bluuebunny/crossref_metadata_2025 huggingface dataset:
Focal Gains of VEGFA and Molecular Classification of Hepatocellular Carcinoma
Authors: Chiang Derek Y. , Villanueva Augusto , Hoshida Yujin , Peix Judit , Newell Philippa , Minguez Beatriz , LeBlanc Amanda C. , Donovan Diana J. , Thung Swan N. , Solé Manel , Tovar Victoria , Alsinet Clara , Ramos Alex H. , Barretina Jordi , Roayaie Sasan , Schwartz Myron , Waxman Samuel , Bruix Jordi , Mazzaferro Vincenzo , Ligon Azra H. , Najfeld Vesna , Friedman Scott L. , Sellers William R. , Meyerson Matthew , Llovet Josep M.
Published: August 2008

Hepatocellular carcinomas represent the third leading cause of cancer-related deaths worldwide. The vast majority of cases arise in the context of chronic liver injury due to hepatitis B virus or hepatitis C virus infection. To identify genetic mechanisms of hepatocarcinogenesis, we characterized copy number alterations and gene expression profiles from the same set of tumors associated with hepatitis C virus. Most tumors harbored 1q gain, 8q gain, or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 of 103 tumors, 4 tumors harbored focal gains at 6p21 incorporating vascular endothelial growth factor A (VEGFA). Fluorescence in situ hybridization on an independent validation set of 210 tumors found 6p21 high-level gains in 14 tumors, as well as 2 tumors with 6p21 amplifications. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain in hepatocellular carcinomas suggested a novel, non–cell-autonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 of these tumors identified five classes, including “CTNNB1”, “proliferation”, “IFN-related”, a novel class defined by polysomy of chromosome 7, and an unannotated class. These class labels were further supported by molecular data; mutations in CTNNB1 were enriched in the “CTNNB1” class, whereas insulin-like growth factor I receptor and RPS6 phosphorylation were enriched in the “proliferation” class. The enrichment of signaling pathway alterations in gene expression classes provides insights on hepatocellular carcinoma pathogenesis. Furthermore, the prevalence of VEGFA high-level gains in multiple tumor types suggests indications for clinical trials of antiangiogenic therapies. [Cancer Res 2008;68(16):6779–88]
Suppression of Inhibitor of Differentiation 2, a Target of Mutant p53, Is Required for Gain-of-Function Mutations
Authors: Yan Wensheng , Liu Gang , Scoumanne Ariane , Chen Xinbin
Published: August 2008

Overexpression of mutant p53 is a common theme in human tumors, suggesting a tumor-promoting gain-of-function for mutant p53. To elucidate whether and how mutant p53 acquires its gain-of-function, mutant p53 is inducibly knocked down in the SW480 colon cancer cell line, which contains mutant p53(R273H/P309S), and the MIA PaCa-2 pancreatic cancer cell line, which contains mutant p53(R248W). We found that knockdown of mutant p53 markedly inhibits cell proliferation. In addition, knockdown of mutant p53 sensitizes tumor cells to growth suppression by various chemotherapeutic drugs. To determine whether a gene involved in cell growth and survival is regulated by mutant p53, gene expression profiling analysis was performed and showed that the expression level of Id2, a member of the inhibitor of differentiation (Id) family, was markedly increased upon knockdown of mutant p53. To confirm this, Northern blot analysis was performed and showed that the expression level of Id2 was regulated by various mutant p53s in multiple cell lines. In addition, we found that the Id2 promoter is responsive to mutant but not wild-type p53, and mutant p53 binds to the Id2 promoter. Consistent with these observations, expression of endogenous Id2 was found to be inhibited by exogenous mutant p53 in p53-null HCT116 cells. Finally, we showed that knockdown of Id2 can restore the proliferative potential of tumor cells inhibited by withdrawal of mutant p53. Together, these findings suggest that one mechanism by which mutant p53 acquires its gain-of-function is through the inhibition of Id2 expression. [Cancer Res 2008;68(16):6789–96]
Mouse Mesenchymal Stem Cells Expressing PAX-FKHR Form Alveolar Rhabdomyosarcomas by Cooperating with Secondary Mutations
Authors: Ren Yue-Xin , Finckenstein Friedrich Graf , Abdueva Diana A. , Shahbazian Violette , Chung Brile , Weinberg Kenneth I. , Triche Timothy J. , Shimada Hiroyuki , Anderson Michael J.
Published: August 2008

Alveolar rhabdomyosarcomas (ARMS) are highly malignant soft-tissue sarcomas that arise in children, adolescents, and young adults. Although formation and expression of the PAX-FKHR fusion genes is thought to be the initiating event in this cancer, the role of PAX-FKHR in the neoplastic process remains largely unknown in a progenitor cell that is undefined. We hypothesize that PAX-FKHR determine the ARMS progenitor to the skeletal muscle lineage, which when coupled to the inactivation and/or activation of critical cell signaling pathways leads to the formation of ARMS. Because a number of studies have proposed that mesenchymal stem cells (MSC) are the progenitor for several of the sarcomas, we tested this hypothesis in MSCs. We show that PAX-FKHR induce skeletal myogenesis in MSCs by transactivating MyoD and myogenin. Despite exhibiting enhanced growth in vitro, the PAX-FKHR–expressing populations do not form colonies in soft agar or tumors in mice. Expression of dominant-negative p53, or the SV40 early region, elicits tumor formation in some of the PAX-FKHR–expressing populations. Additional activation of the Ras signaling pathway leads to highly malignant tumor formation for all of the populations. The PAX-FKHR–expressing tumors were shown to have histologic, immunohistochemical, and gene expression profiles similar to human ARMS. Our results show the critical role played by PAX-FKHR in determining the molecular, myogenic, and histologic phenotype of ARMS. More importantly, we identify MSCs as a progenitor that can give rise to ARMS. [Cancer Res 2008;68(16):6587–97]
Effects of the Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235 on the Tumor Vasculature: Implications for Clinical Imaging
Authors: Schnell Christian R. , Stauffer Frédéric , Allegrini Peter R. , O'Reilly Terence , McSheehy Paul M.J. , Dartois Celine , Stumm Michael , Cozens Robert , Littlewood-Evans Amanda , García-Echeverría Carlos , Maira Sauveur-Michel
Published: August 2008

Dysregulated angiogenesis and high tumor vasculature permeability, two vascular endothelial growth factor (VEGF)-mediated processes and hallmarks of human tumors, are in part phosphatidylinositol 3-kinase (PI3K) dependent. NVP-BEZ235, a dual PI3K/mammalian target of rapamycin (mTOR) inhibitor, was found to potently inhibit VEGF-induced cell proliferation and survival in vitro and VEGF-induced angiogenesis in vivo as shown with s.c. VEGF-impregnated agar chambers. Moreover, the compound strongly inhibited microvessel permeability both in normal tissue and in BN472 mammary carcinoma grown orthotopically in syngeneic rats. Similarly, tumor interstitial fluid pressure, a phenomenon that is also dependent of tumor permeability, was significantly reduced by NVP-BEZ235 in a dose-dependent manner on p.o. administration. Because RAD001, a specific mTOR allosteric inhibitor, was ineffective in the preceding experiments, we concluded that the effects observed for NVP-BEZ235 are in part driven by PI3K target modulation. Hence, tumor vasculature reduction was correlated with full blockade of endothelial nitric oxide (NO) synthase, a PI3K/Akt-dependent but mTORC1-independent effector involved in tumor permeability through NO production. In the BN472 tumor model, early reduction of permeability, as detected by Ktrans quantification using the dynamic contrast-enhanced magnetic resonance imaging contrasting agent P792 (Vistarem), was found to be a predictive marker for late-stage antitumor activity by NVP-BEZ235. [Cancer Res 2008;68(16):6598–607]
K-Ras Nanoclustering Is Subverted by Overexpression of the Scaffold Protein Galectin-3
Authors: Shalom-Feuerstein Ruby , Plowman Sarah J. , Rotblat Barak , Ariotti Nicholas , Tian Tianhai , Hancock John F. , Kloog Yoel
Published: August 2008

The spatial organization of K-Ras proteins into nanoclusters on the plasma membrane is essential for high-fidelity signal transduction. The mechanism underlying K-Ras nanoclustering is unknown. We show here that K-Ras.GTP recruits Galectin-3 (Gal-3) from the cytosol to the plasma membrane where it becomes an integral nanocluster component. Importantly, we show that the cytosolic level of Gal-3 determines the magnitude of K-Ras.GTP nanoclustering and signal output. The β-sheet layers of the Gal-3 carbohydrate recognition domain contain a hydrophobic pocket that may accommodate the farnesyl group of K-Ras. V125A substitution within this hydrophobic pocket yields a dominant negative Gal-3(V125A) mutant that inhibits K-Ras activity. Gal-3(V125A) interaction with K-Ras.GTP reduces K-Ras.GTP nanocluster formation, which abrogates signal output from the Raf/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) pathway. Gal-3(V125A) negatively regulates cell growth and reduces cellular transformation. Thus, regulation of K-Ras nanocluster formation and signal output by Gal-3 critically depends on the integrity of the Gal-3 hydrophobic pocket. These results show that Gal-3 overexpression in breast cancer cells, which increases K-Ras signal output, represents oncogenic subversion of plasma membrane nanostructure. [Cancer Res 2008;68(16):6608–16]
A Novel Acetylenic Tricyclic bis-(Cyano Enone) Potently Induces Phase 2 Cytoprotective Pathways and Blocks Liver Carcinogenesis Induced by Aflatoxin
Authors: Liby Karen , Yore Mark M. , Roebuck Bill D. , Baumgartner Karen J. , Honda Tadashi , Sundararajan Chitra , Yoshizawa Hidenori , Gribble Gordon W. , Williams Charlotte R. , Risingsong Renee , Royce Darlene B. , Dinkova-Kostova Albena T. , Stephenson Katherine K. , Egner Patricia A. , Yates Melinda S. , Groopman John D. , Kensler Thomas W. , Sporn Michael B.
Published: August 2008

A novel acetylenic tricyclic bis-(cyano enone), TBE-31, is a lead compound in a series of tricyclic compounds with enone functionalities in rings A and C. Nanomolar concentrations of this potent multifunctional molecule suppress the induction of the inflammatory protein, inducible nitric oxide synthase, activate phase 2 cytoprotective enzymes in vitro and in vivo, block cell proliferation, and induce differentiation and apoptosis of leukemia cells. Oral administration of TBE-31 also significantly reduces formation of aflatoxin-DNA adducts and decreases size and number of aflatoxin-induced preneoplastic hepatic lesions in rats by >90%. Because of the two cyano enones in rings A and C, TBE-31 may directly interact with DTT and protein targets such as Keap1 that contain reactive cysteine residues. The above findings suggest that TBE-31 should also be tested for chemoprevention and chemotherapy in relevant models of cancer and against other chronic, degenerative diseases in which inflammation and oxidative stress contribute to disease pathogenesis. [Cancer Res 2008;68(16):6727–33]
Different Calculations of Ankle-Brachial Index and Their Impact on Cardiovascular Risk Prediction
Authors: Espinola-Klein Christine , Rupprecht Hans J. , Bickel Christoph , Lackner Karl , Savvidis Savvas , Messow Claudia M. , Munzel Thomas , Blankenberg Stefan
Published: August 2008

Background—

An ankle-brachial index (ABI; ratio of ankle and brachial systolic blood pressure) <0.9 indicates peripheral arterial disease (PAD) and is a strong predictor of cardiovascular events. The aim of the present study was to address the prognostic value of different methods of ABI calculation.

Methods and Results—

In 831 patients admitted with chest pain for diagnostic heart catheterization, blood pressure of both anterior and posterior tibial arteries was measured. ABI was calculated for each leg with the higher of the 2 ankle pressures (current definition of the American Heart Association) or with the lower of the 2 ankle pressures (modified definition) in relation to the higher of the left or right brachial systolic blood pressure. For each patient, the lower ABI from both legs was used for further evaluation. Fifteen patients (1.8%) with ABI >1.5 were excluded. We compared patients with ABI <0.9 according to the current definition (
with PAD
, n=204 [25.0%]), those with ABI ≥0.9 according to the modified definition (
without PAD
, n=524 [64.2%]), and those with ABI <0.9 according to the modified definition and ≥0.9 according to the current definition (
suspected PAD
, n=88 [10.8%]). Follow-up data (median 6.6 years) were available for 812 patients (99.5%); 157 patients (19.3%) experienced cardiovascular events (cardiovascular death, myocardial infarction, or stroke). Patients without PAD had the lowest cardiovascular event rate, whereas event rates were comparable for patients with PAD and those with suspected PAD (14.8% versus 28.4% versus 25.0%, respectively). In a fully adjusted Cox regression analysis that included patients without PAD as the reference group, the hazard ratio (95% CI) was 1.56 (0.97 to 2.53) for patients with suspected PAD and 1.67 (1.16 to 2.40) for patients with PAD.

Conclusions—

When the higher ankle pressure is used for ABI calculation, a group of patients at high risk for cardiovascular events is overlooked. With a simple modification of ABI (use of the lower instead of the higher ankle pressure), more patients at risk could be identified.
Neural Mechanisms of Paroxysmal Atrial Fibrillation and Paroxysmal Atrial Tachycardia in Ambulatory Canines
Authors: Tan Alex Y. , Zhou Shengmei , Ogawa Masahiro , Song Juan , Chu Matthew , Li Hongmei , Fishbein Michael C. , Lin Shien-Fong , Chen Lan S. , Chen Peng-Sheng
Published: August 2008

Background—

The relationship between autonomic activation and the mechanisms of paroxysmal atrial fibrillation remains unclear.

Methods and Results—

We implanted a pacemaker and a radio transmitter in 7 dogs (group 1). After baseline recording, we paced the left atrium at 20 Hz for 1 week and then monitored left stellate ganglion nerve activity, left vagal nerve activity, and left atrial electrogram without pacing for 24 hours. This protocol repeated itself until sustained atrial fibrillation (>48 hours) was induced in 3±1 weeks. In another 6 dogs (group 2), we cryoablated left and right stellate ganglia and the cardiac branch of the left vagal nerve during the first surgery and then repeated the same pacing protocol until sustained atrial fibrillation was induced in 7±4 weeks (
P
=0.01). There were 4±2 episodes of paroxysmal atrial fibrillation per day and 10±3 episodes of paroxysmal atrial tachycardia per day in group 1. Simultaneous sympathovagal discharges were observed to immediately precede the onset of atrial arrhythmias in 73% of episodes. In comparison, group 2 dogs had no paroxysmal atrial fibrillation (
P
=0.046) or paroxysmal atrial tachycardia (
P
<0.001) episodes. Nerve sprouting, sympathetic hyperinnervation, and a massive elevation of transcardiac norepinephrine levels occurred in both groups.

Conclusions—

Intermittent rapid left atrial pacing results in sympathetic hyperinnervation, paroxysmal atrial fibrillation, and paroxysmal atrial tachycardia. Simultaneous sympathovagal discharges are common triggers of these arrhythmias. Cryoablation of extrinsic sympathovagal nerves eliminated paroxysmal atrial fibrillation and paroxysmal atrial tachycardia, which suggests that simultaneous sympathovagal discharges and these arrhythmias are causally related. Because cryoablation only delayed but did not prevent sustained atrial fibrillation, autonomic nerve activity is not the only factor that determines atrial fibrillation maintenance.
Numerical Simulations of the Formation of Hurricane Gabrielle (2001)
Authors: Musgrave K. D. , Davis C. A. , Montgomery M. T.
Published: August 2008

This study examines the formation of Hurricane Gabrielle (2001), focusing on whether an initial disturbance and vertical wind shear were favorable for development. This examination is performed by running numerical experiments using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5). Gabrielle is chosen as an interesting case to study since it formed in the subtropics only a few days before making landfall in Florida. Three simulations are run: a control run and two sensitivity experiments. The control run is compared with observations to establish the closeness of the model output to Gabrielle’s observed formation. The two sensitivity experiments are designed to test the response of the developing tropical cyclone to alterations in the initial conditions. The first sensitivity experiment removes the initial (or precursor) disturbance, a midtropospheric vortex located over Florida. The second sensitivity experiment reduces the vertical wind shear over the area of formation. The control run produces a system comparable to Gabrielle. The convection in the control run is consistently located downshear of the center of circulation. In the first sensitivity experiment, with the removal of the initial disturbance, no organized system develops. This indicates the importance of the midtropospheric vortex in Gabrielle’s formation. The second sensitivity experiment, which reduces the vertical wind shear over the area of Gabrielle’s formation, produces a system that can be identified as Gabrielle. This system, however, is weaker than both the control run and the observations of Gabrielle. This study provides direct evidence of a favorable influence of modest vertical wind shear on the formation of a tropical cyclone in this case.
Error Covariance Modeling in the GMAO Ocean Ensemble Kalman Filter
Authors: Keppenne Christian L. , Rienecker Michele M. , Jacob Jossy P. , Kovach Robin
Published: August 2008

In practical applications of the ensemble Kalman filter (EnKF) for ocean data assimilation, the computational burden and memory limitations usually require a trade-off between ensemble size and model resolution. This is certainly true for the NASA Global Modeling and Assimilation Office (GMAO) ocean EnKF used for ocean climate analyses. The importance of resolution for the adequate representation of the dominant current systems means that small ensembles, with their concomitant sampling biases, have to be used. Hence, strategies have been sought to address sampling problems and to improve the performance of the EnKF for a given ensemble size. Approaches assessed herein consist of spatiotemporal filtering of background-error covariances, improving the system-noise representation, imposing a steady-state error covariance model, and speeding up the analysis by performing the most expensive operation of the analysis on a coarser computational grid. A judicious combination of these approaches leads to significant performance improvements, especially with very small ensembles.
The Boundary Layer Winds in Hurricanes Danielle (1998) and Isabel (2003)
Authors: Schwendike Juliane , Kepert Jeffrey D.
Published: August 2008

This paper describes the boundary layer wind structure and dynamics of Hurricanes Danielle (1998) and Isabel (2003), based on the analysis of high-resolution global positioning system dropwindsonde data and simulation of the flow by a three-dimensional boundary layer model produced by Kepert and Wang. The observations show that the hurricane boundary layer has a complex three-dimensional structure with large variability over small distances. The analysis emphasizes three aspects: the degree of gradient-wind balance, the radially varying depth of the boundary layer, and the strength of the near-surface wind speed relative to that at a higher level. Each aspect is compared both with results obtained in a simulation of the individual storm by Kepert and Wang’s model and with theoretical predictions. The observations show that the boundary layer depth decreases toward the center of the storm, consistent with theoretical arguments. The strongest azimuthal winds occur near the top of, but still within, the frictional inflow layer. These strong azimuthal winds are marginally supergradient in Hurricane Danielle but strongly so in Hurricane Isabel, where the imbalance amounts to approximately 10 m s−1 near the radius of maximum winds and is statistically significantly nonzero. This layer of supergradient flow is surmounted by a layer of outflow, in which the flow returns to gradient balance. The maximum storm-relative azimuthal wind occurs in the left front of Hurricane Danielle, and the strongest inflow is located in the right front. These asymmetries rotate anticyclonically with height, but there is also a clear wavenumber-2 asymmetry superimposed, which shows less rotation with height and is possibly forced by environmental factors associated with the storm’s impending recurvature. In Hurricane Isabel, the azimuthal wind maximum is located in the left rear and the inflow maximum in the left front, with neither showing much tendency to vary in azimuth with height. The ratio of the near-surface wind speed to that farther aloft increases toward the storm center for both storms. The largest values are located near the radius of maximum wind, and in general higher values are found on the left of the storm’s track than on the right. Simulations of the two storms with the boundary layer model are able to explain several of these factors; they also show some ability to reproduce individual dropsonde wind observed profiles. Important is that the model predicts weakly supergradient flow in Danielle and strongly supergradient flow in Isabel, in excellent agreement with the observational analysis. Based on these simulations, physical arguments, and earlier studies, the authors conclude that the differences between these storms in this respect result from their differing radial profiles of gradient wind and argue that the occurrence of supergradient flow in the upper boundary layer of individual hurricanes should be readily predictable.
On the Sensitivity Equations of Four-Dimensional Variational (4D-Var) Data Assimilation
Authors: Daescu Dacian N.
Published: August 2008

The equations of the forecast sensitivity to observations and to the background estimate in a four-dimensional variational data assimilation system (4D-Var DAS) are derived from the first-order optimality condition in unconstrained minimization. Estimation of the impact of uncertainties in the specification of the error statistics is considered by evaluating the sensitivity to the observation and background error covariance matrices. The information provided by the error covariance sensitivity analysis is used to identify the input components for which improved estimates of the statistical properties of the errors are of most benefit to the analysis and forecast. A close relationship is established between the sensitivities within each input pair data/error covariance such that once the observation and background sensitivities are available the evaluation of the sensitivity to the specification of the corresponding error statistics requires little additional computational effort. The relevance of the 4D-Var sensitivity equations to assess the data impact in practical applications is discussed. Computational issues are addressed and idealized 4D-Var experiments are set up with a finite-volume shallow-water model to illustrate the theoretical concepts. Time-dependent observation sensitivity and potential applications to improve the model forecast are presented. Guidance provided by the sensitivity fields is used to adjust a 4D-Var DAS to achieve forecast error reduction through assimilation of supplementary data and through an accurate specification of a few of the background error variances.
Acne Through the Ages: Case-Based Observations Through Childhood and Adolescence
Authors: Tom Wynnis L. , Fallon Friedlander Sheila
Published: August 2008

Acne vulgaris is a common disorder that affects more than 17 million individuals in the United States. Knowledge of the disease is an important part of clinical practice, particularly for the pediatric practitioner. Contrary to common belief, acne is not a disease limited to adolescents and young adults but can occur at any stage of life. This article is a case-based review of acne during childhood and adolescence. Workup is based on age and concurrent physical findings, whereas therapy depends on the type of skin lesions along with patient characteristics and preferences.
Solitary Kidney
Authors: Hellerstein Stanley , Chambers Luke
Published: August 2008

The study provides the pediatric practitioner with a tool to determine whether the child with an apparently normal solitary kidney requires an in-depth investigation. Medical records from January 1, 1995 to December 31, 2006 identified 96 children with solitary kidneys and showed 78 with a normal appearing, hypertrophied solitary kidney. Study groups included (1) children 1 to 2 years, (2) girls older than 2 years and boys 2 to 13 years, and (3) boys older than 13 years. Serum creatinine concentrations and estimated glomerular filtration rate were calculated for each group. The mean serum creatinine concentrations in group 1 was 0.4 ± 0.1 mg/dL, group 2 was 0.6 ± 0.2 mg/dL, and group 3 was 1.1 ± 0.2 mg/dL. An estimated glomerular filtration rate 2 SD below the mean suggests further investigation. An estimated glomerular filtration rate 2 SD below the mean was 78 mL/min/1.73m2 in group 1, 73 mL/min/1.73m2 in group 2, and 70 mL/min/1.73m2 in group 3.
An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population
Authors: Ryan J. , Croft K. , Mori T. , Wesnes K. , Spong J. , Downey L. , Kure C. , Lloyd J. , Stough C.
Published: August 2008

The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60—85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.
The Effects of Team Personality Awareness Exercises on Team Satisfaction and Performance
Authors: Lancellotti Matthew P. , Boyd Thomas
Published: August 2008

Marketing courses heavily utilize team projects that can enhance student learning and make students more desirable to recruiters seeking greater teamwork skills and experience from students. Unfortunately team projects that provide opportunities to learn and improve such skills can also be great sources of frustration and dissatisfaction for instructors and students. This research investigates the effects of exercises designed to encourage student reflection on their behavior as team members and engage in proactive communications with teammates. The exercises are based on a set of humorous personality types derived from common maladaptive student behavior in teams (e.g., “The Dictator,” “The Monarchist”). The exercises are tested in a field study, which shows their use results in greater student satisfaction with the team and team output. They also result in increased student learning as measured by improved team project performance and better individual exam and course grades compared to students who engage in the same team projects without participating in the exercises. Details on the personalities and how to run the exercises are provided along with reflections from 8 years of their use in the classroom.
A Mixed Method Look at State Growth Management Policy
Authors: Howell-Moroney Michael E.
Published: August 2008

Using a mixed method approach, this article investigates growth management policy in the American states, presenting an event history analysis of state growth management policy adoptions, supplemented by a case study of growth management's evolution in the state of Maryland. Empirical results from the event history analysis suggest that growth pressures, the countervailing forces of state environmentalism and building interests, stronger gubernatorial powers, and citizen liberalism are all important factors associated with state adoptions of growth management. The Maryland case triangulates and contextualizes these key empirical findings, demonstrating the importance of those variables in a state-specific context. Beyond triangulating the empirical results, Maryland's legislative history with growth management highlights the importance of civic engagement as a means to both formulate and build sustained support for state growth management policy, even in the face of significant opposition from development interests.
Ruminations on the Study of American Public Bureaucracies
Authors: Kaufman Herbert
Published: August 2008

Public bureaucracies warrant the attention of political scientists because bureaucrats help determine the contents and effectiveness of public policies. Although the relationships between them and the other participants in public policy making can theoretically range from bureaucratic dominance, or at least autonomy, to passive bureaucratic subservience, most political scientists tend to treat American bureaucrats as significant but not commanding partners in the interplay of checks and balances in the political process. Understanding their roles in this process, however, is beset by ambiguities about when and to what extent their behavior is controlled or controlling. These uncertainties, plus incessant changes in their roles, may mean that we cannot hope for universal, long-enduring generalizations about their place in the polity. Consequently, to fully understand our political system, we must continuously observe, analyze, and reassess the influence they exert and the influences on them.
Performance time productivity and versatility estimates for 102 classical composers
Authors: Kozbelt Aaron
Published: August 2008

Performance time productivity estimates for 102 classical composers are reported. For each composer, the grand total and totals within several musical genres (e.g., symphonies, concerti, operas) are provided, which are used to generate a measure of composer versatility, or the extent to which each composer's output spans multiple genres. Estimated durations of lost works for each composer are also summarized. Descriptive results identify the most prolific composers in the overall sample and within each genre. Illustrative correlational analyses revealed reliable overall associations between average annual productivity, eminence and composer birth year; versatility was related only to birth year. However, composers in different periods of musical history (Baroque/Classical, Romantic and 20th century) showed different patterns of correlations between the variables, with 20th-century composers showing no reliable correlations at all. Implications and suggestions for incorporating the reported productivity estimates into multi-level statistical analyses of composers' lifespan creative productivity are discussed.
Sexual Offenders in Prison Psychiatric Treatment
Authors: Young Myla H. , Justice Jerald V. , Edberg Philip
Published: August 2008

In this study, 120 males (60 sexual offenders and 60 non—sexual offenders) in psychiatric treatment while in prison were evaluated using neuropsychological, psychological, and sociological/demographic measures. All sexual offenders ( N = 60) would be evaluated for potential civil commitment as sexually violent predators before prison release. Non—sexual offenders ( N = 60) had not been convicted of a sexual offense. Sexual offenders demonstrated significantly more overall neuropsychological impairment suggesting diffuse brain differences, with dysfunction primarily associated with temporal and frontal brain cortexes; higher Psychopathy Checklist—Revised Factor 1 (Interpersonal/Affective) ratings and Rorschach responses indicated disordered attachment, disordered self-perception, and impulsive emotionality. Sexual offenders also were more likely to be younger and unmarried. Stepwise logistic regression analysis resulted in 80.20% accuracy of prediction of sexual offenders. Potential application of this empirically derived multidimensional description to treatment of sexual offenders is discussed. Potential limitations to generalization of this information are also discussed.
Mental Health Performance Measurement in Corrections
Authors: Hoge Steven K. , Greifinger Robert B. , Lundquist Thomas , Mellow Jeff
Published: August 2008

Correctional facilities have become, by default, one of the largest providers of mental health care for patients with serious mental illness. In its 2002 Report to Congress, the National Commission on Correctional Health Care has reported that most facilities do not provide quality mental health care, nor do they conform to nationally accepted guidelines for mental health screening and treatment. This article describes the product of a consensus panel of correctional health care experts, charged to develop performance measures, based on nationally accepted standards, for selected elements of psychiatric treatment behind bars, aimed to improve the quality of care. Performance measures were developed for medication adherence, suicide prevention, mental health treatment planning, and sleep medication usage.
Clinical Outcomes after Subpectoral Biceps Tenodesis with an Interference Screw
Authors: Mazzocca Augustus D. , Cote Mark P. , Arciero Cristina L. , Romeo Anthony A. , Arciero Robert A.
Published: August 2008

Background

Subpectoral biceps tenodesis with an interference screw has been shown to be an effective procedure from both an anatomic and biomechanical perspective. There have been no clinical outcome data on this procedure to date.

Hypothesis

Subpectoral biceps tenodesis is an effective procedure in eliminating biceps tendinosis symptoms.

Study Design

Case series; Level of evidence, 4.

Methods

Patients who underwent subpectoral biceps tenodesis with a minimum follow-up of 1 year were evaluated using a battery of clinical outcome measures, biceps apex difference, and pain scores. A diagnosis of biceps tendinosis was made using a specific diagnostic protocol coupled with observation of biceps tendon fraying and increased erythema on dry arthroscopy.

Results

Between November 2002 and August 2005, 50 patients underwent subpectoral biceps tenodesis. Complete follow-up examinations were performed in 41 of 50 (82%). There were 16 women and 25 men (mean age, 50 years). Follow-up averaged 29 months (range, 12–49 months). The mean scores were 86, Rowe; 81, American Shoulder and Elbow Surgeons (ASES); 9, Simple Shoulder Test (SST); 87, Constant Murley; and 84, Single Assessment Numeric Evaluation (SANE). There was 1 failure as demonstrated by pull-out of the tendon from the bone tunnel resulting in a “Popeye” deformity on physical examination. The mean value for biceps apex distance was 0.15 cm, with 35 of 41 patients demonstrating no difference on physical examination. Twenty-three of 41 patients had complete preoperative and postoperative examinations. All clinical outcome measures demonstrated a statistically significant improvement at follow-up when compared with the preoperative scores. Thirty-one patients had identified lesions of the rotator cuff at time of arthroscopy. The mean ASES score in patients without rotator cuff lesion (89.2 ± 10.3) was significantly greater than the mean ASES for those with rotator cuff lesion (78.0 ± 21.0) ( P = .0324). The mean SST score in patients without rotator cuff lesion (10.6 ± 1.5) was significantly greater than the mean ASES score for those with rotator cuff lesion (8.8 ± 2.7) ( P = .0132).

Conclusion

Subpectoral biceps tenodesis with an interference screw is a viable treatment option for patients with symptomatic biceps tendinosis. Anterior shoulder pain and biceps symptoms were resolved with this technique. Patients with coexistent rotator cuff lesion had less favorable outcomes.
A Phospholipid-modified Polystyrene—Polyisobutylene— Polystyrene (SIBS) Triblock Polymer for Enhanced Hemocompatibility and Potential Use in Artificial Heart Valves
Authors: Duraiswamy Nandini , Choksi Tejas D. , Pinchuk Leonard , Schoephoerster Richard T.
Published: August 2008

Poly(styrene-block-isobutylene-block-styrene) (`SIBS') is selected for a novel trileaflet heart valve due to its high resistance to oxidation, hydrolysis, and enzyme attack. SIBS is modified using six different phospholipids and its mechanical properties characterized by tensile stress, peel strength, shear strength, contact angle, and surface energy, and then for hemocompatibility by studying the adhesion of fluorescently labeled platelets in a parallel plate chamber under physiological flow conditions. Phospholipid modification decreases SIBS tensile stress (at 45% strain) by 30% and reduces platelet adhesion by a factor of 10, thereby improving its hemocompatibility and its potential use as a synthetic heart valve.
Water Policy Networks in Egypt and Ethiopia
Authors: Luzi Samuel , Abdelmoghny Hamouda Mohamed , Sigrist Franziska , Tauchnitz Evelyne
Published: August 2008

This article presents data illustrating the networked structure of the water sector in two Nile Basin states, Egypt and Ethiopia. Social network analysis is applied to quantify network characteristics. Implications for water policy design and implementation processes are discussed. Governmental agencies occupy the most central network positions in both countries. Intersectoral cooperation is weak, impeding effective policy integration. The limited connectedness to nonstate actors prevents the central policy makers from tapping all available expertise and implementation capacities. International donor agencies play an important role by connecting different types of actors. The higher prominence of NGOs and decentralized water authorities in the Ethiopian water sector indicates a comparably higher potential for pluralistic policy making. Social network analysis is found to be a useful tool to highlight cooperation patterns in the water sector, but its utility for explaining policy processes without supplementary qualitative information is limited.
Toward Sustainable Energy Development in Bangladesh
Authors: Sk Noim Uddin  , Taplin Ros
Published: August 2008

Bangladesh is one of the most electricity deprived nations in the world. Despite large potential for renewable energy sources in Bangladesh, currently their contribution to the electricity supply remains insignificant. Use of renewable energy is considered an indispensable component of sustainable energy systems, as renewables emit less greenhouse gas emissions compared to fossil fuel energy systems. However, to advance such sustainable energy systems, appropriate strategies and institutional settings need to be put in place for all nations. To address this, this article examines Bangladesh's current energy strategies and institutional settings and investigates future strategies for the advancement of renewables. This article argues that further significant efforts could be made toward energy sustainability in Bangladesh and the development for a national sustainable energy strategy. Among other future strategies, implementation of the Clean Development Mechanism under the Kyoto Protocol could assist in facilitation of energy sustainability for Bangladesh.
Weighing the Consequences
Authors: Valle Maribel , Levy Judith
Published: August 2008

Theorists posit that personal decisions to disclose being HIV positive are made based on the perceived consequences of that disclosure. This study examines the perceived costs and benefits of self-disclosure among African American injection drug users (IDUs). A total of 80 African American IDUs were interviewed in-depth subsequent to testing HIV positive. Participants reported that interpersonal costs of self-disclosure included stigma, loss of sexual/romantic partners, emotional harming of family/friends, shattering of privacy, physical isolation, blame, and loss of income. The benefits of disclosure included social support, emotional catharsis, and income. Four factors that help to tip the scales in either direction were identified. Study findings have implications for the delivery of counseling, testing, and partner notification services to African American IDUs living with HIV.
County Funding Versus Municipal Aspiration
Authors: Houck Eric A.
Published: August 2008

One town in a countywide school district wants to provide additional financial support for its students. The ensuing debate over governance, finance, and authority strains relationships across the county as multiple political actors and interest groups take sides. The school superintendent takes steps to provide a peaceful resolution to the issue, but uncomfortable questions raised by the debate remain. This case is designed to highlight issues in local school governance, political coalitions, and systemwide leadership.
Complete genome of Phenylobacterium zucineum – a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562
Authors: Luo Yingfeng , Xu Xiaoli , Ding Zonghui , Liu Zhen , Zhang Bing , Yan Zhiyu , Sun Jie , Hu Songnian , Hu Xun
Published: August 2008

Background

Phenylobacterium zucineum is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, P. zucineum maintains a stable association with its host cell without affecting the growth and morphology of the latter.

Results

Here, we report the whole genome sequence of the type strain HLK1T. The genome consists of a circular chromosome (3,996,255 bp) and a circular plasmid (382,976 bp). It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to Caulobacter crescentus, a model species for cell cycle research. Notably, P. zucineum has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of C. crescentus, and most of the genes directly regulated by CtrA in the latter have orthologs in the former.

Conclusion

This work presents the first complete bacterial genome in the genus Phenylobacterium. Comparative genomic analysis indicated that the CtrA regulon is well conserved between C. crescentus and P. zucineum.
Activated Akt1 accelerates MMTV-c-ErbB2 mammary tumourigenesis in mice without activation of ErbB3
Authors: Young Christian D , Nolte Erica C , Lewis Andrew , Serkova Natalie J , Anderson Steven M
Published: August 2008

Introduction

ErbB2, a member of the epidermal growth factor receptor (EGFR) family, is overexpressed in 20% to 30% of human breast cancer cases and forms oncogenic signalling complexes when dimerised to ErbB3 or other EGFR family members.

Methods

We crossed mouse mammary tumour virus (MMTV)-myr-Akt1 transgenic mice (which express constitutively active Akt1 in the mammary gland) with MMTV-c-ErbB2 transgenic mice to evaluate the role of Akt1 activation in ErbB2-induced mammary carcinoma using immunoblot analysis, magnetic resonance spectroscopy and histological analyses.

Results

Bitransgenic MMTV-c-ErbB2, MMTV-myr-Akt1 mice develop mammary tumours twice as fast as MMTV-c-ErbB2 mice. The bitransgenic tumours were less organised, had more mitotic figures and fewer apoptotic cells. However, many bitransgenic tumours displayed areas of extensive necrosis compared with tumours from MMTV-c-ErbB2 mice. The two tumour types demonstrate dramatically different expression and activation of EGFR family members, as well as different metabolic profiles. c-ErbB2 tumours demonstrate overexpression of EGFR, ErbB2, ErbB3 and ErbB4, and activation/phosphorylation of both ErbB2 and ErbB3, underscoring the importance of the entire EGFR family in ErbB2-induced tumourigenesis. Tumours from bitransgenic mice overexpress the myr-Akt1 and ErbB2 transgenes, but there was dramatically less overexpression and phosphorylation of ErbB3, diminished phosphorylation of ErbB2, decreased level of EGFR protein and undetectable ErbB4 protein. There was also an observable attenuation in a subset of tyrosine-phosphorylated secondary signalling molecules in the bitransgenic tumours compared with c-ErbB2 tumours, but Erk was activated/phosphorylated in both tumour types. Finally, the bitransgenic tumours were metabolically more active as indicated by increased glucose transporter 1 (GLUT1) expression, elevated lactate production and decreased intracellular glucose (suggesting increased glycolysis).

Conclusion

Expression of activated Akt1 in MMTV-c-ErbB2 mice accelerates tumourigenesis with a reduced requirement for signalling through the EGFR family, as well as a reduced requirement for a subset of downstream signaling molecules with a metabolic shift in the tumours from bitransgenic mice. The reduction in signalling downstream of ErbB2 when Akt is activated suggest a possible mechanism by which tumour cells can become resistant to ErbB2-targeted therapies, necessitating therapies that target oncogenic signalling events downstream of ErbB2.
Analysis of the mouse embryonic stem cell regulatory networks obtained by ChIP-chip and ChIP-PET
Authors: Mathur Divya , Danford Timothy W , Boyer Laurie A , Young Richard A , Gifford David K , Jaenisch Rudolf
Published: August 2008

Background

Genome-wide approaches have begun to reveal the transcriptional networks responsible for pluripotency in embryonic stem (ES) cells. Chromatin Immunoprecipitation (ChIP) followed either by hybridization to a microarray platform (ChIP-chip) or by DNA sequencing (ChIP-PET), has identified binding targets of the ES cell transcription factors OCT4 and NANOG in humans and mice, respectively. These studies have provided an outline of the transcriptional framework involved in maintaining pluripotency. Recent evidence with comparing multiple technologies suggests that expanding these datasets using different platforms would be a useful resource for examining the mechanisms underlying pluripotency regulation.

Results

We have now identified OCT4 and NANOG genomic targets in mouse ES cells by ChIP-chip and provided the means to compare these data with previously reported ChIP-PET results in mouse ES cells. We have mapped the sequences of OCT4 and NANOG binding events from each dataset to genomic coordinates, providing a valuable resource to facilitate a better understanding of the ES cell regulatory circuitry. Interestingly, although considerable differences are observed in OCT4 and NANOG occupancy as identified by each method, a substantial number of targets in both datasets are enriched for genes that have known roles in cell-fate specification and that are differentially expressed upon Oct4 or Nanog knockdown.

Conclusion

This study suggests that each dataset is a partial representation of the overall ES cell regulatory circuitry, and through integrating binding data obtained by ChIP-chip and ChIP-PET, the methods presented here provide a useful means for integrating datasets obtained by different techniques in the future.
Suspected SSPE – a Delayed Psychiatric Presentation
Authors: Mattinson Peter J. B.
Published: August 2008

A case of suspected subacute sclerosing panencephalitis is described, presenting to a psychiatric hospital 39 years after a natural measles infection.