Doctor of Philosophy

dissertationEvery year millions of children are born with a birth defect. Birth defects, which can be described as abnormalities of structure or function that is present from birth, are the leading cause of infant death in developed countries and a significant cause of morbidity and economic burden in low- or middle-income countries. This dissertation addresses the genetic basis of distal arthrogryposes (DAs), a subgroup of birth defects that are characterized by contractures of the distal joints of a limb. Based on previous research of our laboratory, we hypothesized that DAs are defects of contractile apparatus in fast twitch skeletal myofibers and tested this hypothesis in four DA syndromes. We found that mutations of the embryonic myosin heavy chain gene cause DA2A and DA2B, whereas a missense mutation of the perinatal myosin heavy chain gene is responsible for DA7. Furthermore, we found mutations in the adult and extraocular myosin heavy chain genes in some DA5 patients. Furthermore, we noticed some patients with similar findings who do not meet the diagnostic criteria of the known DA syndromes. We proposed one of these conditions to be named as DA10, and mapped this condition to the long arm of chromosome 2. We named the other condition as the CATSHL syndrome, which we showed to be caused by a loss-of-function mutation in the fibroblast growth factor receptor 3 gene. The main contribution of this research is to benefit affected individuals and their families, since molecular testing can now be offered to them. In addition, through further studies leading to a better understanding of normal and abnormal development, effective strategies for prevention and treatment of congenital limb malformations can be developed

Structural Identification of Masonry Residential Buildings Considering Wall Openings

Although one-story residential masonry structures are thought not to be vulnerable to seismic actions, many heavily damaged and/or collapsed instances of these types of structures have been observed in the past strong earthquake events. Hence, the evaluation of their safety requires much attention in terms of more precise numerical models. In-situ vibration tests together with laboratory tests on masonry specimens provide valuable information for structural parameter identification that can be used to develop accurate numerical models. These numerical models then can be used for evaluation of the response and seismic safety. While many specific methods and parameters can be adopted in numerical modeling, linear material properties of a structure are expedient in response analysis. Hence, an equation to be used to determine the homogenized linear model parameters for masonry walls with openings is proposed in this study. The equation has been developed based on the percentage of the openings on the wall. The effect of wall openings on the stiffness and the total strength of one-story masonry structures have been evaluated by using the experimental data and the calibrated finite element models. In-situ ambient vibration and material tests have been conducted on three masonry buildings with identical materials and the results from these experiments were used to verify the accuracy of the formulation

Fibromatosis of the cecum presenting with acute appendicitis: a case report

Although acute appendicitis is a common clinical condition in general surgical practice, <1% of them are associated with malignancies. Appendiceal carcinoids make up most of those malignancies and acute appendicitis cases associated with benign cecal neoplasias are very uncommon. In this study, a 25-year-old female patient who presented with distinct acute appendicitis symptoms is reported. The patient was operated on via open technique. Exploration revealed an appendix with advanced edema and hyperemia. While the cecum was observed to be normal, a solid mass of 2.5 cm diameter was palpated in the appendiceal base. Following the ileocecal resection, histopathological examination revealed the mass as a fibromatosis. The goals of this report are to remind health care professionals that some very rare etiologies may be involved in acute appendicitis diagnosis and treatment, and to underscore the place of laparoscopic approach and preoperative computed tomography in this disease

The Effects Of Nectar Processing On Sour Cherry Antioxidant Compounds: Changes In Metabolite Profile And Bioavailability

Tez (Doktora) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2013Thesis (PhD) -- İstanbul Technical University, Institute of Science and Technology, 2013Bu tez kapsamında, vişne nektarı prosesindeki tüm üretim basamaklarının vişne antioksidanlarının, özellikle de antosiyaninlerin, miktarı ve profili üzerindeki etkisi incelenmiştir. Bunun yanı sıra, in vitro mide-bağırsak sistemi simülasyonu modeli ve in vitro Caco-2 hücre modeli kullanılarak vişne antosiyaninlerinin in vitro biyoyararlığı çalışılmıştır. In vitro Caco-2 hücre modeli analizlerinde, nektar ingredientleri olan sukroz ve sitrik asitin ve gıda matriksinin antosiyanin biyoyararlılığı üzerindeki etkisi de incelenmiştir. Nektar işleme basamaklarından iki tanesi antioksidan madde içeriklerinde istatistiksel olarak önemli değişimlere neden olmuştur. İlki, meyvenin pres suyuna işlenmesi ile miktarlarda (kuru-madde bazında) saptanan 2-3 kat artışlardır. Bu artış, düşük antioksidan madde içeriğine sahip olan posanın presleme aşamasından sonra uzaklaştırılması ile açıklanmaktadır. Posada antioksidan madde içeriğinin düşük olması, posanın ekstraksiyonu için tekrarlanan presleme basamaklarının antioksidan bileşenlerin pres suyuna kazanımını arttırması ile ilişkilendirilmektedir. İkinci önemli değişim, konsantre vişne suyunun nektara işlenmesi ile miktarlarda tespit edilen 2-4 kat azalıştır. Kuru-madde bazındaki bu azalış, nektara işleme sırasında ilave edilen sukroz şurubunun nektarın kuru maddesinin % 50’sinden daha fazlasının sukrozdan oluşmasına neden olmasıyla açıklanmaktadır. Sukroz ve sitrik asit başta olmak üzere, toplam 11 metabolitin nektarda daha yüksek oranlarda bulunduğu ve nektar ile meyvenin metabolit profilleri arasındaki farklılığı oluşturduğu belirlenmiştir. Metabolomik analizleri ile vişnede ilk defa askorbik asit-glikozit varlığı tespit edilmiştir. In vitro biyoyararlılık analizleri nektarda antosiyaninlerin in vitro biyoyararlılığının daha yüksek olduğunu göstermiştir. Sitrik asit ve/veya sukroz ilavesinin her ikisinin de antosiyanin biyoyararlılığını arttırmada rolü olduğu söylenebilir. Bütün meyve ve bütün nektar örneklerinin biyoyararlılığı, meyve ve nektardan ekstrakte edilerek hücrelere verilen antosiyaninlerin biyoyararlılığından daha yüksektir.In this thesis, each step of nectar processing was studied to evaluate the changes in quantity and profile of sour cherry antioxidants. Additionally, bioavailability of sour cherry anthocyanins was assessed using in vitro simulated gastrointestinal digestion and in vitro Caco-2 cell model. In Caco-2 cell experiments the effects of sucrose and citric acid, as well as the food matrix on anthocyanin bioavailability were examined. Two of the applied treatments during nectar processing resulted in significant changes in antioxidant contents. First, steps leading from fruit to pressed-juice led to 2-3-fold increases, on dry-weight-basis. This was linked to the press-cake removal, which was mainly relevant to the removal of dry-weight poor in antioxidants. The lower contents of antioxidants in press-cake was linked to the efficient compound recovery into the juice by facilitated extraction with repeated press-cake-extraction steps. Second, processing of concentrated-juice into nectar gave rise to 2-4-fold reduction in values. This reduction was related to the addition of sucrose to concentrated- juice during nectar processing, which led to a more than 50% sucrose containing in dry matter nectar. Metabolites that strongly distinguished nectar from fruit were in total 11 metabolites, dominated by sucrose and citric acid. Metabolomics analysis also revealed the existence of ascorbic acid-glucoside in sour cherry, for the first time. A higher in vitro anthocyanin bioavailability was determined in nectar sample. Citric acid and/or sucrose inclusion resulted in an enhanced transport of anthocyanins. The anthocyanins in whole fruit and whole nectar were found to be more bioavailable than extracts.DoktoraPh

FCER2 (Fc fragment of IgE, low affinity II, receptor for (CD23))

Review on FCER2 (Fc fragment of IgE, low affinity II, receptor for (CD23)), with data on DNA, on the protein encoded, and where the gene is implicated

Sheldon-Hall syndrome

Sheldon-Hall syndrome (SHS) is a rare multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs, triangular face, downslanting palpebral fissures, small mouth, and high arched palate. Epidemiological data for the prevalence of SHS are not available, but less than 100 cases have been reported in the literature. Other common clinical features of SHS include prominent nasolabial folds, high arched palate, attached earlobes, mild cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus. Typically, the contractures are most severe at birth and non-progressive. SHS is inherited in an autosomal dominant pattern but about half the cases are sporadic. Mutations in either MYH3, TNNI2, or TNNT3 have been found in about 50% of cases. These genes encode proteins of the contractile apparatus of fast twitch skeletal muscle fibers. The diagnosis of SHS is based on clinical criteria. Mutation analysis is useful to distinguish SHS from arthrogryposis syndromes with similar features (e.g. distal arthrogryposis 1 and Freeman-Sheldon syndrome). Prenatal diagnosis by ultrasonography is feasible at 18–24 weeks of gestation. If the family history is positive and the mutation is known in the family, prenatal molecular genetic diagnosis is possible. There is no specific therapy for SHS. However, patients benefit from early intervention with occupational and physical therapy, serial casting, and/or surgery. Life expectancy and cognitive abilities are normal

Effects of honey addition on antioxidative properties of different herbal teas

Tea and herbal infusions are among the major contributors of phenolic compounds, specifically flavonoids, in our daily diet. Honey is another antioxidant-rich food that is widely used as a natural sweetener. In this work, the effects of honey addition on antioxidant properties of different herbal teas were investigated. For this purpose, 2 different types of honey (flower and pine honey) were added into 9 different herbal teas (melissa, green tea, rosehip, sage, echinacea, fennel, linden, daisy, and ginger) at 4 different temperatures (55°C, 65°C, 75°C, and 85°C), and the changes in the content of total pheolics, total flavonoids, and total antioxidant capacity were determined. The total phenolic content and the total antioxidant capacity of the honey-added-tea samples were found to be increased (up to 57% for both), especially with pine honey and at higher temperatures of honey addition. The findings of this study supported the use of honey as a natural sweetener in tea in order to be able to benefit from the health-enhancing antioxidative properties of these two promising food products