Downregulation of major histocompatibility complex class I in bovine papillomas

Bovine papillomavirus (BPV) induces papillomas in cattle; in the great majority of cases, these regress due to the host immune response, but they can persist and progress to malignancy. Even in the absence of malignant transformation, BPV infection persists for a significant period of time before activation of the host immune system, suggesting that the host immune system is unaware of, or disabled by, BPV. E5 is the major oncoprotein of BPV, which, in addition to its transforming properties, downregulates the expression and transport to the cell surface of major histocompatibility complex class I (MHC I). Here, it is shown that co-expression of MHC I and E5 in papillomas caused by BPV-4 infection is mutually exclusive, in agreement with the inhibition of surface MHC I expression by E5 that is observed in vitro. The inhibition of MHC expression in E5-expressing papilloma cells could explain the long period that is required for activation of the immune response and has implications for the progression of papillomas to the malignant stage; absence of peptide presentation by MHC I to cytotoxic T lymphocytes would allow the infected cells to evade the host cellular immune response and allow the lesions to persist

The role of the arterial glycocalyx in sphingosine-1- phosphate induced cardioprotection in the isolated heart of the Wistar rat

Background: Ischemic heart diseases (IHD) are a leading cause of death among cardiovascular diseases. Unfortunately, the myocardial damage due to ischemia in IHD may be worsened by reperfusion therapy, a phenomenon called ischemic-reperfusion (I/R) injury. Coronary vascular damage is a key feature of I/R injury. Among the coronary vascular structures, the endothelial glycocalyx is a delicate polysaccharide and protein-rich layer that plays an important role in the regulation of vascular permeability, and is easily damaged during I/R. Sphingosine-1-phosphate (S1P) is a membrane phospholipid metabolite that has been shown to protect the heart against I/R. It has also been shown to regulate the synthesis of glycocalyx, but its effects on coronary endothelial glycocalyx damage and possible mechanism during I/R are unknown. Therefore, we hypothesized that S1P-induced cardioprotection is mediated by modulation of the glycocalyx during I/R in the isolated rat heart. Methods: Isolated male Wistar hearts were perfused on a Langendorff system with Krebs-Henseleit buffer via retrograde perfusion at constant temperature and pressure. The hearts were stabilized and pre-treated with S1P (10 nM for 7 minutes) before inducing 20 minutes of global ischemia, followed by 60 minutes reperfusion. Functional parameters were recorded throughout the protocol, including left ventricular developed pressure (LVDP), left ventricular end diastolic pressure (LVEDP), heart rate (HR) and coronary flow (CF). Ventricular infarct size was measured by using triphenyltetrazolium chloride stain. Coronary net filtration rate (NFR) was calculated as a ratio of the amount of transudate to CF. Cardiac edema was assessed by calculating the heart wet/dry weight ratio and histologically quantifying size of the interstitial compartment. The shedding of the glycocalyx was estimated by measuring the release of the glycocalyx component syndecan-1 in the coronary effluent using enzyme-linked immunosorbent assay (ELISA) and determining relative syndecan-1 staining intensity between groups in immuno-stained wax sections of perfusion-fixed hearts. In addition, the histo-morphology of the myocardium was assessed using hematoxylin and eosin staining. Results: The cardiac performance was depressed after I/R, as was reflected by decreased LVDP (P=0.02 vs. control), and an increased LVEDP (P<0.0001 vs. control). I/R also significantly increased infarct size (P=0.04 vs. control). Treatment with S1P before I/R significantly decreased infarct size (P=0.01 vs. I/R), but did not improve the post-ischemic decrease in LVDP or stabilize the LVEDP, and had no effect on CF. I/R significantly increased release of syndecan-1 in the coronary effluent (P=0.0002 vs. control). Immunohistochemically-stained imaging also revealed syndecan-1 staining intensity was significantly decreased or absent in ischemic hearts (P≤0.001 vs. control). Pretreatment with S1P had neither effect on syndecan-1 level in the coronary effluent nor on the intensity of syndecan-1 signal in immuno-stained sections (P=n.s vs. I/R). Histological analysis of cardiac edema revealed an increase in the extracellular area in ischemic hearts compared to the control hearts (P≤0.001 vs. control), and S1P treatment decreased the extracellular area (P≤0.01 I/R+S1P vs. I/R). The NFR, and heart wet/dry ratio were not significantly different post-reperfusion between the groups and S1P had no effect on these parameters. Conclusion: This study showed that pretreatment with S1P protects the heart against I/R injury, as was indicated by the decreased infarct size, and decreased extracellular cardiac edema. S1P had no effect on hemodynamic performance or the shedding of syndecan-1. These results suggest that S1P-induced cardioprotection is not mediated by protection of the glycocalyx via stabilization of syndecan-1. However, it is possible that S1P may stabilize other minor glycocalyx components which were not measured in this study, such as heparan sulphate and hyaluronic acid. This is the first study that evaluated syndecan-1 in the cardiac effluent of the isolated heart of rats with global ischemia, and the study opens up prospects for further investigation of the role of the glycocalyx in other models of I/R injury, such as the more clinically-relevant regional ischemia disease model

The Effect of Product Differentiation on Local Brand Positioning: A Case Study of “Venus” Brand Shampoos in the Algerian Market

Due to the high development of global markets and the growing number of competitive rivals, product differentiation has become the solution to be positioned differently from the rival offers. This research aims to examine the effect of product differentiation on the brand positioning of the competing companies in the Algerian shampoo market, with a highlight on Venus brand as it is the only local shampoo producer in Algeria. The multi-dimensional scaling (MDS) technique using factor analysis is employed for data analysis to draw a perceptual map that displays the relative position of twelve shampoo brands including Venus. The results show a significant difference between the position of the standard Venus shampoo and Venus differentiated product. The differentiation strategy illustrated in our case, enabled Venus Company to improve its brand positioning, which made it closer to the different market segments. Keywords: local brands, differentiation strategy, brand positioning, MDS analysis, perceptual map

The E5 protein of BPV-4 interacts with the heavy chain of MHC class I and irreversibly retains the MHC complex in the Golgi apparatus

BPV-4 E5 inhibits transcription of the bovine MHC class I heavy chain (HC) gene, increases degradation of HC and downregulates surface expression of MHC class I by retaining the complex in the Golgi apparatus (GA). Here we report that transcription inhibition can be alleviated by interferon treatment and the degradation of HC can be reversed by treatment with inhibitors of proteasomes and lysosomes. However, the inhibition of transport of MHC class I to the cell surface is irreversible. We show that E5 is capable of physically interacting with HC. Together with the inhibition of the vacuolar ATPase (due to the interaction between E5 and 16k subunit c), the interaction between E5 and HC is likely to be responsible for retention of MHC class I in the GA. C-terminus deletion mutants of E5 are incapable of either downregulating surface MHC class I or interacting with HC, establishing that the C-terminus domain of E5 is important in the inhibition of MHC class I

Ant Colony Method to Minimize Single Machine Scheduling Problem

The study deal with a single machine scheduling problem where the objective is to find the sequence which it give the optimal or efficient solution for the objective function the sum of discounted weighted completion time and number of tardy jobs. The optimal solution was found for some special cases. Ant colony optimization (ACO) using to found an approximate solution. Results of extensive computational tests show that proposed (ACO) is effective in solving problems up to (1000) jobs at a time less than or equal to (10) minutes

Ant Colony Method to Minimize Single Machine Scheduling Problem

The study deal with a single machine scheduling problem where the objective is to find the sequence which it give the optimal or efficient solution for the objective function the sum of discounted weighted completion time and number of tardy jobs. The optimal solution was found for some special cases. Ant colony optimization (ACO) using to found an approximate solution. Results of extensive computational tests show that proposed (ACO) is effective in solving problems up to (1000) jobs at a time less than or equal to (10) minutes

The role of unconformities in the distribution of clay and porosity in North Sea clastic reservoirs

The effect of an unconformity surface on the quality of underlying clastic reservoirs has long been a matter of considerable debate. Two opposing hypotheses have been proposed. One supports a relationship between the presence of an unconformity surface and the quality of the underlying reservoir, either by enhancement or reduction of porosity (e.g. Ketzer et al., 2009 and Shanmugam, 1990). By contrast, the opposing hypothesis argues that there is no evidence for the existence of such a relationship (e.g. Ehrenberg and Jakobsen, 2001 and Bjorkum et al., 1990). In this study, both hypotheses were examined by evaluating the role of the unconformity surfaces on the quality of selected North Sea clastic reservoirs. In particular, the study focussed on the Late Triassic Skagerrak Formation in Kittiwake Field, Central North Sea, which underlies the Mid-Cimmerian unconformity, and the Middle Jurassic Brent Group sandstones in the Tampen Spur area, Northern North Sea, which underlie the BaseCretaceous Unconformity. This thesis presents the results of detailed sedimentological and petrographic analysis of over 200 core samples, including their lithology, texture, mineralogy and diagenetic characteristics, in order to investigate the existence of any diagenetic changes that may have affected the reservoir quality, and to consider any possible relationship with the overlying unconformity surfaces. Thin-section petrography and SEM analysis shows that there are several lines of evidence for the existence of post-depositional diagenetic changes within the studied sandstones, which included the generation of secondary porosity and the formation of authigenic kaolinite. These diagenetic changes are mainly due to the dissolution of detrital framework grains (particularly feldspar) and intergranular cement (particularly calcite), and the local precipitation of authigenic clay. Both of these diagenetic processes have had a significant effect on the reservoir properties. The distribution of the secondary porosity and authigenic kaolinite clearly indicate late stage diagenetic processes, which clearly post-date the majority of mechanical compaction, and therefore also post-date the origin of the unconformity surfaces. The study demonstrates that there is no relationship between the studied unconformity surfaces and the observed diagenetic changes (i.e., secondary porosity and authigenic kaolinite) within the selected reservoirs. Therefore, any such relationship reported elsewhere is most likely to be a localised phenomenon, and should not be extended as a general rule to all unconformities

Entrances to strategic refocus to improve the performance and balance of the corporate activities portfolio: the case of the National Painting Establishment in Algeria - ENAP

تهدف هذه الدراسة لتحليل مفهوم الحرفة الأساسية على مستوى محفظة نشاطات المؤسسة والبحث عن أهمالمداخل لإعادة التركيز الاستراتيجي على الحرفة الأساسية لتحسين أداء وتوازن محفظة نشاطات المؤسسة. كما اهتمت الدراسة الميدانية بتحليل الوضعية الاستراتيجية للمؤسسة الوطنية للدهن بالجزائر باعتماد نموذج BCG.وخلصنا بتقديم عدة خيارات لإعادة التركيز لحل مشكل اختلال توازن وأداء محفظة نشاطات المؤسسة بإعادة تعريف حرفة المؤسسة واقتراح أقسام استراتيجية جديدة تتناسب والتموقع الاستراتيجي المستقبلي للمؤسسة.This study aims to analyze the core business on the firm’s business portfolio and research the different modes of strategic refocusing on core business to improve performance and balance portfolio. The practice study interest to analyze the strategic position by using BCG model on the Algerian National Paintings Company. The study’s conclusion resolves this problematic of performance and balance of portfolio activity by redefine core business and formulate different adequate strategic business unit to the new future company strategic position

The E5 oncoprotein of BPV-4 does not interfere with the biosynthetic pathway of non-classical MHC class I

The major histocompatibility complex (MHC) class I region in mammals contains both classical and non-classical MHC class I genes. Classical MHC class I molecules present antigenic peptides to cytotoxic T lymphocytes, whereas non-classical MHC class I molecules have a variety of functions. Both classical and non-classical MHC molecules interact with natural killer cell receptors and may under some circumstances prevent cell death by natural killer cytotoxicity. The E5 oncoprotein of BPV-4 down-regulates the expression of classical MHC class I on the cell surface and retains the complex in the Golgi apparatus. The inhibition of classical MHC class I to the cell surface results from both the impaired acidification of the Golgi, due to the interaction of E5 with subunit c of the H+ V-ATPase, and to the physical binding of E5 to the heavy chain of MHC class I. Despite the profound effect of E5 on classical MHC class I, E5 does not retain a non-classical MHC class I in the Golgi, does not inhibit its transport to the cell surface and does not bind its heavy chain. We conclude that, as is the case for HPV-16 E5, BPV-4 E5 does not down-regulate certain non-classical MHC class I, potentially providing a mechanism for the escape of the infected cell from attack by both cytotoxic T lymphocytes and NK cells