bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of CD47 receptors causes proliferation of human astrocytoma but not normal astrocytes via an Akt‐dependent pathway
Authors: Sick Emilie , Boukhari Abdelaziz , Deramaudt Thérèse , Rondé Philippe , Bucher Bernard , André Philippe , Gies Jean‐Pierre , Takeda Kenneth
Published: December 2010

CD47 is a membrane receptor that plays pivotal roles in many pathophysiological processes, including infection, inflammation, cell spreading, proliferation, and apoptosis. We show that activation of CD47 increases proliferation of human U87 and U373 astrocytoma cells but not normal astrocytes. CD47 function‐blocking antibodies inhibit proliferation of untreated U87 and U373 cells but not normal astrocytes, suggesting that CD47 may be constitutively activated in astrocytoma. CD47 expression levels were similar in our three cell types. CD47 couples to G‐proteins in astrocytes and astrocytoma and especially to the Gβγ dimer. Downstream signaling following CD47 activation involves Gβγ dimer‐dependent activation of the PI3K/Akt pathway in astrocytoma cells but not in normal astrocytes. This pathway is known to be deregulated in astrocytoma, leading to cell proliferation and enhanced survival signals. Putative PLIC‐1 interaction with CD47 in astrocytoma cells but not astrocytes may contribute to the proliferative effect observed upon activation of CD47. Our data indicate that CD47 receptors have a stimulatory role in cell proliferation and demonstrate for the first time that CD47 signals via the PI3K/Akt pathway in cancerous cells but not normal cells. © 2010 Wiley‐Liss, Inc.
Drosophila glia use a conserved cotransporter mechanism to regulate extracellular volume
Authors: Leiserson William M. , Forbush Biff , Keshishian Haig
Published: December 2010

The nervous system is protected by blood barriers that use multiple systems to control extracellular solute composition, osmotic pressure, and fluid volume. In the human nervous system, misregulation of the extracellular volume poses serious health threats. Here, we show that the glial cells that form the Drosophila blood–nerve barrier have a conserved molecular mechanism that regulates extracellular volume: the Serine/Threonine kinase Fray, which we previously showed is an ortholog of mammalian PASK/SPAK; and the Na‐K‐Cl cotransporter Ncc69, which we show is an ortholog of human NKCC1. In mammals, PASK/SPAK binds to NKCC1 and regulates its activity. In Drosophila, larvae mutant for Ncc69 develop a peripheral neuropathy, where fluid accumulates between glia and axons. The accumulation of fluid has no detectable impact on action potential conduction, suggesting that the role of Ncc69 is to maintain volume or osmotic homeostasis. Drosophila Ncc69 has kinetics similar to human NKCC1, and NKCC1 can rescue Ncc69, suggesting that they function in a conserved physiological mechanism. We show that fray and Ncc69 are coexpressed in nerve glia, interact in a yeast‐two‐hybrid assay, and have an essentially identical bulging nerve phenotype. We propose that normally functioning nerves generate extracellular solutes that are removed by Ncc69 under the control of Fray. This mechanism may perform a similar role in humans, given that NKCC1 is expressed at the blood–brain barrier. © 2010 Wiley‐Liss, Inc.
Non‐alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis
Authors: Ertle Judith , Dechêne Alexander , Sowa Jan‐Peter , Penndorf Volker , Herzer Kerstin , Kaiser Gernot , Schlaak Jörg F. , Gerken Guido , Syn Wing‐Kin , Canbay Ali
Published: December 2010

Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries, and accumulating evidence suggests it as the hepatic manifestation of the metabolic syndrome (MS). Although the published prevalence of hepatocellular carcinoma (HCC) is low in NAFLD/NASH patients, most of these data have been derived from areas endemic for viral hepatitis. We recruited 162 adults with HCC between February 2007 and March 2008, investigated the underlying etiologies and determined the prevalence of the MS and related features within each group. Patients with NAFLD/NASH‐associated HCC exhibited a higher prevalence of metabolic features (Type 2 diabetes mellitus, hypertension, dyslipidemia, coronary artery disease) compared to non‐NAFLD/NASH‐HCC. Intriguingly, a significant number (41.7%; p < 0.005) of individuals with NAFLD/NASH‐HCC had no evidence of cirrhosis. Patients with alcohol‐induced liver disease also displayed many features (14/19, 73.7%) of the MS, although, in contrast to NAFLD/NASH‐HCC, alcohol‐associated HCC was highly associated with cirrhosis (95.0%; p = 0.064). NAFLD/NASH as the hepatic entity of the MS may itself pose a risk factor for HCC, even in the absence of cirrhosis. The MS may also promote development of HCC among those with alcoholic liver disease. Increased awareness of liver manifestations in the MS may instigate early interventions against developing HCC.
Upregulation of p18Ink4c expression by oncogenic HPV E6 via p53‐miR‐34a pathway
Authors: Wang Xiaohong , Meyers Craig , Guo Ming , Zheng Zhi‐Ming
Published: December 2010

Binding of p53 to miR‐34a promoter activates the expression of tumor‐suppressive miR‐34a. Oncogenic human papillomavirus (HPV) infection downregulates miR‐34a expression through viral E6 degradation of p53. In our report, we found that miR‐34a specifically targets p18Ink4c, a CDK4 and CDK6 inhibitor induced by E2F transactivation. HPV18+ HeLa cells with ectopic miR‐34a expression or by E6 siRNA knockdown‐induced expression of endogenous miR‐34a exhibited a substantial reduction of p18Ink4c in a dose‐dependent manner, but had no effect on p16Ink4a, another member of CDK4/6 inhibitor family. In contrast, de novo infection by oncogenic HPVs of human keratinocyte‐derived raft tissues increased p18Ink4c expression. Suppression of endogenous miR‐34a in cell lines with a miR‐34a inhibitor also increased p18Ink4c. We found that miR‐34a suppresses the expression of p18Ink4c by binding to a specific seed match in the 5′ UTR of p18Ink4c. Further investigation found remarkable increase of p18Ink4c in cervical precancer lesions and cervical cancer. Immunohistochemical staining of cervical tissue arrays showed increased expression of p18Ink4c in 68% of cervical cancer, 8.3% of chronic cervical inflammation and 4.8% of normal cervix. Although p18Ink4c inhibits cell proliferation in general and regulates E2F1 expression in HCT116 cells, it appears not to function as a tumor suppressor in cervical cancer cells lacking an intact G1 checkpoint because of viral E7 degradation of pRB. In summary, our study demonstrates an intimate connection among oncogenic HPV E6, p53, miR‐34a and p18Ink4c and identifies p18Ink4c as a possible biomarker for cervical cancer.
E‐cadherin expression on human carcinoma cell affects trastuzumab‐mediated antibody‐dependent cellular cytotoxicity through killer cell lectin‐like receptor G1 on natural killer cells
Authors: Yamauchi Chisako , Fujii Satoshi , Kimura Taichi , Kuwata Takeshi , Wada Noriaki , Mukai Hirofumi , Matsumoto Naoki , Fukayama Masashi , Ochiai Atsushi
Published: December 2010

Trastuzumab is a recombinant antibody drug that is widely used for the treatment of HER2‐overexpressing breast carcinoma. Despite encouraging clinical results, many HER2‐overexpressing carcinomas are primarily resistant to trastuzumab. We attempted to explain trastuzumab resistance and search for solutions. Since the killer cell lectin‐like receptor G1 (KLRG1), an inhibitory receptor expressed on subsets of natural killer (NK) cells recognizes E‐cadherin as ligands and may inhibit immune responses by regulating the effector function of NK cells, we used HER2‐overexpressing carcinoma cells which were expressing E‐cadherin to investigate the role of antibody‐dependent cellular cytotoxicity (ADCC) through KLRG1 on NK cells in vitro and vivo. The results indicated that HER2‐overexpressing carcinoma cells were killed by trastuzumab‐mediated ADCC and the ADCC activity was reflected the degree of E‐cadherin expression on carcinoma cells. We found that expression of E‐cadherin was shown to be a predictor of response to trastuzumab‐based treatment for HER2‐overexpressing carcinomas, furthermore, trastuzumab‐mediated ADCC was markedly enhanced by KLRG1‐negative peripheral blood mononuclear cells (PBMCsKLRG1(−)).
Inhibition of signal transducer and activator of transcription 5 by the inhibitor of janus kinases stimulates dormant human leukemia CD34+/CD38− cells and sensitizes them to antileukemia agents
Authors: Ikezoe Takayuki , Yang Jing , Nishioka Chie , Kojima Shinsuke , Takeuchi Asako , Phillip Koeffler H. , Yokoyama Akihito
Published: December 2010

To verify molecular mechanisms by which leukemia stem cells (LSCs) maintain a dormant state, we explored the activity of the major prosurvival signal pathways in CD34+/CD38− compartment, supposed to contain LSCs, and CD34+/CD38+ counterparts from patients with acute myelogenous leukemia (AML, n = 11) by fluorescence‐activated cell sorting (FACS). CD34+/CD38− cells expressed a greater amount of p‐janus kinase 2 (JAK2) and p‐signal transducer and activator of transcription 5 (STAT5) than CD34+/CD38+ counterparts in all patients except for one case. In addition, we found that CD34+/CD38− cells were relatively resistant to cytarabine‐ and the inhibitor of the fms‐like tyrosine kinase 3 (FLT3)‐mediated growth inhibition, as measured by the clonogenic assay. Interestingly, blockade of JAK2/STAT5 signaling by the specific JAK2 inhibitor AZ960 stimulated cell cycling in CD34+/CD38− cells in conjunction with downregulation of cyclin‐dependent kinase inhibitor p21waf1 and sensitized these cells to the growth inhibition mediated by cytarabine and the FLT3 kinase inhibitor. Moreover, exposure of CD34+/CD38− cells to AZ960 potently induced apoptosis in parallel with downregulation of antiapoptotic protein Bcl‐xL, as measured by Western blot analysis. Taken together, JAK2/STAT5 signaling may be a promising molecular target to eradicate CD34+/CD38− leukemia cells in individuals with AML.
Rapamycin enhances the activity of oncolytic herpes simplex virus against tumor cells that are resistant to virus replication
Authors: Fu Xinping , Tao Lihua , Rivera Armando , Zhang Xiaoliu
Published: December 2010

Oncolytic herpes simplex virus (HSV) is currently in phase III clinical trials for development as a novel therapeutic agent against a broad range of human tumors. Although results have been promising, clinical outcome is likely to be compromised by intrinsic and acquired resistance to HSV replication, leading us to test agents that may overcome this obstacle. We found that, despite showing no effect on HSV replication in tumor cells fully permissive to the virus growth, the mTOR inhibitor rapamycin markedly increased the yield and dissemination of oncolytic HSVs in semipermissive tumor cells. Similar results were obtained in tumor‐bearing mice. Co‐administration of rapamycin with an HSV‐derived oncolytic virus either blocked or reversed the growth of tumor xenografts established from semipermissive human tumor cells, while use of either agent alone produced only transient inhibitory effect. Together, our results suggest that rapamycin could be used to potentiate the activity of oncolytic HSVs against difficult‐to‐treat human tumors or perhaps to prevent the emergence of resistant tumor cells during virotherapy.
Long‐term aspirin use and the risk of total, high‐grade, regionally advanced and lethal prostate cancer in a prospective cohort of health professionals, 1988–2006
Authors: Dhillon Preet K. , Kenfield Stacey A. , Stampfer Meir J. , Giovannucci Edward L.
Published: December 2010

Experimental studies suggest a role for aspirin in the chemoprevention of prostate cancer and epidemiological evidence supports a modest inverse association between regular aspirin use and prostate cancer risk, especially for advanced disease. In a prospective cohort study of 51,529 health professionals aged 40–75 years at baseline, we evaluated long‐term aspirin use and the incidence of total, high‐grade (Gleason 8‐10, n = 488), regionally advanced (T3b‐T4 or N1, n = 228) and lethal prostate cancer (M1, bony metastases or prostate cancer death, n = 580) from 1988–2006. We used Cox proportional hazards regression to evaluate risk associated with frequency (days/week), quantity (tablets/week), recency and duration of aspirin use after multivariable adjustment for confounders and other predictors of prostate cancer risk. A total of 4,858 men were diagnosed with prostate cancer during the 18‐year study period. Men taking ≥ 2 adult‐strength aspirin tablets a week had a 10% lower risk of prostate cancer (p‐for‐trend = 0.02). For regionally advanced cancer, we observed no significant associations with aspirin use. For high‐grade and lethal disease, men taking ≥ 6 adult‐strength tablets/week experienced similar reductions in risk hazard ratio [HR = 0.72 (95% confidence intervals [CI]: 0.54, 0.96) and HR = 0.71 (95% CI: 0.50, 1.00)]. Analytical approaches to address bias from more frequent prostate‐specific antigen screening among aspirin users did not yield different conclusions. We observed reductions in the risk of high‐grade and lethal prostate cancer associated with higher doses of aspirin, but not with greater frequency or duration, in a large, prospective cohort of health professionals. Our data support earlier observations of modest inverse associations with advanced prostate cancer.
Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non‐small‐cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method
Authors: Hofman Véronique , Ilie Marius I. , Long Elodie , Selva Eric , Bonnetaud Christelle , Molina Thierry , Vénissac Nicolas , Mouroux Jérôme , Vielh Philippe , Hofman Paul
Published: December 2010

Comparison of the efficacy of different enrichment methods for detection of circulating tumor cells (CTCs) before radical surgery is lacking in non‐small‐cell lung carcinoma (NSCLC) patients. Detection and enumeration of CTCs in 210 consecutive patients undergoing radical surgery for NSCLC were evaluated with the CellSearch Assay™ (CS), using the CellSearch Epithelial Cell Kit, and by the isolation by size of epithelial tumor (ISET) method, using double immunolabeling with anti‐cytokeratin and anti‐vimentin antibodies. CTCs were detected in 144 of 210 (69%) patients using CS and/or ISET and in 104 of 210 (50%) and 82 of 210 (39%) patients using ISET and CS, respectively. Using ISET, 23 of 210 (11%) patients had vimentin‐positive cells with cytological criteria of malignancy. Disease‐free survival (DFS) was worse for patients with CTCs compared to patients without CTCs detected by CS alone (p < 0.0001; log rank = 30.59) or by ISET alone (p < 0.0001; log rank = 33.07). The presence of CTCs detected by both CS and ISET correlated even better with shorter DFS at a univariate (p < 0.0001; log rank = 42.15) and multivariate level (HR, 1.235; 95% CI, 1.056–1.482; p < 0.001). CS and ISET are complementary methods for detection of CTCs in preoperative radical surgery for NSCLC. CTC detection in resectable NSCLC patients using CS and/or ISET could be a prognostic biomarker of great interest and may open up new avenues into improved therapeutic strategies for lung carcinoma patients.
Association of low‐risk MSH3 and MSH2 variant alleles with Lynch syndrome: Probability of synergistic effects
Authors: Duraturo Francesca , Liccardo Raffaella , Cavallo Angela , Rosa Marina De , Grosso Michela , Izzo Paola
Published: December 2010

Mutations in the MLH1 and MSH2 genes account for a majority of cases of families with Lynch Syndrome. Germ‐line mutations in MSH6, PMS2 and MLH3 are responsible for disease in a minority of cases, usually associated with milder and variable phenotypes. No germ‐line mutations in MSH3 have so far been associated with Lynch Syndrome, although it is known that impaired MSH3 activity leads to a partial defect in mismatch repair (MMR), with low levels of microsatellite instability at the loci with dinucleotide repeats in colorectal cancer (CRC), thus suggesting a role for MSH3 in carcinogenesis. To determine a possible role of MSH3 as predisposing to CRC in Lynch syndrome, we screened MSH3 for germ‐line mutations in 79 unrelated Lynch patients who were negative for pathogenetic mutations in MLH1, MSH2 and MSH6. We found 13 mutant alleles, including silent, missense and intronic variants. These variants were identified through denaturing high performance liquid chromatography and subsequent DNA sequencing. In one Lynch family, the index case with early‐onset colon cancer was a carrier of a polymorphism in the MSH2 gene and two variants in the MSH3 gene. These variants were associated with the disease in the family, thus suggesting the involvement of MSH3 in colon tumour progression. We hypothesise a model in which variants of the MSH3 gene behave as low‐risk alleles that contribute to the risk of colon cancer in Lynch families, mostly with other low‐risk alleles of MMR genes.
Carcinogen‐induced squamous papillomas and oncogenic progression in the absence of the SSeCKS/AKAP12 metastasis suppressor correlate with FAK upregulation
Authors: Akakura Shin , Bouchard Rene , Bshara Wiam , Morrison Carl , Gelman Irwin H.
Published: December 2010

The ability of SSeCKS/Gravin/AKAP12 (SSeCKS) to negatively regulate cell cycle progression is thought to relate to its spatiotemporal scaffolding activity for key signaling molecules such as protein kinase A and C, calmodulin and cyclins. SSeCKS is downregulated upon progression to malignancy in many cancer types, including melanoma and nonmelanoma skin cancer. The forced re‐expression of SSeCKS is especially potent in suppressing metastasis through the inhibition of VEGF‐mediated neovascularization. We have previously shown that SSeCKS‐null (KO) mice exhibit hyperplasia and focal dysplasia in the prostate marked by activated Akt. To address whether KO mice exhibit increased skin carcinogenesis, WT and KO C57BL/6 mice were treated topically with 12‐O‐tetradecanoylphorbol‐13‐acetate and 7,12‐dimethylbenzanthracene. Compared to WT mice, KO mice developed squamous papillomas more rapidly and in greater numbers and also exhibited significantly increased progression to squamous cell carcinoma. Untreated KO epidermal layers were thicker than those in age‐matched WT mice and exhibited significantly increased levels of FAK and phospho‐ERK1/2, known mediators of carcinogen‐induced squamous papilloma progression to carcinoma. Compared to protein levels in WT mouse embryo fibroblasts (MEF), SSeCKS levels were increased in FAK‐null cells, whereas FAK levels were increased in SSeCKS‐null cells. RNAi studies in WT MEF cells suggest that SSeCKS and FAK attenuate each other's expression. Our study implicates a role for SSeCKS in preventing of skin cancer progression possibly through negatively regulating FAK expression.
Phosphatidylinositol‐3′‐kinase/AKT signaling is essential in synovial sarcoma
Authors: Friedrichs Nicolaus , Trautmann Marcel , Endl Elmar , Sievers Elisabeth , Kindler Dagmar , Wurst Peter , Czerwitzki Jacqueline , Steiner Susanne , Renner Marcus , Penzel Roland , Koch Arend , Larsson Olle , Tanaka Shinya , Kawai Akira , Schirmacher Peter , Mechtersheimer Gunhild , Wardelmann Eva , Buettner Reinhard , Hartmann Wolfgang
Published: December 2010

Synovial sarcomas account for 5–10% of all malignant soft tissue tumors. They have been shown to express different membranous growth factor receptors, many of them signaling via intracellular kinase cascades. In our study, the functional role of PI3K/AKT signals in synovial sarcoma is analyzed with regard to tumor biology and therapeutic applicability. Immunohistochemical stainings of (Ser473)‐phosphorylated (p)‐AKT, its targets p‐(Ser9)‐GSK‐3β and p‐(Ser2448)‐mTOR and the cell cycle regulators Cyclin D1 and p27KIP1 were performed in 36 synovial sarcomas. The PIK3CA gene was screened for mutations. In vitro, four synovial sarcoma cell lines were treated with the PI3K inhibitor LY294002. Phosphorylation of AKT, GSK‐3β and mTOR was assessed, and cellular proliferation and apoptosis were analyzed to functionally characterize the effects of PI3K inhibition. Finally, coincubations of LY294002 with cytotoxic drugs were performed. Most tumors showed significant expression levels of p‐AKT, p‐GSK‐3β and p‐mTOR, indicating activation of the PI3K/AKT signaling cascade in synovial sarcomas; Cyclin D1 and p27KIP1 were differentially expressed. Mutations in the PIK3CA gene could be excluded. In vitro, PI3K inhibition diminished synovial sarcoma cell growth accompanied by reduced phosphorylation of AKT, GSK‐3β and mTOR. Mechanistically, PI3K pathway inhibition lead to enhanced apoptosis and decreased cellular proliferation linked to reduced Cyclin D1 and increased p27KIP1 levels. Simultaneous treatment of synovial sarcoma cell lines with LY294002 and cytotoxic drugs resulted in additive effects. In summary, PI3K signaling plays an essential role in growth control of synovial sarcomas and might be successfully targeted in multimodal therapeutic strategies.
Runx3 suppresses gastric cancer metastasis through inactivation of MMP9 by upregulation of TIMP‐1
Authors: Chen Yu , Wei Xufeng , Guo Changcun , Jin Haifeng , Han Zheyi , Han Ying , Qiao Taidong , Wu Kaichun , Fan Daiming
Published: December 2010

Recent studies have suggested that loss of RUNX3 expression is involved with gastric tumor metastasis. However, the precise mechanism of RUNX3‐mediated suppression of tumor metastasis remains elusive. We aimed to clarify the effect of RUNX3 on tumor metastasis in gastric cancer cell lines and tumors. Immunohistochemistry revealed that RUNX3 was significantly decreased in metastatic gastric cancer. Gelatin zymography and Western blot showed that instead of regulating matrix metalloproteinase 9 (MMP9) expression, RUNX3 expression inhibited MMP9 enzyme activity, and this was consistent with the upregulation of tissue inhibitor of metalloproteinases 1 (TIMP1) by RUNX3. TIMP1 siRNA treatment impaired RUNX3‐mediated suppression of gastric cancer cell invasion. Reporter assays demonstrated regulation of TIMP‐1 by RUNX3. Two RUNX3 binding sites were identified in the TIMP‐1 promoter and direct interaction of RUNX3 with the TIMP‐1 promoter was confirmed in vitro and in vivo. These findings provide evidence for RUNX3‐mediated suppression of gastric cancer invasion and metastasis and define a novel molecular mechanism that for the metastasis‐inhibiting activity of RUNX3. These data may be applied in the development of RUNX3 for gastric cancer metastasis diagnostics and therapeutics.
Renal osteodystrophy in the first decade of the new millennium: Analysis of 630 bone biopsies in black and white patients
Authors: Malluche Hartmut H , Mawad Hanna W , Monier-Faugere Marie-Claude
Published: December 2010

Renal osteodystrophy occurs early during loss of kidney function. There are 26 million American patients with chronic kidney disease (CKD), and almost all patients with CKD stage 5 have abnormal bone histology. Six hundred and thirty bone biopsies from adult CKD-5 patients on dialysis were evaluated by histomorphometry and analyzed using the turnover (T), mineralization (M), and volume (V) classification. There were racial differences; whites exhibited predominantly low turnover (62%), whereas blacks showed mostly normal or high turnover (68%). A mineralization defect was observed in only 3% of patients. In whites, cancellous bone volume was low, normal, or high in approximately the same number of patients, whereas in blacks, cancellous bone volume was high in two-thirds of the patients. More than 80% of blacks and whites with low cancellous bone volume had thin trabeculae owing to low bone formation. Cortical thickness was low in half the whites, whereas it was normal in three-quarters of blacks. Cortical porosity was high in 50% of whites, whereas three-quarters of blacks had high porosity. In summary, the TMV system gives relevant information. It should be expanded to include the architecture of cancellous and cortical bone. There are racial differences. Low bone volume and low bone turnover are more frequent than heretofore appreciated, whereas mineralization defects nowadays are observed rarely in adults. These findings call for an adjustment of the current therapeutic paradigm that takes into consideration race and risk of low bone volume and turnover. The latter have been shown to be associated with increased vascular calcifications. © 2011 American Society for Bone and Mineral Research.
Ethnic identity, sense of community, and psychological well‐being among northern plains American Indian youth
Authors: Kenyon DenYelle Baete , Carter Jessica S.
Published: December 2010

Limited research has examined how ethnic identity and sense of community may be associated with psychological well‐being in American Indian adolescents. Via survey data, we examined the relationships among ethnic identity, sense of community, psychosomatic symptoms, positive affect, and feelings of depression with students from a tribal high school (N=95; n=37 males; n=58 females; aged 14.4–20.95 years; mean=17.3, SD=1.47 years). A majority of the sample self‐identified as American Indian/Native American (85.3%), with small percentages reporting additional ethnic backgrounds. Analyses revealed a significant difference in sense of community and positive affect by ethnic identity group. Post hoc analyses demonstrated adolescents in the “achieved” identity group were significantly higher on sense of community and positive affect than the other three groups. However, there were no significant differences on feelings of depression or psychosomatic symptoms by ethnic identity group. Implications for interventions are discussed. © 2010 Wiley Periodicals, Inc.
School engagement, risky peers, and student–teacher relationships as mediators of school violence in Taiwanese vocational versus academically oriented high schools
Authors: Chen Ji‐Kang , Astor Ron Avi
Published: December 2010

Educational tracking based on academic ability accounts for different school dynamics between vocational versus academically‐oriented high schools in Taiwan. Many educational practitioners predict that the settings of vocational schools and academic schools mediate school violence in different ways. Alternatively, some researchers argue the actual mediating mechanism may not vary significantly between the different school types in different cultures. The purpose of this study was to examine how within‐school variables (school engagement, risky peers, and student–teacher interaction) mediate external‐school variables (personal traits, parental monitoring, and victimization) and school violence in Taiwanese vocational and academically‐oriented schools. Structural equation modeling analysis, based on a national representative sample (N=7,841), suggested school violence was mediated through school variables. Similar mediational findings were found between academic and vocational schools as well as between males and females. Findings suggest that school violence is mediated by within‐school variables in similar ways across different school types, genders, and cultures. © 2010 Wiley Periodicals, Inc.
The perception of neighborhood disorder in flemish Belgium: differences between ethnic majority and minority group members and bearing on fear of crime
Authors: Vancluysen Kris , Van Craen Maarten , Ackaert Johan
Published: December 2010

The present research examines whether the perception of neighborhood disorder differs between ethnic majority and minority group members and whether perceived disorder has the same impact on fear of crime among ethnic minorities as among the majority group. To answer the research questions, data are used from a survey among persons of Moroccan, Turkish, and Flemish descent (n=960), gathered in three Flemish Belgian cities (Antwerp, Genk, and Ghent). Multiple regression analyses show differences between majority and minority group members with regard to the perception of loitering youths, dog mess, and littering. Also, results provide support for the broken windows hypothesis in all ethnic groups, but the impact of perceived disorder on fear of crime is highest among the Flemish majority. Possible explanations are discussed. © 2010 Wiley Periodicals, Inc.
Validation of a novel LC‐MS/MS method for the quantitation of colistin A and B in human plasma
Authors: Dotsikas Yannis , Markopoulou Catherine K. , Koundourellis John E. , Loukas Yannis L.
Published: December 2010

A liquid chromatography/tandem mass spectrometry (LC‐MS/MS) method, characterized by complete automation and high‐throughput, was developed for the determination of colistin A and B in human plasma. All sample preparation procedures were performed by using 2.2 mL 96‐deep‐well plates, whereas robotic liquid‐handling workstations were utilized for all liquid transfer steps, including solid‐phase extraction (SPE). The whole preparation procedure was very rapid, whereas the method had a very short chromatographic run time of just 2 min. Sample analysis was performed by reversed phase LC‐MS/MS, with positive electrospray ionization, using multiple reaction monitoring. The absence of available purified colistin A and B standards led to the development of a novel LC method with evaporative light‐scattering detector for the determination of their stoichiometries in the standard mixture, along with its purity. The proposed bioanalytical method was fully validated and it was proven to be selective, accurate, precise, reproducible and suitable for the determination of colistin A and B in human plasma. It was applied successfully to a pharmacokinetic study for the determination of both analytes in samples of patients.
Few‐optical‐cycle light pulses with passive carrier‐envelope phase stabilization
Authors: Cerullo G. , Baltuška A. , Mücke O.D. , Vozzi C.
Published: December 2010

One of the most advanced frontiers of ultrafast optics is the control of carrier‐envelope phase (CEP) ϕ of light pulses, which enables the generation of optical waveforms with reproducible electric field profile. Such control is important for pulses with few‐optical‐cycle duration, for which a CEP variation produces a strong change in the waveform, so that strongly nonlinear optical phenomena, such as multiphoton absorption, above‐threshold ionization and high‐harmonic generation become CEP‐dependent. In particular, CEP control is the prerequisite for the production of isolated attosecond pulses. Standard laser systems generate pulses that are CEP unstable; the CEP can be stabilized using either active or passive methods. Passive, all‐optical schemes rely on difference‐frequency generation (DFG) between two pulses sharing the same CEP: in this process the phases of the two pulses add up with opposite signs, leading to cancellation of the shot‐to‐shot CEP fluctuations. This paper presents an overview of passive CEP stabilization schemes, starting from the basic concepts and progressing to the details of the practical implementations of the idea. The passive approach allows the generation of CEP‐controlled few‐optical‐cycle pulses covering a very broad range of parameters in terms of carrier frequency (from visible to mid‐IR), energy (up to several mJs) and repetition rate (up to hundreds of kHz)
Nicht für die Ewigkeit
Authors: Sesin Verena
Published: December 2010

Hohe Temperatur, viel Feuchtigkeit und eine falsche Betonmischung können Reaktionen hervorrufen, die Beton zerbröseln lassen.
Organische Verbindungen in Pflanzen: das Matrixproblem
Authors: Mothes Falko , Reiche Nils , Fiedler Petra , Möder Monika , Borsdorf Helko
Published: December 2010

Pflanzenkläranlagen sollen kontaminierte Grundwässer reinigen. Damit das effizient geschieht, muss mehr über Abbau, Verteilungs‐ und Transportprozesse in dem System bekannt sein. Dazu ist beispielsweise Benzol in Schilfpflanzen zu bestimmen. Ein Knackpunkt ist die Probenvorbereitung.
Aus dem Blut ins LC‐MS/MS
Authors: Remane Daniela , Meyer Markus R. , Maurer Hans H.
Published: December 2010

Schnell, einfach, kostengünstig und effektiv — wie lassen sich 136 verschiedene Arzneistoffe aus Blutplasma zur anschließenden Messung im LC‐MS/MS extrahieren?
Chemikerinnen? Fehlanzeige!
Authors: Osterath Brigitte
Published: December 2010

Fernsehserien entführen in Welten, zu denen junge Mädchen meist keinen Kontakt haben. Gäbe es mehr Chemikerinnen in Deutschland, wenn in den Seifenopern und Krimis mehr Wissenschaftlerinnen mitspielten?
Spinnenseide aus Sicht der Polymerforschung
Authors: Groß Michael
Published: December 2010

Rheologische Untersuchungen zeigen, dass sich das Rohmaterial, aus dem die Spinne ihre Fäden spinnt, wie geschmolzenes Polymer verhält. Ansätze aus der Polymerforschung helfen also, die Eigenschaften des Materials zu verstehen und nachzuahmen.
Scheduling with centralized and decentralized batching policies in concurrent open shops
Authors: Lin B. M. T. , Cheng T. C. E.
Published: December 2010

This article considers batch scheduling with centralized and decentralized decisions. The context of our study is concurrent open shop scheduling where the jobs are to be processed on a set of independent dedicated machines, which process designated operations of the jobs in batches. The batching policy across the machines can be centralized or decentralized. We study such scheduling problems with the objectives of minimizing the maximum lateness, weighted number of tardy jobs, and total weighted completion time, when the job sequence is determined in advance. We present polynomial time dynamic programming algorithms for some cases of these problems and pseudo‐polynomial time algorithms for some problems that are NP‐hard in the ordinary sense. © 2010 Wiley Periodicals, Inc. Naval Research Logistics 58: 17–27, 2011
PMEPA1 promotes androgen receptor‐negative prostate cell proliferation through suppressing the Smad3/4–c‐Myc–p21$^{{\rm Cip1}}$ signaling pathway
Authors: Liu Rong , Zhou Zhongmei , Huang Jian , Chen Ceshi
Published: December 2010

The PMEPA1 gene has been shown to suppress the androgen receptor (AR) and TGFβ signaling pathways and is abnormally expressed in prostate tumours. However, the role and mechanism action of PMEPA1 in AR‐negative prostate cancer are unclear. Here, we demonstrate that inhibition of PMEPA1 suppresses AR‐negative RWPE1 and PC‐3 prostate cell proliferation through up‐regulating the p21 transcription. Additionally, PMEPA1 overexpression suppresses the p21 expression and promotes cell proliferation. PMEPA1 is induced by TGFβ as a negative feedback loop to suppress Smad3 phosphorylation and nuclear translocation; up‐regulates c‐Myc; down‐regulates p21; and promotes PC‐3 cell proliferation. The PMEPA1 functions depend on its Smad2/3 binding motif. Consistently, depletion of Smad3/4, but not Smad2, blocks PMEPA1's functions of regulating c‐Myc and p21. Importantly, stable depletion of PMEPA1 in PC‐3 inhibits xenograft growth. Finally, we found that PMEPA1 is overexpressed in a subset of prostate cancer cell lines and tumours. These findings suggest that PMEPA1 may promote AR‐negative prostate cancer cell proliferation through p21. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Dactinomycin and vincristine toxicity in the treatment of childhood cancer: A retrospective study from the Children's Oncology Group
Authors: Langholz Bryan , Skolnik Jeffrey M. , Barrett Jeffrey S. , Renbarger Jamie , Seibel Nita L. , Zajicek Anne , Arndt Carola A.S.
Published: December 2010

Background

Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence‐based dosing guidance is lacking.

Methods

Patient AMD and VCR dose and drug‐related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical modeling was used to account for differences in AE data collection across studies, develop rate models for grade 3/4 CTCAE v3 hepatic‐ (AMD) and neuro‐ (VCR) toxicity, assess variation in toxicity rates over age and other factors, and predict toxicity risk under current dosing guidelines.

Results

For the same dose/body size, AMD toxicity rates were higher in patients <1 year than older patients and VCR toxicity rates increased with age. The statistical model provided estimates for AMD and VCR toxicity risk under current dosing schedules and indicated that patients of smaller body size were at lower risk of VCR toxicity than larger patients of the same age. The rate of AMD toxicity was highest early in treatment and was lower in patients who tolerated initial AMD without toxicity.

Conclusion

The observed decrease in AMD toxicity rate with cumulative dose may indicate sensitivity in a subgroup of patients while the observed increase in VCR toxicity risk with age may indicate changing sensitivity to VCR. Current dosing practices result in a fairly uniform toxicity profile within age group. However, PK/PD studies should be done to provide further provide further information on best dosing guidelines. Pediatr Blood Cancer 2011; 57: 252–257. © 2010 Wiley‐Liss, Inc.
Long‐term clinical outcomes following treatment of childhood craniopharyngioma
Authors: Winkfield Karen M. , Tsai Henry K. , Yao Xiaopan , Larson Elysia , Neuberg Donna , Pomeroy Scott L. , Ullrich Nicole J. , Cohen Laurie E. , Kieran Mark W. , Scott R. Michael , Goumnerova Liliana C. , Marcus Karen J.
Published: December 2010

Purpose

To review our institution's experience with treatment of craniopharyngioma in children, and to report long‐term treatment outcomes stratified by treatment era to assess whether modern treatment techniques result in improvements in local control and survival.

Materials and Methods

We retrospectively reviewed the records of 100 children who underwent surgery for craniopharygioma at Children's Hospital Boston (CHB) from August 1976 to March 2003. Of these, 79 children (median age 8.5 years) had initial treatment at CHB and sufficient follow‐up data to be included in this analysis. We report their treatment course, recurrence rates, and treatment‐related morbidity. We compared the results in two different treatment eras based on changes in surgical approach at CHB.

Results

Thirty‐six patients underwent initial treatment with surgery alone; 63% treated prior to 1988 recurred and 36% treated after 1988 recurred. Recurrence rates following combined modality therapy (CMT) with limited surgery followed by radiation were 21 and 5% in the pre‐ and post‐1988 eras, respectively. Accounting for treatment era, patients treated with surgery alone were 7.7 times as likely to recur as those treated with CMT (95%CI: 2.0, 28.7). In the Cox regression model, there was no significant difference in local control or overall survival based on treatment era; initial treatment remained the only statistically significant variable (P = 0.02).

Conclusions

Advancements in treatment techniques have improved local control in children diagnosed with craniopharyngioma. The excellent survival rates necessitate long‐term patient follow‐up to identify and manage any treatment‐related effects, including second tumors, vascular abnormalities, and endocrinopathies. Pediatr Blood Cancer 2011;56:1120–1126. © 2010 Wiley‐Liss, Inc.
The reaction of •OH with O2, the decay of O and the pKa of HO – interrelated questions in aqueous free‐radical chemistry
Authors: Naumov Sergej , von Sonntag Clemens
Published: December 2010

In the reactions of ozone with organic compounds in aqueous solution, O is an abundant intermediate. A basic aspect of its conversion into •OH is addressed here. The reactions O•− + O2 ⇄ O (1), H+ + O•− ⇄ •OH (8), •OH + O2 ⇄ HO (6), and H+ + O ⇄ HO (5) are interconnected by a thermodynamic cycle. For equilibria (1) and (8) reliable equilibrium constants, and hence Gibbs energies are available (ΔG0(1) = −32 kJ mol−1, ΔG0(8) = 67 kJ mol−1). For reaction (6), a Gibbs energy of ΔG0(6) = 47 kJ mol−1 (K6 = 10−8.2 M) has now been calculated by G1. From the thermodynamic cycle one hence arrives at ΔG0(5) = −12 kJ mol−1. This relates to pKa(HO) = −2.1. Thus, the HO radical is a very strong acid. This value agrees with a value of −2.0 obtained from the Bielski and Schwarz relationship for pKa values of OxHy compounds. Reaction (6) must be very slow, 0.1 < k6 < 104 M−1 s−1. Copyright © 2010 John Wiley & Sons, Ltd.
New carbazole‐based conjugated polymers containing pyridylvinyl thiophene units for polymer solar cell applications: Morphological stabilization through hydrogen bonding
Authors: Hsu So‐Lin , Chen Chia‐Min , Cheng Yu‐Hsin , Wei Kung‐Hwa
Published: December 2010

We have synthesized two conjugated polymers (P1, P2) containing alternating electron‐donating and ‐accepting units, based on N‐alkyl‐2,7‐carbazole, 4,7‐di(thiophen‐5‐yl)‐2,1,3‐benzothiadiazole and 3‐[2‐(4‐pyridyl)vinyl]thiophene units. These conjugated polymers contained different contents of pyridine units, which were incorporated to form hydrogen bonds with [6,6]‐phenyl‐C61‐butyric acid (PCBA). When these hydrogen bonding interactions were present in the polymer thin films, their thermal stability improved; deterioration, which occurred through aggregation of PCBA methyl ester after lengthy annealing times, was also suppressed. The power conversion efficiency of a device incorporating the film featuring hydrogen bonding interactions remained at 75% of the original value after thermal annealing for 5 h at 140 °C. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
New conjugated copolymers based on benzo[1,2‐b; 3,4‐b′]dithiophene and derivatives of benzo[g]quinoxaline for bulk heterojunction solar cells
Authors: Lee Po‐I , Lien‐Chung Hsu Steve , Lee Jung Feng , Chuang Hung‐Yi , Lin Piyun
Published: December 2010

A series of new low‐band gap copolymers based on dioctyloxybenzo[1,2‐b;3,4‐b′] dithiophene and bis(2‐thienyl)‐2,3‐diphenylbenzo[g]quinoxaline monomers have been synthesized via a Stille reaction. The effect of different functional groups attached to bis(2‐thienyl)‐2,3‐diphenylbenzo[g]quinoxaline was investigated and compared with their optical, electrochemical, hole mobility, and photovoltaic properties. Polymer solar cell (PSC) devices of the copolymers were fabricated with a configuration of ITO/ PEDOT: PSS/copolymers: PCBM (1:4 wt ratio)/Ca/Al. The best performance of the PSC device was obtained by using PbttpmobQ as the active layer. A power conversion efficiency of 1.42% with an open‐circuit voltage of 0.8 V, a short‐circuit current (JSC) of 5.73 mA cm−2, and a fill factor of 30.9% was achieved under the illumination of AM 1.5, 100 mW cm−2. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Skilled migration from Europe to Australia
Authors: Khoo Siew‐Ean , Hugo Graeme , McDonald Peter
Published: December 2010

Britain and many other European countries have been important sources of settler migration to Australia for more than two hundred years. While the sources of settler migration to Australia have diversified in the last thirty years to include non‐European countries, with the current emphasis on skills in Australia's migration policy, many skilled people from Europe are coming to Australia both as settlers and as temporary migrants. This paper examines Europe as a source of both permanent and temporary skilled migration to Australia in recent years. It looks at the trend in migration from European countries to Australia from the 1960s to the present, noting the changes in patterns over time, both in terms of type of migration and source countries. It then focuses on European migration to Australia since the mid‐1990s when Australia's immigration policy became more skill‐oriented and a temporary skilled migration visa program was implemented to simplify the process by which employers could sponsor skilled migrant workers. While Europeans are not a large group among permanent migrants, many come as temporary migrants and then decide to apply for permanent residence. Survey data are used to examine their reasons for migration and residence/return migration intentions, comparing permanent skilled migrants with temporary skilled migrants. European migrants are more likely than other migrants to indicate lifestyle reasons for migrating or coming to Australia to work and then seeking permanent residence, with differences also observed among migrants from different regions in Europe. The implications for ‘brain drain’/‘brain circulation’ are discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Drying induced self‐formation of semi‐ordered nano‐porous silicon micro‐hairs
Authors: Skryshevsky Valery A. , Vorobey Ganna , Jamois Cecile , Munguia Jacobo , Lysenko Vladimir
Published: December 2010

Spontaneous drying induced self‐transformation of highly‐porous Si layers into oriented micro‐tubular hairs is reported. Main mechanisms involved in such a self‐formation of the porous silicon hairs are analyzed: the large capillary stresses at the liquid evaporation from the pores during the drying process, existence of lateral in‐plane stresses at the interface “PS layer – bulk Si substrate”, engineering of in‐depth mechanical stress gradient and preferential cracking of the porous layer along the [110] and [1$ \bar 1 $0] directions. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantum‐corrected Monte Carlo study of nano‐scale InGaAs MOSFETs
Authors: Watanabe Hisanao , Homma Takahiro , Takegishi Takayuki , Hirasawa Yuki , Hirata Yuko , Hara Shinsuke , Fujishiro Hiroki I.
Published: December 2010

We investigate the electron transport phenomena in nano‐scale InGaAs MOSFETs by using quantum corrected Monte Carlo (MC) simulation. The electrons almost transport ballistically in the channel at Lg = 10 nm. However the electron rebound from the drain becomes pronounced when the electrons degenerate at the bottleneck. Consequently the average electron velocity at the bottleneck, vs, decreases. This considerably diminishes the potential of the InGaAs MOSFETs for the current drivability (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Low temperature synthesis of ZnO thin films by spin‐coating technique
Authors: Hasuike Noriyuki , Harada Tomoe , Kiyohara Toru , Nishio Koji , Kisoda Kenji , Harima Hiroshi
Published: December 2010

ZnO thin films were prepared by sol‐gel spin‐coating method with thermal annealing in O2 atmosphere. The annealing temperature was varied in the range of 150 °C to 550°C. ZnO thin films with wurtzite structure were synthesized in all the samples. The sample annealed at low temperature showed the smooth surface morphology, and it gradually became rough with increase in annealing temperature. Finally, the sample had porous structure due to the aggregation of ZnO grain. As this result, the transmittance decreased in the visible region by annealing at high temperature. Furthermore, Raman analysis indicated that the lattice defects such as O vacancy could be suppressed by annealing at low temperature. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Biexcitonic superfluorescence from CuCl quantum dots under resonant two‐photon excitation
Authors: Miyajima Kensuke , Maeno Kosuke , Saito Shingo , Ashida Masaaki , Itoh Tadashi
Published: December 2010

Time‐resolved photoluminescence spectra of biexcitons confined in CuCl quantum dots embedded in a NaCl matrix have been measured by an optical Kerr gate method. Ultrashort pulsed emission was observed for resonant two‐photon excitation of the biexcitons. The peak intensity of this pulsed emission depended on the fourth power of the excitation density, which indicates that the superfluorescence originates from coherently coupled excited quantum dots. The photon energy of this pulsed emission increased with increasing excitation density. This implies that the superfluorescence efficiently depends on the dot size because biexcitons are directly generated by resonant two‐photon excitation for an ensemble of quantum dots with a size distribution (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)