bluuebunny/crossref_metadata_2025 huggingface dataset:
PREPARATION AND CHARACTERIZATION OF SOL–GEL-DERIVED TiO2/ITO PHOTOELECTRODES
Authors: LIANG CHIA-HUNG , CHANG HUNG-YI , LIOU TSZ-WEI , CHEN HUEY-ING
Published: March 2008

In this work, nanocrystalline TiO 2/ ITO electrodes were prepared by sol–gel method starting from tetrabutyl orthotitanate ( Ti ( OBu n)4) reacted with hydrogen peroxide in the ice-water bath. The sol–gel derived TiO 2 films were characterized by XRD, SEM, BET, and UV/Vis absorption spectroscopic techniques. The preparation conditions, including the number of coats and calcination temperature, were also investigated. Furthermore, PEC cells were constructed for testing the activities of prepared TiO 2/ ITO photoelectrodes. The photo-currents for hydrogen production via the PEC reaction were measured under UV irradiation (λ max = 253.7 nm ). The experimental results showed that the sol–gel derived TiO 2 films calcined at 300°C–600°C were anatase structure and they showed a maximum UV/Vis absorption at about 380 nm. Moreover, from the result of PEC reactions, it was found that the TiO 2/ ITO photoelectrode (calcined at 600°C, with the thickness of TiO 2 layer of about ~0.2 μm) demonstrated a large saturation current (0.326 mA/cm2) with a quite high photoelectrochemical conversion efficiency of 2.39%.
STUDY ON METAL MEMBRANE TEMPERATURE SENSOR AND MICROHEATER FOR PCR CHIP
Authors: YAN WEIPING , XUE NING , SHI XINGHUI , LIU JUNSHAN , GUO JIHONG
Published: March 2008

The development of PCR chip shortens the reaction time of DNA amplification, reduces the bulk of reaction reagents; therefore, it is widely applied to biomedicine and other related fields. Since PCR reaction is completed through three different precise temperature zones periodically, the sensitivity of temperature measurement and the heating property of the metal membrane must be highly regarded. In this paper, three kinds of membranes, Ni , Pt , and Ni – Cr , were fabricated on silicon substrates; their resistance–temperature characteristics and heating properties are discussed. The results show that Ni and Pt films have good linear resistance–temperature relationship; the heating property of Pt film is superior to that of Ni – Cr film. The PCR chip with Pt film microheater can reach 150°C in a short time with 25 V voltage.
The Descriptive Epidemiology of Commonly Occurring Mental Disorders in the United States
Authors: Kessler Ronald C. , Wang Philip S.
Published: March 2008

Data are reviewed on the descriptive epidemiology of commonly occurring DSM-IV mental disorders in the United States. These disorders are highly prevalent: Roughly half the population meets criteria for one or more such disorders in their lifetimes, and roughly one fourth of the population meets criteria in any given year. Most people with a history of mental disorder had first onsets in childhood or adolescence. Later onsets typically involve comorbid disorders. Some anxiety disorders (phobias, separation anxiety disorder) and impulse-control disorders have the earliest age of onset distributions. Other anxiety disorders (panic disorder, generalized anxiety disorder, post-traumatic stress disorder), mood disorders, and substance disorders typically have later ages of onset. Given that most seriously impairing and persistent adult mental disorders are associated with child-adolescent onsets and high comorbidity, increased efforts are needed to study the public health implications of early detection and treatment of initially mild and currently largely untreated child-adolescent disorders.
Regionalization of Local Public Health Systems in the Era of Preparedness
Authors: Koh Howard K. , Elqura Loris J. , Judge Christine M. , Stoto Michael A.
Published: March 2008

Post-9/11, preparedness planning has catalyzed intrastate regionalization of local public health resources throughout the United States. Investigating this trend unveils several regionalization themes, relevant in other sectors of government, which are applicable to local public health. In this review article, we begin by briefly examining the lessons learned from regionalization for police and fire services, drawing comparisons to public health. Then we provide a brief history of the accelerating regionalization of local public health services sparked by the current attention to emergency preparedness. In particular, we offer case studies from Massachusetts and the National Capital Region to highlight examples of regionalization outcomes related to networking, coordination, standardization, and centralization of public health services. The impact of social capital on preparedness is also explored. Finally, we summarize research needs for the future.
The Diffusion and Impact of Clean Indoor Air Laws
Authors: Eriksen Michael P. , Cerak Rebecca L.
Published: March 2008

Over the past quarter century, primarily as a result of scientific discovery, citizen advocacy, and legislative action, comprehensive clean indoor air laws have spread rapidly throughout the world. Laws that establish completely smoke-free indoor environments have many relative advantages including being low cost, safe, effective, and easy to implement. The diffusion of these laws has been associated with a dramatic and rapid reduction in population levels of serum cotinine among nonsmokers and has also contributed to a reduction in overall cigarette consumption among smokers, with no adverse economic impact, except to the tobacco industry. Currently, nearly half of the U.S. population lives in jurisdictions with some combination of completely smoke-free workplaces, restaurants, or bars. The diffusion of clean indoor air laws is spreading rapidly throughout the world, stimulated by the first global health treaty, the Framework Convention on Tobacco Control.
Invariant Regions and Global Existence of Solutions for Reaction-Diffusion Systems with a Tridiagonal Matrix of Diffusion Coefficients and Nonhomogeneous Boundary Conditions
Authors: Salem Abdelmalek
Published: March 2008

The purpose of this paper is the construction of invariant regions in which we establish the global existence of solutions for reaction-diffusion systems (three equations) with a tridiagonal matrix of diffusion coefficients and with nonhomogeneous boundary conditions after the work of Kouachi (2004) on the system of reaction diffusion with a full 2-square matrix. Our techniques are based on invariant regions and Lyapunov functional methods. The nonlinear reaction term has been supposed to be of polynomial growth.
Extraordinary Transmission and Enhanced Emission with Metallic Gratings Having Converging-Diverging Channels
Authors: Battula Arvind , Lu Yalin , Knize R. J. , Reinhardt Kitt , Chen Shaochen
Published: March 2008

Transmission metallic gratings having the shape of converging-diverging channel (CDC) give an extra degree of freedom to exhibit enhanced transmission resonances. By varying the gap size at the throat of CDC, the spectral locations of the transmission resonance bands can be shifted close to each other and have high transmittance in a very narrow energy band. Hence, the CDC shape metallic gratings can lead to almost perfect transmittance for any desired wavelength by carefully optimizing the metallic material, gap at the throat of CDC, and grating parameters. In addition, a cavity surrounded by the CDC shaped metallic grating and a one-dimensional (1D) photonic crystal (PhC) can lead to an enhanced emission with properties similar to a laser. The large coherence length of the emission is achieved by exploiting the coherence properties of the surface waves on the gratings and PhC. The new multilayer structure can attain the spectral and directional control of emission with onlyp-polarization. The resonance condition inside the cavity is extremely sensitive to the wavelength, which would then lead to high emission in a very narrow wavelength band. Such simple 1D multilayer structure should be easy to fabricate and have applications in photonic circuits, thermophotovoltaics, and potentially in energy efficient incandescent sources.
A Note on Wave Equation and Convolutions
Authors: Kılıçman Adem , Eltayeb Hassan
Published: March 2008

We study the first‐order nonhomogenous wave equation. We extend the convolution theorem into a general case with a double convolution as the nonhomogenous term. The uniqueness and continuity of the solution are proved and we provide some examples in order to validate our results.
Prostate-Specific Membrane Antigen Expression Is a Potential Prognostic Marker in Endometrial Adenocarcinoma
Authors: Mhawech-Fauceglia Paulette , Smiraglia Dominic J. , Bshara Wiam , Andrews Christopher , Schwaller Juerg , South Stacey , Higgs Donald , Lele Shashikant , Herrmann Francois , Odunsi Kunle
Published: March 2008

The aim of this study was to determine the role of prostate-specific membrane antigen (PSMA) as a prognostic marker in endometrial adenocarcinoma (EAC) and to explore whether its down-regulation could be due to epigenetic mechanism. First, we examined the expression and the prognostic value of PSMA by semiquantitative reverse transcription-PCR and immunohistochemistry in EAC tissue samples. Second, to explore the role of CpG methylation in down-regulation PSMA in EAC, we evaluated PSMA CpG island methylation using methylation-specific PCR in cells lines and in a subset of patients' samples. Furthermore, association of the status of tumor methylation to the clinical and histologic variables was also evaluated. Higher PSMA mRNA levels were associated with stage I (P = 0.046) and PSMA protein intensity by immunohistochemistry (P = 0.032). In multivariate analysis, loss of PSMA expression was associated with a worse disease-free survival (P = 0.02). PSMA was methylated in prostate cell lines (DU145 and PC3) and endometrial cell lines. In addition, PSMA was methylated in 5 of 18 samples (all 5 had low PSMA mRNA value). There was a significant association between PSMA methylation and loss of protein expression by immunohistochemistry and PSMA-RNA level with P value of 0.036 and 0.011, respectively. In addition, there was an association between PSMA methylation and tumor size (P = 0.025). In summary, (a) PSMA is underexpressed in advanced stage EAC, (b) loss of PSMA expression can be considered as a prognostic marker in patients with EAC, and (c) loss of PSMA expression in a subset of EAC cases could be due to epigenetic silencing. (Cancer Epidemiol Biomarkers Prev 2008;17(3):571–7)
Progestin Treatment Induces Apoptosis and Modulates Transforming Growth Factor-β in the Uterine Endometrium
Authors: Rodriguez Gustavo C. , Rimel B.J. , Watkin William , Turbov Jane M. , Barry Cathy , Du Hongyan , Maxwell George L. , Cline J.M.
Published: March 2008

Background: Epidemiologic, animal, and human data suggest that progestins are potent endometrial cancer preventive agents. In the ovarian surface epithelium, progestins have been hypothesized to confer a cancer preventive effect via apoptosis and modulation of transforming growth factor-β (TGF-β). Given that the ovarian epithelium and endometrium share a common embryologic origin and similar reproductive and hormonal risk factors for malignancy, we tested the hypothesis that progestins confer biological effects in the endometrium similar to those in the ovary.

Methods: Postmenopausal female macaques (n = 78) were randomized into four groups to receive a diet for 36 months containing no hormone versus conjugated equine estrogen (CEE), medroxyprogesterone acetate (MPA), or CEE + MPA. The endometrium was then examined immunohistochemically for treatment-specific changes using antibodies to activated caspase-3 (for apoptosis), Ki-67 (proliferation), and the TGF-β1, TGF-β2, and TGF-β3 isoforms.

Results: Percentages of caspase-positive endometrial glandular cells were 3- to 5-fold higher in CEE + MPA–treated animals compared with all others (P < 0.05). Caspase-expressing cells were six times more numerous in the endometrial stroma of animals treated with MPA alone relative to other groups (P < 0.0001). Induction of endometrial glandular cell apoptosis in the CEE + MPA–treated group was associated with a dramatic increase in expression of TGF-β2 and TGF-β3 in the stromal compartment of the endometrium (P < 0.0001).

Conclusion: Progestin treatment activates chemopreventive biological effects in the endometrium that are similar to those in the ovarian surface epithelium. These data may facilitate identification of a chemopreventive approach that dramatically lessens the risk of both uterine and ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):578–84)
DNA Repair Gene XPD Polymorphisms and Cancer Risk: A Meta-analysis Based on 56 Case-Control Studies
Authors: Wang Fan , Chang Dong , Hu Fu-lan , Sui Hong , Han Bing , li Dan-dan , Zhao Ya-shuang
Published: March 2008

Genetic variations in the XPD gene may increase cancer susceptibility by affecting the capacity for DNA repair. Several studies have investigated this possibility; however, the conclusions remain controversial. Therefore, we did a systematic review and executed a meta-analysis to explore the association. From 56 studies, a total of 61 comparisons included 25,932 cases and 27,733 controls concerning the Lys751Gln polymorphism; 35 comparisons included 16,781 cases and 18,879 controls in the case of Asp312Asn were reviewed. In this analysis, small associations of the XPD Lys751Gln polymorphism with cancer risk for esophageal cancer [for Lys/Gln versus Lys/Lys: odds ratio (OR), 1.34; 95% confidence interval (95% CI), 1.10-1.64; for Gln/Gln versus Lys/Lys: OR, 1.61; 95% CI, 1.16-2.25] and acute lymphoblastic leukemia (for Gln/Gln versus Lys/Lys: OR, 1.83; 95% CI, 1.21-2.75) are revealed. Overall, individuals with the Gln/Gln genotype have a small cancer risk compared with Lys/Lys genotype for the reviewed cancer in total (OR, 1.10; 95% CI, 1.03-1.16). Subtle but significant cancer risk was observed for the XPD Asp312Asn polymorphism in bladder cancer (for Asp/Asn versus Asp/Asp: OR, 1.24; 95% CI, 1.06-1.46). No significant associations were found for other cancers separately and all the reviewed cancer in total assessed for the Asp312Asn polymorphism. Our study suggests that XPD is a candidate gene for cancer susceptibility regardless of environmental factors. (Cancer Epidemiol Biomarkers Prev 2008;17(3):507–17)
Does Breast Size Modify the Association between Mammographic Density and Breast Cancer Risk?
Authors: Stuedal Anne , Ma Huiyan , Bernstein Leslie , Pike Malcolm C. , Ursin Giske
Published: March 2008

Background: Both the absolute and the percent of mammographic density are strong and independent risk factors for breast cancer. Previously, we showed that the association between mammographic density and breast cancer risk tended to be weaker in African American than in White U.S. women. Because African American women have a larger breast size, we assessed whether the association between mammographic density and breast cancer was less apparent in large than in small breasts.

Methods: We assessed mammographic density on mammograms from 348 African American and 507 White women, 479 breast cancer patients and 376 control subjects, from a case-control study conducted in Los Angeles County. We estimated odds ratios (OR) for breast cancer with increasing mammographic density, and the analyses were stratified by mammographic breast area.

Results: Median breast size was 168.4 cm2 in African American women and 121.7 cm2 in White women (P for difference <0.001). For absolute density, adjusted ORs (95% confidence intervals) per increase of 10 cm2 were 1.32 (1.13-1.54), 1.14 (1.03-1.26), and 1.02 (0.98-1.07) in the first, second, and third tertiles of breast area, respectively (P for effect modification by breast area = 0.005). The results for percent density were similar although weaker; adjusted ORs per 10% increase (absolute value) in percent density were 1.22 (1.05-1.40), 1.22 (1.06-1.41), and 1.03 (0.90-1.18 P for effect modification by breast area = 0.34).

Conclusion: Our results indicate that the association between mammographic density and breast cancer may be weaker in women with larger breasts. (Cancer Epidemiol Biomarkers Prev 2008;17(3):621–7)
Multiple Diagnostic X-rays for Spine Deformities and Risk of Breast Cancer
Authors: Ronckers Cécile M. , Doody Michele M. , Lonstein John E. , Stovall Marilyn , Land Charles E.
Published: March 2008

Background: Ionizing radiation is a well-established human mammary carcinogen. Women historically monitored by radiography at young ages for abnormal spinal curvature are an exposed population suitable for investigating radiation-related risk and its variation by modifying factors. In this historic cohort, 95% of daily dose increments (when exposure to the breast occurred) were under 2.4 cGy, with mean 1.1 cGy.

Methods: A retrospective cohort of 3,010 women, diagnosed with spinal curvature between 1912 and 1965 in 14 U.S. pediatric orthopedic centers and who completed a questionnaire by telephone interview or mail survey in 1992, were studied for risk of breast cancer by radiation dose to the breast (mean, 12 cGy) after adjustment for established breast cancer risk factors.

Results: A borderline-significant radiation dose response (excess relative risk/Gy = 2.86; P = 0.058; one-tailed P = 0.029) was observed during 118,905 woman-years of follow-up (median, 35.5 years) based on 78 cases of invasive breast cancer. The dose response was significantly greater (P = 0.03) for women who reported a family history of breast cancer in first- or second-degree relatives (excess relative risk/Gy = 8.37; 95% confidence interval, 1.50-28.16). Radiation-related risk did not vary significantly by stage of reproductive development at exposure.

Conclusions: Assuming that repair of radiation-related DNA damage requires at most a few hours, our data argue against existence of a low-dose threshold on the order of 1 to 3 cGy for radiation exposure contributing to breast carcinogenesis. The possibility that a family history of breast cancer may have enhanced a carcinogenic radiation effect requires confirmation in other studies. (Cancer Epidemiol Biomarkers Prev 2008;17(3):605–13)
Postmenopausal Hormone Therapy and Lung Cancer Risk in the Cancer Prevention Study II Nutrition Cohort
Authors: Rodriguez Carmen , Spencer Feigelson Heather , Deka Anusila , Patel Alpa V. , Jacobs Eric J. , Thun Michael J. , Calle Eugenia E.
Published: March 2008

Background: Studies of postmenopausal hormone therapy and lung cancer incidence have reported positive, negative, and null associations. Most of these studies, however, have had limited ability to control rigorously for cigarette smoking or to examine risk separately by smoking status.

Methods: We examined the association between postmenopausal hormone therapy and lung cancer incidence by smoking status among 72,772 women in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate rate ratios (RR).

Results: During follow-up from 1992 to 2003, we identified 659 cases of incident lung cancer. Current use of any postmenopausal hormone therapy was significantly associated with decreased risk of incident lung cancer [multivariate RR, 0.76; 95% confidence interval (95% CI), 0.62-0.92]. Similar risk estimates were observed for unopposed estrogen use (RR, 0.76; 95% CI, 0.60-0.94) and for estrogen plus progestin (RR, 0.76; 95% CI, 0.57-1.01). Risk associated with current use of postmenopausal hormone therapy was decreased among never smokers (RR, 0.56; 95% CI, 0.33-0.95) as well as current smokers (RR, 0.76; 95% CI, 0.55-1.05) and former smokers (RR, 0.76; 95% CI, 0.58-0.99). Former hormone use was not associated with lung cancer. No trend with duration of hormone use was detected.

Conclusion: These results support the hypothesis that postmenopausal hormone therapy is associated with reduced risk of lung cancer, although the absence of a dose-response relationship weakens the evidence for causality. (Cancer Epidemiol Biomarkers Prev 2008;17(3):655–60)
Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China
Authors: Andreotti Gabriella , Chen Jinbo , Gao Yu-Tang , Rashid Asif , Chen Bingshu E. , Rosenberg Philip , Sakoda Lori C. , Deng Jie , Shen Ming-Chang , Wang Bing-Sheng , Han Tian-Quan , Zhang Bai-He , Yeager Meredith , Welch Robert , Chanock Stephen , Fraumeni Joseph F. , Hsing Ann W.
Published: March 2008

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by TaqMan assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% CI), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% CI, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% CI, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% CI, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct. (Cancer Epidemiol Biomarkers Prev 2008;17(3):525–34)
Genetic Polymorphisms and Head and Neck Cancer Outcomes: A Review
Authors: Hopkins Jessica , Cescon David W. , Tse Darren , Bradbury Penelope , Xu Wei , Ma Clement , Wheatley-Price Paul , Waldron John , Goldstein David , Meyer Francois , Bairati Isabelle , Liu Geoffrey
Published: March 2008

Head and neck cancer (HNC) patients have variable prognoses even within the same clinical stage and while receiving similar treatments. The number of studies of genetic polymorphisms as prognostic factors of HNC outcomes is growing. Candidate polymorphisms have been evaluated in DNA repair, cell cycle, xenobiotic metabolism, and growth factor pathways. Polymorphisms of XRCC1, FGFR, and CCND1 have been consistently associated with HNC survival in at least two studies, whereas most of the other polymorphisms have either conflicting data or were from single studies. Heterogeneity and lack of description of patient populations and lack of accounting for multiple comparisons were common problems in a significant proportion of studies. Despite a large number of exploratory studies, large replication studies in well-characterized HNC populations are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(3):490–9)
Prostate Cancer, Serum Parathyroid Hormone, and the Progression of Skeletal Metastases
Authors: Schwartz Gary G.
Published: March 2008

Bony metastases from prostate cancer are a significant cause of morbidity and mortality. These metastases are predominantly blastic (bone-forming) and commonly cause increased serum levels of parathyroid hormone (PTH) as calcium ions are transferred from serum into blastic bone. The epidemiologic and clinical significance of secondary hyperparathyroidism in advanced prostate cancer have not been widely appreciated. Prostate cancer bony metastases show increased expression of the PTH receptor (PTH-IR) and PTH promotes the growth and invasiveness of prostate cancer cells in bone. Thus, blastic metastases appear to induce a “vicious cycle” in which PTH resorbs normal bone to support the growth of blastic bone. Recognition of the potential role of PTH in the progression of skeletal metastases suggests novel opportunities for prostate cancer secondary prevention. In particular, we propose that suppressing serum PTH in advanced prostate cancer may reduce morbidity by decreasing fractures and pain caused by bone resorption and may reduce mortality by retarding the progression of metastatic disease. (Cancer Epidemiol Biomarkers Prev 2008;17(3):478–83)
Increased levels of circulating microparticles in patients with severe aortic valve stenosis
Authors: Sossong Verena , Helbing Thomas , Beyersdorf Friedhelm , Olschewski Manfred , Bode Christoph , Diehl Philipp , Nagy Ferenc , Moser Martin
Published: March 2008

The mechanisms of the progression of aortic valve stenosis are unknown. The involvement of mononuclear cells and of chronic systemic inflammation has been suggested by analysis of pathological specimens. We hypothesize that shear stress caused by the constricted aortic orifice contributes to systemic proinflammation by activation of circulating blood cells and thereby generation of microparticles. Using flow cytometry we analyzed 22 patients with severe aortic valve stenosis (AVS) and 18 patient controls for the generation of circulating microparticles from platelet-(PMPs: CD31+/CD61+ or CD62P+), leukocyte-(LMPs: CD11b+) and endothelial cell (EMPs: CD62E+) origin. Apart from the constricted valve orifice groups were similar. PMPs were increased in AVS patients and their number correlated with valvular shear stress. Monocytes were activated in AVS patients, an observation that was also reflected by increased numbers of LMPs and by the detection of PMP-monocyte conjugates. Furthermore, EMPs reflecting the activation of endothelial cells but also conferring systemic inflammatory activity were increased in AVS patients and correlated with the number of activated monocytes. In conclusion, we show that AVS is accompanied by increased levels of microparticles and that shear stress can induce the formation of microparticles. Based on our results and histologic findings of other investigators the speculation that shear stress related to aortic valve stenosis induces a vicious circle including the generation of PMPs, the subsequent activation of monocytes and LMPs and finally the activation of endothelial cells contributing to the progress of aortic valve stenosis appears to be justified.
Cleavage of factor XIII by human neutrophil elastase results in a novel active truncated form of factor XIII A subunit
Authors: Bagoly Zsuzsa , Fazakas Ferenc , Komáromi István , Haramura Gizella , Tóth Eszter , Muszbek László
Published: March 2008

The first step in the activation of plasma factor XIII (FXIII) is the cleavage of R37-G38 bond in FXIIIA subunit (FXIII-A) by thrombin, which makes the subsequent formation of an active transglutaminase possible. No active truncated form of FXIII-A, other than G38-FXIII-A, has been identified. In contrast to thrombin, which has a preference toward arginine residues, human neutrophil elastase (HNE) cleaves peptide bonds at small side-chain aliphatic amino acids, preferably at valine. As there are several valine residues close to the thrombin cleavage-site, we tested if an active truncated FXIII-A was formed during fragmentation of FXIII by HNE. It was demonstrated by Western blotting and transglutaminase assay that HNE induced a limited cleavage of FXIII-A resulting in the activation of both plasma and cellular FXIII; the maximal transglutaminase activities were 52.5% and 67.4% of thrombin-activated FXIII, respectively. After the relatively rapid activation a much slower inactivation occurred. HNE-activated FXIII cross-linked fibrin γ- and α-chains in the clot formed by batroxobin moojeni. MALDI-TOF analysis of the cleaved fragments and N-terminal Edman degradation of the truncated protein identified V39-N40 as the primary cleavagesite and N40-FXIII-A as the active form. No primary cleavage occurred at V34, V35, V47, V50 residues. FXIII-A V34L polymorphism, which increases the rate of FXIII-A cleavage by thrombin, was without effect on FXIII activation by HNE. Molecular modeling located the primary HNE cleavage-site in the middle of the flexible and accessible Q32-L45 loop and showed that other neighboring valine residues were in less favorable position.
Influence of coagulation factors and tissue factor concentration on the thrombin generation test in plasma
Authors: Pan-Petesch Brigitte , Arnaud Bertrand , Blouch Marie-Thérèse , Abgrall Jean-François , Duchemin Jérôme
Published: March 2008

The thrombin generation test is used to study coagulation in patients with haemorrhagic diseases or with high thrombotic risk. To our knowledge, this is the first study investigating the relative influence of coagulation factors on thrombin generation in plasma. The aim was to investigate the influence of coagulant factors, anticoagulant factors, and tissue factor (TF) on three parameters: endogenous thrombin potential (ETP), peak thrombin concentration, and lag time for the appearance of thrombin. At a low TF concentration, all factors except factor XI influenced thrombin generation. At a high TF concentration, only the factors of the extrinsic pathway exerted an influence. ETP and peak thrombin were linearly correlated to factor II concentration. Factor V and factor VII effects increased hyperbolically with factor concentration. The influence of factor X on thrombin generation depended onTF concentration. In the absence of factorVIII and factor IX, ETP fell to 60–70% of the normal when peak thrombin fell to 25–30% of the normal. Fibrinogen concentration influenced ETP and peak thrombin and decreasing fibrinogen levels shortened the lag time. As expected, decreasing antithrombin concentration caused dramatic increases in thrombin generation. Protein S prolonged the lag time, especially at a low TF concentration. No effect of protein C was observed, likely due to the absence of thrombomodulin. The thrombin generation test was more sensitive to factor deficiencies at low than at high TF concentration. ETP was not the most critical parameter for studying coagulation factor deficiencies. Instead, peak thrombin was the most sensitive parameter.
Dose-dependent thrombus resolution due to oral plasminogen activator inhibitor (PAI)-1 inhibition with tiplaxtinin in a rat stenosis model of venous thrombosis
Authors: Baxi Sanjiv , Crandall David , Meier Thomas , Wrobleski Shirley , Hawley Angela , Farris Diana , Elokdah Hassan , Sigler Robert , Schaub Robert , Wakefield Thomas , Myers Daniel
Published: March 2008

This study aimed to evaluate a small-molecule PAI-1 inhibitor (PAI-039; tiplaxtinin) in a rodent stenosis model of venous thrombosis in a two-phase experiment. Phase 1 determined the efficacy of tiplaxtinin against Lovenox (LOV), while phase 2 determined the dose-dependent efficacy. For both phases, drug treatment began 24 hours after surgically induced venous thrombosis and continued for four days. Phase 1 animals (n = 24) receiving low-dose (LD; 1 mg/kg oral gavage) PAI-1 inhibitor demonstrated a 52% decrease in thrombus weight (TW) versus controls (p < 0.05) with significant reductions in active plasma PAI-1, while the high-dose (HD; 10 mg/kg oral gavage) group demonstrated a 23% reduction in TW versus controls. Animals treated subcutaneously with LOV (3 mg/kg) showed a 39% decrease in TW versus controls (p < 0.05). Coagulation tests (aPTT and TCT) were significantly different in LOV compared to PAI-1 inhibitor groups. PAI-039 treatment was also associated with significantly increased return of inferior vena cava blood flow four days post-thrombosis versus controls (p < 0.05). In phase 2 (n = 30), TW was reduced from the 0.5 mg/kg to 5 mg/ kg experimental groups, with the 10 mg/kg group demonstrating a paradoxical increase. The 5 mg/kg group showed statistically significant decreases in TW versus controls after four treatment days (p < 0.05). This is the first study to demonstrate dose related effects of PAI-039 on increasing thrombus resolution and inferior vena cava blood flow without adverse effects on anti-coagulation in a rat stenosis model of venous thrombosis.
Microsomal Prostaglandin E
2
Synthase-1 Deletion Leads to Adverse Left Ventricular Remodeling After Myocardial Infarction
Authors: Degousee Norbert , Fazel Shafie , Angoulvant Denis , Stefanski Eva , Pawelzik Sven-Christian , Korotkova Marina , Arab Sara , Liu Peter , Lindsay Thomas F. , Zhuo Sun , Butany Jagdish , Li Ren-Ke , Audoly Laurent , Schmidt Ronald , Angioni Carlo , Geisslinger Gerd , Jakobsson Per-Johan , Rubin Barry B.
Published: March 2008

Background—

Pharmacological inhibition of cyclooxygenase-2 increases the risk of myocardial infarction (MI) and stroke. Microsomal prostaglandin (PG) E
2
synthase-1 (mPGES-1), encoded by the
Ptges
gene, functions downstream from cyclooxygenase-2 in the inducible PGE
2
biosynthetic pathway. We caused acute MI in

Ptges
+/+

and

Ptges
−/−

mice to define the role of mPGES-1 in cardiac ischemic injury.

Methods and Results—

Twenty-eight days after MI,

Ptges
−/−

mice develop more left ventricular (LV) dilation, have worse LV systolic and diastolic function, and have higher LV end-diastolic pressure than

Ptges
+/+

mice but have similar pulmonary wet-to-dry weight ratios, cardiac mass, infarct size, and mortality. The length-to-width ratio of individual cardiomyocytes is significantly greater in

Ptges
−/−

than

Ptges
+/+

mice after MI, a finding consistent with eccentric cardiomyocyte hypertrophy in

Ptges
−/−

mice. Expression of atrial natriuretic peptide, brain natriuretic peptide, and α- and β-myosin heavy chain, markers of ventricular hypertrophy, is higher in the LV of

Ptges
−/−

than

Ptges
+/+

mice after MI.

Ptges
+/+

mice express cyclooxygenase-2 and mPGES-1 protein in inflammatory cells adjacent to the infarct after MI but do not express these proteins in cardiomyocytes.

Ptges
−/−

mice express cyclooxygenase-2 in inflammatory cells adjacent to the infarct and do not express mPGES-1 in any cells in the heart. Levels of PGE
2
but not PGD
2
, thromboxane A
2
, PGI
2
, or PGF
2α
are higher in the infarct and LV remote from the infarct after MI in

Ptges
+/+

than

Ptges
−/−

mice.

Conclusions—

In

Ptges
+/+

mice, mPGES-1 in inflammatory cells catalyzes PGE
2
biosynthesis in the LV after MI. Deletion of mPGES-1 leads to eccentric cardiac myocyte hypertrophy, LV dilation, and impaired LV contractile function after acute MI.
Glucocorticoid-Related Signaling Effects in Vascular Smooth Muscle Cells
Authors: Molnar Gergö A. , Lindschau Carsten , Dubrovska Galyna , Mertens Peter R. , Kirsch Torsten , Quinkler Marcus , Gollasch Maik , Wresche Stefanie , Luft Friedrich C. , Muller Dominik N. , Fiebeler Anette
Published: March 2008

Mineralocorticoid receptor blockade protects from angiotensin II–induced target-organ damage. 11β-Hydroxysteroid dehydrogenase type 2 protects the mineralocorticoid receptor from activation by glucocorticoids; however, high glucocorticoid concentrations and absent 11β-hydroxysteroid dehydrogenase type 2 in some tissues make glucocorticoids highly relevant mineralocorticoid receptor ligands. We investigated the effects of corticosterone (10
−6
to 10
−12
mol/L) on early vascular mineralocorticoid receptor signaling by Western blotting, confocal microscopy, and myography. Corticosterone initiated extracellular signal–regulated kinase 1/2 phosphorylation in rat vascular smooth muscle cells at ≥10
−11
mol/L doses. Protein synthesis inhibitors had no effect, indicating a nongenomic action. Corticosterone also stimulated c-Jun N-terminal kinase, p38, Src, and Akt phosphorylation at 15 minutes and enhanced angiotensin II–induced signaling at 5 minutes. A specific epidermal growth factor receptor blocker, AG1478, as well as the Src inhibitor PP2, markedly reduced corticosterone-induced extracellular signal–regulated kinase 1/2 phosphorylation, as did preincubation of cells with the mineralocorticoid receptor antagonist spironolactone. Silencing mineralocorticoid receptor with small interfering RNA abolished corticosterone-induced effects. Corticosterone (10
−9
mol/L) enhanced phenylephrine-induced contraction of intact aortic rings. These effects were dependent on the intact endothelium, mineralocorticoid receptor, and mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase signaling. We conclude that corticosterone induces rapid mineralocorticoid receptor signaling in vascular smooth muscle cells that involves mitogen-activated protein kinase kinase/extracellular signal–regulated kinase–dependent pathways. These new mineralocorticoid receptor–dependent signaling pathways suggest that glucocorticoids may contribute to vascular disease via mineralocorticoid receptor signaling, independent of circulating aldosterone.
Modulation of Reflex Function by Endogenous Angiotensins in Older Transgenic Rats With Low Glial Angiotensinogen
Authors: Arnold Amy C. , Sakima Atsushi , Ganten Detlev , Ferrario Carlos M. , Diz Debra I.
Published: March 2008

Age-related impairments in baroreflex sensitivity in Sprague-Dawley rats are associated with low solitary tract nucleus content of angiotensin-(1-7). However, transgenic rats with low-brain angiotensinogen resulting from glial overexpression of an antisense oligonucleotide to angiotensinogen (ASrAOGEN) are spared age-related declines in cardiovascular function characteristic of Sprague-Dawley rats. We examine whether cardiovascular and reflex actions of angiotensin-(1-7) persist in the solitary tract nucleus of older (16 to 22 months) ASrAOGEN rats. Baroreflex sensitivity for control of heart rate and chemosensitive vagal afferent activation in response to phenylbiguanide were measured before and after bilateral microinjection of the angiotensin II type 1 receptor antagonist candesartan and angiotensin-(1-7) receptor antagonist (D-Ala
7
)-angiotensin-(1-7) in urethane/chloralose-anesthetized rats. In older anesthetized ASrAOGEN rats, candesartan had no effect, whereas (D-Ala
7
)-angiotensin-(1-7) significantly reduced baroreflex sensitivity (1.80±0.43 versus 0.50±0.17 ms/mm Hg). Phenylbiguanide responses were attenuated by injection of candesartan (−79±6 versus −55±12 mm Hg and −277±12 versus −156±27 bpm;
P
<0.05). In addition, resting blood pressure was reduced by injection of candesartan or (D-Ala
7
)-angiotensin-(1-7). Within the solitary tract nucleus of older ASrAOGEN rats, it appears that glial angiotensinogen is the main source of angiotensin II attenuation of baroreflex sensitivity; endogenous angiotensin-(1-7) from nonglial sources enhances baroreflex sensitivity; nonglial sources of angiotensin II contribute to chemosensitive vagal afferent activation; and receptors for both peptides modulate resting arterial pressure under anesthesia. These results suggest a novel mechanism for the preservation of baroreflex sensitivity during aging.
Does Space Matter?
Authors: Hannes Els , Janssens Davy , Wets Geert
Published: March 2008

This research project aims at revealing the variety of critical spatial factors in an individual's mental map that influence daily activity travel behavior. A qualitative travel survey and in-depth interviews are used to identify spatial factors that appear in respondents' travel mode decisions when discussing their daily activity space. Recorded interviews are processed through ATLAS.ti. First, representative If—Then (—Else) heuristics used by respondents are identified and framed within the daily activity travel decision process and classified in a script network view. In addition, the spatial elements occurring are indicated. To conclude, this article suggests a new “script” approach to grasp the behavioral mechanisms present in daily activity travel decisions and argues that further research along this line would contribute to the understanding of the impact of travel demand measures and its assessment in activity-based travel demand models by means of an agent-based computational process model.
International Organizations Count
Authors: Hafner-Burton Emilie M. , von Stein Jana , Gartzke Erik
Published: March 2008

This special issue seeks to move forward the development of an empirical research agenda that takes seriously the complexity of how international organizations (IOs) function and the need to study that complexity at all levels of analysis by using robust research tools. We advocate for a broad empirical research approach that molds and sharpens theories about IOs by conducting systematic tests in large-sample environments. Two themes create a common thread throughout this issue. First, shifting the focus from whether IOs matter to how they work requires acknowledgment of the contingency of cause and effect. A second common thread lies in the authors' treatment of IO membership as an aggregate phenomenon—that is, as a set of institutions and relationships evolving over time and with many members rather than as a single organization.
Power or Plenty
Authors: Hafner-Burton Emilie M. , Montgomery Alexander H.
Published: March 2008

Does the dramatic rise of the number of preferential trade agreements (PTAs) worldwide make economic sanctions more likely through increasing the leverage of the powerful and pitting states against each other in competition (power) or less likely through increasing the benefits of trade, resolving disputes, and promoting like-minded communities (plenty)? The authors offer the first systematic test of these propositions, testing hypotheses on sanctions onset using a data set of episodes from 1947 through 2000. In favor of the plenty argument, increases in bilateral trade do decrease sanctioning behavior; in favor of the power argument, an increase in the potential sanctioner's GDP or centrality in the network of all PTAs make sanctioning much more likely. However, mutual membership in PTAs has no direct effect on the propensity of states to sanction each other.
The Man Behind the Woman
Authors: Ezzedeen Souha R. , Ritchey Kristen Grossnickle
Published: March 2008

Little is known about the spousal support received by married executive women and the support behaviors that they value. This article details the results of a qualitative study of 20 senior and executive-level women, with the aim of understanding their received and valued spousal support. An inductive typology was developed through semistructured interviews of the supportive behaviors deemed general, most valued, and least valued, as well as those behaviors perceived as being unsupportive, across six categories: emotional support, help with household, help with family members, career support, esteem support, and husbands' career and lifestyle choices. This article concludes by contextualizing the results relative to existing research, discussing study implications and limitations, and presenting recommendations.
Succession Planning in Family-owned Businesses
Authors: Tatoglu Ekrem , Kula Veysel , Glaister Keith W.
Published: March 2008

A key issue for many family-owned businesses (FOBs) is intergenerational management succession.This article investigates the dynamics of the succession process for FOBs that have already taken the succession decision and have selected their successors.The primary goal of the study is to delineate the factors behind the succession process by investigating selection, training and entry mode of successors as well as the involvement of family members and stakeholders in the succession process. Data from the predecessors of 408 FOBs in Turkey reveals a number of insightful findings regarding major characteristics of the FOB succession process including the views of predecessors on the succession process, successor selection criteria and the post-succession period.This is the first systematic study to deal with the succession process in Turkish FOBs, which previously has been informed only by anecdotal evidence.
Regulating the `Animal Spirits' of Entrepreneurs?
Authors: Hirschsohn Philip
Published: March 2008

Despite a highly regulated economy under Apartheid, the espoused beliefs of South African entrepreneurs today are founded on Anglo-Saxon ideals of liberal markets and weak regulatory institutions.This belief system is confronted by an influential labour movement that initiated legislative reforms to transform labour market institutions towards a coordinated market economy model regulated by business, labour and the state. The country's skill development legislation aims to shift the low-wage, low-skill economy onto a growth path founded on the empowerment of workers into a skilled labour force by encouraging firms to increase their training expenditure. Case study evidence from food and beverages, manufacturing and services sectors suggests that SME approaches to training are not influenced by this legislation but by the requirements of the competitive business context, sector skill intensity and the entrepreneurs' business growth strategy. For SMEs the appropriateness of the new skill development framework to existing market conditions and institutional foundations is questioned.
Effect of the Temperature of Polyurethane Wet-Casting Membrane Formation on the Physico-Mechanical Properties
Authors: Oprea S. , Ciobanu C.
Published: March 2008

A series of polyurethane membranes were prepared by direct immersion of a polyurethane/dimethylformamide solution into a water bath at different temperatures. Depending on the temperature of the water immersion bath the films exhibited variations in morphology and mechanical properties. As the temperature of the immersion bath was increased, the membrane structure changed from a cellular to a particulate morphology. The properties of polyurethane membrane such as mechanical and gas permeability were measured. It is proposed that the change in membrane structure is due to the variation of polymer chain mobility, influenced by the water bath temperature, during membrane formation
Development and Validation of the Chinese Making Sense of Adversity Scale: Acculturative Stressors as an Example
Authors: Pan Jia-Yan , Fu Keung Wong Daniel , Kin Sun Chan  , Lai Wan Chan Cecilia
Published: March 2008

Objective: The objective of this study is to develop and validate the Chinese Making Sense of Adversity Scale (CMSAS) to measure the cognitive coping strategies that Chinese people adopt to make sense of adversity. Method: A 12-item CMSAS was developed by in-depth interview and item analysis. The scale was validated with a sample of 627 Chinese international students in Australia and Mainland Chinese students in Hong Kong. Results: Exploratory factor analysis identified two factors: making positive sense and making negative sense of adversity. The CMSAS exhibited high internal consistency reliability and good concurrent validity. Conclusion: The CMSAS is a reliable and valid instrument for measuring the coping strategies used by Chinese people to make sense of adversity. However, further validation of the scale is needed.
Orientations to Social Constructionism: Relationally Responsive Social Constructionism and its Implications for Knowledge and Learning
Authors: Cunliffe Ann L.
Published: March 2008

This article maps the various interests and orientations of social constructionism as a basis for: (1) situating work in the field, (2) understanding differences in its interests and scope, (3) making deliberate choices about our own approach to social constructionist research and (4) thinking about how these choices might play through our teaching. The article suggests that these orientations are based on various underlying assumptions about the nature of social reality, which influence how we conceptualize and study organizations and management. It offers an example of one such orientation—relationally responsive social constructionism—and explores its implications for knowledge and learning.