SOLKATERM@SES 36 SOĞUTUCU AKIŞKANININ SOĞUTMA UYGULAMALARINDA PERFORMANS İNCELEMESİ

Bu çalışmada yeni bir akışkan türü olan Solkaterm@ses36 akışkanın, buhar sıkıştırmalı soğutma çevriminin etkinliği (COP) ve ekserji verimi teorik olarak incelenmiştir. Solkaterm@ses36 akışkanı daha önce literatürde çok fazla kullanılmadığından dolayı yeni bir akışkan olan bu akışkanın COP ve ekserji verim değerleri buharlaşma ve yoğuşma sıcaklıklarına bağlı olarak değişimi incelenmiş ve grafikler halinde verilmiştir. Evaporatör sıcaklığı -10 oC de kondenser sıcaklığı 30 oC de iken çevrim COP değeri ve ekserji verimi sırasıyla 1,75- ve % 13 olarak hesaplanmıştır. Akışkanın küresel ısınma (GWP) ve ozon delme potansiyel (ODP) değerleri de incelenerek çevre dostu olup olmadığı araştırılmıştır

Sulforaphane Inhibits Inflammatory Responses of Primary Human T-Cells by Increasing ROS and Depleting Glutathione

The activity and function of T-cells are influenced by the intra- and extracellular redox milieu. Oxidative stress induces hypo responsiveness of untransformed T-cells. Vice versa increased glutathione (GSH) levels or decreased levels of reactive oxygen species (ROS) prime T-cell metabolism for inflammation, e.g., in rheumatoid arthritis. Therefore, balancing the T-cell redox milieu may represent a promising new option for therapeutic immune modulation. Here we show that sulforaphane (SFN), a compound derived from plants of the Brassicaceae family, e.g., broccoli, induces a pro-oxidative state in untransformed human T-cells of healthy donors or RA patients. This manifested as an increase of intracellular ROS and a marked decrease of GSH. Consistently, increased global cysteine sulfenylation was detected. Importantly, a major target for SFN-mediated protein oxidation was STAT3, a transcription factor involved in the regulation of TH17-related genes. Accordingly, SFN significantly inhibited the activation of untransformed human T-cells derived from healthy donors or RA patients, and downregulated the expression of the transcription factor RORγt, and the TH17-related cytokines IL-17A, IL-17F, and IL-22, which play a major role within the pathophysiology of many chronic inflammatory/autoimmune diseases. The inhibitory effects of SFN could be abolished by exogenously supplied GSH and by the GSH replenishing antioxidant N-acetylcysteine (NAC). Together, our study provides mechanistic insights into the mode of action of the natural substance SFN. It specifically exerts TH17 prone immunosuppressive effects on untransformed human T-cells by decreasing GSH and accumulation of ROS. Thus, SFN may offer novel clinical options for the treatment of TH17 related chronic inflammatory/autoimmune diseases such as rheumatoid arthritis

Expression of TRX1 optimizes the antitumor functions of human CAR T cells and confers resistance to a pro-oxidative tumor microenvironment

Use of chimeric antigen receptor (CAR) T cells to treat B cell lymphoma and leukemia has been remarkably successful. Unfortunately, the therapeutic efficacy of CAR T cells against solid tumors is very limited, with immunosuppression by the pro-oxidative tumor microenvironment (TME) a major contributing factor. High levels of reactive oxygen species are well-tolerated by tumor cells due to their elevated expression of antioxidant proteins; however, this is not the case for T cells, which consequently become hypo-responsive. The aim of this study was to improve CAR T cell efficacy in solid tumors by empowering the antioxidant capacity of CAR T cells against the pro-oxidative TME. To this end, HER2-specific human CAR T cells stably expressing two antioxidant systems: thioredoxin-1 (TRX1), and glutaredoxin-1 (GRX1) were generated and characterized. Thereafter, antitumor functions of CAR T cells were evaluated under control or pro-oxidative conditions. To provide insights into the role of antioxidant systems, gene expression profiles as well as global protein oxidation were analyzed. Our results highlight that TRX1 is pivotal for T cell redox homeostasis. TRX1 expression allows CAR T cells to retain their cytolytic immune synapse formation, cytokine release, proliferation, and tumor cell-killing properties under pro-oxidative conditions. Evaluation of differentially expressed genes and the first comprehensive redoxosome analysis of T cells by mass spectrometry further clarified the underlying mechanisms. Taken together, enhancement of the key antioxidant TRX1 in human T cells opens possibilities to increase the efficacy of CAR T cell treatment against solid tumors

Ulusaldan Küresele: Popülizm, Demokrasi, Güvenlik Konferansı

Öngörülmesi giderek güçleşen, sarsıntılı ve savrulmalı zamanlardan geçiyoruz. İkinci Dünya Savaşı ve Soğuk Savaş ortak deneyimleri sonrasında 1950’lerden ve 1990’lardan itibaren demokratik sistemlerin peş peşe dalgalarla meşrulaşacağı, yaygınlaşacağı ve güçleneceği öngörüsü hakimdi. Ancak son yıllarda yaşanan bazı gelişmelerle demokrasilerin geleceği tekrar sorgulanmaya başladı. Gerek 11 Eylül ile başlayan ve IŞİD ile devam eden ve şiddet içeren İslamcı radikalizm, gerek Batı demokrasilerinde popülist radikal sağ hareketlerin ve beyaz ırkçı grupların yükselişi ve iktidara gelişi, bir yandan güvenlik-özgürlük ikileminin demokrasi dengesini bozdu, bir yandan da hem demokratik sistemlerin hem dünya barışının geleceğini bizi tekrar sorgular, sorgulatır hale getirdi. Demokrasileri bildiğimizi zannediyoruz, ama demokrasiler ile ilgili daha öğrenmemiz gereken çok şey var. Demokrasi kaderimiz de geleceğimiz de olmak zorunda değil belki de. Ya da belki yanlış yerden soru sormaya başlıyoruz, belki demokrasi yerine yeni bir referansa ihtiyacımız var. Aslında demokrasileri çantada keklik görmeyip, sabırla büyütüp yeşertmek, geliştirmek, korumak, ileri safhalara taşımak ve bizden sonraki nesillere aktarmak bir sorumluluk, ve bu sorumluluk bizlere ait. Popülizm, demokrasi, güvenlik kavramlarının her biri bugün sıkça ve yaygın olarak kullandığımız kavramlar olarak gündelik sohbetlerimizin içine kadar girmiş durumda. Bu yaygın kullanımlarına rağmen her bir kavram, üzerine düşünmeye, tartışmaya ve değerlendirmeye tekrar tekrar olanak verecek derinlikte. Her bir tartışma bir diğerini açarken, farklı gibi görünen bu kavramların birbirleriyle kesiştikleri zeminler bulmak mümkün. Popülist liderlerin politikaları bütün siyaset yapma biçimlerini kendine çeken ya da kendinden uzaklaştıran eksenler yaratarak her ikisini de aynı anda besleyebiliyor. Popülist politikaya angaje olan liderler ve grupların yanında bu politikaya karşı mücadele eden kişiler ve kitleler de yok değil, ancak kimi zaman bu kitleler eleştirdiği bu siyaset biçiminin kurucu öznesi haline de gelebiliyor. Bunun karşısında tabandan gelen demokratikleşme talepleri ve popülist siyasetle beraber kurumsallaşan diğer politika yapma biçimleri, demokrasi anlayışımızı farklı yönlere çekebiliyor. Bu demokratikleşme talepleri kimi zaman olumlu karşılıklar alsa da, kimi zaman devletlerin güvenlik politikaları ile etkisizleştirilmeye ve bastırılmaya çalışılıyor. Güvenlik politikalarının alanı günümüz teknolojisi sebebiyle o kadar genişledi ki, bu politikanın nesnesi haline gelmemiş varlık ve alan bulmak neredeyse mümkün değil. Ulusaldan Küresele: Popülizm, Demokrasi, Güvenlik konferansımız bu alanların kendine özgülüklerini göz önünde bulundururken, aralarındaki kesişimleri de ortaya koyan pek çok değerli sunuma ev sahipliği yaptı. Konferansın düzenlenmesinde emeği geçen herkese, ve bu bildiri kitabında tam metinleri ve özetleri bulunan bütün katılımcılarımıza çok teşekkür ederiz.Publisher's Versio

Optimal controller design for autonomous flight of a quadcopter

Yüksek Lisans TeziQuadcopterler; askeri operasyonlarda, arama kurtarma faaliyetlerinde, tarımsal uygulamalarda, haritalama, gözetleme ve teslimat gibi çeşitli alanlarda yaygın olarak kullanılan insansız hava araçlarıdır (İHA). Bir quadcopterin kararlı ve hassas kontrolünü sağlamak, güvenli ve verimli çalışma için çok önemlidir. PID (Orantılı-İntegral-Türev) denetleyici, quadcopter kontrolünde literatürde yaygın olarak kullanılan bir denetleyici tipidir. PID denetleyicisi, quadcopterin motor hızlarını sürekli olarak ayarlamak ve havadaki yönelimini ve konumunu kontrol etmek için sensörlerden gelen geri bildirimleri kullanır. Bu tez, quadcopterin PID kazançlarını metasezgisel algoritmalar yardımıyla optimum ayarlayarak uçuş performansını ve stabilitesini artıran etkili bir yöntem sunmaktadır. Bu tez kapsamında, çevrim dışı bir yaklaşım benimsenmiş ve Kaskat PID kontrolcü kazançlarının optimum değerlerini bulmak için metasezgisel algoritmalar kullanılmıştır. Quadcopterin PID parametreleri, Parçacık Sürü Optimizasyonu (PSO), Bozkurt Optimizasyonu (GWO), Yapay Arı Kolonisi (ABC) ve Diferansiyel Gelişim (DE) algoritmaları kullanılarak simülasyon ortamında optimize edilmiştir. Optimizasyon problemini çözmek için; İntegral Mutlak Hatası (IAE), İntegral Kare Hatası (ISE), İntegral Zaman Mutlak Hatası (ITAE) ve İntegral Zaman Kare Hatası (ITSE) olmak üzere dört farklı uygunluk fonksiyonu kullanılmıştır. Bu uygunluk fonksiyonları, quadcopterin doğrusal olmayan matematik modeli için ağırlıklandırma katsayıları ile özelleştirilmiştir ve arama algoritmaları tarafından minimize edilecek şekilde tasarlanmıştır. Daha sonra özelleştirilmiş uygunluk fonksiyonlarını minimize eden optimum kontrolcü kazançları belirlenmiştir. Kazançları optimize dilen Kaskat PID kontrolcüler, spiral ve kare yörünge üzerinde test edilmiştir. Kontrolcü performansları tablo ve grafikler halinde sunulmuştur.A quadcopter is an unmanned aerial vehicle (UAV) widely used in various applications such as military, search and rescue, agriculture, mapping, surveillance, and delivery. For safe and efficient operations, it is critical to ensure stable and precise control of quadcopter. PID (Proportional-Integral-Derivative) controller is commonly used in quadcopter control in the literature. PID controller uses feedback information from sensors to continuously adjust the motor speeds of the quadcopter in the attitude and position control. This thesis offers an effective method that enhances flight performance and stability by tuning PID gains with the help of metaheuristic algorithms. Within the scope of this thesis, metaheuristic algorithms were utilized by using an offline approach to find the optimal values of the Cascade PID gains. The PID parameters of the quadcopter were optimized in a simulation environment using Particle Swarm Optimization (PSO), Grey Wolf Optimization (GWO), Artificial Bee Colony (ABC), and Differential Evolution (DE) algorithms. Four different fitness functions, Integral Absolute Error (IAE), Integral Square Error (ISE), Integral Time Absolute Error (ITAE), and Integral Time Square Error (ITSE), were used to solve the optimization problem. These fitness functions have been customized by using the weighting coefficients for the nonlinear mathematical model of the quadcopter and designed to be minimized by the research algorithms. Then the optimal controller gains minimizing the customized fitness functions were determined. The Cascade PID controllers whose gains were optimized were tested on spiral and square trajectories. The performances of the controllers were presented in tables and graphs

Performance analyses of CO2-N2O cascade system for cooling

WOS: 00038903720003

Incidence of &ITH . pylori&IT in the tonsillar specimens of the children with chronic tonsillitis with Giemsa stain

Objective: Although H . pylori (Hp) colonisation in the gastric tissue has been proven, Hp has been also reported to be seen in tonsillar and adenoid tissues. While its presence in the gastric tissue is effective in the development of gastritis, peptic ulcus and adenocarcinoma, it has been reported that its presence in tonsillar and adenoid tissue may be a precursor of malignant diseases such as MALT lymphoma. Therefore, we aimed to investigate the incidence of H . pylori in tonsillar tissue.& para;& para;Methods: The presence of H . pylori was investigated histochemically in the tonsillectomy materials of children and young patients who were diagnosed with chronic tonsillitis. Giemsa stain was applied to the tonsillar specimens examined in our hospital pathology laboratory between August 1, 2013 and August 1, 2017.& para;& para;Results: Sixty-eight patients aged between 1 and 18 years who were examined in the Department of Pathology of the Erzurum Regional Education and Research Hospital during the last 4 years were investigated. Of these, 28 (41.2%) were female and 40 (58.8%) were male. The mean age of all patients was 9 +/- 4.02 years. Giemsa staining was applied to the tissue specimens prepared from specimens, and examined under microscope to look for Hp. Hp was positive in tonsillar tissue specimens of 31 patients. H . pylori was detected in a single (n=13: 19.1%) or both tonsils (n=18: 26.5%). H . pylori was isolated from 12 (42.9%) tonsillectomy materials (unilateral, n=4: 14.3% and bilateral, n=8: 28.6%) of 28 female patients. H . pylori was seen in tonsillectomy materials of 19 (47.5%) of 40 male patients (unilateral, n=9: 22.5%, and bilateral, n=10: 25%).& para;& para;Conclusion: As a result, H . pylori was detected in 45.6% of all cases with a slight male predominance. Chi-square test was performed using SPSS 20.0. The presence of Hp was not found to be directly related to age and gender when the tonsillectomy materials of the patients with chronic tonsillitis in 1-18 age group were analyzed

Prevalence of H pylorii In The Tonsillar Tissue of The Children With Giemsa Stain.

Objective: Although H . pylori (Hp) colonisation in the gastric tissue has been proven, Hp has been also reported to be seen in tonsillar and adenoid tissues. While its presence in the gastric tissue is effective in the development of gastritis, peptic ulcus and adenocarcinoma, it has been reported that its presence in tonsillar and adenoid tissue may be a precursor of malignant diseases such as MALT lymphoma. Therefore, we aimed to investigate the incidence of H . pylori in tonsillar tissue.& para;& para;Methods: The presence of H . pylori was investigated histochemically in the tonsillectomy materials of children and young patients who were diagnosed with chronic tonsillitis. Giemsa stain was applied to the tonsillar specimens examined in our hospital pathology laboratory between August 1, 2013 and August 1, 2017.& para;& para;Results: Sixty-eight patients aged between 1 and 18 years who were examined in the Department of Pathology of the Erzurum Regional Education and Research Hospital during the last 4 years were investigated. Of these, 28 (41.2%) were female and 40 (58.8%) were male. The mean age of all patients was 9 +/- 4.02 years. Giemsa staining was applied to the tissue specimens prepared from specimens, and examined under microscope to look for Hp. Hp was positive in tonsillar tissue specimens of 31 patients. H . pylori was detected in a single (n=13: 19.1%) or both tonsils (n=18: 26.5%). H . pylori was isolated from 12 (42.9%) tonsillectomy materials (unilateral, n=4: 14.3% and bilateral, n=8: 28.6%) of 28 female patients. H . pylori was seen in tonsillectomy materials of 19 (47.5%) of 40 male patients (unilateral, n=9: 22.5%, and bilateral, n=10: 25%).& para;& para;Conclusion: As a result, H . pylori was detected in 45.6% of all cases with a slight male predominance. Chi-square test was performed using SPSS 20.0. The presence of Hp was not found to be directly related to age and gender when the tonsillectomy materials of the patients with chronic tonsillitis in 1-18 age group were analyzed

3D Cellular Architecture Modulates Tyrosine Kinase Activity, Thereby Switching CD95-Mediated Apoptosis to Survival

The death receptor CD95 is expressed in every cancer cell, thus providing a promising tool to target cancer. Activation of CD95 can, however, lead to apoptosis or proliferation. Yet the molecular determinants of CD95’s mode of action remain unclear. Here, we identify an optimal distance between CD95Ligand molecules that enables specific clustering of receptor-ligand pairs, leading to efficient CD95 activation. Surprisingly, efficient CD95 activation leads to apoptosis in cancer cells in vitro and increased tumor growth in vivo. We show that allowing a 3D aggregation of cancer cells in vitro switches the apoptotic response to proliferation. Indeed, we demonstrate that the absence or presence of cell-cell contacts dictates the cell response to CD95. Cell contacts increase global levels of phosphorylated tyrosines, including CD95’s tyrosine. A tyrosine-to-alanine CD95 mutant blocks proliferation in cells in contact. Our study sheds light into the regulatory mechanism of CD95 activation that can be further explored for anti-cancer therapies

Table_1_Expression of TRX1 optimizes the antitumor functions of human CAR T cells and confers resistance to a pro-oxidative tumor microenvironment.xlsx

Use of chimeric antigen receptor (CAR) T cells to treat B cell lymphoma and leukemia has been remarkably successful. Unfortunately, the therapeutic efficacy of CAR T cells against solid tumors is very limited, with immunosuppression by the pro-oxidative tumor microenvironment (TME) a major contributing factor. High levels of reactive oxygen species are well-tolerated by tumor cells due to their elevated expression of antioxidant proteins; however, this is not the case for T cells, which consequently become hypo-responsive. The aim of this study was to improve CAR T cell efficacy in solid tumors by empowering the antioxidant capacity of CAR T cells against the pro-oxidative TME. To this end, HER2-specific human CAR T cells stably expressing two antioxidant systems: thioredoxin-1 (TRX1), and glutaredoxin-1 (GRX1) were generated and characterized. Thereafter, antitumor functions of CAR T cells were evaluated under control or pro-oxidative conditions. To provide insights into the role of antioxidant systems, gene expression profiles as well as global protein oxidation were analyzed. Our results highlight that TRX1 is pivotal for T cell redox homeostasis. TRX1 expression allows CAR T cells to retain their cytolytic immune synapse formation, cytokine release, proliferation, and tumor cell-killing properties under pro-oxidative conditions. Evaluation of differentially expressed genes and the first comprehensive redoxosome analysis of T cells by mass spectrometry further clarified the underlying mechanisms. Taken together, enhancement of the key antioxidant TRX1 in human T cells opens possibilities to increase the efficacy of CAR T cell treatment against solid tumors.</p