bluuebunny/crossref_metadata_2025 huggingface dataset:
The radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide induces DNA damage in EMT-6 mammary carcinoma cells
Authors: Haykal Joelle , Geara Fady , Haddadin Makhluf J , Smith Colin A , Gali-Muhtasib Hala
Published: July 2009

Background

DCQ (2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide), a synthetic quinoxaline 1,4-dioxide, enhances the cytotoxic effect of ionizing radiation (IR) in vivo and in vitro. We sought to clarify whether increased radiation-induced DNA damage, decreased rate of damage repair, and the generation of reactive oxygen species (ROS) contribute to DCQ enhancement of IR.

Methods

Murine mammary adenocarcinoma EMT-6 cells were treated with DCQ for 4 h before exposure to 10 Gy IR. Treated cells were monitored for modulations in cell cycle, induction of DNA damage, and generation of ROS.

Results

Combined DCQ and IR treatments (DCQ+IR) induced rapid cell-cycle arrests in EMT-6 cells, particularly in S and G2/M phases. Alkaline comet assays revealed high levels of DNA damage in cells after exposure to DCQ+IR, consistent with damage-induced arrest. Unlike IR-only and DCQ-only treated cells, the damage induced by combined DCQ+IR was repaired at a slower rate. Combined treatment, compared to separate DCQ and IR treatments, activated DNA-protein kinase and induced more p-ATM, supporting a role for double strand breaks (DSBs), which are more toxic and difficult to repair than single strand breaks (SSBs). Contributing factors to DCQ radiosensitization appear to be the induction of ROS and DSBs.

Conclusion

Collectively, our findings indicate that radiosensitization by DCQ is mediated by DNA damage and decreased repair and that ROS are at least partially responsible.
Dendrites differ from axons in patterns of microtubule stability and polymerization during development
Authors: Kollins Katherine M , Bell Robert L , Butts Matthew , Withers Ginger S
Published: July 2009

Background

Dendrites differ from axons in patterns of growth and development, as well as in morphology. Given that microtubules are key structural elements in cells, we assessed patterns of microtubule stability and polymerization during hippocampal neuron development in vitro to determine if these aspects of microtubule organization could distinguish axons from dendrites.

Results

Quantitative ratiometric immunocytochemistry identified significant differences in microtubule stability between axons and dendrites. Most notably, regardless of developmental stage, there were high levels of dynamic microtubules throughout the dendritic arbor, whereas dynamic microtubules were predominantly concentrated in the distal end of axons. Analysis of microtubule polymerization using green fluorescent protein-tagged EB1 showed both developmental and regional differences in microtubule polymerization between axons and dendrites. Early in development (for example, 1 to 2 days in vitro), polymerization events were distributed equally in both the anterograde and retrograde directions throughout the length of both axons and dendrites. As development progressed, however, polymerization became biased, with a greater number of polymerization events in distal than in proximal and middle regions. While polymerization occurred almost exclusively in the anterograde direction for axons, both anterograde and retrograde polymerization was observed in dendrites. This is in agreement with predicted differences in microtubule polarity within these compartments, although fewer retrograde events were observed in dendrites than expected.

Conclusion

Both immunocytochemical and live imaging analyses showed that newly formed microtubules predominated at the distal end of axons and dendrites, suggesting a common mechanism that incorporates increased microtubule polymerization at growing process tips. Dendrites had more immature, dynamic microtubules throughout the entire arbor than did axons, however. Identifying these differences in microtubule stability and polymerization is a necessary first step toward understanding how they are developmentally regulated, and may reveal novel mechanisms underlying neuron maturation and dendritic plasticity that extend beyond the initial specification of polarity.
Identification of potential therapeutic targets in human head & neck squamous cell carcinoma
Authors: Han Jing , Kioi Mitomu , Chu Wei-Sing , Kasperbauer Jan L , Strome Scott E , Puri Raj K
Published: July 2009

Background

Human head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy. Identification of unique or overexpressed cell-associated or cell surface antigens is critical for diagnosis and development of cancer vaccines and targeted therapies for HNSCC. We have used high throughput microarray technology to search for candidate targets in HNSCC.

Methods

Gene expression profiling in 17 HNSCC tumors and 3 normal tonsil tissues was performed by microarray. QRT-PCR analysis was performed to validate the microarray results. The five candidate genes were further characterized by immunohistochemical technique in surgical samples and tissue arrays.

Results

A total of 192 up-regulated genes at statistical significance of p < 0.01 and log2 ratio ≥ 1 were identified in HNSCC tumors compared to normal tissues. These genes belong to immune response, cell growth, cell cycle regulation, oncogenes, metabolism and others. Five potential novel target genes (FABP5, CD24, CD44, CD74, and HSP27) were identified, which were highly expressed in HNSCC tumor samples and tissue arrays. CD24, CD44, and CD74 proteins were expressed on the cell surface, and FABP5 and HSP27 proteins were predominantly expressed in the cytoplasm of HNSCC.

Conclusion

Five genes and their products may serve as a diagnostic biomarker or therapeutic target for HNSCC. While additional work is needed to elucidate the biological significance of these proteins, CD24 and CD74 expressed only in small proportion of cells indicating tumor heterogeneity and subtypes of tumor initiating cells (CD24+/CD44+) present in HNSCC.
DHEA-dependent and organ-specific regulation of TNF-α mRNA expression in a murine polymicrobial sepsis and trauma model
Authors: Barkhausen Tanja , Hildebrand Frank , Krettek Christian , van Griensven Martijn
Published: July 2009

Introduction

Dehydroepiandrosterone (DHEA) improves survival after trauma and sepsis, while mechanisms of action are not yet fully understood. Therefore, we investigated the influence of DHEA on local cytokine expression in a two-hit model.

Methods

Male NMRI mice were subjected to femur fracture/hemorrhagic shock and subsequent sepsis. Sham-operated animals were used as controls. DHEA (25 mg/kg) or vehicle was administered daily. Mortality rate, activity and body temperature were determined daily after sepsis induction. TNF-α, IL-1β and IL-10 mRNA expression pattern were investigated in lung and liver tissue after 48 and 96 hours.

Results

DHEA treatment resulted in a significantly reduced mortality rate and improvements in the clinical status. On cytokine level, only TNF-α was significantly reduced in the cecal ligation and puncture (CLP)-vehicle group in both tissues after 48 hours. This suppression could be restored by DHEA administration. In contrast, after 96 hours, TNF-α was up-regulated in the CLP-vehicle group while remaining moderate by DHEA treatment in liver tissue.

Conclusions

The improved outcome after DHEA treatment and trauma is coherent with restoration of TNF-α in liver and lung after 48 hours and a counter-regulatory attenuation of TNF-α in liver after 96 hours. Thus, DHEA seems to act, time and organ dependent, as a potent modulator of TNF-α expression.
A randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients
Authors: Scannapieco Frank A , Yu Jihnhee , Raghavendran Krishnan , Vacanti Angela , Owens Susan I , Wood Kenneth , Mylotte Joseph M
Published: July 2009

Introduction

Dental plaque biofilms are colonized by respiratory pathogens in mechanically-ventilated intensive care unit patients. Thus, improvements in oral hygiene in these patients may prevent ventilator-associated pneumonia. The goal of this study was to determine the minimum frequency (once or twice a day) for 0.12% chlorhexidine gluconate application necessary to reduce oral colonization by pathogens in 175 intubated patients in a trauma intensive care unit.

Methods

A randomized, double-blind, placebo-controlled clinical trial tested oral topical 0.12% chlorhexidine gluconate or placebo (vehicle alone), applied once or twice a day by staff nurses. Quantitation of colonization of the oral cavity by respiratory pathogens (teeth/denture/buccal mucosa) was measured.

Results

Subjects were recruited from 1 March, 2004 until 30 November, 2007. While 175 subjects were randomized, microbiologic baseline data was available for 146 subjects, with 115 subjects having full outcome assessment after at least 48 hours. Chlorhexidine reduced the number of Staphylococcus aureus, but not the total number of enterics, Pseudomonas or Acinetobacter in the dental plaque of test subjects. A non-significant reduction in pneumonia rate was noted in groups treated with chlorhexidine compared with the placebo group (OR = 0.54, 95% CI: 0.23 to 1.25, P = 0.15). No evidence for resistance to chlorhexidine was noted, and no adverse events were observed. No differences were noted in microbiologic or clinical outcomes between treatment arms.

Conclusions

While decontamination of the oral cavity with chlorhexidine did not reduce the total number of potential respiratory pathogens, it did reduce the number of S. aureus in dental plaque of trauma intensive care patients.

Trial Registration

clinicaltrials.gov NCT00123123.
Variation in gene duplicates with low synonymous divergence in Saccharomyces cerevisiae relative to Caenorhabditis elegans
Authors: Katju Vaishali , Farslow James C , Bergthorsson Ulfar
Published: July 2009

Background

The direct examination of large, unbiased samples of young gene duplicates in their early stages of evolution is crucial to understanding the origin, divergence and preservation of new genes. Furthermore, comparative analysis of multiple genomes is necessary to determine whether patterns of gene duplication can be generalized across diverse lineages or are species-specific. Here we present results from an analysis comprising 68 duplication events in the Saccharomyces cerevisiae genome. We partition the yeast duplicates into ohnologs (generated by a whole-genome duplication) and non-ohnologs (from small-scale duplication events) to determine whether their disparate origins commit them to divergent evolutionary trajectories and genomic attributes.

Results

We conclude that, for the most part, ohnologs tend to appear remarkably similar to non-ohnologs in their structural attributes (specifically the relative composition frequencies of complete, partial and chimeric duplicates), the discernible length of the duplicated region (duplication span) as well as genomic location. Furthermore, we find notable differences in the features of S. cerevisiae gene duplicates relative to those of another eukaryote, Caenorhabditis elegans, with respect to chromosomal location, extent of duplication and the relative frequencies of complete, partial and chimeric duplications.

Conclusions

We conclude that the variation between yeast and worm duplicates can be attributed to differing mechanisms of duplication in conjunction with the varying efficacy of natural selection in these two genomes as dictated by their disparate effective population sizes.
Risk of Death From Prostate Cancer After Brachytherapy Alone or With Radiation, Androgen Suppression Therapy, or Both in Men With High-Risk Disease
Authors: D'Amico Anthony V. , Moran Brian J. , Braccioforte Michelle H. , Dosoretz Daniel , Salenius Sharon , Katin Michael , Ross Rudi , Chen Ming-Hui
Published: July 2009

Purpose

We estimated the risk of prostate cancer (PC) –specific mortality (PCSM) after brachytherapy alone or in conjunction with androgen suppression therapy (AST), external-beam radiation therapy (EBRT), or both in men with high-risk PC.

Patients and Methods

The study cohort comprised 1,342 men with a prostate-specific antigen level more than 20 ng/mL and clinical T3 or 4 and/or Gleason score 8 to 10 disease. Competing risks multivariable regression was performed to estimate the risk of PCSM in men treated with brachytherapy alone or with supplemental AST, EBRT, or both, adjusting for age, year of treatment, and known PC prognostic factors.

Results

Despite higher baseline probabilities of PCSM after a median follow-up of 5.1 years, there was a significant reduction in the risk of PCSM (adjusted hazard ratio [AHR], 0.32; 95% CI, 0.14 to 0.73; P = .006) in men treated with brachytherapy and both AST and EBRT as compared with neither. When compared with brachytherapy alone, a significant decrease in the risk of PCSM was not observed in men treated with either supplemental AST (AHR, 0.63; 95% CI, 0.27 to 1.47; P = .28) or EBRT (AHR, 0.57; 95% CI, 0.21 to 1.52; P = .26). There was a near-significant reduction (AHR, 0.53; 95% CI, 0.27 to 1.07; P = .079) in the risk of PCSM in men treated with tri- as compared with bimodality therapy.

Conclusion

Supplemental AST and EBRT but not either supplement compared with brachytherapy alone was associated with a decreased risk of PCSM in men with high-risk PC.
Risk of Bilateral Renal Cell Cancer
Authors: Wiklund Fredrik , Tretli Steinar , Choueiri Toni K. , Signoretti Sabina , Fall Katja , Adami Hans-Olov
Published: July 2009

Purpose

The risk of developing bilateral kidney cancer has not been adequately defined in any large, population-based study with long-term follow-up to our knowledge.

Patients and Methods

We estimated the risk of metachronous bilateral renal cell cancer in patients diagnosed with unilateral kidney cancer, as recorded in the nationwide cancer registries of Norway and Sweden. Altogether 28,642 patients were followed for an average of 4.4 years. The standardized incidence ratio—the ratio of the observed number of bilateral cancers to the number expected on the basis of the incidence in the Norwegian and Swedish population at large—was used as a measure of relative risk. We used multivariate Poisson regression to separate the effects of the explanatory variables.

Results

A synchronous bilateral renal cell cancer was reported in 86 patients. A total of 112 metachronous bilateral cancers were recorded during 126,493 person-years of follow-up compared with 35.8 expected, yielding an overall relative risk (RR) of 3.1 (95% CI, 2.6 to 3.8) and a cumulative incidence of 0.8% after 20 or more years of follow-up. In the multivariate analyses, risk increased monotonically with younger age at first diagnosis (P for trend < .001); compared with patients who were 60 years or older, those younger than 40 years were at a 17-fold higher risk (RR = 17.4; 95% CI, 10.1 to 29.8). We also found a modest but statistically significant decreasing trend with increasing duration of follow-up.

Conclusion

The risk of metachronous bilateral renal cell cancer is drastically higher among patients first affected at a young age, suggesting a subset of early onset renal cell cancer with a strong genetic component.
Are There Any Differences in the Clinical and Economic Outcomes Between US Cancer Patients Receiving Appropriate or Inappropriate Venous Thromboembolism Prophylaxis?
Authors: Amin Alpesh N. , Lin Jay , Yang Guiping , Stemkowski Stephen
Published: July 2009

Prophylaxis is often underused and inappropriately prescribed. This study compares the efficacy and cost of appropriate and partial prophylaxis in cancer patients at risk for VTE.
Poor Documentation Prevents Adequate Assessment of Quality Metrics in Colorectal Cancer
Authors: Abernethy Amy P. , Herndon James E. , Wheeler Jane L. , Rowe Krista , Marcello Jennifer , Patwardhan Meenal
Published: July 2009

To standardize oncology clinical practice and improve patient outcomes, multiple organizations have developed cancer-specific metrics on the basis of a systematic background review, expert guidance, and fundamental elements of cancer care—staging and treatment.
Provider Practice Models in Ambulatory Oncology Practice: Analysis of Productivity, Revenue, and Provider and Patient Satisfaction
Authors: Buswell Lori A. , Ponte Patricia Reid , Shulman Lawrence N.
Published: July 2009

Physicians, nurse practitioners, and physician assistants often work in teams to deliver cancer care in ambulatory oncology practices. This is likely to become more prevalent as the demand for oncology services rises, and the number of providers increases only slightly.
FAK, PIP5KIγ and gelsolin cooperatively mediate force-induced expression of α-smooth muscle actin
Authors: Chan Matthew W. C. , Arora Pamma D. , Bozavikov Peter , McCulloch Christopher A.
Published: July 2009

During the development of pressure-induced cardiac hypertrophy, fibroblasts are activated to become myofibroblasts, which exhibit actin-cytoskeletal remodeling and express α-smooth muscle actin (SMA; encoded by ACTA2). Currently, the mechanosensing signaling pathways that regulate SMA expression are not defined. Because focal-adhesion complexes are putative mechanosensing organelles, we examined the role of focal adhesion kinase (FAK) and its interaction with gelsolin in the regulation of SMA expression. We subjected NIH3T3 cells to tensile forces (0.65 pN/μm2) by using collagen-coated magnetite beads attached to integrins. After stimulation by mechanical force, FAK and gelsolin were recruited to magnetite beads and there was increased phosphorylation of Tyr397FAK. Mechanical force enhanced SMA promoter activity by twofold; this increased activity was blocked by FAK knockdown using siRNA and by deletion of gelsolin. Force-induced nuclear translocation of MRTF-A, a transcriptional co-activator of SMA that is regulated by actin filaments, was also reduced by FAK knockdown. Phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2], which uncaps gelsolin from actin filaments, was enriched at sites of force application. Type-I phosphatidylinositol 4-phosphate 5 kinase-γ (PIP5KIγ), which generates PtdIns(4,5)P2, associated with FAK and was required for force-mediated SMA-promoter activity and actin assembly. Catalytically inactive PIP5KIγ inhibited force-induced phosphorylation of FAK at Tyr397. These data suggest a novel pathway in which mechanosensing by FAK regulates actin assembly via gelsolin and the activity of PIP5KIγ; actin assembly in turn controls SMA expression via MRTF-A.
Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3T3-L1 preadipocytes
Authors: Zhu Di , Shi Shuo , Wang Hongzhong , Liao Kan
Published: July 2009

The first stage of 3T3-L1 adipocyte differentiation is growth arrest, which is achieved by contact inhibition at confluence. In growth-arrested confluent 3T3-L1 preadipocytes, α-tubulin acetylation and primary-cilium formation were induced. The blockade of primary-cilium formation by suppressing IFT88 or Kif3a inhibited 3T3-L1 adipocyte differentiation. IGF-1 (IGF-I)-receptor signaling, which is essential for differentiation induction, was sensitized by the formation of a primary cilium in confluent 3T3-L1 preadipocytes. The receptor located in primary cilium was more sensitive to insulin stimulation than that not located in cilia. During cilium formation, insulin receptor substrate 1 (IRS-1), one of the important downstream signaling molecules of the IGF-1 receptor, was recruited to the basal body at which it was phosphorylated on tyrosine by the receptor kinase in cilia. Akt-1, an important signal molecule of the IGF-1 receptor in adipocyte differentiation, was also activated at the basal body. These IGF-1-receptor signaling processes were all inhibited in IFT88- or Kif3a-knockdown cells. Thus, the primary cilium and its basal body formed an organized signaling pathway for the IGF-1 receptor to induce adipocyte differentiation in confluent 3T3-L1 preadipocytes.
Corneodesmosin gene ablation induces lethal skin-barrier disruption and hair-follicle degeneration related to desmosome dysfunction
Authors: Leclerc Emilie A. , Huchenq Anne , Mattiuzzo Nicolas R. , Metzger Daniel , Chambon Pierre , Ghyselinck Norbert B. , Serre Guy , Jonca Nathalie , Guerrin Marina
Published: July 2009

Corneodesmosin (CDSN) is specific to desmosomes of epithelia undergoing cornification, mainly the epidermis and the inner root sheath of the hair follicles. CDSN nonsense mutations are associated with hypotrichosis simplex of the scalp, a rare disease that leads to complete baldness in young adults. CDSN displays adhesive properties, mostly attributable to its N-terminal glycine-rich domain, and is sequentially proteolyzed as corneocytes migrate towards the skin surface. K14-promoter driven Cre-mediated deletion of Cdsn in mice resulted in neonatal death as a result of epidermal tearing upon minor mechanical stress. Ultrastructural analyses revealed a desmosomal break at the interface between the living and cornified layers. After grafting onto nude mice, knockout skin showed a chronic defect in the epidermal permeability barrier. The epidermis was first hyperproliferative with a thick cornified layer, then, both the epidermis and the hair follicles degenerated. In adults, Cdsn deletion resulted in similar histological abnormalities and in a lethal barrier defect. We demonstrate that Cdsn is not essential for skin-barrier formation in utero, but is vital throughout life to preserve this barrier by maintaining desmosome integrity. The strong adhesive function that the protein confers on corneodesmosomes also seems necessary for maintaining the architecture of the hair follicle.
Advertising Competition in a Dynamic Oligopoly with Multiple Brands
Authors: Erickson Gary M.
Published: July 2009

A model is developed that allows the derivation of feedback Nash equilibrium advertising strategies for oligopolistic competitors. The model is an extension of a modified Vidale-Wolfe model that incorporates multiple brands per competitor. The resulting expressions of feedback advertising strategies are combined with those for sales dynamics in an empirical model that is applied to the carbonated soft drink market, which involves three primary competitors and five primary brands. The research provides the following contributions: A modification of the Vidale-Wolfe model is extended to allow dynamic analysis of an oligopoly in which the competitors each offer multiple brands. The model extension permits the derivation of a feedback Nash equilibrium. The determination of a feedback Nash equilibrium enhances empirical analysis by allowing an expanded empirical model that includes the explicit modeling of endogenous advertising along with demand relationships.
Dantzig-Wolfe Decomposition for Solving Multistage Stochastic Capacity-Planning Problems
Authors: Singh Kavinesh J. , Philpott Andy B. , Wood R. Kevin
Published: July 2009

We describe a multistage, stochastic, mixed-integer programming model for planning capacity expansion of production facilities. A scenario tree represents uncertainty in the model; a general mixed-integer program defines the operational submodel at each scenario-tree node, and capacity-expansion decisions link the stages. We apply “variable splitting” to two model variants, and solve those variants using Dantzig-Wolfe decomposition. The Dantzig-Wolfe master problem can have a much stronger linear programming relaxation than is possible without variable splitting, over 700% stronger in one case. The master problem solves easily and tends to yield integer solutions, obviating the need for a full branch-and-price solution procedure. For each scenario-tree node, the decomposition defines a subproblem that may be viewed as a single-period, deterministic, capacity-planning problem. An effective solution procedure results as long as the subproblems solve efficiently, and the procedure incorporates a good “duals stabilization method.” We present computational results for a model to plan the capacity expansion of an electricity distribution network in New Zealand, given uncertain future demand. The largest problem we solve to optimality has six stages and 243 scenarios, and corresponds to a deterministic equivalent with a quarter of a million binary variables.
A Decomposition Approach for a Class of Capacitated Serial Systems
Authors: Janakiraman Ganesh , Muckstadt John A.
Published: July 2009

We study a class of two-echelon serial systems with identical ordering/production capacities or limits for both echelons. Demands are assumed to be integer valued. For the case where the lead time to the upstream echelon is one period, the optimality of state-dependent modified echelon base-stock policies is proved using a decomposition approach. For the case where the upstream lead time is two periods, we introduce a new class of policies called “two-tier base-stock policies,” and prove their optimality. Some insight about the inventory control problem in N echelon serial systems with identical capacities at all stages and arbitrary lead times everywhere is also provided. We argue that a generalization of two-tier base-stock policies, which we call “multitier base-stock policies,” are optimal for these systems; we also provide a bound on the number of parameters required to specify the optimal policy.
Disjunctive Decomposition for Two-Stage Stochastic Mixed-Binary Programs with Random Recourse
Authors: Ntaimo Lewis
Published: July 2009

This paper introduces disjunctive decomposition for two-stage mixed 0-1 stochastic integer programs (SIPs) with random recourse. Disjunctive decomposition allows for cutting planes based on disjunctive programming to be generated for each scenario subproblem under a temporal decomposition setting of the SIP problem. A new class of valid inequalities for mixed 0-1 SIP with random recourse is presented. In particular, we derive valid inequalities that allow for scenario subproblems for SIP with random recourse but deterministic technology matrix and right-hand side vector to share cut coefficients. The valid inequalities are used to derive a disjunctive decomposition method whose derivation has been motivated by real-life stochastic server location problems with random recourse, which find many applications in operations research. Computational results with large-scale instances to demonstrate the potential of the method are reported.
A Stochastic Programming Duality Approach to Inventory Centralization Games
Authors: Chen Xin , Zhang Jiawei
Published: July 2009

In this paper, we present a unified approach to study a class of cooperative games arising from inventory centralization. The optimization problems corresponding to the inventory games are formulated as stochastic programs. We observe that the strong duality of stochastic linear programming not only directly leads to a series of recent results concerning the nonemptiness of the core of such games, but also suggests a way to find an element in the core. The proposed approach is also applied to inventory games with concave ordering cost. In particular, we show that the newsvendor game with concave ordering cost has a nonempty core. Finally, we prove that it is NP-hard to determine whether a given allocation is in the core of the inventory games even in a very simple setting.
Großbritannien und die Neue Ostpolitik der Bundesrepublik
Authors: Geppert Dominik
Published: July 2009

Vorspann

Über die britische Reaktion auf die „Neue Ostpolitik“ der Bundesrepublik Deutschland wissen wir bisher viel weniger als über die der USA und Frankreichs. Willy Brandts Einschätzung, sein Kurs sei in Großbritannien auf weniger Skepsis gestoßen als bei den anderen beiden Westmächten, hallt in der Forschung nach. Dominik Geppert zeigt aber jetzt, dass auch auf der Insel die Dinge komplizierter lagen: Alte Befürchtungen gegenüber Deutschland beeinflussten die Rezeption der Ostpolitik ebenso wie der letztlich entscheidende britische Pragmatismus.
Collaboration Between the Essential Esa1 Acetyltransferase and the Rpd3 Deacetylase Is Mediated by H4K12 Histone Acetylation in Saccharomyces cerevisiae
Authors: Chang Christie S , Pillus Lorraine
Published: July 2009

Histone modifications that regulate chromatin-dependent processes are catalyzed by multisubunit complexes. These can function in both targeting activities to specific genes and in regulating genomewide levels of modifications. In Saccharomyces cerevisiae, Esa1 and Rpd3 have opposing enzymatic activities and are catalytic subunits of multiple chromatin modifying complexes with key roles in processes such as transcriptional regulation and DNA repair. Esa1 is an essential histone acetyltransferase that belongs to the highly conserved MYST family. This study presents evidence that the yeast histone deacetylase gene, RPD3, when deleted, suppressed esa1 conditional mutant phenotypes. Deletion of RPD3 reversed rDNA and telomeric silencing defects and restored global H4 acetylation levels, in addition to rescuing the growth defect of a temperature-sensitive esa1 mutant. This functional genetic interaction between ESA1 and RPD3 was mediated through the Rpd3L complex. The suppression of esa1's growth defect by disruption of Rpd3L was dependent on lysine 12 of histone H4. We propose a model whereby Esa1 and Rpd3L act coordinately to control the acetylation of H4 lysine 12 to regulate transcription, thereby emphasizing the importance of dynamic acetylation and deacetylation of this particular histone residue in maintaining cell viability.
The Action of Purifying Selection, Mutation and Drift on Fitness Epistatic Systems
Authors: Pérez-Figueroa Andrés , Caballero Armando , García-Dorado Aurora , López-Fanjul Carlos
Published: July 2009

For different fitness mutational models, with epistasis introduced, we simulated the consequences of drift (D scenario) or mutation, selection, and drift (MSD scenario) in populations at the MSD balance subsequently subjected to bottlenecks of size N = 2, 10, 50 during 100 generations. No “conversion” of nonadditive into additive variance was observed, all components of the fitness genetic variance initially increasing with the inbreeding coefficient F and subsequently decreasing to zero (D) or to an equilibrium value (MSD). In the D scenario, epistasis had no appreciable effect on inbreeding depression and that on the temporal change of variance components was relevant only for high rates of strong epistatic mutation. In parallel, between-line differentiation in mean fitness accelerated with F and that in additive variance reached a maximum at F ∼ 0.6–0.7, both processes being intensified by strong epistasis. In the MSD scenario, however, the increase in additive variance was smaller, as it was used by selection to purge inbreeding depression (N ≥ 10), and selection prevented between-line differentiation. Epistasis, either synergistic or antagonistic (this leading to multiple adaptive peaks), had no appreciable effect on MSD results nor, therefore, on the evolutionary rate of fitness change.
Can Exergaming Contribute to Improving Physical Activity Levels and Health Outcomes in Children?
Authors: Daley Amanda J.
Published: July 2009

Physical inactivity among children is a serious public health problem. It has been suggested that high levels of screen time are contributory factors that encourage sedentary lifestyles in young people. As physical inactivity and obesity levels continue to rise in young people, it has been proposed that new-generation active computer- and video-console games (otherwise known as “exergaming”) may offer the opportunity to contribute to young people's energy expenditure during their free time. Although studies have produced some encouraging results regarding the energy costs involved in playing active video-console games, the energy costs of playing the authentic versions of activity-based video games are substantially larger, highlighting that active gaming is no substitute for real sports and activities. A small number of exergaming activities engage children in moderate-intensity activity, but most do not. Only 3 very small trials have considered the effects of exergaming on physical activity levels and/or other health outcomes in children. Evidence from these trials has been mixed; positive trends for improvements in some health outcomes in the intervention groups were noted in 2 trials. No adequately powered randomized, controlled trial has been published to date, and no trial has assessed the long-term impact of exergaming on children's health. We now need high-quality randomized, controlled trials to evaluate the effectiveness and sustainability of exergaming, as well as its clinical relevance; until such studies take place, we should remain cautious about its ability to positively affect children's health.
Playing Active Video Games Increases Energy Expenditure in Children
Authors: Graf Diana L. , Pratt Lauren V. , Hester Casey N. , Short Kevin R.
Published: July 2009

OBJECTIVE: To compare energy expenditure rates in children playing the physically active video games, Dance Dance Revolution (DDR) and Nintendo's Wii Sports in relation to treadmill walking.

METHODS: Energy expenditure, heart rate, step rate, and perceived exertion were measured in 14 boys and 9 girls (ages 10–13 years; BMI at 3–98th percentile for age and gender) while watching television at rest, playing DDR at 2 skill levels, playing Wii bowling and boxing, and walking at 2.6, 4.2, and 5.7 km/h. Arterial elasticity was measured at rest and immediately after gaming.

RESULTS: Compared with watching television, energy expenditure while gaming or walking increased 2- to 3-fold. Similarly, high rates of energy expenditure, heart rate, and perceived exertion were elicited from playing Wii boxing, DDR level 2, or walking at 5.7 km/h. This occurred despite variations in step rate among activities, reflecting greater use of upper body during Wii play (lowest step rate) than during walking (highest step rate) or DDR play. Wii bowling and beginner level DDR elicited a 2-fold increase in energy expenditure compared to television watching. Large-artery elasticity declined immediately after both DDR and Wii. The change was inversely related to the increment in energy expenditure above rest achieved during the activity.

CONCLUSIONS: Energy expenditure during active video game play is comparable to moderate-intensity walking. Thus, for children who spend considerable time playing electronic screen games for entertainment, physically active games seem to be a safe, fun, and valuable means of promoting energy expenditure.
Terrorism-Related Perceived Stress, Adolescent Depression, and Social Support From Friends
Authors: Shahar Golan , Cohen Guina , Grogan Kathryn E. , Barile John P. , Henrich Christopher C.
Published: July 2009

BACKGROUND: Terrorism leads to adolescent depression, but little is known about protective factors. We investigated 90 adolescents (in grades 7–9) residing in Dimona, Israel, before and after their exposure to a suicide bombing.

OBJECTIVE: To examine the prospective effect of social support from friends, parents, and school personnel on the link between bombing-related perceived stress and adolescent depression.

METHODS: Seven months prior to the suicide bombing, adolescents completed questionnaires as part of an ongoing investigation of youth risk/resilience under stress. The focus of the present study was on the Perceived Social Support Scale. One month subsequent to the suicide bombing, participants were interviewed by telephone about their bombing-related perceived stress (a 1-item measure) and depression (the Center for Epidemiologic Studies Child Depression Scale).

RESULTS: Bombing-related perceived stress was associated with an increase in continuous levels of depression from before to after the bombing (β = .29; P = .006). Prebombing social support from friends buffered against this effect (β = −.29; P = .010). Adolescents reporting high bombing-related perceived stress evinced an increase in depression if they reported low levels of friends' support (β = .61; P < .001) but not high levels of friends' support (β = .00; P = .98). In addition, social support from friends predicted an increase in adolescent depression over time when bombing-related perceived stress was low (β = .34; P = .026).

CONCLUSION: In adolescence, social support from friends might protect against the depressogenic effect of terrorism-related perceived stress.
Predictors of Clinical Outcomes and Hospital Resource Use of Children After Tracheotomy
Authors: Berry Jay G. , Graham Dionne A. , Graham Robert J. , Zhou Jing , Putney Heather L. , O'Brien Jane E. , Roberson David W. , Goldmann Don A.
Published: July 2009

OBJECTIVES: The objectives are to describe health outcomes and hospital resource use of children after tracheotomy and identify patient characteristics that correlate with outcomes and hospital resource use.

PATIENTS AND METHODS: A retrospective analysis of 917 children aged 0 to 18 years undergoing tracheotomy from 36 children's hospitals in 2002 with follow-up through 2007. Children were identified from ICD-9-CM tracheotomy procedure codes. Comorbid conditions (neurologic impairment [NI], chronic lung disease, upper airway anomaly, prematurity, and trauma) were identified with ICD-9-CM diagnostic codes. Patient characteristics were compared with in-hospital mortality, decannulation, and hospital resource use by using generalized estimating equations.

RESULTS: Forty-eight percent of children were ≤6 months old at tracheotomy placement. Chronic lung disease (56%), NI (48%), and upper airway anomaly (47%) were the most common underlying comorbid conditions. During hospitalization for tracheotomy placement, children with an upper airway anomaly experienced less mortality (3.3% vs 11.7%; P < .001) than children without an upper airway anomaly. Five years after tracheotomy, children with NI experienced greater mortality (8.8% vs 3.5%; P ≤ .01), less decannulation (5.0% vs 11.0%; P ≤ .01), and more total number of days in the hospital (mean [SE]: 39.5 [4.0] vs 25.6 [2.6] days; P ≤ .01) than children without NI. These findings remained significant (P < .01) in multivariate analysis after controlling for other significant cofactors.

CONCLUSIONS: Children with upper airway anomaly experienced less mortality, and children with NI experienced higher mortality rates and greater hospital resource use after tracheotomy. Additional research is needed to explore additional factors that may influence health outcomes in children with tracheotomy.
AE energy release during the fracture of HSC beams
Authors: Vidya Sagar R. , Raghu Prasad B.K.
Published: July 2009

An attempt has been made experimentally to investigate the acoustic emission (AE) energy release in high-strength concrete (HSC) beams subjected to monotonically increasing load. Acoustic emission energy release during the fracture process of the HSC beams is measured. Stress waves released during the fracture process in materials cause acoustic emissions. AE energy released during the fracture of a notched three-point bend plain concrete beam specimens having 28-day compressive strengths of 50·0 MPa, 69·0 MPa and 78·0 MPa and mortar (cement:sand (1:4) by weight) specimens are studied. Mortar consists of one part cement and four parts sand by weight. The specimens were tested by a material testing system of 1200 kN capacity employing crack mouth opening displacement control at the rate of 0·0004 mm/s. The fracture energy and the AE energy released during the fracture process of all the tested TPB and mortar specimens are compared and discussed. The observations made in the present experimental study have some applications for monitoring the integrity of structures.
Comparison of deflection calculations and span-to-depth ratios in BS 8110 and Eurocode 2
Authors: Vollum R.L.
Published: July 2009

The current paper proposes a procedure for calculating deflections with Eurocode 2, which is subsequently used to evaluate the span-to-effective-depth rules in Eurocode 2 and British Standard (BS) 8110. The theoretical background to span-to-depth rules is examined. The Eurocode 2 span-to-depth rules were derived by curve-fitting the results of a parametric study in which deflections were calculated in simply supported beams under a permanent load equal to half the design ultimate load. The loading assumed in the derivation of the Eurocode 2 span-to-depth rules is unrealistic for lightly reinforced slabs where self-weight can exceed half the design ultimate load. The procedure used to modify the Eurocode 2 span-to-depth rules for different stress levels is also shown to be questionable. An amendment is proposed that is shown to improve the accuracy of the Eurocode 2 span-to-depth rules.
Management Forecast Characteristics: Effects on Venture Capital Investment Screening Judgments
Authors: Fleming Damon M.
Published: July 2009

ABSTRACT: This study examines the effects of the quantification and precision of forecast disclosures in new venture proposals on 62 experienced venture capitalists’ initial investment screening judgments. It was predicted that including quantitative estimates for key components of earnings forecasts in the proposal enhances its persuasive power and, thus, more favorable investment screening judgments. It was also predicted that while quantification can increase the persuasive power of forecast disclosures, it may also evoke expectancies about forecast precision and that violation of these expectancies adversely affects investment screening judgments. Experimental results generally support the research predictions and additional analyses reveal that perceptions of management’s credibility mediate the main effect of forecast quantification. Combined, these results provide evidence that managers should carefully consider the information content and consistency of forecast disclosures.
The Judgmental Effects of Management Communications and a Fifth Balanced Scorecard Category on Performance Evaluation
Authors: Kaplan Steven E. , Wisner Priscilla S.
Published: July 2009

ABSTRACT: This study extends prior balanced scorecard (BSC) research by examining management’s choice of whether to include four or five BSC categories when a specific nontraditional strategic objective is present. The results of the study show that when management communications about a specific nontraditional strategic objective are limited and a set of specific strategic performance measures indicate superior performance by one manager over another, evaluators discount their reliance on these measures in their performance-related judgments when these measures are clustered into a fifth BSC category relative to when these measures are integrated among the four traditional BSC categories. That is, adding a fifth BSC category resulted in a de-emphasis of the relevant information about the specific nontraditional strategic objective. But, when a fifth BSC category is present, enhancing management communications about a specific strategic objective resulted in greater emphasis on the relevant information about the specific nontraditional strategic objective. When a traditional, four-category BSC is used, enhancing management communications about a specific strategic objective did not result in greater emphasis on the relevant information about the specific nontraditional strategic objective. Our results showing that under certain conditions information presented in a fifth BSC category is discounted by evaluators runs counter to professional literature and has practical implications for companies considering the use of additional BSC categories to communicate strategic objectives.
Hydrogen-Rich Saline Protects Myocardium Against Ischemia/Reperfusion Injury in Rats
Authors: Sun Qiang , Kang Zhimin , Cai Jianmei , Liu Wenwu , Liu Yun , Zhang John H. , Denoble Petar J. , Tao Hengyi , Sun Xuejun
Published: July 2009

Protective effect of hydrogen (H2) gas on cardiac ischemia-reperfusion (I/R) injury has been demonstrated previously. This study was designed to test the hypothesis that hydrogen-rich saline (saline saturated with molecular hydrogen), which is easy to use, induces cardioprotection against ischemia (30 min) and reperfusion (24 h) injury in rats. Adult male Sprague-Dawley rats underwent 30-min occlusion of the left anterior descending (LAD) coronary artery and 24-h reperfusion. Intraperitoneal injection of hydrogen-rich saline before reperfusion significantly decreased plasma and myocardium malondialdehyde (MDA) concentration, decreased cardiac cell apoptosis, and myocardial 8-hydroxydeoxyguanosine (8-OHdG) in area at risk zones (AAR), suppressed the activity of caspase-3, and reduced infarct size. The heart function parameters including left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), +(dP/dt)max and −(dP/dt)max were also significantly improved 24 h after reperfusion. It is concluded that hydrogen-rich saline is a novel, simple, safe, and effective method to attenuate myocardial I/R injury.
Altering and Assessing Persistence of Genetically Modified E. coli MG1655 in the Large Bowel
Authors: Barbas Andrew S. , Lesher Aaron P. , Thomas Anitra D. , Wyse Aaron , Devalapalli Aditya P. , Lee Yu-Huei , Tan Hung-Enn , Orndorff Paul E. , Bollinger R. Randal , Parker William
Published: July 2009

One of the primary factors limiting the efficacy of probiotic therapies is short persistence time. Utilizing a novel method for assessment of persistence in the large bowel independent of survival of the organisms in the upper GI tract, we tested whether overexpression of the type 1 pilus, a colonization factor, or the presence of secretory immunoglobulin A (sIgA) might increase the persistence time of a laboratory strain of E. coli in the gut. For this purpose, cecal ostomies were created in mice and bacteria were placed in the ostomies, with or without sIgA. The persistence of the bacteria was assessed by evaluating the length of time after placement in which the bacteria were found in fecal samples. E. coli MG1655 expressing pili with the mannose-specific adhesin persisted in vivo significantly longer [mean (hours) ± SEM: 91.50 ± 15.98, n = 12] than bacteria expressing pili without adhesin [43.67 ± 8.22, n = 12] ( P = 0.01) and significantly longer than bacteria expressing neither pili nor adhesin [22.00 ± 4.22, n = 12] ( P = 0.0004). Although the persistence time of bacteria was not significantly affected by the presence of sIgA, the sIgA did cause a relative increase in retention of inert particles. These results, combined with an acute increase in stool production and stool water content in those animals not receiving sIgA following introduction of bacteria, suggest that sIgA might have anti-inflammatory properties in the gut when administered with enteric bacteria. Modifying expression of probiotic colonization factors may provide substantial benefit to patients with digestive tract diseases by virtue of increased persistence of the probiotic and, in the case of sIgA, an anti-inflammatory effect. This novel in vivo model may be useful in evaluating persistence time in a variety of current and future probiotic regimens.