bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal testing of a numerical model of hillslope–channel coupling using laboratory flume experiments
Authors: Michaelides Katerina , Wainwright John
Published: October 2007

The numerical model COUP2D simulates the hydrological coupling between hillslopes and the river channel during a rainfall event. In order to test the numerical model, a 1:100 scaled laboratory flume which was modified to incorporate lateral hillslope elements, was used to run a series of experiments in which hillslope angle, channel angle, hillslope discharge and channel discharge were the varying parameters. Overall, there were 18 different experimental configurations with three replicates carried out for each condition, leading to a total of 54 experiments. These conditions were then used to parameterize and run COUP2D. Internal model outputs of flow depth and flow velocity at four cross‐sections in the channel were compared to the measurements made in the physical model for the same parameter conditions. Statistical comparisons of the measured and modelled data were carried out for each experiment and across all experiments, using two goodness‐of‐fit measures—root mean square error and Nash–Sutcliffe coefficient of efficiency—in order to assess the performance of the model over an entire simulation as well as over all the simulations. The main effects on the goodness‐of‐fit measures for flow depth of each experimental variable, as well as the interactions between variables, were evaluated using statistical modelling. The results show that the model captures flow‐depth variations in response to changing channel and hillslope parameters. Statistical modelling suggests that the main effects on model error are cross‐section position, channel angle and channel discharge. Significant interactions also occur between all the channel variables and between the channel variables and hillslope discharge. The results of the testing procedure have significant implications for the consideration of different model components and for the interaction between data‐ and model evaluation. Copyright © 2007 John Wiley & Sons, Ltd.
Fog interception by non‐vascular epiphytes in tropical montane cloud forests: dependencies on gauge type and meteorological conditions
Authors: Villegas Juan Camilo , Tobón Conrado , Breshears David D.
Published: October 2007

Precipitation is the most fundamental input of water for terrestrial ecosystems. Most precipitation inputs are vertical, via rain, but can be horizontal, via wind‐driven rain and snow, or, in some ecosystems such as tropical montane cloud forests (TMCFs), via fog interception. Fog interception can be particularly important in ecosystems where fog is frequently present and there are seasonal periods of lower rainfall. Epiphytes in trees are a major ecological component of TMCFs and are particularly dependent on fog interception during periods of lower rainfall because they lack access to soil water. But assessing fog interception by epiphytes remains problematic because: (i) a variety of field or laboratory methods have been used, yet comparisons of interception by epiphytes versus interception by various types of fog gauge are lacking; (ii) previous studies have not accounted for potential interactions between meteorological factors. We compared fog interception by epiphytes with two kinds of commonly used fog gauges and developed relations between fog interception and meteorological variables by conducting laboratory experiments that manipulated key fog characteristics and from field measurements of fog interception by epiphytes. Fog interception measured on epiphytes was correlated with that measured from fog gauges but was more than an order of magnitude smaller than the actual measurements from fog gauges, highlighting a key measurement issue. Our laboratory measurements spanned a broad range of liquid water content (LWC) values for fog and indicate how fog interception is sensitive to an interaction between wind speed and LWC. Based on our results, considered in concert with those from other studies, we hypothesize that fog interception is constrained when LWC is low or high, and that fog interception increases with wind speed for intermediate values of LWC—a net result of deposition, impaction, and evaporation processes—until interception begins to decrease with further increases in wind speed. Copyright © 2007 John Wiley & Sons, Ltd.
Oldest known case of metastasizing prostate carcinoma diagnosed in the skeleton of a 2,700‐year‐old Scythian king from Arzhan (Siberia, Russia)
Authors: Schultz Michael , Parzinger Hermann , Posdnjakov Dmitrij V. , Chikisheva Tatjana A. , Schmidt‐Schultz Tyede H.
Published: October 2007

To determine whether a 2,700‐year‐old tumor can be reliably diagnosed using microscopic and proteomic techniques and whether such prostate carcinomas show the same morphological pattern at the micro‐level as modern‐day carcinomas, this case was investigated. A 40–50‐year‐old Scythian king who lived during the Iron Age in the steppe of Southern Siberia (Russia) suffered from macroscopically visible osteoblastic and osteoclastic lesions throughout his entire skeleton. Macro‐morphological (macroscopy, endoscopy, radiology) and micro‐morphological techniques (histology, scanning‐electron microscopy) as well as proteomic techniques (1‐D‐ and 2‐D‐electrophoresesis, Western blot) were applied. The results of the morphological and biochemical investigation proved that this mature male suffered for many years from and probably died of a carcinoma of the prostate. The diagnosis mainly rests on the results of the microscopic examination of the lesions and the positive evidence of PSA, which is an important marker for the diagnosis of prostate cancer. It is remarkable that, in this ancient case, the morphological pattern at the microlevel is the same as in recent cases. The loss of the spongy bone substance (red bone marrow) provoked chronic anemia during the final months of the life of this king. The proteomic techniques applied are new for the investigation of recent and ancient macerated bones. Sensitive and reliable biochemical markers (PSA) are an important precondition to detect such tumors in recent and ancient materials. Currently, this is the oldest known case of prostate cancer diagnosed reliably by morphological and biochemical techniques. © 2007 Wiley‐Liss, Inc.
Akt promotes cisplatin resistance in human ovarian cancer cells through inhibition of p53 phosphorylation and nuclear function
Authors: Fraser Michael , Bai Tao , Tsang Benjamin K.
Published: October 2007

Resistance to cisplatin‐based chemotherapy is a major cause of treatment failure in human ovarian cancer. Wild‐type TP53 status is often, but not always, associated with cisplatin sensitivity, suggesting that additional factors may be involved. Overexpression/activation of the phosphatidylinositol‐3‐kinase/Akt pathway is commonly observed in ovarian cancer, and Akt activation is a determinant of chemoresistance in ovarian cancer cells, an effect that may be due, in part, to its inhibitory actions on p53‐dependent apoptosis. To that end, we examined the role and regulation of p53 in chemosensitive ovarian cancer cells, as well as in their chemoresistant counterparts, and investigated if and how Akt influences this pathway. Cisplatin induced apoptosis in chemosensitive, but not chemoresistant cells, and this was inhibited by downregulation of p53. Cisplatin upregulated PUMA in a p53‐dependent manner, and the presence of PUMA was necessary, but not sufficient for cisplatin‐induced apoptosis. p53 was phosphorylated on numerous N‐terminal residues, including Ser15, Ser20, in response to cisplatin in chemosensitive, but not chemoresistant cells. Furthermore, activation of Akt inhibited the cisplatin‐induced upregulation of PUMA, and suppressed cisplatin‐induced p53 phosphorylation, while inhibition of Akt increased total and phospho‐p53 contents and sensitized p53 wild‐type, chemoresistant cells to cisplatin‐induced apoptosis. Finally, mutation of Ser15 and/or Ser20, but not of Ser37, to alanine significantly attenuated the ability of p53 to facilitate CDDP‐induced apoptosis, and this was independent of PUMA expression. These results support the hypothesis that p53 is a determinant of CDDP sensitivity, and suggest that Akt contributes to chemoresistance, in part, by attenuating p53‐mediated PUMA upregulation and phosphorylation of p53, which are essential, but independent determinants of sensitivity to CDDP‐induced apoptosis. © 2007 Wiley‐Liss, Inc.
Downregulation of IFN‐γR in association with loss of Fas function is linked to tumor progression
Authors: Yang Dafeng , Stewart Trina J. , Smith Kimberly K. , Georgi David , Abrams Scott I. , Liu Kebin
Published: October 2007

The host immune system functions as an intrinsic surveillance network in the recognition and destruction of tumor cells, and it has been demonstrated that lymphocytes and IFN‐γ are the primary tumor suppressors of the immune system. However, the immune system can concurrently select for tumor variants with reduced immunogenicity and aggressive phenotypes. We report here that tumor escape variants that have survived CTL adoptive immunotherapy exhibited decreased expression levels of both Fas and IFN‐γR in vitro. Furthermore, examination of spontaneously arising mouse primary mammary carcinoma and lung metastases revealed that both Fas and IFN‐γR protein levels were dramatically lower in lung metastases than in primary tumors in vivo. Functional disruption of either the Fas‐ or the IFN‐γ signaling pathway enhanced the colonization efficiency of preexisting metastatic tumor cells, whereas disruption of both Fas and IFN‐γR pathways resulted in synergistic augmentation of the colonization efficiency of the preexisting metastatic tumor cells, as determined by experimental lung metastases assay. Gene expression profiling revealed that altered expression of genes involved in immediate IFN‐γR signaling, the interferon primary response, apoptosis and tumor colonization is associated with loss of IFN‐γR function and enhanced metastatic potential. Interestingly, disruption of IFN‐γR function did not alter tumor cell susceptibility to CTL‐mediated cytotoxicity, but is linked to enhanced infiltration of endogenous T cells in the tumor microenvironment in vivo. These findings suggest that coordinate downregulation of Fas and IFN‐γR, 2 key components of cancer immunosurveillance system on tumor cells, leads to a more aggressive metastatic phenotype. © 2007 Wiley‐Liss, Inc.
Retracted: Dose‐dependent dual effect of HTLV‐1 tax oncoprotein on p53‐dependent nucleotide excision repair in human T‐cells
Authors: Schavinsky‐Khrapunsky Yana , Priel Esther , Aboud Mordechai
Published: October 2007

The above article, published online on 4 October 2007 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 122, pp. 305‐316, has been retracted by agreement between the journal Editor in Chief, Professor Peter Lichter, and John Wiley & Sons Ltd. The retraction has been agreed as the bands in Figs 1, 2, 5 and 6 appear to have been manipulated.

Reference

Schavinsky‐Khrapunsky, Y.,
Priel, E. and
Aboud, M. (2008), . J. Cancer, 122: 305–316. doi:10.1002/ijc.23091
Naftopidil, a selective α‐1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest
Authors: Kanda Hideki , Ishii Kenichiro , Ogura Yuji , Imamura Tetsuya , Kanai Masahiro , Arima Kiminobu , Sugimura Yoshiki
Published: October 2007

α‐1 adrenoceptor antagonists are generally prescribed for benign prostate hyperplasia with lower urinary tract symptoms. Naftopidil, a selective α‐1 adrenoceptor antagonist, is frequently used in Japan because it has fewer side effects. Here we demonstrate for the first time that naftopidil has growth inhibitory effect in androgen‐sensitive and ‐insensitive human prostate cancer cell lines. The concentrations causing 50% inhibition (IC50) of cancer cell growth were 22.2 ± 4.0 μM in androgen‐sensitive LNCaP cells and 33.2 ± 1.1 μM in androgen‐insensitive PC‐3 cells. FACS analysis revealed that cell growth inhibition by naftopidil was due to the arrest of the G1 cell cycle. Expressions of p27kip1 and p21cip1 were significantly increased in LNCaP cells treated with naftopidil. In PC‐3 cells, naftopidil induced p21cip1 but not p27kip1. In vivo, oral administration of naftopidil to nude mice inhibited the growth of PC‐3 tumors as compared to vehicle‐treated controls. These results suggest that naftopidil may be useful in the chemoprevention of prostate cancer and the intervention of hormone refractory prostate cancer. © 2007 Wiley‐Liss, Inc.
Curcumin enhances the effects of 5‐fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF‐1R
Authors: Patel Bhaumik B. , Sengupta Radha , Qazi Sadia , Vachhani Hetal , Yu Yingjie , Rishi Arun K. , Majumdar Adhip P.N.
Published: October 2007

Curcumin (diferuloylmethane), which has been shown to inhibit growth of transformed cells, has no discernible toxicity and achieves high levels in colonic mucosa. 5‐fluorouracil (5‐FU) or 5‐FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but with limited success. The present investigation was, therefore, undertaken to examine whether curcumin in combination with conventional chemotherapeutic agent(s)/regimen will be a superior therapeutic strategy for colorectal cancer. Indeed, results of our in vitro studies demonstrated that curcumin together with FOLFOX produced a significantly greater inhibition (p < 0.01) of growth and stimulated apoptosis (p < 0.001) of colon cancer HCT‐116 and HT‐29 cells than that caused by curcumin, 5‐FU, curcumin + 5‐FU or FOLFOX. These changes were associated with decreased expression and activation (tyrosine phosphorylation) of EGFR, HER‐2, HER‐3 (72–100%) and IGF‐1R (67%) as well as their downstream effectors such as Akt and cycloxygenase‐2 (51–97%). Furthermore, while these agents produced a 2–3‐fold increase in the expression of IGF‐binding protein‐3 (IGFBP‐3), curcumin together with FOLFOX caused a 5‐fold increase in the same, when compared to controls. This in turn led to increased sequestration of IGF by IGFBP‐3 rendering IGF‐1 unavailable for binding to and activation of IGF‐1R. We conclude that the superior effects of the combination therapy of curcumin and FOLFOX are due to attenuation of EGFRs and IGF‐1R signaling pathways. We also suggest that inclusion of curcumin to the conventional chemotherapeutic agent(s)/regimen could be an effective therapeutic strategy for colorectal cancer. © 2007 Wiley‐Liss, Inc.
The role of insulin‐like growth factor binding protein‐3 in the growth inhibitory actions of androgens in LNCaP human prostate cancer cells
Authors: Peng Lihong , Wang Jining , Malloy Peter J. , Feldman David
Published: October 2007

Insulin‐like growth factor binding protein‐3 (IGFBP‐3), an antiproliferative and proapoptotic protein, has been shown to be upregulated by growth inhibitory concentrations of androgens in LNCaP human prostate cancer (PCa) cells, but the mechanism of regulation and the role of IGFBP‐3 in the modulation of PCa cell proliferation are unknown. In this study, we have examined the effects of a range of concentrations of the synthetic androgen R1881 on IGFBP‐3 expression and cell growth in LNCaP cells. We have also investigated the role of androgen‐stimulated IGFBP‐3 in androgen‐induced growth inhibition. We show that low doses of R1881 stimulate LNCaP cell proliferation, but do not induce IGFBP‐3 expression, whereas high doses of R1881 that inhibit cell growth, significantly increase expression of IGFBP‐3. Importantly, we demonstrate that the combination of calcitriol and androgens not only synergistically upregulates IGFBP‐3 expression but also inhibits cell growth better than either hormone alone. siRNA knockdown of IGFBP‐3 expression partially reverses the growth inhibition by calcitriol and by androgens. Furthermore, we find that the growth inhibitory dose of R1881 leads to increases in the cyclin dependent kinase inhibitors (CDKIs), p21 and p27 as well as to G1 arrest. These changes can be blocked or partially reversed by IGFBP‐3 siRNA, indicating that the induction of CDKIs is downstream of IGFBP‐3. Our data suggest, for the first time, that IGFBP‐3 is involved in the antiproliferative action of high doses of androgens partly through p21 and p27 pathways and that IGFBP‐3 may contribute significantly to androgen‐induced changes in LNCaP cell growth. © 2007 Wiley‐Liss, Inc.
EGFR induces expression of IRF‐1 via STAT1 and STAT3 activation leading to growth arrest of human cancer cells
Authors: Andersen Peter , Pedersen Mikkel Wandahl , Woetmann Anders , Villingshøj Mette , Stockhausen Marie‐Thérése , Ødum Niels , Poulsen Hans Skovgaard
Published: October 2007

Recently, we reported that epidermal growth factor receptor (EGFR) induce expression of a module of genes known to be inducible by interferons and particularly interferon‐γ. Here we show that the module is tightly regulated by EGFR in the 2 human cancer cell lines that overexpress EGFR, A431 and HN5. The module of genes included the tumor suppressor IRF‐1, which was used as a prototypical member to further investigate the regulation and function of the module. Ligand‐activated EGFR induce expression of IRF‐1 via phosphorylation of STAT1 and STAT3. In contrast, cells expressing the constitutively active cancer specific receptor EGFRvIII are unable to mediate phosphorylation of these STATs and thereby incapable of inducing IRF‐1. We also demonstrate that IRF‐1 is expressed in an EGF dose‐dependent manner, which correlates with inhibition of cell proliferation, and that the regulation of IRF‐1 is partially dependent on intracellular Src family kinase activity. Treatment with the dual specific Abl/c‐Src kinase inhibitor AZD0530 significantly reduces the growth inhibitory effect of high EGF concentrations, signifying that EGFR induced IRF‐1 is responsible for the observed growth inhibition. In addition, we show that media from these EGF treated cancer cells upregulate the activation marker CD69 on both B‐cells and T‐cells in peripheral blood. Taken together, these results suggest that cells acquiring sustained high activity of oncogenes such as EGFR are able to activate genes, whose products mediate growth arrest and activate immune effector cells, and which potentially could be involved in alerting the immune system in vivo leading to elimination of the transformed cells. © 2007 Wiley‐Liss, Inc.
Identification of parameters in normal error component logit‐mixture (NECLM) models
Authors: Walker Joan L. , Ben‐Akiva Moshe , Bolduc Denis
Published: October 2007

Although the basic structure of logit‐mixture models is well understood, important identification and normalization issues often get overlooked. This paper addresses issues related to the identification of parameters in logit‐mixture models containing normally distributed error components associated with alternatives or nests of alternatives (normal error component logit mixture, or NECLM, models). NECLM models include special cases such as unrestricted, fixed covariance matrices; alternative‐specific variances; nesting and cross‐nesting structures; and some applications to panel data. A general framework is presented for determining which parameters are identified as well as what normalization to impose when specifying NECLM models. It is generally necessary to specify and estimate NECLM models at the levels, or structural, form. This precludes working with utility differences, which would otherwise greatly simplify the identification and normalization process. Our results show that identification is not always intuitive; for example, normalization issues present in logit‐mixture models are not present in analogous probit models. To identify and properly normalize the NECLM, we introduce the ‘equality condition’, an addition to the standard order and rank conditions. The identifying conditions are worked through for a number of special cases, and our findings are demonstrated with empirical examples using both synthetic and real data. Copyright © 2007 John Wiley & Sons, Ltd.
On the intra‐annual variability of atmospheric circulation in the Mediterranean region
Authors: Lolis C. J. , Metaxas D. A. , Bartzokas A.
Published: October 2007

Some aspects on the intra‐annual variability and the seasonal peculiarities of the atmospheric circulation in the Mediterranean region are examined. T‐mode factor analysis is applied on the long‐term (1948–2003) 5‐day mean values of relative geostrophic vorticity for the 73 5‐day periods of the year. The analysis is applied for sea‐surface and 500‐hPa levels. For sea level, two circulation types are found to be dominant: the type of the warm period and the type of the cold period, characterizing the so‐called Mediterranean climate; they are strongly dependent on the thermal and humidity characteristics of the earth's surface and the position and strength of the sub‐tropical (Azores) anti‐cyclone. For 500‐hPa level, two extra but weaker circulation types are added, prevailing mainly during the transitional seasons and modifying the smooth intra‐annual variation of the atmospheric circulation. In this case, the thermal influence of the earth's surface appears to be weaker, while other circulation features, such as blocking activity and/or cut‐off lows, seem to play an important role too. Copyright © 2007 Royal Meteorological Society
Expression of nuclear notch3 in pancreatic adenocarcinomas is associated with adverse clinical features, and correlates with the expression of STAT3 and phosphorylated Akt
Authors: Doucas Helena , Mann Christopher D. , Sutton Christopher D. , Garcea Guiseppe , Neal Christopher P. , Berry David P. , Manson Margaret M.
Published: October 2007

Background and Objectives

Reactivation of the Notch signalling pathway occurs in a range of human malignancies. Previous research suggests that Notch3 is expressed in pancreatic adenocarcinomas, but neither cellular location nor association with clinical parameters has been described. The relationship between Notch3, clinical endpoints, and other proteins with potential to interact with Notch was therefore examined.

Methods

An immunohistochemical study was performed on human pancreatic adenocarcinoma (n = 23) and normal pancreas (n = 12), to assess expression of Notch3, cyclin D1, pAkt, STAT3 and pSTAT3. Immunohistochemical data were then correlated with clinicopathological characteristics.

Results

Notch3 was significantly overexpressed in the cytoplasm of 73.9% of tumours. Nuclear expression was not observed in normal pancreatic ductal tissue, but was noted in 43.5% of tumours. No tumour expressing nuclear Notch3 was resectable. There were significant correlations between expression and intracellular location of Notch3 and each of STAT3, pSTAT3 and pAkt, but not cyclin D1.

Conclusion

The presence of Notch3 in tumour nuclei is likely to represent functional activation of the protein, and is clearly linked to a more aggressive tumour phenotype. The correlation with STAT3, pSTAT3 and pAkt expression has not previously been described and the concurrent intracellular localisation of these proteins suggests a functional relationship between them. J. Surg. Oncol. 2008;97:63–68. © 2007 Wiley‐Liss, Inc.
Breast cancer screening compliance among young women in a free access healthcare system
Authors: Amin Asna , Shriver Craig D. , Henry Leonard R. , Lenington Sarah , Peoples George E. , Stojadinovic Alexander
Published: October 2007

Background and Objectives

To examine mammographic screening compliance among young military healthcare beneficiaries and to examine factors related to one time and recent mammographic compliance.

Methods

Medical records were reviewed for 1,073 subjects (age 41–47) recording dates of the two most recent screening mammograms. Examined outcomes were: whether the woman ever had mammography and, if so, whether she had a mammogram within 400 days. Examined predictors were: ethnicity, age, Gail Model risk score, family history, whether the woman knew a young woman with breast cancer, and importance attributed to breast cancer screening.

Results

90.4% of women studied had at least one mammogram. 71.1% underwent screening within 400 days. Rates of ever having mammography were higher for women with family history of breast cancer and Asian, Pacific Islander, Black or Hispanic women. No measured covariate correlated with having mammography within 400 days.

Conclusions

One time screening participation was high in this select group of women for whom cost and access barriers were removed, but was lower with regard to having a recent mammogram. Correlates of ever having and recent mammography are not synonymous. J. Surg. Oncol. 2008;97:20–24. © 2007 Wiley‐Liss, Inc.
The value of expert second opinion in diagnosis of soft tissue sarcomas
Authors: Lehnhardt Marcus , Daigeler Adrien , Hauser Joerg , Puls Alexander , Soimaru Christian , Kuhnen Cornelius , Steinau Hans Ulrich
Published: October 2007

Introduction

Soft tissue sarcomas represent a heterogenous group of tumours with a wide range of clinical behaviour. Exact determination of diagnosis and prognosis is critical in order to guide surgical decisions and provide systemic therapy or radiation for patients. The value of consultative second opinions has been proven for general surgical pathology; some studies suggest an even higher value for the soft tissue tumour specimens in particular.

Methods

We reviewed 603 patients who were operated on at our institution with the diagnosis of soft tissue sarcoma and aggressive fibromatosis; we focused on mismatches in primary and definite tumour‐entity and ‐grading with respect to the diagnosing institution and the primary surgical procedure.

Results

We found concordant primary diagnosis in 28.3% for pathologists in private clinics, 29.6% for hospital pathologists, 36.8% for academic medical centres (university hospitals) and 70.5% for the Department of Pathology at our institution. An improvement in diagnosis or confirmation of the correct primary diagnosis by the second opinion was seen in 73.1% of the patients; in 2.5%, the second opinion was false.

Discussion

For accurate determination of prognosis and to provide optimal therapeutic decisions we consider expert second opinion essential for optimal treatment of soft tissue sarcomas. J. Surg. Oncol. 2008;97:40–43. © 2007 Wiley‐Liss, Inc.
Curing hepatocellular carcinomatosis with biologic therapy and surgery: Achieving the impossible?
Authors: Thomas Melanie B. , Tetzlaff Eric , Lozano Richard , Samp Leigh , Butler Charles E. , Gannon Christopher , Hamilton Stanley , Vauthey Jean Nicholas , Abdalla Eddie
Published: October 2007

Hepatocellular carcinoma (HCC) that present as hemoperitoneum are uncommon, often recur as peritoneal carcinomatosis, and have poor prognosis. Systemic chemotherapies are minimally effective in advanced HCC and less so as neo‐adjuvant therapy. This report describes a 47‐year woman with ruptured HCC who developed recurrent carcinomatosis. She received biologically targeted systemic therapy which resulted in significant radiographic tumor response. Salvage surgery revealed complete pathologic response in all tumor nodules, thus the patient was rendered cancer‐free. J. Surg. Oncol. 2008;97:82–84. © 2007 Wiley‐Liss, Inc.
p53 Codon 72 polymorphism and the risk of esophageal squamous cell carcinoma
Authors: Yang Wenjun , Zhang Yanyan , Tian Xiuyun , Ning Tao , Ke Yang
Published: October 2007

The polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous malignant tumors, particularly carcinomas associated with human papillomavirus (HPV) infection. However, the results remain controversial. To address a potential correlation between the p53 genotypes and the risk of esophageal squamous cell carcinoma (ESCC), we investigated the p53 codon 72 polymorphism in 435 patients with ESCC and 550 cancer‐free subjects from the same geographical region. p53 Arg/Arg genotype was significantly increased in ESCC cases compared with control subjects (85.7 vs. 49.6%, P < 0.001), resulting in an elevated ESCC risk (OR = 6.48, 95% CI = 4.65–9.03). In addition, among p53 Arg/Arg carriers, HPV infection, smoking, and drinking might further increase the risk of ESCC development. © 2007 Wiley‐Liss, Inc.
Loss of the eukaryotic initiation factor 3f in pancreatic cancer
Authors: Doldan Adriana , Chandramouli Anupama , Shanas Reneé , Bhattacharyya Achyut , Cunningham John T. , Nelson Mark A. , Shi Jiaqi
Published: October 2007

Aberrant regulation of the translation initiation is known to contribute to tumorigenesis. eIF3 plays an important role in translation initiation. eIF3f is the p47 subunit of the eIF3 complex whose function in cancer is not clear. Initial studies from our group indicated that eIF3f expression is decreased in pancreatic cancer. Overexpression of eIF3f induces apoptosis in pancreatic cancer cells. The eIF3f gene is located at chromosome band region 11p15.4. Loss of 11p15.4 is a common event in many tumors including pancreatic cancer. In order to investigate the molecular mechanism of the decreased expression of eIF3f in pancreatic cancer, we performed loss of heterozygosity (LOH) analysis in 32 pancreatic cancer specimens using three microsatellite markers encompassing the eIF3f gene. We showed that the prevalence of LOH ranged from 71% to 93%. We also performed eIF3f gene copy number analysis using quantitative real time PCR to further confirm the specific allelic loss of eIF3f gene in pancreatic cancer. We demonstrated a statistically significant decrease of eIF3f gene copy number in pancreatic tumors compared with normal tissues with a tumor/normal ratio of 0.24. Furthermore, RNA in situ hybridization and tissue microarray immunohistochemistry analysis demonstrated that eIF3f expression is significantly decreased in human pancreatic adenocarcinoma tissues compared to normal pancreatic tissues. These data provides new insight into the understanding of the molecular pathogenesis of eIF3f during pancreatic tumorigenesis. © 2007 Wiley‐Liss, Inc.
Retinol decreases phosphatidylinositol 3‐kinase activity in colon cancer cells
Authors: Park Eun Young , Wilder Erik T. , Chipuk Joseph E. , Lane Michelle A.
Published: October 2007

Previously, we showed that retinol inhibited all‐trans‐retinoic acid (ATRA)‐resistant human colon cancer cell invasion via a retinoic acid receptor‐independent mechanism. Because phosphatidylinositol 3‐kinase (PI3K) regulates cell invasion, the objective of the current study was to determine if retinol affected PI3K activity. Following 24 h of serum starvation, the ATRA resistant human colon cancer cell lines HCT‐116 and SW620 were treated with 0, 1, or 10 µM retinol. Thirty minutes of retinol treatment resulted in a significant decrease in PI3K activity in both cell lines. To determine the mechanism by which retinol reduces PI3K activity, the levels and heterodimerization of the regulatory subunit, p85, and the catalytic subunit, p110, of PI3K were examined. Retinol treatment did not alter p85 or p110 protein levels or the heterodimerization of these subunits at any time point examined. To determine if retinol affected the ability of PI3K to phosphorylate the substrate, phosphatidylinositol (PI), PI3K was immunoprecipitated from control cells and incubated with 10 µg PI and increasing concentrations of retinol or 10 µg retinol and increasing concentrations of PI. Retinol decreased PI3K activity in a dose‐responsive manner and increased PI suppressed the inhibitory effect of retinol on PI3K activity. Finally, the PI3K inhibitor, LY294002, mimicked the ability of retinol to decrease cell invasion. Computational modeling revealed that retinol may inhibit PI3K activity in a manner similar to that of wortmannin. Thus, a decrease in PI3K activity due to retinol treatment may confer the ability of retinol to inhibit ATRA‐resistant colon cancer cell invasion. © 2007 Wiley‐Liss, Inc.
Preventing cell death induced by carbonyl stress, oxidative stress or mitochondrial toxins with vitamin B anti‐AGE agents
Authors: Mehta Rhea , Shangari Nandita , O'Brien Peter J.
Published: October 2007

Carbonyls generated by autoxidation of carbohydrates or lipid peroxidation have been implicated in advanced glycation end product (AGE) formation in tissues adversely affected by diabetes complications. Tissue AGE and associated pathology have been decreased by vitamin B1/B6 in trials involving diabetic animal models. To understand the molecular cytoprotective mechanisms involved, the effects of B1/B6 vitamers against cytotoxicity induced by AGE/advanced lipid end product (ALE) carbonyl precursors (glyoxal/acrolein) have been compared to cytotoxicity induced by oxidative stress (hydroperoxide) or mitochondrial toxins (cyanide/copper). Thiamin was found to be best at preventing cell death induced by carbonyl stress and mitochondrial toxins but not oxidative stress cell death suggesting that thiamin pyrophosphate restored pyruvate and α‐ketoglutarate dehydrogenases inhibited by mitochondrial toxicity. However, B6 vitamers were most effective at preventing oxidative stress or lipid peroxidation cytotoxicity suggesting that pyridoxal or pyridoxal phosphate were antioxidants and/or Fe/Cu chelators. A therapeutic vitamin cocktail could provide maximal prevention against carbonyl stress toxicity associated with diabetic complications.
Does garlic have a role as an antidiabetic agent?
Authors: Liu Cheng‐Tzu , Sheen Lee‐Yan , Lii Chong‐Kuei
Published: October 2007

Diabetes affects a large segment of the population worldwide, and the prevalence of this disease is rapidly increasing. Despite the availability of medication for diabetes, traditional remedies are desirable and are currently being investigated. Garlic (Allium sativum), which is a common cooking spice and has a long history as a folk remedy, has been reported to have antidiabetic activity. However, there is no general agreement on the use of garlic for antidiabetic purposes, primarily because of a lack of scientific evidence from human studies and inconsistent data from animal studies. The validity of data from previous studies of the hypoglycemic effect of garlic in diabetic animals and the preventive effects of garlic on diabetes complications are discussed in this review. The role of garlic as both an insulin secretagogue and as an insulin sensitizer is reviewed. Evidence suggests that garlic's antioxidative, antiinflammatory, and antiglycative properties are responsible for garlic's role in preventing diabetes progression and the development of diabetes‐related complications. Large‐scale clinical studies with diabetic patients are warranted to confirm the usefulness of garlic in the treatment and prevention of diabetes.
Towards automatic structured multiblock mesh generation using improved transfinite interpolation
Authors: Allen C. B.
Published: October 2007

The quality of any numerical flowfield solution is inextricably linked to the quality of the mesh used. It is normally accepted that structured meshes are of higher quality than unstructured meshes, but are much more difficult to generate and, furthermore, for complex topologies a multiblock approach is required. This is the most resource‐intensive approach to mesh generation, since block structures, mesh point distributions, etc., need to be defined before the generation process, and so is seldom used in an industrial design loop, particularly where a novice user may be involved. This paper considers and presents two significant advances in multiblock mesh generation: the development of a fast, robust, and improved quality interpolation‐based generation scheme and a fully automatic multiblock optimization and generation method. A volume generation technique is presented based on a form of transfinite interpolation, but modified to include improved orthogonality and spacing control and, more significantly, an aspect ratio‐based smoothing algorithm that removes grid crossover and results in smooth meshes even for discontinuous boundary distributions. A fully automatic multiblock generation scheme is also presented, which only requires surface patch(es) and a target number of mesh cells. Hence, all user input is removed from the process, and a novice user is able to obtain a high‐quality mesh in a few minutes. It also means the code can be run in batch mode, or called as an external function, and so is ideal for incorporation into a design or optimization loop. To demonstrate the power and efficiency of the code, multiblock meshes of up to 256 million cells are presented for wings and rotors in hover and forward flight. Copyright © 2007 John Wiley & Sons, Ltd.
A combined extended finite element and level set method for biofilm growth
Authors: Duddu Ravindra , Bordas Stéphane , Chopp David , Moran Brian
Published: October 2007

This paper presents a computational technique based on the extended finite element method (XFEM) and the level set method for the growth of biofilms. The discontinuous‐derivative enrichment of the standard finite element approximation eliminates the need for the finite element mesh to coincide with the biofilm–fluid interface and also permits the introduction of the discontinuity in the normal derivative of the substrate concentration field at the biofilm–fluid interface. The XFEM is coupled with a comprehensive level set update scheme with velocity extensions, which makes updating the biofilm interface fast and accurate without need for remeshing. The kinetics of biofilms are briefly given and the non‐linear strong and weak forms are presented. The non‐linear system of equations is solved using a Newton–Raphson scheme. Example problems including 1D and 2D biofilm growth are presented to illustrate the accuracy and utility of the method. The 1D results we obtain are in excellent agreement with previous 1D results obtained using finite difference methods. Our 2D results that simulate finger formation and finger‐tip splitting in biofilms illustrate the robustness of the present computational technique. Copyright © 2007 John Wiley & Sons, Ltd.
Metabolic syndrome traits in long‐term survivors of pediatric sarcoma
Authors: Hoffman Karen E. , Derdak Joanne , Bernstein Donna , Reynolds James C. , Avila Nilo A. , Gerber Lynn , Steinberg Seth M. , Chrousos George , Mackall Crystal L. , Mansky Patrick J.
Published: October 2007

Purpose

The metabolic syndrome (MS), a cluster of central obesity, dyslipidemia, hyperglycemia, and hypertension, conveys an increased risk of type 2 diabetes and cardiovascular disease. This cross‐sectional study investigated the prevalence of metabolic syndrome traits (MST) in long‐term survivors of pediatric sarcoma (SARC) who received multi‐modality therapy (MMT).

Methods

Thirty‐two SARC survivors (predominantly Ewings; median age 36.5; median age at MMT 15) underwent body composition, activity, and psychosocial analysis. Serum endocrine and inflammatory parameters and urine beta(2)‐microglobulin (B2M) were evaluated. The prevalence of MST was compared to age‐ and gender‐matched U.S. population data.

Results

SARC survivors were more likely to have two or more MST (OR 2.38 95% CI: [1.14, 5.04]). Analysis of individual MST demonstrated higher prevalence of hypertension (OR 2.61 95% CI: [1.20, 5.59]), hypertriglyceridemia (OR 3.63 95% CI: [1.75, 7.60]), and male visceral abdominal obesity (20–39 years old OR 4.63 95% CI: [0.91, 21.63], 40–59 years old OR infinity). Survivors 18–39 years old had a higher prevalence of the MS (OR 4.29 95% CI: [1.50, 11.21]), defined as three or more MST. Plasminogen activator inhibitory activity (P = 0.016) and B2M (P = 0.027) increased with increasing numbers of MST. In males, total testosterone declined (P = 0.0027) as the number of MST increased. Average (P = 0.014) and maximum (P = 0.021) activity levels decreased as the number of MST increased.

Conclusion

After a median follow up of 17 years, adult SARC survivors of MMT had an increased prevalence of MST, especially those less than 40 years old. The development of MST in this population was associated with decreased testosterone and activity levels. Pediatr Blood Cancer 2008;50:341–346. © 2007 Wiley‐Liss, Inc.
A comparison of community pharmacists' views of over‐the‐counter omeprazole and simvastatin
Authors: Stewart Derek , John Dai , Cunningham Scott , McCaig Dorothy , Hansford Denise
Published: October 2007

Purpose

Simvastatin and omeprazole were re‐classified to pharmacy status in Great Britain in summer 2004. The purpose of this study was to compare the views of community pharmacists on over‐the‐counter (OTC) omeprazole and simvastatin.

Methods

A pre‐piloted questionnaire mailed to 2000 randomly selected community pharmacy premises, with open questions relating to pharmacists' views. Pharmacists' attitudes on aspects of supply were sought using Likert scales. Content analysis was performed on responses to the open question and Wilcoxon signed ranks test (z) used to compare responses to the attitudinal statements.

Results

One thousand one hundred and fifty‐six questionnaires were returned (57.8%). Themes around omeprazole illustrated positive views compared to concerns relating to simvastatin. Whereas omeprazole was seen as a welcome addition, there were issues around the poor evidence base for simvastatin. Further simvastatin related concerns were in areas of cardiovascular risk assessment, adverse drug reactions and likelihood of patients not committing to therapy. For both agents, excessive cost was an issue. Nearly three‐quarters of pharmacists agreed they were entirely confident about selling omeprazole (835, 73%), significantly more than simvastatin (691, 60%); (z = 9.243, p < 0.001).

Conclusions

Two re‐classified medicines have raised common and product‐specific themes. Many themes relate to clinical governance such as evidence‐based practice, risk management and continuing professional development (CPD). Views on the availability and circumstances surrounding the OTC supply differ in certain regards, for example, more believe that they should be involved in the sale of simvastatin personally than for sales of omeprazole. Copyright © 2007 John Wiley & Sons, Ltd.
PS/PMMA mixed polymer brushes on the surface of clay layers: Preparation and application in polymer blends
Authors: Zhang Jian , Yang Yongfang , Zhao Chuanzhuang , Zhao Hanying
Published: October 2007

Polystyrene (PS) and poly(methyl methacrylate) (PMMA) mixed polymer brushes on the surface of clay layers were prepared by using in situ free radical polymerization. Free radical initiator molecules with two quaternary ammonium groups at both ends were intercalated into the interlayer spacing of clay layers. The amount of polymer brushes grafted on the surface of clay layers can be controlled by controlling the polymerization time. Thermogravimetric analysis, X‐ray diffraction, and high‐resolution transmission electron microscope results indicated successful preparation of the mixed polymer brushes on the surface of clay layers. The kinetics of the grafting of the monomers was also studied. The mixed polymer brushes on the surface of clay layers were used as compatibilizers in blends of PS and PMMA. In the blends, the intercalated clay particles tend to locate at the interface of two phases reducing the interfacial tension. In the meanwhile, PMMA homopolymer chains tend to intercalate into clay layers. The driving force for the intercalation is the compatibility between homo‐PMMA chains and PMMA brushes on the surface of clay layers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5329–5338, 2007
Incidents of bee poisoning with pesticides in the United Kingdom, 1994–2003
Authors: Barnett Elizabeth A , Charlton Andrew J , Fletcher Mark R
Published: October 2007

For over 20 years, the UK Agriculture Departments have monitored the direct effects of pesticides on beneficial insects, mainly honeybees (Apis mellifera, L.) and bumblebees (Bombus terrestris, L.), as part of the Wildlife Incident Investigation Scheme (WIIS). The Central Science Laboratory (CSL) has contributed to WIIS by providing the required laboratory skills for the determination of bee diseases and the expert analytical experience necessary to determine low‐level pesticide residues and interpret these results. The results from WIIS form part of the pesticide regulatory process coordinated by the Pesticides Safety Directorate (PSD) and are published each year. This paper has reviewed the data from WIIS over the 10 year period from 1994 to 2003. The overall trend is that suspected poisoning incidents, reported by beekeepers and the general public, have declined from 56 incidents per year to 23 incidents per year. The number of these incidents that have been attributed to pesticide poisoning has also declined, from 25 incidents to five incidents per year. The possible reasons for these changes and the circumstances involved in the bee poisoning incidents are discussed. However, the source of the pesticide in bee poisoning incidents is often uncertain and the likely cause of these incidents and any trends over time are also discussed. © Crown copyright 2007. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
A new look at thermal properties of nanotubes
Authors: Zettl A. , Chang C. W. , Begtrup G.
Published: October 2007

The thermal conductance of nanotubes is examined over a wide temperature range and as a function of mechanical manipulation. It is found that carbon nanotubes maintain impressive thermal conductance up to their decomposition temperature of ∼3200 K. For both carbon and boron nitride multiwalled nanotubes the thermal conductance is relatively independent of tube bending angle, but it can be substantially tuned by “telescoping” the tubes. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Interlayer asymmetry gap in the electronic band structure of bilayer graphene
Authors: McCann Edward
Published: October 2007

The low‐energy electronic band structure of bilayer graphene consists of four bands: a pair of bands split from zero energy by the interlayer coupling and a pair of bands which touch at zero energy in a nominally undoped system. The latter support massive, chiral quasiparticles with a parabolic dispersion and Berry phase 2π. Asymmetry between the potential energies of the layers opens a tuneable gap between the conduction and valence bands. A self‐consistent Hartree approximation is used to model the control of such an interlayer asymmetry gap induced by a transverse electric field in a graphene‐based field‐effect transistor. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of catalysts' activation on their activity and selectivity in carbon nanotubes synthesis
Authors: Usoltseva A. , Kuznetsov V. , Rudina N. , Moroz E. , Haluska M. , Roth S.
Published: October 2007

In this paper we have investigated the influence of catalysts' activation conditions on their selectivity in carbon nanotubes CVD synthesis by means of methane decomposition reaction using Fe‐ and FeCo‐catalysts synthesized via polymerized complex rout providing homogeneous distribution of catalytic components. It was shown that variation of catalysts' reduction conditions results in formation of different types of NTs (MWNTs or SWNTs). The most effective catalyst activation leading to formation of SWNTs consists in catalyst reduction by reaction mixture at high temperature. That can be explained in terms of carbon deposits nucleation on metals. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)