bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial dysfunction after subarachnoid haemorrhage and tako-tsubo cardiomyopathy: a differential diagnosis?
Authors: Trio Olimpia , de Gregorio Cesare , Andò Giuseppe
Published: February 2010

The frequent occurrence of a reversible left ventricular dysfunction complicating subarachnoid haemorrhage raises a number of issues about the clinical and pathophysiological similarities with the transient left ventricular apical ballooning syndrome (TLVABS) or tako-tsubo cardiomyopathy (TTC). Given the latest clinical and pathophysiological evidence about neurogenic cardiomyopathies, the diagnosis of TTC should not be ruled out in patients experiencing acute brain injury and cerebrovascular events. Each type of reversible left ventricular dysfunction mediated by the central nervous system and initiated by acute brain injury, both physical, such as intracranial bleeding or head traumas, and psychological, such as sudden emotional stress, could be encompassed in a single definition with larger inclusion criteria, such as ‘acute ballooning cardiomyopathy’ (ABC), that is likely to be more representative of the real needs in the clinical setting.
Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells
Authors: Sinclair Angus M. , Coxon Angela , McCaffery Ian , Kaufman Stephen , Paweletz Katherine , Liu Liqin , Busse Leigh , Swift Susan , Elliott Steven , Begley C. Glenn
Published: February 2010

Erythropoiesis stimulating agents (ESAs) have been reported to activate erythropoietin receptors (EpoR) on cell types, including endothelial, neuronal, renal tubule, and cardiac cells. ESAs have also been reported to promote angiogenesis. However, those findings are controversial and confounded by methodologic issues. We show that EpoR mRNA was detected in essentially all cell types examined, including primary human endothelial, renal, cardiac, and neuronal cells but 10- to 100-fold lower than Epo-responsive cells using quantitative reverse-transcribed polymerase chain reaction. Total endothelial EpoR protein examined using a new monoclonal antibody was low to undetectable. Surface EpoR on endothelial cells was not detected using [125I]-rHuEpo surface-binding studies. There was no evidence of ESA-induced intracellular signaling in endothelial cells. There was a similar lack of EpoR expression and signaling in other cell types examined. Experiments were performed examining ESA function on these cells. An in vivo rat corneal angiogenesis assay demonstrated neo-vessel formation in response to recombinant human vascular endothelial growth factor (rHuVEGF). However, recombinant mouse Epo did not induce vessel formation. Similarly, ESAs did not reproducibly provide cytoprotection to neuronal, renal, or cardiac cells. Taken together, our data challenge the notion of presence or function of EpoR on nonhematopoietic cells, and call into question the preclinical basis for clinical studies exploring direct, “pleiotropic” actions of ESAs.
Superior results of Total Therapy 3 (2003-33) in gene expression profiling–defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance
Authors: Nair Bijay , van Rhee Frits , Shaughnessy John D. , Anaissie Elias , Szymonifka Jackie , Hoering Antje , Alsayed Yazan , Waheed Sarah , Crowley John , Barlogie Bart
Published: February 2010

The Total Therapy 3 trial 2003-33 enrolled 303 newly diagnosed multiple myeloma patients and was noted to provide superior clinical outcomes compared with predecessor trial Total Therapy 2, especially in gene expression profiling (GEP)–defined low-risk disease. We report here on the results of successor trial 2006-66 with 177 patients, using bortezomib, lenalidomide, and dexamethasone maintenance for 3 years versus bortezomib, thalidomide, and dexamethasone in year 1 and thalidomide/dexamethasone in years 2 and 3 in the 2003-33 protocol. Overall survival (OS) and event-free survival (EFS) plots were super-imposable for the 2 trials, as were onset of complete response and complete response duration (CRD), regardless of GEP risk. GEP-defined high-risk designation, pertinent to 17% of patients, imparted inferior OS, EFS, and CRD in both protocols and, on multivariate analysis, was the sole adverse feature affecting OS, EFS, and CRD. Mathematical modeling of CRD in low-risk myeloma predicted a 55% cure fraction (P < .001). Despite more rapid onset and higher rate of CR than in other molecular subgroups, CRD was inferior in CCND1 without CD20 myeloma, resembling outcomes in MAF/MAFB and proliferation entities. The robustness of the GEP risk model should be exploited in clinical trials aimed at improving the notoriously poor outcome in high-risk disease.
Monkey hybrid stem cells develop cellular features of Huntington's disease
Authors: Laowtammathron Chuti , Cheng Eric CH , Cheng Pei-Hsun , Snyder Brooke R , Yang Shang-Hsun , Johnson Zach , Lorthongpanich Chanchao , Kuo Hung-Chih , Parnpai Rangsun , Chan Anthony WS
Published: February 2010

Background

Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research.

Results

To test this hypothesis, a pluripotent Huntington's disease monkey hybrid cell line (TrES1) was established from a tetraploid Huntington's disease monkey blastocyst generated by the fusion of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological features that paralleled neural development. It expressed mutant huntingtin and stem cell markers, was capable of differentiating to neural cells, and developed teratoma in severely compromised immune deficient (SCID) mice. Interestingly, the expression of mutant htt, the accumulation of oligomeric mutant htt and the formation of intranuclear inclusions paralleled neural development in vitro , and even mutant htt was ubiquitously expressed. This suggests the development of Huntington's disease cellular features is influenced by neural developmental events.

Conclusions

Huntington's disease cellular features is influenced by neural developmental events. These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis.
Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole
Authors: Ferrari-Toninelli Giulia , Maccarinelli Giuseppina , Uberti Daniela , Buerger Erich , Memo Maurizio
Published: February 2010

Background

Pramipexole exists as two isomers. The S(-) enantiomer is a potent D3/D2 receptor agonist and is extensively used in the management of PD. In contrast, the R(+) enantiomer is virtually devoid of any of the DA agonist effects. Very limited studies are available to characterize the pharmacological spectrum of the R(+) enantiomer of pramipexole.

Results

Using differentiated SH-SY5Y neuroblastoma cells as an experimental model, here we show that S(-) and R(+) pramipexole are endowed with equipotent efficacy in preventing cell death induced by H2O2 and inhibiting mitochondrial reactive oxygen species generation. Both pramipexole enantiomers prevented mitochondrial ROS generation with a potency about ten times higher then that elicited for neuroprotection.

Conclusions

These results support the concept of both S(-) and R(+) pramipexole enantiomers as mitochondria-targeted antioxidants and suggest that the antioxidant, neuroprotective activity of these drugs is independent of both the chiral 6-propylamino group in the pramipexole molecule and the DA receptor stimulation.
Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells
Authors: Zheng Liduan , Jiang Guosong , Mei Hong , Pu Jiarui , Dong Jihua , Hou Xiaohua , Tong Qiangsong
Published: February 2010

Background

Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells.

Methods

Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The in vitro invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells.

Results

Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the in vitro invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the in vitro angiogenesis of cancer cells in a dose-dependent manner.

Conclusions

These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells in vitro, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer.
Heterologous expression of leader-less pga gene in Pichia pastoris: intracellular production of prokaryotic enzyme
Authors: Marešová Helena , Marková Zdena , Valešová Renáta , Sklenář Jan , Kyslík Pavel
Published: February 2010

Background

Penicillin G acylase of Escherichia coli (PGAEc) is a commercially valuable enzyme for which efficient bacterial expression systems have been developed. The enzyme is used as a catalyst for the hydrolytic production of β-lactam nuclei or for the synthesis of semi-synthetic penicillins such as ampicillin, amoxicillin and cephalexin. To become a mature, periplasmic enzyme, the inactive prepropeptide of PGA has to undergo complex processing that begins in the cytoplasm (autocatalytic cleavage), continues at crossing the cytoplasmic membrane (signal sequence removing), and it is completed in the periplasm. Since there are reports on impressive cytosolic expression of bacterial proteins in Pichia, we have cloned the leader-less gene encoding PGAEc in this host and studied yeast production capacity and enzyme authenticity.

Results

Leader-less pga gene encoding PGAEcunder the control of AOX1 promoter was cloned in Pichia pastoris X-33. The intracellular overproduction of heterologous PGAEc(hPGAEc) was evaluated in a stirred 10 litre bioreactor in high-cell density, fed batch cultures using different profiles of transient phases. Under optimal conditions, the average volumetric activity of 25900 U l-1 was reached. The hPGAEc was purified, characterized and compared with the wild-type PGAEc. The α-subunit of the hPGAEc formed in the cytosol was processed aberrantly resulting in two forms with C- terminuses extended to the spacer peptide. The enzyme exhibited modified traits: the activity of the purified enzyme was reduced to 49%, the ratios of hydrolytic activities with cephalexin, phenylacetamide or 6-nitro-3-phenylacetylamidobenzoic acid (NIPAB) to penicillin G increased and the enzyme showed a better synthesis/hydrolysis ratio for the synthesis of cephalexin.

Conclusions

Presented results provide useful data regarding fermentation strategy, intracellular biosynthetic potential, and consequences of the heterologous expression of PGAEc in P. pastoris X-33. Aberrant processing of the precursor of PGAEc in the cytosol yielded the mature enzyme with modified traits.
Determinants of compliance with malaria chemoprophylaxis among French soldiers during missions in inter-tropical Africa
Authors: Resseguier Noémie , Machault Vanessa , Ollivier Lénaick , Orlandi-Pradines Eve , Texier Gaetan , Pradines Bruno , Gaudart Jean , Buguet Alain , Tourette-Turgis Catherine , Rogier Christophe
Published: February 2010

Background

The effectiveness of malaria chemoprophylaxis is limited by the lack of compliance whose determinants are not well known.

Methods

The compliance with malaria chemoprophylaxis has been estimated and analysed by validated questionnaires administered before and after the short-term missions (about four months) in five tropical African countries of 2,093 French soldiers from 19 military companies involved in a prospective cohort study. "Correct compliance" was defined as "no missed doses" of daily drug intake during the entire mission and was analysed using multiple mixed-effect logistic regression model.

Results

The averaged prevalence rate of correct compliance was 46.2%, ranging from 9.6%to 76.6% according to the companies. Incorrect compliance was significantly associated with eveningness (p = 0.028), a medical history of clinical malaria (p < 0.001) and a perceived mosquito attractiveness inferior or superior to the others (p < 0.007). Correct compliance was significantly associated with the systematic use of protective measures against mosquito bites (p < 0.001), the type of military operations (combat vs. training activities, p < 0.001) and other individual factors (p < 0.05).

Conclusions

The identification of circumstances and profiles of persons at higher risk of lack of compliance would pave the way to specifically targeted strategies aimed to improve compliance with malaria chemoprophylaxis and, therefore, its effectiveness.
Activity-based protein profiling of the hepatitis C virus replication in Huh-7 hepatoma cells using a non-directed active site probe
Authors: Singaravelu Ragunath , Blais David R , McKay Craig S , Pezacki John Paul
Published: February 2010

Background

Hepatitis C virus (HCV) poses a growing threat to global health as it often leads to serious liver diseases and is one of the primary causes for liver transplantation. Currently, no vaccines are available to prevent HCV infection and clinical treatments have limited success. Since HCV has a small proteome, it relies on many host cell proteins to complete its life cycle. In this study, we used a non-directed phenyl sulfonate ester probe (PS4≡) to selectively target a broad range of enzyme families that show differential activity during HCV replication in Huh-7 cells.

Results

The PS4≡ probe successfully targeted 19 active proteins in nine distinct protein families, some that were predominantly labeled in situ compared to the in vitro labeled cell homogenate. Nine proteins revealed altered activity levels during HCV replication. Some candidates identified, such as heat shock 70 kDa protein 8 (or HSP70 cognate), have been shown to influence viral release and abundance of cellular lipid droplets. Other differentially active PS4≡ targets, such as electron transfer flavoprotein alpha, protein disulfide isomerase A5, and nuclear distribution gene C homolog, constitute novel proteins that potentially mediate HCV propagation.

Conclusions

These findings demonstrate the practicality and versatility of non-directed activity-based protein profiling (ABPP) to complement directed methods and accelerate the discovery of altered protein activities associated with pathological states such as HCV replication. Collectively, these results highlight the ability of in situ ABPP approaches to facilitate the identification of enzymes that are either predominantly or exclusively labeled in living cells. Several of these differentially active enzymes represent possible HCV-host interactions that could be targeted for diagnostic or therapeutic purposes.
Performance of circulating cathodic antigen (CCA) urine-dipsticks for rapid detection of intestinal schistosomiasis in schoolchildren from shoreline communities of Lake Victoria
Authors: Standley CJ , Lwambo NJS , Lange CN , Kariuki HC , Adriko M , Stothard JR
Published: February 2010

For disease surveillance and mapping within large-scale control programmes, RDTs are becoming popular. For intestinal schistosomiasis, a commercially available urine-dipstick which detects schistosome circulating cathodic antigen (CCA) in host urine is being increasingly applied, however, further validation is needed. In this study, we compared the CCA urine-dipstick test against double thick Kato-Katz faecal smears from 171 schoolchildren examined along the Tanzanian and Kenyan shorelines of Lake Victoria. Diagnostic methods were in broad agreement; the mean prevalence of intestinal schistosomiasis inferred by Kato-Katz examination was 68.6% (95% confidence intervals (CIs) = 60.7-75.7%) and 71.3% (95% CIs = 63.9-78.8%) by CCA urine-dipsticks. There were, however, difficulties in precisely 'calling' the CCA test result, particularly in discrimination of 'trace' reactions as either putative infection positive or putative infection negative, which has important bearing upon estimation of mean infection prevalence; considering 'trace' as infection positive mean prevalence was 94.2% (95% CIs = 89.5-97.2%). A positive association between increasing intensity of the CCA urine-dipstick test band and faecal egg count was observed. Assigning trace reactions as putative infection negative, overall diagnostic sensitivity (SS) of the CCA urine-dipstick was 87.7% (95% CIs = 80.6-93.0%), specificity (SP) was 68.1% (95% CIs = 54.3-80.0%), positive predictive value (PPV) was 86.1% (95% CIs = 78.8-91.7%) and negative predictive value (NPV) was 71.1% (95% CIs = 57.2-82.8%). To assist in objective defining of the CCA urine-dipstick result, we propose the use of a simple colour chart and conclude that the CCA urine-dipstick is a satisfactory alternative, or supplement, to Kato-Katz examination for rapid detection of intestinal schistosomiasis.
Identification of complex metabolic states in critically injured patients using bioinformatic cluster analysis
Authors: Cohen Mitchell J , Grossman Adam D , Morabito Diane , Knudson M Margaret , Butte Atul J , Manley Geoffrey T
Published: February 2010

Introduction

Advances in technology have made extensive monitoring of patient physiology the standard of care in intensive care units (ICUs). While many systems exist to compile these data, there has been no systematic multivariate analysis and categorization across patient physiological data. The sheer volume and complexity of these data make pattern recognition or identification of patient state difficult. Hierarchical cluster analysis allows visualization of high dimensional data and enables pattern recognition and identification of physiologic patient states. We hypothesized that processing of multivariate data using hierarchical clustering techniques would allow identification of otherwise hidden patient physiologic patterns that would be predictive of outcome.

Methods

Multivariate physiologic and ventilator data were collected continuously using a multimodal bioinformatics system in the surgical ICU at San Francisco General Hospital. These data were incorporated with non-continuous data and stored on a server in the ICU. A hierarchical clustering algorithm grouped each minute of data into 1 of 10 clusters. Clusters were correlated with outcome measures including incidence of infection, multiple organ failure (MOF), and mortality.

Results

We identified 10 clusters, which we defined as distinct patient states. While patients transitioned between states, they spent significant amounts of time in each. Clusters were enriched for our outcome measures: 2 of the 10 states were enriched for infection, 6 of 10 were enriched for MOF, and 3 of 10 were enriched for death. Further analysis of correlations between pairs of variables within each cluster reveals significant differences in physiology between clusters.

Conclusions

Here we show for the first time the feasibility of clustering physiological measurements to identify clinically relevant patient states after trauma. These results demonstrate that hierarchical clustering techniques can be useful for visualizing complex multivariate data and may provide new insights for the care of critically injured patients.
Adenosine 5′-Monophosphate-Activated Protein Kinase-Mammalian Target of Rapamycin Cross Talk Regulates Brown Adipocyte Differentiation
Authors: Vila-Bedmar Rocio , Lorenzo Margarita , Fernández-Veledo Sonia
Published: February 2010

Brown adipose tissue (BAT) is considered of metabolic significance in mammalian physiology, because it plays an important role in regulating energy balance. Alterations in this tissue have been associated with obesity and type 2 diabetes. The molecular mechanisms modulating brown adipocyte differentiation are not fully understood. Using a murine brown preadipocyte cell line, primary cultures, and 3T3-L1 cells, we analyzed the contribution of various intracellular signaling pathways to adipogenic and thermogenic programs. Sequential activation of p38MAPK and LKB1-AMPK-tuberous sclerosis complex 2 (TSC2) as well as significant attenuation of ERK1/2 and mammalian target of rapamycin (mTOR)-p70 S6 kinase 1 (p70S6K1) activation was observed through the brown differentiation process. This study demonstrates a critical role for AMPK in controlling the mTOR-p70S6K1 signaling cascade in brown but not in 3T3-L1 adipocytes. We observed that mTOR activity is essential in the first stages of differentiation. Nevertheless, subsequent inhibition of this cascade by AMPK activation is also necessary at later stages. An in vivo study showed that prolonged 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced AMPK activation increases uncoupling protein 1 expression and induces an accumulation of brown adipocytes in white adipose tissue (WAT), as revealed by immunohistology. Moreover, the induction of brown adipogenesis in areas of white fat partially correlates with the body weight reduction detected in response to treatment with AICAR. Taken together, our study reveals that differentiation of brown adipocytes employs different signaling pathways from white adipocytes, with AMPK-mTOR cross talk a central mediator of this process. Promotion of BAT development in WAT by pharmacological activation of AMPK may have potential in treating obesity by acting on energy dissipation.
Three-dimensional organization of promyelocytic leukemia nuclear bodies
Authors: Lang Marion , Jegou Thibaud , Chung Inn , Richter Karsten , Münch Sandra , Udvarhelyi Anikó , Cremer Christoph , Hemmerich Peter , Engelhardt Johann , Hell Stefan W. , Rippe Karsten
Published: February 2010

Promyelocytic leukemia nuclear bodies (PML-NBs) are mobile subnuclear organelles formed by PML and Sp100 protein. They have been reported to have a role in transcription, DNA replication and repair, telomere lengthening, cell cycle control and tumor suppression. We have conducted high-resolution 4Pi fluorescence laser-scanning microscopy studies complemented with correlative electron microscopy and investigations of the accessibility of the PML-NB subcompartment. During interphase PML-NBs adopt a spherical organization characterized by the assembly of PML and Sp100 proteins into patches within a 50- to 100-nm-thick shell. This spherical shell of PML and Sp100 imposes little constraint to the exchange of components between the PML-NB interior and the nucleoplasm. Post-translational SUMO modifications, telomere repeats and heterochromatin protein 1 were found to localize in characteristic patterns with respect to PML and Sp100. From our findings, we derived a model that explains how the three-dimensional organization of PML-NBs serves to concentrate different biological activities while allowing for an efficient exchange of components.
Phosphorylation of adhesion- and growth-regulatory human galectin-3 leads to the induction of axonal branching by local membrane L1 and ERM redistribution
Authors: Díez-Revuelta Natalia , Velasco Silvia , André Sabine , Kaltner Herbert , Kübler Dieter , Gabius Hans-Joachim , Abad-Rodríguez José
Published: February 2010

Serine phosphorylation of the β-galactoside-binding protein galectin-3 (Gal-3) impacts nuclear localization but has unknown consequences for extracellular activities. Herein, we reveal that the phosphorylated form of galectin-3 (pGal-3), adsorbed to substratum surfaces or to heparan sulphate proteoglycans, is instrumental in promoting axon branching in cultured hippocampal neurons by local actin destabilization. pGal-3 interacts with neural cell adhesion molecule L1, and enhances L1 association with Thy-1-rich membrane microdomains. Concomitantly, membrane-actin linker proteins ezrin-radixin-moesin (ERM) are recruited to the same membrane site via interaction with the intracellular domain of L1. We propose that the local regulation of the L1-ERM-actin pathway, at the level of the plasma membrane, underlies pGal-3-induced axon branching, and that galectin phosphorylation in situ could act as a molecular switch for the axon response to Gal-3.
Analysis and simulation on the bumpy-ridge structure of heavy equipment
Authors: Zhang H , Yan Y , Zhang R
Published: February 2010

The bumpy-ridge structure applied in the field of heavy equipment is analysed based on fracture mechanics and contact theory. At the same time, the elastic—plastic contact of the ridges is simulated using the finite element method. Having been researched, the separated bumpy-ridge structure can be seen as a special integral structure that has a through crack. It was also found that, as long as there are adequate normal forces and treated contact surfaces, this kind of separated structure has the ability to resist detachment and parallel slide. The height of the notch and radius of the contact zone are the foremost indexes affecting the application of the bumpy-ridge technique, and these parameters are influenced by several factors, such as the shape of the ridges, the curvature of the contact point, the distance between neighbouring ridges, etc. The elastic contact of the ridge can be solved completely by the use of theoretical calculation and graphical method. Through comparison with the elastic contact, some principles of the elastic—plastic contact can be obtained with a finite element analysis method. A bumpy-ridge structure has been successfully applied to a 350 MN die forging press and a 360 MN extrusion press in China.
Attempt at unitary magnetorheological finishing for a pierced die cavity
Authors: Han F , Ai F , Wang Y
Published: February 2010

A novel polishing method for a pierced die cavity, unitary magnetorheological finishing (UMRF), was proposed in this study. UMRF used a permanent magnet as the polishing tool, the shape of which was the same as that of the pierced die cavity's polished surface, and the permanent magnet's size was a little smaller than that of the pierced die cavity in order to form a certain gap between them. The magnetic polishing tool absorbed ferrite particles and abrasives, which were suspended in the magnetorheological (MR) fluid. This was done in order to polish the surface of the pierced die cavity by a high-frequency reciprocating movement occurring along the die cavity surface. Owing to its shape adaptability and high flexibility, this method accomplished a unitary polishing. The whole inner cavity surface was polished in one working cycle. The polishing technology used in this method was also studied, and the influence of the MR fluid concentration, the polishing gap, the reciprocating linear velocity, and the stroke of the polishing tool on the polishing performance was investigated. The experimental results clearly showed that UMRF was an effective polishing method that polished the whole inner cavity surface to a mirror-like finish. At present, this achieved a surface polish, Ra of 42 nm.
Parameter study of stretch—blow moulding process of polyethylene terephthalate bottles using finite element simulation
Authors: Bagherzadeh S , Biglari F R , Nikbin K
Published: February 2010

In this paper, the analysis of the stretch—blow moulding (SBM) process of polyethylene terephthalate (PET) bottles is studied by the finite element method (FEM). In this simulation, owing to the symmetry of bottle geometry, the parts are considered as an axisymmetric model. A hyperelastic constitutive behaviour was calibrated using material data available in literature in variant high temperatures and strain rates and was used in the numerical simulation. Hydrostatic pressure with convention heat transfer has been used instead of a blowing process. Comparisons of numerical results with experimental observations demonstrate that the model can predict an overall trend of thickness distribution, especially in regions between 30 mm to 90 mm from the bottle bottom. However, some differences can be seen in regions 10 mm and 125 mm. These results can be used for an overall prediction of bottle properties such as final bottle thickness and a defect-free production because they are governed by orientation and crystallinity, which are highly temperature and strain dependent. Also, with definition of the critical area in bottle forming, the parametric studies are conducted on the effect of friction condition, heat transfer coefficient, and initial pre-blowing air entrance time delay on bottle thickness. Through the study, it becomes clear that the proposed model is applicable for simulating the stretch-blow moulding process of PET bottles, and is capable of offering helpful knowledge in the production of bottles and the design of an optimum preform.
Preliminary study of the effects of crystal orientation of a CVD monocrystalline diamond in micromilling of Ti—6Al—4V
Authors: Butler-Smith P W , Axinte D A , Limvachirakom V
Published: February 2010

Monocrystalline diamond structures (synthetic and naturally occurring), offer the potential to exploit the anisotropic characteristics of this material in cutting tools by enabling the best crystallographic orientation to be selected to suit the application conditions of the tool. This paper investigates the performance of monocrystalline chemical vapour deposition (CVD) diamond tools in micromilling of a titanium based alloy, Ti—6Al—4V. A comparison of single-blade milling cutters using two different crystallographic orientations is made on a high-precision four-axis miniature machine tool. Employing the cutting edges of the monocrystalline diamond with the rake/flank faces of {100}/{110} and {110}/{100} orientations respectively, the progressive wear of the tools has been micrographed, the coincidental workpiece surface quality assessed, and machined chips inspected. Examinations using scanning electron microscopy reveal clear differences in the predominant failure modes of the cutting edges: the {110} rake orientation showing abrasion; the {100} rake orientation showing fracture/cleavage. While the measured roughness ( Ra, Rz) of the micromilled workpiece surfaces for the two diamond cutting edge orientations were not significantly different, the surface morphologies show the transition from cutting to tearing and dragging of the workpiece material. The analyses of tool wear and workpiece surface quality proved that monocrystalline CVD diamond cutting edges with preferential crystallographic orientation along rake and clearance faces can be successfully utilized for interrupted cutting operations (i.e. micromilling) of alloys which react with diamond, such as those based on titanium.
Free convection heat and mass transfer flow in a vertical channel with the Dufour effect
Authors: Jha B K , Ajibade A O
Published: February 2010

The purpose of this work is to investigate analytically the free-convection and mass transfer flow in a vertical channel formed by two vertical parallel plates. Fully developed laminar flow was considered with uniform temperature and concentration on the plates. The diffusion-thermo effect was taken into consideration. The velocity, temperature, and concentration profiles were obtained analytically using the Laplace transform technique and were used to compute the shear stress, Nusselt number, and mass flux. The present analytical results were compared with those available in the literature without mass transfer and the diffusion-thermo effect and excellent agreement was observed (Singh, A. K., Gholami, H. R., and Soundalgekar, V. M. Transient free convection flow between two vertical parallel plates. J. Heat Mass Transf., 1996, 31, 329—331.). During the course of computation, it was found that the transient solution at large time coincides with the steady-state solution derived separately. The diffusion-thermo effect is observed to create an anomalous situation in temperature and velocity profiles for small Prandtl numbers. The study also revealed that the steady state of the problem is independent of the Dufour effect.
Modelling and simulation of a two-axis tracking system
Authors: Zhao Z M , Yuan X Y , Guo Y , Xu F , Li Z G
Published: February 2010

In this paper, the modelling and simulation of a two-axis tracking system are introduced. First, dynamic modelling of a two-axis tracking system that is based on the Lagrange-Maxwell dynamic equation is presented. According to the established dynamic equation the coupling of system velocity and the inertia characteristics between the two axes are analysed. Then, the controller of the tracking system is designed using the inverse system method. Based on a certain type two-axis tracking system, the simulation is then made with MATLAB/Simulink, which includes position tracking and tracking error analysis. The simulation using Adams and Simulink is also presented. A comparison of the results from the two kinds of simulation indicates that the modelling of the two-axis tracking system is reasonable and the simulation results are rational.
Optimal control using derivative feedback for linear systems
Authors: Abdelaziz T H S
Published: February 2010

This paper presents the solution of the linear optimal control problem using derivative feedback for continuous, time-invariant, linear systems. The state-derivative and output-derivative feedback controllers are investigated. In this work, the optimal feedback gain matrices are derived which minimize the non-standard quadratic performance index. An explicit expression of the optimal state-derivative feedback gain is derived. Additionally, a convergent algorithm to solve the output-derivative feedback gains is demonstrated. The problems are studied for non-singular and singular open-loop state matrices. The necessary conditions for the existence of optimal gains are established. Finally, simulation results are included to show the effectiveness of the proposed approach.
New insight into the average probability of failure on demand and the probability of dangerous failure per hour of safety instrumented systems
Authors: Innal F , Dutuit Y , Rauzy A , Signoret J-P
Published: February 2010

The aim of this paper is to give a new insight into some fundamental concepts of the IEC 61508 standard. First, low and high or continuous demand modes of operation of safety instrumented systems are examined by analysing their official definitions given in the IEC 61508 and IEC 61511 standards. In this context, the paper proposes a new criterion for distinguishing these two modes of operation. A study allowing the determination of accident frequency is also presented, where the system under study consists of one element under control and its associated safety instrumented system. Second, the relationship between the average probabilities of failure on demand and the risk reduction factor is studied. It is shown that the commonly used approach (the standard approach) may lead to an optimistic value for the risk reduction factor. Finally, the paper clarifies the nature of the probability of failure per hour of a safety instrumented system and proposes different ways to compute this in the general case, based on fault tree, Markov model, and Petri nets approaches.
How Much Demand Should Be Fulfilled?
Authors: Sapra Amar , Truong Van-Anh , Zhang Rachel Q.
Published: February 2010

We study the inventory replenishment of a product whose demand can be manipulated by restricting the supply. This research is motivated by a novel marketing tactic employed by manufacturers of fashion and luxury items. Such a tactic combines innovative marketing with deliberate understocking in an attempt to create shortages (i.e., waitlists) that add to the allure and sense of exclusivity of a product and stimulate its demand. We model the problem as a finite-horizon, periodic-review system where demand in each period is a decreasing function of the net ending inventory in the previous period. Although the optimal structure can be complex in general, under certain conditions we are able to characterize the optimal policy as a state-dependent, monotone, base-stock policy. We compare this policy with the optimal policy for the case in which demand is independent of the net inventory. We also show that understocking is optimal in various scenarios. We then propose a novel strategy, called the inventory-withholding strategy, to further explore the wait-list effect by making customers wait even when there is inventory on hand to satisfy them. Our numerical experiments study the impact of various model parameters in combination with the wait-list effect on the optimal policy and the corresponding expected profits.
Contractualism and social inclusion: strands of policy emulation in UK and Australian local employment services
Authors: Carson Ed , Kerr Lorraine
Published: February 2010

Over the past decade, the dominance of ‘new localism’, ‘partnerships’ and ‘social inclusion’ in policy discourse in countries of the Organisation for Economic Co-operation and Development (OECD) has influenced Australian stated policy directions in employment services. In contrast to other OECD countries, however, Australian federal legislators have excluded local government in contractual service delivery and governance arrangements. In response, some Australian local governments draw on UK practice to guide social inclusion agendas and inclusive partnership models. There is irony in such use of policy transfer strategies given that the UK is currently reforming public employment services to emphasise the contractualism that typifies the Australian Job Network.
Patients' Benefit-Risk Preferences for Chronic Idiopathic Thrombocytopenic Purpura Therapies
Authors: Hauber A Brett , Johnson F Reed , Grotzinger Kelly M , Özdemir Semra
Published: February 2010

Background:

Idiopathic thrombocytopenic purpura (ITP) primarily is a disorder of adults characterized by autoantibody-induced platelet destruction and reduced platelet production, leading to a low peripheral blood platelet count. The long-term management of many patients with chronic ITP is unsatisfactory, largely due to the variable efficacy and risks of severe adverse effects associated with current treatment options.

Objective:

To estimate patients' benefit-risk preferences for treatments for ITP.

Methods:

Patients' adverse event risk tolerance and the levels of benefit required to offset possible risks were evaluated using choice-format conjoint analysis. Subjects chose between pairs of hypothetical treatment alternatives defined by probability of achieving safe platelet levels, need for corticosteroids, mode of administration, risk of rebound, risk of elevated liver enzyme levels, and risk of thromboembolism.

Results:

In this study, we demonstrate that patients have clear and measurable benefit-risk preferences that physicians should consider when discussing treatment options with their patients. Patients were willing to accept significant risks of adverse events in return for an increase in the probability of achieving safe platelet levels, to avoid corticosteroids, and for more convenient administration. Patients were willing to accept significant risks of rebound and elevated liver enzymes for improvements in outcomes.

Conclusions:

These results demonstrate that patients with ITP are willing to accept treatment-related risks in exchange for improvements in treatment efficacy and administration attributes and suggest the importance of considering a patient's benefit-risk preferences during discussions of therapeutic options.
Takotsubo Cardiomyopathy, or Broken-Heart Syndrome
Authors: Nykamp Diane , Titak John Adam
Published: February 2010

Objective:

To report a case of takotsubo cardiomyopathy, also known as apical ballooning syndrome or stress cardiomyopathy.

Case Summary:

A 68-year-old female with a history of hypertension, hyperlipidemia, and anxiety presented with symptoms that mimicked acute coronary syndrome (ACS); the chief symptom was chest tightness. An electrocardiogram showed normal sinus rhythm, with minimal ST elevation in the anterior leads. The patient was initially treated for ST-segment elevation myocardial infarction and symptoms resolved. Coronary angiography ruled out ACS and confirmed a diagnosis of takotsubo cardiomyopathy.

Discussion:

Takotsubo cardiomyopathy is commonly triggered by severe emotional or psychological stress and occurs primarily in postmenopausal women. A reversible contractility abnormality of the left ventricle causes the ventricle to take on a balloon-like appearance; hence the name of tako-tsubo, a Japanese octopus fishing pot that has a narrow neck and a wide midsection. Signs and symptoms of takotsubo cardiomyopathy mimic those of ACS. Takotsubo cardiomyopathy is best diagnosed with coronary angiography, which can rule out blockage. Treatment usually consists of carvedilol and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocking agent it left ventricular ejection fraction is less than 40%. The syndrome is usually spontaneously reversible and cardiovascular function returns to normal after a few weeks.

Conclusions:

Takotsubo cardiomyopathy causes a reversible left ventricle dysfunction which occurs most commonly in postmenopausal women with or without cardiovascular disease. Recognition is detected with coronary angiography. It is thought to primarily be due to an abnormally high sympathetic stimulation after emotional or psychological stress. Treatment consists of an angiotensin-converting enzyme inhibitor and/or beta blocker if needed for left ventricular dysfunction and possibly an anxiolytic agent.
The implicit identity effect: Identity primes, group size, and helping
Authors: Levine Mark. , Cassidy Clare. , Jentzsch Ines.
Published: February 2010

Three studies consider the implicit bystander effect in the light of recent advances in social identity approaches to helping. Drawing on the social identity model of deindividuation effects we argue that the implicit bystander effect is shaped not by the number of others imagined, but by who those others are imagined to be. Studies 1 and 2 demonstrate that, when group membership is primed, increasing group size can facilitate helping in line with the norms and values of the group. Study 3 explores mediation processes in group level helping. As group size increases, female participants react faster to words associated with communalism when others are imagined as women rather than strangers. The paper demonstrates that group size and helping behaviour is qualified by an implicit identity effect.
Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation
Authors: Ohler Anke , Debela Mekdes , Wagner Susanne , Magdolen Viktor , Becker-Pauly Christoph
Published: February 2010

The metalloproteases meprin α and β are expressed in several tissues, leukocytes, and cancer cells. In skin, meprins are located in separate layers of human epidermis indicating distinct physiological functions, supported by effects on cultured keratinocytes. Meprin β induces a dramatic change in cell morphology and a significant reduction in cell number, whereas in vitro evidence suggests a role for meprin α in basal keratinocyte proliferation. Meprins are secreted as zymogens that are activated by tryptic proteolytical processing. Here, we identify human kallikrein-related peptidases (KLKs) 4, 5, and 8 to be specific activators of meprins. KLK5 is capable of activating both metalloproteases. Interestingly, KLK4 and 8 cleave off the propeptide of meprin β only, whereas in contrast plasmin exclusively transforms meprin α to its mature form. Moreover, we show that proKLK7 is processed by meprins. N-terminal sequencing revealed cleavage by meprin β two amino acids N-terminal to mature KLK7. Interestingly, this triggering led to an accelerated activation of the serine protease in the presence of trypsin, but not of other tryptic KLKs, such as KLK2, 4, 5, 8, or 11. In summary, we demonstrate a specific interaction between meprin metalloproteases and kallikrein-related peptidases, revealing possible interactions within the proteolytic web.
Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation
Authors: Malcikova Jitka , Tichy Boris , Damborsky Jiri , Kabathova Jitka , Trbusek Martin , Mayer Jiri , Pospisilova Sarka
Published: February 2010

Sequence-specific DNA binding is the key function through which tumor suppressor p53 exerts transactivation of the downstream target genes, often being impaired in cancer cells by mutations in the TP53 gene. Functional protein microarray technology enables a high-throughput parallel analysis of protein properties within one experiment under the same conditions. Using an array approach, we analyzed the DNA binding activity of wild type p53 protein and of 49 variants. Our results show significant differences in the binding properties between the p53 mutants. The C-terminal mutant R337C displayed the highest DNA binding activity on the array. However, the same mutant showed only a partial activation in the reporter gene assay and almost no activation of downstream target genes after transfection of expression vector into cells lacking endogenous p53. These observations demonstrate that DNA binding itself is not sufficient for activating the p53 target genes in at least some of the p53 mutants and, therefore, in vitro studies might not always reflect in vivo conditions.