bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Machine Direction Orientation Conditions On Properties of Hdpe Films
Authors: Tabatabaei S.H. , Parent L. , Cigana P. , Ajji A. , Carreau P.J.
Published: May 2010

In this study, the effects of machine direction orientation (MDO) conditions on crystalline orientation, morphology, and mechanical performance of a high-density polyethylene film were investigated. The MDO variables studied were feed speed, stretching temperature, draw ratio (DR) as well as annealing temperature. The type of crystals (spherulites or fibrils) and crystallinity of the films were considered using differential scanning calorimetry. The MDO process increased the film crystallinity by 18% and melting temperature (Tm ) by 5°C. The crystalline phase orientation was measured using Fourier transform infrared and wide angle X-ray diffraction. Stretching noticeably increased the crystalline alignment. The Young’s modulus decreased with increasing extrusion temperature and feed speed and enhanced with rising annealing temperature. However, up to DR = 6, the Young’s modulus decreased with draw ratio whereas it increased beyond DR = 6. Upon drawing, the tear resistance along the machine direction decreased significantly, but the puncture resistance along the normal direction increased drastically. Finally, drawing lowered haze for the films dramatically, hence, improved the clarity significantly.
Effect of molybdenum on microstructure and wear properties of Fe–Ti–Mo–C laser clad coatings
Authors: Wang X H , Qu S Y , Du B S , Zou Z D , Wang X R
Published: May 2010

The AISI 1045 steel surface was alloyed with preplaced ferrotitanium (Fe–Ti), ferromolybdenum (Fe–Mo) and graphite powders using a 5 kW CO2 laser. In situ carbide reinforced Fe based surface composite coating was fabricated. The results showed that (Ti,Mo)C particles with flower-like and cubic shapes were formed during laser cladding process. The growth morphology of the reinforcing (Ti,Mo)C carbide has typically faceted features, indicating that the lateral growth mechanism is still the predominant growth mode under rapid solidification conditions. Increasing the amount of Fe–Mo in the reactants led to a decrease in carbide size and an increase in volume fraction of carbide but increased the crack sensitivity of the coating. The multiple carbides of (Ti,Mo)C created a higher microhardness and excellent wear resistance than TiC alone under dry sliding wear test condition.
Studies on influence of reheating temperature and cooling rate on structure–property behaviour of lean chemistry HSLA-100 steel
Authors: Dhua S K
Published: May 2010

Simulation studies on the influence of reheating temperature on austenite grain coarsening in lean chemistry high strength low alloy (HSLA)-100 steel were carried out to establish optimum soaking temperature before hot rolling. Experiments carried out in ‘Gleeble-3500’ dynamic thermomechanical simulator revealed that prior austenite grain sizes varied between 26 and 98 and 34 and 126 μm after soaking at 1150, 1200 and 1250°C for 1 and 5 min respectively; a soaking temperature of 1200°C was found to be optimum. Simulation experiments on the influence of cooling rate on microstructural changes and dilatometric studies indicated lowering of transformation temperature with faster cooling. Microstructural examination of dilatometric samples confirmed martensitic transformation at faster cooling rate. The martensite structure is desirable to achieve better strength and toughness. The findings of simulation studies were subsequently used for standardising thermomechanical treatments of Nb–Cu bearing lean chemistry HSLA-100 steels. One laboratory heat of Cu bearing HSLA steel containing 0·028%Nb was made. This heat was hot rolled into 12·5 mm thick plate by varying finish rolling temperature in the range of 800–1000°C. The soaking temperature was maintained at 1200°C. The rolled plates were heat treated by both conventional reheat quenching and tempering (RQT) as well as direct quenching and tempering (DQT) techniques. Evaluation of mechanical properties revealed that plates processed through DQT route were superior to those processed through RQT route. Transmission electron microscopy revealed that martensite structure and finer interlath spacing in DQT plates resulted in superior strength and impact toughness properties as compared to RQT steels.
Powdery mildew fungal effector candidates share N-terminal Y/F/WxC-motif
Authors: Godfrey Dale , Böhlenius Henrik , Pedersen Carsten , Zhang Ziguo , Emmersen Jeppe , Thordal-Christensen Hans
Published: May 2010

Background

Powdery mildew and rust fungi are widespread, serious pathogens that depend on developing haustoria in the living plant cells. Haustoria are separated from the host cytoplasm by a plant cell-derived extrahaustorial membrane. They secrete effector proteins, some of which are subsequently transferred across this membrane to the plant cell to suppress defense.

Results

In a cDNA library from barley epidermis containing powdery mildew haustoria, two-thirds of the sequenced ESTs were fungal and represented ~3,000 genes. Many of the most highly expressed genes encoded small proteins with N-terminal signal peptides. While these proteins are novel and poorly related, they do share a three-amino acid motif, which we named "Y/F/WxC", in the N-terminal of the mature proteins. The first amino acid of this motif is aromatic: tyrosine, phenylalanine or tryptophan, and the last is always cysteine. In total, we identified 107 such proteins, for which the ESTs represent 19% of the fungal clones in our library, suggesting fundamental roles in haustoria function. While overall sequence similarity between the powdery mildew Y/F/WxC-proteins is low, they do have a highly similar exon-intron structure, suggesting they have a common origin. Interestingly, searches of public fungal genome and EST databases revealed that haustoria-producing rust fungi also encode large numbers of novel, short proteins with signal peptides and the Y/F/WxC-motif. No significant numbers of such proteins were identified from genome and EST sequences from either fungi which do not produce haustoria or from haustoria-producing Oomycetes.

Conclusion

In total, we identified 107, 178 and 57 such Y/F/WxC-proteins from the barley powdery mildew, the wheat stem rust and the wheat leaf rust fungi, respectively. All together, our findings suggest the Y/F/WxC-proteins to be a new class of effectors from haustoria-producing pathogenic fungi.
The effect of flower position on variation and covariation in floral traits in a wild hermaphrodite plant
Authors: Zhao Zhi-Gang , Du Guo-Zhen , Huang Shuang-Quan
Published: May 2010

Background

Floral traits within plants can vary with flower position or flowering time. Within an inflorescence, sexual allocation of early produced basal flowers is often female-biased while later produced distal flowers are male-biased. Such temporal adjustment of floral resource has been considered one of the potential advantages of modularity (regarding a flower as a module) in hermaphrodites. However, flowers are under constraints of independent evolution of a given trait. To understand flower diversification within inflorescences, here we examine variation and covariation in floral traits within racemes at the individual and the maternal family level respectively in an alpine herb Aconitum gymnandrum (Ranunculaceae).

Results

We found that floral traits varied significantly with flower position and among families, and position effects were family-specific. Most of the variance of floral traits was among individuals rather than among flowers within individuals or among families. Significant phenotypic correlations between traits were not affected by position, indicating trait integration under shared developmental regulation. In contrast, positive family-mean correlations in floral traits declined gradually from basal to distal flowers (nine significant correlations among floral traits in basal flowers and only three in distal flowers), showing position-specificity. Therefore, the pattern and magnitude of genetic correlations decreased with flower position.

Conclusions

This finding on covariation pattern in floral reproductive structures within racemes has not been revealed before, providing insights into temporal variation and position effects in floral traits within plants and the potential advantages of modularity in hermaphrodites.
Seroprevalence of Bartonella in Eastern China and analysis of risk factors
Authors: Sun Jimin , Fu Guiming , Lin Junfen , Song Xiuping , Lu Liang , Liu Qiyong
Published: May 2010

Background

Bartonella infections are emerging in the Zhejiang Province of China. However, there has been no effort to date to explore the epidemiology of these infections in this region, nor to identify risk factors associated with exposure to Bartonella. The aim of this study was to investigate the seroprevalence of Bartonella in both patients bitten by dogs and blood donors (for control) in Eastern China, and to identify risk factors associated with exposure to Bartonella. As no previous data for this region have been published, this study will provide baseline data useful for Bartonella infection surveillance, control, and prevention.

Methods

Blood samples were collected from industrial rabies clinic attendees and blood donors living in eight areas of the Zhejiang Province of China, between December 2005 and November 2006. An indirect immunofluorescent antibody test was used to determine the presence of Bartonella in these samples. Risk factors associated with Bartonella exposure were explored using Chi-square tests and logistic regression analysis of epidemiological data relating to the study's participants.

Results

Bartonella antibodies were detected in 19.60% (109/556) of blood samples. Seroprevalence varied among the eight areas surveys, ranging from over 32% in Hangzhou to only 2% in Jiangshan (X2 = 28.22, P < 0.001). We detected a significantly higher prevalence of Bartonella antibodies in people who had been bitten by dogs than in blood donors (X2 = 13.86, P < 0.001). Seroprevalence of Bartonella was similar among males (18.61%, n = 317) and females (20.92%, n = 239).

Conclusions

Bartonella antibodies were encountered in people living across Zhejiang Province and the seropositivity rate among those exposed to dog bites was significantly higher than that among blood donors, indicating that dog bites may be a risk factor for Bartonella infection.
Improving capacity for evidence-based practice in South East Asia: evaluating the role of research fellowships in the SEA-ORCHID Project
Authors: Short Jacki , McDonald Steve , Turner Tari , Martis Ruth ,   the SEA-ORCHID Study Group
Published: May 2010

Background

Fellowships are a component of many professional education programs. They provide opportunities to develop skills and competencies in an environment where time is protected and resources and technical support are more readily available. The SEA-ORCHID fellowships program aimed to increase capacity for evidence-based practice and research synthesis, and to encourage fellows to become leaders in these areas.

Methods

Fellows included doctors, nurses, midwives and librarians working in the maternal and neonatal areas of nine hospitals in South East Asia. Fellowships were undertaken in Australia and involved specific outputs related to evidence-based practice or research synthesis. Training and support was tailored according to the type of output and the fellow's experience and expertise. We evaluated the fellowships program quantitatively and qualitatively through written evaluations, interviews and follow-up of fellowship activities.

Results

During 2006-07, 23 fellows from Thailand, Indonesia, Malaysia and the Philippines undertook short-term fellowships (median four weeks) in Australia. The main outputs were drafts of Cochrane systematic reviews, clinical practice guidelines and protocols for randomised trials, and training materials to support evidence-based practice. Protocols for Cochrane systematic reviews were more likely to be completed than other outcomes. The fellows identified several components that were critical to the program's overall success; these included protected time, tailored training, and access to technical expertise and resources. On returning home, fellows identified a lack of time and limited access to the internet and evidence-based resources as barriers to completing their outputs. The support of colleagues and senior staff was noted as an important enabler of progress, and research collaborators from other institutions and countries were also important sources of support.

Conclusions

The SEA-ORCHID fellowships program provided protected time to work on an output which would facilitate evidence-based practice. While the fellows faced substantial barriers to completing their fellowship outputs once they returned home, these fellowships resulted in a greater understanding, enthusiasm and skills for evidence-based practice. The experience of the SEA-ORCHID fellowships program may be useful for other initiatives aiming to build capacity in evidence-based practice.
Novel approach of high cell density recombinant bioprocess development: Optimisation and scale-up from microlitre to pilot scales while maintaining the fed-batch cultivation mode of E. coli cultures
Authors: Šiurkus Juozas , Panula-Perälä Johanna , Horn Uwe , Kraft Mario , Rimšeliene Renata , Neubauer Peter
Published: May 2010

Background

Bioprocess development of recombinant proteins is time consuming and laborious as many factors influence the accumulation of the product in the soluble and active form. Currently, in most cases the developmental line is characterised by a screening stage which is performed under batch conditions followed by the development of the fed-batch process. Performing the screening already under fed-batch conditions would limit the amount of work and guarantee that the selected favoured conditions also work in the production scale.

Results

Here, for the first time, high throughput multifactorial screening of a cloning library is combined with the fed-batch technique in 96-well plates, and a strategy is directly derived for scaling to bioreactor scale. At the example of a difficult to express protein, an RNase inhibitor, it is demonstrated that screening of various vector constructs and growth conditions can be performed in a coherent line by (i) applying a vector library with promoters and ribosome binding sites of different strength and various fusion partners together with (ii) an early stage use of the fed-batch technology. It is shown that the EnBase®technology provides an easy solution for controlled cultivation conditions in the microwell scale. Additionally the high cell densities obtained provide material for various analyses from the small culture volumes. Crucial factors for a high yield of the target protein in the actual case were (i) the fusion partner, (ii) the use of of a mineral salt medium together with the fed-batch technique, and (iii) the preinduction growth rate. Finally, it is shown that the favorable conditions selected in the microwell plate and shake flask scales also work in the bioreactor.

Conclusions

Cultivation media and culture conditions have a major impact on the success of a screening procedure. Therefore the application of controlled cultivation conditions is pivotal. The consequent use of fed-batch conditons from the first screening phase not only shortens the developmental line by guarantying that the selected conditions are relevant for the scale up, but in our case also standard batch cultures failed to select the right clone or conditions at all.
Image reconstruction of fluorescent molecular tomography based on the tree structured Schur complement decomposition
Authors: Zou Wei , Wang Jiajun , Feng David Dagan
Published: May 2010

Background

The inverse problem of fluorescent molecular tomography (FMT) often involves complex large-scale matrix operations, which may lead to unacceptable computational errors and complexity. In this research, a tree structured Schur complement decomposition strategy is proposed to accelerate the reconstruction process and reduce the computational complexity. Additionally, an adaptive regularization scheme is developed to improve the ill-posedness of the inverse problem.

Methods

The global system is decomposed level by level with the Schur complement system along two paths in the tree structure. The resultant subsystems are solved in combination with the biconjugate gradient method. The mesh for the inverse problem is generated incorporating the prior information. During the reconstruction, the regularization parameters are adaptive not only to the spatial variations but also to the variations of the objective function to tackle the ill-posed nature of the inverse problem.

Results

Simulation results demonstrate that the strategy of the tree structured Schur complement decomposition obviously outperforms the previous methods, such as the conventional Conjugate-Gradient (CG) and the Schur CG methods, in both reconstruction accuracy and speed. As compared with the Tikhonov regularization method, the adaptive regularization scheme can significantly improve ill-posedness of the inverse problem.

Conclusions

The methods proposed in this paper can significantly improve the reconstructed image quality of FMT and accelerate the reconstruction process.
Synthetic rabbit-human antibody conjugate as a control in immunoassays for immunoglobulin M specific to hepatitis E virus
Authors: Zhang Kuo , Wang Lunan , Liu Min , Zhang Rui , Li Jinming
Published: May 2010

Background

In assays for anti-hepatitis E virus (HEV) immunoglobulin M (IgM), large volumes of the patient's sera cannot be easily obtained for use as a positive control. In this study, we investigated an alternative chemical method in which rabbit anti-HEV IgG was conjugated with human IgM and was used as a positive control in the anti-HEV IgM assay. Rabbit anti-HEV IgG was isolated from immune sera by chromatography on protein A-Sepharose and was conjugated with human IgM by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as a crosslinker.

Results

The specific anti-HEV IgG antibody titer was 100,000 times that of the negative control, i.e., prebleed rabbit serum. The results of anti-HEV IgM enzyme-linked immunosobent assay showed that the antibody conjugate was similar to anti-HEV IgM antibodies produced in humans. The results of a stability experiment showed that the antibody conjugate was stable for use in external quality assessment or internal quality control trials.

Conclusions

We concluded that the chemically conjugated rabbit-human antibody could be used instead of the traditional serum control as a positive control in the anti-HEV IgM assay.
p38 Mediates Mechanical Allodynia in a Mouse Model of Type 2 Diabetes
Authors: Cheng Hsinlin T , Dauch Jacqueline R , Oh Sang Su , Hayes John M , Hong Yu , Feldman Eva L
Published: May 2010

Background:

Painful Diabetic Neuropathy (PDN) affects more than 25% of patients with type 2 diabetes; however, the pathogenesis remains unclear due to lack of knowledge of the molecular mechanisms leading to PDN. In our current study, we use an animal model of type 2 diabetes in order to understand the roles of p38 in PDN. Previously, we have demonstrated that the C57BLK db/db (db/db) mouse, a model of type 2 diabetes that carries the loss-of-function leptin receptor mutant, develops mechanical allodynia in the hind paws during the early stage (6–12 wk of age) of diabetes. Using this timeline of PDN, we can investigate the signaling mechanisms underlying mechanical allodynia in the db/db mouse.

Results:

We studied the role of p38 in lumbar dorsal root ganglia (LDRG) during the development of mechanical allodynia in db/db mice. p38 phosphorylation was detected by immunoblots at the early stage of mechanical allodynia in LDRG of diabetic mice. Phosphorylated p38 (pp38) immunoreactivity was detected mostly in the small-to medium-sized LDRG neurons during the time period of mechanical allodynia. Treatment with an antibody against nerve growth factor (NGF) significantly inhibited p38 phosphorylation in LDRG of diabetic mice. In addition, we detected higher levels of inflammatory mediators, including cyclooxygenase (COX) 2, inducible nitric oxide synthases (iNOS), and tumor necrosis factor (TNF)-α in LDRG neurons of db/db mice compared to non-diabetic db + mice. Intrathecal delivery of SB203580, a p38 inhibitor, significantly inhibited the development of mechanical allodynia and the upregulation of COX2, iNOS and TNF-α.

Conclusions:

Our findings suggest that NGF activated-p38 phosphorylation mediates mechanical allodynia in the db/db mouse by upregulation of multiple inflammatory mediators in LDRG.
Argatroban therapy for heparin-induced thrombocytopenia in ICU patients with multiple organ dysfunction syndrome: a retrospective study
Authors: Saugel Bernd , Phillip Veit , Moessmer Georg , Schmid Roland M , Huber Wolfgang
Published: May 2010

Introduction

Heparin-induced thrombocytopenia (HIT) is a serious, prothrombotic, immune-mediated adverse reaction triggered by heparin therapy. When HIT is diagnosed or suspected, heparins should be discontinued, and an alternative, fast-acting, parenteral, nonheparin anticoagulation such as argatroban should be initiated. Limited and inconsistent data exist about dosing of argatroban in intensive care unit (ICU) patients with critical illnesses.

Methods

Retrospective analysis of 12 ICU patients with multiple organ dysfunction syndrome (MODS) treated with argatroban for suspected or diagnosed HIT.

Results

The 12 ICU patients with a mean platelet count of 46,000 ± 30,310 had a mean APACHE II score of 26.7 ± 7.8 on ICU admission and a mean SAPS II score of 61.5 ± 16.3 on the first day of argatroban administration. A mean argatroban starting dose of 0.32 ± 0.25 μg/kg/min (min, 0.04; max, 0.83) was used to achieve activated partial thromboplastin times (aPTTs) >60 sec or aPTTs of 1.5 to 3 times the baseline aPTT. Adjustment to aPTT required dose reduction in six (50%) patients. Patients were treated for a mean of 5.5 ± 3.3 days. The final mean dose in these critically ill patients was 0.24 ± 0.16 μg/kg/min, which is about one eighth of the usually recommended dose and even markedly lower than the previously suggested dose for critically ill ICU patients. In all patients, desired levels of anticoagulation were achieved. The mean argatroban dose was significantly lower in patients with hepatic insufficiency compared with patients without hepatic impairment (0.10 ± 0.06 μg/kg/min versus 0.31 ± 0.14 μg/kg/min; P = 0.026). The mean argatroban dose was significantly correlated with serum bilirubin (r = -0.739; P = 0.006).

Conclusions

ICU Patients with MODS and HIT can be effectively treated with argatroban. A decrease in the initial dosage is mandatory in this patient population. Further studies are needed to investigate argatroban elimination and dosage adjustments for critically ill patients.
Natural Foxp3+ regulatory T cells inhibit Th2 polarization but are biased toward suppression of Th17-driven lung inflammation
Authors: Girtsman Teri , Jaffar Zeina , Ferrini Maria , Shaw Pamela , Roberts Kevan
Published: May 2010

Natural Tregs are highly effective at inhibiting Th2 differentiation but restrictive in their ability to suppress airway inflammatory processes.

nTregs prevent autoimmunity and modulate immune and inflammatory responses to foreign antigens. CD4+Foxp3+ nTregs from DO11.10 mice were expanded ex vivo, and their effectiveness in suppressing the development of lung inflammatory responses, elicited by differentiated CD4+ T cells following antigen inhalation, was examined. Effector DO11.10 CD4+ Th2 cells, when adoptively transferred into BALB/c mice that subsequently inhaled OVA, elicited a pronounced pulmonary, eosinophilic inflammation. Surprisingly, the cotransfer of expanded nTregs failed to suppress the Th2-mediated airway inflammation. Nevertheless, expanded OVA-specific CD4+Foxp3+ nTregs were highly effective at inhibiting the polarization of naïve CD4+ T cells into a Th2 phenotype. This suppression was reversed by an antibody to GITR but was not affected by the presence of the soluble OX40L. Further analysis revealed that although nTregs also failed to inhibit the lung neutrophilic inflammation induced by effector CD4+ Th1 cells, they markedly suppressed pulmonary inflammation elicited by CD4+ Th17 cells but not AHR. The suppression of the Th17-mediated response was evident from a striking reduction in the proportion of OVA-specific T cells expressing IL-17 and the numbers of neutrophils present in the airways of Th17 recipient mice. Collectively, these results demonstrate that expanded nTregs clearly limit the Th2 polarization process and that Th17-mediated inflammatory responses are particularly prone to the immunoregulatory properties of nTregs. These findings thus indicate that expanded nTregs are restrictive in their ability to suppress airway inflammatory processes and AHR.
Regulation of corneal inflammation by neutrophil-dependent cleavage of keratan sulfate proteoglycans as a model for breakdown of the chemokine gradient
Authors: Carlson Eric C , Sun Yan , Auletta Jeffery , Kao Winston W Y , Liu Chia-Yang , Perez Victor L , Pearlman Eric
Published: May 2010

Keratan sulfate proteoglycans are degraded by PMNs and detected with CXC chemokines in the anterior chamber to initiate the resolution process of LPS-induced inflammation.

Keratocan and lumican are small, leucine-rich repeat KSPGs in the extracellular matrix (ECM) of the mammalian cornea, whose primary role is to maintain corneal transparency. In the current study, we examined the role of these proteoglycans in the breakdown of the chemokine gradient and resolution of corneal inflammation. LPS was injected into the corneal stroma of C57BL/6 mice, and corneal extracts were examined by immunoblot analysis. We found reduced expression of the 52-kD keratocan protein after 6 h and conversely, increased expression of 34/37 kD immunoreactive products. Further, appearance of the 34/37-kD proteins was dependent on neutrophil infiltration to the cornea, as the appearance of these products was coincident with neutrophil infiltration, and the 34/37-kD products were not detected in explanted corneas or in CXCR2−/− corneas with deficient neutrophil recruitment. Furthermore, the 34/37-kD products and CXCL1/KC were detected in the anterior chamber, into which the corneal stroma drains; and CXCL1/KC was elevated significantly in keratocan−/− and lumican−/− mice. Together, these findings indicate that the inflammatory response in the cornea is regulated by proteoglycan/CXCL1 complexes, and their diffusion into the anterior chamber is consistent with release of a chemokine gradient and resolution of inflammation.
How specificity for self-peptides shapes the development and function of regulatory T cells
Authors: Simons Donald M , Picca Cristina Cozzo , Oh Soyoung , Perng Olivia A , Aitken Malinda , Erikson Jan , Caton Andrew J
Published: May 2010

Review discusses studies analyzing how the immune system generates Treg cells that can recognize self-peptides and prevent harmful autoimmune responses.

The cataclysmic disease that develops in mice and humans lacking CD4+ T cells expressing the transcription factor Foxp3 has provided abundant evidence that Foxp3+CD4+ Tregs are required to suppress a latent autoreactivity of the immune system. There is also evidence for the existence of tissue-specific Tregs that can act to suppress regional autoimmune responses, suggesting that Tregs exert their effects, in part, through responding to self-peptides. However, how the immune system generates a repertoire of Tregs that is designed to recognize and direct regulatory function to self-peptides is incompletely understood. This review describes studies aimed at determining how T cell recognition of self-peptide(s) directs Treg formation in the thymus, including discussion of a modified “avidity” model of thymocyte development. Studies aimed at determining how TCR specificity contributes to the ability of Tregs to suppress autoimmune diseases are also discussed.
Cevoglitazar, a Novel Peroxisome Proliferator-Activated Receptor-α/γ Dual Agonist, Potently Reduces Food Intake and Body Weight in Obese Mice and Cynomolgus Monkeys
Authors: Chen Hong , Dardik Beatriz , Qiu Ling , Ren Xianglin , Caplan Shari L. , Burkey Bryan , Boettcher Brian R. , Gromada Jesper
Published: May 2010

Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-α and -γ subtypes. Dual activation of PPARα and -γ is a therapeutic approach in development for the treatment of type 2 diabetes mellitus and diabetic dyslipidemia. In this report, we show that, in addition to improving insulin sensitivity and lipid metabolism like other dual PPAR agonists, cevoglitazar also elicits beneficial effects on energy homeostasis in two animal models of obesity. In leptin-deficient ob/ob mice, administration of cevoglitazar at 0.5, 1, or 2 mg/kg for 18 d led to acute and sustained, dose-dependent reduction of food intake and body weight. Furthermore, plasma levels of glucose and insulin were normalized after 7 d of cevoglitazar treatment at 0.5 mg/kg. Plasma levels of free fatty acids and triglycerides were dose-dependently reduced. In obese and insulin-resistant cynomolgus monkeys, treatment with cevoglitazar at 50 and 500 μg/kg for 4 wk lowered food intake and body weight in a dose-dependent manner. In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%. These preclinical results demonstrate that cevoglitazar holds promise for the treatment of diabetes and obesity-related disorders because of its unique beneficial effect on energy balance in addition to improving glycemic and metabolic control.
Peroxisome Proliferator-Activated Receptor-γ Increases Adiponectin Secretion via Transcriptional Repression of Endoplasmic Reticulum Chaperone Protein ERp44
Authors: Long Qinqiang , Lei Ting , Feng Bin , Yin Changjun , Jin Dan , Wu Yanling , Zhu Xiaoyue , Chen Xiaodong , Gan Li , Yang Zaiqing
Published: May 2010

Adiponectin, an adipocyte-derived hormone, is a versatile player involved in the regulation of energy homeostasis, cardiovascular disease, and diabetes. Within adipocytes, adiponectin is retained in the lumen of the endoplasmic reticulum (ER) by binding to the thiol protein ER resident protein 44 kDa (ERp44), which is apparently regulated by the activation of nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ. However, the precise role of ERp44 in adiponectin secretion remains elusive. In the present study, we investigated the functional correlation between ERp44 and adiponectin in a pig model. The transcription of porcine ERp44 was regulated by PPARγ, which was consistent with the finding of putative peroxisome proliferator response element sites within ERp44 promoter. Using chromatin immunoprecipitation and luciferase reporter assays, we demonstrated that the transcription of porcine ERp44 is repressed through binding of PPARγ to a peroxisome proliferator response element site located between positions −981 and −1004 in its 5′-flanking region. In human embryonic kidney 293 cells stably transfected with cDNA encoding porcine adiponectin, the secretion of adiponectin was significantly up-regulated and the ERp44 mRNA was down-regulated observably, by either the treatment of PPARγ agonist rosiglitazone or the overexpression of PPARγ in these cells. Taken together, our results indicated that PPARγ is an essential regulatory factor for the transcriptional activity of ERp44, which in turn controls the secretion of adiponectin.
The Mineralocorticoid Receptor Is a Constitutive Nuclear Factor in Cardiomyocytes due to Hyperactive Nuclear Localization Signals
Authors: Hernández-Díaz Iván , Giraldez Teresa , Arnau María Rosa , Smits Veronique A. J. , Jaisser Frederic , Farman Nicolette , Alvarez de la Rosa Diego
Published: May 2010

The mineralocorticoid receptor (MR), a member of the nuclear receptor family, mediates the action of aldosterone in target epithelia, enhancing sodium reabsorption. In addition, MR may have other physiological functions in nonepithelial tissues. Altered expression or inappropriate activation of cardiac MR is directly linked to the development of cardiac fibrosis, and MR blockade is beneficial for the treatment of heart failure. However, the physiological role, activation status, and target genes of MR in the heart are poorly known. Because ligand-free steroid receptors are typically cytoplasmic and translocate to the nucleus upon ligand binding, we examined the subcellular localization of MR under different corticosteroid levels using subcellular fractionation and immunostaining. Our results demonstrate that MR is a chromatin-bound factor in mouse left ventricle and in a cultured model of cardiomyocytes, HL-1 cells, regardless of circulating corticosteroid levels. Immunohistochemical localization of MR in human heart confirms the subcellular localization pattern. Mutation of nuclear localization signals (NLSs) demonstrates that MR constitutive nuclear localization mainly depends on the synergistic contribution of NLS0 and NLS1. Constitutive nuclear localization in HL-1 cells can be reverted by cotransfection of heat shock protein 90. Heat shock protein 90 expression levels in the mouse heart and HL-1 cells are lower than those found in other tissues, suggesting that low levels of cochaperones render MR NLSs hyperactive in cardiomyocytes. Even though MR is constitutively nuclear, corticosteroids still control the transactivation properties of the receptor in a model promoter, although other MR ligand-independent activities cannot be excluded.
Comparative Validation of the Growth Hormone-Releasing Hormone and Arginine Test for the Diagnosis of Adult Growth Hormone Deficiency Using a Growth Hormone Assay Conforming to Recent International Recommendations
Authors: Chanson Philippe , Cailleux-Bounacer Anne , Kuhn Jean-Marc , Weryha Georges , Chabre Olivier , Borson-Chazot Françoise , Dubois Séverine , Vincent-Dejean Caroline , Brue Thierry , Fedou Christine , Bresson Jean-Louis , Demolis Pierre , Souberbielle Jean-Claude
Published: May 2010

Context: The GHRH plus arginine (GHRH+Arg) test is a promising alternative to the insulin tolerance test (ITT) for diagnosis of adult GH deficiency (AGHD).

Objectives: The objectives of the study were to validate the GHRH+Arg test for diagnosis of AGHD, using the ITT as comparator and a GH assay calibrated according to recent international recommendations, and to study the repeatability and tolerance of both tests.

Design: This was a multicenter, randomized, open-label, phase III study.

Setting: The study was conducted at 10 French university hospitals.

Subjects: Sixty-nine subjects (38 and 15 with high and low probability of GH deficiency, respectively, and 16 healthy controls) were randomized: 35 to the GHRH+Arg-GHRH+Arg-ITT test sequence and 34 to the ITT-ITT-GHRH+Arg test sequence.

Interventions: Each subject underwent three tests of GH secretion separated by 24 h or more.

Main Outcome Measures: The primary variable used for response assessments was serum peak GH response. Test results were compared with the final AGHD diagnosis.

Results: Peak GH responses in the two tests were strongly correlated. A cutoff value of 7.89 μg/liter for GHRH+Arg corresponding to 3 μg/liter for ITT was calculated. The cutoff value leading to 95% specificity with the GHRH+Arg test was measured at about 3.67 μg/liter (sensitivity 79.0%). Intermethod agreement and repeatability were high. Both tests were well tolerated. A preference for the GHRH+Arg test was expressed by 74% of subjects.

Conclusions: The GHRH+Arg test demonstrated good accuracy and repeatability, was at least as sensitive as the ITT, and was associated with better subject acceptability. The GHRH+Arg test represents a good alternative to the ITT for the diagnosis of AGHD.
A Trajectory of Competing Narratives: The Turkish Media Debate Ergenekon
Authors: Balci Ali
Published: May 2010

The history of the “deep state”—also known as Ergenekon—in Turkey starts with the foundation of the modern republic. Although references to the deep state date back to an earlier period, this essay examines coverage of it in the Turkish media during the late 1990s and the early-twenty-first century. Ergenekon was conceptualized, debated, defined, and redefined by the media; it was brought to public attention by the media, not by state officials, the police, politicians, inspectors, or members of the organization. The author's intent is not to redefine Ergenekon yet again but to analyze the meaning of the organization Ergenekon, how that meaning is continually defined and redefined by the media, and how the facts related to Ergenekon are interpreted by the media.
Production order quantity for economical and quality consideration
Authors: Jeang A
Published: May 2010

In the conventional production-inventory management approach, the production order quantity is determined by referring to costs such as the ordering cost and inventory cost. However, the quality level being produced may change during the production process owing to process deterioration. Thus, under process deterioration, a production order quantity based solely on the conventional production-inventory management system may be overproduced, due to a lack of consideration of varied quality costs at different points of time, along with the production run length. Hence, for cyclical quality promotion and cost reduction, there is a motivation to extend the conventional production-inventory management approach by adding the process-quality design approach which considers the varied quality-related costs as a function of time. The decision variables include the initial setting, process tolerance, and production order quantity, which have to be determined simultaneously for true optimization so that the average total cost, which includes the setup cost for production reordering and process resetting, quality loss, and tolerance cost for process quality, and the inventory cost for production inventory, is minimized. An example of a production process subject to process deterioration is presented for illustrating the possible application of the proposed model.
Novel cost–tolerance model based on fuzzy neural networks
Authors: Cao Y , Zhang H , Mao J , Yang J
Published: May 2010

The conventional cost–tolerance model is constructed by linear or non-linear regression analysis based upon empirical data from all frequently used production processes. These approaches suffer relatively large model-fitting errors and also fail to consider the varying manufacturing environment due to the simplicity of the mathematical models used. In the present study, a novel, multi-parameter cost–tolerance model is developed based on a fuzzy neural network (FNN) that has tolerance and a cost influence coefficient as inputs and manufacturing cost as output. First, the cost influence coefficient is introduced based on analysis of the manufacturing environment. Then, a multi-input, FNN-based cost–tolerance model is constructed. Analysis of the model is conducted and comparison is made with existing models. Analytical results show that the proposed model yields better performance in controlling the average fitting error and is flexible to varying manufacturing environment. It can provide more reliable results and reduce the chances of error in the tolerance design.
Evaluating and predicting the collapsing tendency of fully penetrated gas tungsten arc weld pools
Authors: Zhao M , Wu C S , Jiang S Y
Published: May 2010

In numerical modelling and simulation of fluid flow and heat transfer phenomena, it should be ensured that the output data have practical meaning, so that the models are capable of automatic judging and evaluation of functions to predict the collapsing tendency of a fully-penetrated weld pool for any input process parameters. In this study, a subprogram is combined with a comprehensive model for weld pool behaviours in gas tungsten arc welding (GTAW) to evaluate and predict the tendency or possibility of the weld pool collapsing so as to avoid over-penetration and/or burn-through. The forces acting on a weld pool are analysed in detail. A model of static force conditions for a fully-penetrated weld pool is developed, and a criterion is set up to judge and evaluate the tendency for occurrence of over-penetration and/or burn-through defects. The transient variations of the forces affecting surface deformation and collapse of the weld pool are computed, and the percentages of their influencing roles are obtained. For a specific material and workpiece thickness, the threshold values below which the burn-through phenomenon does not occur are determined, and compared to the experimental results.
Modelling and experimental investigation on the effect of nanopowder-mixed dielectric in micro-electrodischarge machining of tungsten carbide
Authors: Jahan M P , Rahman M , Wong Y S
Published: May 2010

Micro-electrodischarge machining (micro-EDM) is one of the most effective methods used in die and mould industries for machining difficult-to-cut tool and die materials such as tungsten carbide (WC). The quality and integrity of the surface finish resulting from the micro-EDM process in die and mould making can have a significant impact on the product performance. The present study intends to investigate the feasibility of improving the surface finish in micro-EDM of WC in a dielectric mixed with graphite (Gr), aluminium (Al), and alumina (Al2O3) nanopowders. The mechanism of powder-mixed micro-EDM is presented theoretically in terms of the effect of additive powder characteristics on the dielectric breakdown and gap width. In addition, the effect of the nanopowders’ mixed dielectric on surface topography, average surface roughness ( Ra), peak-to-valley roughness ( Rmax), material removal rate (MRR), and electrode wear ratio (EWR) was studied experimentally. It has been shown theoretically that the presence of a conductive or semi-conductive powder lowers the breakdown strength and increases the spark gap during powder-mixed micro-EDM. The surface finish and topography was improved significantly owing to the increased spark gap and uniform discharging in powder-mixed micro-EDM. In addition, the lower breakdown strength of dielectric and increased spark gap contribute to higher MRR and lower EWR in addition to improved surface finish. Among the three types, semi-conductive graphite nanopowder was found to provide a smooth and shiny surface with lower Ra and Rmax, whereas the spark gap and MRR was found to be higher when aluminium powder was used. The non-conductive alumina powder was found to have very little effect on the performance of powder-mixed micro-EDM of WC. Finally, from analytical and experimental study, it has been concluded that the particle size, concentration, density, and thermal and electrical conductivity of powder materials are the most influencing factors in powder-mixed micro-EDM of WC.
Application of robust prediction for a laser–GMA hybrid welding process and parameter optimization of 6061-T6 aluminium alloy
Authors: Jang I , Lee K Y
Published: May 2010

A methodology to predict and optimize the ultimate tensile strength of 6061-T6 aluminium (Al) alloy under a laser–GMA hybrid welding process is presented. Experiments were performed by changing welding process parameters. For the evaluation of weldability, the ultimate tensile strength in the weld zone was considered to be the most important criterion. In order to determine the optimum welding parameters, a robust regression analysis was performed to present a reliable prediction and a genetic algorithm was used. Based on the results of robust regression analysis and the genetic algorithm, the optimal process parameters were obtained. The ultimate tensile strength result obtained by the optimal parameters was much improved, when compared with that specified by the American Welding Society.
An investigation of the effect of under-ballast reinforcing geogrids in laboratory and operating conditions
Authors: Horníček L , Tyc P , Lidmila M , Krejčiříková H , Jasanský P , Břešt?'ovský P
Published: May 2010

This article presents the results of research focused on the use of reinforcing geosynth-etics inserted directly under the ballast. This technology appears to be a beneficial, cost-effective solution in cases of need for enhancing the bearing capacity of existing railway tracks with poorer track bed quality. Model constructions in a 1:1 scale with reinforcing geogrids of three types inserted under the ballast were investigated in laboratory conditions under short-term static loading and long-term cyclic loading. The contribution of geosynthetics is evaluated by comparing the values of settlement and bearing capacity of individual layers with those of a non-reinforced construction. The article also describes the up-to-date experience in the verification of the geocomposite-reinforced ballast bed in operating conditions. It is performed on a trial section of a single-rail track 200 m in length characterized by persisting long-term problems with the track geometry. The authors evaluate the used technology of mechanical geosynthetic laying by means of the ballast cleaning machine.
A methodology for geophysical investigation of track defects
Authors: Barta J
Published: May 2010

This article presents possibilities of application of selected geophysical methods in railway engineering. Geophysical methods are used to observe a physical field. The measured data are interpreted in order to provide findings on geotechnical conditions of railway substructure and its surroundings. Geophysical methods have been unsystematically applied on European railways in the past. This paper's text is supported mainly by the measurements performed under the INNOTRACK projects at the sites in the Czech Republic, France, Spain, and Sweden. The geophysical testing has proved that the geophysical methods can reliably, quickly, in detail, and at a relatively low cost, inform about the problematic zones of the track. The effect of the geophysical application can be enhanced by long-term monitoring of track segments.
The Biomechanics of a Validated Finite Element Model of Stress Shielding in a Novel Hybrid Total Knee Replacement
Authors: Bougherara H , Zdero R , Mahboob Z , Dubov A , Shah S , Schemitsch E H
Published: May 2010

This study proposes a novel hybrid total knee replacement (TKR) design to improve stress transfer to bone in the distal femur and, thereby, reduce stress shielding and consequent bone loss. Three-dimensional finite element (FE) models were developed for a standard and a hybrid TKR and validated experimentally. The Duracon knee system (Stryker Canada) was the standard TKR used for the FE models and for the experimental tests. The FE hybrid device was identical to the standard TKR, except that it had an interposing layer of carbon fibre-reinforced polyamide 12 lining the back of the metallic femoral component. A series of experimental surface strain measurements were then taken to validate the FE model of the standard TKR at 3000 N of axial compression and at 0° of knee flexion. Comparison of surface strain values from FE analysis with experiments demonstrated good agreement, yielding a high Pearson correlation coefficient of R2 = 0.94. Under a 3000 N axial load and knee flexion angles simulating full stance (0°), heel strike (20°), and toe off (60°) during normal walking gait, the FE model showed considerable changes in maximum Von Mises stress in the region most susceptible to stress shielding (i.e. the anterior region, just behind the flange of the femoral implant). Specifically, going from a standard to a hybrid TKR caused an increase in maximum stress of 87.4 per cent (0°; from 0.15 to 0.28 MPa), 68.3 per cent (20°; from 1.02 to 1.71 MPa), and 12.6 per cent (60°; from 2.96 to 3.33 MPa). This can potentially decrease stress shielding and subsequent bone loss and knee implant loosening. This is the first report to propose and biomechanically to assess a novel hybrid TKR design that uses a layer of carbon fibre-reinforced polyamide 12 to reduce stress shielding.