Identification of Predictive Response Markers and Novel Treatment Targets for Gliomas

Gliomas are the most frequent primary brain tumors in adults. Despite multimodality treatment strategies, the survival of patients with a diffuse glioma remains poor. There has been an increasing use of molecular markers to assist diagnosis and predict prognosis and response to therapy. Although several prognostic and predictive response markers have been identified, considerable research still needs to be done to improve on these. Therefore, the identification of novel predictive response markers and therapeutic targets are desperately needed for this dismal disease. In this thesis, we describe prognostic and identify novel predictive markers in randomized clinical trials. We determined the gene expression profiles of samples of anaplastic oligodendrogliomas and oligoastrocytomas from the EORTC 26951 study and samples of recurrent glioblastomas of the BELOB study to evaluate the treatment responses within defined intrinsic glioma subtypes (IGSs). IGSs are molecularly similar tumors that have been previously identified by unsupervised gene expression analysis. We found that IGSs can be used to assess the molecular heterogeneity within clinical trials. In addition, we confirmed that IGS subtypes are prognostic for survival and predictive. Tumors assigned to IGS-9 showed benefit from adjuvant PCV chemotherapy. In the BELOB study, we found that tumors assigned to IGS-18 (classical GBMs) showed a trend towards benefit from Beva+CCNU treatment. Expression of FMO4 and OSBPL3 were particularly associated with treatment response. Intrinsic subtypes can therefore be used to assess the molecular heterogeneity within clinical trials and may be used as a prognostic and predictive marker. Another method to profile gliomas is based on DNA methylation. We performed genome-wide methylation profiling on material from EORTC 26951 and assessed CIMP and MGMT-STP27 status. We have shown that survival in patients with CIMP+ or MGMT-STP27 methylated tumors was improved compared to CIMP- and/or MGMT-STP27 unmethylated tumors. Importantly, the MGMT-STP27 status was predictive for response to adjuvant PCV chemotherapy in these tumors. MGMT-STP27 may therefore be used to identify AODs and AOAs with improved prognosis and identify patients that are likely to benefit from adjuvant PCV chemotherapy. We also performed functional analysis on different mutations on the EGFR gene and infrequently mutated genes in oligodendrogliomas. We have shown that different mutations within a single gene (EGFR) can have different molecular consequences and have different binding partners for EGFRvIII, EGFRL858 and EGFRwildtype. As these mutations have different functions, each mutation may need its own unique treatment. Functional analysis on infrequently mutated genes showed that the function of many of ‘low frequency’ genes, differs from its wildtype counterpart. This differential effect suggests that these genes can contribute to the disease and therefore may offer new therapeutic targets for oligodendrogliomas

Tumor-specific mutations in low-frequency genes affect their functional properties

Causal genetic changes in oligodendrogliomas (OD) with 1p/19q co-deletion include mutations in IDH1, IDH2, CIC, FUBP1, TERT promoter and NOTCH1. However, it is generally assumed that more somatic mutations are required for tumorigenesis. This study aimed to establish whether genes mutated at low frequency can be involved in OD initiation and/or progression. We performed whole-genome sequencing on three anaplastic ODs with 1p/19q co-deletion. To estimate mutation frequency, we performed targeted resequencing on an additional 39 ODs. Whole-genome sequencing identified a total of 55 coding mutations (range 8–32 mutations per tumor), including known abnormalities in IDH1, IDH2, CIC and FUBP1. We also identified mutations in genes, most of which were previously not implicated in ODs. Targeted resequencing on 39 additional ODs confirmed that these genes are mutated at low frequency. Most of the mutations identified were predicted to have a deleterious functional effect. Functional analysis on a subset of these genes (e.g. NTN4 and MAGEH1) showed that the mutation affects the subcellular localization of the protein (n = 2/12). In addition, HOG cells stably expressing mutant GDI1 or XPO7 showed altered cell proliferation compared to those expressing wildtype constructs. Similarly, HOG cells expressing mutant SASH3 or GDI1 showed altered migration. The significantly higher rate of predicted deleterious mutations, the changes in subcellular localization and the effects on proliferation and/or migration indicate that many of these genes functionally may contribute to gliomagenesis and/or progression. These low-frequency genes and their affected pathways may provide new treatment targets for this tumor type

The prevalence of stillbirths: a systematic review

BACKGROUND: Stillbirth rate is an important indicator of access to and quality of antenatal and delivery care. Obtaining overall estimates across various regions of the world is not straightforward due to variation in definitions, data collection methods and reporting. METHODS: We conducted a systematic review of a range of pregnancy-related conditions including stillbirths and performed meta-analysis of the subset of studies reporting stillbirth rates. We examined variation across rates and used meta-regression techniques to explain observed variation. RESULTS: We identified 389 articles on stillbirth prevalence among the 2580 included in the systematic review. We included 70 providing 80 data sets from 50 countries in the meta-analysis. Pooled prevalence rates show variation across various subgroup categories. Rates per 100 births are higher in studies conducted in less developed country settings as compared to more developed (1.17 versus 0.50), of inadequate quality as compared to adequate (1.12 versus 0.66), using sub-national sample as compared to national (1.38 versus 0.68), reporting all stillbirths as compared to late stillbirths (0.95 versus 0.63), published in non-English as compared to English (0.91 versus 0.59) and as journal articles as compared to non-journal (1.37 versus 0.67). The results of the meta-regression show the significance of two predictor variables – development status of the setting and study quality – on stillbirth prevalence. CONCLUSION: Stillbirth prevalence at the community level is typically less than 1% in more developed parts of the world and could exceed 3% in less developed regions. Regular reviews of stillbirth rates in appropriately designed and reported studies are useful in monitoring the adequacy of care. Systematic reviews of prevalence studies are helpful in explaining sources of variation across rates. Exploring these methodological issues will lead to improved standards for assessing the burden of reproductive ill-health

The Investigation Of Scientific Survey Methods For Subjective Analysis In The Field Of Lighting With Application

Tez (Yüksek Lisans) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2007Thesis (M.Sc.) -- İstanbul Technical University, Institute of Science and Technology, 2007Aydınlatma tasarımlarında belli aydınlık düzeyleri ve parıltı oranlarının hedeflenmesinin yanı sıra, kullanıcıların görsel algılarının da dikkate alınması büyük önem taşımaktadır. Bu nedenle gerçekleştirilen objektif ölçümlere ek olarak, aydınlatmanın temel hedefi olan kullanıcıların görsel konforu için sübjektif analizlere de başvurmak bir zorunluluktur. Bu tez çalışması, aydınlatmada sübjektif analizin gerçekleştirilmesi için izlenmesi gereken bilimsel araştırma yöntemlerini incelemektedir. Bilimsel araştırma yöntemlerinde sübjektif analiz için anket çalışmalarına başvurulmaktadır. Anket çalışmalarının tercih edilmesinin en önemli nedeni, bilimsel esaslar çerçevesinde yürütüldükleri takdirde bu çalışmalardan elde edilen verilerin güvenilir, geçerli ve istatistiksel analize tabi tutulabilecek kalitede olmasıdır. Burada, İstanbul Teknik Üniversitesi Elektrik-Elektronik Fakültesi’nde yürütülen bir deney kapsamında, otomatik kontrollü bir Işık Rafı Sistemi ile, manuel kontrollü bir Geleneksel Aydınlatma Sistemi arasında bir karşılaştırma yapılmıştır. Bu çalışma için Işık Rafı’nı barındıran bir test odasıyla, Geleneksel Aydınlatma Sistemli bir referans oda hazırlanarak, gönüllü örnekleme yöntemiyle seçilmiş 76 denek, bu odalarda belli görsel işleri tamamladıktan sonra, odalar için özel hazırlanmış olan anket sorularına cevap vermişlerdir. Deneklerden elde edilen veriler parametrik t-testi ve Pearson Korelasyonuna tabi tutularak, odalar arası farklılıklar ve degişkenler arası ilişkiler incelenmiştir. Elde edilen sonuçlar, Işık Rafı Sistemi’nin, Geleneksel Aydınlatma Sistemi’nden, aydınlatma tasarımında çok önemli olan kamaşma, rahatsız edici yansıma, parıltı farkları ve aydınlatma memnuniyeti konularında üstün olduğunu göstermektedir.In lighting design, while the main aim is to maintain specific illuminance levels and luminance ratios, it is also very important to take the visual perceptions of the users into consideration. In order to maintain visual comfort, in addition to the objective measurements performed in lighting, consulting the subjective analysis performed by the users, who actually are the main target of lighting, is a must. This thesis investigates the scientific methods of research that should be followed for the subjective analysis of lighting. The method used in scientific research for subjective analysis are questionnaires, as the results obtained from questionnaires are valid, reliable and can be statistically analysed. In the application part of the theses, a Light Shelf System (LSS) equipped with automatic control has been compared to a Traditional Lighting System with manual control in the scope of an experiment carried out in the Electrical and Electronics Engineering Faculty of Istanbul Technical University. For this study, 76 subjects, answered questions specifically prepared for a test and reference room where the lighting systems were isntalled, after completing several visual tasks in these rooms. The data obtained from the subjects have been statistically analysed through parametric t-tests and Pearson Correlations in order to examine the differences between the lighting systems and the relationships within variables. The results show that the LSS has advantages over the traditional lighting system, in very important areas of lighting such as glare, unwanted reflection, luminance differences and lighting satisfaction.Yüksek LisansM.Sc

Energy Efficient Illumination Of Historical Mosques Using Modern Technologies

Tez (Doktora) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2014Thesis (Ph.D.) -- İstanbul Technical University, Institute of Science and Technology, 2014Bu doktora çalışmasında, aydınlatma alanındaki en güncel teknolojilerden biri olan LEDler kullanılarak, tarihi camilerin iç aydınlatmasında gerekli aydınlık düzeyleri ve konfor koşullarından feragat etmeden enerji tasarrufu sağlayacak ve tarihi yapıya sadık kalacak bir aydınlatma elemanının tasarlanması hedeflenmiştir. Buna ek olarak tarihi cami iç aydınlatmasının enerji tüketiminin yenilenebilir enerji kaynaklarından güneş enerjisiyle karşılanabilmesi için gerekli fotovoltaik sistemin seçilmesi ve bu sayede kendi enerjisini üretebilen ve aydınlatma konusunda yeşil-enerji özelliklerine sahip bir tarihi cami kavramı oluşturulması hedeflenmiştir. Doktora tez çalışmasının gerçekleştirilebilmesi için İstanbul tarihi camilerinden Mimar Sinan'ın Şemsi Ahmet Paşa Camii seçilmiş ve Cami içinde çeşitli ölçüm çalışmaları gerçekleştirilmiştir. Cami daha sonra Dialux aydınlatma simülasyon programıyla modellenerek iç aydınlatma koşulları bilgisayar ortamına aktarılmıştır. Tarihi cami aydınlatması için gerekli koşullar göz önünde bulundurularak doktora tez çalışmasının odağını oluşturan LEDli cami kandilinin tasarımı gerçekleştirilmiş, ölçümleri yapılmış ve elde edilen sonuçlar Dialux modeline yerleştirilerek Cami içinde elde edilen fotometrik sonuçlar incelenmiştir. Aydınlatma tasarımının tamamlanmasıyla, talep edilen enerji miktarı elde edilmiş ve bu güç miktarına göre de Cami avlusuna veya Cami etrafındaki boş alanlara yerleştirilebilecek bir fotovoltaik sistem seçimi yapılmıştır. Bu çalışmalar doğrultusunda Şemsi Ahmet Paşa Camii'nin fotometrik koşulları ve buna bağlı olarak görsel konfor koşulları iyileştirilirken, iç aydınlatma yükü azaltılmış ve bu yükü karşılayacak fotovoltaik sistemin tasarımı ile Cami'nin iç aydınlatması için gerekli enerjiyi kendisinin üretebileceği bir model sunulmuştur. Tezin giriş bölümünde çalışmanın yapılma sebeplerine dair gerekli bilgiler verildikten sonra ikinci bölümde tarihi camilerde aydınlatma konusu ele alınmış, doktora tez çalışması için seçilen tarihi Şemsi Ahmet Paşa Camii'nde yapılan fotometrik incelemelere yer verilmiştir. Cami içindeki yapma ve doğal aydınlatma koşulları incelenmiş, aydınlık düzeyi ve iç yüzeylerin yansıtma katsayısı ölçümleri gerçekleştirilmiştir. Mimari çizimlerden faydalanılarak, Cami'nin 3 boyutlu modeli Dialux aydınlatma simülasyon programı ile hazırlanmıştır. Cami içindeki mevcut aydınlatma sisteminin ışık dağılım eğrisi çıkartılarak Dialux programına tanıtılmış ve hazırlanan modelin doğrulanması için Cami içindeki mevcut koşullar simüle edilmiştir. Simülasyon sonuçları, gerçek sonuçlarla örtüşmüştür. Son olarak Cami içinde kullanılan kandilin tarihte kullanıldığı şeklini inceleyebilmek için kandil zeytinyağı ile doldurulup bir fitil yardımıyla yakılmış ve ışık dağılım eğrisi çıkarılmıştır. Çalışmanın bir sonraki adımı olan aydınlatma tasarımında bu ışık dağılım eğrisinin formundan faydalanılmıştır. Üçüncü bölümde çalışmanın aydınlatma tasarımı kısmına yoğunlaşılmıştır. Bu amaçla öncelikle kullanılacak yeni teknoloji olan LEDlerle ilgili araştırmalar yapılmıştır. Bundan sonra LEDli kandil tasarımında izlenen adımlar sırasıyla açıklanmıştır. Kullanılan fotometrik yaklaşım, cami içindeki gerekli aydınlık düzeylerini ve görsel konfor koşullarını sağlayabilmek için hem mevcut sistemin olumlu özelliklerini, hem de tarihi kandilin yapısal özelliklerini bir arada barındıran yeni bir ışık dağılımı elde edilmesidir. Buna göre tasarlanan kandilin tüm uzaya ışık göndermesi hedeflenmiştir. Hedeflenen tasarım için uygun LEDler seçilmiş, çeşitli prototipler hazırlanıp, bu prototiplerin ışık dağılım eğrileri çıkarılmıştır. Bu eğriler yardımıyla Dialux simülasyonları gerçekleştirilerek gerekli koşulları sağlayabilmek için uygun olan LED sayı ve konumu belirlenmiştir. Bundan sonraki adım hedeflenen ışık dağılımı için uygun soğutucu sistemin tasarlanması olmuştur. Solidworks paket programı ile tasarlanan soğutucunun LEDler ve içine yerleştirileceği kandil ile birlikte ısıl simülasyonu gerçekleştirilmiş ve LED paket sıcaklığı uygun bulunarak yapılan tasarımın üretimine geçilmesine karar verilmiştir. Üretilen prototip soğutucu, ısıl testlere tabi tutularak simülasyon sonuçları doğrulanmış ve gerçek koşullardaki jonksiyon sıcaklığı elde edilmiştir. Isıl tasarım tamamlandıktan sonra sürücü devre seçimi gerçekleştirilmiştir. Tüm sistem elemanlarının hazırlanmasından sonra, tasarlanan aydınlatma sisteminin ışık dağılım eğrileri çıkarılmıştır. Eğriler Dialux modeline tanıtılarak ilk işletme durumu, 6000 saat ve 25000 saatlik süreler sonucunda Cami içinde elde edilecek fotometrik koşullar incelenmiştir. Sonuçlar standartlarla belirlenen cami içi aydınlık düzeylerine erişildiğini ve mevcut akkor telli lambalı sisteme göre çok daha kaliteli bir aydınlatma elde edildiğini göstermektedir. Bunlara ek olarak, fotometrik sonuçların görsel konfor açısından değerlendirilmesi için tasarlanan sistemin kamaşma açısından incelemeleri de gerçekleştirilmiştir. Yapılan araştırmalar LEDler ve kamaşma konusunun henüz yeterince araştırılmamış bir konu olduğunu göstermektedirler. Bu sebeple mevcut hesap ve inceleme yöntemlerinin doğurduğu sonuçlar tartışmalıdır. Bununla beraber, standartlara uygunluğun onaylanması için hesaplar yapılmış ve en azından mevcut hesap yöntemlerine göre görsel konfor koşullarının sağlandığı tespit edilmiştir. Dördüncü bölümde, bir önceki bölümde tasarlanan aydınlatma sisteminin enerji tüketimini karşılamak için gerekli olan fotovoltaik sistemin seçimi ve hesapları üzerine yoğunlaşılmıştır. Türkiye'de fotovoltaik enerjiyle ilgili bir literatür taramasından sonra fotovoltaik sistemler ile ilgili genel bilgiler verilmiş ve Şemsi Ahmet Paşa Camii için fotovoltaik sistem seçimi açıklanmıştır. Bunun için Cami iç aydınlatma enerji talebi hesaplanmış, Cami'nin konumlanmış olduğu Üsküdar ilçesi için güneşlenme verileri üzerinde çalışılmış ve sonuç olarak PVsyst paket programının deneme sürümü kullanılarak iki farklı fotovoltaik sistem seçimi yapılmıştır. Bu sistemlerden daha küçük olan ilki Cami'nin sadece iç aydınlatma ihtiyacına denk bir üretim sağlarken, ikinci büyük sistemle iç aydınlatma ihtiyacının yanı sıra Cami'nin diğer elektrik tüketimlerine de denk düşecek bir üretim elde edilmesi hedeflenmiştir. Beşinci bölümde, önerilen modern sistemlerin ekonomik incelemesi gerçekleştirilmiş, elde edilen enerji tasarrufu ve sistemlerin ilk yatırım masraflarını geri ödeme süreleri 10 yıllık bir dönem için incelenmiştir. Buna göre tasarlanan LEDli sistem, armatür başına 10,5 W'lık enerji tüketimiyle, mevcut 40 W'lık sisteme göre % 74'lük enerji tasarrufu sağlamaktadır. Buna ek olarak Cami'ye kurulması hedeflenen fotovoltaik sistem devreye girdiğinde, Cami'nin mevcut durumdaki yıllık 5840 kWh'lik tüketimine eşit miktarda bir üretim elde edilmekte ve Cami iç aydınlatma elektrik yükünü kendi ürettiği enerjiyle karşılayabilir hale gelmektedir. Önerilen ikinci fotovoltaik sistemle ise daha yüksek miktarda enerji üretilerek Cami'nin iç aydınlatma dışındaki enerji ihtiyaçlarının önemli bir kısmını da karşılamak mümkün olmaktadır. LEDli sistem enerji tasarrufu sayesinde kendi masrafını 1,5 yıl içerisinde çıkarmış, LEDli sisteme fotovoltaik sistemin de eklenmesiyle farklı senaryolar için geri ödeme sürelerinin 7,25 yıl ile 8,50 yıl arasında değiştikleri görülmüştür. 10 yıllık süre içinde önerilen tüm sistemler ilk yatırım masraflarını çıkarmış ve ek kazanımların elde edilmesini sağlamışlardır. Sonuç olarak bu doktora tez çalışmasında tasarlanan, seçilen ve önerilen modern teknolojilerle Cami aydınlatma ve enerji tüketimine dair sistemlerin ömür süreleri ve sürdürülebilirlikleri yükseltilmiş, Cami içi fotometrik değerler iyileştirilmiş, önemli miktarlarda enerji tasarrufu ve buna bağlı olarak ekonomik kazanımlar elde edilmiş ve tarihi yapılarda modern teknolojilerin kullanımı teşvik edilmiştir. Önerilen enerji etkin sistemler ile oluşturulan, modern teknolojileri ve yenilenebilir enerji kaynaklarını kullanan "yeşil" kavramlı cami modelinin sadece tarihi camilerde değil, tüm tarihi ibadethaneler ve ek olarak yeni inşa edilen ibadethanelerde de kullanılmasıyla Türkiye'de ciddi anlamda enerji tasarrufları elde edilecektir. Bu şekilde hem ülke ekonomisine hem de Türkiye'nin takip ettiği uluslararası enerji politikalarına katkıda bulunulmuş olacaktır.This study aims at creating a "Green" Historical Mosque Concept, capable of producing its own electricity while using energy-efficient lighting technologies for its interior illumination. In order to do this, the cutting edge technology in the field of lighting, LEDs are used to design a luminaire which maintains the necessary illuminance levels and comfort conditions in the interior lighting of historical mosques while achieving substantial energy savings and preserving the historical texture of the mosque. In addition to this, the energy consumption of the mosque is met by solar power, a renewable energy source, through the correct choice of solar panels and necessary equipment for the system. For the application of the proposed system, Şemsi Ahmet Paşa Mosque, one of Istanbul's historical mosques designed by the famous Ottoman architect Mimar Sinan was chosen, and measurements were carried out in the Mosque. Consequently, the Mosque was 3D modeled using the lighting calculation program Dialux. The LED mosque lantern, which is the main focus of this study, was designed taking into consideration the necessary conditions for the lighting of historical mosques. The photometric measurements of the lantern were carried out and the luminous intensity distributions were turned into digital files, which can be introduced to Dialux. Using these measurement results, Dialux simulations of the mosque were carried out and the photometric results in the Mosque interior were obtained and analyzed. With the finalization of the lighting design, the power consumption was determined and the photovoltaic system that meets this power consumption was chosen. Thus, a model in which the photometric conditions along with the comfort conditions inside Şemsi Ahmet Paşa Mosque was ameliorated, the interior lighting consumption was reduced and a system enabling the Mosque to produce its own interior lighting energy was proposed. With the completion of the lighting design, the energy demand was determined. According to the energy demand, the design of a photovoltaic system was performed. The photovoltaic system was planned to be installed in the yard of the mosque or the unoccupied spaces around the mosque. Thus the study does not only ameliorate the photometric and comfort conditions of the mosque but at the same time provides a new model in which the energy demand of the interior lighting of the mosque is produced by the mosque itself through the installed photovoltaic system. The introduction chapter provides the motivation of the study which is followed by Chapter 2, in which the lighting of historical mosques is handled. The photometric measurements made in Şemsi Ahmet Pasha Mosque are discussed. The artificial and natural illumination conditions inside the mosque are analyzed; illuminance levels and coefficients of reflection which were measured and calculated according to the luminance measurements made on the Mosque interior surfaces are given. The architectural drawings of the Mosque were obtained from the Turkish Directorate General of Foundations. Using these drawings, a 3D model of the Mosque was drawn with the lighting simulation program Dialux. The model was then equipped with the results of the coefficient of reflection measurement in order to simulate the real conditions within the Mosque. To verify the prepared model, the polar photometric curves of the current lighting system within the Mosque were prepared. In order to do this, a special measurement setup was prepared in the Lighting and Installation Laboratory of Istanbul Technical University, in which the luminous intensity distribution of the current mosque lantern with incandescent lamp was deducted. The distribution was then introduced to Dialux and the current situation in the Mosque was simulated. The results of the simulation are very similar to the real life measurements, proving that the model was intrinsically prepared. In addition to the current lighting system in the Mosque, the historical lighting system of the Mosque is also an important parameter in designing a novel lighting system while trying to preserve the historical characteristics. Therefore, the historical system was revived through filling the lantern with olive oil and lighting it up with a wick. The luminous intensity measurements of the historical lantern were also performed and the luminous intensity distribution was prepared. The input obtained from the form of the historical luminous intensity distribution was also taken into consideration in the design of the novel system. Chapter 3 focuses on the lighting design phase of the study. In order to master the topic of LEDs which were used in the design of the new lantern, a comprehensive research on the regarding topic was carried out. After sharing a summary of the research, the steps taken in designing the new lantern are described. The photometric approach in designing the new system is to incorporate all positive characteristics of the actual and the historical systems, while containing the original texture of the lantern in itself. The historical system sends most of the light to the dome of the mosque while the current system sends most of the light to the mosque floor. For a more uniform illuminance level in the mosque, it is necessary to illuminate all the surfaces of the mosque. Therefore, the new design aims at sending the light to all directions. With the determination of the photometric approach, the LEDs which will be used in the system were chosen. Measurements were carried out with the chosen LEDs at the Energy Institute of Istanbul Technical University, Energy Efficiency and Illumination Technique Laboratory using an Ulbricht sphere to determine the effect of junction temperature on LED voltage, luminous flux, efficacy and luminous efficiency. With the results of the measurements, equations on the relationship between junction temperature and luminous flux and luminous efficacy were deducted. Consequently, the design process of the heatsink for the new lantern was started. As LEDs require thermal management systems for their efficient functioning, numerous heat sinks that are readily available in the market were obtained. Using these heat sinks, different designs and configurations were obtained with the LEDs, resulting in different prototype systems. All prototypes were then measured to prepare their luminous intensity distributions. The results were introduced to Dialux and simulations were performed to see which configurations create the most suitable lighting conditions within the mosque. Through comparing the results of the simulations, the best number and configuration of LEDs, along with the general shape of the lighting system were chosen. As the heat sinks used for the prototypes are not specific to this application, their utilization for a novel system has proved to be inefficient. Therefore, using Solidworks, a new heat sink was designed to obtain the proposed luminous distribution. Thermal simulations of the heat sink including the LEDs and the glass lantern in which the heat sink will be positioned were carried out. The results of the simulations show that the solder point and package temperatures obtained with the designed heat sink are convenient for the operation of LEDs. While the heat sink provided suitable conditions for the operation of the LEDs, a lower junction temperature would provide longer lifetimes along with a higher maintenance of luminous output. Therefore, ways to improve the junction temperature were elaborated. The final decision was to make an opening on the bottom part of the glass lantern to enable more efficient air circulation therefore a more efficient cooling process. Simulations were repeated to see the effect of the opening on the base of the lantern and the results were satisfactory. Thus, a prototype of the designed heatsink was manufactured. The LEDs were positioned on the heatsink and the necessary electrical connections were established. The original glass lantern was cut from the bottom as well to obtain the new glass lantern with extra air circulation. The prototype lighting system was then thermally tested to confirm the results of the simulation. The experimental results validated the Solidworks model with very similar values to the simulation. As a result of this study, the junction temperatures of the LEDs in the new lighting system were obtained. The temperatures were then used to calculate the actual luminous flux of the LEDs, using the formulas that were deducted from the Ulbricht sphere measurements. Following the thermal design of the system, the driver for the LEDs providing 350 mA constant current was chosen through experimentally examining several drivers in the market. Finally, all the system elements were made ready and the new lighting system was completed. Then the luminous intensity distributions of the new lighting system were measured and turned into digital files to introduce to Dialux. Dialux simulations were carried out for the initial operation, as well as the results of operation after periods of 6000 hours and 25000 hours using the corresponding maintenance factor values. The obtained photometric values show that with the designed LED mosque lantern, it is possible to meet the illuminance levels specified for the interior lighting of mosques. The new lighting design proves to be highly superior compared to the current lighting system with incandescent lamps inside the Mosque. In addition to the illuminance levels, unified glare rating calculations were also performed to analyze the visual comfort conditions inside the mosque. The research on the field of discomfort glare of LED lighting systems proves to be insufficient, with very little research on the area. Therefore, whether the results obtained from current calculations and analysis methods created for traditional lighting systems apply to LEDs or not is a question mark. In order to emphasize the inadequacy of the current analysis methods, luminance measurements were made with several LED lighting systems at the Lighting Technology Institute of the Karlsruhe Institute of Technology. Comparisons of the LED systems to the traditional systems, which form the bases of the current calculation methods, were made. Calculations were carried out using the results of the luminance measurements of the LED systems and the importance of further research on the field of discomfort glare from LEDs was strongly emphasized. Having mentioned the problems of unified glare rating and LEDs, the calculations using the UGR were nevertheless made, as this is the only evaluation system in the literature for the time being. The results show that the designed system satisfies the necessary visual comfort conditions inside the Mosque. Chapter 4 focuses on the selection and the calculations of the photovoltaic system which will generate the necessary energy to meet the energy demand of the designed lighting system. A literature survey on the status of solar energy in Turkey is provided, followed by information on photovoltaic systems. Consequently the process of choosing the necessary photovoltaic system for Şemsi Ahmet Pasha Mosque was explained. The process includes the calculation of the mosque's interior lighting energy demand, analysis of the solar data for Üsküdar District where the mosque is located and the simulation of the chosen system using the trial version of PVsyst photovoltaic simulation program. Two different grid-connected photovoltaic systems are proposed in the study. The first system only meets the interior lighting demand of the Mosque and the second system is capable of providing more energy to account for other energy demands of the Mosque. The fifth and the final chapter provides an economic analysis of the proposed modern systems. Energy savings as well as payback periods for the systems have been analyzed for a duration of 10 years. The results show that the designed LED system provides an energy saving of 74 % with its 10.5 W energy consumption, compared to the 40 W current lighting system. In addition to this, through the first proposed photovoltaic system, it is possible to reset the current 5840 kWh energy consumption of the Mosque and meet the interior lighting energy demand with solely the energy produced by the Mosque itself. The second proposed system can produce more energy and meet other energy demands of the mosque. The calculations were carried out for four separate scenarios differentiating from each other by means of energy production and the amount of government incentives. The results of the calculations demonstrate that the energy savings obtained by the LED system translate into economic savings and ensure a payback period of 1.5 years. With the addition of the photovoltaic system to the LED lighting system, the payback period remains between 7.25 years and 8.50 years for the four different scenarios. To sum up, all the proposed systems can repay their investment costs and even provide extra savings in 10 years. To conclude, using the modern technologies designed, chosen and proposed in this study, the lifetime and the sustainability of the systems used in the interior lighting of mosques are increased, the photometric conditions are ameliorated, important amounts of energy an

Comparisons of the effects of the sevoflurane and propofol on acute ischemia reperfusion and DNA damages in rabbits

Abstract Background and objectives: The aim of this study was to compare the effects of sevoflurane and propofol anesthesia on oxidative DNA damage that occurs in low-extremity ischemia and is caused by tourniquet application. Methods: Fourteen New Zealand rabbits were randomly allocated into two equal groups. Group S (n = 7) received sevoflurane (2.5-4 percent) inhalation and Group P (n = 7) received a propofol infusion (1-2 mg·kg-1·min-1), after which a pneumatic tourniquet was placed on the right lower extremity. Blood samples were collected prior to tourniquet placement (baseline), 120 min after ischemia, 15 min after ischemia and 120 minutes (min) after ischemia. Malondialdehyde (MDA) levels were analyzed to determine lipid peroxidation, and single cell gel electrophoresis (SCGE) was used to determine DNA damage. Results: At 15 min after ischemia, the MDA levels in Group P (8.15 ± 2.61 µM) were higher than baseline (6.26 ± 3.19 µM, p = 0.026) and Group S (4.98 ± 0.77 µM, p = 0.01). DNA damage was similar in both groups, although DNA damage was higher than baseline (tail moment 0.63 ± 0.27, tail intensity 3.76 ± 1.26) in Group P at the 15th minute of reperfusion (tail moment 1.05 ± 0.45, p = 0.06; tail intensity 5.33 ± 1.56, p = 0.01). The increase in tail moment and tail intensity returned to normal levels in both groups 2 hours after the termination of ischemia. Conclusion: Given that oxidative stress and genotoxic effect disappear in the late stages of reperfusion, we conclude that neither sevoflurane nor propofol can be considered superior to the other in anesthesia practices for extremity surgeries involving the use of a tourniquet