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Sialidaz NEU3'ün Tay-Sachs hastalığı fare modelindeki biyolojik rolünün anlaşılması
No full textThesis (Doctoral)--Izmir Institute of Technology, Molecular Biology and Genetics, Izmir, 2019Includes bibliographical references (leaves: 92-99)Text in English; Abstract: Turkish and EnglishTay-Sachs disease is a severe lysosomal storage disorder characterized by mutations in the lysosomal β-Hexosaminidase A (HEXA) enzyme which converts GM2 to GM3 ganglioside. The GM2 ganglioside accumulation is observed predominantly in the neurons. The infants appear normal in their inborn time, but the progressive accumulation of undegraded GM2 results with death. Hexa-/- mice were created. However, they have a normal lifespan with no obvious neurological impairment until one year. It was thought that stored GM2 catabolized to GA2 using sialidase(s), which is further processed by HEXB. To determine the contribution of sialidase NEU3 to degradation of GM2, a mouse with combined deficiencies of Hexa and Neu3 genes was generated. The Hexa-/-Neu3-/- mice were healthy at birth, but they died between 1.5 and 5 months of age. Thin-layer chromatography and mass spectrometric analysis of the brains of Hexa-/-Neu3-/- mice revealed the abnormal accumulation of GM2. The progressive GM2 accumulation was also verified on testes, liver, and kidney of Hexa-/- Neu3-/- mice. GM2 accumulation in the brain leads to increased lysosomes with membranous cytoplasmic bodies, Purkinje cell depletion, cytoplasmic vacuolization, astrogliosis, and age-dependent lessening in neurons and oligodendrocytes. These mice have prominent disorders such as growth impairment, skeletal bones abnormalities, slow movement, tremors, anxiety and age-dependent loss in both memory and muscle strength. Consequently, the Hexa-/-Neu3-/- mice mimic the pathological, biochemical and clinical abnormalities of the Tay-Sachs patients, and useful model for the future understanding of cellular pathologies that drive the progression of the disease. They are a suitable model for the future pre-clinical testing of possible treatments.Tay-Sachs hastalığı, GM2'yi GM3 gangliosidine dönüştüren lizozomal β-Heksosaminidaz A (HEXA) enzimindeki mutasyonlarla karakterize edilen şiddetli lizozomal depo hastalığıdır. GM2 gangliosit birikimi ağırlıklı olarak nöronlarda gözlenir. Hastalar doğduklarında normal görünür, ancak ilerlemeyen parçalanmamış GM2 birikimi ölümle sonuçlanır. Hexa-/- fareler oluşturuldu. Ancak, bu fareler bir yıla kadar gözle görünür bir nörolojik bozulma olmadan normal yaşam sürdürdüler. GM2'nin, sialidaz(lar) kullanılarak GA2'ye yıkıldığı HEXB tarafından daha fazla işlendiği düşünülmüştür. Sialidaz NEU3'ün GM2'nin bozulmasına katkısını belirlemek için, Hexa ve Neu3 genlerinin birleşik eksikliklerine sahip bir fare üretildi. Hexa-/-Neu3-/- fareleri doğumda sağlıklıydı, ancak 1.5 ile 5 ay arasında öldüler. İnce tabaka kromatografisi ve kütle spektrometrik analizi Hexa-/-Neu3-/- farelerinin beyinlerininde GM2'nin anormal birikimini ortaya koydu. Artan GM2 birikimi ayrıca Hexa-/-Neu3-/- farelerinin testis, karaciğer ve böbreklerinde de doğrulandı. Beyindeki GM2 birikimi, membranöz sitoplazmik cisimler içeren artan lizozom, Purkinje hücre bozulması, sitoplazmik vakuolizasyon, astroglioziz ve nöron ve oligodendrositlerde yaşa bağlı azalmaya yol açar. Bu fareler, hastalara benzer şekilde büyüme bozukluğu, iskelet kemiklerinde anormalliklere, harekette yavaşlama, titreme, anksiyete ve yaşa bağlı hem hafıza hem de kas gücünde kayıp gibi belirgin bozukluklara sahiptir. Bu sonuçlar göstermektedir ki, Hexa-/-Neu3-/- fareler, erken başlangıçlı Tay-Sachs hastalık fare modeli olarak kullanılabilir ve gelecekteki olası tedavilerin klinik öncesi testleri için uygun bir model sunar.Marie Skłodowska-Curie Actions (FP7-PEOPLE-2010-RG) and The Scientific and Technological Research Council of Turkey (215Z083
Kaktüs geometrisinden esinlenilmiş çekirdek yapının dinamik ezilme davranışı
No full textThesis (Master)--Izmir Institute of Technology, Mechanical Engineering, Izmir, 2019Includes bibliographical references (leaves: 76-81)Text in English; Abstract: Turkish and EnglishCactus geometry inspired core structure was manufactured with the fused deposition modelling method by a 3D printer using Acrylonitrile Butadiene Styrene (ABS) material filament. The characterization of ABS was made by performing compression tests to take some parameters for numerical models. Numerical preliminary studies were carried out by using the areal density concept and direct-impact Hopkinson pressure bar test method to compare the cactus geometry with the conventional ones in point of the specific energy absorption capacity (SEA). It was understood that from the preliminary work, the cactus inspired structure is intriguing to investigate the dynamic crushing behaviour at least. Quasi-static, drop weight and direct-impact Hopkinson pressure bar tests were conducted to comprehend the energy absorption and crushing behavior in all cases, then to investigate the strain rate and inertia effects on the structure. Implicit and explicit numerical models were made by using LS-DYNA software to validate experiments and to set a precedent for future works. It was seen that the result of numerical models is in harmony with that of experiments excluding the non-fracture structure at the quasi-static implicit model. Moreover, although quasi-static compression gave the structure more stable deformation behavior compared to drop weight impact, higher energy absorption capability was observed on drop-weight tests. In addition, the strain rate effect is more forceful in point of loading carrying capacity compared to the inertia effect despite the fact that it provides the development of buckling and damage formation.Kaktüs geometrisinden esinlenilmiş çekirdek yapı, Akrilonitril Bütadien Stiren (ABS) malzeme filamenti kullanılarak 3 boyutlu yazıcı vasıtasıyla birleştirmeli yığma modelleme metodu ile üretildi. ABS, nümerik modeller için bazı parametreleri elde etmek amacıyla basma testleri gerçekleştirilerek karakterize edildi. Nümerik ön çalışmalar, spesifik enerji emilim kapasitesi bakımından kaktüs geometriyi geleneksel olanlarla kıyaslamak amacıyla alansal yoğunluk kavramı ve Hopkinson doğrudan darbeli basınç bar testlerini kullanarak yürütüldü. Ön çalışmadan, kaktüsten ilham alan yapının en azından dinamik ezilme davranışının incelenmesi amacıyla ilgi çekici olduğu anlaşıldı. Yarı-statik, düşen ağırlık ve Hopkinson doğrudan darbeli basınç bar testleri, tüm durumlarda ezilme davranışını ve enerji emilimini kavramak ve daha sonra yapı üzerinde şekil değiştirme hızı ve atalet etkilerini incelemek amacıyla yapılmıştır. Örtük ve açık sayısal modeller, deneyleri doğrulamak ve gelecek çalışmalar için bir emsal oluşturmak için LS-DYNA yazılımı kullanılarak yapılmıştır. Nümerik modellerin sonucunun, yarı-statik modelde kırılmayan yapı hariç deneyler ile uyum içinde olduğu görülmüştür. Ayrıca, yarı-statik basma yapıya, düşen ağırlık darbesine kıyasla daha kararlı bir deformasyon davranışı vermesine rağmen, düşen ağırlık testlerinde daha yüksek enerji emme kabiliyeti gözlenmiştir. Ek olarak, gerilme hızı etkisinin, burkulma ve hasar oluşumunun gelişmesini sağlamasına rağmen atalet etkisine kıyasla yükleme taşıma kapasitesi açısından daha etkin olduğu görülmüştür
Tarihi kütüphaneler için HAD (Hesaplamalı Akışkanlar Dinamiği) simülasyonu ile doğal havalandırma tasarımı
No full textThesis (Master)--Izmir Institute of Technology, Energy Engineering, Izmir, 2019Includes bibliographical references (leaves: 61-66)Text in English; Abstract: Turkish and EnglishLibraries accumulate and protect written and printed works that make permanent knowledge and cultures have been accumulated throughout human history. Paper-based collections kept in libraries are the heritage of humanity. They are under risk of mechanical, biological and chemical degradation over the years caused by the fluctuations in temperature and relative humidity values and inability to control these values. The aim of the Thesis is to reduce degradation risks on paper-based collections in historic libraries by providing preventive conservation without damaging the structure of the building. The historic Necip Paşa Library which is home for 1147 manuscripts was chosen as a case study. In order to provide preventive conservation for manuscripts, firstly indoor microclimatic data were collected for one year and analyzed to observe the risks that may cause degradation types on manuscripts. Only chemical degradation risk was detected. Window controlled seven natural ventilation scenarios were developed to reduce the risk. Finally, ventilation scenarios were analyzed by Ansys Fluent 17.1. Computational Fluid Dynamics (CFD) modelling was used to observe the effect of natural ventilation scenarios on indoor relative humidity according to outdoor relative humidity and wind direction. Finally, k-ε turbulence model was used in CFD analysis. Results shows that during the high chemical degradation risk period (May-October), outdoor air temperature and relative humidity are suitable only 7.53% of the total time which allows appropriate natural ventilation. As a conclusion, natural ventilation is not enough to decrease chemical degradation risk totally for the Library. Therefore, additional mechanical ventilation is required.Kütüphaneler, insanlık tarihi boyunca biriktirilen bilgi ve kültürlerin kalıcı olmasını sağlayan yazılı ve basılı eserleri biriktirir, korur ve geleceğe aktarılmasını sağlar. İnsanlığın mirası olan bu belgeler, yıllar içinde mekanik, biyolojik ve kimyasal bozulma riski taşımaktadır. Risklerin temel nedenleri sıcaklık ve nem değerlerinde meydana gelen dalgalanmalar ve bu değerlerin gerektiği gibi kontrol edilememesidir. Bu tezin amacı, tarihi kütüphanelerdeki kağıt bazlı eserlerin binanın yapısına zarar vermeden önleyici koruma sağlayarak bozulma riskini azaltmaktır. 1827 yılında Tire-İzmir-Türkiye'de inşa edilen ve XII. yüzyıla dayanan 1147 değerli el yazmasına ev sahipliği yapan Necip Paşa Kütüphanesi örnek çalışma olarak incelenmiştir. Binanın ana yapısında ısıtma/soğutma ve mekanik havalandırma sistemi yoktur. El yazmalarının önleyici korunmasını sağlamak için, ilk olarak iç ortam mikroklima verileri bir yıl boyunca toplanmıştır. Veriler, el yazmalarının kimyasal, biyolojik ve mekanik bozulmalarına neden olabilecek riskleri belirlemek için analiz edilmiş. Yalnızca kimyasal bozulma riski tespit edilmiştir. Kimyasal bozulma riskini azaltmak için pencere kontrollü doğal havalandırma senaryoları geliştierilmiştir. Son olarak, bina modellenmiş ve pencere kontrollü yedi doğal havalandırma senaryosu dış ortamdaki bağıl nem, sıcaklık ve rüzgâr yönüne bağlı olarak iç ortamdaki bağıl nem üzerindeki etkisini gözlemlemek için Hesaplamalı Akışkanlar Dinamiği (HAD) yönetemi kullanılarak Ansys Fluent 17.1 ile analiz edilmiştir. HAD analizinde k-ɛ türbülans modeli kullanılmıştır. Sonuçlar kimyasal bozulma riski olan dönem (Mayıs-Ekim) için dış hava sıcaklığı ve bağıl nem değerlerinin uygun doğal havalandırma senaryosu kullanıldığında 7.53% iyileşme meydana geldiğini gösterdi. Ayrıca sonuç göre doğal havalandırmanın tek başına kullanılmasının Necip Paşa Kütüphanesi-Tire-İzmir-Türkiye içinde bulunan kağıt bazlı koleksiyonların korunmasında yetersiz kaldığını ve ek olarak mekanik havalandırma gerektiğini ortaya koydu
Offshore wind energy estimation in the Bay of Bengal with satellite wind measurement
No full text1st International Conference on Advances in Science, Engineering and Robotics Technology, ICASERT 2019; 3 May 2019 through 5 May 2019The objective of this paper is to obtain appropriate offshore location in the Bay of Bengal, Bangladesh for further development of wind energy. Through analyzing the previous published works, no offshore wind energy estimation has been found related to the Bay of Bengal. Therefore, this study can be claimed as the first footstep towards offshore wind energy analysis for this region. Generally, it is difficult to find offshore wind data relative to the wind turbine hub heights, thus a starting point is necessary to identify the possible wind power density of the region. In such scenario, Synthetic Aperture radars (SAR) have proven useful in previous studies. In this study, SAR based dataset- ENVISAT ASAR has been used for Wind Atlas generation of the Bay of Bengal. Furthermore, a comparative study has been performed with Global Wind Atlas (GWA) to determine a potential offshore wind farm production in a reasonable location at the bay. The annual energy production of that offshore windfarm has been analyzed by combining SAR, GWA and ASCAT datasets. Through ASAR based Wind Atlas and GWA comparison, some differences have been found where there are less samples from the ASAR datasets. Thus, Weibull statistical analysis are performed to have a better Weibull fitting and accurate estimation of Annual Energy production (AEP). The study summarizes that, satellite datasets can be a very useful method to detect potential zone if compared with any long time statistical result and bathymetry data together. © 2019 IEEE
Measureability of functional size in agile software projects: Multiple case studies with COSMIC FSM
No full text45th Euromicro Conference on Software Engineering and Advanced Applications, SEAA 2019; 28 August 2019 through 30 August 2019Functional size measurement (FSM) has been used in software engineering for decades as a main driver for estimation and significant input for other various project management activities throughout the project life span. To apply FSM accurately at the early stages of software development process, especially for estimation purposes, functional user requirements need to be available in detail as required by the adopted FSM method. However, in agile software development, requirement specifications, in general, are kept minimal. For this reason, the adjustment of the requirements to the necessary granularity level has been articulated as one of the barriers preventing the diffusion of FSM practices among agile teams. In this paper, we take a closer look at this problem in order to investigate the usability of FSM and to reveal FSM related challenges empirically through case studies on real agile projects from different software organizations. This study also provides a snapshot of agile organizations in terms of requirement specification and estimation related practices. © 2019 IEEE
Microfluidic platform for sorting materials based on their densities using magnetic levitation
No full text2019 Innovations in Intelligent Systems and Applications Conference, ASYU 2019; 31 October 2019 through 2 November 2019Circulating Tumor Cells (CTCs) play a vital role in cancer diagnosis, prognosis and personalized medicine. However, CTCs are extremely rare in blood (i.e., down to 1-100 CTC per 1 mL human blood) and hard to isolate because of the heterogeneity of CTCs in biomarker expression. The current CTC separation and identification techniques use numerous differences between cells such as size, electric charges, density and expression of cell surface markers. However, these techniques have many limitations in terms of laborious sample preparation steps, inconsistent results caused by low specificity and efficiency and high cost. Hence, there is no standard method for isolating CTCs yet. With this study, it was aimed to fill the gap in CTC isolation and identification by proposing to develop a new method based on magnetic levitation principle, which has recently been demonstrated as a highly acceptable method for biological characterization of cells and monitoring of their cellular events. In this study, we have developed a new label-free microfluidic sorter to separate microparticles/cells based on their densities using magnetic levitation principle. Two different density microparticles (1.02 g/mL and 1.09 g/ mL) have been sorted and quantified in a continuous flow using a set of permanent magnets located in a 3D printed structure surrounding the microfluidic channel. This device can be used for rapid, low cost and label-free in-vitro diagnosis of cancer by sorting CTCs from whole blood in a high-Throughput manner. The sorted cells might further be used for downstream analysis for personalized and precision medicine. © 2019 IEEE
Astragalus trojanus Stev. Kesikli Kültürleri: pH, Sükroz ve Kazein Hidrolizat Etkisi ile Sikloartan-tip Metabolit Birikimi
No full textI n this study, two grams of callus regenerated from stem and leaf explants of Astragalus trojanus Stev. were cultured in Woody Plant Medium (WPM) supplemented with 1 mg/L 2,4-D for four weeks and used as inoculum in order to investigate the effects of working volume and media composition. The highest biomass was obtained in 250 mL flask with astragaloside IV (1.66 µg/mg) and cycloastragenol (0.19 µg/mg) accumulation. Different concentrations of sucrose and casein hydrolysate (1 and 2 g/L) were also tested and the effect of pH was also investigated. Biomass accumulation cannot be enhanced, however, astragaloside IV and cycloastragenol content was ascended. The highest astragaloside IV (95.23 µg/mg) and cycloastragenol (5.93 mg/mg) accumulations were obtained at pH 6.8 and 2 g/L casein hydrolysate, respectivelyBu çalışmada, Astragalus trojanus Stev. gövde ve yaprak eksplantlarından elde edilen iki gram ağırlığında kalluslar 1 mg/L 2,4-D içeren Woody Plant Medium (WPM) besin ortamında dört hafta boyunca kültüre alınmışlar ve çalışma hacminin ve besin ortamının etkilerinin incelenmesi için başlangıç materyali (inokulum) olarak kullanılmışlardır. En fazla biyokütle astragaloside IV (1.66 µg/mg) ve cycloastragenol (0.19 g/mg) içeriğiyle 250 ml’lik erlenden elde edilmiştir. Farklı konsantrasyonlarda sükroz ve kazein hidrolizat (1 ve 2 g/L) denemeleri yapılmış ve pH’ın etkisi de incelenmiştir. Biyokütle birikiminde artış sağlanamamış ancak astragaloside IV ve cycloastragenol içerikleri artmıştır. En yüksek astragaloside IV (95.23 µg/mg) ve cycloastragenol (5.93 µg/mg) içerikleri pH 6.8’de ve 2 g/L kazein hidrolizat denemesinde elde edilmiştir
Telomerase activators derived from Astragalus sapogenins via biotransformation with the recently discovered endophytic fungus Camarosporium laburnicola
No full text67th International Congress and Annual Meeting of the Society-for-Medicinal-Plant-and-Natural-Product-Research (GA); SEP 01-05, 2019; Innsbruck, AustriaTelomeres are nucleotide sequences that are located at the end of chromosomes shortening with each cell division. Telomerase is a reverse transcriptase enzyme, and it helps to replenish telomere ends that are truncated by aging and stress factors [1].
Telomere shortening is considered not only a result of the biological aging process but also a risk factor for many disorders such as neurodegeneration, macular degeneration, coronary artery diseases, hypertension, diabetes, pulmonary fibrosis. Thus, activation of telomerase enzyme introduces a great promise for the treatment of many chronic and degenerative diseases. Cycloastragenol, isolated from Astragalus species, is the only natural product as a telomerase activator in the dietary supplement market. The initiation of clinical studies with Cycloastragenol derivatives in Alzheimer’s disease and metabolic syndrome is a sign of their potential [2],[3],[4]
Heteroglossia in and of Film: La Haine
No full textBu makale Mathieu Kassovitz’in yönetmenliğini üstlendiği La Haine (1995) adlı filmi Bakhtin’in “heteroglossia” kavramı özelinde analiz etmektedir. Heteroglossia kavramıyla “dil, belirli ideolojik inanç sistemlerinin temsil edildiği bir sosyal söylemler alanı olarak” (Morris, 2003: p. 73) tanımlanmaktadır. Avrupa’yı sarsmaya devam eden mülteci krizinin, yükselen İslamofobinin ve yabancı düşmanlığının gölgesinde film güncelliğini, dolayısıyla sosyal ve politik önemini korumaktadır. Film, teması ve merkezi karakterleri itibariyle, “diyasporik sinema”, “beur sinema”, “banliyö sineması” ve “Fransız sineması” gibi ceşitli tanımlayıcı kategoriler içinde değerlendirilebilmektedir. Fakat çalışma kapsamında, Fransız sineması ve banliyö sineması bağlamı içinde, çok sesli, çok dilli bir anlatı olarak özellikle filmsel metnin kendisine odaklanılmaktadır. Bu doğrultuda, filmdeki karakterlerin ifadeleri ve bu ifadelerin sosyal ve kültürel yananlamları/çağrışımları baz alınarak, sanayi sonrası ve sömürgecilik sonrası Fransa’da bu karakterlerin nasıl birer “öteki” olarak çerçevelendiği analiz edilmektedir. Yapılan detaylı metin analizi, bu görsel işitsel anlatının çok katmanlı yapısını vurgulayacak şekilde farklı “heteroglossia” kullanımlarının varlığını göstermektedir.This article evaluates the film La Haine (1995) directed by Mathieu Kassovitz with specific reference to the Bakhtinian concept of “heteroglossia”. The term addresses “language [as] perceived [and] stratified through and through into multiple social discourses each representing a specific ideological belief system” (Morris, 2003: p. 73). The film is still socially and politically significant and relevant especially in relation to the refugee crisis, the increasing xenophobia and islamophobia that continue burdening Europe today. The film can be considered under the rubrics of diasporic cinema, beur cinema, banlieue cinema and French cinema based on its thematic concerns and its central characters. This article, however, particularly focuses on the work itself as a heteroglot, polyglot utterance in the contexts of French film and banlieue film. Secondly, it analyses the framing of the characters as Others in the context of post-industrial, post-colonial France by focusing on their utterances and the social and cultural connotations of these utterances throughout the film. The close textual analysis reveals that there are several registers of heteroglossia detectable in this audio-visual narrative, underlying its multilayered character
A new semi-synthetic sapogenol derivative inducing regulated necrosis
No full text67th International Congress and Annual Meeting of the Society-for-Medicinal-Plant-and-Natural-Product-Research (GA); SEP 01-05, 2019; Innsbruck, AustriaSince saponin’s antitumor potency is relatively weak, researchers focus on their semi-synthetic modification to obtain structures with higher potencies. With the same motivation, we prepared a cytotoxic sapogenol
derivative (AG-08) from cycloastragenol. Our preliminary studies revealed that AG-08 induced primarily necrotic cell death along with autophagic
inhibition. Furthermore, immunoblotting experiments demonstrated that AG-08 promoted cleavage of various proteins such as ATGs, p62, and
PARP-1