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Toll-Like Receptor 4 and High-Mobility Group Box 1 Are Critical Mediators of Tissue Injury and Survival in a Mouse Model for Heatstroke
Mohammed Dehbi, Taher Uzzaman, Engin Baturcam, Abdelmoneim Eldali, Wilhelmina Ventura, Abderrezak Bouchama
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044100
Abstract: The molecular mechanisms that initiate the inflammatory response in heatstroke and their relation with tissue injury and lethality are not fully elucidated. We examined whether endogenous ligands released by damaged/stressed cells such as high-mobility group box 1 (HMGB1) signaling through Toll-like receptor 4 (TLR4) may play a pathogenic role in heatstroke. Mutant TLR4-defective (C3H/HeJ) and wild type (C3H/HeOuJ) mice were subjected to heat stress in an environmental chamber pre-warmed at 43.5°C until their core temperature reached 42.7°C, which was taken as the onset of heatstroke. The animals were then allowed to recover passively at ambient temperature. A sham-heated group served as a control. Mutant mice displayed more histological liver damage and higher mortality compared with wild type mice (73% vs. 27%, respectively, P<0.001). Compared to wild type mice, mutant mice exhibited earlier plasma release of markers of systemic inflammation such as HMGB1 (206±105 vs. 63±21 ng/ml; P = 0.0018 and 209±100 vs. 46±32 ng/ml; P<0.0001), IL-6 (144±40 vs. 46±20 pg/ml; P<0.001 and 184±21 vs. 84±54 pg/ml; P = 0.04), and IL-1β (27±4 vs. 1.7±2.3 pg/ml; P<0.0001 at 1 hour). Both strains of mice displayed early release of HMGB1 into the circulation upstream of IL-1β and IL-6 responses which remained elevated up to 24 h. Specific inhibition of HMGB1 activity with DNA-binding A Box (600 μg/mouse) protected the mutant mice against the lethal effect of heat stress (60% A Box vs. 18% GST protein, P = 0.04). These findings suggest a protective role for the TLR4 in the host response to severe heat stress. They also suggest that HMGB1 is an early mediator of inflammation, tissue injury and lethality in heatstroke in the presence of defective TLR4 signaling.
sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy
Yaseen M Arabi, Mohammed Dehbi, Asgar H Rishu, Engin Baturcam, Salim H Kahoul, Riette J Brits, Brintha Naidu, Abderrezak Bouchama
Critical Care , 2011, DOI: 10.1186/cc10420
Abstract: A predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls.Both diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality.These findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.Hyperglycemia represents an important independent risk factor for morbidity and mortality in critically ill patients admitted to ICU [1,2]. Accordingly, the benefit of strict control of blood sugar with intensive insulin therapy (IIT) versus conventional insulin therapy (CIT) has been greatly debated with some studie
A Review of Security Concerns in Internet of Things  [PDF]
Engin Leloglu
Journal of Computer and Communications (JCC) , 2017, DOI: 10.4236/jcc.2017.51010
Abstract: The Internet of Things (IoT) represents a technologically optimistic future where objects will be connected to the internet and make intelligent collaborations with other objects anywhere, anytime. Although it makes appreciable development, there are still uncertainties about security concepts of its usage that is usually considered as a major concern in the design of IoT architectures. This paper presents a general survey of all the security issues in IoT along with an analysis of IoT architectures. The study defines security requirements and challenges that are common in IoT implementations and discusses security threats and related solutions on each layer of IoT architecture to make this technology secure and more widespread accordingly.
DNAJB3/HSP-40 Cochaperone Is Downregulated in Obese Humans and Is Restored by Physical Exercise
Jehad Abubaker, Ali Tiss, Mohamed Abu-Farha, Fahad Al-Ghimlas, Irina Al-Khairi, Engin Baturcam, Preethi Cherian, Naser Elkum, Maha Hammad, Jeena John, Sina Kavalakatt, Abdelkrim Khadir, Samia Warsame, Said Dermime, Kazem Behbehani, Mohammed Dehbi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069217
Abstract: Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT2-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001), triglycerides (P = 0.035) and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively). DNAJB positively correlated with maximum oxygen consumption (P = 0.031). Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity.
Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity
Mohamed Abu-Farha, Ali Tiss, Jehad Abubaker, Abdelkrim Khadir, Fahad Al-Ghimlas, Irina Al-Khairi, Engin Baturcam, Preethi Cherian, Naser Elkum, Maha Hammad, Jeena John, Sina Kavalakatt, Samia Warsame, Kazem Behbehani, Said Dermime, Mohammed Dehbi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075342
Abstract: Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs) extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max) but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent a potential therapeutic target for the control and management of obesity and presumably insulin resistance.
Contour-Based Image Segmentation Using Selective Visual Attention  [PDF]
Engin Mendi, Mariofanna Milanova
Journal of Software Engineering and Applications (JSEA) , 2010, DOI: 10.4236/jsea.2010.38092
Abstract: In many medical image segmentation applications identifying and extracting the region of interest (ROI) accurately is an important step. The usual approach to extract ROI is to apply image segmentation methods. In this paper, we focus on extracting ROI by segmentation based on visual attended locations. Chan-Vese active contour model is used for image segmentation and attended locations are determined by SaliencyToolbox. The implementation of the toolbox is extension of the saliency map-based model of bottom-up attention, by a process of inferring the extent of a proto-object at the attended location from the maps that are used to compute the saliency map. When the set of regions of interest is selected, these regions need to be represented with the highest quality while the remaining parts of the processed image could be represented with a lower quality. The method has been successfully tested on medical images and ROIs are extracted.
Effects of At2 Receptor Agonist Novokinin on Oxidative Stress, Inflammation and Infarct Size Due to Myocardial Ischemia-Reperfusion  [PDF]
Esra Gunduz, Engin Sahna
Journal of Biomedical Science and Engineering (JBiSE) , 2017, DOI: 10.4236/jbise.2017.105020
Abstract: Aim: Ischemia and reperfusion (IR) injury is a serious problem that is occured during thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass. There is an increase in the number of AT2 receptors in some pathological conditions such as cardiac hypertrophy, myocardial infarction, congestive heart failure. This study was designed to investigate the effects AT2 receptor agonist Novokinin on infarct size, caveolin-1 (CAV-1), HSP90, ADMA, NADPH oxidase and Rhokinase associated to endothelial dysfunction and oxidative stress, and NFκB and TLR-4 levels induced by inflammation on myocardial IR. Methods: The experimental groups: Sham (C), Novokinin (N), IR and IRN. Novokinin was performed with infusion pump before ischemia, and during IR. The left main coronary artery was occluded for 30 minutes ischemia followed by 120 minutes reperfusion in anesthetized rats. CAV-1, HSP90, and NFκB levels were measured by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), ADMA, TLR-4, NADPH oxidase, and Rhokinase levels were measured by ELISA, infarct size was measured by ImageJ, an image analysis software, in the heart tissue. Results: NFκB, HSP90, NADPH oxidase and TLR-4 levels increased with IR and significantly decreased with Novokinin. CAV-1 levels were not different between the groups. ADMA and Rhokinase levels were increased due to IR but decreased with Novokinin. Novokinin reduced infarct size due to IR. Conclusion: Our results showed that, ADMA, HSP90, NFκB, TLR-4, Rhokinase, and NADPH oxidase levels play important roles on IR injury. AT2 receptor agonist Novokinin may affect positively oxidative changes, inflammation, and endothelial function in myocardial IR injury.
lk retim Okulu retmenlerinin Alg lad klar Liderlik Bi imleri le Doyumlar Aras ndaki li ki(The Relationship between the Leadership Styles and Job Satisfaction As Perceived By Teachers in Turkish Elementary Schools)
Engin KARADA????,Engin KARADA?,Engin KARADA????
Bal?kesir üniversitesi Sosyal Bilimler Dergisi , 2009,
Abstract: The Relationship between the Leadership Styles and Job Satisfaction As Perceived By Teachers in Turkish Elementary SchoolsProblem Statement: Education leaderships behaviors and styles effect the schools improvement, the aims of schools, students achievement and workers jobs satisfaction. Purpose of the Study: This research, aims to find out the determination of the relationship between the leadership styles perceived by teachers of primary schools and their job satisfaction. Methods: Relational cross-hatching model was used to determine the relation between these concepts. The sample consisted of 253 primary school teachers. Pearson moment correlation, ANOVA and t-test were used to analyze the data. Findings, Results and Conclusions: As the results of the analyses; it there is a significant difference between the jobs satisfactions of elementary school teachers and priority, educational state and gender of their directors. And also there is a significant difference between “Transformational Leadership” styles and priority, educational state and gender of their principals. This significant difference has not found in “Transactional Leadership” style and “Laissez-faire Leadership” styles. Also, there is a high relation between teachers’ perception of leadership styles and “Transformational Leadership” styles; moreover, the same relation is on the low level in “Transactional Leadership” style. There is no relation between “Laissez-faire Leadership” dimension and satisfaction.
Structural deformations analysis by means of Kalman-filtering
Gulal, Engin;
Boletim de Ciências Geodésicas , 2013, DOI: 10.1590/S1982-21702013000100007
Abstract: the surveillance of engineering structures like dams is an interdisciplinary task and mainly focused on the assessment of stability and reliability of the objects to be monitored. to show the co-operation of the disciplines involved in a comprehensible manner, it is suitable to use system analysis approaches. structural deformations analysis by means of system analysis is explained in the following with an example of a dam. the determination of the dam deformations is demonstrated by an integration of computed and measured data by using kalman filtering.
Nicolau Syndrome: A Review of the Literature
Engin Senel
Clinical Medicine Insights: Dermatology , 2012, DOI: 10.4137/CMD.S3630
Abstract: Nicolau Syndrome, first described in the 1920’s in patients treated with bismuth salts for syphilis, is a rare adverse reaction at the site of intramuscular drug injection. It is clinically characterized by severe pain immediately after injection, and rapid development of blanched skin or livedoid reticular patches. Occlusion of peripheral arterial vessels is suggested to play a major pathogenic role. Since there is no specific therapy for this condition, an appropriate conservative treatment should be applied.
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