bluuebunny/crossref_metadata_2025 huggingface dataset:
Smoking and mortality from esophageal cancer in China: A large case‐control study of 19,734 male esophageal cancer deaths and 104,846 living spouse controls
Authors: Jiang Jing‐mei , Zeng Xian‐jia , Chen Jun‐shi , Ping‐zhao  , Li Jun‐yao , Zhang Kong‐lai , Wu Ya‐ping , Liu Bo‐qi
Published: April 2006

An innovative population‐based case‐control study was conducted in a national mortality survey to assess the hazards of tobacco use on esophageal cancer among Chinese men. Cases were 19,734 males aged 35 years or older, who died of esophageal cancer during 1986–1988. Controls were 104,846 male living spouses of the same age when their wife died (of any cause) during the same period in the same county or city. The absolute esophageal cancer death rates were higher in smokers than those in nonsmokers in all geographical groups. The relative risks for esophageal cancer were 1.88 (95% CI: 1.73–2.05) and 1.39 (95% CI: 1.28–1.50) in urban and rural men, respectively, after adjustment for other relevant covariates including age group (5 years) and locality. When the calculation was restricted to men aged 35–69, the risk ratios for current cigarette smokers increased significantly with increasing number of cigarettes smoked daily and duration of smoking. Tobacco use, in any form, is an important risk factor for esophageal cancer in Chinese men. Selecting living spouses as controls is a unique and useful approach in the design of case‐control studies of cigarette smoking. © 2006 Wiley‐Liss, Inc.
A microsatellite polymorphism in the heme oxygenase‐1 gene promoter is associated with risk for melanoma
Authors: Okamoto Ichiro , Krögler Julia , Endler Georg , Kaufmann Stefan , Mustafa Stefan , Exner Markus , Mannhalter Christine , Wagner Oswald , Pehamberger Hubert
Published: April 2006

Heme oxygenase‐1 (HO‐1) has been demonstrated to play an important role in the regulation of signaling systems, which are involved in the control of cell cycle progression and apoptosis. Recently, a (GT)n dinucleotide repeat polymorphism in the HO‐1 promoter was shown to modulate HO‐1 gene expression. Short (<25 GT) repeats are associated with an increased HO‐1 upregulation after stimulation than are longer repeats. Malignant melanoma (MM) is the most serious cutaneous malignancy with high tendency to aggressive growth and resistance to apoptosis. Therefore, we sought to study the influence of this polymorphism on the progression of MM. We determined the HO‐1 promoter genotype in 152 patients with MM and 398 healthy controls and studied their association in regard to susceptibility to MM, Breslow thickness and disease‐free survival. In our study, the homozygous short allele with <25 (GT)n repeats (S/S) was found more frequently in the melanoma group compared to the healthy control population (21 and 12%, respectively). The calculated risk for acquiring primary MM in S/S carriers was 2‐fold higher compared to those with L‐allele types (95% confidence interval: 1.2–2.4, p = 0.03). Additionally, the S/S genotype was significantly associated with primary tumors with deeper Breslow thickness compared to L‐allele (>25 repeats) carriers (mean Breslow thickness: 4.0 ± 2.9 mm versus 3.1 ± 1.7 mm, p = 0.03). These data suggest that HO‐1 might render a higher risk for MM in S/S genotype individuals and could represent an important candidate gene in the pathogenesis and growth of malignant melanoma. © 2006 Wiley‐Liss, Inc.
Monitoring of WT1‐specific cytotoxic T lymphocytes after allogeneic hematopoietic stem cell transplantation
Authors: Morita Yuriko , Heike Yuji , Kawakami Mami , Miura Osamu , Nakatsuka Shin‐ichi , Ebisawa Michiko , Mori Shin‐ichiro , Tanosaki Ryuji , Fukuda Takahiro , Kim Sung‐Won , Tobinai Kensei , Takaue Yoichi
Published: April 2006

Donor‐derived cytotoxic T lymphocytes (CTL) that respond to tumor antigens emerge after hematopoietic stem cell transplantation (HSCT), particularly in association with the status of immune recovery. To analyze the frequency of CTL against PR1, PRAME and WT1 after HSCT, a tetramer‐based analysis was performed in 97 samples taken from 35 patients (9 AML, 11 MDS, 2 CML, 4 ALL, 7 lymphoma and 2 renal cell carcinoma [RCC]) with the HLA‐A02 phenotype. Regarding PR1, only 1 sample showed the presence of tetramer‐positive cells (0.04%/lymphocyte). Similarly, in PRAME, only 10 of 97 samples were sporadically positive with low titers. For WT1, positive results were detected in 39 of 97 samples and 7 (2 CML, 1 ALL, 2 lymphoma and 2 RCC) patients clearly showed positive results more than once. On the basis of these results, we performed serial analyses of WT1‐specific CTL during the clinical course in 2 patients with RCC, who underwent HSCT with a reduced‐intensity regimen, to examine the precise correlation between the kinetics of CTL, the occurrence of GVHD and the observed clinical response. A higher positive rate for WT1‐specific CTL and a correlation with the clinical response suggest that WT1 may be a useful antigen for a wider monitoring application. © 2006 Wiley‐Liss, Inc.
The structure of the bond between bone and porous silicon‐substituted hydroxyapatite bioceramic implants
Authors: Porter Alexandra E. , Buckland Tom , Hing Karin , Best Serena M. , Bonfield William
Published: April 2006

The significance of micrometer‐sized strut porosity in promoting bone ingrowth into porous hydroxyapatite (HA) scaffolds has only recently been noted. In this study, silicon‐substituted HA (0.8 wt % Si‐HA) with approximately 8.5% of the total porosity present as microporosity within the struts of the implant was prepared for high‐resolution transmission electron microscopy (HR‐TEM) via both ultramicrotomy and focused ion beam milling. Between the struts of the porous Si‐HA, pores with varying shapes and sizes (1–10 μm in diameter) were characterized. Within the struts, the Si‐HA contained features such as grain boundaries and triple‐junction grain boundaries. Bone ingrowth and dissolution from a Si‐HA implant were studied using HR‐TEM after 6 weeks in vivo. Minor local dissolution occurred within several pores within the struts. Organized, mineralized collagen fibrils had grown into the strut porosity at the interface between the porous Si‐HA implant and the surface of the surrounding bone. In comparison, deeper within the implant, disorganized and poorly mineralized fibers were observed within the strut porosity. These findings provide valuable insight into the development of bone around porous Si‐HA implants. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Polymethylmethacrylate particles inhibit osteoblastic differentiation of bone marrow osteoprogenitor cells
Authors: Chiu Richard , Ma Ting , Smith R. Lane , Goodman Stuart B.
Published: April 2006

Aseptic implant loosening of total joint replacements often results from particle‐mediated bone loss, which may be a combined effect of osteolysis and suppressed bone formation. Bone regeneration in the prosthetic bed depends on the activity of osteoblasts and their differentiation from osteoprogenitors in the bone marrow. This study investigated the effects of polymethylmethacrylate (PMMA) particles on the ability of bone marrow osteoprogenitors to differentiate into osteoblasts in vitro. Murine bone marrow cells challenged with PMMA particles on the first day of differentiation in osteogenic medium showed a dose‐dependent decrease in osteoprogenitor proliferation, alkaline phosphatase expression, and mineralization. Undifferentiated bone marrow cells pretreated with PMMA particles in nonosteogenic medium for 5 days also showed a dose‐dependent loss in osteogenic potential, which was sustained throughout subsequent growth in particle‐free, osteogenic medium. Bone marrow cells challenged with PMMA particles after the fifth day of differentiation in osteogenic medium showed significant reductions in cellular proliferation, but not alkaline phosphatase expression and mineralization, indicating that bone marrow cells were most sensitive to particle treatment during the first 5 days of differentiation. This study demonstrated that PMMA particles inhibit osteoblastic differentiation of bone marrow osteoprogenitor cells, which may contribute to periprosthetic bone loss and implant failure. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Intra‐ and intermolecular interactions between cyclic‐AMP receptor protein and DNA: Ab initio fragment molecular orbital study
Authors: Fukuzawa Kaori , Komeiji Yuto , Mochizuki Yuji , Kato Akifumi , Nakano Tatsuya , Tanaka Shigenori
Published: April 2006

The ab initio fragment molecular orbital (FMO) calculations were performed for the cAMP receptor protein (CRP) complexed with a cAMP and DNA duplex to elucidate their sequence‐specific binding and the stability of the DNA duplex, as determined by analysis of their inter‐ and intramolecular interactions. Calculations were performed with the AMBER94 force field and at the HF and MP2 levels with several basis sets. The interfragment interaction energies (IFIEs) were analyzed for interactions of CRP–cAMP with each base pair, DNA duplex with each amino acid residue, and each base pair with each residue. In addition, base–base interactions were analyzed including hydrogen bonding and stacking of DNA. In the interaction between DNA and CRP–cAMP, there was a significant charge transfer (CT) from the DNA to CRP, and this CT interaction played an important role as well as the electrostatic interactions. It is necessary to apply a quantum mechanical approach beyond the “classical” force‐field approach to describe the sequence specificity. In the DNA intramolecular interaction, the dispersion interactions dominated the stabilization of the base‐pair stacking interactions. Strong, attractive 1,2‐stacking interactions and weak, repulsive 1,3‐stacking interactions were observed. Comparison of the intramolecular interactions of free and complexed DNA revealed that the base‐pairing interactions were stronger, and the stacking interactions were weaker, in the complexed structure. Therefore, the DNA duplex stability appears to change due to both the electrostatic and the CT interactions that take place under conditions of DNA–CRP binding. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 948–960, 2006
Rapidly convergent procedure to solve the density profile equation in the classical density functional theory
Authors: Zhou Shiqi
Published: April 2006

An efficient recursive procedure to solve the density profile equation in the classical density functional theory (DFT) using an inverse Broyden method is described. The present iterative procedure is free of calculation of the Jacobian matrix, and its inversion unavoidable for the well‐known Newton–Raphson (NR) method and its variants. Numerical calculation indicates that only the approximate solution and iterative matrix of the lower bulk density case are employed as the corresponding initial guesses of the higher bulk density case, the present recursive procedure can converge quickly to the physical solution with an accuracy of ε = 10−14; thererfore, the procedure provides an efficient numerical algorithm for the theory in which acquirement of a density profile of high accuracy is a key step. Extensive numerical calculation shows the advantage of the present inverse Broyden method over Broyles' mixing procedure and a modified Powell hybrid algorithm (a variation of the NR method). © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 941–947, 2006
Determination of the ΔpKa between the active site cysteines of thioredoxin and DsbA
Authors: Carvalho Alexandra T. P. , Fernandes P. A. , Ramos Maria J.
Published: April 2006

Thioredoxin superfamily members share a considerable degree of structural similarity, with a conserved CXiXjC motif at the active site, where C stand for two cysteines that alternate between a reduced thiol and oxidized disulfide states, and Xiand Xj are two amino acids different in each family member. Despite these similarities, they display very different redox potentials and pKas for the active site dithiol, and fulfill different physiological roles. Thioredoxin, for example, promotes the reduction of disulfide bonds, while DsbA promotes their oxidation in prokaryotic cells. The factors that promote these differences are still not fully understood. However, it is generally accepted that the different stabilities of the redox active disulfide bond depends on the degree of stabilization, in the reduced state, of the thiolate of one of the active site cysteines (nucleophilic cysteine). In this work we have used QM/MM methods to compare and characterize the active site dithiols of both enzymes, and to shed some light on the structural features responsible for the large differences in pKa and redox potential between two homologous enzymes, thioredoxin and DsbA. We have also analyzed the main factors pointed out in the literature as responsible for their different properties. We obtained the value of 4.5 for pKa difference (ΔpKa) between the nucleophilic cysteines of both enzymes, which is in excellent agreement with most of the experimental values. Additionally, we found that the principal differentiating factor responsible for this observed ΔpKa are the α2‐alpha helices, which greatly contribute to the mentioned value, by stabilizing the DsbA thiolate in a much greater extend than the thioredoxin thiolate. A double mutation of the conserved residues Asp26 and Lys57, in thioredoxin, and Glu24 Lys58, in DsbA, by alanines did not change the ΔpKa value; this supports the hypothesis that these residues are not involved in the differentiation of the properties of the active centre dithiol. However, we found out that these residues are important for the stabilization of the nucleophilic thiolate. The Xi and Xj residues also do not seem to promote the stabilization of the thiolates. In fact, the corresponding double alanine mutants are more stable than the wild‐type enzymes. However, these residues are involved in the differentiation between thioredoxin and DsbA, stabilizing the DsbA thiolate by a larger extent than the thioredoxin thiolate. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 966–975, 2006
On the joint time‐frequency characteristics of chemical oscillations
Authors: Darowicki K. , Felisiak W.
Published: April 2006

A method of time‐frequency transformations of nonstationary signals has been discussed and applied to the analysis of oscillatory Belousov—Zhabotinsky (BZ) reaction. Selected registers of BZ reactions, that represent regular and complex dynamic behavior, have been submitted to the detailed spectral analysis using the short time Fourier transform (STFT). It has been demonstrated that the STFT is an accurate and suitable method for decomposition of chemical oscillations in the joint time and frequency domain. The energy distribution via STFT, presented in this article, revealed some specific characteristics of transitions between different regimes in the closed system of BZ reaction. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 961–965, 2006
Phosphorylation regulates Myc expression via prolonged activation of the mitogen‐activated protein kinase pathway
Authors: Wang Ziqiu , Ge Lisheng , Wang Meifang , Carr Brian I.
Published: April 2006

We previously showed that prolonged and strong ERK phosphorylation induced by Compound 5 (Cpd 5), a Cdc25A protein phosphatase inhibitor, was involved in its mechanism of cell growth inhibition. To study the relationship between ERK phosphorylation and cell growth inhibition, we used Cpd 5 as a tool to investigate ERK‐regulated c‐Myc expression in Hep3B hepatoma cells. We found that ERK phosphorylation caused by Cpd 5 induced c‐Myc phosphorylation, but suppressed c‐Myc expression at the mRNA and protein levels. Furthermore, Cpd 5 inhibited c‐Myc transcriptional activity and DNA binding ability, and this inhibition was antagonized by ERK kinase (MEK) inhibitor U‐0126, implying that the ERK pathway was involved in regulating c‐Myc expression. Since the participation of c‐Myc protein in transcription requires its dimerization with Max protein, we examined the Myc‐Max association in Cpd 5‐treated cells and found that Cpd 5 suppressed Myc‐Max dimerization. Transfection of Hep3B cells with mutated ERK (T188A/Y190F), which has lost its dual‐phosphorylation sites, attenuated the actions of Cpd 5 on Myc‐Max association. To further demonstrate whether Myc phosphorylation by Cpd 5‐induced ERK activation was able to directly regulate c‐myc gene expression, a chromatin immunoprecipitation (ChIP) assay was used to examine the binding of phospho‐Myc to the c‐myc promoter region. We found that phospho‐Myc induced by Cpd 5 had lost its ability to bind to the c‐myc promoter, whereas MEK inhibitor U‐0126 antagonized this inhibitory effect. These data suggest that an increase in c‐Myc phosphorylation in response to prolonged ERK phosphorylation negatively auto‐regulates c‐Myc gene expression, leading to the suppression of its target gene expression and cell cycle block. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Impact of reliance on CT pulmonary angiography on diagnosis of pulmonary embolism: A Bayesian analysis
Authors: Ranji Sumant R. , Shojania Kaveh G. , Trowbridge Robert L. , Auerbach Andrew D.
Published: April 2006

BACKGROUND

Spiral computed tomographic pulmonary angiography (CTPA) has become the primary test used to investigate suspected pulmonary embolism (PE) at many institutions, despite uncertainty regarding its sensitivity and specificity. Although CTPA‐based diagnostic algorithms focus on minimizing the false‐negative rate, we hypothesized that increasing use of CTPA also might lead to false‐positive diagnoses.

OBJECTIVE

Determine the frequency of possible false‐positive diagnoses of PE when CTPA is the primary diagnostic test.

DESIGN

Retrospective cohort study.

SETTING

Two academic teaching hospitals.

PARTICIPANTS

322 patients with suspected PE evaluated with CTPA.

MEASUREMENTS

We used a validated prediction rule to determine the pretest probability of PE in each patient. We combined these pretest probabilities with published estimates of CTPA test characteristics to generate expected posttest probabilities of PE. We compared these posttest probabilities to actual treatment decisions to determine the rate of false‐positive diagnoses of PE.

RESULTS

Among 322 patients investigated for PE, 37 (12%) had high pretest probability, 101 (32%) moderate, and 184 (57%) low. CT scans were interpreted as positive for PE in 57 patients (17.8%). Regardless of the pretest probability of PE, 96.5% of patients with a positive CTPA were treated with anticoagulants. Even under an optimistic assumption of CTPA test characteristics, as many as 25.4% of these patients may have been treated unnecessarily as a result of a false‐positive diagnosis. Most of these patients had a low pretest probability of PE.

CONCLUSIONS

Failure to utilize Bayesian reasoning when interpreting CTPA may lead to false‐positive diagnoses of pulmonary embolism in a substantial proportion of patients. Journal of Hospital Medicine 2006;1:81–87. © 2006 Society of Hospital Medicine
Topography and recent winter rainfall regime change in temperate Western European areas: a case study in the Rhine‐Meuse basin
Authors: Gilles Drogue , Christian Wagner , Nicole Mahr , Lucien Hoffmann , Laurent Pfister
Published: April 2006

Earlier trend analyses on rainfall series have clearly shown that the winter rainfall regime has changed since World War II over Northwestern Europe as a consequence of an enhanced westerly atmospheric circulation. However, few studies have been conducted on the potential link between the spatial variability of winter rainfall regime change and the topography. In the present study, a time series analysis of winter rainfall due to atmospheric westerly fluxes is performed and related to the topography of the middle Rhine‐Meuse area. The resulting geographical patterns show a zonal anisotropism of the winter rainfall regime change implying an intensification of horizontal rainfall gradients. More contrasted westerly winter rainfall amounts are observed in mountainous areas during the post‐1979 period following the changing‐point year of atmospheric circulation over Northwestern Europe. Copyright © 2006 Royal Meteorological Society.
Relevance of Osteoinductive Biomaterials in Critical‐Sized Orthotopic Defect
Authors: Habibovic Pamela , Yuan Huipin , van den Doel Mirella , Sees Tara M. , van Blitterswijk Clemens A. , de Groot Klaas
Published: April 2006

Several publications have shown the phenomenon of osteoinduction by biomaterials to be real. However, whether the ability of a biomaterial to initiate bone formation in ectopic implantation sites improves the performance of such osteoinductive biomaterial in clinically relevant orthotopic sites remains unclear. No studies have been published in which osteoinductive potential of a biomaterial is directly related to its performance orthotopically. In this study, we compared osteoinductive and nonosteoinductive biphasic calcium–phosphate (BCP) ceramics ectopically and in a clinically relevant critical‐sized orthotopic defect in goats. The two materials, BCP1150 and BCP1300, had similar chemical compositions, crystallinities, and macrostructures, but their microstructures differed significantly. BCP1150, sintered at a lower temperature, had a large amount of micropores, small average crystal size, and hence a high specific surface area. In contrast, BCP1300, with few micropores, had a significantly lower specific surface area as compared to BCP1150. Twelve‐week intramuscular implantation in goats (n = 10) showed that bone was induced in all BCP1150 implants, while no signs of bone formation were found in any of the BCP1300 implants. After 12 weeks of implantation in a bilateral critical‐sized iliac wing defect in the same goats, BCP1150 showed significantly more bone than BCP1300. In addition, the analysis of fluorochrome markers, which were administered to the animals 4, 6, and 8 weeks after implantation to follow the bone growth dynamics, showed an earlier start of bone formation in BCP1150 as compared to BCP1300. Significantly better performance of an osteoinductive ceramic in a critical‐sized orthotopic defect in a large animal model in comparison to a nonosteoinductive ceramic suggests osteoinduction to be clinically relevant. Further improvement of material osteoinductive properties is thus a significant step forward in the search for alternatives for autologous bone graft. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures
Authors: Hildebrand Kevin A. , Zhang Mei , Hart David A.
Published: April 2006

To evaluate changes in matrix molecules of the joint capsule, the right knees of 24 skeletally mature female NZW rabbits were immobilized while the contralateral limb served as an unoperated control. The immobilization was discontinued at 8 weeks and the rabbits were divided among four groups (n = 6) based on the number of weeks the right knees were remobilized: 0, 8, 16, or 32. Three rabbits (six knees) that did not have operations provided normal control joint capsules. The mRNA levels for collagen types I, II, and III, and MMP‐1 and ‐13 were significantly increased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. In contrast, the mRNA levels for TIMP‐1, ‐2, and ‐3 were decreased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. The mRNA levels for lumican and decorin were increased in the joint capsules of the contracture knees in all groups when compared to normal capsules. Many of the changes observed in this animal model are similar to those observed in human joint capsules from posttraumatic elbow contractures, supporting the value of this rabbit model. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Raman spectral study on the thermal stability of Ni/Zr/Ni/Si and Ni/Co/Ni/Si structures
Authors: Shao Jia , Lu Jianzheng , Huang Wei , Gao Yuzhi , Zhang Lichun , Zhang Shu‐Lin
Published: April 2006

Nickel silicide is becoming an important candidate material for the future generation of complementary metal‐oxide semiconductor (CMOS) devices and nanowire hetero‐structures. The Raman spectral measurement demonstrates quickly and nondestructively that instead of the more expensive Ni(Pt)Si sandwich structure, a new Ni/Zr/Ni/Si structure can raise the temperature of thermal stability from 650 °C to above 800 °C, thereby helping to improve device technology. Copyright © 2006 John Wiley & Sons, Ltd.
Distribution of co‐activators CBP and p300 during mouse oocyte and embryo development
Authors: Kwok Roland P.S. , Liu Xiao‐Tie , Smith Gary D.
Published: April 2006

cAMP response element binding protein (CREB)‐binding protein (CBP) and p300 are two structurally related transcriptional co‐activators that activate expression of many eukaryotic genes. Current dogma would suggest that these transcriptional co‐activators have similar mechanisms of transcription regulation. Studies of CBP or p300 homozygotic mouse mutants indicate that normal embryogenesis requires the existence of both factors. However, whether this is indicative of a dosage effect of these two proteins, or whether these proteins play different roles in mouse embryo development is not clear. Here we demonstrated that both factors are first found in the cytoplasm of oocytes within primordial follicles, and that they enter into the oocyte nucleus at different stages of oocyte growth, suggesting that they may play different roles in gene expression during oocyte growth and development. Consistent with this model, in the pre‐implantation mouse embryos, from the two‐cell stage to the blastocyst stage, the localizations of CBP and p300 are different, at times opposite, indicating that CBP and p300 also have different functions in early mouse embryogenesis. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
hCG‐dependent regulation of angiogenic factors in human granulosa lutein cells
Authors: Phan B. , Rakenius A. , Pietrowski D. , Bettendorf H. , Keck C. , Herr D.
Published: April 2006

As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases‐1 (TIMP‐1), Leptin, connective tissue growth factor (CTGF), meningioma‐associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP‐1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Study of the polyol pathway in the porcine epididymis
Authors: Pruneda Anna , Pinart Elisabet , Bonet Sergi , Yeung Ching‐Hei , Cooper Trevor G.
Published: April 2006

Concentrations of D‐glucose, D‐fructose and D‐sorbitol were quantified in porcine epididymal fluid by spectrofluorimetric assays and aldose reductase (AR) and sorbitol dehydrogenase (SDH) were located immunohistochemically in the epididymal epithelium. Glucose and fructose concentrations were low (<1 mM) and decreased in the cauda whereas sorbitol concentration (4–7 mM) was rather uniform along the duct. AR was luminally located on microvilli in the caput and corpus with less presence distally and was present in the lumen. SDH was present apically and basally in epithelial cells throughout the epididymis and in the lumen. The observations are consistent with diffusion of circulating glucose into the lumen, its conversion via AR to sorbitol which accumulates in the lumen and the action of SDH on sorbitol to produce fructose. Sperm metabolism of glucose and fructose may explain their lower concentrations in the cauda and sorbitol could be a metabolic substrate or osmolyte required for volume regulation. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Tektin 4 is located on outer dense fibers, not associated with axonemal tubulins of flagella in rodent spermatozoa
Authors: Iida Hiroshi , Honda Yoshiko , Matsuyama Takuya , Shibata Yosaburo , Inai Tetsuichiro
Published: April 2006

Tektins, which are thought to be the constitutive proteins of microtubules in cilia, flagella, basal bodies, and centrioles, have been reported to be involved in the stability and structural complexity of axonemal microtubules. Four types of mammalian Tektins have been reported, and at least two types of Tektins, Tektin 2 and Tektin 4, have been verified to be present in sperm flagella. To elucidate the molecular localization of Tektin 4 in flagella of rodent spermatozoa, we performed immunocytochemistry, fractionation study followed by immunoblot analysis, and immunogold electron microscopy. Confocal laser scanning microscopy and immunogold electron microscopy indicated that Tektin 4 was associated with outer dense fibers (ODFs) in both the middle and principal piece of flagella in rat and mouse spermatozoa. Tektin 4 in rat spermatozoa is completely released by 6 M urea treatment, but not extracted by 1% Triton X‐100 and 0.6 M potassium thiocyanate. Pre‐embedding immunoelectron microscopy demonstrated that Tektin 4 located on the abaxial (convex) surface of ODFs in flagella, not associate with axonemal microtubules. Our data strongly suggested that Tektin 4 is not associated with axonemal tubulins but an ODFs‐affiliated molecule in rodent spermatozoa. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Effect of sperm DNA vaccine on fertility of female mice
Authors: Naz Rajesh K.
Published: April 2006

Our laboratory has identified a sperm‐specific dodecamer peptide sequence, designated as YLP12, vaccination with which causes a long‐term reversible immunocontraceptive effect in female mice. In the present study, the effects of YLP12 DNA vaccine were examined. YLP12 36 bp cDNA was cloned into pVAX1 vector to prepare the DNA vaccine. Two additional vaccine constructs were made by in frame cloning of one and two CpG repeats in the YLP12‐cDNA vaccine. Five groups of female mice were immunized intradermally by using gene gun with YLP12‐cDNA, YLP12‐cDNA‐CpG, YLP12‐cDNA‐CpG‐CpG, YLP12‐cDNA mixed with exogenous synthetic CpG oligodeoxynucleotide (ODN), or vector DNA alone, respectively. Vaccination with all three constructs and the YLP12 vaccine mixed with exogenous ODN raised antibody response both in the sera as well as locally in the vaginal tract. There was no antibody response in the mice injected with the vector alone. In sera, the highest titers were obtained for the IgG class for all constructs and formulation followed by IgA class. In vaginal washings the highest titers were obtained for the IgA class followed by IgG class. Within the IgG class, the titers for the IgG2a subclass were significantly greater than the IgG1 subclass. Immunization with all constructs and formulation caused a significant (P < 0.05 to <0.001) reduction (20–43%) in fertility of female mice. The highest reductions were seen in mice immunized with YLP12‐cDNA‐CpG‐CpG (two repeats) (43% reduction) and with the YLP12 vaccine administered with exogenous CpG ODN (42% reduction). T lymphocytes obtained from DNA‐vaccinated mice showed clearly distinguished comparative RT‐PCR analysis of cytokine mRNA expression for Th1 and Th2 immune responses compared to T lymphocytes obtained from control animals injected with vector DNA. Expression of both Th1 cytokines (IL‐2 and IFN‐gamma) and Th2 cytokines (IL‐4 and IL‐10) was enhanced after DNA vaccination as compared to controls, with a bias towards Th1 response. The immunocontraceptive effects were long‐lasting observed up to 1.3 years of the observation period and increased with time. These novel findings indicate that the intradermal immunization with a sperm‐specific DNA vaccine causes a long‐term circulating and local immune response resulting in immunocontraceptive effects in female mice. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Electron paramagnetic resonance imaging of tumor hypoxia: Enhanced spatial and temporal resolution for in vivo pO2 determination
Authors: Matsumoto Ken‐ichiro , Subramanian Sankaran , Devasahayam Nallathamby , Aravalluvan Thirumaran , Murugesan Ramachandran , Cook John A. , Mitchell James B. , Krishna Murali C.
Published: April 2006

The time‐domain (TD) mode of electron paramagnetic resonance (EPR) data collection offers a means of estimating the concentration of a paramagnetic probe and the oxygen‐dependent linewidth (LW) to generate pO2 maps with minimal errors. A methodology for noninvasive pO2 imaging based on the application of TD‐EPR using oxygen‐induced LW broadening of a triarylmethyl (TAM)‐based radical is presented. The decay of pixel intensities in an image is used to estimate T, which is inversely proportional to pO2. Factors affecting T in each pixel are critically analyzed to extract the contribution of dissolved oxygen to EPR line‐broadening. Suitable experimental and image‐processing parameters were obtained to produce pO2 maps with minimal artifacts. Image artifacts were also minimized with the use of a novel data collection strategy using multiple gradients. Results from a phantom and in vivo imaging of tumor‐bearing mice validated this novel method of noninvasive oximetry. The current imaging protocols achieve a spatial resolution of ∼1.0 mm and a temporal resolution of ∼9 s for 2D pO2 mapping, with a reliable oxygen resolution of ∼1 mmHg (0.12% oxygen in gas phase). This work demonstrates that in vivo oximetry can be performed with good sensitivity, accuracy, and high spatial and temporal resolution. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
The bi‐criteria doubly weighted center‐median path problem on a tree
Authors: Puerto J. , Rodríguez‐Chía A.M. , Tamir A. , Pérez‐Brito D.
Published: April 2006

Given a tree network T with n nodes, let 𝒫L be the subset of all discrete paths whose length is bounded above by a prespecified value L. We consider the location of a path‐shaped facility P ∈ 𝒫L, where customers are represented by the nodes of the tree. We use a bi‐criteria model to represent the total transportation cost of the customers to the facility. Each node is associated with a pair of nonnegative weights: the center‐weight and the median‐weight. In this doubly weighted model, a path P is assigned a pair of values (MAX(P),SUM(P)), which are, respectively, the maximum center‐weighted distance and the sum of the median‐weighted distances from P to the nodes of the tree. Viewing 𝒫L and the planar set {(MAX(P),SUM(P)) : P ∈ 𝒫L} as the decision space and the bi‐criteria or outcome space respectively, we focus on finding all the nondominated points of the bi‐criteria space. We prove that there are at most 2n nondominated outcomes, even though the total number of efficient paths can be Ω(n2), and they can all be generated in O(n log n) optimal time. We apply this result to solve the cent‐dian model, whose objective is a convex combination of the weighted center and weighted median functions. We also solve the restricted models, where the goal is to minimize one of the two functions MAX or SUM, subject to an upper bound on the other one, both with and without a constraint on the length of the path. All these problems are solved in linear time, once the set of nondominated outcomes has been obtained, which in turn, results in an overall complexity of O(n log n). The latter bounds improve upon the best known results by a factor of O(log n). © 2006 Wiley Periodicals, Inc. NETWORKS, Vol. 47(4), 237–247 2006
The emergence and future of the modern women's philanthropy movement
Authors: Shaw‐Hardy Sondra
Published: April 2006

Why did the modern women's philanthropy movement come about, and how did it happen? Who was involved, and what were their motivations? What does this new way of giving and fundraising mean for the future of philanthropy?
Women executives and business owners: A new philanthropy
Authors: Jasper Cynthia R.
Published: April 2006

Philanthropic giving of both time and money is increasingly an important part of the expectations of the role of businesswomen. Women in the corporate world are emerging as some of the most generous and creative new philanthropists.
The dynamics of women and family philanthropy
Authors: Remmer Ellen E.
Published: April 2006

The stewardship of wealth is key to the growth of many family foundations. What is women's important role in this trend? How is women's leadership affecting family philanthropy?
Giving circles: A powerful vehicle for women
Authors: Bearman Jessica , Beaudoin‐Schwartz Buffy , Rutnik Tracey A.
Published: April 2006

A powerful new vehicle for women as philanthropists has exploded across the nation. An outgrowth of quilting bees and book and investment clubs reflect women's growing economic power and concern for their communities.
Women's volunteerism and philanthropy at Princeton University
Authors: Minter Michele
Published: April 2006

This chapter explains the dramatic fundraising results that can occur by involving women as volunteers, donors, and leaders.
Investigation of fracture mechanism on liquid crystalline epoxy networks arranged by a magnetic field
Authors: Harada Miyuki , Akamatsu Naoki , Ochi Mitsukazu , Tobita Masayuki
Published: April 2006

A liquid crystalline epoxy resin was cured under non‐ and 10T‐magnetic fields, and polydomain and monodomain networks were obtained, respectively. The fracture toughness of these systems was evaluated and it was clarified that the toughness of the magnetic field system showed a higher value. To investigate the toughening mechanism, polarized micro FTIR measurements were carried out. As a result, it was clarified that their mechanisms were quiet different. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1406–1412, 2006
Unfolding transition state and intermediates of the tumor suppressor p16INK4a investigated by molecular dynamics simulations
Authors: Interlandi Gianluca , Settanni Giovanni , Caflisch Amedeo
Published: April 2006

The ankyrin repeat is one of the most common protein motifs and is involved in protein–protein interactions. It consists of 33 residues that assume a β‐hairpin helix‐loop‐helix fold. Mutagenesis and kinetic experiments (Φ‐value analysis of the folding transition state) have shown that the tumor suppressor p16INK4a, a four‐repeat protein, unfolds sequentially starting from the two N‐terminal repeats. Here, the flexibility of p16INK4a at room temperature and its unfolding mechanism at high temperature have been investigated by multiple molecular dynamics runs in explicit water for a total simulation time of 0.65 μs. The transition state ensemble (TSE) of p16INK4a was identified by monitoring both the deviation from the experimental Φ values and sudden conformational changes along the unfolding trajectories. Conformations in the TSE have a mainly unstructured second repeat whereas the other repeats are almost completely folded. A rigid‐body displacement of the first repeat involving both a rotation and translation is observed in all molecular dynamics simulations at high temperature. The Trp15, Pro75, and Ala76 side‐chains are more buried in the TSE than the native state. The sequential unfolding starting at the second repeat is in agreement with the mutagenesis studies whereas the displacement of the first repeat and the presence of nonnative interactions at the TSE are simulation results which supplement the experimental data. Furthermore, the unfolding trajectories reveal the presence of two on‐pathway intermediates with partial α‐helical structure. Finally, on the basis of the available experimental and simulation results we suggest that in modular proteins the shift of the folding TSE toward the native structure upon reduction of the number of tandem repeats is consistent with the Hammond effect. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Xα‐DVM modelling of oxygen transport in YBa2Cu3O7‐δ and SrFeO3
Authors: Yuryeva Elmira I.
Published: April 2006

The reasons for oxygen transport in YBa2Cu3O7‐δ and SrFeO3 were investigated, using the Xα‐discrete variation method. Reduced binding energy and other parameters of the electronic energy structure were calculated for a number of crystal fragments within the T and O phases of YBa2Cu3O7‐δ and the cubic phase of SrFeO3. The following results were obtained: (i) test calculations of reduced binding energy confirmed that high temperature should be a condition of existence of the T phase, as compared with the O phase of YBa2Cu3O7‐δ; (ii) an increase in temperature up to ∼400°C points to the beginning of the Jahn–Teller dynamic effect in SrFeO3; and (iii) transport of neutral and charged oxygen atoms results in distributions of stable and unstable oxygen vacancies, respectively. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Optimization of strong and weak coordinates
Authors: Swart Marcel , Matthias Bickelhaupt F.
Published: April 2006

We present a new scheme for the geometry optimization of equilibrium and transition state structures that can be used for both strong and weak coordinates. We use a screening function that depends on atom‐pair distances to differentiate strong coordinates from weak coordinates. This differentiation significantly accelerates the optimization of these coordinates, and thus of the overall geometry. An adapted version of the delocalized coordinates setup is used to generate automatically a set of internal coordinates that is shown to perform well for the geometry optimization of systems with weak and strong coordinates. For the Baker test set of 30 molecules, we need only 173 geometry cycles with PW91/TZ2P calculations, which compares well with the best previous attempts reported in literature. For the localization of transition state structures, we generate the initial Hessian matrix, using appropriate force constants from a database. In this way, one avoids the explicit computation of the Hessian matrix. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Some design issues of strata‐matched non‐randomized studies with survival outcomes
Authors: Mazumdar Madhu , Tu Donsheng , Zhou Xi Kathy
Published: April 2006

Non‐randomized studies for the evaluation of a medical intervention are useful for quantitative hypothesis generation before the initiation of a randomized trial and also when randomized clinical trials are difficult to conduct. A strata‐matched non‐randomized design is often utilized where subjects treated by a test intervention are matched to a fixed number of subjects treated by a standard intervention within covariate based strata. In this paper, we consider the issue of sample size calculation for this design. Based on the asymptotic formula for the power of a stratified log‐rank test, we derive a formula to calculate the minimum number of subjects in the test intervention group that is required to detect a given relative risk between the test and standard interventions. When this minimum number of subjects in the test intervention group is available, an equation is also derived to find the multiple that determines the number of subjects in the standard intervention group within each stratum. The methodology developed is applied to two illustrative examples in gastric cancer and sarcoma. Copyright © 2006 John Wiley & Sons, Ltd.
Much ado about nothing: a comparison of the performance of meta‐analytical methods with rare events
Authors: Bradburn Michael J. , Deeks Jonathan J. , Berlin Jesse A. , Russell Localio A.
Published: April 2006

For rare outcomes, meta‐analysis of randomized trials may be the only way to obtain reliable evidence of the effects of healthcare interventions. However, many methods of meta‐analysis are based on large sample approximations, and may be unsuitable when events are rare. Through simulation, we evaluated the performance of 12 methods for pooling rare events, considering estimability, bias, coverage and statistical power. Simulations were based on data sets from three case studies with between five and 19 trials, using baseline event rates between 0.1 and 10 per cent and risk ratios of 1, 0.75, 0.5 and 0.2. We found that most of the commonly used meta‐analytical methods were biased when data were sparse. The bias was greatest in inverse variance and DerSimonian and Laird odds ratio and risk difference methods, and the Mantel–Haenszel (MH) odds ratio method using a 0.5 zero‐cell correction. Risk difference meta‐analytical methods tended to show conservative confidence interval coverage and low statistical power at low event rates. At event rates below 1 per cent the Peto one‐step odds ratio method was the least biased and most powerful method, and provided the best confidence interval coverage, provided there was no substantial imbalance between treatment and control group sizes within trials, and treatment effects were not exceptionally large. In other circumstances the MH OR without zero‐cell corrections, logistic regression and the exact method performed similarly to each other, and were less biased than the Peto method. Copyright © 2006 John Wiley & Sons, Ltd.
Interval estimation for rank correlation coefficients based on the probit transformation with extension to measurement error correction of correlated ranked data
Authors: Rosner Bernard , Glynn Robert J.
Published: April 2006

The Spearman (ρs) and Kendall (τ) rank correlation coefficient are routinely used as measures of association between non‐normally distributed random variables. However, confidence limits for ρs are only available under the assumption of bivariate normality and for τ under the assumption of asymptotic normality of . In this paper, we introduce another approach for obtaining confidence limits for ρs or τ based on the arcsin transformation of sample probit score correlations. This approach is shown to be applicable for an arbitrary bivariate distribution. The arcsin‐based estimators for ρs and τ (denoted by s,a, a) are shown to have asymptotic relative efficiency (ARE) of 9/π2 compared with the usual estimators s and when ρs and τ are, respectively, 0.

In some nutritional applications, the Spearman rank correlation between nutrient intake as assessed by a reference instrument versus nutrient intake as assessed by a surrogate instrument is used as a measure of validity of the surrogate instrument. However, if only a single replicate (or a few replicates) are available for the reference instrument, then the estimated Spearman rank correlation will be downwardly biased due to measurement error. In this paper, we use the probit transformation as a tool for specifying an ANOVA‐type model for replicate ranked data resulting in a point and interval estimate of a measurement error corrected rank correlation. This extends previous work by Rosner and Willett for obtaining point and interval estimates of measurement error corrected Pearson correlations. Copyright © 2006 John Wiley & Sons, Ltd.