure is formed by two adjacent vertical fins and vertical base in the fin array. Results obtained from this enclosure are used to predict heat transfer rate from a vertical fin array. All the governing equations related to fluid in the enclosure, together with the heat conduction equation in both fins are solved by using the Alternating Direction Implicit (ADI) method for getting the temperatures along the height of the fin and the temperature of the fluid in the enclosure. Separate analysis is carried out to calculate the heat transfer rates from the end fins in the fin array. A numerical study has been carried out for the effect of fin height, fin spacing, fin array base temperature, and fin emissivity on total heat transfer rates and effectiveness of the fin array. The numerical results obtained for an eight‐fin array show good agreement with the available experimental data. Results show that the fin spacing is the most significant parameter and there exists an optimum value for the fin spacing for which the heat transfer rate from the fin array is maximum. Correlations are presented for predicting the total heat transfer rate, average Nusselt number, and effectiveness of the fin array. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20360
Species sensitivity distribution evaluation for selenium in fish eggs: Considerations for development of a Canadian tissue-based guideline
Authors: DeForest David K , Gilron Guy , Armstrong Sarah A , Robertson Erin L
Published: July 2011

A freshwater Se guideline was developed for consideration based on concentrations in fish eggs or ovaries, with a focus on Canadian species, following the Canadian Council of Ministers of the Environment protocol for developing guideline values. When sufficient toxicity data are available, the protocol recommends deriving guidelines as the 5th percentile of the species sensitivity distribution (SSD). When toxicity data are limited, the protocol recommends a lowest value approach, where the lowest toxicity threshold is divided by a safety factor (e.g., 10). On the basis of a comprehensive review of the current literature and an assessment of the data therein, there are sufficient egg and ovary Se data available for freshwater fish to develop an SSD. For most fish species, Se EC10 values (10% effect concentrations) could be derived, but for some species, only no-observed-effect concentrations and/or lowest-observed-effect concentrations could be identified. The 5th percentile egg and ovary Se concentrations from the SSD were consistently 20 µg/g dry weight (dw) for the best-fitting distributions. In contrast, the lowest value approach using a safety factor of 10 would result in a Se egg and ovary guideline of 2 µg/g dw, which is unrealistically conservative, as this falls within the range of egg and ovary Se concentrations in laboratory control fish and fish collected from reference sites. An egg and ovary Se guideline of 20 µg/g dw should be considered a conservative, broadly applicable guideline, as no species mean toxicity thresholds lower than this value have been identified to date. When concentrations exceed this guideline, site-specific studies with local fish species, conducted using a risk-based approach, may result in higher egg and ovary Se toxicity thresholds. Integr Environ Assess Manag 2012;8:6–12. © 2011 SETAC
CONSTRUCTION AND EVALUATION OF THE BIVAL AUTOMATIC CONTROL SYSTEM FOR IRRIGATION CANALS IN A LABORATORY FLUME
Authors: Shahverdi Kazem , Monem Mohammad Javad
Published: July 2011

Automation of structures is one of the main options for improving operations to increase the flexibility of irrigation canals. For local development of automatic system technology and its application, the facilities have to be constructed, and after testing in the laboratory, the system can be introduced for practical application in irrigation canals. One of the important automatic downstream control systems is the Bival control system. In this research, the Bival downstream control system is constructed and tested. Experiments of the automatic control system were performed in a rectangular laboratory flume with dimensions of 0.3 × 0.45 × 10 m. The hardware of the system includes depth and gate opening sensors, motors, slide gates, electronic boards and a computer. The system's software is the Bival automatic control system, which was developed and connected with equipment using LABVIEW software. To study the performance of the developed system, different scenarios of gradual and sudden downstream flow variations were tested. Maximum absolute error (MAE), integral of absolute magnitude of error (IAE), system response time (SRT) and percentage of volume variation (PVV) indicators, in addition to depth variations in time, were used to assess system performance. For a case of sudden flow decrease, the indicators value are obtained as 0.22, 0.06, 1.51 min, and 0.62, respectively, which are acceptable and indicate a smooth action of the control system. The results showed that the performance of the developed Bival automatic control system is appropriate, and it could be introduced to be applied in irrigation canals. Copyright © 2011 John Wiley & Sons, Ltd.
Bone remodeling in postmenopausal women who discontinued denosumab treatment: Off-treatment biopsy study
Authors: Brown Jacques P , Dempster David W , Ding Beiying , Dent-Acosta Ricardo , San Martin Javier , Grauer Andreas , Wagman Rachel B , Zanchetta Jose
Published: July 2011

Denosumab is a fully human monoclonal antibody that neutralizes the activity of RANKL, leading to the inhibition of osteoclast maturation, bone-resorbing activity, and survival. Evaluation of trans–iliac crest bone biopsy specimens in the phase 3 pivotal fracture study with denosumab in postmenopausal women with osteoporosis showed evidence of reduced bone turnover at the tissue level in subjects receiving denosumab, and up to one-third of subjects did not have evidence of tetracycline labeling in trabecular or cortical bone. Discontinuation of denosumab therapy has demonstrated that the effects of denosumab are reversible, as assessed by biochemical markers of bone turnover (BTM) and BMD. The precise nature of changes that occur at the tissue level with denosumab discontinuation have not been explored. Fifteen subjects were enrolled in a cohort study to evaluate the effects of denosumab discontinuation at the tissue level. Subjects had discontinued osteoporosis treatment for a mean time of 25.1 months (range 21 to 29 months). Bone histomorphometry results were compared with results from placebo-treated women with osteoporosis in the denosumab phase 3 pivotal fracture bone biopsy substudy, and BTMs were compared with subjects' pretreatment values. The results of this study showed normal histology and bone remodeling similar to those observed in untreated postmenopausal women with osteoporosis. With treatment cessation, 100% of biopsy specimens had evidence of tetracycline labels. Biochemical markers were comparable to and highly correlated with pretreatment levels. These data confirm that the effects of denosumab on bone turnover at the tissue level are fully reversible. © 2011 American Society for Bone and Mineral Research
PTH(1–84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism
Authors: Rubin Mishaela R , Dempster David W , Sliney Jr. James , Zhou Hua , Nickolas Thomas L , Stein Emily M , Dworakowski Elzbieta , Dellabadia Maryann , Ives Rebecca , McMahon Donald J , Zhang Chiyuan , Silverberg Shonni J , Shane Elizabeth , Cremers Serge , Bilezikian John P
Published: July 2011

Hypoparathyroidism is associated with abnormal structural and dynamic skeletal properties. We hypothesized that parathyroid hormone(1–84) [PTH(1–84)] treatment would restore skeletal properties toward normal in hypoparathyroidism. Sixty-four subjects with hypoparathyroidism were treated with PTH(1–84) for 2 years. All subjects underwent histomorphometric assessment with percutaneous iliac crest bone biopsies. Biopsies were performed at baseline and at 1 or 2 years. Another group of subjects had a single biopsy at 3 months, having received tetracycline before beginning PTH(1–84) and prior to the biopsy (quadruple-label protocol). Measurement of biochemical bone turnover markers was performed. Structural changes after PTH(1–84) included reduced trabecular width (144 ± 34 µm to 128 ± 34 µm, p = 0.03) and increases in trabecular number (1.74 ± 0.34/mm to 2.07 ± 0.50/mm, p = 0.02) at 2 years. Cortical porosity increased at 2 years (7.4% ± 3.2% to 9.2% ± 2.4%, p = 0.03). Histomorphometrically measured dynamic parameters, including mineralizing surface, increased significantly at 3 months, peaking at 1 year (0.7% ± 0.6% to 7.1% ± 6.0%, p = 0.001) and persisting at 2 years. Biochemical measurements of bone turnover increased significantly, peaking at 5 to 9 months of therapy and persisting for 24 months. It is concluded that PTH(1–84) treatment of hypoparathyroidism is associated with increases in histomorphometric and biochemical indices of skeletal dynamics. Structural changes are consistent with an increased remodeling rate in both trabecular and cortical compartments with tunneling resorption in the former. These changes suggest that PTH(1–84) improves abnormal skeletal properties in hypoparathyroidism and restores bone metabolism toward normal euparathyroid levels. © 2011 American Society for Bone and Mineral Research
Cell line IDG-SW3 replicates osteoblast-to-late-osteocyte differentiation in vitro and accelerates bone formation in vivo
Authors: Woo Stacey M , Rosser Jennifer , Dusevich Vladimir , Kalajzic Ivo , Bonewald Lynda F
Published: July 2011

Osteocytes are the most abundant cells in bone yet are the most challenging to study because they are embedded in a mineralized matrix. We generated a clonal cell line called IDG-SW3 (for Immortomouse/Dmp1-GFP-SW3) from long-bone chips from mice carrying a Dmp1 promoter driving GFP crossed with the Immortomouse, which expresses a thermolabile SV40 large T antigen regulated by interferon γ (IFN-γ). Cells from these mice can be expanded at 33 °C in the presence of IFN-γ and then allowed to resume their original phenotype at 37 °C in the absence of IFN-γ. IDG-SW3 cells are Dmp1-GFP− and T antigen+ under immortalizing conditions but Dmp1-GFP+ and T antigen− under osteogenic conditions. Like osteoblasts, they express alkaline phosphatase and produce and mineralize a type 1 collagen matrix containing calcospherulites. Like early osteocytes, they express E11/gp38, Dmp1, MEPE, and Phex. Like late osteocytes, they develop a dendritic morphology and express SOST/sclerostin and fibroblast growth factor 23 (FGF-23), regulated by parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3. When cultured on 3D matrices, they express Dmp1-GFP and sclerostin. When the 3D cultures are implanted in calvarial defects in vivo, they accelerate bone healing. This cell line should prove useful for studying osteoblast-to-osteocyte transition, mechanisms for biomineralization, osteocyte function, and regulation of SOST/sclerostin and FGF-23. © 2011 American Society for Bone and Mineral Research
Is the spin‐orbit coupling important in the prediction of the 51V hyperfine coupling constants of VIVO2+ species? ORCA versus Gaussian performance and biological applications
Authors: Micera Giovanni , Garribba Eugenio
Published: July 2011

Density functional theory calculations of the 51V hyperfine coupling (HFC) tensor A, have been completed for eighteen VIVO2+ complexes with different donor set, electric charge and coordination geometry. A tensor was calculated with ORCA software with several functionals and basis sets taking into account the spin‐orbit coupling contribution. The results were compared with those obtained with Gaussian 03 software using the half‐and‐half functional BHandHLYP and 6‐311g(d,p) basis set. The order of accuracy of the functionals in the prediction of Aiso, Az and dipolar term Az,anis is BHandHLYP > PBE0 >> B3PW > TPSSh >> B3LYP >> BP86 > VWN5 (for Aiso), BHandHLYP > PBE0 >> B3PW > TPSSh > B3LYP >> BP86 > VWN5 (for Az), B3LYP > PBE0 ∼ B3PW ∼ BHandHLYP >> TPSSh > BP86 ∼ VWN5 (for Az,anis). The good agreement in the prediction of Az with BHandHLYP is due to a compensation between the overestimation of Aiso and underestimation of Az,anis (Az = Aiso + Az,anis), whereas among the hybrid functionals PBE0 performs better than the other ones. BHandHLYP functional and Gaussian software are recommended when the VIVO2+ species contains only V‐O and/or V‐N bonds, whereas PBE0 functional and ORCA software for VIVO2+ complexes with one or more VS bonds. Finally, the application of these methods to the coordination environment of VIVO2+ ion in V‐proteins, like vanadyl‐substituted insulin, carbonic anhydrase, collagen and S‐adenosylmethionine synthetase, was discussed. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Toward a computational tool predicting the stereochemical outcome of asymmetric reactions: Development of the molecular mechanics‐based program ACE and application to asymmetric epoxidation reactions
Authors: Weill Nathanael , Corbeil Christopher R. , De Schutter Joris W. , Moitessier Nicolas
Published: July 2011

The development and application of ACE, a program that predicts the stereochemical outcome of asymmetric reactions is presented. As major implementations, ACE includes a genetic algorithm to carry out an efficient global conformational search combined with a conjugate gradient minimization routine for local optimization and a corner flap algorithm to search ring conformations. Further improvements have been made that enable ACE to generate Boltzmann populations of conformations, to investigate highly asynchronous reactions, to compute fluctuating partial atomic charges and solvation energy and to automatically construct reactants and products from libraries of catalysts and substrates. Validation on previously investigated reactions (asymmetric Diels Alder cycloadditions and organocatalyzed aldol reactions) followed by application to a number of alkene epoxidation reactions and a comparative study of DFT‐derived and ACE‐derived predictions demonstrate the accuracy and usefulness of ACE in the context of asymmetric catalyst design. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Surveying implicit solvent models for estimating small molecule absolute hydration free energies
Authors: Knight Jennifer L. , Brooks Charles L.
Published: July 2011

Implicit solvent models are powerful tools in accounting for the aqueous environment at a fraction of the computational expense of explicit solvent representations. Here, we compare the ability of common implicit solvent models (TC, OBC, OBC2, GBMV, GBMV2, GBSW, GBSW/MS, GBSW/MS2 and FACTS) to reproduce experimental absolute hydration free energies for a series of 499 small neutral molecules that are modeled using AMBER/GAFF parameters and AM1‐BCC charges. Given optimized surface tension coefficients for scaling the surface area term in the nonpolar contribution, most implicit solvent models demonstrate reasonable agreement with extensive explicit solvent simulations (average difference 1.0–1.7 kcal/mol and R2 = 0.81–0.91) and with experimental hydration free energies (average unsigned errors = 1.1–1.4 kcal/mol and R2 = 0.66–0.81). Chemical classes of compounds are identified that need further optimization of their ligand force field parameters and others that require improvement in the physical parameters of the implicit solvent models themselves. More sophisticated nonpolar models are also likely necessary to more effectively represent the underlying physics of solvation and take the quality of hydration free energies estimated from implicit solvent models to the next level. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Comparison of osmotic swelling influences on meniscal fibrocartilage and articular cartilage tissue mechanics in compression and shear
Authors: Nguyen An M. , Levenston Marc E.
Published: July 2011

Although the contribution of the circumferential collagen bundles to the anisotropic tensile stiffness of meniscal tissue has been well described, the implications of interactions between tissue components for other mechanical properties have not been as widely examined. This study compared the effects of the proteoglycan‐associated osmotic swelling stress on meniscal fibrocartilage and articular cartilage (AC) mechanics by manipulating the osmotic environment and tissue compressive offset. Cylindrical samples were obtained from the menisci and AC of bovine stifles, equilibrated in phosphate‐buffered saline solutions ranging from 0.1× to 10×, and tested in oscillatory torsional shear and unconfined compression. Biochemical analysis indicated that treatments and testing did not substantially alter tissue composition. Mechanical testing revealed tissue‐specific responses to both increasing compressive offset and decreasing bath salinity. Most notably, reduced salinity dramatically increased the shear modulus of both axially and circumferentially oriented meniscal tissue explants to a much greater extent than for cartilage samples. Combined with previous studies, these findings suggest that meniscal proteoglycans have a distinct structural role, stabilizing, and stiffening the matrix surrounding the primary circumferential collagen bundles. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:95–102, 2012
Correlating Alpine glaciation with Adriatic sea‐level changes through lake and alluvial stratigraphy
Authors: Monegato Giovanni , Pini Roberta , Ravazzi Cesare , Reimer Paula J. , Wick Lucia
Published: July 2011

We compare lake and alluvial stratigraphy along a frame connecting the southern Alpine foothills and the Adriatic Sea, with the aim of matching the effects of Alpine glaciation and sea‐level changes on sedimentation during the last glacial cycle. The palynostratigraphy of Lake Fimon provided proxies for regional vegetation and climate change and was coupled with sediment petrography, loss on ignition and magnetic susceptibility, disentangling alluvial phases from fluvioglacial activity related to culminations of the southeastern Alpine glaciers. The Fimon area was not reached by alluvial fans during the penultimate glacial maximum, nor by the sea transgression during the last interglacial, but a closed lake soon developed at the Eemian onset due to enhanced rainfall. Sea‐level fall at glacial inception triggered the entrenchment of the drainage network in the plain reaching the outer Fimon Basin. Slow aggradation, but no sign of fluvioglacial activity, lasted to 38.2 ± 1.45 cal. ka BP, when a major forest withdrawal took place, coeval to the spread of alluvial fans. By 27.5 ± 0.5 cal. ka BP the Fimon Basin was dammed by the Brenta outwash system. The main step of of forest recovery commenced at around (15.8) cal. ka BP, when apex trenching of the outwash fans was triggered by the glacier's decay. Copyright © 2011 John Wiley & Sons, Ltd.