bluuebunny/crossref_metadata_2025 huggingface dataset:
ALCOHOLISM: IS THERE A ROLE FOR PSYCHIATRY?
Authors: Large Robert G.
Published: August 2010

The contribution of psychiatry to the treatment of alcoholism is discussed in the broad context of currently available data on the epidemiology, natural history and efficacy of treatment of the disorder. The epidemiological evidence does not support a disease concept but, rather, links the disorder to the level of per capita consumption of alcohol in a community. The natural history of alcoholism suggests a substantial spontaneous remission, while treatment programmes are shown to have a limited effect. A model of alcoholism is derived from the data which implies that action which will reduce the per capita consumption of alcohol is likely to be more effective in reducing alcohol‐related problems than the setting up of secondary preventative programmes. The profession is urged to consider taking political action by advising government to steadily introduce price control measures on alcoholic liquor.
DIAGNOSIS RELATED GROUP REIMBURSEMENT OF HOSPITAL SERVICES IN THE UNITED STATES: POTENTIAL FOR INTRODUCTION IN AUSTRALIA
Authors: Doman Andrew S.
Published: August 2010

This article reviews progress in the United States towards implementing the concept of diagnosis related group reimbursement for hospital admissions. Although the basis of payments to public hospitals in Australia differs significantly from the basis of funding of hospitals in the United States, this article argues there is value in exploring further the possibility of introducing diagnosis related reimbursement in Australia.
COMMENTARY: THE PROPOSED GENERAL PRACTICE DESCRIPTORS ‐ WILL THEY INFLUENCE PREVENTIVE MEDICINE?
Authors: Moorhead R.G.
Published: August 2010

The proposed descriptor bill to change Medicare rebates to general practice patients could have a benefit to general practice preventive medicine. This seems possible through rewarding practitioners who spend more time with their patients and the positive effects of continuing medical education. However, the potential exists for whittling away any rewards for these practitioners by future governments and the audit of general practices could become a method of political control of Australian general practice.
EMPIRE ET PATRIE
Authors: Baridon Michel
Published: August 2010

A study of the relation of politics to aesthetics in the works of Hume, Gibbon and Rousseau.
Review Article
Authors: Rainey E.
Published: August 2010

Project for Historical Biobibliography, University of Newcastle upon Tyne. Eighteenth‐Century British Books: an Author Union Catalogue extracted from the British Museum General Catalogue of Printed Books, the Catalogues of the Bodleian Library, and of the University Library, Cambridge. By F.J.G. Robinson, G. Averley, D. R. Esslemont and P. J. Wallis.

Eighteenth‐Century British Books: a Subject Catalogue extracted from the British Museum General Catalogue of Printed Books. By G. Averley, A. Flowers, F. J. G. Robinson, E. A. Thompson, R. V. and P. J. Wallis.
Carboniferous Stratigraphy of Northwestern Kansu.§
Authors: Yuan P. L.
Published: August 2010

(Abstract) The specimen is collected from a small outcrop near the Lolo village of Mao Mao Kou, some 30 km. N.N.W. of Hui Li district in S. Szechuan, on the N. slope of Lung Tsao Shan, a prominant mountain some 8,000 feet above the sea, entirely covered by a basaltic lava of Permian age. The latter weathers into a residual red clay which covers the lower slopes. The contact of the syenite with the Lung Tsao Shan lava was not observed owing to the thick cover. East of the occurrence a series of steep dipping red shales appears. The exact relation of this series with the syenite is not clear, but it is probable that they are in actual contact. Further east the red shale series is thrown into contact with a coal series containing Rhætic plant fossils—probably by an overthrust as the whole coal series is highly folded.
New Vertebrate Horizons in China*
Authors: Young C. C.
Published: August 2010

The nine levels of vertebrate fauna described above have either been recorded or extensively worked within the last few years. The Triassic, Miocene, Cyprinidæ, Base of the Pleistocene and the Anyang fauna are new while the remaining four have been recorded earlier. Nevertheless, a considerable number of additional facts both geographically and palæontologically were reported. In Figure 1, I give a sketch showing the various levels recognized after 1920. With the almost continuous excavation carried in Choukoutien as well as in other parts, it has become possible to trace the Cenozoic sequence from the Upper Miocene to prehistórical time with the exception of a few gaps only. Material derived from those new levels have been described in various recent publications, or else are being such studied and prepared for description as for instance, the Sauropoda of Sinkiang and Szechuan ; additional mammalian collection of Yuanchü; the Miocene mammals of Shanwang; the fishes of Locality 14 of Choukoutien und of the Yûshê basin ; and the large collection of material recovered from Locality 13 and the Upper Cave of Choukoutien.

From the accompanying Plate, it is evident that during the last six years surveys have been considerably extended to the south and west. We now have a Theromorpha‐ and dinosaurian fauna extending as far as to Sinkiang and western Szechuan as also the fissure and cave d epe «its in Yunnan and Kwangsi. The extension (distribution) of Mongolian early Tertiary mammals to the Huangho and Yangtze Valleys is of particular
On Two Skulls of Machairodus from the Lower Pleistocene Beds of Choukoutien
Authors: Teilhard De Chardin P.
Published: August 2010

Two exceptionally well preserved skulls of Machairodus found in the Lower Pleistocene of Choukoutien are described herein. They belong to two different sections of the Machairodus group, roughly referable to the European Epimachairodus and Megantereon respectively. The persistence and development of the two forms side‐by‐side since the Pliocene is suggested.
Development of a Vertically Stabilized Thermal Probe for Studies in and Below Ice Sheets
Authors: Aamot H. W. C.
Published: August 2010

The pendulum probe is described. It is an instrumented device that penetrates polar ice sheets for remote measurements of geophysical parameters. It can only move downward by melt penetration; its instrumentation is permanently installed, sealed in the ice. The power requirements and operating costs are derived from the heat transfer analysis. The pendulum steering principle, which assures a vertical probe attitude and course, also explains its performance flexibility. The results from the first trials verify the probe’s feasibility and supply additional design information. The probe offers a unique opportunity for access to, and study of, the Antarctic Ocean waters under the Ross and Filchner ice shelves.
Analysis of Tube Extrusion
Authors: Mehta H. S. , Shabaik A. H. , Kobayashi Shiro
Published: August 2010

Two solutions for the detailed mechanics of tube extrusion are presented. One is based on the theoretical velocity field, and the other on the flow field observed experimentally. The theoretical solution makes use of admissible velocity fields containing no velocity discontinuities. Experimental flow patterns are obtained for commercially pure lead and a superplastic alloy of the eutectic of lead and tin. The two solutions are compared in terms of velocity components, grid distortions, and strain and stress distributions, and very good agreement between the two solutions is revealed.
A New Approach to Plasticity and Its Application to Blunt Two Dimensional Indenters
Authors: Shaw M. C. , DeSalvo G. J.
Published: August 2010

The classical slip line field solution for a two-dimensional punch is found to give a constraint factor (2.57) which is too small when the specimen beneath the punch is extensive. A new approach based on elasticity provides a constraint factor of 2.75. The new method of analysis also enables residual stresses to be estimated and indicates that plastic flow occurs not only when the specimen is loaded, but also when it is unloaded. Several details concerning the performance of hardness indenters are explained by the new theory for the first time.
Interactions of the Transmembrane Polymeric Rings of the Salmonella enterica Serovar Typhimurium Type III Secretion System
Authors: Sanowar Sarah , Singh Pragya , Pfuetzner Richard A. , André Ingemar , Zheng Hongjin , Spreter Thomas , Strynadka Natalie C. J. , Gonen Tamir , Baker David , Goodlett David R. , Miller Samuel I.
Published: August 2010

The type III secretion system (T3SS) is an interspecies protein transport machine that plays a major role in interactions of Gram-negative bacteria with animals and plants by delivering bacterial effector proteins into host cells. T3SSs span both membranes of Gram-negative bacteria by forming a structure of connected oligomeric rings termed the needle complex (NC). Here, the localization of subunits in the
Salmonella enterica
serovar Typhimurium T3SS NC were probed via mass spectrometry-assisted identification of chemical cross-links in intact NC preparations. Cross-links between amino acids near the amino terminus of the outer membrane ring component InvG and the carboxyl terminus of the inner membrane ring component PrgH and between the two inner membrane components PrgH and PrgK allowed for spatial localization of the three ring components within the electron density map structures of NCs. Mutational and biochemical analysis demonstrated that the amino terminus of InvG and the carboxyl terminus of PrgH play a critical role in the assembly and function of the T3SS apparatus. Analysis of an InvG mutant indicates that the structure of the InvG oligomer can affect the switching of the T3SS substrate to translocon and effector components. This study provides insights into how structural organization of needle complex base components promotes T3SS assembly and function.

IMPORTANCE
Many biological macromolecular complexes are composed of symmetrical homomers, which assemble into larger structures. Some complexes, such as secretion systems, span biological membranes, forming hydrophilic domains to move substrates across lipid bilayers. Type III secretion systems (T3SSs) deliver bacterial effector proteins directly to the host cell cytoplasm and allow for critical interactions between many Gram-negative pathogenic bacterial species and their hosts. Progress has been made towards the goal of determining the three-dimensional structure of the secretion apparatus by determination of high-resolution crystal structures of individual protein subunits and low-resolution models of the assembly, using reconstructions of cryoelectron microscopy images. However, a more refined picture of the localization of periplasmic ring structures within the assembly and their interactions has only recently begun to emerge. This work localizes T3SS transmembrane rings and identifies structural elements that affect substrate switching and are essential to the assembly of components that are inserted into host cell membranes.
IDENTIFICATION OF EXCITABLE MEDIA USING A SCALAR COUPLED MAP LATTICE MODEL
Authors: GUO YUZHU , ZHAO YIFAN , BILLINGS S. A. , COCA DANIEL , RISTIC R. I. , DEMATOS L. L.
Published: August 2010

The identification problem for excitable media is investigated in this paper. A new scalar coupled map lattice (SCML) model is introduced and the orthogonal least squares algorithm is employed to determinate the structure of the SCML model and to estimate the associated parameters. A simulated pattern and a pattern observed directly from a real Belousov–Zhabotinsky reaction are identified. The identified SCML models are shown to possess almost the same local dynamics as the original systems and are able to provide good long term predictions.
A STUDY ON PENETRATION DEPTH OF POLARIZATION IMAGING
Authors: LIAO RAN , ZENG NAN , LI DONGZHI , YUN TIANLIANG , HE YONGHONG , MA HUI
Published: August 2010

Optical clearing improves the penetration depth of optical measurements in turbid tissues. Polarization imaging has been demonstrated as a potentially promising tool for detecting cancers in superficial tissues, but its limited depth of detection is a major obstacle to the effective application in clinical diagnosis. In the present paper, detection depths of two polarization imaging methods, i.e., rotating linear polarization imaging (RLPI) and degree of polarization imaging (DOPI), are examined quantitatively using both experiments and Monte Carlo simulations. The results show that the contrast curves of RLPI and DOPI are different. The characteristic depth of DOPI scales with transport mean free path length, and that of RLPI increases slightly with g. Both characteristic depths of RLPI and DOPI are on the order of transport mean free path length and the former is almost twice as large as the latter. It is expected that they should have different response to optical clearing process in tissues.
PARAMETRIC STUDY OF TISSUE OPTICAL CLEARING BY LOCALIZED MECHANICAL COMPRESSION USING COMBINED FINITE ELEMENT AND MONTE CARLO SIMULATION
Authors: VOGT WILLIAM C. , SHEN HAIOU , WANG GE , RYLANDER CHRISTOPHER G.
Published: August 2010

Tissue Optical Clearing Devices (TOCDs) have been shown to increase light transmission through mechanically compressed regions of naturally turbid biological tissues. We hypothesize that zones of high compressive strain induced by TOCD pins produce localized water displacement and reversible changes in tissue optical properties. In this paper, we demonstrate a novel combined mechanical finite element model and optical Monte Carlo model which simulates TOCD pin compression of an ex vivo porcine skin sample and modified spatial photon fluence distributions within the tissue. Results of this simulation qualitatively suggest that light transmission through the skin can be significantly affected by changes in compressed tissue geometry as well as concurrent changes in tissue optical properties. The development of a comprehensive multi-domain model of TOCD application to tissues such as skin could ultimately be used as a framework for optimizing future design of TOCDs.
ASSESSMENT OF TISSUE OPTICAL CLEARING AS A FUNCTION OF GLUCOSE CONCENTRATION USING OPTICAL COHERENCE TOMOGRAPHY
Authors: SUDHEENDRAN NARENDRAN , MOHAMED MOHAMED , GHOSN MOHAMAD G. , TUCHIN VALERY V. , LARIN KIRILL V.
Published: August 2010

One of the major challenges in imaging biological tissues using optical techniques, such as optical coherence tomography (OCT), is the lack of light penetration due to highly turbid structures within the tissue. Optical clearing techniques enable the biological samples to be more optically homogeneous, allowing for deeper penetration of light into the tissue. This study investigates the effect of optical clearing utilizing various concentrations of glucose solution (10%, 30%, and 50%) on porcine skin. A gold-plated mirror was imaged beneath the tissue and percentage clearing was determined by monitoring the change in reflected light intensity from the mirror over time. The ratio of percentage clearing per tissue thickness for 10%, 30% and 50% glucose was determined to be 4.7 ±1.6% mm-1 (n = 6), 10.6 ±2.0% mm-1 (n = 7) and 21.8 ±2.2% mm-1 (n = 5), respectively. It was concluded that while higher glucose concentration has the highest optical clearing effect, a suitable concentration should be chosen for the purpose of clearing, considering the osmotic stress on the tissue sample.
Mouse embryonic phenotyping by morphometric analysis of MR images
Authors: Zamyadi M. , Baghdadi L. , Lerch J. P. , Bhattacharya S. , Schneider J. E. , Henkelman R. M. , Sled J. G.
Published: August 2010

A new method is described for automatic detection of subtle morphological phenotypes in mouse embryos. Based on high-resolution magnetic resonance imaging scanning and nonlinear image alignment, this method is demonstrated by comparing the morphology of two inbred strains, C57BL/6J and 129Sv/S1ImJ, at 15.5 days postconception. Mouse embryo morphology was found to be highly amenable to this kind of analysis with very low levels (on average 110 μm) of residual anatomical variation within strains after linear differences in pose and scale are removed. Mapping of local size differences showed that C57BL/6J embryos were larger than 129Sv/S1ImJ embryos, although these differences were not uniformly distributed across the anatomy. Expressed in terms of organ volumes, heart and lung were larger in C57BL/6J embryos, while brain and liver were comparable in volume between strains. The positive relationship between organ size and embryo size was consistent for the two strains but differed by organ, with the brain and liver being the least variable. Together these findings suggest the power of this technique for detecting subtle phenotypic differences arising from mutated genes.
Recent Visual Decline—A Health Hazard with Consequences for Social Life: A Study of Home Care Clients in 12 Countries
Authors: Grue Else Vengnes , Finne-Soveri Harriet , Stolee Paul , Poss Jeff , Sörbye Liv Wergeland , Noro Anja , Hirdes John P. , Ranhoff Anette Hylen
Published: August 2010

Information about recent visual decline (RVD) and its consequences is limited. The aim was to investigate this in an observational, prospective study. Participants were recipients of community home services,≥65 years, from Ontario (Canada,n=101618), Finland (the-RAI-database, STAKES,n=1103), and 10 other European countries (the-Aged-in-HOmeCarestudy (AdHOC),n=3793). The instrument RAI-HC version 2.0 was used in all sites. RVD was assessed by the item “Worsening of vision compared to status 90 days ago” and was present in 6–49% in various sites, more common among persons living alone, and in females. In the AdHOC sample, RVD was independently associated with declining social activity and limited outdoors activities due to fear of falling. The combination of stable vision impairment (SVI) and RVD was independently associated with IADL loss. RVD is common and has greater impact than SVI on social life and function. Caregivers should be particularly aware of RVD, its consequences, and help patients to seek assessments, treatment, and rehabilitation.
Immunologic Consequences of Signal Transducers and Activators of Transcription 3 Activation in Human Squamous Cell Carcinoma
Authors: Albesiano Emilia , Davis Meghan , See Alfred P. , Han James E. , Lim Michael , Pardoll Drew M. , Kim Young
Published: August 2010

Paracrine cross-talk between tumor cells and immune cells within the tumor microenvironment underlies local mechanisms of immune evasion. Signal transducer and activator of transcription 3 (STAT3), which is constitutively activated in diverse cancer types, is a key regulator of cytokine and chemokine expression in murine tumors, resulting in suppression of both innate and adaptive antitumor immunity. However, the immunologic effects of STAT3 activation in human cancers have not been studied in detail. To investigate how STAT3 activity in human head and neck squamous cell carcinoma (HNSCC) might alter the tumor microenvironment to enable immune escape, we used small interfering RNA and small-molecule inhibitors to suppress STAT3 activity. STAT3 inhibition in multiple primary and established human squamous carcinoma lines resulted in enhanced expression and secretion of both proinflammatory cytokines and chemokines. Although conditioned medium containing supernatants from human HNSCC inhibited lipopolysaccharide-induced dendritic cell activation in vitro, supernatants from STAT3-silenced tumor cells reversed this immune evasion mechanism. Moreover, supernatants from STAT3-silenced tumor cells were able to stimulate the migratory behavior of lymphocytes from human peripheral blood in vitro. These results show the importance of STAT3 activation in regulating the immunomodulatory mediators by human tumors and further validate STAT3 as a promising target for therapeutic intervention. Cancer Res; 70(16); 6467–76. ©2010 AACR.
Fluorescence-Based Codetection with Protein Markers Reveals Distinct Cellular Compartments for Altered MicroRNA Expression in Solid Tumors
Authors: Sempere Lorenzo F. , Preis Meir , Yezefski Todd , Ouyang Haoxu , Suriawinata Arief A. , Silahtaroglu Asli , Conejo-Garcia Jose R. , Kauppinen Sakari , Wells Wendy , Korc Murray
Published: August 2010

Purpose: High-throughput profiling experiments have linked altered expression of microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. To clarify the clinical significance of altered miRNA expression in solid tumors, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was implemented to be compatible with routine clinical immunohistochemical (IHC) assays to enable the detection of miRNAs and protein markers in the same tissue section for colocalization and functional studies.

Experimental Design: We used this combined ISH/IHC assay to study a subset of cancer-associated miRNAs, including miRNAs frequently detected at low (miR-34a and miR-126) and high (miR-21 and miR-155) levels, in a panel of breast, colorectal, lung, pancreas, and prostate carcinomas.

Results: Despite the distinct histopathologic alterations of each particular cancer type, general trends emerged that pinpointed distinct source cells of altered miRNA expression. Although altered expressions of miR-21 and miR-34a were manifested within cancer cells, those of miR-126 and miR-155 were predominantly confined to endothelial cells and immune cells, respectively. These results suggest a heterogeneous participation of miRNAs in carcinogenesis by intrinsically affecting cancer cell biology or by modulating stromal, vascular, and immune responses.

Conclusions: We described a rapid and sensitive multicolor ISH/IHC assay and showed that it could be broadly applied as an investigational tool to better understand the etiologic relevance of altered miRNA expression in cancer. Clin Cancer Res; 16(16); 4246–55. ©2010 AACR.
Converging Evidence for Efficacy from Parallel EphB4-Targeted Approaches in Ovarian Carcinoma
Authors: Spannuth Whitney A. , Mangala Lingegowda S. , Stone Rebecca L. , Carroll Amy R. , Nishimura Masato , Shahzad Mian M.K. , Lee Sun-Joo , Moreno-Smith Myrthala , Nick Alpa M. , Liu Ren , Jennings Nicholas B. , Lin Yvonne G. , Merritt William M. , Coleman Robert L. , Vivas-Mejia Pablo E. , Zhou Yue , Krasnoperov Valery , Lopez-Berestein Gabriel , Gill Parkash S. , Sood Anil K.
Published: August 2010

EphB4 is a transmembrane receptor tyrosine kinase that plays an important role in neural plasticity and angiogenesis. EphB4 is overexpressed in ovarian cancer and is predictive of poor clinical outcome. However, the biological significance of EphB4 in ovarian cancer is not known and is the focus of the current study. Here, we examined the biological effects of two different methods of EphB4 targeting (a novel monoclonal antibody, EphB4-131 or siRNA) using several ovarian cancer models. EphB4 gene silencing significantly increased tumor cell apoptosis and decreased migration (P < 0.001) and invasion (P < 0.001). Compared with controls, EphB4 siRNA–1,2-dioleoyl-sn-glycero-3-phosphatidylcholine alone significantly reduced tumor growth in the A2780-cp20 (48%, P < 0.05) and IGROV-af1 (61%, P < 0.05) models. Combination therapy with EphB4 siRNA–1,2-dioleoyl-sn-glycero-3-phosphatidylcholine and docetaxel resulted in the greatest reduction in tumor weight in both A2780-cp20 and IGROV-af1 models (89–95% reduction versus controls; P < 0.05 for both groups). The EphB4-131 antibody, which reduced EphB4 protein levels, decreased tumor growth by 80% to 83% (P < 0.01 for both models) in A2780-cp20 and IGROV-af1 models. The combination of EphB4-131 and docetaxel resulted in the greatest tumor reduction in both A2780-cp20 and IGROV-af1 models (94–98% reduction versus controls; P < 0.05 for both groups). Compared with controls, EphB4 targeting resulted in reduced tumor angiogenesis (P < 0.001), proliferation (P < 0.001), and increased tumor cell apoptosis (P < 0.001), which likely occur through modulation of phosphoinositide 3-kinase signaling. Collectively, these data identify EphB4 as a valuable therapeutic target in ovarian cancer and offer two new strategies for further development. Mol Cancer Ther; 9(8); 2377–88. ©2010 AACR.
Prenatal Flutamide Enhances Survival in a Myogenic Mouse Model of Spinal Bulbar Muscular Atrophy
Authors: Johansen Jamie A. , Troxell-Smith Sandra M. , Yu Zhigang , Mo Kaiguo , Monks D. Ashley , Lieberman Andrew P. , Breedlove S. Marc , Jordan Cynthia L.
Published: August 2010

Background: Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene, and mutant AR is presumed to act in motoneurons to cause SBMA. However, we found that mice overexpressing wild-type (wt) AR solely in skeletal muscle fibers display the same androgen-dependent disease phenotype as when mutant AR is broadly expressed, challenging the assumptions that only an expanded AR can induce disease and that SBMA is strictly neurogenic. We have previously reported that AR toxicity was ligand dependent in our model, and that very few transgenic (tg) males survived beyond birth. Methods: We tested whether the AR antagonist flutamide could block perinatal toxicity. tg males were treated prenatally with flutamide and assessed for survival and motor behavior in adulthood. Results: Prenatal treatment with flutamide rescued tg male pups from perinatal death, and, as adults, such perinatally rescued tg males showed an SBMA phenotype that was comparable to that of previously described untreated tg males. Moreover, tg males carrying a mutant endogenous allele for AR – the testicular feminization mutation (tfm) – and thus having functional AR only in muscle fibers nevertheless displayed the same androgen-dependent disease phenotype as adults. Conclusions: These mice represent an excellent model to study the myogenic contribution to SBMA as they display many of the core features of disease as other mouse models. These data demonstrate that AR acting exclusively in muscle fibers is sufficient to induce SBMA symptoms and that flutamide is protective perinatally.
TASTPM Mice Expressing Amyloid Precursor Protein and Presenilin-1 Mutant Transgenes Are Sensitive to γ-Secretase Modulation and Amyloid-β42 Lowering by GSM-10h
Authors: Hussain Ishrut , Harrison David C. , Hawkins Julie , Chapman Trevor , Marshall Ian , Facci Laura , Ahmed Sharlin , Brackenborough Kim , Skaper Stephen D. , Mead Tania L. , Smith Beverley B. , Giblin Gerard M.P. , Hall Adrian , Gonzalez M. Isabel , Richardson Jill C.
Published: August 2010

Background: Cleavage of the amyloid precursor protein (APP) by β-site APP-cleaving enzyme and γ-secretase results in the generation of amyloid-β (Aβ) peptides that aggregate and deposit as senile plaques in brains of Alzheimer disease patients. Due to the fundamental role γ-secretase plays in the proteolysis of a number of proteins including Notch, pharmacological inhibition of γ-secretase has been associated with mechanism-based toxicities. Therefore, efforts have focussed on the modulation of γ-secretase activity to selectively decrease levels of Aβ42 peptide while avoiding deleterious activity on Notch processing. Objective: Here, we describe the in vitro and in vivo characterisation of a novel γ-secretase modulator, GSM-10h, and investigate the potential for shorter Aβ peptides to induce neurotoxicity in rat primary cortical neurons. Methods: The effect of GSM-10h on Aβ levels was investigated in SH-SY5Y cells expressing mutant APP and in TASTPM mice expressing APP and presenilin-1 mutant transgenes. The effect of GSM-10h on Notch processing was also determined. Results:In cells, GSM-10h decreased levels of Aβ42 while concomitantly increasing levels of Aβ38 in the absence of effects on Aβ40 levels. In TASTPM mice, GSM-10h effectively lowered brain Aβ42 and increased brain Aβ38, with no effect on Notch signalling. Unlike Aβ42, which causes neuronal cell death, neither Aβ37 nor Aβ38 were neurotoxic. Conclusions: These findings confirm GSM-10h exhibits the profile of a γ-secretase modulator. In addition, TASTPM mice are shown to be responsive to treatment with a γ-secretase modulator, thereby highlighting the utility of this bitransgenic mouse model in drug discovery efforts focussed on the development of γ-secretase modulators.
Left Ventricular Mass Index Is an Independent Determinant of Diastolic Dysfunction in Patients on Chronic Hemodialysis: A Tissue Doppler Imaging Study
Authors: Kimura Hiroshi , Takeda Kazuhito , Tsuruya Kazuhiko , Mukai Hideyuki , Muto Yoshiharu , Okuda Hiroshi , Furusho Masahide , Ueno Toshiharu , Nakashita Satsuki , Miura Shuhei , Maeda Atsuhiro , Kondo Hideki
Published: August 2010

Background: Diastolic heart failure is the most common clinical form of heart failure. Tissue Doppler imaging (TDI) is often used to quantitate left ventricular (LV) diastolic function. The purpose of this study was to identify the determinant(s) of diastolic dysfunction in patients with end-stage renal disease on hemodialysis (HD), using the TDI method. Methods: The study subjects were 53 patients with end-stage renal disease and preserved LV systolic function on maintenance HD. LV function was assessed by conventional echocardiography. The ratio of early trans-mitral flow velocity to early mitral annular velocity (E/e′) was measured by TDI. Patients were stratified into two groups based on E/e′ value (≤15 and >15 groups). Arterial stiffness was evaluated by pulse wave velocity and cardio-ankle vascular index. Results: Patients of the E/e′ >15 group were older (p = 0.025). There were no significant differences in blood pressure, ejection fraction, E/A, deceleration time, and pulse wave velocity between the E/e′ >15 and E/e′ ≤15 groups. However, there were significant differences in LV mass index (LVMI; p < 0.001) and cardio-ankle vascular index (p = 0.048) between the two groups. Multiple regression analysis identified that LVMI was an independent determinant of E/e′ (p = 0.003). Conclusions:Our findings suggest that LVMI is an independent determinant of LV diastolic dysfunction in patients on HD.
Improving Extraseasonal Summer Rainfall Prediction by Merging Information from GCMs and Observations
Authors: Lang Xianmei , Wang Huijun
Published: August 2010

A new prediction approach for summer (June–August) rainfall in China was designed by considering both preceding observations and numerically predicted summer rainfall through a multivariate linear regression analysis. First, correlation analyses revealed close relationships between summer rainfall in parts of China with the Antarctic Oscillation (AAO), the Arctic Oscillation (AO), and sea surface temperatures (SSTs) in the preceding winter (December–February). The Huang-Huai Valley, two subregions of the Jiang-Huai Valley, the southern Yangtze River, south China, and southeastern Xinjiang were then chosen as targets for their regional climate characteristics. Following this, an extraseasonal (one season in advance) regression prediction model for regionally averaged summer rainfall was constructed by using these three climate factors and a 3-month lead-time forecast of summer rainfall, undertaken by an atmospheric general circulation model (GCM) forced by observed SSTs, as predictors region by region. To improve the accuracy of prediction, the systematic error between the original regression model’s results and its observational counterparts, averaged for the last 10 yr, was corrected. Using this new approach, real-time prediction experiments and cross-validation analyses were performed for the periods 2002–07 and 1982–2007, respectively. It was found that the new prediction approach was more skillful than the original or corrected GCM prediction alone in terms of sign, magnitude, and interannual variability of regionally averaged summer rainfall anomalies in all regions. The preceding observations were the major source of the prediction skill of summer rainfall in each region, and the GCM predictions added additional prediction skill in the western Jiang-Huai Valley and southeastern Xinjiang, in both of which the GCM prediction was used as a predictor.
Effect of Epinephrine and Insulin Resistance on Human Monocytes Obtained From Lean and Obese Healthy Participants: A Pilot Study
Authors: Sarigianni Maria , Bekiari Eleni , Tsapas Apostolos , Konstantinidis Diamantis , Kaloyianni Martha , Koliakos George , Paletas Konstantinos
Published: August 2010

We assessed the effect of epinephrine on human monocytes. Monocytes were isolated from 16 healthy obese and 10 lean healthy subjects. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Obese subjects were subdivided into 2 sub-groups, insulin sensitive (IS) and insulin resistant (IR). Monocyte properties [attachment to laminin 1, migration through laminin 1, oxidized-low density lipoprotein (oxLDL) phagocytosis] were assessed pre- and post-stimulation in vitro with epinephrine. Experiments were repeated after incubation with a Na+/H + exchanger-1 inhibitor (NHE-1) (cariporide). Epinephrine increased monocyte attachment to laminin in lean and obese IR subjects through involvement of NHE-1, PKC, NO synthase, NADPH oxidase and actin polymerization. In contrast, epinephrine did not affect monocyte migration. Epinephrine increased oxLDL phagocytosis in all groups studied. Incubation with cariporide attenuated oxLDL phagocytosis. Epinephrine induces monocyte dysfunction which may be atherogenic.
Acute Effects of Passive Smoking on Endothelial Function
Authors: Gül İbrahim , Karapınar Hekim , Yarlıoğlueş Mikail , Ozdogru İbrahim , Kaya Mehmet Gungor , Yılmaz Ahmet , Turgut Okan Onur , Tandoğan İzzet , Eryol Namık Kemal
Published: August 2010

Impairment of endothelial functions has been shown to occur after acute and chronic exposure to passive smoking (PS), as assessed by flow-mediated dilatation (FMD) of the brachial artery. A total of 61 participants, 30 male and 31 female, mean ages 26 (18-36) were enrolled in the study. All were clinically well and nonsmokers. All participants stayed for 30 minutes in the smoking room. Carbon monoxide (CO) level was 7.42 ± 0.98 ppm (4.71-10.50). Mean carboxyhemoglobin (COHb) levels of participants were significantly elevated after PS. Mean FMD was 18.6% ± 9% and decreased to 12.4% ± 7% after PS (P < .001). In the current study, with more number of participants at lower CO concentrations (7.42 ppm) and with smaller increase in COHb (51%) significant reduction (33%, P < .001) in FMD was observed.
Self-Organization and Self-Governance
Authors: Ismael J.T.
Published: August 2010

The intuitive difference between a system that choreographs the motion of its parts in the service of goals of its own formulation and a system composed of a collection of parts doing their own thing without coordination has been shaken by now familiar examples of self-organization. There is a broad and growing presumption in parts of philosophy and across the sciences that the appearance of centralized information-processing and control in the service of system-wide goals is mere appearance, i.e., an explanatory heuristic we have evolved to predict behavior, but one that will eventually get swept away in the advancing tide of self-organization. I argue that there is a distinction of central importance here, and that no adequate science of complex systems can dispense with it.
An Alternative to the Bar-Lev, Bobovitch, and Boukai Randomized Response Model
Authors: Odumade Oluseun , Singh Sarjinder
Published: August 2010

In this article, an alternative randomized response model is proposed. The proposed model is found to be more efficient than the randomized response model studied by Bar-Lev, Bobovitch, and Boukai (2004). The relative efficiency of the proposed model is studied with respect to the Bar-Lev et al. (2004) model under various situations.
Sexual Orientation Perception Involves Gendered Facial Cues
Authors: Freeman Jonathan B. , Johnson Kerri L. , Ambady Nalini , Rule Nicholas O.
Published: August 2010

Perceivers can accurately judge a face’s sexual orientation, but the perceptual mechanisms mediating this remain obscure. The authors hypothesized that stereotypes casting gays and lesbians as gender “inverts,” in cultural circulation for a century and a half, lead perceivers to use gendered facial cues to infer sexual orientation. Using computer-generated faces, Study 1 showed that as two facial dimensions (shape and texture) became more gender inverted, targets were more likely to be judged as gay or lesbian. Study 2 showed that real faces appearing more gender inverted were more likely to be judged as gay or lesbian. Furthermore, the stereotypic use of gendered cues influenced the accurate judgment of sexual orientation. Although using gendered cues increased the accuracy of sexual orientation judgments overall, Study 3 showed that judgments were reliably mistaken for targets that countered stereotypes. Together, the findings demonstrate that perceivers utilize gendered facial cues to glean another’s sexual orientation, and this influences the accuracy or error of judgments.
The Social Construction of a Contraceptive Technology: An Investigation of the Meanings of Norplant
Authors: Siegel Watkins Elizabeth
Published: August 2010

This essay looks at Norplant qua technology and uses analytic frameworks from the social construction of technology to explain the trajectory of its brief history. The author contend that there were multiple uses of Norplant, in terms of rhetorical strategies, symbolic representations, and contraceptive intentions, constructed by reproductive scientists, population control advocates, pharmaceutical manufacturers, doctors, birth control clinic staffers, government regulators, legislators, judges, women’s health activists, potential users, and actual users. However, while relevant social groups shaped the discourse surrounding Norplant in the 1990s, its ultimate fate was determined by choices made by potential users. At the ‘‘consumption junction’’ of the late twentieth-century contraceptive marketplace, American women ignored the meanings constructed for Norplant by developers, producers, providers, and policy makers and made their decisions based on what Norplant meant to them. Individuals’ decisions to choose other methods of preventing pregnancy coalesced into a collective rejection of this contraceptive technology.
On the bending characteristics of damaged composite conoidal shells - a finite element approach
Authors: Kumari Suman , Chakravorty Dipankar
Published: August 2010

A finite element analysis of composite conoidal shells with delamination damage is carried out to explore the bending characteristics of such shell configurations. Civil and structural engineers have always preferred conoidal shell configuration, which is a ruled and aesthetically pleasant shape. The introduction of laminated composite as the structural material has provided the impetus to explore the different behavioral aspects of composite conoids. The laminated composites are susceptible to delamination damage, occurring due to manufacturing defects or over loadings. Keeping the above points in mind, a finite element analysis using isoparametric shell bending element is presented here, incorporating a multipoint constraint algorithm to take care of compatibility of deformation and equilibrium of forces and moments at the delamination crack front. The formulation is validated through solution of benchmark problems, and a number of delaminated conoidal shells with different boundary conditions are solved for different extents of delamination damage and stacking sequences under uniformly distributed load. The truncation ratio, and hence curvature values, are also varied keeping in mind the industrial requirements of both full and truncated conoids. Results are carefully analyzed to arrive at a set of meaningful conclusions.
A new method for predicting dome thickness of composite pressure vessels
Authors: Rongguo Wang  , Weicheng Jiao  , Wenbo Liu  , Fan Yang
Published: August 2010

This research aims to establish a new method to predict the dome thickness of composite pressure vessels. A cubic spline function was presented to calculate the dome thickness. Using this cubic spline function, the dome thickness of an arbitrary composite pressure vessel was forecasted. The predictive results were compared with the existing methods and actual measured thickness. Then, the accuracy of this cubic spline function was discussed for predicting the dome thickness of composite pressure vessels with different polar radii and different fiber band width values. The results showed that dome thickness obtained from the cubic spline function could reflect the actual measured thickness well and it could provide an accurate model for the finite element analysis.
Policy Implications of the Effects of Maltreatment Type, Age, Recurrence, Severity, and Other Ecological Risks on Persistent Offending Among Disadvantaged Boys
Authors: Verrecchia P.J. , Fetzer Matthew D. , Lemmon John H. , Austin Thomas L.
Published: August 2010

Although research indicates that the presence of maltreatment affects delinquency when comparing maltreated with nonmaltreated children, studies examining maltreatment dimensions have been confounded by conceptual and methodological problems. This study featured within-group analyses that included methodological controls to examine effects of four maltreatment dimensions and other ecological risks on persistent youth offending among maltreated children. Results indicate that supervisory neglect, maltreatment recurrence, and maltreatment severity produce direct effects on persistent youth offending after controlling for individual and other environmental risks. Comparisons of effects indicate that supervisory neglect is the strongest predictor. The study highlights the value of an ecological approach in explaining the maltreatment/ delinquency link and discusses the implications for policy and research.
From Diversion to Reentry: Recidivism Risks Among Graduates of an Alternative to Incarceration Program
Authors: Sung Hung-En
Published: August 2010

Reentry usually refers to the transition from incarceration to community living. However, offenders diverted from prison to community-based restrictive sanctions also face the challenge of social reintegration. This study uses a postmatching case—control design to identify risk and protective factors for 1-year recidivism among completers of the Drug Treatment Alternative to Prison (DTAP) program in Brooklyn, New York. DTAP is a deferred-sentencing program targeting repeat drug-abusing felons arrested for drug sales. Participants are required to plead to a felony charge and spend 18 to 24 months in residential treatment. Forty-seven DTAP completers who had been re-arrested within a year of their dismissal are compared to 47 matched nonrecidivists. Results suggest that weak treatment engagement and social isolation considerably increase the risk of recidivism. Certain health conditions and/or medical needs also significantly correlate to reoffending. Implications for reentry policy making and research are discussed.
A History of Massage in Nurse Training School Curricula (1860-1945)
Authors: Ruffin Paula Thomas
Published: August 2010

Introduction: Guided by Florence Nightingale, massage nurse training instruction methods were duplicated in the U.S. nurse training curricula. In the 1880s to 1900s massage training and instruction was delivered by physicians, nurses, or masseurs for many disease conditions. In the 1930s to 1940s, influential nurse authors and educators began to recommend specialization in physiotherapy for nurses. Scientific and pharmacological solutions for symptoms of disease became popular, thus practicing basic nursing comfort measures using massage declined. Purposes: To trace roots of massage in the medical literature, the inclusion of massage in U.S. nurse training school curricula, and examine the historical shift from massage as a basic nursing comfort measure to a specialization of physiotherapy. Method: Primary text books by physicians, nurses, massage instructors; medical/nursing journals; nursing curriculum guidelines—archival collections of the Center for Historical Nursing Inquiry; Historical Collections at the University of Virginia Claude Moore Health Sciences Library; private historical collections; and secondary published books/ articles were used. Findings: Prior to increase in scientific care, use of analgesics, and specialization of physiotherapy departments, the nurse provided basic comfort measures that included massage. Historical research in the use of massage in nursing may help refocus attention on the healing of the mind/body and reinforce the value of compassionate touch and balance in nursing practice today.
Talking back through ‘talking Black’: African American English and agency in Walter Mosley’s Devil In a Blue Dress
Authors: Giaimo Genie
Published: August 2010

With the rise in the number of ethnic detective novels published yearly it is important to consider how this new genre deviates from its predecessor, hard-boiled detective fiction; language is a place where this deviation is most apparent. Authors of ethnic detective fiction use marked varieties of English to call attention to the ethnicity of protagonists but, more important to this discussion, to highlight the complex ways in which they position themselves against White male hegemony. Ethnic detective fiction highlights the struggles, complications, dangers, and joys of the Other, a character who is typically marked by sexual, racial, or ethnic marginality, as he or she moves towards autonomy. This article examines how Walter Mosley’s Devil in a Blue Dress upends stereotypical assumptions about the legitimacy and complexity of African American English (AAE) and demonstrates how the protagonist, Easy Rawlins, utilizes certain aspects of AAE, such as signifying, multiple negatives, and the invariant form of the verb ‘be’ at key moments in the text to assert himself and shape his identity as an ethnic detective.
Review Article: A modest proposal for a reorientation in literary studies
Authors: Francis Norbert
Published: August 2010

This essay offers a review of Literature, Science and a New Humanities by Jonathan Gottschall. The author challenges the field of literary studies to rethink long-held assumptions about the nature of knowledge and human nature. In particular, what appear to be dominant tendencies in the field have strongly resisted the inclusion of findings from biology and genetics specifically. This resistance is tied to a view that scientific methods do not apply to the study of literature, and that radical social-constructivist theory presents a general alternative to the traditional methods of scientific inquiry. A proposal is made to incorporate recent advances in the cognitive sciences into the analysis of literature. Specifically, concepts drawn from evolutionary psychology might be especially useful in the analysis of narrative themes.