Enhanced immunomodulatory applications of nucleic acid encapsulating liposomes

Ankara : The Department of Moleculer Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2009.Thesis (Master's) -- Bilkent University, 2009.Includes bibliographical references leaves 82-90.Recent studies have demonstrated that innate immune system has great ability to discriminate self from non-self through the action of innate immune receptors. The most extensively studied innate immune receptor family is the Toll-like receptors (TLRs). Endosomal/intracellular TLR3, TLR7/8 and TLR9 recognize dsRNA, ssRNA and unmethylated CpG DNA respectively. Upon activation following recognition of nucleic acids by endosomal TLRs, B cells secrete IL6, dendritic cells and macrophages secrete type I IFNs, IL12 and NK cells secrete IFNγ which yields Th1 type immune response. Modulating the immune response to mount such an immune response by TLR ligands are harnessed in medical applications such as anticancer, antiviral, antibacterial therapies, anti-allergen, as vaccine adjuvant and as immunoprotective agents. Promising clinical applications of TLR ligand nucleic acids are hampered due to their premature in vivo digestion by endonucleases and rapid clearance via serum protein absorption leading to limited stability and bioavailability. A powerful tool to overcome this problem can be achieved by encapsulating TLR ligands within liposomes, which increase in vivo stability as well as augment targeting and internalization to relevant innate immune cells. In this study we aimed to establish the most immunostimulatory liposome type encapsulating or coencapsulating CpG ODN and pIC. Five different liposomes possessing different physicochemical properties were prepared and their immunostimulatory potential when nucleic acid TLRs are loaded, were assessed. Following stimulation of splenocytes with combinations of these liposome types we have observed that neutral, anionic and stealth liposome encapsulating D-ODN, led to a dose dependent significantly higher IFNγ production over free counterpart. Stealth liposome encapsulating pIC induced both IL6 and IFNγ 10 and 250 fold respectively over free pIC. Neutral and anionic liposome coencapsulating D-ODN with pIC were very strong type 1 IFN as well as Th1 cytokine inducers both in vitro and ex vivo. Then, we immunized B6 mice with anionic liposome coencapsulating D-ODN and OVA to establish the immuno-adjuvant properties of liposome formulations in vivo. We assessed primary and secondary anti-OVA IgG subclass responses of mice. Results strongly implicated that even after primary immunization, we could obtain significantly higher anti-OVA IgG and IgG2a response over OVA mixed D-ODN group. After booster injection, 22 fold more IgG, 26 fold more IgG1 and 13 fold more IgG2a were obtained compared to free group. Our findings demonstrated that when simultaneous delivery of adjuvant (D-ODN) and antigen (OVA) within a proper depot system is given to a host, very potent antigen specific immunity is achieved. This knowledge will pave the way to design of novel effective vaccine adjuvants.Erikçi, ErdemM.S

Analyzing the effect of consumer returns in a multi-period inventory system

Ankara : The Department of Industrial Engineering and the Graduate School of Engineering and Science of Bilkent University, 2012.Thesis (Master's) -- Bilkent University, 2012.Includes bibliographical references.Return of a sold item by a customer becomes tremendously common situation in many industries. Increase in the amount of returned items promotes return information to be a critical factor for inventory control. Undoubtedly another critical parameter for an inventory system is the length of the review period. Effect of the review period or length of the time-bucket is amplified with returned items, because available return information at a decision point is related to the frequency of the review. In this study, we analyze the effects of these two parameters over a multiperiod inventory system where the length of a time horizon is fixed. Dynamic programming approach is used to calculate the optimal inventory positions. In dynamic programming, it is assumed that a fixed proportion of sold items are returned. Computational results are obtained to compare the effects of return information under different return proportions and period lengths. These results are used to conduct various analyses to explore the level of the advantage gained by using return information.Erikçi, İsmailM.S

Slow City Movement is an Utopia of Livable City?

The Slow Food and as an extension of it, Slow City (Cittaslow) Movement is born when these disadvantages are posed by modernity and globalization. Slow city is a way of life that cultural richness and quality of life are preserved and defended in the city's local scale. Also, it is an urban model which may be prevented in the standardization of lifestyles to achieve the environmentally-conscious and tourism-based of local development. Thus, it is aimed to improve the quality of life in cities and opposed the homogenization of cities. Slow City Movement is adopted day by day in terms of societal, cultural and social needs and as a model of local government. Slow city movement aims to create livable cities. It is important that how much of this discourse can be perform. This discourse contains similarities with the concept of "utopia" which was put forward for creating an ideal society and was effective for constructing the cities after the II World War. "Ideal urban designs" are asked for "ideal society" with design utopias that give the meaning of the conceptual contrasts of "Ideal location" (Eutopia) and "non-place" (Outopia). Does Slow City Movement, which suggests the new layout / space organization about the city and the society and approach from a critical perspective to the current plans, create the concept of "ideal city"? How will ideal societies and ideal spaces be meaningful and accessible when creating the ideal cities? In this study, the aims of creating livable city, similarities and differences of "utopia urban designs", which is developed as a design and a discourse, but not being successful in practice, and "Slow City Movement" are questioned. The main problematic of this study are how much the Slow City Movement performs the livable discourse and how much of it remains utopias

Serum lipid leves in patients with coronary heart disease are related to their body fatness and fat distribution

Bu çalışma, koroner kalp hastalarında serum total kolesterol ve trigliserit düzeyleri ile vücut yağ miktarı ve yağ dağılımı arasındaki ilişkileri araştırmak amacıyla yapılmıştır. Vücut yağ miktarı ve ağ dağılımını saptamak için Vücut Kitlesi indeksi, Bel-Kalça Oranı, Triceps Deri Kıvrım Kalınlığı gibi antropometrik ölçümler ve bilgisayarlı tomografiden yararlanılmıştır. Eldeki sonuçlara göre koroner kalp hastalarında Vücut Kitlesi indeksi, Bel-Kalça Oranı ve Triceps Deri Kıvrım Kalınlığı antropometrik ölçümleri ile hastaların lipid profili arasında anlamlı bir ilişki bulunamamıştır. Bilgisayarlı tomografi ile belirlenen abdominal visseral ve deri altı yağ alanları ile serum total kolesterol ve trigliserit düzeyleri arasında da bir ilişki saptanmamıştır. Fakat abdominal visseral yağ alanını deri altı yağ alanına bölünmesi ile elde edilen V/ D oranı ile serum total kolesterolü arasında negatif yönde kuvvetli bir ilişki saptanmıştır. Aynı oran ile serum trigliserit düzeyleri arasında bir ilişki bulunamamıştır. Abdominal visseral ve deri altı yağ alanları arasında ise pozitif yönde anlamlı bir ilişki belirlenmiştir.This study was conducted to investigate whether serum total cholesterol, and triglyceride levels in patients with coronary heart disease are related to their body fatness and fat distribution. Several anthropometric measurements such as body mass index, waist-to-hip ratio, triceps skinfold thickness and computed tomography were used to determine body fatness and fat distribution pattern. Body mass index, waist-to-hip ratio, triceps skinfold thickness measurements in patients with coronary heart disease showed no relationship with their lipid profiles. Furthermore, serum total cholesterol, and triglyceride levels in this patient group were not associated with the abdominal visceral and subcutaneous areas which were determined by computed tomography. There was a negative significant correlation between serum total cholesterol and VIS (visceral and to subcutaneous fat area ratio) which was obtained by dividing visceral fat area by subcutaneous fat area. A significant relationship was not found between serum triglyceride levels and VIS ratio. Additionally a positive and statistically significant correlation was observed between abdominal visceral and subcutaneous fat areas

Sticky Platelet Syndrome in Patients with Uninduced Venous Thrombosis

Abstract: Objective: Sticky platelet syndrome (SPS) is a common autosomal dominant inherited platelet disorder. SPS is characterized by platelet hyperreactivity and is associated with arterial and venous thrombosis. The aim of this study was to determine the role of SPS in patients with uninduced venous thrombosis. Material and Methods: The study included 28 patients (15 male and 13 female) with uninduced venous thrombosis. SPS was defined according to Mammen's aggregation method, which is described in detail elsewhere. Results: According to the defined ranges for platelet hyperreactivity, 3 (50%) patients, 2 (33%), and 1 (17%) (n =6 [21%]) with a confirmed diagnosis were classified as type II, I, and III SPS, respectively. In 1 patient SPS was the only hereditary abnormality noted. The other 5 patients carried other inherited coagulation defects, in addition to SPS. Conclusio

England's Middle East policies and Wahability (XIX-XX. centuries)

Yüksek Lisans TeziBu çalışmada İngiltere için Orta Doğu’nun önemi, İngiltere’nin Orta Doğu politikası ve bu politikanın temel direklerinden biri olan Vehhabilik ve onun en önemli destekçisi olan Suud ailesi incelendi. İngilizler, bütün planlarını sömürgecilik yarışında öne geçmelerini sağlayan Hindistan’ı koruma üzerine kurmuşlar ve Hindistan’ın korunması adına da en önemli duraklarından biri olarak Arap Yarımadası’nı görmüşlerdir. Bu Yarımada’nın ele geçirilmesi hususunda pek çok aşiretle çalışmışlar ancak yapılan iç savaşlar nedeniyle geriye Şerif Hüseyin’in başında bulunduğu Haşimiler ile İbn Suud’un başında bulunduğu Vehhabi Suudlar kalmış, Suudların baskın gelmesi neticesinde Şerif Hüseyin coğrafyayı terk etmek durumunda kalmıştır. Böylelikle coğrafyanın yönetimi tamamen Vehhabi Suud ailesinin eline geçmiştir. Aslına bakılırsa bölgenin Vehhabi Suudların eline geçmesi, İngilizlerine eline geçmesi ile eş anlamlıdır. Erken tarihlerde başlayan İngiliz-Vehhabi Suud iş birliği Osmanlıya, Arap ve İslam âlemine büyük zarar vermiştir ve hâlen vermektedir. Çalışmada iş birliğinin neden ve nasıl gerçekleştiği ile sonuçları incelendi.In this study, the importance of the Middle East for England, Britain's Middle East policy and Wahhabism, which is one of the main pillars of this policy, and its most important supporter, the Saud family, were examined. The British built all their plans on the protection of India, which enabled them to take the lead in the colonial race, and they saw the Arabian Peninsula as one of their most important stops for the protection of India. They worked with many tribes to seize this Peninsula, but due to the civil wars, the Hashemites led by Sheriff Hussein and the Wahhabi Sauds led by Ibn Saud remained. As a result of the raids of the Saudis, Sheriff Hussein had to leave the region. Thus, the administration of the geography passed completely into the hands of the Wahhabi Saud family. In fact, the region's falling into the hands of the Wahhabi Sauds is synonymous with the British governance of the region. The British-Wahhabi Saudi cooperation, which started at an early date, caused great harm to the Ottoman, Arab and Islamic worlds and still does. In the study, why and how this cooperation took place and its results were examined

Serotoninin Renal Hasardaki Rolü

In various acute and chronic renal diseases, tissue damage occurs and platelet activation is observed. Recent studies suggest that some factors released from activated platelets may participate in inflammation and fibrosis observed after renal injury. Serotonin is stored in platelets and is released upon platelet activation into the local microenvironment. Serotonin is released upon platelet activation and its effect on proximal tubular epithelial cells has not been determined yet. In this thesis, it was investigated whether platelets and platelet-released serotonin are involved in the function of renal proximal tubular epithelial cells. For this purpose, renal proximal tubular epithelial epithelial cells were stimulated with various concenrations of platelet lysate (PL) or serotonin for different periods and the phenotypic transition of these cells into myofibroblasts were demonstrated under light microscobe. This transition is confirmed by the determination of upregulation in α-SMA gene expression, which is known as fibroblast-myofibroblast transdifferantiation marker. Martix metalloproteinase-2 (MMP-2), tissue inhibitors of metalloproteinase-1 (TIMP-1) and collagen-α1 (COL-α1) upregulations in gene and protein levels, which are reported to be changed in renal inury, were also demonstrated. After stimulation with serotonin and PL, expressions of some inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) were increased in both protein and gene levels. Recently, there isn’t any published report on the effect of serotonin on renal injury. Platelets are known as the cells that aggregate in the injury site in the early stage and serotonin is released in excess amounts into the local microenvironment following the activation. Therefore it is important to define the role of serotonin both in damage and in healing process.Çeşitli akut ve kronik böbrek hastalıklarında doku hasarı oluşmakta ve platelet aktivasyonu gözlenmektedir. Son yıllarda yapılan çalışmalarda aktive olmuş plateletlerden salınan bazı faktörlerin organ hasarı sırasında gözlenen enflamasyonda ve sonrasında gelişen fibrozis oluşumunda rol aldıkları ileri sürülmüştür. Serotonin, plateletlerde depo edilmekte ve plateletlerin aktivasyonu sonucunda ortama salınmaktadır. Renal hasar sırasında erken dönemde gözlenen platelet aktivasyonu sonucu ortama salınan serotoninin, proksimal tübül epitel hücreleri üzerine etkileri ise henüz araştırılmamıştır. Bu tez kapsamında, plateletlerin ve plateletlerden salınan serotoninin, renal proksimal tübül epitel hücrelerinin işlevine etkileri incelenmiştir. Bu amaçla proksimal tübül epitel hücreleri farklı süre ve dozlarda platelet lizatı (PL) ve serotonin ile uyarılmış ve bu hücrelerin fenotip değiştirerek miyofibroblastlara dönüştüğü ışık mikroskobu altında gösterilmiştir. Bu değişim, fibroblastmiyofibroblast dönüşümünün bir belirteci olan α-SMA gen ekspresyonundaki artışın tayini ile de doğrulanmıştır. Renal hasar sırasında gen ve protein düzeyinde ekspresyonlarında değişiklik olduğu rapor edilen matriks metalloproteinaz-2 (MMP- 2), metalloproteinaz doku inhibitörü-1 (TIMP-1) ve kollajen-α1 (COL-α1) gen ekspresyonlarında artış gösterilmiştir. Serotonin ve PL ile uyarımı takiben tümör nekroze edici faktör-α (TNF-α), interlökin-6 (IL-6) ve transforme edici büyüme faktörü-β1 (TGF-β1) gibi enflamatuar sitokinlerin ekspresyonları gen ve protein düzeyinde artmıştır. Literatürde serotoninin renal hasar üzerindeki etkinliğini konu alan bir çalışma bulunmamaktadır. Hasarlı bölgeye ilk olarak ulaşan hücrelerden birisi olan plateletlerin aktivasyonu sonucunda, hasarlı bölgedeki hücrelerin maruz kaldığı serotonin düzeyinin arttığı bilinmektedir. Bu açıdan serotoninin hasarda ya da iyileşme sürecindeki rolünün belirlenmesi önemlidir

Sofralık Fermente Zeytinlerden (Olea europaea L.) İzole edilen Laktik Asit Bakterilerinin Antimikrobiyal Aktivitesinin ve Bazı Metabolik Özelliklerinin Belirlenmesi

Dünyada ve ülkemizde yaygın olarak tüketilen zeytin (Olea europaea L.)  beslenme açısından büyük öneme sahiptir. Doğal gıdalara yönelişin arttığı günümüzde önemi gittikçe artmaktadır. Bu çalışmada ülkemizde üretilen fermente olmuş ticari ve evde üretilen zeytin örneklerinden izole edilen laktik asit bakterilerinin antimikrobiyal aktivitesi ile bazı metabolik özellikleri belirlenmiştir. On sofralık yeşil zeytin ve 10 sofralık siyah zeytin örneklerinden 50 laktik asit bakterisi izole edilmiştir. Bu izolatların antimikrobiyal etkisi agar difüzyon yöntemi ve sandvic overlay yöntemi ile belirlenmiştir. Etkili izolatlar tanımlanarak bunların laktik asit, hidrojen peroksit ve proteolitik aktivitesi belirlenmiştir. Antimikrobiyal aktiviteye sahip 6 izolattan SZ5 L.plantarum, DZ2 E. facium, EZ8, BZ1, SZ1 ve BZ4 izolatları L. brevis olarak tanımlanmıştır. Laktik asit bakterilerinin pH aralığı 5.3-6.8 arasında, laktik asit miktarları 0.261- 1.818 mg/mL arasında saptanmıştır. Proteolitik aktivite miktarları 0.003-0.011 tirosin mg/mL arasında ve hidrojen peroksit miktarları ise 0.218-0,96mg/mL arasında değişiklik göstermiştir.   Sonuç olarak L. brevis SZ1, E. faeciumDZ2 ve L. brevis BZ1 izolatları yüksek tuz konsantrasyonlarında ve  düşük pH da gelişebilmeleri  ve yüksek laktik asit üretmeleri nedeniyle  starter kültür olmaya aday izolatlar olarak belirlenmiştir

The Evaluation of Secondary Education Basic Mathematics Curriculum through Stake’s Responsive Evaluation Model

The major aim of this study is to evaluate the 11th grade Basic Mathematics (BM) Curriculum implemented at a Vocational and Technical Anatolian High School (Tourism and Hotel Management) through Stake’s Responsive Evaluation Model, and to depict to what extent it responds to the needs and career plans of its students. In this study, qualitative case study design and criterion sampling methods were employed. The data were gathered via observation schedules, document analysis, and semi-structured interviews with 43 participants. Data were analysed via systematic content analysis, inductive coding, and thematising. The results showed that the implementation of the 11th grade BM Curriculum, to a large extent, did not respond to the needs of this specific school, and the students were not able to transfer their math skills to other courses. Though the students used their math skills in their daily lives to an extent, their utilisation of mathematics in their vocations was quite limited. Implications suggest that teachers in the school (micro-level) need interdisciplinary cooperation, setting school performance criteria relevant to vocational high schools at the district level (mezzo-level) and creating and implementing relevant curricula for vocational high schools at the state level (macro-level)