bluuebunny/crossref_metadata_2025 huggingface dataset:
Blocking transforming growth factor–beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells
Authors: Fransvea Emilia , Angelotti Umberto , Antonaci Salvatore , Giannelli Gianluigi
Published: February 2008

Hepatocellular carcinoma (HCC) treatment is challenging because the mechanisms underlying tumor progression are still largely unknown. Transforming growth factor (TGF)–β1 is considered a crucial molecule in HCC tumorigenesis because increased levels of patients' serum and urine are associated with disease progression. The aim of the present study was to investigate the inhibition of TGF-β signaling and its impact on HCC progression. Human HCC cell lines were treated with a TGF-β receptor kinase inhibitor (LY2109761) whose selectivity was determined in a kinase assay. Exogenous TGF-β1 phosphorylates the TGF-β receptor, consequently activating Smad-2, whereas the drug selectively blocks this effect and dephosphorylates autocrine p-Smad-2 at concentrations ranging from 0.001 to 0.1 μM. A cytotoxic effect documented by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), trypan blue, and propidium iodide staining assays was observed at 10μM, whereas the drug inhibits (

P

< 0.001) the migration of HCC cells on fibronectin, laminin-5, and vitronectin and invasion through Matrigel (

P

< 0.001) at concentrations up to 0.1 μM. LY2109761 up-regulates (

P

< 0.001) E-cadherin mRNA and protein levels. This increase was localized at the cellular membrane where E-cadherin mediates anchorage that is cell–cell dependent. Consistently, a functional monoclonal antibody that inhibits E-cadherin–dependent cell–cell contact restores the migratory and invasive activity. Finally, nonmetastatic HCC tissues from 7 patients were cultured with TGF-β1 in the presence or absence of LY2109761. E-cadherin expression was reduced by TGF-β1 and was significantly (

P

< 0.0001) increased by LY2109761 treatment, measured by quantitative real-time PCR on microdissected tissues and by immunohistochemistry on serial sections. In 72 patients, E-cadherin tissue expression was more weakly expressed in metastatic than in nonmetastatic HCC (

P

< 0.0001).

Conclusion:

LY2109761 blocks migration and invasion of HCC cells by up-regulating E-cadherin, suggesting that there could be a mechanistic use for this molecule in clinical trials.
Coordinate regulation of gallbladder motor function in the gut-liver axis
Authors: Portincasa Piero , Di Ciaula Agostino , Wang Helen H. , Palasciano Giuseppe , van Erpecum Karel J. , Moschetta Antonio , Wang David Q.-H.
Published: February 2008

Gallstones are one of the most common digestive diseases with an estimated prevalence of 10%-15% in adults living in the western world, where cholesterol-enriched gallstones represent 75%-80% of all gallstones. In cholesterol gallstone disease, the gallbladder becomes the target organ of a complex metabolic disease. Indeed, a fine coordinated hepatobiliary and gastrointestinal function, including gallbladder motility in the fasting and postprandial state, is of crucial importance to prevent crystallization and precipitation of excess cholesterol in gallbladder bile. Also, gallbladder itself plays a physiopathological role in biliary lipid absorption. Here, we present a comprehensive view on the regulation of gallbladder motor function by focusing on recent discoveries in animal and human studies, and we discuss the role of the gallbladder in the pathogenesis of gallstone formation.
Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C
Authors: Loustaud-Ratti Véronique , Alain Sophie , Rousseau Annick , Hubert Isabelle Fouchard , Sauvage François Ludovic , Marquet Pierre , Denis François , Lunel Françoise , Calès Paul , Lefebvre Annie , Fauchais Anne-Laure , Liozon Eric , Vidal Elisabeth
Published: February 2008

The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin. This study was conducted to determine whether early ribavirin global exposure is related with SVR. An exploratory pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in genotype 1 hepatitis C patients treated with peginterferon alfa-2a and ribavirin (dose-adjusted for BW) for 12 weeks, to which amantadine was added for the following 36 weeks. Full and abbreviated ribavirin area under the concentration time curves (AUC0–12h, AUC0–4h) were derived from plasma concentration profiles at day 0 (D0), week 12 (W12), W12 + 1 day, and W24. Virological follow-up was performed at D0 (0, 12, and 24 hours), W2, W4, W6, and monthly until W72 (TaqMan polymerase chain reaction, cut-off 15 international units/mL). Twenty-eight patients were enrolled in the study and 24 completed it. Patients with a SVR had a significantly higher D0 AUC0–12h (3695 [1571–6916] versus 2937 [1266–4913] μg/hour/L,

P

= 0.03) and D0 AUC0–4h (2010 [615–3175] versus 1340 [622–2246] μg/hour/L,

P

= 0.03). Patients with D0 AUCs above the cut-off values defined by receiver operating characteristic curves (3014 μg/hour/L and 1755 μg/hour/L for AUC0–12h and AUC0–4h, respectively) had a significantly better chance of achieving an SVR than patients with AUCs under the thresholds (odds ratio = 16.0, 95% confidence interval 1.54–166.6,

P

= 0.02 and odds ratio = 8.9, 95% confidence interval, 1.4–56.6;

P

= 0.02).

Conclusion

: Ribavirin exposure at D0 is significantly related to SVR. To our knowledge, this is the first study to give an early pharmacokinetic predictor of SVR. We propose a minimum AUC0–4h threshold of 1755 μg/hour/L at D0 as a target for ribavirin dose adjustment.
Prevention of free fatty acid–induced hepatic lipotoxicity by 18β-glycyrrhetinic acid through lysosomal and mitochondrial pathways
Authors: Wu Xudong , Zhang Luyong , Gurley Emily , Studer Elaine , Shang Jing , Wang Tao , Wang Cuifen , Yan Ming , Jiang Zhenzhou , Hylemon Phillip B. , Sanyal Arun J. , Pandak William M. , Zhou Huiping
Published: February 2008

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and affects millions of people worldwide. Despite the increasing prevalence of NAFLD, the exact molecular/cellular mechanisms remain obscure and effective therapeutic strategies are still limited. It is well-accepted that free fatty acid (FFA)-induced lipotoxicity plays a pivotal role in the pathogenesis of NAFLD. Inhibition of FFA-associated hepatic toxicity represents a potential therapeutic strategy. Glycyrrhizin (GL), the major bioactive component of licorice root extract, has a variety of pharmacological properties including anti-inflammatory, antioxidant, and immune-modulating activities. GL has been used to treat hepatitis to reduce liver inflammation and hepatic injury; however, the mechanism underlying the antihepatic injury property of GL is still poorly understood. In this report, we provide evidence that 18 β-glycyrrhetinic acid (GA), the biologically active metabolite of GL, prevented FFA-induced lipid accumulation and cell apoptosis in

in vitro

HepG2 (human liver cell line) NAFLD models. GA also prevented high fat diet (HFD)-induced hepatic lipotoxicity and liver injury in

in vivo

rat NAFLD models. GA was found to stabilize lysosomal membranes, inhibit cathepsin B expression and enzyme activity, inhibit mitochondrial cytochrome c release, and reduce FFA-induced oxidative stress. These characteristics may represent major cellular mechanisms, which account for its protective effects on FFA/HFD-induced hepatic lipotoxicity.

Conclusion:

GA significantly reduced FFA/HFD-induced hepatic lipotoxicity by stabilizing the integrity of lysosomes and mitochondria and inhibiting cathepsin B expression and enzyme activity.
A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients
Authors: Campos Guilherme M. , Bambha Kiran , Vittinghoff Eric , Rabl Charlotte , Posselt Andrew M. , Ciovica Ruxandra , Tiwari Umesh , Ferrel Linda , Pabst Mark , Bass Nathan M. , Merriman Raphael B.
Published: February 2008

Nonalcoholic steatohepatitis (NASH) is common in morbidly obese persons. Liver biopsy is diagnostic but technically challenging in such individuals. This study was undertaken to develop a clinically useful scoring system to predict the probability of NASH in morbidly obese persons, thus assisting in the decision to perform liver biopsy. Consecutive subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. The outcome was pathologic diagnosis of NASH. Predictors evaluated were demographic, clinical, and laboratory variables. A clinical scoring system was constructed by rounding the estimated regression coefficients for the independent predictors in a multivariate logistic model for the diagnosis of NASH. Of 200 subjects studied, 64 (32%) had NASH. Median body mass index was 48 kg/m2 (interquartile range, 43-55). Multivariate analysis identified six predictive factors for NASH: the diagnosis of hypertension (odds ratio [OR], 2.4; 95% confidence interval [CI], 1-5.6), type 2 diabetes (OR, 2.6; 95% CI, 1.1-6.3), sleep apnea (OR, 4.0; 95% CI, 1.3-12.2), AST > 27 IU/L (OR, 2.9; 95% CI, 1.2-7.0), alanine aminotransferase (ALT) > 27 IU/L (OR, 3.3; 95% CI, 1.4-8.0), and non-Black race (OR, 8.4; 95% CI, 1.9-37.1). A NASH Clinical Scoring System for Morbid Obesity was derived to predict the probability of NASH in four categories (low, intermediate, high, and very high).

Conclusion:

The proposed clinical scoring can predict NASH in morbidly obese persons with sufficient accuracy to be considered for clinical use, identifying a very high-risk group in whom liver biopsy would be very likely to detect NASH, as well as a low-risk group in whom biopsy can be safely delayed or avoided.
Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis
Authors: Straub Beate Katharina , Stoeffel Pamela , Heid Hans , Zimbelmann Ralf , Schirmacher Peter
Published: February 2008

Fatty change (steatosis) is the most frequent liver pathology in western countries and is caused by a broad range of disorders such as alcohol abuse and metabolic syndrome. The surface layer of lipid droplets (LDs) contains members of a protein family that share homologous sequences and domains, the so-called PAT proteins, named after their constituents, perilipin, adipophilin, and TIP47. We characterized the LD-associated proteins in normal and diseased liver connected with LD accumulation. Adipophilin and TIP47 are expressed in LDs of vitamin A-storing hepatic stellate cells and additionally in LDs of steatotic hepatocytes. Perilipin, which was thought to be characteristic for LDs of adipocytes and steroidogenic cells, becomes

de novo

expressed in hepatocytes of human steatotic liver. Perilipin splice variant A was found in human steatotic hepatocytes by biochemical, molecular biological, and immunohistochemical methods. Its association with LDs is different from TIP47 and adipophilin, and depends on size and localization of the LDs, suggesting that the different PAT proteins play specific roles during maturation of LDs.
Synthesis, characterization, bioactivity and biocompatibility of nanostructured materials based on the wollastonite‐poly(ethylmethacrylate‐co‐vinylpyrrolidone) system
Authors: Rodríguez‐Lorenzo L. M. , García‐Carrodeguas R. , Rodríguez M. A. , De Aza S. , Jiménez J. , López‐Bravo A. , Fernandez M. , Román J. San
Published: February 2008

Composite materials are very promising biomaterials for hard tissue augmentation. The approach assayed in this work involves the manufacturing of a composite made of a bioactive ceramic, natural wollastonite (W) and a nanostructured copolymer of ethylmethacrylate (EMA) and vinylpyrrolidone (VP) to yield a bioresorbable and biocompatible VP–EMA copolymer. A bulk polymerization was induced thermally at 50°C, using 1 wt % azobis(isobutyronitrile) (AIBN) as free‐radical initiator. Structural characterization, compressive strength, flexural strength (FS), degradation, bioactivity, and biocompatibility were evaluated in specimens with a 60/40 VP/EMA ratio and ceramic content in the range 0–60%. A good integration between phases was achieved. Greater compression and FS, in comparison with the pure copolymer specimens was obtained only when the ceramic load got up to 60% of the total weight. The soaking in NaCl solution resulted in the initial swelling of the specimens tested. The maximum swelling was reached after 2–3 h of immersion and it was significantly greater for lower ceramic loads. This result makes the polymer component the main responsible for the interactions with the media. After soaking in SBF, microdomains segregation can be observed in the polymer component that can be related with a dramatic difference in the reactivity of both monomers in free radical polymerization, whereas the formation of an apatite‐like layer on the W surfaces can be observed. Biocompatibility in vitro studies showed the absence of cytotoxicity of all formulations. The cells were able to adhere on the polystyrene negative control and on specimens containing 60 wt % wollastonite forming a monolayer and showing a normal morphology. However, a low cellular growth was observed. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Surface immobilization of poly(ethyleneimine) and plasmid DNA on electrospun poly(L‐lactic acid) fibrous mats using a layer‐by‐layer approach for gene delivery
Authors: Sakai Shinji , Yamada Yusuke , Yamaguchi Tetsu , Ciach Tomasz , Kawakami Koei
Published: February 2008

The method of coating electrospun ultrafine poly(L‐lactic acid) fibers with DNA, by building up polyelectrolyte layer(s) of poly(ethyleneimine) (PEI) and plasmid DNA using an electrostatic layer‐by‐layer deposition method, for gene delivery is presented. The pGL3 encoding luciferase was applied as plasmid DNA. The quantity of pGL3 immobilized on individual fibers increased with increasing pGL3 concentration in the immersion solution (0.017–0.870 mg/mL) and increasing bilayer number of PEI/pGL3 (single–triple). With the exception of one specimen prepared under the condition 0.870 mg/mL pGL3 solution and double PEI/pGL3 layers, the transfection efficiency of COS‐7 cells, defined by the ratio of fluorescence intensity (resulting from the presence of luciferase) with respect to the quantity of cellular protein on the fibrous mat increased with increasing quantity of pGL3 on the fibers. In addition to the ease of controlling the quality of polyelectrolyte bilayer(s) by simply changing the concentrations of substances and number of immersing cycles, the features of the electrospun fibrous mat such as a very large surface‐to‐volume ratio and flexibility, could potentially be employed as a strategy for gene therapy combined with tissue engineering technology. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Effect of nicotine in matrix mineralization by human bone marrow and Saos‐2 cells cultured on the surface of plasma‐sprayed titanium implants
Authors: Pereira M. L. , Carvalho J. C. , Peres F. , Fernandes M. H.
Published: February 2008

Smoking has an established negative impact in the clinical outcome of dental implants. This work analyses the response of human osteoblastic cells to nicotine, at the surface of plasma‐sprayed commercial titanium implants. Human bone marrow (HBM) and Saos‐2 cells, seeded on the surface of titanium implants and cultured in experimental conditions favoring osteoblastic differentiation, were exposed continuously to nicotine (0.0001 to 0.5 mg mL−1) and characterized for cell proliferation and function. Exposure of HBM cells resulted in increased cell proliferation, higher alkaline phosphatase (ALP) activity, and earlier onset of matrix mineralization at levels up to 0.2 mg mL−1, an initial inhibitory effect in cell growth and functional activity followed by a recovery in the presence of 0.3 mg mL−1 and a dose‐dependent deleterious effect at higher levels. By contrast, exposure to nicotine did not affect cell proliferation of Saos‐2 cells at levels up to 0.2 mg mL−1, and caused only a small positive effect in ALP activity in the presence of 0.05 and 0.1 mg mL−1; however, matrix mineralization by Saos‐2 cells also occurred earlier in the cultures exposed to levels of nicotine up to 0.1 mg mL−1. Higher concentrations caused dose‐dependent inhibitory effects. Considering the high diffusion potential of nicotine, results suggest a local role of nicotine in modulating bone formation events at the implant surface. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Ontogenetic Sequence Analysis: using parsimony to characterize developmental sequences and sequence polymorphism
Authors: Colbert Matthew W. , Rowe Timothy
Published: February 2008

Ontogenetic sequences are a pervasive aspect of development and are used extensively by biologists for intra‐ and interspecific comparisons. A tacit assumption behind most such analyses is that sequence is largely invariant within a species. However, recent embryological and experimental work emphasizes that ontogenetic sequences can be variable and that sequence polymorphism may be far more prevalent than is generally realized. We present a method that uses parsimony algorithms to map hierarchic developmental patterns that capture variability within a sample. This technique for discovering and formalizing sequences is called the “Ontogenetic Sequence Analysis” (OSA). Results of OSA include formalized diagrams of reticulating networks, describe all most parsimonious sequences, and can be used to develop statistics and metrics for comparison of both intraspecific and interspecific sequence variation. The method is tested with examples of human postnatal skeletal ossification, comprising a time‐calibrated data set of human hand and wrist epiphyseal unions, and a longitudinal data set of human wrist ossification. Results illustrate the validity of the method for discovering sequence patterns and for predicting morphologies not represented in analytic samples. OSA demonstrates the potential and challenges of incorporating ontogenetic sequences of morphological information into evolutionary analyses. J. Exp. Zool. (Mol. Dev. Evol.) 310B:398–416, 2008. © 2008 Wiley‐Liss, Inc.
Side populations of gastrointestinal cancers are not enriched in stem cells
Authors: Burkert J , Otto WR , Wright NA
Published: February 2008

The side population (SP) phenotype, defined as the reserpine‐blockable ability to efflux the nucleic acid dye Hoechst 33342, has been claimed to be enriched for stem cells in several human normal tissues, cancers and cell lines, and thus may be useful for the identification and isolation of cancer stem cells. We demonstrated the presence of SP fractions in all of seven tested gastrointestinal cancer cell lines. Four cell lines were selected (HT29, HGT101, Caco2 and HRA19a1.1) for detailed phenotypic and behavioural analysis with respect to stem cell characteristics. Cell surface marker analysis showed that, contrary to non‐SP cells, the SPs entirely lack the expression of CD34. This difference, however, disappeared when the cells were cultured, rendering both populations CD34‐positive. Expression of other putative stem cell markers (CD133, CD44, Hes‐1, β‐catenin, Musashi‐1, Oct‐4 and CD117) was identical on SP and non‐SPs before and after culturing. Sorted SP and non‐SP cells were similarly clonogenic in vitro, tumourigenic in vivo, and displayed similar multipotential differentiation potential in vitro and in vivo. Additionally, culturing cytometrically‐sorted SP and non‐SP cells showed that the populations are interconvertible, each giving rise to the other. Expression of ABCG2 and Mdr‐1, two membrane transporter proteins that have been suggested to be responsible for the drug‐effluxing capacities of SP cells, including Hoechst 33342, was identical in non‐SP and SP cells, indicating that there may be additional factors responsible for the Hoechst effluxing property in gastrointestinal cancer SP cells. Here, we show that the SP and non‐SP fractions, albeit phenotypically distinct populations, do not differ with respect to stem cell‐like cell number or behaviour. We thus conclude that the concept of the SP phenotype as a universal marker for stem cells does not apply to gastrointestinal cancer cells. These findings stand in contrast to the observations made in many other tissues and harbour important implications for the future search for intestinal cancer stem cell markers. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Poly(ether imide)/N‐methyl pyrrolidinone solutions: kinetics of water vapour absorption and surface layer formation
Authors: Pochat‐Bohatier Céline , Cohen‐Addad Jean‐Pierre , Chinpa Watchanida , Deratani André
Published: February 2008

BACKGROUND: Water sorption by polymer solutions during film fabrication may affect the film morphology and thereby the film properties.

RESULTS: Water vapour sorption isotherms at 40 °C of poly(ether imide) (PEI)/N‐methyl pyrrolidinone (NMP) solutions were experimentally determined. Considering PEI concentrations ranging from 0 to 20 wt%, results obtained from gravimetric measurements and near‐infrared (NIR) spectroscopy, indicative of the total weight uptake and the local water concentration in the bulk solution, respectively, showed that a first stage occurred featuring a quasi‐linear time dependence of the weight fraction of absorbed water. Deviations from linearity dependent on the PEI concentration were afterwards observed, this behaviour being more marked for concentrations higher than 14 wt%. To achieve good predictions, the mathematical description of the sorption results must take into consideration both the classical approach using diffusion equations and the possible time dependence of the surface concentration of water at the air‐facing interface.

CONCLUSION: This paper presents an analysis of water vapour sorption in PEI/NMP solutions combining local and global quantifications of the water content through NIR and gravimetric methods. The development of a mathematical model suggests a possible surface layer formation at the air‐facing interface. Copyright © 2008 Society of Chemical Industry
Structural studies of shikimate 5‐dehydrogenase from Mycobacterium tuberculosis
Authors: Arcuri Helen A. , Borges Júlio C. , Fonseca Isabel O. , Pereira José H. , Neto João Ruggiero , Basso Luiz A. , Santos Diógenes S. , de Azevedo Walter F.
Published: February 2008

Tuberculosis (TB) remains the leading cause of mortality due to a single bacterial pathogen, Mycobacterium tuberculosis. The reemergence of TB as a potential public health threat, the high susceptibility of human immunodeficiency virus‐infected persons to the disease, the proliferation of multi‐drug‐resistant strains (MDR‐TB) and, more recently, of extensively drug resistant isolates (XDR‐TB) have created a need for the development of new antimycobacterial agents. Amongst the several proteins and/or enzymes to be studied as potential targets to develop novel drugs against M. tuberculosis, the enzymes of the shikimate pathway are attractive targets because they are essential in algae, higher plants, bacteria, and fungi, but absent from mammals. The mycobacterial shikimate pathway leads to the biosynthesis of chorismate, which is a precursor of aromatic amino acids, naphthoquinones, menaquinones, and mycobactins. Here we report the structural studies by homology modeling and circular dichroism spectroscopy of the shikimate dehydrogenase from M. tuberculosis (MtSDH), which catalyses the fourth step of the shikimate pathway. Our structural models show that the MtSDH has similar structure to other shikimate dehydrogenase structures previously reported either in presence or absence of NADP, despite the low amino acid sequence identity. The circular dichroism spectra corroborate the secondary structure content observed in the MtSDH models developed. The enzyme was stable up to 50°C presenting a cooperative unfolding profile with the midpoint of the unfolding temperature value of ∼63–64°C, as observed in the unfolding experiment followed by circular dichroism. Our MtSDH structural models and circular dichroism data showed small conformational changes induced by NADP binding. We hope that the data presented here will assist the rational design of antitubercular agents. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Determination of lopinavir and ritonavir in blood plasma, seminal plasma, saliva and plasma ultra‐filtrate by liquid chromatography/tandem mass spectrometry detection
Authors: Estrela Rita C. E. , Ribeiro Fabio S. , Seixas Brayan V. , Suarez‐Kurtz Guilherme
Published: February 2008

A method based on liquid‐liquid extraction followed by high‐performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometry (ESI‐MS/MS) detection was developed for the simultaneous determination of lopinavir (LPV) and ritonavir (RTV) in human blood, semen and saliva samples. The acquisition was performed in multiple reaction monitoring (MRM) mode, monitoring the transitions: m/z 629 > 447.1 for LPV, 721.18 > 268.02 for RTV and m/z 747.22 > 322.03 for the internal standard (IS). The limit of quantification was 1 ng/mL for both analytes in all matrices. The method was linear in the studied range (1–2000 ng/mL for LPV and 1–200 ng/mL for RTV), with r2 > 0.99 for each drug, and the run time was 4.5 min. The intra‐assay precisions (%) were in the ranges of 0.1–14.2 (LPV) and 0.4–12.7 (RTV), the inter‐assay precisions were in the ranges of 2.8–15.3 (LPV) and 1.1–12.8 (RTV) and the intra‐and inter‐assay recoveries were >85% for both drugs. The extraction efficiencies were 73.5–118.4% for LPV and 74.4–126.2% for RTV. The analytical method was applied to measure LPV and RTV concentrations in blood plasma (total and unbound fraction), saliva and semen of six HIV+ individuals under stable treatment with Kaletra® soft gel capsules. The results were consistent with previously published data. Copyright © 2008 John Wiley & Sons, Ltd.
An optimized forwarding protocol for lifetime extension of wireless sensor networks
Authors: Azim Mohammad Abdul , Kibria M. Rubaiyat , Jamalipour Abbas
Published: February 2008

Optimized routing (from source to sink) in wireless sensor networks (WSN) constitutes one of the key design issues in prolonging the lifetime of battery‐limited sensor nodes. In this paper, we explore this optimization problem by considering different cost functions such as distance, remaining battery power, and link usage in selecting the next hop node among multiple candidates. Optimized selection is carried out through fuzzy inference system (FIS). Two differing algorithms are presented, namely optimized forwarding by fuzzy inference systems (OFFIS), and two‐layer OFFIS (2L‐OFFIS), that have been developed for flat and hierarchical networks, respectively. The proposed algorithms are compared with popular routing protocols that are considered as the closest counterparts such as minimum transmit energy (MTE) and low energy adaptive clustering hierarchy (LEACH). Simulation results demonstrate the superiority of the proposed algorithms in extending the WSN lifetime. Copyright © 2008 John Wiley & Sons, Ltd.
Differentiation of Insulin Secretion Patterns in Insulinoma
Authors: Saddig Christiane , Goretzki Peter E. , Starke Achim A. R.
Published: February 2008

Background

In patients with insulinoma, biochemical proof of inappropriately elevated insulin secretion during hypoglycemia is required prior to surgery. Because circulating insulin levels usually vary widely, we have used the combined OGTT‐fasting test to define new normative criteria for a retrospective systematic analysis.

Methods

We retrospectively analyzed insulin concentrations from OGTT‐fasting tests of 64 patients with surgically removed insulinomas. In addition, the response to intravenous somatostatin infusions was estimated. Normative criteria were defined to obtain comparable estimates of insulin concentrations: basal, glucose‐stimulated maximum, postglucose plateau, and secretory bursts.

Results

Three types of insulin secretion patterns were identified: (1) the autonomous secretion pattern (type 1, N = 17) with basal and post‐OGTT plateau insulin concentrations of approximately 50 mU/L, suppression after OGTT by 41%, virtual absence of distinctive secretory bursts, and resistance to somatostatin‐mediated suppression (25 %); (2) the inadequate suppression pattern (type 2, N = 28) with moderately elevated basal and post‐OGTT insulin concentrations of approximately 20 mU/L, suppression after OGTT by 73%, absence of secretory bursts, and incomplete somatostatin‐induced suppression (56 %); (3) the late‐burst secretion pattern (type 3, N = 19) with similar basal and post‐OGTT insulin concentrations of 17 mU/L, suppression after OGTT by 76%, true insulin bursts of Δ 13 ± 11 mU/L (184%), and nearly complete somatostatin‐induced suppression by 64%.

Conclusions

By means of a new normative analysis of the combined OGTT‐fasting test, three different patterns of insulin secretion can be described in patients with insulinoma: the autonomous secretion type, the inadequate suppression type, and the late‐burst secretion type.
Antimicrobial properties of avian eggshell‐specific C‐type lectin‐like proteins
Authors: Wellman-Labadie Olivier , Lakshminarayanan Rajamani , Hincke Maxwell T.
Published: February 2008

C‐type lectin‐like proteins are major components of the calcified eggshell of multiple avian species. In this study, two representative avian C‐type lectin‐like proteins, ovocleidin‐17 and ansocalcin, were purified from decalcified chicken and goose eggshell protein extracts and investigated for carbohydrate binding activity as well as antimicrobial activity. Purified ovocleidin‐17 and ansocalcin were found to bind bacterial polysaccharides, and were bactericidal against Bacillus subtilis, Staphylococcus aureus and Pseudomona aeruginosa. Bactericidal activity was found to be enhanced in the presence of calcium but was not dependent on its presence. The results suggest that avian C‐type lectin‐like proteins may play an important antimicrobial role in defence of the avian embryo.
An independent Ukraine: Sustainable or unsustainable development?
Authors: Gorobets Alexander
Published: February 2008

In this paper the current problems of socio-economic development, such as population loss, public health, and others, in independent Ukraine are presented and analyzed. Their main causes are identified as follows: extensive type of economic development, absence of the clear, sustainable goals and appropriate programs, high level of corruption, general socio-cultural (moral) crisis, passive civil position of society, lack of democracy, and inadequacy of institutions, for example, the higher education system. The contemporary problems of social capital development and inefficiency of science and higher education institutions in Ukraine are examined.
The effects of milk as a food matrix for polyphenols on the excretion profile of cocoa ( − )-epicatechin metabolites in healthy human subjects
Authors: Roura Elena , Andrés-Lacueva Cristina , Estruch Ramon , Lourdes Mata Bilbao M. , Izquierdo-Pulido Maria , Lamuela-Raventós Rosa M.
Published: February 2008

The effect of different food matrices on the metabolism and excretion of polyphenols is uncertain. The objective of the study was to evaluate the possible effect of milk on the excretion of ( − )-epicatechin metabolites from cocoa powder after its ingestion with and without milk. Twenty-one volunteers received the following three test meals each in a randomised cross–over design with a 1-week interval between meals: (1) 250 ml whole milk as a control; (2) 40 g cocoa powder dissolved in 250 ml whole milk (CC–M); (3) 40 g cocoa powder dissolved in 250 ml water (CC–W). Urine was collected before consumption and during the 0–6, 6–12 and 12–24 h periods after consumption. ( − )-Epicatechin metabolite excretion was measured using liquid chromatography–MS. One ( − )-epicatechin glucuronide and three ( − )-epicatechin sulfates were detected in urine excreted after the intake of the two cocoa beverages (CC–M and CC–W). The results show that milk does not significantly affect the total amount of metabolites excreted in urine. However, differences in metabolite excretion profiles were observed; there were changes in the glucuronide and sulfate excretion rates, and the sulfation position between the period of excretion and the matrix. The matrix in which polyphenols are consumed can affect their metabolism and excretion, and this may affect their biological activity. Thus, more studies are needed to evaluate the effect of these different metabolite profiles on the body.
Multitrophic effects of nutrient addition in upland grassland
Authors: Fountain M.T. , Brown V.K. , Gange A.C. , Symondson W.O.C. , Murray P.J.
Published: February 2008

Although the effects of nutrient enhancement on aquatic systems are well documented, the consequences of nutritional supplements on soil food webs are poorly understood, and results of past research examining bottom-up effects are often conflicting. In addition, many studies have failed to separate the effects of nutrient enrichment and the physical effects of adding organic matter. In this field study, we hypothesised that the addition of nitrogen to soil would result in a trophic cascade, through detritivores (Collembola) to predators (spiders), increasing invertebrate numbers and diversity.

Nitrogen and lime were added to plots in an upland grassland in a randomised block design. Populations of Collembola and spiders were sampled by means of pitfall traps and identified to species.

Seventeen species of Collembola were identified from the nitrogen plus lime (N+L) and control plots. Species assemblage, diversity, richness, evenness and total number were not affected by nutrient additions. However, there was an increase in the number of Isotomidae juveniles and Parisotoma anglicana trapped in the N+L plots.

Of the 44 spider species identified, over 80% were Linyphiidae. An effect on species assemblage from the addition of N+L to the plots was observed on two of the four sampling dates (July 2002 and June 2003). The linyphiid, Oedothorax retusus, was the only species significantly affected by the treatments and was more likely to be trapped in the control plots.

The increased number of juvenile Collembola, and change in community composition of spiders, were consequences of the bottom-up effect caused by nutrient inputs. However, despite efforts to eliminate the indirect effects of nutrient inputs, a reduction in soil moisture in the N+L plots cannot be eliminated as a cause of the invertebrate population changes observed. Even so, this experiment was not confounded by the physical effects of habitat structure reported in most previous studies. It provides evidence of moderate bottom-up influences of epigeic soil invertebrate food webs and distinguishes between nutrient addition and plant physical structure effects. It also emphasises the importance of understanding the effects of soil management practices on soil biodiversity, which is under increasing pressure from land development and food production.
An algebra-level version of a link-polynomial identity of Lickorish
Authors: LARSEN MICHAEL J. , ROWELL ERIC C.
Published: February 2008

We establish isomorphisms between certain specializations of BMW algebras and the symmetric squares of Temperley–Lieb algebras. These isomorphisms imply a link-polynomial identity due to W. B. R. Lickorish. As an application, we compute the closed images of the irreducible braid group representations factoring over these specialized BMW algebras.
The support of tempered distributions
Authors: Graham Colin C.
Published: February 2008

We identify the support of a tempered distribution by evaluation of a sequence of test functions against the Fourier transform of the distribution. This improves previous results by removing the restriction that the distribution's Fourier transform be in $L^1_{loc}$ and be of polynomial growth. We use an apparently new technical lemma that implies that certain bounded approximate identities for $L^1(\R^n)$ are also topological approximate identities for elements of the space $\Sl$ of Schwartz functions.
Something from (almost) nothing: the impact of multiple displacement amplification on microbial ecology
Authors: Binga Erik K , Lasken Roger S , Neufeld Josh D
Published: February 2008

Microbial ecology is a field that applies molecular techniques to analyze genes and communities associated with a plethora of unique environments on this planet. In the past, low biomass and the predominance of a few abundant community members have impeded the application of techniques such as PCR, microarray analysis and metagenomics to complex microbial populations. In the absence of suitable cultivation methods, it was not possible to obtain DNA samples from individual microorganisms. Recently, a method called multiple displacement amplification (MDA) has been used to circumvent these limitations by amplifying DNA from microbial communities in low-biomass environments, individual cells from uncultivated microbial species and active organisms obtained through stable isotope probing incubations. This review describes the development and applications of MDA, discusses its strengths and limitations and highlights the impact of MDA on the field of microbial ecology. Whole genome amplification via MDA has increased access to the genomic DNA of uncultivated microorganisms and low-biomass environments and represents a ‘power tool’ in the molecular toolbox of microbial ecologists.
Induction of SM‐20 in PC12 cells leads to increased cytochrome c levels, accumulation of cytochrome c in the cytosol, and caspase‐dependent cell death
Authors: Straub Jennifer A. , Lipscomb Elizabeth A. , Yoshida Eileen S. , Freeman Robert S.
Published: February 2008

Sympathetic neurons deprived of nerve growth factor (NGF) release cytochrome c into the cytosol and undergo caspase‐dependent cell death through a process that requires de novo gene expression. Expression of the SM‐20 gene increases after NGF withdrawal, and ectopic SM‐20 expression induces cell death in NGF‐maintained neurons. To further evaluate the mechanism by which SM‐20 promotes cell death, we developed a PC12‐derived cell line in which SM‐20 expression can be induced by addition of doxycycline to the culture medium. Induction of SM‐20 in either undifferentiated or NGF‐differentiated cells resulted in cell death. Cell death was accompanied by an increase in caspase activity and was inhibited by the caspase inhibitor zVAD‐FMK. Analysis of cytochrome c in cytosolic and mitochondria‐enriched subcellular fractions revealed that induction of SM‐20 led to the accumulation of cytochrome c in the cytosol. Surprisingly, SM‐20 expression also resulted in a selective increase in the total amount of cytochrome c protein. Thus, induction of SM‐20 expression appears to affect both the amount and subcellular localization of cytochrome c in PC12 cells. These results suggest that SM‐20 promotes caspase‐dependent cell death through a mechanism involving cytochrome c.
CAT2 arginine transporter deficiency significantly reduces iNOS‐mediated NO production in astrocytes
Authors: Manner Cathyryne K. , Nicholson Benjamin , MacLeod Carol L.
Published: February 2008

We have previously demonstrated that genetic ablation of cationic amino acid transporter 2 (Cat2) significantly inhibits nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) in activated macrophages. Here we report that iNOS activity is impaired by 84% in activatedCat2‐deficient astrocytes.Cat2ablation appears to reduce astrocyte NO synthesis by decreasing the uptake of the sole precursor, arginine, as well as by reducing the expression of iNOS following activation. Excessive or dysregulated NO production by activated astrocytes and other CNS cell types has been implicated in the pathogenesis of neurological disorders. Our results support the idea that manipulation of CAT2 transporter function might be useful for the therapeutic modulation of iNOS activity.
Acceleration of ampere class H− ion beam by MeV accelerator
Authors: Taniguchi M. , Inoue T. , Umeda N. , Kashiwagi M. , Watanabe K. , Tobari H. , Dairaku M. , Sakamoto K.
Published: February 2008

The H− ion accelerator R&D to realize the international thermonuclear experimental reactor neutral beam is ongoing at Japan Atomic Energy Agency (JAEA). The required performance for the prototype MeV accelerator developed at JAEA is 1MeV, 500mA (current density of 200A∕m2) H− ion beam at the beamlet divergence angle of less than 7mrad. Up to 2005, 836keV, 146A∕m2 H− ion beam was successfully accelerated as the highest record of the current density at MeV class energy beams. In the present work, high current negative ion beam acceleration test was performed by increasing the beam extraction apertures from 3×3 (9 apertures) to 3×5 (15 apertures). By fixing the air leak at the source chamber due to backstream ions as well as the improvement of voltage holding capability by a new fiber reinforced plastic insulator ring, the performance of the MeV accelerator was improved. So far, H− ion beam of 320mA was successfully accelerated up to 796keV with the beam divergence angle of 5.5mrad. The accelerated drain current including the electron reaches close to the power supply limit for the MeV test facility. The heat flux by the backstream ion during the above beam acceleration was estimated to be 360W∕cm2. The Cs leakage to the accelerator during the test campaign (Cs total input of 5.0g) was 0.26mg (7.0μg∕cm2). This is considered to be the allowable level from the viewpoint of voltage holding.
Hydrogen absorption and desorption kinetics in fullerite C60 single crystals. Low-temperature micromechanical and structural characteristics of the interstitial solid solution C60(H2)x
Authors: Fomenko L. S. , Lubenets S. V. , Natsik V. D. , Stetsenko Yu. E. , Yagotintsev K. A. , Strzhemechny M. A. , Prokhvatilov A. I. , Osipyan Yu. A. , Izotov A. N. , Sidorov N. S.
Published: February 2008

The microhardness HV and lattice parameter a of C60 single crystals are measured at room temperature as functions of the hydrogen saturation time t for several values of the saturation temperature (250, 300, and 350°C) at a fixed hydrogen pressure p=30atm. According to the measurements of HV and a, the kinetics of hydrogen absorption is described by a simple exponential law with a single, temperature-dependent characteristic time. In highly saturated samples the microhardness is 4 times greater than for the initial C60 crystal, while the lattice parameter is 0.2% larger. The temperature dependence of the microhardness HV and lattice parameter a of C60(H2)x crystals is investigated in the temperature interval 77–300K. The introduction of hydrogen lowers the temperature of the fcc–sc phase transition, and the transition becomes strongly broadened in temperature. The dependence of the microhardness of the saturated sample on the hold time in air at room temperature is described by the sum of two exponentials with different characteristic times. Kinetics of this kind is presumably due to two processes: desorption of hydrogen from the sample, which causes a decrease of the microhardness, and a simultaneous penetration of gaseous impurities into the sample from the surrounding air, which is accompanied by hardening. The influence of the H2 molecules on the characteristic of the intermolecular interaction in fullerite C60 is discussed and the intercalation-induced processes of dislocation slip and microfracture.
Contribution of the shrunk interface and the convex surface of grains on magnetic behavior in granular film
Authors: Lee Jehyun , Suess Dieter , Schrefl Thomas , Oh Kyu Hwan , Fidler Josef
Published: February 2008

In this paper, we studied the intergranular interaction in realistically shaped grains which have convex vacuum surface. The convex surface is evaluated by utilizing the SURFACE EVOLVER, a software package for grain growth simulation. Various shapes of grains are obtained by changing the wetting angles between the top surface and the grain boundaries. From finite element micromagnetic simulations, which are used to simulate the magnetization reversal in the simple granular structure, it is found that the exchange field decreases with increasing wetting angle. We studied the effect of the intergranular exchange and the magnetostatic interactions individually. In order to study the intergranular exchange coupling effect quantitatively, an analytic energy surface model for the exchange coupled system is developed. The results agree very well with those of micromagnetic simulation. Magnetostatic interactions reduce the exchange field by making the antiparallel state more favorable than the parallel.
Ion beam assisted deposition of MgO barriers for magnetic tunnel junctions
Authors: Cardoso S. , Macedo R. J. , Ferreira R. , Augusto A. , Wisniowski P. , Freitas P. P.
Published: February 2008

This work reports for the first time results on MgO tunnel junctions prepared by ion beam. The MgO barrier was deposited from a ceramic MgO target using an assisted beam, following the deposition and assisted beam phase diagram which relate the beam profile with the current and energy. The deposition rate for MgO is calculated with and without assisted beam, and compared with the experimental values. The MgO film growth on Ta∕CoFeB∕MgO simple stacks was optimized aiming at a (002) preferred orientation for the MgO growth, measured by x-ray diffraction. The optimum assist beam energy was tuned for each deposition beam condition (+800,+1000,+1200V), using assist beams of 40mA (∼130μA∕cm2) with 0to+600V. Without assist beam, no texture is observed for the MgO, while the (002) orientation appears for assisted deposition. The optimum range of assist voltages is large, being limited by the onset of etching at high voltages, reducing the deposition rate. Magnetic tunnel junctions were deposited with the structure Ta 50Å∕Ru 200Å∕Ta 50Å∕Mn78Ir22 150Å∕Co90Fe10 30Å∕Ru 8Å∕Co56Fe24B20 40Å∕MgO t∕Co56Fe24B20 30Å∕Ru 30Å∕Ta 50Å, with the MgO barrier deposited with the conditions optimized by x rays. The effect of the assist beam energy on the junction properties (magnetoresistance and magnetization) are discussed. Tunnel magnetoresistance values up to 110%, with RA products of 100–400Ωμm2, for 11Å thick MgO barriers are obtained using assisted deposition with a +100V assist beam, which is a major improvement of the ∼30% of TMR, if no beam is used.
Explicit solutions to an effective Gross–Pitaevskii equation: One-dimensional Bose–Einstein condensate in specific traps
Authors: Kengne E. , Liu X. X. , Malomed B. A. , Chui S. T. , Liu W. M.
Published: February 2008

An effective Gross–Pitaevskii equation, which describes the dynamics of quasi-one-dimensional Bose–Einstein condensates in specific potential traps, is considered, and new families of exact solutions are reported, which include periodic and solitary waves. The solutions are applied to the description of BEC patterns trapped in optical-lattice potentials.
Anomalous two-photon generation of excitons in CuCl pellets
Authors: Jang J. I. , Anderson M. A. , Ketterson J. B. , Chang R. P. H.
Published: February 2008

We report on an anomalous excitation of excitonic matter in pressed CuCl pellets. In these random materials, we find that excitons are initially created for an excitation energy in the range of 1892–2843meV, which is far below the bandgap of this semiconductor. The excitation-power dependence from the population dynamics of excitonic matter strongly indicates an unusual two-photon generation of ground-state excitons. Considering this off-resonance effect, excitons are probably generated from a continuum of impurity-induced levels excited by two-photon pumping.