bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro
Authors: Aljofan Mohamad , Sganga Michael L , Lo Michael K , Rootes Christina L , Porotto Matteo , Meyer Adam G , Saubern Simon , Moscona Anne , Mungall Bruce A
Published: November 2009

Background

Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 μM compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC50), cytotoxicity (CC50) and thein vitrotherapeutic index in live virus and pseudotype assay formats.

Results

While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound.

Conclusion

All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.
Human cases of simultaneous echinococcosis and tuberculosis - significance and extent in China
Authors: Yang Yu Rong , Gray Darren J , Ellis Magda K , Yang Shu Kun , Craig Philip S , McManus Donald P
Published: November 2009

During analysis of retrospective community survey data, we identified two patients from Xiji County, south Ningxia Hui Autonomous Region with simultaneous echinococcosis and tuberculosis (TB), representing the first such reports for China. As the echinococcosis chronicity increased, the immune profile in both subjects changed from a Th1 to Th2 response, as shown by a TB skin test, originally positive, becoming negative. Such an elevated Th2 immune profile, with subsequent suppression of the Th1 immune response, is a common feature of chronic helminth infections. Given the difficulties in definitive diagnosis, and the potential increased susceptibility for TB infection in patients with advanced echinococcosis, we suggest that combined TB/echinococcosis surveys be undertaken in this area in the future. This would allow early diagnosis of both TB and echinococcosis cases with better prognosis for effective and sustainable treatment outcomes, ultimately reducing associated morbidity and mortality, and also the overall financial costs to the individual and the public health care system in this under developed part of China.
The molecular basis for stability of heterochromatin-mediated silencing in mammals
Authors: Hiragami-Hamada Kyoko , Xie Sheila Q , Saveliev Alexander , Uribe-Lewis Santiago , Pombo Ana , Festenstein Richard
Published: November 2009

The archetypal epigenetic phenomenon of position effect variegation (PEV) in Drosophila occurs when a gene is brought abnormally close to heterochromatin, resulting in stochastic silencing of the affected gene in a proportion of cells that would normally express it. PEV has been instrumental in unraveling epigenetic mechanisms. Using an in vivo mammalian model for PEV we have extensively investigated the molecular basis for heterochromatin-mediated gene silencing. Here we distinguish 'epigenetic effects' from other cellular differences by studying ex vivo cells that are identical, apart from the expression of the variegating gene which is silenced in a proportion of the cells. By separating cells according to transgene expression we show here that silencing appears to be associated with histone H3 lysine 9 trimethylation (H3K9me3), DNA methylation and the localization of the silenced gene to a specific nuclear compartment enriched in these modifications. In contrast, histone H3 acetylation (H3Ac) and lysine 4 di or tri methylation (H3K4me2/3) are the predominant modifications associated with expression where we see the gene in a euchromatic compartment. Interestingly, DNA methylation and inaccessibility, rather than H3K9me3, correlated most strongly with resistance to de-repression by cellular activation. These results have important implications for understanding the contribution of specific factors involved in the establishment and maintenance of gene silencing and activation in vivo.
Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion
Authors: Cohen Mitchell J , Brohi Karim , Calfee Carolyn S , Rahn Pamela , Chesebro Brian B , Christiaans Sarah C , Carles Michel , Howard Marybeth , Pittet Jean-François
Published: November 2009

Introduction

High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.

Methods

One hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.

Results

Plasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.

Conclusions

The results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.
Correlation between parameters at initiation of renal replacement therapy and outcome in patients with acute kidney injury
Authors: Ostermann Marlies , Chang René WS
Published: November 2009

Introduction

Renal replacement therapy (RRT) is a fully established treatment for critically ill patients with acute kidney injury (AKI) but there are no scientifically established criteria when to initiate it. Our objectives were to describe the epidemiology of critically ill patients with AKI receiving RRT and to evaluate the relationship between biochemical, physiological and comorbid factors at time of RRT and ICU mortality.

Methods

Retrospective analysis of demographic and physiologic data of 1,847 patients who received RRT for AKI in 22 ICUs in UK and Germany between 1989 - 1999.

Results

54.1% of RRT patients died in ICU. ICU survivors were younger, had a lower APACHE II score and fewer failed organ systems on admission to ICU compared to non-survivors. Multivariate analysis showed that at time of initiation of RRT, independent risk factors for ICU mortality were mechanical ventilation [odds ratio (OR) 6.03], neurological failure (OR 2.48), liver failure (OR 2.44), gastrointestinal failure (OR 2.04), pre-existing chronic illnesses (OR 1.74), haematological failure (OR 1.74), respiratory failure (OR 1.62), oligoanuria (OR 1.6), age (OR 1.03), serum urea (OR 1.004) and cardiovascular failure (OR 1.3). A higher pH at initiation of RRT was independently associated with a better outcome. Failure to correct acidosis and development of more organ failure within 48 hours after initiation of RRT were also associated with an increased risk of dying in ICU.

Conclusions

Oligoanuria, acidosis and concomitant dysfunction of other organs at time of RRT were associated with poor survival. In contrast, serum creatinine and urea levels only had a weak correlation with outcome after RRT.
Rerouting of a Follicle-Stimulating Hormone Analog to the Regulated Secretory Pathway
Authors: Pearl Christopher A. , Jablonka-Shariff Albina , Boime Irving
Published: November 2009

LH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. This coordinated secretion of LH and FSH is essential for normal follicular development and ovulation in females and for spermatogenesis in males. The structural signals encoded in the LH and FSH subunits that govern the intracellular sorting of LH through the regulated secretory pathway and FSH through the constitutive pathway are largely unknown. Our laboratory recently identified the seven amino acid carboxy tail of LHβ as a sorting signal for LH in GH3 cells. Here we compared the morphological features of GH3 cells expressing an FSH analog containing the heptapeptide (FL7AA) with wild-type FSH using confocal microscopy. These experiments were performed to develop a rerouting model for examining structure-function links between secretion pathways of FSH/LH and their biological action. Both FSH- and LH-expressing cells exhibit a fluorescence pattern of randomly dispersed cytoplasmic puncta. FL7AA expressing cells have more intracellular accumulation compared with wild-type FSH and display a unique halo pattern of fluorescence near the plasma membrane. Such a pattern was not observed in cells expressing FSH or LH. Our results demonstrate that this FSH analog containing the carboxy heptapeptide of LHβ is rerouted to the regulated secretory pathway in GH3 cells. This rerouted gonadotropin provides a unique model to study the trafficking, regulation, and function of LH and FSH.
Insulin Sensitization of Human Preadipocytes through Glucocorticoid Hormone Induction of Forkhead Transcription Factors
Authors: Tomlinson Julianna J. , Boudreau Adèle , Wu Dongmei , Salem Houssein Abdou , Carrigan Amanda , Gagnon Annemarie , Mears Alan J. , Sorisky Alexander , Atlas Ella , Haché Robert J. G.
Published: November 2009

Glucocorticoids are synthesized locally in adipose tissue and contribute to metabolic disease through the facilitation of adipose tissue expansion. Here we report that exposure of human primary preadipocytes to glucocorticoids increases their sensitivity to insulin and enhances their subsequent response to stimuli that promote differentiation. This effect was observed in primary human preadipocytes but not in immortalized 3T3-L1 murine preadipocytes or in fully differentiated primary human adipocytes. Stimulation of insulin signaling was mediated through induction of insulin receptor (IR), IR substrate protein 1 (IRS1), IRS2, and the p85 regulatory subunit of phosphoinositide-3-3-kinase, which led to enhanced insulin-mediated activation of Akt. Although induction of IRS2 was direct, induction of IR and IRS1 by glucocorticoids occurred subsequent to primary induction of the forkhead family transcription factors FoxO1A and FoxO3A. These results reveal a new role for glucocorticoids in preparing preadipocytes for differentiation.
Structure-function insights into the yeast Dam1 kinetochore complex
Authors: Nogales Eva , Ramey Vincent H.
Published: November 2009

Faithful segregation of genetic material during cell division requires the dynamic but robust attachment of chromosomes to spindle microtubules during all stages of mitosis. This regulated attachment occurs at kinetochores, which are complex protein organelles that are essential for cell survival and genome integrity. In budding yeast, in which a single microtubule attaches per kinetochore, a heterodecamer known as the Dam1 complex (or DASH complex) is required for proper chromosome segregation. Recent years have seen a burst of structural and biophysical data concerning this interesting complex, which has caught the attention of the mitosis research field. In vitro, the Dam1 complex interacts directly with tubulin and self-assembles into ring structures around the microtubule surface. The ring is capable of tracking with depolymerizing ends, and a model has been proposed whereby the circular geometry of the oligomeric Dam1 complex allows it to couple the depolymerization of microtubules to processive chromosome movement in the absence of any additional energy source. Although it is attractive and simple, several important aspects of this model remain controversial. Additionally, the generality of the Dam1 mechanism has been questioned owing to the fact that there are no obvious Dam1 homologs beyond fungi. In this Commentary, we discuss recent structure-function studies of this intriguing complex.
Prohibitins and the functional compartmentalization of mitochondrial membranes
Authors: Osman Christof , Merkwirth Carsten , Langer Thomas
Published: November 2009

Prohibitins constitute an evolutionarily conserved and ubiquitously expressed family of membrane proteins that are essential for cell proliferation and development in higher eukaryotes. Roles for prohibitins in cell signaling at the plasma membrane and in transcriptional regulation in the nucleus have been proposed, but pleiotropic defects associated with the loss of prohibitin genes can be largely attributed to a dysfunction of mitochondria. Two closely related proteins, prohibitin-1 (PHB1) and prohibitin-2 (PHB2), form large, multimeric ring complexes in the inner membrane of mitochondria. The absence of prohibitins leads to an increased generation of reactive oxygen species, disorganized mitochondrial nucleoids, abnormal cristae morphology and an increased sensitivity towards stimuli-elicited apoptosis. It has been found that the processing of the dynamin-like GTPase OPA1, which regulates mitochondrial fusion and cristae morphogenesis, is a key process regulated by prohibitins. Furthermore, genetic analyses in yeast have revealed an intimate functional link between prohibitin complexes and the membrane phospholipids cardiolipin and phosphatidylethanolamine. In light of these findings, it is emerging that prohibitin complexes can function as protein and lipid scaffolds that ensure the integrity and functionality of the mitochondrial inner membrane.
p53-dependent control of transactivation of the Pen2 promoter by presenilins
Authors: Dunys Julie , Sevalle Jean , Giaime Emilie , Pardossi-Piquard Raphaëlle , Vitek Michael P. , Renbaum Paul , Levy-Lahad Ephrat , Zhang Yun-wu , Xu Huaxi , Checler Frédéric , da Costa Cristine Alves
Published: November 2009

The senile plaques found in the brains of patients with Alzheimer's disease are mainly due to the accumulation of amyloid β-peptides (Aβ) that are liberated by γ-secretase, a high molecular weight complex including presenilins, PEN-2, APH-1 and nicastrin. The depletion of each of these proteins disrupts the complex assembly into a functional protease. Here, we describe another level of regulation of this multimeric protease. The depletion of both presenilins drastically reduces Pen2 mRNA levels and its promoter transactivation. Furthermore, overexpression of presenilin-1 lowers Pen2 promoter transactivation, a phenotype abolished by a double mutation known to prevent presenilin-dependent γ-secretase activity. PEN-2 expression is decreased by depletion of β-amyloid precursor protein (APP) and increased by the APP intracellular domain (AICD). We show that AICD and APP complement for Pen2 mRNA levels in APP/APLP1-2 knockout fibroblasts. Interestingly, overexpression of presenilin-2 greatly increases Pen2 promoter transactivation. The opposite effect triggered by both presenilins was reminiscent of our previous study, which showed that these two proteins elicit antagonistic effects on p53. Therefore, we examined the contribution of p53 on Pen2 transcription. Pen2 promoter transactivation, and Pen2 mRNA and protein levels were drastically reduced in p53–/– fibroblasts. Furthermore, PEN-2 expression could be rescued by p53 complementation in p53- and APP-deficient cells. Interestingly, PEN-2 expression was also reduced in p53-deficient mouse brain. Overall, our study describes a p53-dependent regulation of PEN-2 expression by other members of the γ-secretase complex, namely presenilins.
Integrin signal masks growth-promotion activity of HB-EGF in monolayer cell cultures
Authors: Mizushima Hiroto , Wang Xiaobiao , Miyamoto Shingo , Mekada Eisuke
Published: November 2009

The extracellular environment and tissue architecture contribute to proper cell function and growth control. Cells growing in monolayers on standard polystyrene tissue culture plates differ in their shape, growth rate and response to external stimuli, compared with cells growing in vivo. Here, we showed that the EGFR (epidermal growth factor receptor) ligand heparin-binding EGF-like growth factor (HB-EGF) strongly stimulated cell growth in nude mice, but not in cells cultured in vitro. We explored the effects of HB-EGF on cell growth under various cell culture conditions and found that growth promotion by HB-EGF was needed in three-dimensional (3D) or two-dimensional (2D) culture systems in which cell-matrix adhesion was reduced. Under such conditions, cell growth was extremely suppressed in the absence of HB-EGF, but markedly potentiated in the presence of HB-EGF. When the integrin signal was reduced using antibodies or knockout of either integrin β1 or focal adhesion kinase (FAK), cells showed HB-EGF-dependent growth. We also showed that EGF, transforming growth factor-α (TGFα) or ligands of other receptor tyrosine kinases (RTKs) stimulated cell growth in 3D culture, but not in tissue culture plates. These results indicate that the integrin signal was sufficient to support cell growth in 2D tissue culture plates without addition of the growth factor, whereas stimulation by growth factors was clearly demonstrated in culture systems in which integrin signals were attenuated.
Fission yeast Myo51 is a meiotic spindle pole body component with discrete roles during cell fusion and spore formation
Authors: Doyle Alex , Martín-García Rebeca , Coulton Arthur T. , Bagley Steve , Mulvihill Daniel P.
Published: November 2009

Class V myosins are dimeric actin-associated motor proteins that deliver cellular cargoes to discrete cellular locations. Fission yeast possess two class V myosins, Myo51 and Myo52. Although Myo52 has been shown to have roles in vacuole distribution, cytokinesis and cell growth, Myo51 has no as yet discernible function in the vegetative life cycle. Here, we uncover distinct functions for this motor protein during mating and meiosis. Not only does Myo51 transiently localise to a foci at the site of cell fusion upon conjugation, but overexpression of the Myo51 globular tail also leads to disruption of cell fusion. Upon completion of meiotic prophase Myo51 localises to the outside of the spindle pole bodies (SPBs), where it remains until completion of meiosis II. Association of Myo51 with SPBs is not dependent upon actin or the septation initiation network (SIN); however, it is dependent on a stable microtubule cytoskeleton and the presence of the Cdc2-CyclinB complex. We observe a rapid and dynamic exchange of Myo51 at the SPB during meiosis I but not meiosis II. Finally, we show that Myo51 has an important role in regulating spore formation upon completion of meiosis.
PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions
Authors: van den Bout Iman , Divecha Nullin
Published: November 2009

It has long been known that phosphoinositides are present in cellular membranes, but only in the past four decades has our understanding of their importance for proper cell function advanced significantly. Key to determining the biological roles of phosphoinositides is understanding the enzymes involved in their metabolism. Although many such enzymes have now been identified, there is still much to learn about their cellular functions. Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) are a group of kinases that catalyse the production of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2]. As well as being a substrate for the enzymes phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K), PtdIns(4,5)P2 acts as a second messenger in its own right, influencing a variety of cellular processes. In this Commentary, we review how PIP5Ks are modulated to achieve regulated PtdIns(4,5)P2 production, and discuss the role of these proteins in different cellular processes.
TGFβ-induced endothelial podosomes mediate basement membrane collagen degradation in arterial vessels
Authors: Rottiers Patricia , Saltel Frédéric , Daubon Thomas , Chaigne-Delalande Benjamin , Tridon Viviane , Billottet Clotilde , Reuzeau Edith , Génot Elisabeth
Published: November 2009

Podosomes are specialized plasma-membrane actin-based microdomains that combine adhesive and proteolytic activities to spatially restrict sites of matrix degradation in in vitro assays, but the physiological relevance of these observations remain unknown. Inducible rings of podosomes (podosome rosettes) form in cultured aortic cells exposed to the inflammatory cytokine TGFβ. In an attempt to prove the existence of podosomes in living tissues, we developed an ex vivo endothelium observation model. This system enabled us to visualize podosome rosettes in the endothelium of native arterial vessel exposed to biologically active TGFβ. Podosomes induced in the vessel appear similar to those formed in cultured cells in terms of molecular composition, but in contrast to the latter, arrange in a protruding structure that is similar to invadopodia. Local degradation of the basement membrane scaffold protein collagen-IV, is observed underneath the structures. Our results reveal for the first time the presence of podosome rosettes in the native endothelium and provide evidence for their capacity to degrade the basement membrane, opening up new avenues to study their role in vascular pathophysiology. We propose that podosome rosettes are involved in arterial vessel remodeling.
Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins
Authors: Jessop Catherine E. , Watkins Rachel H. , Simmons Jennifer J. , Tasab Mohammed , Bulleid Neil J.
Published: November 2009

At least 17 members of the protein disulphide isomerase (PDI) family of oxidoreductases are present in the endoplasmic reticulum (ER) of mammalian cells. They are thought to catalyse disulphide formation to aid folding or to regulate protein function; however, little is known about their individual functions. Here, we show that some proteins that enter the ER are clients for single oxidoreductases, whereas others are clients for several PDI-like enzymes. We previously identified potential substrates for ERp57, and here identify substrates for ERp18 and ERp46. In addition, we analysed the specificity of substrates towards PDI, ERp72, ERp57, ERp46, ERp18 and P5. Strikingly, ERp18 shows specificity towards a component of the complement cascade, pentraxin-related protein PTX3, whereas ERp46 has specificity towards peroxiredoxin-4, a thioredoxin peroxidase. By contrast, most PDI family members react with Ero1α. Moreover, P5 forms a non-covalent complex with immunoglobulin heavy chain binding protein (BiP) and shows specificity towards BiP client proteins. These findings highlight cooperation between BiP and P5, and demonstrate that individual PDI family members recognise specific substrate proteins.
Mitotic chromosome interactions of Epstein-Barr nuclear antigen 1 (EBNA1) and human EBNA1-binding protein 2 (EBP2)
Authors: Nayyar Vipra Kapur , Shire Kathy , Frappier Lori
Published: November 2009

The Epstein-Barr nuclear antigen 1 (EBNA1) protein enables the stable persistence of Epstein-Barr virus episomal genomes during latent infection, in part by tethering the episomes to the cellular chromosomes in mitosis. A host nucleolar protein, EBNA1-binding protein 2 (EBP2), has been shown to be important for interactions between EBNA1 and chromosomes in metaphase and to associate with metaphase chromosomes. Here, we examine the timing of the chromosome associations of EBNA1 and EBP2 through mitosis and the regions of EBNA1 that mediate the chromosome interactions at each stage of mitosis. We show that EBP2 is localized to the nucleolus until late prophase, after which it relocalizes to the chromosome periphery, where it remains throughout telophase. EBNA1 is associated with chromosomes early in prophase through to telophase and partially colocalizes with chromosomal EBP2 in metaphase through to telophase. Using EBNA1 deletion mutants, the chromosome association of EBNA1 at each stage of mitosis was found to be mediated mainly by a central glycine-arginine region, and to a lesser degree by N-terminal sequences. These sequence requirements for chromosome interaction mirrored those for EBP2 binding. Our results suggest that interactions between EBNA1 and chromosomes involve at least two stages, and that the contribution of EBP2 to these interactions occurs in the second half of mitosis.
Multiple impact modelling for shot peening and peen forming
Authors: Kang X , Wang T , Platts J
Published: November 2009

Impact modelling for shot peening or peen forming has progressed from simulating a single impact (or local multiple impacts) to simulating a large number of multiple impacts. It is the aim of this paper to provide quantitative results with a detailed finite element study, and to compare the effects of a single impact and global multiple impacts. Using a two-dimensional (2D) axisymmetric single impact model with a very fine mesh as reference, an appropriate three-dimensional (3D) mesh density for the target material is chosen by evaluating the 3D results against the axisymmetric results. A 3D explicit dynamic finite element analysis combined with a static springback analysis is then used to simulate a large number of steel shot impacts on an aluminium 2024-T351 target. The multiple impact modelling results indicate a clear difference of residual stress profiles between those obtained from single and multiple impact modelling. This difference is due to the global uniformity effects of shot peening, which involves numerous impacts. In addition, equivalent plastic strain obtained from the analysis is compared with microhardness test data on an experimental sample. Finally, the shot peen forming effect of multiple impacts is also evaluated by showing the macroscopic surface deformation. The comparison between single and multiple impact modelling results indicates that it is appropriate and important to model an appropriate coverage of multiple impacts for shot peening and peen forming at its various coverage.
Effects of machining parameters on surface integrity of hard machined surfaces
Authors: Choi Y , Liu C R
Published: November 2009

This study investigates the effects of machining parameters on the surface integrity of hard machined surfaces. The residual stress distribution of hard machined surfaces is characterized by compressive stresses in the range between 150 and 1000 MPa. Typically, residual stresses in the feed direction are more compressive above a depth of 12.7 μm, while residual stresses in the cutting direction are more compressive below a depth of 12.7 μm. The micro-hardness distribution of hard machined surfaces is characterized by a lower surface hardness and a stable bulk hardness. It is noted that a higher cutting speed induces a more softened layer. The machining-induced residual stress and micro-hardness distribution can increase the crack initiation life by 39 per cent, while increasing the crack propagation life by more than four times. Accordingly, it can increase the fatigue life by more than three times. The results are presented that demonstrate that the machining parameters significantly influence the residual stress and micro-hardness distribution of hard machined surfaces and that the fatigue performance of hard machined surfaces can be significantly enhanced by optimizing the machining parameters.
Comparison of position controllers designed for an elastic system using its complete and deficient dynamic models
Authors: Özgören M K
Published: November 2009

This article is concerned with comparing the position controllers designed for an elastic system using its complete and deficient dynamic models. The system considered here as an application example consists of three rotors connected with two elastic shafts. Three kinds of controller are designed and compared. Controller-3 is designed using the complete dynamic model of the system. Therefore, it works perfectly, satisfying all the specified requirements. Controller-2 is designed based on a deficient model that consists of two rotors connected with a single elastic shaft. Therefore, it works with an acceptable performance only for limited magnitudes of its gains. If its gains are increased too much to improve the steady-state accuracy, the closed-loop system becomes unstable owing to the spillover effect induced by the unmodelled dynamic feature, which is the inertia at the midpoint of the shaft. Controller-1 is designed based on a more deficient model that consists of a single rotor mounted on a rigid shaft. Therefore, it also works with an acceptable performance only for limited magnitudes of its gains. With too large gains, it also suffers from the spillover effect induced by the unmodelled dynamic feature, which is the elasticity of the shaft. However, with the increasing gains, the spillover effect caused by controller-1 makes the closed-loop system increasingly oscillatory but never unstable. In other words, controller-1 is robust against the destabilizing tendency of the spillover effect. From this point of view, controller-1 is better than controller-2, even though the model used for controller-1 is more deficient than that used for controller-2. Another prominent feature of controller-1 is that it is highly sensitive to the location where the position and velocity sensors are placed to acquire the necessary feedback signals. If this location is different from the location where the controlling torque is applied, controller-1 destabilizes the closed-loop system.
Alleviating the Constant Stochastic Variance Assumption in Decision Research: Theory, Measurement, and Experimental Test
Authors: Salisbury Linda Court , Feinberg Fred M.
Published: November 2009

Analysts often rely on methods that presume constant stochastic variance, even though its degree can differ markedly across experimental and field settings. This reliance can lead to misestimation of effect sizes or unjustified theoretical or behavioral inferences. Classic utility-based discrete-choice theory makes sharp, testable predictions about how observed choice patterns should change when stochastic variance differs across items, brands, or conditions. We derive and examine the implications of assuming constant stochastic variance for choices made under different conditions or at different times, in particular, whether substantive effects can arise purely as artifacts. These implications are tested via an experiment designed to isolate the effects of stochastic variation in choice behavior. Results strongly suggest that the stochastic component should be carefully modeled to differ across both available brands and temporal conditions, and that its variance may be relatively greater for choices made for the future. The experimental design controls for several alternative mechanisms (e.g., flexibility seeking), and a series of related models suggest that several econometrically detectable explanations like correlated error, state dependence, and variety seeking add no explanatory power. A series of simulations argues for appropriate flexibility in discrete-choice specification when attempting to detect temporal stochastic inflation effects.
The Length of Product Line in Distribution Channels
Authors: Liu Yunchuan , Cui Tony Haitao
Published: November 2009

This paper studies a manufacturer's optimal decisions on extending its product line when the manufacturer sells through either a centralized channel or a decentralized channel. We show that a manufacturer may provide a longer product line for consumers in a decentralized channel than in a centralized channel if the market is fully covered. In addition, a manufacturer's decisions on the length of its product line may not always be optimal from a social welfare perspective in either a centralized or a decentralized channel. Under certain conditions, a decentralized channel can provide the product line length that is socially optimal, whereas a centralized channel cannot.
Prevalence and Risk Factors for Acute Kidney Injury Associated with Parenteral Polymyxin B Use
Authors: Mendes Carlos AC , Cordeiro José A , Burdmann Emmanuel A
Published: November 2009

Background:

The main adverse effect of polymyxin B is nephrotoxicity. There are few data on polymyxin-associated renal injury.

Objective:

To assess the prevalence of and risk factors for acute kidney injury (AKI) in patients treated with polymyxin B.

Methods:

The studied population included 114 patients who received at least 3 consecutive days of intravenous polymyxin B and had baseline serum creatinine (SCr) and at least one further SCr measurement during treatment. AKI was defined as an SCr increase to 1.8 mg/dL or greater in patients with baseline SCr less than 1.5 mg/dL, or an increase greater than or equal to 50% in baseline SCr when it was already greater than or equal to 1.5 mg/dL, or need for dialysis.

Results:

AKI developed in 22% of the patients. They were older, had a higher baseline SCr, had a higher frequency of baseline SCr greater than or equal to 1.5 mg/dL, used other nephrotoxic drugs and furosemide more often, and required vasoactive drugs and mechanical ventilation more frequently. Progression to renal failure was significantly more probable when the bacteria were isolated in the abdomen, catheter, or blood. AKI patients had a higher mortality rate (92% vs 53%; p < 0.001). Logistic regression identified abnormal baseline SCr (odds ratio [OR] 3.51); need for vasoactive drugs (OR 3.03); and abdomen, blood, or catheter as the infection site (OR 3.82) as independent risk factors for AKI.

Conclusions:

Patients who developed AKI had a strikingly elevated mortality rate. Polymyxin B should be used with extreme caution in patients who have an abnormal baseline SCr; use vasoactive drugs; or have abdomen, blood, or catheter as the infection site.
Role of reaction media in "green" radiation-induced polymerization of white phosphorus
Authors: Tarasova Natalia P. , Smetannikov Yury V. , Vilesov Alexander S. , Zanin Alexey A.
Published: November 2009

Phosphorus-containing polymers were synthesized using a "green" radiation-induced reaction at room temperature in the presence of ionic liquids (ILs). The nature of ILs allowed us to adjust the properties of reaction media (dimethyl sulfoxide, DMSO–benzene solvents). The effects of various factors on the efficiency of the synthesis of phosphorus-containing polymers are discussed.
Basic ionic liquids based on monoquaternized 1,4-diazobicyclo[2.2.2]octane (dabco) and dicyanamide anion: Physicochemical and solvent properties
Authors: Chiappe Cinzia , Melai Bernardo , Sanzone Angelo , Valentini Giulia
Published: November 2009

In this paper, we report on the synthesis and application of monosubstituted diazabicyclo[2.2.2]octane (dabco) cations associated with a basic anion, dicyanamide. Key properties of these salts—phase transitions, density, and conductivity—were measured and compared to those of other common ionic liquids (ILs). Moreover, solvatochromic dyes were used to assess their solvation properties. The Heck cross-coupling reaction was evaluated in dabco-based ILs and compared with the behavior in common unfunctionalized ILs, evidencing good catalyst stability and a high recyclability in these basic ILs.
Sexual dimorphism in cortical bone size and strength but not density is determined by independent and time-specific actions of sex steroids and IGF-1: Evidence from pubertal mouse models
Authors: Callewaert Filip , Venken Katrien , Kopchick John J , Torcasio Antonia , van Lenthe G Harry , Boonen Steven , Vanderschueren Dirk
Published: November 2009

Although it is well established that males acquire more bone mass than females, the underlying mechanism and timing of this sex difference remain controversial. The aim of this study was to assess the relative contribution of sex steroid versus growth hormone–insulin-like growth factor 1 (GH–IGF-1) action to pubertal bone mass acquisition longitudinally in pubertal mice. Radial bone expansion peaked during early puberty (3 to 5 weeks of age) in male and female mice, with significantly more expansion in males than in females (+40%). Concomitantly, in 5 week old male versus female mice, periosteal and endocortical bone formation was higher (+70%) and lower (−47%), respectively, along with higher serum IGF-1 levels during early puberty in male mice. In female mice, ovariectomy increased radial bone expansion during early puberty as well as the endocortical perimeter. In male mice, orchidectomy reduced radial bone expansion only during late puberty (5 to 8 weeks of age), whereas combined androgen and estrogen deficiency modestly decreased radial bone expansion during early puberty, accompanied by lower IGF-1 levels. GHRKO mice with very low IGF-1 levels, on the other hand, showed limited radial bone expansion and no skeletal dimorphism. From these data we conclude that skeletal sexual dimorphism is established during early puberty and depends primarily on GH–IGF-1 action. In males, androgens and estrogens have stimulatory effects on bone size during late and early puberty, respectively. In females, estrogens limit bone size during early puberty. These longitudinal findings in mice provide strong evidence that skeletal dimorphism is determined by independent and time-specific effects of sex steroids and IGF-1. © 2010 American Society for Bone and Mineral Research
Living on the Ring of Fire: Perspectives on Managing Natural Hazard Risk in Pacific Rim Countries
Authors: Paton Douglas
Published: November 2009

From the perspective of studying natural hazards, the peace and tranquillity that might be expected from a literal translation of its name does not always capture the reality of life for communities on the Pacific Rim. This reality is more readily discerned in its alter ego: the Ring of Fire. The latter leaves one in less doubt as to the hazardous circumstances likely to prevail in this region. In addition to the hazards posed by the numerous volcanoes that resulted in the ‘Ring of Fire’ appellation, communities situated around the Pacific Rim also have to contend with earthquakes, tsunami, storms, cyclones/typhoons, flood and bushfire. To this list of acute events can be added hazards of a chronic nature such as salinity, environmental degradation and sea-level rise that represent growing threats to many Pacific Rim countries. The region also faces increased risk from health-related hazards. Sydney, for example, has been identified as a pandemic hotspot as a result of it being a hub linking the airways of Asia and the United States.
Is Externality a Mediator of Experience–Behaviour and Information–Action Hypothesis in Disaster Preparedness?
Authors: Mishra Sasmita , Suar Damodar , Paton Douglas
Published: November 2009

This study examines whether disaster experience and awareness, mediated by external locus of control, influence disaster preparedness behavior. Data were collected from 300 people in flood-prone and a further 300 in heat-wave affected areas in Orissa (a state situated in south-eastern part of India). Results reveal that prior experience of hazard events and knowledge of protective actions significantly facilitates flood and heat-wave preparedness. However, locus of control mediates this relationship. Disaster experienced and aware people characterised by having an external control were less prepared. External control partially mediates between experience–behaviour and information–action link. These findings suggest that the effects of personal experience and awareness on self-protective behaviour are weakened by external attribution.
Managing Tsunami Risk: Social Context Influences on Preparedness
Authors: Paton Douglas , Houghton Bruce F. , Gregg Chris E. , McIvor David , Johnston David M. , Bürgelt Petra , Larin Penny , Gill Duane A. , Ritchie Liesel A. , Meinhold Steven , Horan Jennifer
Published: November 2009

This article describes the testing of a model that proposes that people's beliefs regarding the effectiveness of hazard preparedness interact with social context factors (community participation, collective efficacy, empowerment and trust) to influence levels of hazard preparedness. Using data obtained from people living in coastal communities in Alaska and Oregon that are susceptible to experiencing tsunami, structural equation modelling analyses confirmed the ability of the model to help account for differences in levels of tsunami preparedness. Analysis revealed that community members and civic agencies influence preparedness in ways that are independent of the information provided per se. The model suggests that, to encourage people to prepare, outreach strategies must (a) encourage community members to discuss tsunami hazard issues and to identify the resources and information they need to deal with the consequences a tsunami would pose for them and (b) ensure that the community-agency relationship is complementary and empowering.
Globalization and African cinema: distribution and reception in the anglophone region
Authors: Mhando Martin
Published: November 2009

When Tommy Lott advanced his 'no-theory theory' on the definition of black cinema, he argued that a theory remains a theory only up to the time when the meanings it advances 'are no longer applicable'. He was aware of the complexity of theorizing on an ongoing activity based on an essentialized
notion.

What I see as a possible arena of contention and re-theorizing is the versatility of cultures in appropriating processes of knowledge distribution. What I am advocating here is seeing the film and video distribution practices that continue to grow in Africa as loci of sociological
and ontological questionings. Is the experience of media within cultures dependent on exposure to western media concepts? Isn't exposure itself merely a limited rather than a limiting experience? How far are 'appropriations' related to media sociality? How do community media express themselves
outside the boundaries of expectations and definitions of authoritative media?
Beyond colonial stereotypes: reflections on postcolonial cinema in the African Great Lakes region
Authors: Nkunzimana Obed
Published: November 2009

The African Great Lakes region – Rwanda, Burundi and Congo-Kinshasa – is usually remembered for its social upheavals and fratricidal wars, rarely for film-making. Moreover, some cinema critics recognize that in the region, like in other African countries, many contemporary
films remain subtly informed by colonial clichés and western sponsors' unilateral choices, with little or no consideration for African film-makers' interests and needs. First, the article describes the core of colonial cinema with its stereotypical and sensationalist images, which are
the ingredients likely to stir western audiences. Second, through the analysis of some representative films, it shows how the colonial-inspired marketable clichés surreptitiously inform today's film-making. Finally, and most importantly, this enquiry examines films that embody what
may be defined as milestones of postcolonial imagination in the region. The conclusion points to production initiatives and to more freedom in the choice of topics.
The rise of the African musical: postcolonial disjunction in Karmen Geï and Madame Brouette
Authors: Petty Sheila
Published: November 2009

This essay explores the rise of the film musical as a unique vehicle for artistic expression by African film-makers. In particular, the essay deals with the films, Karmen Geï and Madame Brouette and considers the ways in which both films employ this genre as a means
of investigating social and political issues affecting postcolonial Senegalese culture. Furthermore, the African musical brings with it new ideological, visual and narrative strategies that are expanding the cinematic grammar of African cinema and creating a hybridized form. The essay demonstrates
how both films engage spectators in the struggle for existence within the postcolonial context, and by foregrounding the complexities of that struggle, create a debate and a call to action that seeks solutions from within African perspectives.
Stimulus-Induced and State-Dependent Sustained Gamma Activity Is Tightly Coupled to the Hemodynamic Response in Humans
Authors: Koch Stefan P. , Werner Peter , Steinbrink Jens , Fries Pascal , Obrig Hellmuth
Published: November 2009

A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus–response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35–70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging.