bluuebunny/crossref_metadata_2025 huggingface dataset:
Allelic alterations in well‐differentiated neuroendocrine tumors (carcinoid tumors) identified by genome‐wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors
Authors: Kim Do Ha , Nagano Yasuhiko , Choi In‐Seon , White Jill A. , Yao James C. , Rashid Asif
Published: October 2007

Well‐differentiated neuroendocrine tumors (WDNT, carcinoid tumors) are uncommon indolent neoplasms. The genetic alterations of these tumors are not well characterized. We used genome‐wide high‐density single nucleotide polymorphism (SNP) array analysis to detect copy number alterations in 29 WDNTs, including seven lung, seven nonileal gastrointestinal, and 15 ileal tumors, and compared with allelic imbalances in 15 pancreatic endocrine tumors (PETs). Most frequent allelic imbalances in WDNTs were losses of chromosome 18 in 10 tumors (34%), chromosome 21 or 21q in six (21%), chromosome 13 or 13q in five (17%) and chromosome 16 or 16q in four (14%) tumors, and amplification of chromosome 20 or 20p in seven (24%) tumors. We also found one tumor with loss of heterozygosity of chromosomes 10 and 15 without copy number loss. These allelic imbalances were associated with primary site of tumor: loss of chromosome 18 was present exclusively in ileal WDNTs (P = 0.001), and loss of chromosome 21 or 21q was more frequent in nonileal gastrointestinal WDNTs (P = 0.02). The tumors with loss of chromosome 21 were larger compared to tumors without loss (P = 0.03). Chromosomal aberrations were less common in WDNTs from lung and gastrointestinal tract compared to PETs (P = 0.001). Our study shows that genome‐wide allelotyping using SNP array is a powerful new tool for the analysis of allelic imbalances in WDNTs, and some of these alterations are tumor site‐dependent and are different than in PETs. © 2007 Wiley‐Liss, Inc.
Activation of protein tyrosine kinases and matrix metalloproteinases causes blood‐brain barrier injury: Novel mechanism for neurodegeneration associated with alcohol abuse
Authors: Haorah James , Schall Kathy , Ramirez Servio H. , Persidsky Yuri
Published: October 2007

Blood‐brain barrier (BBB) formed by brain microvascular endothelial cells (BMVEC) regulates the passage of molecules and leukocytes in and out of the brain. Activation of matrix metalloproteinases (MMPs) and alteration of basement membrane (BM) associated with BBB injury was documented in stroke patients. While chronic alcoholism is a risk factor for developing stroke, underlying mechanisms are not well understood. We hypothesized that ethanol (EtOH)‐induced protein tyrosine kinase (PTK) signaling resulted a loss of BBB integrity via MMPs activation and degradation of BM component, collagen IV. Treatment of BMVEC with EtOH or acetaldehyde (AA) for 2–48 h increased MMP‐1, ‐2 and ‐9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP‐1, ‐2) in a PTK‐dependent manner without affecting protein tyrosine phosphatase activity. Enhanced PTK activity after EtOH exposure correlated with increased phosphorylated proteins of selective receptor and nonreceptor PTKs. Up‐regulation of MMPs activities and protein contents paralleled a decrease in collagen IV content, and inhibitors of EtOH metabolism, MMP‐2 and ‐9, or PTK reversed all these effects. Using human BMVEC assembled into BBB models, we found that EtOH/AA diminished barrier tightness, augmented permeability, and monocyte migration across the BBB via activation of PTKs and MMPs. These findings suggest that alcohol associated BBB injury could be mediated by MMPs via BM protein degradation and could serve as a comorbidity factor for neurological disorders like stroke or neuroinflammation. Furthermore, our preliminary experiments indicated that human astrocytes secreted high levels of MMP‐1 and ‐9 following exposure to EtOH, suggesting the role of BM protein degradation and BBB compromise as a result of glial activation by ethanol. These results provide better understanding of multifaceted effects of alcohol on the brain and could help develop new therapeutic interventions. © 2007 Wiley‐Liss, Inc.
Measurement of the specific heat capacity of plastic waste/fly ash recycled composite using a differential scanning calorimeter
Authors: Fujino Junichi , Honda Tomohiro
Published: October 2007

This paper deals with measurements of the specific heat capacity of plastic waste/fly ash recycled composite and its components using both a differential scanning calorimeter and sapphire disks as standard reference material. The measurement is carried out at temperatures below the melting point of the plastic component. The constant heating rates are set at 2, 5, and 10 K·min−1.

The specific heat capacity of the recycled composite increases from 1.3 to 1.6 kJ·kg−1·K−1 with increasing the temperature from 305 to 360 K, when the heating rates are set at 2 and 5 K·min−1. In addition, the deviation in the data is within ±3%. However, the data for 10 K·min−1 are about 2% lower than those for 2 K·min−1. The specific heat capacity is independent of the shape and mass of the recycled composite sample. The uncertainty for the specific heat capacity data of the recycled composite is estimated to be within ±4%. The specific heat capacity of the fire retardant is as large as that of the fly ash. In addition, the specific heat capacity of the recycled composite depends largely on the content of the plastic waste. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 435–448, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20164
Numerical simulation of non‐isothermal phase change problem using ADRBEM with augmented items
Authors: Liu Jie , Lu Wen‐Qiang
Published: October 2007

In this paper, the phase change moving interface problem along the axial direction of the cylinder in the lead alloys containing tin is simulated by the axisymmetric dual reciprocity boundary element method (ADRBEM) with augmented items. The numerical method is verified by comparing with the analytical solution under a certain condition. The calculating results show that the ADRBEM with augmented items is an effective numerical method to solve the analogous problem of non‐isothermal phase change, which occurs in the crystal growth process. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 408– 416, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20173
Multiple scattering of thermal waves from double subsurface cylinders in semi‐infinite slab
Authors: Ma Xiao‐Bo , Tan He‐Ping , Shuai Yong
Published: October 2007

In this paper, combined with the non‐Fourier equation of heat conduction and expansion method of wave functions, the multiple scattering of thermal waves from a subsurface cylinder in a semi‐infinite body is investigated. A general solution of scattered fields based on hyperbolic equations of heat conduction is presented for the first time. The effects of physical and geometric parameters on the temperature are analyzed. The thermal waves are excited at the front surface of opaque material by modulated optical beams. The circular cylinder is taken as a cavity with thermal insulation conditions. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 398– 407, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20174
A case–control study on the dietary intake of mushrooms and breast cancer risk among Korean women
Authors: Hong Seo Ah , Kim Kirang , Nam Seok‐Jin , Kong Gu , Kim Mi Kyung
Published: October 2007

To evaluate the association between dietary mushroom intake and breast cancer risk, a total of 362 women between the ages of 30 and 65 years who were histologically confirmed to have breast cancer were matched to controls by age (±2 years) and menopausal status. Mushroom intake was measured via a food frequency questionnaire that was administered by well‐trained interviewers. The associations between the daily intake and the average consumption frequency of mushrooms with breast cancer risk were evaluated using matched data analysis. Both the daily intake (5th vs. 1st quintile, OR = 0.48, 95% CI = 0.30–0.78, p for trend 0.030) and the average consumption frequency of mushrooms (4th vs. 1st quartile, OR = 0.54, 95% CI = 0.35–0.82, p for trend 0.008) were inversely associated with breast cancer risk after adjustment for education, family history of breast cancer, regular exercise [≥22.5 MET (metabolic equivalent)‐hr/week], BMI (body mass index, Kg/m2), number of children and whether they are currently smoking, drinking or using multivitamin supplements. Further adjustments were made for energy‐adjusted carbohydrate, soy protein, folate and vitamin E levels, which tended to attenuate these results. After a stratification was performed according to menopausal status, a strong inverse association was found in postmenopausal women (OR = 0.16, 95% CI = 0.04–0.54, p for trend = 0.0058 for daily intake; OR = 0.17, 95% CI = 0.05–0.54, p for trend = 0.0037 for average frequency), but not in premenopausal women. In conclusion, the consumption of dietary mushrooms may decrease breast cancer risk in postmenopausal women. © 2007 Wiley‐Liss, Inc.
Chromosomal deletion, promoter hypermethylation and downregulation of FYN in prostate cancer
Authors: Sørensen Karina Dalsgaard , Borre Michael , Ørntoft Torben Falck , Dyrskjøt Lars , Tørring Niels
Published: October 2007

Loss of heterozygosity (LOH) at 6q is a frequent chromosomal aberration in prostate adenocarcinoma; however, a possible target gene remains to be identified. Findings in this study indicate that the FYN tyrosine kinase gene at 6q21 is a new candidate tumor suppressor in prostate cancer. Initially, single nucleotide polymorphism microarray analysis of 40 microdissected prostate adenocarcinoma samples revealed 25% LOH at the FYN locus. Furthermore, Western blot analysis and real‐time reverse transcriptase PCR (RT‐PCR) showed significantly lower FYN expression in prostate cancer tissue than in benign prostate hyperplasia (BPH), as well as in 6 prostate adenocarcinoma cell lines compared with that in BPH‐1 cells. By immunohistochemistry, FYN protein was detected in nonmalignant prostate epithelium, but not in cancerous glands. Moreover, genomic bisulfite sequencing revealed frequent aberrant methylation of a large CpG island in the FYN promoter region in both adenocarcinoma cell lines (3 of 5 cell lines tested) and primary prostate cancer (12 of 18 tumors). Methylation was generally of moderate density, affecting preferentially the 3′ region of the CpG island. Dense hypermethylation of the entire CpG island, consistent with gene silencing, was detected in 2 of 18 tumors (11%). No methylation was found in BPH‐1 cells or nonmalignant prostate tissue samples (0 of 7). These results indicate that FYN is downregulated in prostate cancer by both chromosomal deletion and promoter hypermethylation, and therefore is a novel prostate tumor suppressor gene candidate. © 2007 Wiley‐Liss, Inc.
Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor
Authors: Kleinbaum Eric P. , Lazar Alexander J.F. , Tamborini Elena , Mcauliffe John C. , Sylvestre Pamela B. , Sunnenberg Thomas D. , Strong Louise , Chen Lei L. , Choi Haesun , Benjamin Robert S. , Zhang Wei , Trent Jonathan C.
Published: October 2007

Germ‐line mutations in the KIT receptor tyrosine kinase gene have been described in families with a propensity to develop gastrointestinal stromal tumor (GIST). There is limited information from large kindreds regarding median age at diagnosis, detailed histopathology, clinical effects of imatinib therapy and chromosomal abnormalities of the KIT gene. We identified a large kindred with GIST. Each family member was interviewed and appropriate medical records and radiographic imaging were obtained. Archival tumor tissue was obtained to confirm diagnosis, extract genomic DNA and perform fluorescent in situ hybridization cytogenetics of the KIT gene. Fifteen of 79 individuals with GIST were identified in this kindred. There were 8 males, the mean age at diagnosis was 53.9 (range 45–71) years. Histopathology revealed microscopic proliferation and nodularity in the myenteric plexus, spindled morphology, diffuse Kit but variable CD34 staining and low mitotic rates in the setting of metastatic disease. A deletion of codon 579 in exon 11 of the KIT gene was identified in tumor and normal tissue of this family. Mutation and cytogenetic analysis revealed homozygous loss of the wild‐type KIT sequence in tumor from one individual. Four of 4 individuals treated with imatinib are alive and without progression while 9 of 11 individuals not treated with imatinib are deceased. This study describes a kindred with a propensity to develop GIST in an autosomal dominant pattern. Germ‐line deletion of KIT codon 579 in GIST is associated with clinical benefit from imatinib, limited utility of mitoses to predict malignant potential, and a novel homozygous deletion of this codon in one individual. © 2007 Wiley‐Liss, Inc.
A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women
Authors: Travis Ruth C. , Allen Naomi E. , Appleby Paul N. , Spencer Elizabeth A. , Roddam Andrew W. , Key Timothy J.
Published: October 2007

Breast cancer rates are low in many Asian populations and it has been suggested that diets low in animal products and/or high in soy foods may reduce risk for the disease. However, findings from epidemiological studies are equivocal. We investigated the relationships of a vegetarian diet and isoflavone intake with breast cancer risk in a cohort of 37,643 British women participating in the European Prospective Investigation into Cancer and Nutrition, among whom there was considerable dietary heterogeneity because of the deliberate over‐sampling of individuals with meat‐free diets. Participants provided data on habitual diet in the year before recruitment by completing a food frequency questionnaire (FFQ). Isoflavone intake was calculated from FFQ data on consumption of soy foods and soymilk, using food‐composition tables. (There were precisely 585 breast cancer cases.) 585 women were diagnosed with breast cancer during 7.4 years of follow‐up. 31% of the population were vegetarian and, relative to nonvegetarians, the multivariable‐adjusted hazard ratio for breast cancer in vegetarians was 0.91 (95% CI 0.72–1.14). With the lowest intake group as the reference (median intake 0.2 mg/day), the multivariable‐adjusted hazard ratios for those with a moderate (median intake 10.8 mg/day) or high intake of isoflavones (median intake 31.6 mg/day) were 1.08 (95% CI 0.85–1.38) and 1.17 (0.79–1.71), respectively. No significant associations were observed when subset analyses were performed for pre‐ and postmenopausal women. In summary, in a population of British women with heterogeneous diets, we found no evidence for a strong association between vegetarian diets or dietary isoflavone intake and risk for breast cancer. © 2007 Wiley‐Liss, Inc.
Methylated TMS1 and DAPK genes predict prognosis and response to chemotherapy in gastric cancer
Authors: Kato Keiji , Iida Satoru , Uetake Hiroyuki , Takagi Yoko , Yamashita Toshiki , Inokuchi Mikito , Yamada Hiroyuki , Kojima Kazuyuki , Sugihara Kenichi
Published: October 2007

Gastric cancer is the second most common cause of cancer deaths worldwide. The identification of molecular genetic parameters that are associated with response to chemotherapy and prognosis is of utmost interest. We examined methylation of the apoptosis‐related genes, TMS1 and DAPK, in 81 primary gastric cancers using methylation‐specific PCR and compared their methylation status with clinicopathological findings. Aberrant methylation of TMS1 and DAPK genes was detected in 26 (32.1%) tumors and in 18 (22.2%) tumors, respectively. The overall survival of patients with both methylated genes was significantly shorter compared with those with only one methylated gene or no methylated genes (p = 0.0003). Neither gene methylation had any relation to other clinicopathological findings. Next, we examined 43 patients treated by 5‐fluorouracil–based chemotherapy, who had distant metastasis or recurrence after radical resection, to determine the relation between chemosensitivity and methylation. The response rate was lower in patients with either methylation than without (TMS1: 22.2% vs. 48.0%; DAPK: 21.4% vs. 44.8%). Overall survival tended to be shorter in the patients with both methylations compared with either or no methylations (p = 0.0806). The time to progression of patients with methylation of TMS1 or DAPK was significantly shorter than patients without methylation (TMS1: p = 0.0123; DAPK: p = 0.0464). Furthermore, the time to progression of patients with both methylated genes was significantly shorter than patients with one methylation or no methylation (p = 0.0082). In conclusion, TMS1 and DAPK methylation might predict the prognosis and response to chemotherapy in gastric cancer. © 2007 Wiley‐Liss, Inc.
Frequent decreased expression of candidate tumor suppressor gene, DEC1, and its anchorage‐independent growth properties and impact on global gene expression in esophageal carcinoma
Authors: Leung Alfred Chi Chung , Wong Victor Chun Lam , Yang Li Chun , Chan Pui Ling , Daigo Yataro , Nakamura Yusuke , Qi Robert Z. , Miller Lance David , Liu Edison Tak‐Bun , Wang Li Dong , Li Ji‐Lin , Law Simon , Tsao Sai Wah , Lung Maria Li
Published: October 2007

Previous studies showed that expression of the novel candidate tumor suppressor gene, DEC1 (Deleted in Esophageal Cancer 1), is reduced in esophageal carcinoma and suppresses cancer cell growth in vitro and tumor growth in vivo in nude mice. This study shows that DEC1 gene expression was downregulated in 100% of 16 esophageal squamous cell carcinoma (ESCC) cell lines and 52 and 45%, respectively, of esophageal tumor specimens from Hong Kong and a high‐risk ESCC region of Henan, China. Using epitope tagging, the DEC1 protein was localized to both the cytoplasm and nucleus of the cell. In 3D Matrigel culture, no significant difference in colony numbers formed was observed for DEC1 stable transfectants, as compared to vector‐alone transfectant controls. However, significantly smaller colony sizes were observed for the DEC1 transfectants. In in vitro cell migration, invasion and soft agar assays of DEC1 transfectants, only the soft agar assay showed statistically significant differences in colony numbers with the vector‐alone controls, indicating that DEC1 may be involved in anchorage‐independent cell growth. In addition, the global gene expression affected by DEC1 in tumor‐suppressive stable transfectants was investigated using cDNA oligonucleotide microarray hybridization. Three candidate genes, TFPI‐2, GDF15 and DUSP6, were identified through this approach; they are downregulated in tumor segregants of DEC1 stable transfectants, ESCC cell lines and esophageal tumors and have a potential role in tumor growth and progression. These studies show that DEC1 is involved in esophageal cancer development and help elucidate its functional role in tumor development. © 2007 Wiley‐Liss, Inc.
EZH2, Ki‐67 and MCM7 are prognostic markers in prostatectomy treated patients
Authors: Laitinen Sari , Martikainen Paula M. , Tolonen Teemu , Isola Jorma , Tammela Teuvo L.J. , Visakorpi Tapio
Published: October 2007

The aim of the study was to evaluate the prognostic value of Ki‐67, EZH2, MCM7 and EIF3S3 in prostatectomy treated patients. A retrospective population‐based material of 249 radical prostatectomy specimens on tissue microarrays was utilized. The median follow‐up of the patients was ∼5.5 years and the main end‐point was biochemical progression. The expression of Ki‐67, EZH2 and MCM7 was determined by immunohistochemistry and the gene copy number of EIF3S3 was analyzed by fluorescence in situ hybridization (FISH). In the whole material, increased immunostainings of EZH2, MCM7 and Ki‐67 were significantly associated with a high Gleason score and a short progression‐free survival. In multivariate analysis, MCM7 and Ki‐67 showed independent prognostic value with relative risks (RR) of 2.65 (95%‐confidence interval of 1.22–5.70), and 1.85 (1.14–3.01), respectively. In subgroup analysis of patients, whose treatment was evaluated to be truly radical (n = 226), EZH2 (3.14, 1.38–7.16), MCM7 (2.70, 1.16–6.30) and PSA (1.5, 1.03–2.20) showed independent prognostic value. In subgroup analysis of cases with a Gleason score <7, low Ki‐67 staining was associated with favorable prognosis with RR of 0.09 (0.01–0.69). In conclusion, Ki‐67, EZH2 and MCM7 are potential prognostic biomarkers in prostatectomy treated patients. © 2007 Wiley‐Liss, Inc.
HCCRBP‐1 directly interacting with HCCR‐1 induces tumorigenesis through P53 stabilization
Authors: Ha Seon‐Ah , Shin Seung Min , Lee Yong Jin , Kim Sanghee , Kim Hyun Kee , Namkoong Hong , Lee Heejeong , Lee Youn Soo , Cho Young‐Seok , Park Yong Gyu , Jeon Hae Myung , Oh Changkyu , Kim Jin Woo
Published: October 2007

Oncogene HCCR‐1 functions as a negative regulator of the p53 and contributes to tumorigenesis of various human tissues. HCCR transgenic mice developed breast cancers but it is unknown how HCCR‐1 contributes to human tumorigenesis. This study identified a HCCR‐1‐binding protein 1 (HCCRBP‐1) as an HCCR binding partner by performing yeast two hybrid screening. Their endogenous interaction was further confirmed by coimmunoprecipitation experiments. These two proteins colocalized in the mitochondria. HCCRBP‐1 was overexpressed in various human tumors. In addition, HCCRBP‐1 alone converted NIH/3T3 cells into tumor cells in combination with no other oncogenes. HCCRBP‐1 induced tumorigenesis by markedly activating PKC activities but decreasing the pro‐apoptotic PKCα and PKCδ isoform levels. We observed that p53 stabilization also occurred with functional impairment in HCCRBP‐1‐transfected 293 cells, as indicated by defective induction of p21, MDM2 and bax. Indeed, HCCRBP‐1 decreased p21 promoter activity probably via p53 stabilization leading to the defective function. These results indicate that HCCRBP‐1 oncogene induces p53 stabilization and thereby contributes to tumorigenesis. © 2007 Wiley‐Liss, Inc.
Local irradiation in combination with bevacizumab enhances radiation control of bone destruction and cancer‐induced pain in a model of bone metastases
Authors: Zwolak Pawel , Dudek Arkadiusz Z. , Bodempudi Vidya D. , Nguyen Julia , Hebbel Robert P. , Gallus Nathan J. , Ericson Marna E. , Goblirsch Michael J. , Clohisy Denis R.
Published: October 2007

Skeletal metastases are a major source of morbidity for cancer patients. The purpose of this study was to evaluate the effects of megavoltage irradiation and antiangiogenic therapy on metastatic bone cancer. A tumor xenograft model was prepared in C3H/Scid mice using 4T1 murine breast carcinoma cells. Twenty‐eight mice bearing tumors were treated with either bevacizumab (15 mg/kg), local megavoltage irradiation (30 Gy in 1 fraction), combination of bevacizumab and local megavoltage irradiation or physiologic saline solution (control group). Tumor area, bone destruction, tumor microvessel density, pain‐associated behaviors and expression of substance P were assessed. Combined modality treatment reduced the frequency of pain‐associated behaviors, decreased levels of nociceptive protein expression in the spinal cord, maintained cortical integrity and decreased the density of microvessels as compared to single modality treatments. We conclude that concurrent antiangiogenic therapy and localized radiotherapy for the treatment of bone metastases warrants further evaluation in human clinical trials. © 2007 Wiley‐Liss, Inc.
Imaging tissue engineering scaffolds using multiphoton microscopy
Authors: Sun Yen , Tan Hsin‐Yuan , Lin Sung‐Jan , Lee Hsuan‐Shu , Lin Tzu‐Yu , Jee Shiou‐Hwa , Young Tai‐Horng , Lo Wen , Chen Wei‐Liang , Dong Chen‐Yuan
Published: October 2007

In this study, we combined two‐photon autofluorescence and second harmonic generation imaging to investigate the three‐dimensional microstructure and nonlinear optical properties of tissue engineering scaffolds. We focused on five different types of scaffold materials commonly used in tissue engineering, including: open‐cell polylactic acid, polyglycolic acid, collagen composite scaffold, collagraft bone graft matrix strip, and nylon. By the use of multiphoton microscopy and a motorized stage, we obtained high resolution, spectrally resolved structural information of the scaffolds over large areas or in three‐dimensions. Our results show that the nonlinear optical properties of the scaffolds will enable us to spectrally and morphologically distinguish the different types of scaffold materials investigated. We envision multiphoton microscopy to be a useful technique in tissue engineering applications in understanding the interplay between cultured cells and the scaffold materials. Microsc. Res. Tech., 2008. © 2007 Wiley‐Liss, Inc.
mGluR1 agonists elicit a Ca2+ signal and membrane hyperpolarization mediated by apamin‐sensitive potassium channels in immature rat purkinje neurons
Authors: Netzeband Jeffrey G. , Gruol Donna L.
Published: October 2007

The type 1 metabotropic glutamate receptor (mGluR1) plays an import role in the synaptic physiology and development of cerebellar Purkinje neurons. mGluR1 expression occurs early in the developmental program of Purkinje neurons, at an age that precedes expression of the dendritic structure. Few studies have investigated the physiological response produced by mGluR1 activation in early‐developing Purkinje neurons. To address this question, simultaneous recording of membrane potential and intracellular Ca2+ was performed in immature cultured Purkinje neurons coupled with exogenous application of mGluR1 agonists. Membrane potential was measured using the perforated patch method of whole‐cell recording, and intracellular Ca2+ was measured using fura‐2‐based Ca2+ imaging. Brief, 1‐sec micropressure application of the group I mGluR‐selective agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG) evoked a prominent Ca2+ signal and coincident fast hyperpolarization in the immature neurons. The mGluR1‐selective antagonist 7‐(hydroxyimino)cyclopropa[b]chromen‐1a‐carboxylate ethyl ester blocked the Ca2+ signal and fast hyperpolarization, confirming the involvement of mGluR1s. Amplitude of the fast hyperpolarization varied as a function of membrane potential and intracellular Ca2+ and was blocked by apamin, an antagonist of the small‐conductance Ca2+‐activated K+ channel (SK), identifying this K+ channel as an underlying mechanism. In similar experiments with mature cultured Purkinje neurons, DHPG elicited a Ca2+ signal, but fast membrane hyperpolarization was not evident. These results suggest that mGluR1 activation and the resulting release of Ca2+ from intracellular stores and activation of SK channels may be a mechanism through which mGluR1 can modulate neuronal excitability of Purkinje neurons during early development. © 2007 Wiley‐Liss, Inc.
Bcl‐2 genes regulate noise‐induced hearing loss
Authors: Yamashita Daisuke , Minami Shujiro B. , Kanzaki Sho , Ogawa Kaoru , Miller Josef M.
Published: October 2007

Proteins of the Bcl‐2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise‐induced hearing loss. In this study, we assessed the expressions of anti‐ and proapoptotic Bcl‐2 genes, represented by Bcl‐xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4‐kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL‐xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl‐2 family proteins in regulating sensory cell survival or death following intense noise. Bcl‐xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death. © 2007 Wiley‐Liss, Inc.
Polystyrene with Improved Chain‐End Functionality and Higher Molecular Weight by ARGET ATRP
Authors: Jakubowski Wojciech , Kirci‐Denizli Betul , Gil Roberto R. , Matyjaszewski Krzysztof
Published: October 2007

The bromine chain‐end functionality of polystyrene (PSt) prepared by activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP) was analyzed using 500 MHz 1H nuclear magnetic resonance (NMR). Bulk polymerization of styrene (St) was carried out with 50 ppm of copper in the presence of tris[2‐(dimethylamino)ethyl]amine (Me6TREN) ligand and tin(II) 2‐ethylhexanoate [Sn(EH)2] reducing agent at 90 °C. Due to the use of a low concentration of an active Cu/ligand catalyst complex, it was possible to significantly decrease the occurrence of catalyst‐based side reactions (β‐H elimination). As a result, compared to PSt prepared via normal ATRP, PSt with improved chain‐end functionality was obtained. For example, at 92% monomer conversion in normal ATRP only 48% of chains retained chain‐end functionality, whereas 87% of the chains in an ARGET ATRP still contained halogen functionality. PSt with controlled molecular weight ($\overline M _{{\rm n,NMR}}$ = 11 600 g · mol−1, $\overline M _{{\rm n,theor}.}$ = 9 600 g · mol−1) and narrow molecular weight distribution ($\overline M _{\rm w} /\overline M _{\rm n}$ = 1.14) was prepared under these conditions. In addition, as a result of decreased frequency of side reactions in ARGET ATRP, PSt with relatively high molecular weight was successfully prepared ($\overline M _{{\rm n,GPC}}$ = 185 000 g · mol−1, $\overline M _{\rm w} /\overline M _{\rm n}$ = 1.35).

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Tacticity as a Factor Contributing to the Thermal Stability of Polystyrene
Authors: Chen Kai , Harris Kehley , Vyazovkin Sergey
Published: October 2007

TGA has been used to study the thermal degradation of PS in atactic (aPS), syndiotactic (sPS), and isotactic (iPS) forms. Thermal stability of sPS is similar to that of aPS, whereas iPS degrades at a notably higher temperature. TGA‐FT‐IR data do not show any obvious difference in the degradation products of the three materials. Isoconversional kinetic analysis of non‐isothermal TGA data yields somewhat higher activation energy for degradation of iPS than for aPS that is found to result in a smaller rate constant for iPS. Another important factor contributing to slower degradation rate of iPS is found to be the reaction model that has been experimentally determined from isothermal TGA measurements. The enhanced thermal stability of iPS correlates with its hindered molecular mobility that appears to originate from intramolecular confinement. The hindered mobility has been detected by comparing the glass transition dynamics in amorphous iPS and aPS samples. By using multi‐frequency temperature modulated DSC (TOPEM®) it has been demonstrated that the activation energy of the glass transition is noticeably larger for iPS than for aPS that supports the hypothesis of the slowed down molecular mobility.

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Extruded Biodegradable Cast Films from Polyhydroxyalkanoate and Thermoplastic Starch Blends: Fabrication and Characterization
Authors: Parulekar Yashodhan , Mohanty Amar K.
Published: October 2007

PHA‐based extruded films were developed by blending PHAs with thermoplastic starch using extensive process engineering based on structure‐property correlations. Starch was destructurized and plasticized followed by melt‐blending with PHA and PBAT. Dynamic mechanical analysis coupled with Gibbs free energy values indicated that the starch plastic was performing the role of a dual compatibilizer in between the PHA and the PBAT phases in the blend. Aging, an inherent problem with starch‐based materials and PHA‐based materials, was effectively reduced by limiting the moisture uptake of the starch component, hindering the leaching of glycerol and inhibiting the secondary crystallization of the PHA component in the films.

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Synthesis of Aminoazobenzene‐Containing Diblock Copolymer and Photoinduced Deformation Behavior of its Micelle‐Like Aggregates
Authors: Wang Dongrui , Ye Gang , Wang Xiaogong
Published: October 2007

A precursor polymer PEO‐b‐PEMA that contains anilino moieties is synthesized from EPAEMA by ATRP by using a PEOBr macroinitiator and CuBr/HMTETA catalyst system. The aminoazobenzene‐containing block copolymer PEO‐b‐PCN is obtained by the azo‐coupling reaction between PEO‐b‐PEMA and the diazonium salt of 4‐aminobenzonitrile. Results show that PEO‐b‐PCN has a narrow molecular weight distribution and the repeat unit numbers of the hydrophilic and hydrophobic blocks are 122 and 200, respectively. PEO‐b‐PCN can form uniform spherical aggregates by gradually adding water into its THF solution. Upon irradiation with a linearly polarized Ar+ laser beam, the spherical aggregates can be significantly elongated in the polarization direction of the light.

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Synthesis of Well‐Defined Amphiphilic Core–Shell Particles Containing Amine‐Rich Shells
Authors: Li Weiying , Li Pei
Published: October 2007

A new route to synthesize amphiphilic core–shell particles that consist of well‐defined hydrophobic polymer cores and poly(vinylamine) (PVAm) shells has been developed. The PVAm was treated with a small amount of tert‐butyl hydroperoxide to generate free radicals that subsequently initiated both graft‐ and homo‐polymerization of vinyl monomer such as n‐butyl acrylate, methyl methacrylate, and styrene. Stable particles in the range from 100 to 250 nm in diameter with very narrow size distributions (polydispersity index between 1.08 and 1.15) were produced in high yields. TEM images of the particles revealed that they had well‐defined core–shell nanostructures with thick and hairy PVAm shells. The structures of the vinyl monomer and water‐soluble polymer were found to strongly influence the formation of particles and their sizes.

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Ordering Cylindrical Microdomains for Binary Blends of Block Copolymers with Graphoepitaxy
Authors: Chen Feng , Akasaka Satoshi , Inoue Tomohiro , Takenaka Mikihito , Hasegawa Hirokazu , Yoshida Hiroshi
Published: October 2007

The morphology of a thin film was studied for a binary mixture of asymmetric PS‐b‐PMMA block copolymers on a flat silicon wafer coated with 50 nm thick silicon oxide. AFM and TEM reveal that the PMMA cylinders orient perpendicular to the substrate by tuning the film thickness. Furthermore, grating substrates with different width and depth are used to guide the alignment of the perpendicular cylinders. As a result, an array of highly ordered, hexagonally packed PMMA cylinders in the PS matrix with a domain spacing of less than 25 nm has been produced.

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Antifreeze Properties of Polyglycidol Block Copolymers
Authors: Baruch Eti , Mastai Yitzhak
Published: October 2007

In this paper, we describe a new biomimetic approach to the synthesis of block copolymers with antifreeze properties. Our approach focuses on the design of block copolymers that mimic the structure and functionality of antifreeze proteins. Hyperbranched copolymers containing poly(ethylene oxide)‐polyethyleneimine blocks and polyglycidol side chains were synthesized and their antifreeze properties were studied. It is shown that these block copolymers can lower the freezing point of water up to 0.8 °C at a relatively low concentration (1 mg · mL−1). From DSC measurements it is proven that polyglycidol block copolymers slow down the crystallization kinetics of ice and lead to changes in the ice crystal morphology, as observed by cryo‐optical microscopy.

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Coarse‐Grained Simulations of Elongational Viscosities, Superposition Rheology and Shear Banding in Model Core–Shell Systems
Authors: van den Noort A. , Briels W. J.
Published: October 2007

A recently developed coarse‐grain model is used to investigate nonlinear rheological properties of model core–shell systems. The influence of several model parameters on the stresses and shear rates is investigated. Continuous planar elongational flow and superposition rheology are studied and compared to simple shear flow results. With particular values of the model parameters, an initially linear velocity profile splits into many bands with different shear rates and different densities, which finally merge into just two bands stacked along the gradient direction. With the box sizes used in our simulations, stick and Lees–Edwards boundary conditions lead to qualitatively similar results, with the stick boundary simulations showing better quantitative agreement with experiments.

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On the Production of Polyolefins with Bimodal Molecular Weight and Copolymer Composition Distributions in Catalytic Gas‐Phase Fluidized‐Bed Reactors
Authors: Chatzidoukas Christos , Kanellopoulos Vassileios , Kiparissides Costas
Published: October 2007

A comprehensive mathematical model is developed for the dynamic calculation of the molecular distributed properties (i.e. MWD and CCD) in a gas‐phase, catalytic, ethylene‐1‐butene copolymerization, FBR, taking into account the various kinetic, micro‐ and macroscopic phenomena in the reactor. The effects of the two single‐site catalyst mass fractions and reactor operating conditions on the production of polyolefins with ‘tailor‐made’ bimodal molecular properties are investigated. It is shown that PE grades with either a bimodal MWD or CCD can be produced in a single FBR, using a mixture of two single‐site catalysts under properly selected operating conditions.

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Characterizing Pseudodendrimers, 1
Authors: Johnson Dave M. , Wang Junyan , Ponomarenko Vadim
Published: October 2007

Graph theory was used to analyze a series of small pseudodendrimeric structures. Descriptive indices were developed to characterize the pseudodendrimer graphs. The relative proportion of these dendrimers in typical samples was estimated based on three growth models. Weighted average values for the descriptive indices over typical aggregate samples were found to differ only slightly from values for perfect dendrimers.

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Morphology Transition of Block Copolymers under Curved Confinement
Authors: Xiao Xingqing , Huang Yongmin , Liu Honglai , Hu Ying
Published: October 2007

The morphology transitions in AB diblock and ABA triblock copolymers confined between flat and curved surfaces were investigated by MC simulations. Upon variation of the extent of frustration between thickness d and bulk lamellae period L0, parallel and vertical or distorted vertical lamellar structures appear in both flat and curved confinements. With increasing curvature, the compatibility of d and L0 becomes more perturbed so that perfectly parallel lamellae are formed with increasing difficulty. Owing to the smaller L0 of ABA as compared to AB, the transformation frequency of the incompatible region of d/L0(ABA) is more notable for ABA and the corresponding transformation period is larger than that of AB.

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A macro‐element for a circular foundation to simulate 3D soil–structure interaction
Authors: Grange S. , Kotronis P. , Mazars J.
Published: October 2007

This paper presents a non‐linear interface element to compute soil–structure interaction (SSI) based on the macro‐element concept. The particularity of this approach lies in the fact that the foundation is supposed to be infinitely rigid and its movement is entirely described by a system of global variables (forces and displacements) defined in the foundation's centre. The non‐linear behaviour of the soil is reproduced using the classical theory of plasticity. Failure is described by the interaction diagram of the ultimate bearing capacity of the foundation under combined loads.

The macro‐element is appropriate for modelling the cyclic or dynamic response of
structures subjected to seismic action. More specifically, the element is able to simulate the behaviour of a circular rigid shallow foundation considering the plasticity of the soil under monotonic static or cyclic loading applied in three directions. It is implemented into FedeasLab, a finite element Matlab toolbox. Comparisons with experimental monotonic static and cyclic results show the good performance of the approach. Copyright © 2007 John Wiley & Sons, Ltd.
Should we explain lower urinary tract symptoms to patients?
Authors: Digesu G. Alessandro , Khullar Vik , Panayi Demetri , Calandrini Marco , Gannon Michael , Nicolini Umberto
Published: October 2007

Aim

The aim of our study was to evaluate the understanding of lower urinary tract symptom (LUTS) terminology used by patients.

Materials and Methods

Women attending urodynamic clinics in United Kingdom, Australia, and Italy were asked to complete a questionnaire testing the women's understanding of stress urinary incontinence, urge urinary incontinence, frequency, urgency, nocturia, and hesitancy. Five possible explanations for the meaning of each symptom were given.

Results

A total of 138 consecutive women were prospectively recruited. The terms of daytime frequency, nocturia, urgency, urge urinary incontinence, stress urinary incontinence, and hesitancy were defined correctly, according to the International Continence Society terminology, only by 33% (45/138), 44% (61/138), 46% (64/138), 39% (54/138), 37% (51/138), and 41% (57/138) of women, respectively. Over 20% of women were unsure about the meaning of each symptom. We did not find any statistical difference between the three groups in determining the correct definition (P = 0.5).

Conclusions

Our findings showed that most women do not know the correct meaning of LUTS terminology currently used by physicians. Neurourol. Urodynam. 27:368–371, 2008. © 2007 Wiley‐Liss, Inc.
Mixed urinary symptoms: What are the urodynamic findings?
Authors: Digesu G. Alessandro , Salvatore Stefano , Fernando Ruwan , Khullar Vik
Published: October 2007

Aim

To define the urodynamic diagnoses of women with mixed urinary incontinence (MUI) symptoms.

Materials and Methods

Women with MUI symptoms were studied. They were divided into stress predominant MUI; urge predominant MUI; or equal severity of stress and urge MUI on the basis of the most severe symptom scored on the King's Health Questionnaire. The frequency of different urodynamic diagnoses for the all women with MUI and in each of the above groups was calculated.

Results

Overall 3,338 women were studied. Of these 49% (1,626/3,338) reported MUI symptoms and were included. In this group 29% (464/1,626) had stress predominant MUI, 15% (248/1,626) had urge predominant MUI and 56% (912/1,626) had equal severity of urge and stress MUI. On urodynamics 42% (665/1,626) had pure urodynamic stress incontinence, 25% (414/1,626) had pure detrusor overactivity, 18% (299/1,626) had both detrusor overactivity and urodynamic stress incontinence and 15% (248/1,626) had normal urodynamic studies. In those with stress predominant MUI, 82% had urodynamic stress incontinence; in those with urge predominant MUI, 64% had detrusor overactivity. The urodynamic diagnoses were significantly different for the different balance of symptoms (P < 0.05, Chi‐Square test). In women with equal severity of urge and stress incontinence, 46% had detrusor overactivity while 54% had urodynamic stress incontinence.

Conclusions

The relative severity of MUI symptoms from a symptom questionnaire significantly distinguishes between different urodynamic diagnoses. Women with urge predominant MUI are more likely to have detrusor overactivity while those with stress predominant MUI are more likely to have urodynamic stress incontinence. Neurourol. Urodynam. 27:372–375, 2008. © 2007 Wiley‐Liss, Inc.
BAP annual conference
Authors: Donoghue John
Published: October 2007

Issues exercising minds at the British Association for Psychopharmacology's annual conference in Harrogate in July are familiar: metabolic problems and schizophrenia, the relationship between sleep and depression, and old versus new antipsychotics. But as research continues, some new insights and ideas emerge. Medical writer, John Donoghue, reports on some of the sessions he attended. Copyright © 2007 Wiley Interface Ltd
Primhe: Primary Care Mental Health & Education
Authors: Fellows Jodie , Parry Carol , Hammond‐Rowley Sara
Published: October 2007

CAMHS training for school nurses in North Wales

School nurses often feel that they have to deal with children with emotional and behavioural problems, but with little training or support. This can lead to feelings of low confidence, which can have a detrimental effect on school nurses' practice. Child and Adolescent Mental Health Services (CAMHS) Early Intervention Service in Flintshire delivered training to school nurses in understanding child and adolescent mental health. Nurses reported feeling more confident in their knowledge and skills in relation to child and adolescent mental health and wanted further training. Copyright © 2007 Wiley Interface Ltd
PBG Fibers for Gas Concentration Measurement
Authors: Pawłat Joanna , Sugiyama Tadashi , Matsuo Takahiro , Ueda Toshitsugu
Published: October 2007

The idea of a high‐sensitivity gas concentration measuring system based on a photonic bandgap fiber (PBG fiber) is studied. Several types of PBG fibers of various parameters have been designed. Core diameters range from 10.9 to 26.25 µm. The capillary gas flow rate within the fiber has been simulated and measured. The attenuation of newly produced fibers is investigated and the concentration of ammonia gas is measured using a proposed sensing system. A new method for cutting the fiber using an Ar ion beam in a vacuumed chamber is tested to obtain the required angle of the fiber's end, and to avoid the destruction of the cladding structure.

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Experimental Study of the Influence of Ar/H2 Microwave Discharges on Lipid A
Authors: Kylián Ondřej , Hasiwa Marina , Gilliland Douglas , Rossi François
Published: October 2007

This paper discusses the influence of microwave discharge plasmas on Lipid A, one of the most problematic compounds from the point of view of conventional decontamination methods. The effect of microwave discharges produced in different Ar/H2 mixtures on Lipid A films has been studied by means of both biological tests and materials characterisation methods (FT‐IR and ToF‐SIMS spectroscopy) in order to identify the main mechanisms leading to the suppression of their pyrogenicity. From the results obtained, it is concluded that most probably chemical modifications, namely the removal of long carboxylic acid chains and mineralisation of the organo‐phosphate group, are responsible for Lipid A depyrogenation.

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Ways to Create New CHNO‐Oxidizers for Stoichiometric Gas‐Generating Compositions with Low Combustion Temperature
Authors: Lempert David B. , Zyuzin Igor N.
Published: October 2007

The investigation is aimed to study the possibility of creation of new CHNO‐oxidizers for smokeless gas‐generating compositions for airbag inflators. For ensuring low amount of CO and nitrogen oxides in combustion products it is necessary to create stoichiometric compositions with a relatively low combustion temperature. Ways to create new oxidizers acceptable to this requirement are examined, mainly by introducing low‐enthalpy oxygen‐containing groups into the oxidizer molecule. Standard enthalpy of formation (ΔfH°) has been calculated for substances with unknown ΔfH°, thermal stability has been qualitatively estimated, and combustion temperatures of stoichiometric compositions have been calculated.