bluuebunny/crossref_metadata_2025 huggingface dataset:
Robustness of convergence in finite time for linear programming neural networks
Authors: Marco Mauro Di , Forti Mauro , Grazzini Massimo
Published: February 2006

A recent work has introduced a class of neural networks for solving linear programming problems, where all trajectories converge toward the global optimal solution in finite time. In this paper, it is shown that global convergence in finite time is robust with respect to tolerances in the electronic implementation, and an estimate of the allowed perturbations preserving convergence is obtained. Copyright © 2006 John Wiley & Sons, Ltd.
Cognitive dysfunction associates with white matter hyperintensities and subcortical atrophy on magnetic resonance imaging of the elderly diabetes mellitus Japanese elderly diabetes intervention trial (J‐EDIT)
Authors: Akisaki Taichi , Sakurai Takashi , Takata Toshihiro , Umegaki Hiroyuki , Araki Atsushi , Mizuno Sachiko , Tanaka Shiro , Ohashi Yasuo , Iguchi Akihisa , Yokono Koichi , Ito Hideki
Published: February 2006

Background

Type 2 diabetes is associated with cognitive dysfunction and increases the risk of dementia in the elderly. The aim of this study was to explore, by means of magnetic resonance (MR) imaging, possible relationships among clinical profiles of diabetes, cognitive function, white matter hyperintensities (WMHs) and subcortical brain atrophy.

Methods

Data were obtained from 95 nondemented type 2 diabetic participants aged 65 years or over, enrolled in an intervention trial for Japanese elderly diabetic patients. Cognitive function was measured with neuropsychiatric tests, including mini‐mental state examination (MMSE), verbal memory, digit symbol substitution and Stroop tests. Hyperintensity was classified into periventricular, deep white matter, thalamic and basal ganglia. Four ventricle‐to‐brain ratios were used to measure subcortical atrophy. To identify clinical features of diabetes, indices of glycemic control, lipid metabolism, blood pressure and complications were examined. Canonical correlation analysis and regression analysis were used to assess correlation.

Results

Scores for digit symbol substitution and MMSE negatively correlated with WMHs in the parietal lobe and hyperintensities in the thalamus, respectively. Lower scores for memory and digit symbol substitution showed positive association with enlarged subcortical atrophy adjacent to lateral ventricles. There was no association between clinical pictures of diabetic patients with cognitive dysfunction and of those with morphological changes in the brain.

Conclusions

Impaired cognitive domains of the speed of mental processes and memory were associated with WMHs and subcortical atrophy. Degenerative changes in the cerebral small vessels may constitute predictive factors for the rate of cognitive dysfunction in elderly diabetic patients. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of pioglitazone on urinary liver‐type fatty acid‐binding protein concentrations in diabetes patients with microalbuminuria
Authors: Nakamura Tsukasa , Sugaya Takeshi , Kawagoe Yasuhiro , Ueda Yoshihiko , Koide Hikaru
Published: February 2006

Background

Urinary liver‐type fatty acid‐binding protein (L‐FABP) is a useful marker for renal tubulointerstitial injury. Pioglitazone is reported to be effective in early diabetic nephropathy. The aim of the present study was to determine whether pioglitazone affects urinary L‐FABP levels in diabetic nephropathy patients with microalbuminuria.

Methods

Sixty‐eight patients with type 2 diabetes and microalbuminuria were randomized to a 12‐month treatment with pioglitazone (30 mg/d, n = 17), glibenclamide (5 mg/d, n = 18), voglibose (0.6 mg/d, n = 17), or nateglinide (270 mg/d, n = 16). Pre‐ and posttreatment urinary albumin excretion (UAE) and urinary L‐FABP concentrations were compared between the four treatment groups and 40 age‐matched healthy subjects.

Results

Pretreatment UAE and urinary L‐FABP levels differed little between the four groups. UAE and urinary L‐FABP levels were significantly greater in the diabetes patients than in the healthy subjects (UAE: p < 0.001; L‐FABP: p < 0.01). After 6 and 12 months, UAE and urinary L‐FABP were significantly lower in the pioglitazone treatment group than in the other treatment groups (UAE: 6 months, p < 0.01 and 12 months, p < 0.001; L‐FABP: 6 months, p < 0.05 and 12 months, p < 0.01).

Conclusions

Pioglitazone, but not glibenclamide, voglibose, or nateglinide, appears to be effective in reducing UAE and the urinary L‐FABP level, suggesting that pioglitazone has a specific role in ameliorating both glomerular and tubulointerstitial lesions associated with early diabetic nephropathy. Copyright © 2006 John Wiley & Sons, Ltd.
Impact of diabetes mellitus on the relationships between iron‐, inflammatory‐ and oxidative stress status
Authors: Van Campenhout Ann , Van Campenhout Christel , Lagrou Albert R. , Abrams Pascale , Moorkens Greta , Van Gaal Luc , Manuel‐y‐Keenoy Begoña
Published: February 2006

Background

Diabetes is an inflammatory condition associated with iron abnormalities and increased oxidative damage. We aimed to investigate how diabetes affects the interrelationships between these pathogenic mechanisms.

Methods

Glycaemic control, serum iron, proteins involved in iron homeostasis, global antioxidant capacity and levels of antioxidants and peroxidation products were measured in 39 type 1 and 67 type 2 diabetic patients and 100 control subjects.

Results

Although serum iron was lower in diabetes, serum ferritin was elevated in type 2 diabetes (p = 0.02). This increase was not related to inflammation (C‐reactive protein) but inversely correlated with soluble transferrin receptors (r = − 0.38, p = 0.002). Haptoglobin was higher in both type 1 and type 2 diabetes (p < 0.001) and haemopexin was higher in type 2 diabetes (p < 0.001). The relation between C‐reactive protein and haemopexin was lost in type 2 diabetes (r = 0.15, p = 0.27 vs r = 0.63, p < 0.001 in type 1 diabetes and r = 0.36, p = 0.001 in controls). Haemopexin levels were independently determined by triacylglycerol (R2 = 0.43) and the diabetic state (R2 = 0.13). Regarding oxidative stress status, lower antioxidant concentrations were found for retinol and uric acid in type 1 diabetes, α‐tocopherol and ascorbate in type 2 diabetes and protein thiols in both types. These decreases were partially explained by metabolic‐, inflammatory‐ and iron alterations. An additional independent effect of the diabetic state on the oxidative stress status could be identified (R2 = 0.5–0.14).

Conclusions

Circulating proteins, body iron stores, inflammation, oxidative stress and their interrelationships are abnormal in patients with diabetes and differ between type 1 and type 2 diabetes. Copyright © 2006 John Wiley & Sons, Ltd.
Verbatim and gist recall of sentences by dyslexic and non‐dyslexic adults
Authors: Miles T. R. , Thierry Guillaume , Roberts Judith , Schiffeldrin Josie
Published: February 2006

Forty‐eight college students, 24 of them dyslexic, were presented with four sentences of increasing complexity. Participants were asked to repeat each sentence and a record was kept of the number of repetitions required before 100% correct accuracy was achieved. None of the 24 control participants required a total of more than eight repetitions over the four sentences, whereas among the dyslexics the total number of repetitions needed ranged from one to 25. Dyslexic participants were unpredictable in their performance from one level of difficulty to the next and inter‐individual variability was far greater in the dyslexic group than in the control group. Overall, despite their relatively poor performance in achieving verbatim accuracy relative to non‐dyslexic participants, dyslexic individuals regularly managed to preserve the gist of the sentences. Some theoretical issues arising from these results are discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Persistence of autoreactive myelin oligodendrocyte glycoprotein (MOG)‐specific T cell repertoires in MOG‐expressing mice
Authors: Fazilleau Nicolas , Delarasse Cécile , Sweenie Claire H. , Anderton Stephen M. , Fillatreau Simon , Lemonnier François A. , Pham‐Dinh Danielle , Kanellopoulos Jean M.
Published: February 2006

Experimental autoimmune encephalomyelitis, an experimental murine model for multiple sclerosis, is induced by stimulation of myelin‐specific T lymphocytes. Myelin oligodendrocyte glycoprotein (MOG), a minor component of myelin proteins, is a potent autoantigen which contributes extensively to the anti‐myelin response. In the present work, immunoscope analyses and sequencing of the oligoclonal expansions revealed anti‐MOG Vα and Vβ public repertoires in lymphocytes infiltrating the CNS of wild‐type (WT) mice. Moreover, a subset of CNS‐infiltrating CD4+ T lymphocytes bearing the public Vβ8.2 segment have an inflammatory phenotype strongly suggesting that it is encephalitogenic. We then observed that, in lymph node cells of MOG‐deficient and WT animals, the Vα and Vβ public repertoires expressed by MOG‐specific T cells are identical in both strains of mice and correspond to those found in the CNS of WT animals. These findings indicate that the MOG immunodominant determinant is unable to induce tolerance by deletion, and public anti‐MOG T cell repertoires are selected for, regardless of the presence of MOG in the thymus and peripheral organs.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200635914
Expression and alternative processing of IL‐18 inhuman neutrophils
Authors: Robertson Susan E. , Young John D. , Kitson Susan , Pitt Andrew , Evans Jamie , Roes Jurgen , Karaoglu Denise , Santora Ling , Ghayur Tariq , Liew Foo Y. , Gracie J. Alastair , McInnes Iain B.
Published: February 2006

Interleukin‐18 (IL‐18), a member of the IL‐1 cytokine superfamily, is an important regulator of both innate and acquired immune responses. We demonstrate here constitutive expression of IL‐18 by human neutrophils. Unexpectedly, we observed that neutrophils from peripheral blood or rheumatoid synovial compartments contained not only pro and mature IL‐18, but also several novel smaller‐molecular‐weight IL‐18‐derived species. Using specific protease inhibitors, and serine protease gene‐targeted mice, we demonstrate that these IL‐18‐derived products arose through caspase‐independent cleavage events mediated by the serine proteases, elastase and cathepsin G. Moreover, we report that the net effect of elastase treatment of mature recombinant IL‐18 was to reduce its IFN‐γ‐inducing activity. Thus, human neutrophils contain IL‐18 and IL‐18‐derived molecular species that can arise through novel enzymatic processing pathways. Through cytosolic, membrane or secretory expression of such processing enzymes, together with generation of IL‐18 itself, neutrophils likely play a critical role in regulating IL‐18 activities during early innate immune responses.
Immediate antigen‐specific effector functions byTCR‐transgenic CD8+ NKT cells
Authors: Wingender Gerhard , Berg Martina , Jüngerkes Frank , Diehl Linda , Sullivan Barbara A. , Kronenberg Mitchell , Limmer Andreas , Knolle Percy A.
Published: February 2006

Only recently have natural antigens for CD1d‐dependent, invariant Vα14+ natural killer T (iNKT) cells been identified. Similar data for CD1d‐independent and CD8+ NKT cell populations are still missing. Here, we show that the MHC class I‐restricted CD8+ TCR‐transgenic mouse lines OT‐I, P14 and H‐Y contain a significant proportion of transgenic CD8+ NK1.1+ T cells. In liver, most of NK1.1+ T cells express CD8αα homodimers. Transgenic NKT cells did not bind invariant Vα14‐to‐Jα18 TCR rearrangement (Vα14i)‐specific CD1d/α‐galactosylceramide tetramers and the frequency of iNKT cells was severely reduced. The activated cell surface phenotype and the distribution of transgenic NKT cells in vivo were similar to that reported for iNKT cells. The OT‐I and P14 CD8+ NKT cells recognized their cognate antigen in the context of H2‐Kb and produced cytokines shortly after TCR stimulation. Importantly, transgenic NKT cells exerted immediate antigen‐specific cytotoxicity in vitro and in vivo. Our results demonstrate the presence of transgenic CD8+ NKT cells in MHC class I‐restricted TCR‐transgenic animals, which are endowed with rapid antigen‐specific effector functions. These data imply that experiments studying naive T cell function in TCR‐transgenic animals should be interpreted with caution, and that such animals could be utilized for studying CD8+ NKT cell function in an antigen‐specific manner.
Intestinal double‐positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines
Authors: Pahar Bapi , Lackner Andrew A. , Veazey Ronald S.
Published: February 2006

Peripheral blood and intestinal CD4+CD8+ double‐positive (DP) T cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single‐positive T cells. Intestinal DP T cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA‐DR, and lower CD62L expression were found on intestinal DP T cells populations compared to CD4+ single‐positive T cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5.
R‐form LPS, the master key to the activation ofTLR4/MD‐2‐positive cells
Authors: Huber Michael , Kalis Christoph , Keck Simone , Jiang Zhengfan , Georgel Philippe , Du Xin , Shamel Louis , Sovath Sosathya , Mudd Suzanne , Beutler Bruce , Galanos Chris , Freudenberg Marina A.
Published: February 2006

Lipopolysaccharide (endotoxin, LPS) is a major recognition marker for the detection of gram‐negative bacteria by the host and a powerful initiator of the inflammatory response to infection. Using S‐ and R‐form LPS from wild‐type and R‐mutants of Salmonella and E. coli, we show that R‐form LPS readily activates mouse cells expressing the signaling receptor Toll‐like receptor 4/myeloid differentiation protein 2 (TLR4/MD‐2), while the S‐form requires further the help of the LPS‐binding proteins CD14 and LBP, which limits its activating capacity. Therefore, the R‐form LPS under physiological conditions recruits a larger spectrum of cells in endotoxic reactions than S‐form LPS. We also show that soluble CD14 at high concentrations enables CD14‐negative cells to respond to S‐form LPS. The presented in vitro data are corroborated by an in vivo study measuring TNF‐α levels in response to injection of R‐ and S‐form LPS in mice. Since the R‐form LPS constitutes ubiquitously part of the total LPS present in all wild‐type bacteria its contribution to the innate immune response and pathophysiology of infection is much higher than anticipated during the last half century.
Organ specific autoantigens and the autoreactiveT cell repertoire: The case of myelin oligodendrocyte glycoprotein
Authors: Wekerle Hartmut , Linington Christopher
Published: February 2006

There is strong evidence that immunological self tolerance critically relies on the elimination of potentially autoaggressive T lymphocyte clones from the emerging immune repertoire during intrathymic T cell differentiation. These ‘forbidden’ T cells are deleted as a result of a confrontation with their specific self antigen as presented on medullary stroma cells. But this purging mechanism is remarkably leaky, allowing numerous autoreactive T cells to join the healthy immune repertoire. A paper in this issue of the European Journal of Immunology studies the effect of organ‐specific autoantigen expression on the cognate T cell repertoire. Myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in human multiple sclerosis, is used as a model self antigen. T cell receptor profiles in wild‐type mice were compared with those in MOG‐knock‐out mice. Surprisingly, significant differences were not found suggesting that, in this particular case, autoantigen expression does not affect the autoreactive T cell repertoire.

See accompanying article: http://dx.doi.org/10.1002/eji.200535021
Structural Studies of β‐Cyclodextrin and Permethylated β‐Cyclodextrin Inclusion Compounds of Cyclopentadienyl Metal Carbonyl Complexes
Authors: Braga Susana S. , Almeida Paz Filipe A. , Pillinger Martyn , Seixas João D. , Romão Carlos C. , Gonçalves Isabel S.
Published: February 2006

[CpM(CO)nCl] complexes with M = Fe (n = 2) and Mo (n = 3) have been immobilised in plain β‐cyclodextrin (β‐CD) and permethylated β‐CD (TRIMEB) by methods tailored according to the stabilities and solubilities of the individual components. Four adducts were obtained with a 1:1 host/guest stoichiometry. The compounds were studied by powder X‐ray diffraction (XRD), thermogravimetric analysis (TGA), 13C{1H} CP/MAS NMR and FTIR spectroscopy. A comparison of the experimental powder XRD data for the TRIMEB/[CpMo(CO)3Cl] inclusion compound with reference patterns revealed that the crystal packing is very similar to that reported previously for a TRIMEB/ethyl laurate inclusion compound. The unit‐cell parameters refined to a = 14.731, b = 22.476, c = 27.714 Å (volume = 9176.3 Å3), and the space group was confirmed as P212121. A hypothetical structural model of the inclusion compound was subsequently obtained by global optimisation using simulated annealing. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Peroxotungstates and Their Citrate and Tartrate Derivatives
Authors: Hou Shu‐Ya , Zhou Zhao‐Hui , Lin Tao‐Ran , Wan Hui‐Lin
Published: February 2006

The reaction of potassium tungstate with the biologically relevant ligands citric and tartaric acid, in the presence of hydrogen peroxide, was investigated to discover the effect of pH variation on the product pattern. The reaction with citric acid led to the formation of the dimer K5[WO(O2)2(Hcit)H(Hcit)(O2)2OW]·6H2O (1; H4cit = citric acid) due to carboxyl‐carboxylic acid hydrogen bonding in the pH range 2–5; this complex can also be obtained by an exchange reaction between the oxo ligands of the dimeric hydrogencitrate tungstate K4[W2O5(Hcit)2]·4H2O (6) and H2O2. Interestingly, a novel dimeric peroxotungstate K3[W2O3(O2)4(OH)]·H2O (2), without the coordination of citrate ligands, was isolated in the pH range 7–9, as confirmed by 17O NMR solution studies. The reaction of potassium tungstate with (R,R)‐tartaric acid afforded the tartratoperoxotungstate K4[W2O2(O2)4{(R,R)‐tart}]·3H2O [3; H4tart = (R,R)‐tartaric acid] in the pH range 1–3. The dimeric peroxotungstate K2[W2O3(O2)4(H2O)2]·2H2O (4) was found to react with citric or tartaric acid at pH 2–5 or 2–3, respectively, to give species 1 and 3. Evidence that 1 exists as a dimer in solution is presented. The three complexes were characterized by elemental analysis, IR and NMR spectroscopy, and X‐ray structural analyses. The formation of these complexes is dictated by pH, and the thermal stabilities of 1 and 3 vary with the coordinated ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Aminoethyl‐Functionalized Cyclopentadienyliridium Complexes: Photochemical C–H Activation and Carbonylation of Cycloalkanes
Authors: Chan Pek Ke , Leong Weng Kee , Krummel Karl I. , Garland Marc V.
Published: February 2006

The photochemical C–H activation of cycloalkanes by aminoethyl‐functionalized cyclopentadienyliridium complexes proceeds in a broadly similar way to that for their unfunctionalized analogues. In a carbon monoxide atmosphere, there is evidence that carbonylation to form the carboxaldehyde occurred with both systems. In situ infrared spectroscopic studies on these reactions allow the identification of several species present in low concentrations in the reaction mixture. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Facile and Reliable Synthesis of Tetraphenoxyborates and Their Properties
Authors: Malkowsky Itamar M. , Fröhlich Roland , Griesbach Ulrich , Pütter Hermann , Waldvogel Siegfried R.
Published: February 2006

Tetraphenoxyborates are reliably prepared in a two‐step sequence, exploiting less corrosive reagents like boric acid and the corresponding phenols. The broad scope of this transformation is demonstrated in 22 examples. Several solid‐state structures reveal the preferential conformation of the phenoxy moieties allowing cation interaction. Furthermore, a novel architecture of a phenoxy‐substituted tetraborate was found. Surprisingly, the tetraphenoxyborates exhibit a good stability in neutral and basic media. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A basic study on humidity recovery using micro‐porous media: General characteristics and effect of material properties on transport performance
Authors: Wang Shixue , Utaka Yoshio , Tasaki Yutaka
Published: February 2006

As a first step toward evaluating factors that influence humidity and heat transfer from moist air to dry air through porous media having very small pores, the present paper attempts to clarify factors that influence moisture transport between constant‐temperature water and dry air through a porous media plate. The effect of the pore diameter of the porous plate on the humidity transport through a porous plate was found to depend strongly on the thickness and pore diameter of the porous plate. That is, the smaller the pore diameter and the thicker the plate, the greater the effect of the pore diameter on the humidity transfer. In addition, the performance of heat and mass transfer were confirmed to increase with respect to the increase of air velocity. In addition, a parameter called the humidity absorption rate was introduced to evaluate the utilization degree of the air capacity to absorb humidity. The humidity absorption rate decreased with increases in both air velocity and plate thickness. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 35(2): 137–151, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20102
Study on the chimney effect in natural air‐cooled electronic equipment casings under inclination: Proposal of a thermal design correlation that includes the porosity coefficient of an outlet opening
Authors: Kitamura Yoji , Ishizuka Masaru , Nakagawa Shinji
Published: February 2006

Natural air‐cooling technologies for electronic equipment have the important advantages of no fan and high reliability. However, natural air cooling has lower cooling capability than fan air cooling, so enhancement of its cooling capability is required. This paper presents the results for experimental casings designed to employ the chimney effect in natural air‐cooled electronic equipment. The system casing is inclined to enhance the effectiveness of natural air cooling. Experiments were carried out using a thin laptop PC. We investigated the effect on cooling capability produced by inclining the casing and by varying the outlet positions and numbers and the porosity coefficient of the outlet openings. The results show that the temperatures inside the casing and heater surfaces are slightly diminished by the effect of increased inclination and porosity coefficient of outlet openings. Moreover, the increase in natural circulation flux in the casing was quantitatively proven by experiments. In addition, the experimental data were reduced to a Nusselt number–Rayleigh number correlation, $Nu_{\beta}^{\ast}=0.432Ra_{\beta}^{\ast0.322}$, by using a modified reference length. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 35(2): 122–136, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20103
The mathematical model of solidification latent heat under high cooling rate
Authors: Shan Yao , Xuena Gong , Lixin Dai , Chunying Ma , Junze Jin , Abudula Abuliti
Published: February 2006

Treatment of solidification latent heat is a key point in solidification simulation by the finite difference method. When latent heat is dealt with in a traditional method of equivalent latent heat, it was found that heat was increased when casting with a high cooling rate, and then the simulation result was distorted. In this paper, a new method is proposed to deal with solidification latent heat. Moreover, a mathematical model was suggested, in which the latent heat can be dealt with accurately under high or normal cooling rates. By contrasting the simulation results from this new method with the traditional one, it was indicated that this new model can obtain more accurate simulation results than the traditional model under high or normal cooling rates. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 35(2): 115–121, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20104
Study on constant stress: Accelerated life tests of fouling thermal resistance
Authors: Shan‐rang Yang , Ling‐fang Sun , Feng Guo , Zhi‐ming Xu , Sheng‐ping Wang
Published: February 2006

To shorten the time of fouling tests, fouling life was defined. The statistical analysis method for type II‐censored exponential life data under constant‐stress accelerated life testing models and the accelerated coefficients a and b were obtained. By using an accelerated model, the estimators of the fouling life under usual stress could be obtained. A computing example was given. Results indicated that it is credible and feasible to perform accelerated life tests of asymptotic fouling thermal resistance, and will be of important value to experimental research of fouling. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 35(2): 110–114, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20105
The effect of operating parameters on water transport in PEM fuel cells
Authors: Hong Sun , Liejin Guo , Hongtan Liu
Published: February 2006

Water content in the membrane and the presence of liquid water in the catalyst layers (CL) and the gas diffusion layers (GDL) play a very important role in the performance of a PEM fuel cell. To study water transport in a PEM fuel cell, a two‐phase flow mathematical model is developed. This model couples the continuity equation, momentum conservative equation, species conservative equation, and water transport equation in the membrane. The modeling results of fuel cell performances agree well with measured experimental results. Then this model is used to simulate water transport and current density distribution in the cathode of a PEM fuel cell. The effects of operating pressure, cell temperature, and humidification temperatures on the net water transfer through the membrane, liquid water saturation, and current density distribution are studied. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 35(2): 89–100, 2006; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/htj.20107
Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells
Authors: Scafoglio Claudio , Ambrosino Concetta , Cicatiello Luigi , Altucci Lucia , Ardovino Mario , Bontempo Paola , Medici Nicola , Molinari Anna Maria , Nebbioso Angela , Facchiano Angelo , Calogero Raffaele A. , Elkon Ran , Menini Nadia , Ponzone Riccardo , Biglia Nicoletta , Sismondi Piero , Bortoli Michele De , Weisz Alessandro
Published: March 2006

Antiestrogens used for breast cancer (BC) treatment differ among each other for the ability to affect estrogen receptor (ER) activity and thereby inhibit hormone‐responsive cell functions and viability. We used high‐density cDNA microarrays for a comprehensive definition of the gene pathways affected by 17β‐estradiol (E2), ICI 182,780 (ICI), 4OH‐tamoxifen (Tamoxifen), and raloxifene (RAL) in ER‐positive ZR‐75.1 cells, a suitable model to investigate estrogen and antiestrogen actions in hormone‐responsive BC. The expression of 601 genes was significantly affected by E2 in these cells; in silico analysis reveals that 86 among them include one or more potential ER binding site within or near the promoter and that the binding site signatures for E2F‐1, NF‐Y, and NRF‐1 transcription factors are significantly enriched in the promoters of genes induced by estrogen treatment, while those for CAC‐binding protein and LF‐A1 in those repressed by the hormone, pointing to novel transcriptional effectors of secondary responses to estrogen in BC cells. Interestingly, expression of 176 E2‐regulated mRNAs was unaffected by any of the antiestrogens tested, despite the fact that under the same conditions the transcriptional and cell cycle stimulatory activities of ER were inhibited. On the other hand, of 373 antiestrogen‐responsive genes identified here, 52 were unresponsive to estrogen and 25% responded specifically to only one of the compounds tested, revealing non‐overlapping and clearly distinguishable effects of the different antiestrogens in BC cells. As some of these differences reflect specificities of the mechanism of action of the antiestrogens tested, we propose to exploit this gene set for characterization of novel hormonal antagonists and selective estrogen receptor modulators (SERMs) and as a tool for testing new associations of antiestrogens, more effective against BC. J. Cell. Biochem. 98: 1163–1184, 2006. © 2006 Wiley‐Liss, Inc.
β‐cryptoxanthin stimulates apoptotic cell death and suppresses cell function in osteoclastic cells: Change in their related gene expression
Authors: Uchiyama Satoshi , Yamaguchi Masayoshi
Published: March 2006

The effect of β‐cryptoxanthin, a kind of carotenoid, on osteoclastic cells in mouse marrow culture system in vitro was investigated. The macrophage colony‐stimulating factor (M‐CSF)‐dependent bone marrow macrophages were cultured in the presence of M‐CSF (10 ng/ml) and receptor activator of NF‐κB ligand (RANKL; 25 ng/ml) for 4 days. The osteoclastic cells formed were further cultured in medium containing either vehicle or β‐cryptoxanthin (10−8–10−6 M) with or without M‐CSF (10 ng/ml) and RANKL (50 ng/ml) for 24–72 h. Osteoclastic cells were significantly decreased with culture of β‐cryptoxanthin (10−7 or 10−6 M) with or without M‐CSF and RANKL for 24, 48, or 72 h. β‐Cryptoxanthin (10−8 M)‐induced decrease in osteoclastic cells were significantly inhibited in the presence of caspase‐3 inhibitor (10−8 or 10−7 M). Agarose gel electrophoresis showed the presence of low‐molecular‐weight deoxyribonucleic acid (DNA) fragments of adherent cells cultured with β‐cryptoxanthin (10−7 or 10−6 M) for 24 or 48 h, indicating that the carotenoid induces apoptotic cell death. Apoptosis‐related gene expression was determined using reverse transcription‐polymerase chain reaction (RT‐PCR). Culture with β‐cryptoxanthin (10−7 or 10−6 M) for 24 or 48 h caused a significant increase in caspase‐3 mRNA expression in the presence or absence of M‐CSF and RANKL, while Bcl‐2 and Apaf‐2 mRNA expressions were significantly increased with culture of β‐cryptoxanthin (10−7 or 10−6 M) without M‐CSF and RANKL for 24 or 48 h. Akt‐1 mRNA expression was not significantly changed with culture of the carotenoid (10−7 or 10−6 M) for 24 or 48 h. Moreover, tartrate‐resistant acid phosphatase (TRACP) activity, or TRACP and cathepsin K mRNA expressions were significantly decreased with culture of β‐cryptoxanthin (10−6 M) in the presence or absence of M‐CSF and RANKL for 48 h. This study demonstrates that β‐cryptoxanthin has stimulatory effects on apoptotic cell death and suppressive effects on osteoclastic cell function. J. Cell. Biochem. 98: 1185–1195, 2006. © 2006 Wiley‐Liss, Inc.
Time sequence of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and cisplatin treatment is responsible for a complex pattern of synergistic cytotoxicity
Authors: Kim Young‐Ho , Lee Yong J.
Published: March 2006

The combination of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and cisplatin resulted in a greater cytotoxicity than could be accounted for by the addition of the cytotoxic effects of the agents alone. In this study, we hypothesized that the synergistic interaction between the two modalities can be changed when both the sequence and the time interval between the two treatments are varied. To test the hypothesis, human head‐and‐neck squamous‐cell carcinoma (HNSCC)‐6 cells were either pretreated with 0.01–0.5 µg/ml TRAIL for various times (0–24 h) followed by treatment with 5 µg/ml cisplatin or pretreated with 5 µg/ml cisplatin for various times (0–24 h) followed by treatment with 0.5 µg/ml TRAIL. In latter case, the synergistic effect was gradually increased when the time interval between the two treatments was increased. In former case, a maximal synergy occurred within 0–4 h of pretreatment with TRAIL. However, the synergistic effect was gradually decreased when the time interval between the two treatments was increased. Data from immunoblotting analysis reveal that a similar pattern emerged for the PARP cleavage and caspase activation. The synergistic effect is not associated with DR4, DR5, FADD, and FLIPL. Interestingly, a complex pattern of synergistic interaction between TRAIL and cisplatin is related to the cleavage of FLIPS. Although overexpression of FLIPS protected cells from FLIPS cleavage and apoptotic death, blockage of FLIPS cleavage by replacing Asp39 and Asp42 residues with alanine did not further enhance FLIPS‐mediated protection. Taken together, FLIPS cleavage reflects apoptotic damage, but it does not cause apoptosis. J. Cell. Biochem. 98: 1284–1295, 2006. © 2006 Wiley‐Liss, Inc.
Phosphatidylinositol 3‐kinase/Akt plays a role in sphingosine 1‐phosphate‐stimulated HSP27 induction in osteoblasts
Authors: Takai Shinji , Tokuda Haruhiko , Matsushima‐Nishiwaki Rie , Hanai Yoshiteru , Kato Kanefusa , Kozawa Osamu
Published: March 2006

We previously reported that p38 mitogen‐activated protein (MAP) kinase plays a part in sphingosine 1‐phosphate‐stimulated heat shock protein 27 (HSP27) induction in osteoblast‐like MC3T3‐E1 cells. In the present study, we investigated whether phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) is involved in the induction of HSP27 in these cells. Sphingosine 1‐phosphate time dependently induced the phosphorylation of Akt. Akt inhibitor, 1L‐6‐hydroxymethyl‐chiro‐inositol 2‐(R)‐2‐O‐methyl‐3‐O‐octadecylcarbonate, reduced the HSP27 induction stimulated by sphingosine 1‐phosphate. The sphingosine 1‐phosphate‐induced phosphorylation of GSK‐3β was suppressed by Akt inhibitor. The sphingosine 1‐phosphate‐induced HSP27 levels were attenuated by LY294002 or wortmannin, PI3K inhibitors. Furthermore, LY294002 or Akt inhibitor did not affect the sphingosine 1‐phosphate‐induced phosphorylation of p38 MAP kinase and SB203580, a p38 MAP kinase inhibitor, had little effect on the phosphorylation of Akt. These results suggest that PI3K/Akt plays a part in the sphingosine 1‐phosphate‐stimulated induction of HSP27, maybe independently of p38 MAP kinase, in osteoblasts. J. Cell. Biochem. 98: 1249–1256, 2006. © 2006 Wiley‐Liss, Inc.
Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin‐5 modulation
Authors: Martin Tracey A. , Das Tapas , Mansel Robert E. , Jiang Wen G.
Published: March 2006

Tight junctions (TJs) in endothelial cells act as cell–cell adhesion structures, governing paracellular permeability (PCP). Disruption can lead to leaky vascular bed and potentially to oedema and swelling of tissues, the aetiology of mastalgia. These changes may also cause vascular spread of cancer cells. This study aimed to determine whether the function of TJs in endothelial cells can be strengthened by gamma linolenic acid (GLA), selenium (Se) and iodine (I) in the presence of 17beta‐estradiol (17β‐estradiol), which causes leakage of endothelial cells by disruption of TJs in endothelium. GLA, I, and Se individually increased transendothelial resistance. The combination of all three agents also had a significant effect on TER. Addition of GLA/Se/I reduced PCP of the endothelial cells. Treatment with GLA/Se/I reversed the effect of 17β‐estradiol in reducing TER and increasing PCP. Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h there was increasing relocation to endothelial cell–cell junctions of the TJ proteins Claudin‐5, Occludin, and ZO‐1. Interestingly, this relocation was particularly evident with treatments containing I when probing with Claudin‐5 and those containing Se for Occludin. There was a small increase in overall protein levels when examined by Western blotting after treatment with GLA/Se/I when probed with Claudin‐5 and Occludin. We report that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells, by way of regulating the distribution of Claudin‐5, Occludin, and ZO‐1. Interestingly, this combination was also able to completely reverse the effect of 17β‐estradiol in these cells. J. Cell. Biochem. 98: 1308–1319, 2006. © 2006 Wiley‐Liss, Inc.
Vitamin D3 suppresses the androgen‐stimulated growth of mouse mammary carcinoma SC‐3 cells by transcriptional repression of fibroblast growth factor 8
Authors: Kawata Hirotoshi , Kamiakito Tomoko , Takayashiki Norio , Tanaka Akira
Published: February 2006

Active metabolites of vitamin A and D are well known to act as growth inhibitors in hormone‐related prostate and breast cancers. When various concentrations of 1α,25‐dihydroxyvitamin D3 (vitamin D3), all‐trans‐retinoic acid (ATRA) and 9‐cis retinoic acid (9‐cis RA) were examined, the androgen‐stimulated growth of mouse mammary carcinoma SC‐3 cells was inhibited by vitamin D3 alone in a dose‐dependent manner. A flow cytometer analysis showed that vitamin D3 leads SC‐3 cells to relative G1‐growth arrest after 72 h. Characterization of vitamin D3‐responsive genes using an oligonucleotide microarray demonstrated that 220 genes were upregulated at more than threefold, and 84 genes were downregulated to less than one‐third, compared with the testosterone‐stimulated SC‐3 cells. Neither cyclin‐dependent kinase inhibitors (CDKIs) nor the antiapoptotic bcl‐2 gene were induced in vitamin D3‐responsive genes, with the exception of a slight induction of p15INK4B. Importantly, fgf8 was markedly repressed in response to vitamin D3. The exogenous addition of FGF8 canceled the growth suppression by vitamin D3 in SC‐3 cells, suggesting that the repression of fgf8 is an indispensable step in vitamin D3‐mediated growth inhibition. In reporter assays using the ARE‐containing artificial construct and the natural androgen‐regulated PSA promoter, co‐transfection of the vitamin D receptor (VDR) and androgen receptor (AR) suppressed AR‐stimulated promoter activity. In addition, vitamin D3 also suppressed androgen‐stimulated promoter activity in the stably transfected SC‐3 cells. Moreover, VDR repressed the core promoter activity of fgf8 in COS1 cells and in the SC‐3 cells. All these findings strongly suggest that vitamin D3 serves as a negative regulator for both androgen‐related and fgf8 transcriptions. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Nuclease sensitive element binding protein 1 associates with the selenocysteine insertion sequence and functions in mammalian selenoprotein translation
Authors: Shen Qichang , Fan Lin , Newburger Peter E.
Published: February 2006

Biosynthesis of selenium‐containing proteins requires insertion of the unusual amino acid selenocysteine by alternative translation of a UGA codon, which ordinarily serves as a stop codon. In eukaryotes, selenoprotein translation depends upon one or more selenocysteine insertion sequence (SECIS) elements located in the 3′‐untranslated region of the mRNA, as well as several SECIS‐binding proteins. Our laboratory has previously identified nuclease sensitive element binding protein 1 (NSEP1) as another SECIS‐binding protein, but evidence has been presented both for and against its role in SECIS binding in vivo and in selenoprotein translation. Our current studies sought to resolve this controversy, first by investigating whether NSEP1 interacts closely with SECIS elements within intact cells. After reversible in vivo cross‐linking and ribonucleoprotein immunoprecipitation, mRNAs encoding two glutathione peroxidase family members co‐precipitated with NSEP1 in both human and rat cell lines. Co‐immunoprecipitation of an epitope‐tagged GPX1 construct depended upon an intact SECIS element in its 3′‐untranslated region. To test the functional importance of this interaction on selenoprotein translation, we used small inhibitory RNAs to reduce the NSEP1 content of tissue culture cells and then examined the effect of that reduction on the activity of a SECIS‐dependent luciferase reporter gene for which expression depends upon readthrough of a UGA codon. Co‐transfection of small inhibitory RNAs directed against NSEP1 decreased its expression by approximately 50% and significantly reduced luciferase activity. These studies demonstrate that NSEP1 is an authentic SECIS binding protein that is structurally associated with the selenoprotein translation complex and functionally involved in the translation of selenoproteins in mammalian cells. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Sphingosine‐1‐phosphate induces COX‐2 expression via PI3K/Akt and p42/p44 MAPK pathways in rat vascular smooth muscle cells
Authors: Hsieh Hsi‐Lung , Wu Chou‐Bing , Sun Chi‐Chin , Liao Chang‐Hui , Lau Ying‐Tung , Yang Chuen‐Mao
Published: February 2006

Sphingosine 1‐phosphate (S1P) has been shown to regulate smooth muscle cell proliferation, migration, and vascular maturation. S1P increases the expression of several proteins including COX‐2 in vascular smooth muscle cells (VSMCs) and contributes to arteriosclerosis. However, the mechanisms regulating COX‐2 expression by S1P in VSMCs remain unclear. Western blotting and RT‐PCR analyses showed that S1P induced the expression of COX‐2 mRNA and protein in a time‐ and concentration‐dependent manner, which was attenuated by inhibitors of MEK1/2 (U0126) and PI3K (wortmannin), and transfection with dominant negative mutants of p42/p44 mitogen‐activated protein kinases (ERK2) or Akt. These results suggested that both p42/p44 MAPK and PI3K/Akt pathways participated in COX‐2 expression induced by S1P in VSMCs. In accordance with these findings, S1P stimulated phosphorylation of p42/p44 MAPK and Akt, which was attenuated by U0126, LY294002, or wortmannin, respectively. Furthermore, this up‐regulation of COX‐2 mRNA and protein was blocked by a selective NF‐κB inhibitor helenalin. Consistently, S1P‐stimulated translocation of NF‐κB into the nucleus was revealed by immnofluorescence staining. Moreover, S1P‐stimulated activation of NF‐κB promoter activity was blocked by phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002 and helenalin, but not by U0126, suggesting that involvement of PI3K/Akt in the activation of NF‐κB. COX‐2 promoter assay showed that S1P induced COX‐2 promoter activity mediated through p42/p44 MAPK, PI3K/Akt, and NF‐κB. These results suggested that in VSMCs, activation of p42/p44 MAPK, Akt and NF‐κB pathways was essential for S1P‐induced COX‐2 gene expression. Understanding the mechanisms involved in S1P‐induced COX‐2 expression on VSMCs may provide potential therapeutic targets in the treatment of arteriosclerosis. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Activation pathways of α4β1 integrin leading to distinct T‐cell cytoskeleton reorganization, Rac1 regulation and Pyk2 phosphorylation
Authors: Maqueda Alfredo , Moyano José V. , Gutiérrez‐López M. Dolores , Ovalle Susana , Rodríguez‐Frade José M. , Cabañas Carlos , Garcia‐Pardo Angeles
Published: March 2006

α4β1 integrin is highly expressed in lymphocytes and is essential in hematopoiesis, extravasation, and the inflammatory response. α4β1 can be activated by intracellular signals elicited upon T‐cell activation by phorbol esters, CD3 crosslinking, or certain chemokine/receptor interactions (inside‐out activation). Divalent cations or certain anti‐ β1 mAbs (i.e., TS2/16) can also bind and activate integrins directly (outside‐in activation). In both cases, activation results in increased adhesion and/or affinity for ligands. It is not known if these various stimuli produce the same or different post‐adhesion events. To address this, we have studied the cytoskeleton organization and intracellular signaling following activation of α4β1 in Jurkat cells and in human T‐lymphoblasts. Treatment with Mn2+, α‐CD3 mAb or the chemokine SDF‐1α followed by attachment to the fibronectin fragment H89 or the endothelial molecule VCAM‐1 (α4β1 ligands), resulted in cell polarization and migration. In contrast, activation with PMA or TS2/16 induced cell spreading and strong adherence. Video microscopy and Transwell analyses confirmed these results, which correlated with different resistance to detachment under flow. Activation of the small GTPase RhoA or transfection with the constitutively active mutants V14RhoA or V12Rac1, abolished the α4β1‐induced cell polarization but did not affect cell spreading. Moreover, Rac1 activity was distinctly modulated by agents that induce a polarized or spread phenotype. The tyrosine kinase Pyk2 was highly phosphorylated upon induction of cell polarity but not during cell spreading. These results reveal novel properties of α4β1 integrin, namely the ability to trigger two types of T‐cell cytoskeletal response with different signaling requirements. J. Cell. Physiol. 207: 746–756, 2006. © 2006 Wiley‐Liss, Inc.
Heparanase is expressed in osteoblastic cells and stimulates bone formation and bone mass
Authors: Kram Vardit , Zcharia Eyal , Yacoby‐Zeevi Oron , Metzger Shula , Chajek‐Shaul Tova , Gabet Yankel , Müller Ralph , Vlodavsky Israel , Bab Itai
Published: March 2006

Heparan sulfate proteoglycans (HSPGs) are ubiquitous macromolecules. In bone, they are associated with cell surfaces and the extracellular matrix (ECM). The heparan sulfate (HS) chains of HSPGs bind a multitude of bioactive molecules, thereby controlling normal and pathologic processes. The HS‐degrading endoglycosidase, heparanase, has been implicated in processes such as inflammation, vascularization associated with wound healing and malignancies, and cancer metastasis. Here we show progressive mRNA expression of the hpa gene (encoding heparanase) in murine bone marrow stromal cells undergoing osteoblastic (bone forming) differentiation and in primary calvarial osteoblasts. Bone marrow stromal cells derived from transgenic mice expressing recombinant human heparanase (rh‐heparanase) and MC3T3 E1 osteoblastic cells exposed to soluble rh‐heparanase spontaneously undergo osteogenic differentiation. In addition, the transgenic bone marrow stromal cells degrade HS chains. In wild‐type (WT) and hpa‐transgenic (hpa‐tg) mice, heparanase is weakly expressed throughout the bone marrow with a substantial increase in osteoblasts and osteocytes, especially in the hpa‐tg mice. Heparanase expression was absent in osteoclasts. Micro‐computed tomographic and histomorphometric skeletal analyses in male and female hpa‐tg versus WT mice show markedly increased trabecular bone mass, cortical thickness, and bone formation rate, but no difference in osteoclast number. Collectively, our data suggest that proteoglycans tonically suppress osteoblast function and that this inhibition is alleviated by HS degradation with heparanase. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.