bluuebunny/crossref_metadata_2025 huggingface dataset:
ETM-ANN Approach Application for Thiobenzamide and Quinolizidine Derivatives
Authors: Saracoglu M. , Kandemirli F. , Kovalishyn V. , Arslan T. , Ebenso E. E.
Published: September 2010

The structure anti-influenza activity relationships of thiobenzamide and quinolizidine derivatives, being influenza fusion inhibitors, have been investigated using the electronic-topological method (ETM) and artificial neural network (ANN) method. Molecular fragments specific for active compounds and breaks of activity were calculated for influenza fusion inhibitors by applying the ETM. QSAR descriptors such as molecular weight,EHOMO,ELUMO,ΔE, chemical potential, softness, electrophilicity index, dipole moment, and so forth were calculated, and it was found to give good statistical qualities (classified correctly 92%, or 48 compounds from 52 in training set, and 69% or 9 compounds from 13 in the external test set). By using multiple linear regression, several QSAR models were performed with the help of calculated descriptors and the compounds activity data. Among the obtained QSAR models, statistically the most significant one is the one of skeleton 1 withR2=0.999.
What Limits Cardiac Performance during Exercise in Normal Subjects and in Healthy Fontan Patients?
Authors: La Gerche André , Gewillig Marc
Published: September 2010

Exercise is an important determinant of health but is significantly reduced in the patient with a univentricular circulation. Normal exercise physiology mandates an increase in pulmonary artery pressures which places an increased work demand on the right ventricle (RV). In a biventricular circulation with pathological increases in pulmonary vascular resistance and/or reductions in RV function, exercise-induced augmentation of cardiac output is limited. Left ventricular preload reserve is dependent upon flow through the pulmonary circulation and this requires adequate RV performance. In the Fontan patient, the reasons for exercise intolerance are complex. In those patients with myocardial dysfunction or other pathologies of the circulatory components, it is likely that these abnormalities serve as a limitation to cardiac performance during exercise. However, in the healthy Fontan patient, it may be the absence of a sub-pulmonary pump which limits normal increases in pulmonary pressures, trans-pulmonary flow requirements and cardiac output. If so, performance will be exquisitely dependent on pulmonary vascular resistance. This provides a potential explanation as to why pulmonary vasodilators may improve exercise tolerance. As has recently been demonstrated, these agents may offer an important new treatment strategy which directly addresses the physiological limitations in the Fontan patient.
In vivo Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner
Authors: Kim Hoe Suk , Cho Hye Rim , Choi Seung Hong , Woo Ji Su , Moon Woo Kyung
Published: September 2010

A combination of reporter genes for magnetic resonance imaging (MRI) and optical imaging can provide an additional level of noninvasive and quantitative information about biological processes occurring in deep tissues. We developed a bimodal lentiviral vector to monitor deep tissue events using MRI to detect myc-tagged human ferritin heavy chain (myc-hFTH) expression and fluorescence imaging to detect green fluorescent protein (GFP) expression. The transgene construct was stably transfected into MCF-7 and F-98 cells. After transplantation of the cells expressing myc-hFTH and GFP into mice or rats, serial MRI and fluorescence imaging were performed with a human wrist coil on a 1.5T MR scanner and optical imaging analyzer for 4 weeks. No cellular toxicity due to overexpression of myc-hFTH and GFP was observed in MTT and trypan blue exclusion assays. Iron accumulation was observed in myc-hFTH cells and tumors by Prussian blue staining and iron binding assays. The myc-hFTH cells and tumors had significantly lower signal intensities in T2-weighted MRI than mock-transfected controls (P ≤ 0.05). This is direct evidence that myc-hFTH expression can be visualized noninvasively with a 1.5T clinical MR scanner. This study shows that MRI and fluorescence imaging of transplanted cells at molecular and cellular levels can be performed simultaneously using our bimodal lentiviral vector system. Our techniques can be used to monitor tumor growth, metastasis, and regression during cell and gene-based therapy in deep tissues. Cancer Res; 70(18); 7315–24. ©2010 AACR.
Discovery and Canine Preclinical Assessment of a Nontoxic Procaspase-3–Activating Compound
Authors: Peterson Quinn P. , Hsu Danny C. , Novotny Chris J. , West Diana C. , Kim Dewey , Schmit Joanna M. , Dirikolu Levent , Hergenrother Paul J. , Fan Timothy M.
Published: September 2010

A critical event in the apoptotic cascade is the proteolytic activation of procaspases to active caspases. The caspase autoactivating compound PAC-1 induces cancer cell apoptosis and exhibits antitumor activity in murine xenograft models when administered orally as a lipid-based formulation or implanted s.c. as a cholesterol pellet. However, high doses of PAC-1 were found to induce neurotoxicity, prompting us to design and assess a novel PAC-1 derivative called S-PAC-1. Similar to PAC-1, S-PAC-1 activated procaspase-3 and induced cancer cell apoptosis. However, S-PAC-1 did not induce neurotoxicity in mice or dogs. Continuous i.v. infusion of S-PAC-1 in dogs led to a steady-state plasma concentration of ∼10 μmol/L for 24 to 72 hours. In a small efficacy trial of S-PAC-1, evaluation of six pet dogs with lymphoma revealed that S-PAC-1 was well tolerated and that the treatments induced partial tumor regression or stable disease in four of six subjects. Our results support this canine setting for further evaluation of small-molecule procaspase-3 activators, including S-PAC-1, a compound that is an excellent candidate for further clinical evaluation as a novel cancer chemotherapeutic. Cancer Res; 70(18); 7232–41. ©2010 AACR.
Ligand-Independent Toll-like Receptor Signals Generated by Ectopic Overexpression of MyD88 Generate Local and Systemic Antitumor Immunity
Authors: Hartman Zachary C. , Osada Takuya , Glass Oliver , Yang Xiao Y. , Lei Gang-jun , Lyerly H. Kim , Clay Timothy M.
Published: September 2010

Although critical for initiating and regulating immune responses, the therapeutic use of individual cytokines as anticancer immunotherapeutic agents has achieved only modest clinical success. Consequently, many current strategies have focused on the use of specific immunotherapeutic agonists that engage individual receptors of innate immune networks, such as the Toll-like receptor (TLR) system, each resulting in specific patterns of gene expression, cytokine production, and inflammatory outcome. However, these immunotherapeutics are constrained by variable cellular TLR expression and responsiveness to particular TLR agonists, as well as the specific cellular context of different tumors. We hypothesized that overexpression of MyD88, a pivotal regulator of multiple TLR signaling pathways, could circumvent these constraints and mimic coordinated TLR signaling across all cell types in a ligand-independent fashion. To explore this hypothesis, we generated an adenoviral vector expressing MyD88 and show that Ad-MyD88 infection elicits extensive Th1-specific transcriptional and secreted cytokine signatures in all murine and human cell types tested in vitro and in vivo. Importantly, in vivo intratumoral injection of Ad-MyD88 into established tumor masses enhanced adaptive immune responses and inhibited local tumor immunosuppression, resulting in significantly inhibited local and systemic growth of multiple tumor types. Finally, Ad-MyD88 infection of primary human dendritic cells, tumor-associated fibroblasts, and colorectal carcinoma cells elicited significant Th1-type cytokine responses, resulting in enhanced tumor cell lysis and expansion of human tumor antigen–specific T cells. Thus, Ad-MyD88 initiated robust antitumor activity in established murine tumor microenvironments and in human contexts, suggesting its potential effectiveness as a clinical immunotherapeutic strategy. Cancer Res; 70(18); 7209–20. ©2010 AACR.
AACR Special Conference on Epithelial-Mesenchymal Transition and Cancer Progression and Treatment
Authors: Roussos Evanthia T. , Keckesova Zuzana , Haley John D. , Epstein David M. , Weinberg Robert A. , Condeelis John S.
Published: September 2010

Epithelial-mesenchymal transition (EMT) is a developmental program implicated in cancer progression and was the subject of the 2010 AACR meeting on the topic of EMT and Cancer Progression and Treatment held on February 28 to March 2 in Arlington, Virginia. A review of the involvement of EMT in gastrulation, organogenesis, carcinogenesis, and metastatic progression elucidated the overlap of EMT in these physiologic and pathologic conditions. Both novel and traditional markers of cells undergoing EMT were discussed and compared with features used to define cancer stem cells. Importantly, these defining characteristics of cells undergoing EMT were discussed in the context of therapeutic and prognostic developments. Cancer Res; 70(19); 7360–4. ©2010 AACR.
Menopausal Hormone Therapy and Subsequent Risk of Specific Invasive Breast Cancer Subtypes in the California Teachers Study
Authors: Saxena Tanmai , Lee Eunjung , Henderson Katherine D. , Clarke Christina A. , West Dee , Marshall Sarah F. , Deapen Dennis , Bernstein Leslie , Ursin Giske
Published: September 2010

Background: Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the effect of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype.

Methods: We investigated hormone therapy (HT) use in relation to breast cancer risk in the California Teachers Study cohort; after a mean follow-up of 9.8 years, 2,857 invasive breast cancers were diagnosed.

Results: Compared with women who had never used HT, women who reported 15 or more years of estrogen therapy (ET) use had a 19% greater risk of breast cancer (95% confidence interval, 1.03-1.37), whereas women using EPT for 15 or more years had an 83% greater risk (95% confidence interval, 1.48-2.26). Breast cancer risk was highest among women using continuous combined EPT regimens. Risks associated with EPT and ET use were increased with duration of HT use for women with a body mass index (BMI) of <29.9 kg/m2 but not for women with BMI of ≥30 kg/m2. Elevated risks associated with EPT and ET use were confined to tumors that were positive for both estrogen and progesterone receptors and those that were HER2+ but were slightly diminished for HER2− tumors.

Conclusions: Breast cancer risks increased with longer duration of ET and EPT use, and risks were highest for continuous-combined EPT use. Furthermore, risks varied by BMI and tumor subtype.

Impact: These findings underscore the need for personalized risk-benefit discussions with women contemplating HT use. Cancer Epidemiol Biomarkers Prev; 19(9); 2366–78. ©2010 AACR.
Epigenetic Modifications in Double-Strand Break DNA Damage Signaling and Repair
Authors: Rossetto Dorine , Truman Andrew W. , Kron Stephen J. , Côté Jacques
Published: September 2010

Factors involved in the cellular response to double-strand break (DSB) DNA damage have been identified as potential therapeutic targets that would greatly sensitize cancer cells to radiotherapy and genotoxic chemotherapy. These targets could disable the repair machinery and/or reinstate normal cell-cycle checkpoint leading to growth arrest, senescence, and apoptosis. It is now clear that a major aspect of the DNA damage response occurs through specific interactions with chromatin structure and its modulation. It implicates highly dynamic posttranslational modifications of histones that are critical for DNA damage recognition and/or signaling, repair of the lesion, and release of cell-cycle arrest. Therefore, drugs that target the enzymes responsible for these modifications, or the protein modules reading them, have very high therapeutic potential. This review presents the current state of knowledge on the different chromatin modifications and their roles in each step of eukaryotic DSB DNA damage response. Clin Cancer Res; 16(18); 4543–52. ©2010 AACR.
Diet-Induced Obesity Accelerates Acute Lymphoblastic Leukemia Progression in Two Murine Models
Authors: Yun Jason P. , Behan James W. , Heisterkamp Nora , Butturini Anna , Klemm Lars , Ji Lingyun , Groffen John , Müschen Markus , Mittelman Steven D.
Published: September 2010

Obesity is associated with an increased incidence of many cancers, including leukemia, although it is unknown whether leukemia incidence is increased directly by obesity or rather by associated genetic, lifestyle, health, or socioeconomic factors. We developed animal models of obesity and leukemia to test whether obesity could directly accelerate acute lymphoblastic leukemia (ALL) using BCR/ABL transgenic and AKR/J mice weaned onto a high-fat diet. Mice were observed until development of progressive ALL. Although obese and control BCR/ABL mice had similar median survival, older obese mice had accelerated ALL onset, implying a time-dependent effect of obesity on ALL. Obese AKR mice developed ALL significantly earlier than controls. The effect of obesity was not explained by WBC count, thymus/spleen weight, or ALL phenotype. However, obese AKR mice had higher leptin, insulin, and interleukin-6 levels than controls, and these obesity-related hormones all have potential roles in leukemia pathogenesis. In conclusion, obesity directly accelerates presentation of ALL, likely by increasing the risk of an early event in leukemogenesis. This is the first study to show that obesity can directly accelerate the progression of ALL. Thus, the observed associations between obesity and leukemia incidence are likely to be directly related to biological effects of obesity. Cancer Prev Res; 3(10); 1259–64. ©2010 AACR.
Drug-Disease Interaction: Reduced Verapamil Response in Isoproterenol-Induced Myocardial Injury in Rats
Authors: Hanafy Sherif , El-Kadi Ayman O. , Jamali Fakhreddin
Published: September 2010

Inflammation is involved in the pathogenesis of cardiovascular diseases. We investigated whether the response to verapamil is altered in experimental acute myocardial injury (AMI). Two groups of male Sprague-Dawley rats (230–280 g) were divided into control (n = 8) and post-AMI (n = 13). Myocardial injury was induced by 2 daily doses of 150 mg·kg–1 isoproterenol (ISP). Subcutaneous ECG leads were implanted, and 2 days following the second injection, each rat was dosed with 25 mg·kg–1 verapamil per os, and an ECG was recorded over 4 h after dosing. The animals were euthanized and blood samples collected for analysis of inflammatory mediators and cardiac troponin I (cTnI). Cardiac L-type calcium channel (Cav1.2) protein levels and mRNA were determined by Western blot and real-time PCR, respectively. ISP treatment caused a 170% increase in serum cTnI, J point elevation, R wave amplitude reduction and Q wave development. Cardiac injury caused a 75% reduction in verapamil potency by prolonging the PR interval and reducing the heart rate. Cardiac tissue injury also caused a significant reduction in the Cav1.2 protein level. Verapamil response was significantly correlated with cTnI. The reduced potency of verapamil in myocardial injury appears to result from a reduction in the drug target protein Cav1.2. If extrapolated to humans, our observations may suggest that downregulation of calcium channel proteins is a contributory factor in the poor outcome in myocardial infarction.
Very Long-Term (15 to 20 Years) Clinical and Angiographic Outcome After Coronary Bare Metal Stent Implantation
Authors: Yamaji Kyohei , Kimura Takeshi , Morimoto Takeshi , Nakagawa Yoshihisa , Inoue Katsumi , Soga Yoshimitsu , Arita Takeshi , Shirai Shinichi , Ando Kenji , Kondo Katsuhiro , Sakai Koyu , Goya Masahiko , Iwabuchi Masashi , Yokoi Hiroyoshi , Nosaka Hideyuki , Nobuyoshi Masakiyo
Published: September 2010

Background—

We previously reported that the long-term luminal response after coronary bare metal stenting is triphasic, with an early restenosis phase spanning the 6 months after the index procedure, an intermediate-term regression phase from 6 months to 3 years, and a late renarrowing phase beyond 4 years. However, the clinical significance of late luminal renarrowing remains unknown.

Methods and Results—

Angiographic and clinical follow-up of the same cohort of 405 patients with successful Palmaz-Schatz stent placement was extended beyond 15 years. Clinical follow-up was completed in 98% of patients at 5 years and in 81% at 15 years. The incidence of death and cardiac death at 15 years was 45.4% and 20.6%, respectively. Paired long-term (4 to 10 years) and very long-term (>10 years) angiographic studies without intercurrent target lesion revascularization were performed in 55 lesions, and minimal luminal diameter further decreased from 1.88±0.50 mm to 1.60±0.73 mm (
P
=0.002). Late target lesion revascularization after initial stabilization of the stented segments occurred rarely within 4 years. Beyond 4 years, however, the incidence of late target lesion revascularization increased steadily from 3.3% at 4 years to 24.7% at 15 years. The incidence of definite very late stent thrombosis was low (1.5% at 15 years).

Conclusions—

Luminal renarrowing of the stented segment beyond 4 years was a progressive process extending beyond 10 years. The angiographic observation of late in-stent restenosis was clinically relevant because a corresponding progressive increase in the incidence of late target lesion revascularization was observed beyond 4 years and up to 15 to 20 years after bare metal stent implantation.
Prophylactic Implantable Defibrillator in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia and No Prior Ventricular Fibrillation or Sustained Ventricular Tachycardia
Authors: Corrado Domenico , Calkins Hugh , Link Mark S. , Leoni Loira , Favale Stefano , Bevilacqua Michela , Basso Cristina , Ward Deirdre , Boriani Giuseppe , Ricci Renato , Piccini Jonathan P. , Dalal Darshan , Santini Massimo , Buja Gianfranco , Iliceto Sabino , Estes N.A. Mark , Wichter Thomas , McKenna William J. , Thiene Gaetano , Marcus Frank I.
Published: September 2010

Background—

The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue.

Methods and Results—

We studied 106 consecutive patients (62 men and 44 women; age, 35.6±18 years) with arrhythmogenic right ventricular cardiomyopathy/dysplasia who received an ICD based on 1 or more arrhythmic risk factors such as syncope, nonsustained ventricular tachycardia, familial sudden death, and inducibility at programmed ventricular stimulation. During follow-up of 58±35 months, 25 patients (24%) had appropriate ICD interventions and 17 (16%) had shocks for life-threatening VF or ventricular flutter. At 48 months, the actual survival rate was 100% compared with the VF/ventricular flutter–free survival rate of 77% (log-rank
P
=0.01). Syncope significantly predicted any appropriate ICD interventions (hazard ratio, 2.94; 95% confidence interval, 1.83 to 4.67;
P
=0.013) and shocks for VF/ventricular flutter (hazard ratio, 3.16; 95% confidence interval, 1.39 to 5.63;
P
=0.005). The positive predictive value of programmed ventricular stimulation was 35% for any appropriate ICD intervention and 20% for shocks for VF/ventricular flutter, with a negative predictive value of 70% and 74%. None of the 27 asymptomatic patients with isolated familial sudden death had appropriate ICD therapy. Twenty patients (19%) had inappropriate ICD interventions, and 18 (17%) had device-related complications.

Conclusions—

One fourth of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior sustained ventricular tachycardia or VF had appropriate ICD interventions. Syncope was an important predictor of life-saving ICD intervention and is an indication for ICD. Prophylactic ICD may not be indicated in asymptomatic patients because of their low arrhythmic risk regardless of familial sudden death and programmed ventricular stimulation findings. Programmed ventricular stimulation had a low predictive accuracy for ICD therapy.
Lower Treatment Blood Pressure Is Associated With Greatest Reduction in Hematoma Growth After Acute Intracerebral Hemorrhage
Authors: Arima Hisatomi , Anderson Craig S. , Wang Ji Guang , Huang Yining , Heeley Emma , Neal Bruce , Woodward Mark , Skulina Christian , Parsons Mark W. , Peng Bin , Tao Qing Ling , Li Yue Chun , Jiang Jian Dong , Tai Li Wen , Zhang Jin Li , Xu En , Cheng Yan , Morgenstern Lewis B. , Chalmers John
Published: September 2010

The pilot phase of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) showed that rapid blood pressure (BP) lowering can attenuate hematoma growth in acute intracerebral hemorrhage. We sought to define the systolic BP level associated with greatest attenuation of hematoma growth. INTERACT included 404 patients with computed tomographic–confirmed intracerebral hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to commence BP lowering treatment within 6 hours of onset. Computed tomography was done at baseline and at 24 hours using standardized techniques, with digital images analyzed centrally, blinded to clinical data. Associations of baseline and achieved on-treatment (mean during the first 24 hours) systolic BP levels with the primary outcome of increase in hematoma volume were explored. There were 346 patients with duplicate computed tomographic scans. There was no significant association between baseline systolic BP levels and either the absolute or proportional growth in hematoma volume (
P
trend=0.26 and 0.12, respectively). By contrast, achieved on-treatment systolic BP levels in the first 24 hours were clearly associated with both absolute and proportional hematoma growth (both
P
trend=0.03). Maximum reduction in hematoma growth occurred in the one third of participants with the lowest on-treatment systolic BP levels (median: 135 mm Hg). Intensive BP reduction to systolic levels between 130 and 140 mm Hg is likely to provide the maximum protection against hematoma growth after intracerebral hemorrhage.
Warming of Global Abyssal and Deep Southern Ocean Waters between the 1990s and 2000s: Contributions to Global Heat and Sea Level Rise Budgets*
Authors: Purkey Sarah G. , Johnson Gregory C.
Published: September 2010

Abyssal global and deep Southern Ocean temperature trends are quantified between the 1990s and 2000s to assess the role of recent warming of these regions in global heat and sea level budgets. The authors 1) compute warming rates with uncertainties along 28 full-depth, high-quality hydrographic sections that have been occupied two or more times between 1980 and 2010; 2) divide the global ocean into 32 basins, defined by the topography and climatological ocean bottom temperatures; and then 3) estimate temperature trends in the 24 sampled basins. The three southernmost basins show a strong statistically significant abyssal warming trend, with that warming signal weakening to the north in the central Pacific, western Atlantic, and eastern Indian Oceans. Eastern Atlantic and western Indian Ocean basins show statistically insignificant abyssal cooling trends. Excepting the Arctic Ocean and Nordic seas, the rate of abyssal (below 4000 m) global ocean heat content change in the 1990s and 2000s is equivalent to a heat flux of 0.027 (±0.009) W m−2 applied over the entire surface of the earth. Deep (1000–4000 m) warming south of the Subantarctic Front of the Antarctic Circumpolar Current adds 0.068 (±0.062) W m−2. The abyssal warming produces a 0.053 (±0.017) mm yr−1 increase in global average sea level and the deep warming south of the Subantarctic Front adds another 0.093 (±0.081) mm yr−1. Thus, warming in these regions, ventilated primarily by Antarctic Bottom Water, accounts for a statistically significant fraction of the present global energy and sea level budgets.
Assessment of the Effects of Tidal Mixing in the Kuril Straits on the Formation of the North Pacific Intermediate Water
Authors: Tanaka Yuki , Hibiya Toshiyuki , Niwa Yoshihiro
Published: September 2010

To assess accurately the effect of tidal mixing in the Kuril Straits on the formation of the North Pacific Intermediate Water (NPIW), the spatial distribution of diapycnal diffusivity recently obtained by the present authors is incorporated into an eddy-permitting OGCM. It is shown that the NPIW is successfully reproduced, although the diapycnal diffusivity averaged over the entire Kuril Straits is an order of magnitude less than has previously been assumed as a tuning parameter to reproduce the NPIW in low-resolution OGCMs. This strongly suggests that the effect of tidal mixing in the Kuril Straits on the formation of the NPIW is relatively minor and that the physical processes omitted by the low-resolution OGCMs, such as isopycnal mixing along the Kuroshio Extension region, are much more important. This suggestion gives warning of the danger that some misleading conclusions might be derived from OGCMs that employ diapycnal diffusivity just as a tuning parameter to reproduce the observed features.
The World Wide Lightning Location Network and Convective Activity in Tropical Cyclones
Authors: Abarca Sergio F. , Corbosiero Kristen L. , Vollaro David
Published: September 2010

Lightning flash density in tropical cyclones (TCs) is investigated to identify whether lightning flashes provide information on TC intensity and/or intensity change, to provide further insight into TC asymmetric convective structure induced by vertical shear and storm motion, and to assess how well the World Wide Lightning Location Network (WWLLN) is suited for the observation of TCs. The 24 Atlantic basin TCs that came within 400 km of the United States from 2004 to 2007 are studied. The National Lightning Detection Network is used to analyze flash density as a function of peak current and to evaluate the WWLLN. Flash density is shown to be smaller for hurricanes than for tropical depressions and storms, with this reduction being gradually more pronounced as flash peak current increases. The results suggest that flash density in the inner core is a parameter with potential for distinguishing intensifying versus nonintensifying TCs, particularly in the weaker storm stages where flash densities are largest.

Vertical wind shear produces a strong downshear left (right) asymmetry in the inner core (outer rainbands), whereas motion asymmetries are less clear. The unprecedented azimuthal resolution used in this study suggests that as shear strengthens, the azimuthal region of convection in the inner core is sharpened from a width of ∼130° to a width of ∼60°. The radial distribution of flash density is shown to exhibit a relatively narrow region of little activity (between 60 and 120 km from the eye), with increased activity in both regions closer to, and more distant from, the center (i.e., the eyewall and outer rainbands, respectively). Finally, it is shown that the WWLLN captures the convective activity in Atlantic basin TCs remarkably well, despite its low detection efficiency.
Predictability of North Atlantic Tropical Cyclone Activity on Intraseasonal Time Scales
Authors: Belanger James I. , Curry Judith A. , Webster Peter J.
Published: September 2010

Recent work suggests that there may exist skill in forecasting tropical cyclones (TC) using dynamically based ensemble products, such as those obtained from the ECMWF Monthly Forecast System (ECMFS). The ECMFS features an ensemble of 51 coupled ocean–atmosphere simulations integrated to 32 days once per week. Predicted levels of TC activity in the North Atlantic Ocean with these monthly ensemble forecasts is compared with the observed variability during the months of June–October during 2008 and 2009. Results indicate that the forecast system can capture large-scale regions that have a higher or lower risk of TC activity and that it has skill above climatology for the Gulf of Mexico and the “Main Development Region” on intraseasonal time scales. Regional forecast skill is traced to the model’s ability to capture the large-scale evolution of deep-layer vertical shear, the frequency of easterly waves, and the variance in 850-hPa relative vorticity. The predictability of TC activity, along with the forecast utility of the ECMFS, is shown to be sensitive to the phase and intensity of the Madden–Julian oscillation at the time of model initialization.
Should The Size Threshold for Elective Abdominal Aortic Aneurysm Repair be Lowered in The Endovascular Era? No
Authors: Avgerinos Efthimios D. , Katsargyris Athanasios , Klonaris Christos , Papapetrou Anastasios , Moulakakis Konstantinos , Liapis Christos D.
Published: September 2010

According to the current international guidelines, patients with infrarenal or juxtarenal abdominal aortic aneurysms (AAAs) measuring ≥5.5 cm should undergo repair to reduce the risk of rupture. The 5.5-cm-diameter threshold is the size when the AAA rupture rate balances the mortality rates of elective open surgical AAA repair (3%). Endovascular AAA repair (EVAR) is associated with lower perioperative mortality and complication rates compared with open surgical repair. This debate addresses the issue whether the current size threshold for elective AAA repair needs to be lowered in the endovascular era. This article supports the position that the size threshold for AAA repair should not be lowered.
Neighbourhood and Class
Authors: La Grange Adrienne
Published: September 2010

This paper investigates the relationship between neighbourhood cohesion and organisation and class in Hong Kong. It draws on a survey of 1200 face-to-face interviews in an up-market private housing estate on Hong Kong Island, a large, neither rich nor poor public housing estate in the New Territories and a mixed-use, low-income inner-city neighbourhood in Kowloon. Four indexes measure interneighbourhood and intraneighbourhood differences—namely, attraction to neighbourhood, neighbouring and psychological sense of community adapted from the Buckner scale of social cohesion, and social organisation developed by the author. There are significant differences between the neighbourhoods. However, these differences are not duplicated between occupation-defined class within the neighbourhoods, although there are some differences based on self-defined social class. The likely explanation lies in the character of the three neighbourhoods, government policy, the effect of private housing management and the low level of spatial differentiation by income across the city.
The Clothing Industry in Istanbul in the Era of Globalisation and Fast Fashion
Authors: Tokatli Nebahat , Kızılgün Ömür , Cho Jinsook Erin
Published: September 2010

This article examines how globalising dynamics have been affecting Istanbul’s urban economy. Our focus is on the part of the clothing industry which is now under tremendous pressure to meet the ever-increasing demands of international clothing retailers. While these retailers have been fuelling globalisation in the clothing industry via global sourcing for some decades now, they have recently placed new demands on their manufacturing supplier firms in Istanbul and elsewhere, and have successfully turned the question of meeting these new demands into a matter of survival. The exact manner in which manufacturers have been coping with these new demands, together with the labour force implications of their efforts (with a special focus on women labourers living in the peripheral neighbourhoods of the city) is the core of this article.
High Fidelity Haptic Rendering of Frictional Contact with Deformable Objects in Virtual Environments using Multi-rate Simulation
Authors: Jacobs Paul , Fu Michael J , Çavuşoğlu M. Cenk
Published: September 2010

Haptics is an increasingly common modality in human-computer interfacing. The focus of this paper is the problem arising from the difference between the high sampling rate requirements of haptic interfaces and the significantly lower update rates for physical models simulated in virtual environments. This is a critical problem, especially for applications involving haptic manipulation of deformable objects simulated in virtual environments, such as in surgical simulation. In this paper, a multi-rate simulation approach was developed to address this problem. The proposed method employs linear low-order approximations to model the inter-sample behavior of the high-order non-linear deformable object models. The basic method is also extended to achieve high-fidelity rendering of haptic manipulations involving sliding-type frictional contact. The proposed approach uses a local geometric model in addition to the local dynamic model, and performs collision detection and response as part of the high update rate haptic loop. Experimental results that validate the proposed methods are also presented.
Reflections on the Project of a Renewed Polis: After Athens and Jerusalem
Authors: Karalis Vrasidas
Published: September 2010

This article discusses the historical opposition in the Western world between Athens as the centre of democratic political thinking, reason and philosophical knowledge and Jerusalem as the centre of religion, faith and revelation. It examines the historical trajectory of the debate from early Christianity to this day with special emphasis on the work of Leo Strauss and Eric Voegelin; it addresses the relation between faith and reason as two existential and political principles reinforcing each other and explores the symbiotic relationship existing today after both symbolic landscapes have been replaced by new patterns of social organization. It suggests that we must recast the duality Athens/ Jerusalem, not as terms of antagonism, but as two complementary dimensions of existence and orders of experience. It proposes that the event of human natality belongs to the religious order while that of human conscience belongs to the political order. It concludes that modern complex trans-national societies must absorb the experience of both traditions and articulate a new conceptual framework about the relationship between faith and reason.
‘Target’, ‘cancer’ and ‘warrior’: Exploring painful metaphors of self-presentation used by girls born of war rape
Authors: Erjavec Karmen , Volčič Zala
Published: September 2010

Children born of war rapes continue to be a marginalized political, media and academic topic in Bosnian and other post-war societies. The goal of this article is to contribute to the research that deals with the life situations of children born of war rape, and to show the usefulness of an analysis of metaphors when a specific topic is emotionally difficult to talk about. The metaphor analysis of life stories of 19 adolescents — all Bosniak girls — born of war rapes in Bosnia and Herzegovina shows that metaphorical language provides abused girls with the only way to express their painful situations. The authors identify three main uses of metaphors as discursive strategies. These are the only possible articulations of their painful situations: the avoidance of the use of vocabulary from the primary domain, the repetition of the metaphor and the immediate use of the metaphor when it collapses into the primary domain. There were three major metaphorical frames that dominated the self-presentation of the girls: ‘ shooting target’, ‘cancer’ and ‘warrior’.
Narratives of transformation: Family discourse, autism and trajectories of hope
Authors: Gainer Sirota Karen
Published: September 2010

This article explores the role of personal life narrative as a self-shaping transformative process in the day-to-day family lives of 17 US children diagnosed with autism. Employing ethnographic video-and audio-taped data of naturalistic family interaction, the article illumines how family members employ conversational narrative in co-creating, with children, possible imagined futures, aspirations, and goals. Despite uncertain futures and unknown clinical outcomes, children are encouraged to engage in self-reflexive narrative practices that portray them in a hopeful yet realistic light. By exploring moment-by-moment details of talk-in-interaction in the lives of children diagnosed with autism, the article contributes to scholarship on how children’s experiences and self-conceptions pertaining to well-being, disability, and difference are configured and shaped via discursive practices carried out within the family sphere. Children with autism display socio-communicative difficulties that call attention to, and render visible, discursive processes involved in children’s acquisition of culturally rooted narrative capacities. As such, analysis is positioned to shed light on children’s narrative proclivities in fathoming and reflecting upon personal life experience.
A Need for Redress
Authors: Wilkinson-Weber Clare M.
Published: September 2010

This article analyzes some Hindi film remakes using the overlooked component of film costume. Costuming in Devdas, Don, and Om Shanti Om can be read as a strategic effort to situate each film along with its predecessors in a new vision of the industry’s past and present. Since the early 1990s, India has been transformed by economic policies that have nurtured the growth of capitalism. Consumerism is celebrated in film at the same time, as filmmaking itself is undergoing structural change. Costume plays a critical role in these processes, operating in remakes to appropriate elements of each film’s forerunners in ways that illustrate the new film’s superiority. The case studies presented here illustrate how this is done: costumes are readily translatable into the commoditized clothing that is part of the new consumerism: they signal high production values; they are complicit in the construction of contemporary stardom; and they embody “professionalism” via the employment of well-connected fashion designers. At the same time, by illustrating the limits of masquerade or by reconfiguring the dilemmas of modernity as a myth, costume assists in the projection of themes that are more conservative than those of each film’s forerunners.
Supporting infection prevention in Romania: working together with Spitalul Judeţean de Urgenţă Zalău
Authors: Hallam Carole , Marincas Ramona
Published: September 2010

In countries with limited resources it is often difficult to see where improvements are being made. Our collaboration with infection prevention colleagues to prevent healthcare-associated infections at Spitalul Judetean de Urgenta Zalau (Zalau Emergency Hospital) has created a strong friendship between UK infection control teams and the staff at Zalau but more importantly has raised the profile of infection prevention and control at this district general hospital in Romania. This paper describes how a project of voluntary working with this hospital has provided an enlightening experience for many of those involved, helping to strengthen leadership and communication skills and being able to engage with the Romanian staff helping them believe in their work and to achieve their vision. This paper elaborates on the poster presented at Infection Prevention 2009.
Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla
Authors: Dai Kuang-Yu , Chan Samuel HH , Chang Alice YW
Published: September 2010

Background

Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM) because it is the origin of a life-and-death signal that sequentially increases (pro-life) and decreases (pro-death) to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1) may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1) and nitric oxide synthase I (NOS I)/protein kinase G (PKG) cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death.

Methods

We performed cardiovascular, pharmacological, biochemical and confocal microscopy experiments in conjunction with an experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM of adult male Sprague-Dawley rats.

Results

Western blot analysis coupled with laser scanning confocal microscopy revealed that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons occurred preferentially during the pro-life phase of experimental brain stem death and was antagonized by immunoneutralization of HIF-1α or HIF-1β in RVLM. On the other hand, the cytoplasmic presence of HO-2 in RVLM neurons manifested insignificant changes during both phases. Furthermore, immunoneutralization of HO-1 or knockdown ofho-1gene in RVLM blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated pro-life NOS I/PKG signaling without affecting the pro-death NOS II/peroxynitrite cascade in RVLM.

Conclusions

We conclude that transcriptional upregulation of HO-1 on activation by HIF-1 in RVLM plays a preferential pro-life role by sustaining central cardiovascular regulatory functions during brain stem death via upregulation of NOS I/PKG signaling pathway. Our results further showed that the pro-dead NOS II/peroxynitrite cascade in RVLM is not included in this repertoire of cellular events.
Distinct α subunit variations of the hypothalamic GABAA receptor triplets (αβγ) are linked to hibernating state in hamsters
Authors: Alò Raffaella , Avolio Ennio , Di Vito Anna , Carelli Antonio , Facciolo Rosa Maria , Canonaco Marcello
Published: September 2010

Background

The structural arrangement of the γ-aminobutyric acid type A receptor (GABAAR) is known to be crucial for the maintenance of cerebral-dependent homeostatic mechanisms during the promotion of highly adaptive neurophysiological events of the permissive hibernating rodent, i.e the Syrian golden hamster. In this study,in vitroquantitative autoradiography andin situhybridization were assessed in major hypothalamic nuclei. Reverse Transcription Reaction-Polymerase chain reaction (RT-PCR) tests were performed for specific GABAAR receptor subunit gene primers synthases of non-hibernating (NHIB) and hibernating (HIB) hamsters. Attempts were made to identify the type of αβγ subunit combinations operating during the switching ON/OFF of neuronal activities in some hypothalamic nuclei of hibernators.

Results

Both autoradiography and molecular analysis supplied distinct expression patterns of all α subunits considered as shown by a strong (p < 0.01) prevalence of α1ratio (over total α subunits considered in the present study) in the medial preoptic area (MPOA) and arcuate nucleus (Arc) of NHIBs with respect to HIBs. At the same time α2subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong α4expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. the suprachiasmatic nucleus (Sch; 60%). Regarding the other two subunits (β and γ), elevated β3and γ3mRNAs levels mostly characterized MPOA of HIBs, while prevalently elevated expression concentrations of the same subunits were also typical of Sch, even though this time during the awakening state. In the case of Arc, notably elevated levels were obtained for β3and γ2during hibernating conditions.

Conclusion

We conclude that different αβγ subunits are operating as major elements either at the onset of torpor or during induction of the arousal state in the Syrian golden hamster. The identification of a brain regional distribution pattern of distinct GABAAR subunit combinations may prove to be very useful for highlighting GABAergic mechanisms functioning at least during the different physiological states of hibernators and this may have interesting therapeutic bearings on neurological sleeping disorders.
Self-reported sexually transmitted infections and their correlates among men who have sex with men in Norway: an Internet-based cross-sectional survey
Authors: Jakopanec Irena , Schimmer Barbara , Grjibovski Andrej M , Klouman Elise , Aavitsland Preben
Published: September 2010

Background

The incidences of reportable sexually transmitted infections (STI) among men who have sex with men (MSM) have increased since the late 1990 s in Norway. The objectives of our study were to assess factors, associated with recent selected STI among MSM, living in Norway in order to guide prevention measures.

Methods

We conducted a cross-sectional Internet-based survey during 1-19 October 2007 among members of a MSM-oriented Norwegian website using an anonymous questionnaire on demographics, sexual behaviour, drug and alcohol use, and STI. The studied outcomes were gonorrhoea, syphilis, HIV or Chlamydia infection in the previous 12 months. Associations between self-reported selected STI and their correlates were analysed by multivariable Poisson regression. P value for trend (p-trend), adjusted prevalence ratios (PR) with 95% confidence intervals [] were calculated.

Results

Among 2430 eligible 16-74 years old respondents, 184 (8%) reported having had one of the following: syphilis (n = 17), gonorrhoea (n = 35), HIV (n = 42) or Chlamydia (n = 126) diagnosed in the past 12 months. Reporting Chlamydia was associated with non-western background (PR 2.8 [1.4-5.7]), number of lifetime male partners (p-trend < 0.001), unsafe sex under the influence of alcohol (PR 1.8 [1.1-2.9]) and with younger age (p-trend = 0.002). Reporting gonorrhoea was associated with unrevealed background (PR 5.9 [1.3-26.3]), having more than 50 lifetime male partners (PR 4.5 [1.3-15.6]) and more than 5 partners in the past 6 months (PR 3.1 [1.1-8.8]), while mid-range income was protective (PR 0.1 [0.0-0.6]). Reporting HIV was associated with residing in Oslo or Akershus county (PR 2.3 [1.2-4.6]), non-western background (PR 5.4 [1.9-15.3]), unrevealed income (PR 10.4 [1.5-71.4]), number of lifetime male partners (p-trend < 0.001) and being under the influence of selected drugs during sex in the past 12 months (PR 5.2 [2.7-11.4]). In addition, the frequency of feeling drunk was reversibly associated with HIV.

Conclusions

Our study demonstrates different associations of demographic and behavioural factors with different STI outcomes in the study population. Number of lifetime male partners was the most important potential predictor for Chlamydia and HIV. The STI prevention efforts among MSM should focus on Oslo and Akershus, promote safe sex practices and tackle sex-related drug and alcohol use.