bluuebunny/crossref_metadata_2025 huggingface dataset:
Nagarjuna and Yoga: complexities in origin and tradition
Authors: Mason G.
Published: January 2010

In this article I attempt to establish a radical hermeneutic for interpreting Nagarjuna's MŪlaMadyamikarika. I argue that understanding the text requires a sensitivity to the subtle fluidity and interconnectedness of Indian cultural ideational forms, particularly those related to yogic meditational practices. I examine the recurrence of one ideational pattern - the two-tiered view of reality - in Hindu yogic and Buddhist texts with particular reference to the MŪlamadyamikakarika. I submit that without an awareness of the fluidity of thought patterns textual interpretations of Nagarjuna's work becomes too confined to immediate historical contexts.
Observations of a Super Cloud Cluster Accompanied by Synoptic-Scale Eastward-Propagating Precipitating Systems over the Indian Ocean
Authors: Yamada Hiroyuki , Yoneyama Kunio , Katsumata Masaki , Shirooka Ryuichi
Published: January 2010

The multiscale structure of a super cloud cluster (SCC) over the equatorial Indian Ocean, observed in November and December 2006, was investigated using data from satellite microwave sensors and surface-based radars. The smaller-scale structure of this SCC was marked by a complicated relationship between rainfall systems and upper-tropospheric cloud shields, which moved eastward and westward, respectively, with a cycle of 2–4 days. In the analyses, attention was given to the structure of slow eastward-propagating (5–11 m s−1) precipitating systems and related synoptic-scale (∼2000 km) disturbances. A case study of one of the systems revealed that it consisted of several lines of convective cells with a depth that was usually shallower than 10 km unless the cells encountered the westward-moving cloud shields. The environment of the convective lines was characterized by persistent unstable conditions with an increase of the westerly flow in the lower troposphere, suggesting the existence of a synoptic-scale upward motion. Composite analyses revealed that each rainfall system formed in a region of zonal flow convergence near the surface and divergence near 300 hPa. The vertical temperature structure tilted westward with height below this pressure level and eastward aloft, similar to that of a convectively coupled Kelvin wave. These results suggest that a SCC involves a group of synoptic-scale shallow waves propagating eastward. An additional analysis over the western Pacific also showed the predominance of eastward propagation in a SCC, demonstrating the advantage of satellite microwave sensors over infrared ones in monitoring the multiscale structure of tropical convection.
An Analysis of Convectively Coupled Kelvin Waves in 20 WCRP CMIP3 Global Coupled Climate Models
Authors: Straub Katherine H. , Haertel Patrick T. , Kiladis George N.
Published: January 2010

Output from 20 coupled global climate models is analyzed to determine whether convectively coupled Kelvin waves exist in the models, and, if so, how their horizontal and vertical structures compare to observations. Model data are obtained from the World Climate Research Program’s (WCRP’s) Coupled Model Intercomparison Project phase 3 (CMIP3) multimodel dataset.

Ten of the 20 models contain spectral peaks in precipitation in the Kelvin wave band, and, of these 10, only 5 contain wave activity distributions and three-dimensional wave structures that resemble the observations. Thus, the majority (75%) of the global climate models surveyed do not accurately represent convectively coupled Kelvin waves, one of the primary sources of submonthly zonally propagating variability in the tropics.

The primary feature common to the five successful models is the convective parameterization. Three of the five models use the Tiedtke–Nordeng convective scheme, while the other two utilize the Pan and Randall scheme. The 15 models with less success at generating Kelvin waves predominantly contain convective schemes that are based on the concept of convective adjustment, although it appears that those schemes can be improved by the addition of convective “trigger” functions.

Three-dimensional Kelvin wave structures in the five successful models resemble observations to a large degree, with vertically tilted temperature, specific humidity, and zonal wind anomalies. However, no model completely captures the observed signal, with most of the models being deficient in lower-tropospheric temperature and humidity signals near the location of maximum precipitation. These results suggest the need for improvements in the representations of shallow convection and convective downdrafts in global models.
Probing the Fast and Slow Components of Global Warming by Returning Abruptly to Preindustrial Forcing
Authors: Held Isaac M. , Winton Michael , Takahashi Ken , Delworth Thomas , Zeng Fanrong , Vallis Geoffrey K.
Published: January 2010

The fast and slow components of global warming in a comprehensive climate model are isolated by examining the response to an instantaneous return to preindustrial forcing. The response is characterized by an initial fast exponential decay with an e-folding time smaller than 5 yr, leaving behind a remnant that evolves more slowly. The slow component is estimated to be small at present, as measured by the global mean near-surface air temperature, and, in the model examined, grows to 0.4°C by 2100 in the A1B scenario from the Special Report on Emissions Scenarios (SRES), and then to 1.4°C by 2300 if one holds radiative forcing fixed after 2100. The dominance of the fast component at present is supported by examining the response to an instantaneous doubling of CO2 and by the excellent fit to the model’s ensemble mean twentieth-century evolution with a simple one-box model with no long times scales.
Understanding the Scale Relationships of Uncertainty Propagation of Satellite Rainfall through a Distributed Hydrologic Model
Authors: Nikolopoulos Efthymios I. , Anagnostou Emmanouil N. , Hossain Faisal , Gebremichael Mekonnen , Borga Marco
Published: January 2010

The study presents a data-based numerical experiment performed to understand the scale relationships of the error propagation of satellite rainfall for flood evaluation applications in complex terrain basins. A satellite rainfall error model is devised to generate rainfall ensembles based on two satellite products with different retrieval accuracies and space–time resolutions. The generated ensembles are propagated through a distributed physics-based hydrologic model to simulate the rainfall–runoff processes at different basin scales. The resulted hydrographs are compared against the hydrograph obtained by using high-resolution radar rainfall as the “reference” rainfall input. The error propagation of rainfall to stream runoff is evaluated for a number of basin scales ranging between 100 and 1200 km2. The results from this study show that (i) use of satellite rainfall for flood simulation depends strongly on the scale of application (catchment area) and the satellite product resolution, (ii) different satellite products perform differently in terms of hydrologic error propagation, and (iii) the propagation of error depends on the basin size; for example, this study shows that small watersheds (<400 km2) exhibit a higher ability in dampening the error from rainfall to runoff than larger-sized watersheds, although the actual error increases as drainage area decreases.
An Eddy-Permitting Southern Ocean State Estimate
Authors: Mazloff Matthew R. , Heimbach Patrick , Wunsch Carl
Published: January 2010

An eddy-permitting general circulation model of the Southern Ocean is fit by constrained least squares to a large observational dataset during 2005–06. Data used include Argo float profiles, CTD synoptic sections, Southern Elephant Seals as Oceanographic Samplers (SEaOS) instrument-mounted seal profiles, XBTs, altimetric observations [Envisat, Geosat, Jason-1, and Ocean Topography Experiment (TOPEX)/Poseidon], and infrared and microwave radiometer observed sea surface temperature. An adjoint model is used to determine descent directions in minimizing a misfit function, each of whose elements has been weighted by an estimate of the observational plus model error. The model is brought into near agreement with the data by adjusting its control vector, here consisting of initial and meteorological boundary conditions. Although total consistency has not yet been achieved, the existing solution is in good agreement with the great majority of the 2005 and 2006 Southern Ocean observations and better represents these data than does the World Ocean Atlas 2001 (WOA01) climatological product. The estimate captures the oceanic temporal variability and in this respect represents a major improvement upon earlier static inverse estimates. During the estimation period, the Drake Passage volume transport is 153 ± 5 Sv (1 Sv ≡ 106 m3 s−1). The Ross and Weddell polar gyre transports are 20 ± 5 Sv and 40 ± 8 Sv, respectively. Across 32°S there is a surface meridional overturning cell of 12 ± 12 Sv, an intermediate cell of 17 ± 12 Sv, and an abyssal cell of 13 ± 6 Sv. The northward heat and freshwater anomaly transports across 30°S are −0.3 PW and 0.7 Sv, with estimated uncertainties of 0.5 PW and 0.2 Sv. The net rate of wind work is 2.1 ± 1.1 TW. Southern Ocean theories involving short temporal- and spatial-scale dynamics may now be tested with a dynamically and thermodynamically realistic general circulation model solution that is known to be compatible with the modern observational datasets.
Thermocline Circulation in the Solomon Sea: A Modeling Study*
Authors: Melet Angélique , Gourdeau Lionel , Kessler William S. , Verron Jacques , Molines Jean-Marc
Published: January 2010

In the southwest Pacific, thermocline waters connecting the tropics to the equator via western boundary currents (WBCs) transit through the Solomon Sea. Despite its importance in feeding the Equatorial Undercurrent (EUC) and its related potential influence on the low-frequency modulation of ENSO, the circulation inside the Solomon Sea is poorly documented. A model has been implemented to analyze the mean and the seasonal variability of the Solomon Sea thermocline circulation. The circulation involves an inflow from the open southern Solomon Sea, which is distributed via WBCs between the three north exiting straits of the semiclosed Solomon Sea. The system of WBCs is found to be complex. Its main feature, the New Guinea Coastal Undercurrent, splits in two branches: one flowing through Vitiaz Strait and the other one, the New Britain Coastal Undercurrent (NBCU), exiting at Solomon Strait. East of the Solomon Sea, the encounter of the South Equatorial Current (SEC) with the Solomon Islands forms a previously unknown current, which the authors call the Solomon Islands Coastal Undercurrent (SICU). The NBCU, SEC, and SICU participate in the feeding of the New Ireland Coastal Undercurrent (NICU), which retroflects to the Equatorial Undercurrent, providing the most direct western boundary EUC connection, which is particularly active in June–August. The Solomon Sea WBC seasonal variability results from the combination of equatorial dynamics, remotely forced Rossby waves north of 10°S, and the spinup and spindown of the subtropical gyre as a response of Rossby waves forced south of 10°S.
The Evaluation of CloudSat and CALIPSO Ice Microphysical Products Using Ground-Based Cloud Radar and Lidar Observations
Authors: Protat A. , Delanoë J. , O’Connor E. J. , L’Ecuyer T. S.
Published: January 2010

In this paper, the statistical properties of tropical ice clouds (ice water content, visible extinction, effective radius, and total number concentration) derived from 3 yr of ground-based radar–lidar retrievals from the U.S. Department of Energy Atmospheric Radiation Measurement Climate Research Facility in Darwin, Australia, are compared with the same properties derived using the official CloudSat microphysical retrieval methods and from a simpler statistical method using radar reflectivity and air temperature. It is shown that the two official CloudSat microphysical products (2B-CWC-RO and 2B-CWC-RVOD) are statistically virtually identical. The comparison with the ground-based radar–lidar retrievals shows that all satellite methods produce ice water contents and extinctions in a much narrower range than the ground-based method and overestimate the mean vertical profiles of microphysical parameters below 10-km height by over a factor of 2. Better agreements are obtained above 10-km height. Ways to improve these estimates are suggested in this study. Effective radii retrievals from the standard CloudSat algorithms are characterized by a large positive bias of 8–12 μm. A sensitivity test shows that in response to such a bias the cloud longwave forcing is increased from 44.6 to 46.9 W m−2 (implying an error of about 5%), whereas the negative cloud shortwave forcing is increased from −81.6 to −82.8 W m−2. Further analysis reveals that these modest effects (although not insignificant) can be much larger for optically thick clouds. The statistical method using CloudSat reflectivities and air temperature was found to produce inaccurate mean vertical profiles and probability distribution functions of effective radius. This study also shows that the retrieval of the total number concentration needs to be improved in the official CloudSat microphysical methods prior to a quantitative use for the characterization of tropical ice clouds. Finally, the statistical relationship used to produce ice water content from extinction and air temperature obtained by the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite is evaluated for tropical ice clouds. It is suggested that the CALIPSO ice water content retrieval is robust for tropical ice clouds, but that the temperature dependence of the statistical relationship used should be slightly refined to better reproduce the radar–lidar retrievals.
False belief, complementation language, and contextual bias in preschoolers
Authors: Ng Lisa , Him Cheung  , Wen Xiao
Published: January 2010

In the present study, we address two questions concerning the relation between children’s false belief and their understanding of complex object complements. The first question is whether the previously demonstrated association between tensed complements and false belief generalizes to infinitival complements (de Villiers & Pyers, 2002). The second question is whether the relation is altered by the perceptual saliency of test objects (i.e., reality pull) and expressed desire of story characters (i.e., desire pull) as extraneous contextual factors. In Study 1, unexpectedly, we showed in a group of 4-year-olds that false belief correlated with comprehension of infinitival but not tensed complements. In Studies 2 and 3 it was found that a significant part of the association was explainable by a reality/desire pull built into the test context. We conclude that the relation between false belief and complementation is context-sensitive. The perceptual saliency of certain test objects and desire of story characters may in some situations bias the child towards attending more to the commonality between false belief and complement understanding, which enhances their association.
Marital Ideoscapes in 21st-Century India: Creative Combinations of Love and Responsibility
Authors: Netting Nancy S.
Published: January 2010

Although arranged marriage has survived in India, the custom is increasingly challenged by the current influx of new commodities, media, and ideas. Interviews with 15 male and 15 female unmarried professionals, age 22 to 29, in Vadodara, Gujarat, showed that educated youth have moved beyond the conventional love-versus-arranged marriage dichotomy. They instead focus on achieving specific goals: intimacy, equality, and personal choice, along with supernatural support, growing into love, and brides joining husbands’ families. To achieve these aims, they use both systems: separately, simultaneously, and in creative combinations. The theories of Arjun Appadurai explain that as the Western-inspired ideoscape of romantic love encounters Indian family values, Indian upper-middle-class youth respond by generating hybrid goals and systems of mate selection. They have linked imagination to hope and are using voice within their families to win the recognition, and often the partners, they seek.
Rape Myth Acceptance, Sexual Trauma History, and Posttraumatic Stress Disorder
Authors: Baugher Shannon N. , Elhai Jon D. , Monroe James R. , Gray Matt J.
Published: January 2010

The prediction of false rape-related beliefs (rape myth acceptance [RMA]) was examined using the Illinois Rape Myth Acceptance Scale (Payne, Lonsway, & Fitzgerald, 1999) among a nonclinical sample of 258 male and female college students. Predictor variables included measures of attitudes toward women, gender role identity (GRI), sexual trauma history, and posttraumatic stress disorder (PTSD) symptom severity. Using linear regression and testing interaction effects, negative attitudes toward women significantly predicted greater RMA for individuals without a sexual trauma history. However, neither attitudes toward women nor GRI were significant predictors of RMA for individuals with a sexual trauma history. PTSD did not moderate RMA’s relationship with attitudes toward women and GRI. This study has clinical implications for treatment as well as for the development of rape myth—dispelling programs.
Study on the Improvement of Hydrophobicity of PVDF Films
Authors: Huang S.-I. , Chen H
Published: January 2010

Poly(vinylidene fluoride) (PVDF) and polyethylene glycol (PEG) were dissolved in N,N-dimethylactamide. The mixture was homogeneous and the concentration of PEG was varied. The mixture was coated on the glass plates, which had a primer made of acrylic resin, to form films. It was found that the surface property of the films varied with the concentration of PEG. In this study, the hydrophobicity of PVDF films was improved by changing the morphology of the surface of the films.
The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats
Authors: Artun BC , Küskü-Kiraz Z. , Güllüoglu M. , Çevikbaş U. , Koçak-Toker N. , Uysal M.
Published: January 2010

Carnosine is a dipeptide having strong antioxidant effects. Oxidative stress plays an important role in pathogenesis of alcohol-induced liver injury. In this study, we investigated the effect of carnosine pretreatment on ethanol-induced oxidative stress and hepatotoxicity. Rats were given carnosine (2 g/L in drinking water) for 4 weeks and then ethanol was administered orally to rats at a dose of 5 g/kg every 12 hours for 3 doses totally (binge model). All rats were killed 6 hours after last ethanol injection. Plasma alanine (ALT) and aspartate (AST) transaminase activities and liver triglyceride, malondialdehyde (MDA), diene conjugate (DC), glutathione (GSH), vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. Binge ethanol administration resulted in significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. However, GSH, vitamin E, vitamin C levels and GSH-Px and GST activities were found to be decreased following ethanol administration. Macromicrovesicular steatosis was also seen. Carnosine pretreatment appeared to prevent the increase of plasma ALT and AST activities and hepatic MDA and DC levels following ethanol treatment. In addition, hepatic GSH levels increased, but there were no changes in triglyceride, vitamin E, vitamin C levels and SOD, GSH-Px and GST activities, following ethanol treatment in carnosine-pretreated rats. There was also no change in liver histopathological appearance. In conclusion, carnosine prevented the increases in serum transaminase activities and lipid peroxides in liver of ethanol-treated rats, without any change on steatosis in liver.
Markers of Marijuana Use Outcomes Within Adolescent Substance Abuse Group Treatment
Authors: Engle Brett , Macgowan Mark J. , Wagner Eric F. , Amrhein Paul C.
Published: January 2010

Objectives: Despite their popularity, little is known about what distinguishes effective from ineffective or even iatrogenic adolescent group interventions. Methods: Audio recordings and transcripts from 19, 8—10 session, school-based treatment groups comprised of 108, substance abusing 10- to 19-year olds were analyzed. Group leader empathy was measured globally, while two new constructs, group commitment and peer response, were measured using discourse analysis. All variables were measured at the group level. Results: Associations among these process variables were tested and supported, as were the hypothesized associations between both group member language constructs and marijuana use outcomes. Conclusions: These findings were consistent with a proposed theoretical model in which group commitment and peer response predict marijuana use outcomes and mediate the effects of group leader empathy. These observable, in-session, verbal behaviors could distinguish whether adolescents in a group intervention will decrease, maintain, or possibly increase the targeted behavior and are likely influenced by group leader empathy.
Peer-Driven Justice: Development and Validation of the Teen Court Peer Influence Scale
Authors: Smith Scott , Chonody Jill M.
Published: January 2010

The authors report a validation study of the Teen Court Peer Influence Scale (TCPIS), a newly developed scale, to examine its factor structure, reliability, and evidence of validity. Methods: The scale was disseminated to 202 participants in six teen courts in the state of Florida, and the authors conducted exploratory factor analyses. Content validity was established conceptually and evidence of concurrent validity, convergent construct validity, and discriminant construct validity were established statistically. Results: Factor analyses suggest that positive peer influence is operationalized by three constructs: positive cognitions/expectations, positive identity development, and modeling/imitation. The TCPIS has good internal consistency with a Cronbach’s alpha of .90. Conclusions: The TCPIS shows preliminary evidence of sound psychometric properties and may be used to inform teen court policy and practice.
Interventions to Prevent and Reduce Cyber Abuse of Youth: A Systematic Review
Authors: Mishna Faye , Cook Charlene , Saini Michael , Wu Meng-Jia , MacFadden Robert
Published: January 2010

Objectives: The Internet has created a new communication tool, particularly for young people whose use of electronic communication is exploding worldwide. While there are many benefits that result from electronic-based communication, the Internet is concurrently a potential site for abuse and victimization. Methods: This paper systematically reviews the effectiveness of cyber abuse interventions in increasing Internet safety knowledge and decreasing risky online behavior. Results: Significant results were found between pre- and posttest scores related to Internet safety knowledge. Most results related to risky online behavior were not significant. Conclusions: Results provide evidence that participation in psychoeducational Internet safety interventions is associated with an increase in Internet safety knowledge but is not significantly associated with a change in risky online behavior.
School Nurse Interventions in Managing Functional Urinary Incontinence in School-Age Children
Authors: Rivers Charisse L.
Published: January 2010

Uncomplicated urinary incontinence (UI) in school-age children is a prevalent yet underrecognized problem that has remained in the shadow of other concerns commonly perceived as more prominent or urgent. There is good evidence that functional UI in children can be treated and managed effectively. When there is no structural or neurologic abnormality and the underlying cause of the UI is related to either the storage or voiding phase of the bladder cycle then it is considered functional. School nurses are in an ideal position to identify, manage, and help children with functional UI cope effectively while maintaining healthy psychosocial well-being and educational success.
An Examination of Shared Variance in Self-Report and Objective Measures of Attention in the Incarcerated Adult Population
Authors: Asbjørnsen Arve E. , Jones Lise Ø. , Munkvold Linda H. , Obrzut John E. , Manger Terje
Published: January 2010

Objective: The present study was designed to test some assumptions about screening procedures for ADHD in adults. Method: Twenty-eight incarcerated male adults completed a self report scale of attention deficits as a part of an examination of attention and reading skills. Further assessment of attention included a battery of tests that assessed vigilance, attention shifts, and other aspects of cognitive control. Results: Fifty seven percent of the sample showed test performance indicating a high probability of ADHD. Correlation analyses yielded significant effects for self report scales and objective tests of attention. Conclusion: The results support the assumption that the self report measures share a significant part of the variance with tests of attention commonly used in clinical assessment. However, the risk of making both false positive and false negative inferences about ADHD is present, as the specificity and the sensitivity of the rating scale needs to be further explored.
Optimization of a Computational Fluid Dynamics Code for the Memory Hierarchy: A Case Study
Authors: Hauser Thomas , LeBeau Raymond
Published: January 2010

With the current shift of increasing the computational power of a processor by including multiple cores instead of increasing the clock frequency, consideration of computational efficiency is gaining increased importance for computational fluid dynamics codes. This is especially critical for applications that require high throughput. For example, applying computational fluid dynamics simulations to multi-disciplinary design optimization requires a large number of similar simulations with different input parameters. Therefore, a reduction in the runtime of the code can lead to large reduction in the design process. In our case study, a two-dimensional, block-structured computational fluid dynamics code was optimized for performance on machines with hierarchical memory systems. This paper illustrates the techniques applied to transform an initial version of the code to an optimized version that yielded performance improvements of 10% for very small cases to about 50% for large test cases that did not fit into the cache memory of the target processor. A detailed performance analysis of the code starting at the global level down to subroutines and data structures is presented in this paper. The performance improvements can be explained through a reduction of cache misses in all levels of the memory hierarchy. The L1 cache misses were reduced by about 50%, the L2 cache misses by about 80% and the translation lookaside buffer misses by about 90% for the optimized version of the code. The code performance was also evaluated for multi-core processors, where efficiency is especially important when several instances of an application are running simultaneously. In this case, the most optimized version, a blocked version of the optimized code, more effectively maintained efficiency as more cores were activated compared to the unblocked version. This illustrates that optimizing cache performance may be increasingly important as the number of cores per processor continues to rise.
A Component-Based Framework for Smoothed Particle Hydrodynamics Simulations of Reactive Fluid Flow in Porous Media
Authors: Palmer Bruce , Gurumoorthi Vidhya , Tartakovsky Alexandre , Scheibe Tim
Published: January 2010

The development of a framework to support smoothed particle hydrodynamics (SPH) simulations of fluid flow and transport in porous media is described. The framework is built using the Common Component Architecture (CCA) toolkit and it supports SPH simulations using a variety of different SPH models and setup formats. The SPH simulation code is decomposed into independent components that represent self-contained units of functionality. Different physics models can be developed within the framework by re-implementing key components but no modification of other components is required. A model for defining components and developing abstract interfaces that support a high degree of modularity and minimal dependencies between components is discussed in detail.
The Importance of Non-Data-Communication Overheads in MPI
Authors: Balaji Pavan , Chan Anthony , Gropp William , Thakur Rajeev , Lusk Ewing
Published: January 2010

With processor speeds no longer doubling every 18—24 months owing to the exponential increase in power consumption and heat dissipation, modern high-end computing systems tend to rely less on the performance of single processing units and instead rely on achieving high performance by using the parallelism of a massive number of low-frequency/low-power processing cores. Using such low-frequency cores, however, puts a premium on end-host pre- and post-communication processing required within communication stacks, such as the Message Passing Interface (MPI) implementation. Similarly, small amounts of serialization within the communication stack that were acceptable on small/medium systems can be brutal on massively parallel systems. Thus, in this paper, we study the different non-data-communication overheads within the MPI implementation on the IBM Blue Gene/P system. Specifically, we analyze various aspects of MPI, including the MPI stack overhead itself, overhead of allocating and queueing requests, queue searches within the MPI stack, multi-request operations, and various others. Our experiments, that scale up to 131,072 cores of the largest Blue Gene/P system in the world (80% of the total system size), reveal several insights into overheads in the MPI stack, which were not previously considered significant, but can have a substantial impact on such massive systems.
Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells
Authors: Grigoriadis Agamemnon E. , Kennedy Marion , Bozec Aline , Brunton Fiona , Stenbeck Gudrun , Park In-Hyun , Wagner Erwin F. , Keller Gordon M.
Published: January 2010

The directed differentiation of human pluripotent stem cells offers the unique opportunity to generate a broad spectrum of human cell types and tissues for transplantation, drug discovery, and studying disease mechanisms. Here, we report the stepwise generation of bone-resorbing osteoclasts from human embryonic and induced pluripotent stem cells. Generation of a primitive streak-like population in embryoid bodies, followed by specification to hematopoiesis and myelopoiesis by vascular endothelial growth factor and hematopoietic cytokines in serum-free media, yielded a precursor population enriched for cells expressing the monocyte-macrophage lineage markers CD14, CD18, CD11b, and CD115. When plated in monolayer culture in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL), these precursors formed large, multinucleated osteoclasts that expressed tartrate-resistant acid phosphatase and were capable of resorption. No tartrate-resistant acid phosphatase-positive multinucleated cells or resorption pits were observed in the absence of RANKL. Molecular analyses confirmed the expression of the osteoclast marker genes NFATc1, cathepsin K, and calcitonin receptor in a RANKL-dependent manner, and confocal microscopy demonstrated the coexpression of the αvβ3 integrin, cathepsin K and F-actin rings characteristic of active osteoclasts. Generating hematopoietic and osteoclast populations from human embryonic and induced pluripotent stem cells will be invaluable for understanding embryonic bone development and postnatal bone disease.
Genetic copy number variants in sib pairs both affected with schizophrenia
Authors: Lee Chia-Huei , Liu Chih-Min , Wen Chun-Chiang , Chang Shun-Min , Hwu Hai-Gwo
Published: January 2010

Background

Schizophrenia is a complex disorder with involvement of multiple genes.

Methods

In this study, genome-wide screening for DNA copy-number variations (CNVs) was conducted for ten pairs, a total of 20 cases, of affected siblings using oligonucleotide array-based CGH.

Results

We found negative symptoms were significantly more severe (p < 0.05) in the subgroup that harbored more genetic imbalance (n ≧ 13, n = number of CNV-disrupted genes) as compared with the subgroup with fewer CNVs (n ≦ 6), indicating that the degree of genetic imbalance may influence the severity of the negative symptoms of schizophrenia. Four central nervous system (CNS) related genes including CCAAT/enhancer binding protein, delta (CEBPD, 8q11.21), retinoid × receptor, alpha (RXRA, 9q34.2), LIM homeobox protein 5 (LHX5, 12q24.13) and serine/threonine kinase 11 (STK11, 19p13.3) are recurrently (incidence ≧ 16.7%) disrupted by CNVs. Two genes, PVR (poliovirus receptor) and BU678720, are concordantly deleted in one and two, respectively, pairs of co-affected siblings. However, we did not find a significant association of this BU678720 deletion and schizophrenia in a large case-control sample.

Conclusions

We conclude that the high genetic loading of CNVs may be the underlying cause of negative symptoms of schizophrenia, and the CNS-related genes revealed by this study warrant further investigation.
Molecular evolution of the three short PGRPs of the malaria vectors Anopheles gambiae and Anopheles arabiensisin East Africa
Authors: Mendes Cristina , Felix Rute , Sousa Ana-Margarida , Lamego Joana , Charlwood Derek , do Rosário Virgílio E , Pinto João , Silveira Henrique
Published: January 2010

Background

Immune responses to parasites, which start with pathogen recognition, play a decisive role in the control of the infection in mosquitoes. Peptidoglycan recognition proteins (PGRPs) are an important family of pattern recognition receptors that are involved in the activation of these immune reactions. Pathogen pressure can exert adaptive changes in host genes that are crucial components of the vector's defence. The aim of this study was to determine the molecular evolution of the three short PGRPs (PGRP-S1, PGRP-S2 and PGRP-S3) in the two main African malaria vectors - Anopheles gambiae and Anopheles arabiensis.

Results

Genetic diversity of An. gambiae and An. arabiensis PGRP-S1, PGRP-S2 and PGRP-S3 was investigated in samples collected from Mozambique and Tanzania. PGRP-S1 diversity was lower than for PGRP-S2 and PGRP-S3. PGRP-S1 was the only gene differentiated between the two species. All the comparisons made for PGRP-S1 showed significant P-values for Fst estimates and AMOVA confirming a clear separation between species. For PGRP-S2 and PGRP-S3 genes it was not possible to group populations either by species or by geographic region. Phylogenetic networks reinforced the results obtained by the AMOVA and Fst values. The ratio of nonsynonymous substitutions (Ka)/synonymous substitutions (Ks) for the duplicate pair PGRP-S2 and PGRP-S3 was very similar and lower than 1. The 3D model of the different proteins coded by these genes showed that amino acid substitutions were concentrated at the periphery of the protein rather than at the peptidoglycan recognition site.

Conclusions

PGRP-S1 is less diverse and showed higher divergence between An. gambiae and An. arabiensis regardless of geographic location. This probably relates to its location in the chromosome-X, while PGRP-S2 and PGRP-S3, located in chromosome-2L, showed signs of autosomal introgression. The two short PGRP genes located in the chromosome-2L were under purifying selection, which suggests functional constraints. Different types of selection acting on PGRP-S1 and PGRP-S2 and S3 might be related to their different function and catalytic activity.
Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background
Authors: de Jong Simone , Fuller Tova F , Janson Esther , Strengman Eric , Horvath Steve , Kas Martien JH , Ophoff Roel A
Published: January 2010

Background

We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. We performed a whole-genome gene expression experiment and applied a systems biology approach using weighted gene co-expression network analysis.

Results

We were able to identify modules of co-expressed genes that distinguish a strain or brain region. Analysis of the networks that are most informative for hippocampus and amygdala revealed enrichment in neurologically, genetically and psychologically related pathways. Close examination of the strain-specific gene expression profiles, however, revealed no functional relevance but a significant enrichment of single nucleotide polymorphisms in the probe sequences used for array hybridization. This artifact was not observed for the modules of co-expressed genes that distinguish amygdala and hippocampus.

Conclusions

The brain-region specific modules were found to be independent of genetic background and are therefore likely to represent biologically relevant molecular networks that can be studied to complement our knowledge about pathways in neuropsychiatric disease.
Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development
Authors: Huang Wen , Yandell Brian S , Khatib Hasan
Published: January 2010

Background

Early embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development.

Results

Using microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF) - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development.

Conclusions

This study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.
Genetic analysis of the Staphylococcus epidermidis Macromolecular Synthesis Operon: Serp1129 is an ATP binding protein and sigA transcription is regulated by both σA- and σB-dependent promoters
Authors: Bryant Kendall A , Kinkead Lauren C , Larson Marilynn A , Hinrichs Steven H , Fey Paul D
Published: January 2010

Background

The highly conserved macromolecular synthesis operon (MMSO) contains both dnaG (primase) and sigA (primary sigma factor). However, in previously evaluated gram-positive species, the MMSO is divergent upstream of dnaG. The MMSO of Bacillus subtilis contains three open reading frames (ORFs) that are differentially regulated by multiple promoters. In conjunction with studies to determine the expression profile of dnaG, the MMSO of Staphylococus epidermidis was characterized.

Results

The ORFs of S. epidermidis were compared to the previously described MMSO of B. subtilis and two additional ORFs in S. epidermidis, serp1129 and serp1130, were identified. The largest transcript, 4.8 kb in length, was expressed only in exponential growth and encompassed all four ORFs (serp1130, serp1129, dnaG, and sigA). A separate transcript (1.5 kb) comprising serp1130 and serp1129 was expressed in early exponential growth. Two smaller transcripts 1.3 and 1.2 kb in size were detected with a sigA probe in both exponential and post-exponential phases of growth. Western blot analysis correlated with the transcriptional profile and demonstrated that Serp1129 was detected only in the exponential phase of growth. Computational analysis identified that Serp1130 contained a CBS motif whereas Serp1129 contained an ATP/GTP binding motif. Functional studies of Serp1129 demonstrated that it was capable of binding both ATP and GTP. Comparisons with a sigB:dhfr mutant revealed that the 1.3 kb sigA transcript was regulated by a σB-dependent promoter.

Conclusions

These studies demonstrated that the S. epidermidis 1457 MMSO contains two ORFs (serp1129 and serp1130) not described within the B. subtilis MMSO and at least three promoters, one of which is σβ-dependent. The transcriptional regulation of sigA by σB provides evidence that the staphylococcal σB-dependent response is controlled at both the transcriptional and post-transcriptional level. The conservation of serp1129 across multiple gram-positive organisms and its capability to bind ATP and GTP support the need for further investigation of its role in bacterial growth.
XIAP is not required for human tumor cell survival in the absence of an exogenous death signal
Authors: Sensintaffar John , Scott Fiona L , Peach Robert , Hager Jeffrey H
Published: January 2010

Background

The X-linked Inhibitor of Apoptosis (XIAP) has attracted much attention as a cancer drug target. It is the only member of the IAP family that can directly inhibit caspase activityin vitro, and it can regulate apoptosis and other biological processes through its C-terminal E3 ubiquitin ligase RING domain. However, there is controversy regarding XIAP's role in regulating tumor cell proliferation and survival under normal growth conditionsin vitro.

Methods

We utilized siRNA to systematically knock down XIAP in ten human tumor cell lines and then monitored both XIAP protein levels and cell viability over time. To examine the role of XIAP in the intrinsic versus extrinsic cell death pathways, we compared the viability of XIAP depleted cells treated either with a variety of mechanistically distinct, intrinsic pathway inducing agents, or the canonical inducer of the extrinsic pathway, TNF-related apoptosis-inducing ligand (TRAIL).

Results

XIAP knockdown had no effect on the viability of six cell lines, whereas the effect in the other four was modest and transient. XIAP knockdown only sensitized tumor cells to TRAIL and not the mitochondrial pathway inducing agents.

Conclusions

These data indicate that XIAP has a more central role in regulating death receptor mediated apoptosis than it does the intrinsic pathway mediated cell death.
Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts
Authors: Appledorn Daniel M , Dao Kim-Hien T , O'Reilly Sandra , Maher Veronica M , McCormick J Justin
Published: January 2010

Background

The activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain.

Methods

Under the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays.

Results

Expression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes,uPAandVEGFwas further validated in both normoxic and hypoxic conditions.

Conclusion(s)

The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas transformed human cells, including their ability to form tumors in athymic mice. Our data also indicate that expression of either activated Rac1 or Cdc42 alone is not sufficient for malignant transformation of human fibroblasts, although each is required for specific transformed phenotypes. Furthermore, our study elucidates that the expression of several highly significant cancer related genes require the activities of Rac1 and/or Cdc42 which may also play a critical role in cellular transformation.
Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues
Authors: Curtis Carol D , Thorngren Daniel L , Nardulli Ann M
Published: January 2010

Background

During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).

Methods

Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.

Results

We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.

Conclusions

Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.