194 research outputs found
sj-docx-1-tae-10.1177_20420188241229540 – Supplemental material for Role of epicardial adipose tissue in diabetic cardiomyopathy through the lens of cardiovascular magnetic resonance imaging – a narrative review
No full textSupplemental material, sj-docx-1-tae-10.1177_20420188241229540 for Role of epicardial adipose tissue in diabetic cardiomyopathy through the lens of cardiovascular magnetic resonance imaging – a narrative review by Sindhoora Kotha, Sven Plein, John P. Greenwood and Eylem Levelt in Therapeutic Advances in Endocrinology and Metabolism</p
Tarih Öğretmeni Eğitiminde Eylem Araştırması Yaklaşımının Kullanılması: Bir Model Önerisi
No full textÖzet: Bu makalede, eylem araştırması yaklaşımının tarih öğretmeni eğitimi alanında kullanımı incelenmektedir. Eylem araştırması, Türkiye’de eğitim araştırmaları alanında son yıllarda oldukça yaygın hale gelse de, bu konudaki metodolojik yaklaşımlar ve sorunlar pek tartışılmamıştır. Bu çalışmanın amacı, hizmet öncesi tarih öğretmeni eğitiminde eylem araştırmasının sunduğu eğitimsel ve metodolojik perspektifleri incelemektir. Makalede, yazarın kendi araştırmalarında kullandığı metodolojik yaklaşım, ilgili bilimsel literatür ışığında değerlendirilmekte ve bir model önerisi sunulmaktadır. Anahtar Kelimeler: Eylem Araştırması, Araştırma Metodolojisi, Tarih Öğretimi, Öğretmen Eğitimi Abstract: This paper analyzes the use of action research design in history teacher education. Although action research is quite common in the field of educational researches in Turkey, the methodological approaches and problems have not been discussed much. The aim of this study is to analyze educational and methodological perspectives provided by the action research in pre-service history teacher education. The methodological approach, used by the author in his research practices, is evaluated in the light of the relevant scientific literature and a proposal of a model is presented. Keywords: Action Research, Research Methodology, History Education, Teacher Educatio
The role of rest and stress cardiac energy metabolism and ectopic lipid deposition in diabetic cardiomyopathy
No full textType 2 diabetes mellitus (T2DM) is associated with an increased risk of heart failure and cardiovascular mortality even in the absence of coronary artery disease. Although the reasons for this are not clear, impaired cardiac high energy phosphate metabolism, coronary microvascular dysfunction and ectopic lipid deposition have emerged among the candidate mechanisms. Cardiac magnetic resonance imaging (CMR) and magnetic resonance spectroscopy (MRS) are powerful tools to characterise these conditions. The findings here suggest that, in diabetes, coronary microvascular dysfunction may potentially exacerbate derangement of cardiac energetics under conditions of increased workload. The relationships amongst ectopic adiposity (myocardial, epicardial and hepatic), myocardial metabolic changes and left ventricular remodelling in T2DM were determined using proton magnetic resonance spectroscopy (1H-MRS), cardiac computer tomography (CT) and multi-parametric liver MR. It was found that cardiac steatosis independently predicted left ventricular concentric remodelling and impairment of systolic strain in patients with T2DM. This work also demonstrated that ectopic adiposity is linked to insulin resistance, liver fibrosis and inflammation, and cardiac contractile dysfunction in diabetes, and that the coexistence of obesity and T2DM leads to higher epicardial fat volumes and significant non-alcoholic fatty liver disease compared to T2DM alone. These findings suggest that, since cardiac steatosis and ectopic adiposity are modifiable, strategies aimed at reducing myocardial triglyceride levels may reverse concentric remodelling and improve contractile function in the diabetic heart. The work on field strength effects on cardiac 31P-MRS has shown that 7T is feasible and reliable with reduced error and increased signal to noise compared to 3T. In summary, the work in this thesis demonstrates the powerful role of CMR and MRS in elucidating the detrimental effects that originate from the metabolic abnormalities in the diabetic heart
Reply: Ectopic Fat Deposition and Diabetes Mellitus.
No full textReply to Drs. Gaborit and Dutour re: "Ectopic Fat Deposition and Diabetes Mellitus" Journal of the American College of Cardiology 68 (23) pp.2594-2595
Advanced spectroscopic imaging techniques for X-nuclei cardiac magnetic resonance imaging
No full textChanges to cardiac metabolism are an important component of heart failure. Understanding these metabolic changes is therefore critical to developing treatments for the failing heart, particularly pharmaceuticals, or other interventions, which aim to restore normal metabolism. A combination of hyperpolarized 13C and 31P magnetic resonance spectroscopic imaging (MRSI) enables quantification of both the substrate usage (13C) and energy output (31P) of cardiac metabolism, allowing a full picture of the metabolic state of the heart to be built up.
Both hyperpolarized 13C and 31P MRSI present significant experimental challenges, which I will address, through the use of advanced acquisition and reconstruction techniques, in this thesis.
The main challenges associated with hyperpolarized 13C MRSI are the short transverse relaxation time of the metabolites, necessitating very rapid readouts, the short half-life of hyperpolarization, which requires the full scan to complete in approximately two minutes, and the bolus injection of hyperpolarized material to the patient, which makes the signal intensity highly dynamic. To address these three challenges, I implemented a hybrid multiple/single-shot spiral sequence, with a rapid readout, which enabled the usual trade-off, inherent to multiple-shot spiral readouts, of temporal and spatial resolution (when selecting the number of shots), to be made at reconstruction, rather than acquisition time.
The principal challenge of 31P MRSI however, is achieving adequate SNR. The low SNR of 31P spectroscopy necessitates significant averaging during the acquisition, which extends scan time and precludes high spatial resolution imaging within a reasonable scan time. In this work I implement two compartmentalized reconstruction techniques, SLAM and SLIM, and apply them at both 3 and 7T, before investigating acquisition parameters, which lead to an improvement in SNR and repeatability over the existing technique used in OCMR.
Together these technological advances have extended our ability to quantify metabolism, which will, through their clinical application, enhance our understanding of heart failure
Predicting myocardial infarction through retinal scans and minimal personal information
No full textIn ophthalmologic practice, retinal images are routinely obtained to diagnose and monitor primary eye diseases and systemic conditions affecting the eye, such as diabetic retinopathy. Recent studies have shown that biomarkers on retinal images, for example, retinal blood vessel density or tortuosity, are associated with cardiac function and may identify patients at risk of coronary artery disease. In this work we investigate the use of retinal images, alongside relevant patient metadata, to estimate left ventricular mass and left ventricular end-diastolic volume, and subsequently, predict incident myocardial infarction. We trained a multichannel variational autoencoder and a deep regressor model to estimate left ventricular mass (4.4 (–32.30, 41.1) g) and left ventricular end-diastolic volume (3.02 (–53.45, 59.49) ml) and predict risk of myocardial infarction (AUC = 0.80 ± 0.02, sensitivity = 0.74 ± 0.02, specificity = 0.71 ± 0.03) using just the retinal images and demographic data. Our results indicate that one could identify patients at high risk of future myocardial infarction from retinal imaging available in every optician and eye clinic
Bir Yönetmenlik Uygulaması Olarak Kesintisiz Eylem Çizgilerinin Oyuncularla Birlikte Oluşturulması
No full textOyuncu, yönetmen, kuramcı Konstantin Stanislavski'nin ortaya attığı "kesintisiz eylem çizgisi" kavramı oyunun üstün görevine karakterlerin izlediği yoldur. Bu tezde yönetmen pozisyonundaki kişinin bu yolu oyuncuların kendi kararlarıyla şekillendirdikleri bir sonuca nasıl ulaşılabileceği üzerine bir araştırma yapılmıştır. Bu amaca ulaşmak adına yönetmenin tiyatronun olmazsa olmaz unsuru olan oyuncu ile kuracağı ilişki merkezinde bir öneri geliştirilmiştir. Konstantin Stanislavski yarattığı oyunculuk kuramının ışığında yönetmenlik anlayışını da geliştirmiştir. Sistemi üzerine çalışmaya başlamasından itibaren oyun yazarının istekleri doğrultusunda oyuncuların eylem seçimleri değer kazanmıştır. Halen varlığını sürdüren, kurucularından olduğu Moskova Sanat Tiyatrosu'nun oyuncuları ile bir yandan sistemini geliştirirken bir yandan da o sistemin oyun yönetirken ne gibi yansımaları olacağını araştırmıştır. Sistemini hiçbir zaman tamamlanmış bir yapı gibi görmeyen Stanislavski, insanla yapılan bu sanat dalının her daim değişime, araştırmaya açık olması gerektiğini salık vermiştir. Kendi yönetmenlik pratiğinin yanında oyunculuk kuramıyla sonraki yönetmenlere, oyunculara ulaşmak adına farklı araçlar sunmuştur. Yönetmen, proje ile kuracağı ilk bağdan, tasarımcılar ile iletişimine, kast sürecine, metin birebir kullanılmadan yapılacak hazırlık provaları ve ardından sahne provalarına uzanan yolda ima edilen türde bir ortak yaratıma nasıl ulaşabilir sorusuna yanıtlar aranan bu tezde, yaratılacak "ensemble"ın da önemi vurgulanır. Yönetmenin oyun dünyası için kuracağı atmosferde oyuncuların kendi bakış açılarından oluşturacakları yolları takip etmelerinin, oyunu çok sesli, çok odaklı bir sonuca götüreceği fikri, bu çalışmaya öncellik etmiştir. Kesintisiz eylem çizgilerinin oyuncuların bireysel kararları doğrultusunda çizildiği bir oyunun ortak yaratıcısı olarak yönetmen bu sayede her şeyi bilen bir otorite figürü değil, organik bir sanatsal yaratının aktörlerinden biri olacaktır.Actor, director and theoretician Konstantin Stanislavski's notion of "through line of action" can be described as the character's path to the play's super task. In this thesis, from the position of a director, a research about the ways of reaching a consequence in which the actors shape their characters' "through line of actions" by making their own decisions is conducted. A proposition has been developed centered on the director's relationship with the most essential element in the theatre: the actor. Konstantin Stanislavski has improved his directing approach according to the acting system he himself had created. After he took off with his system, as a director he began to value the actors' choices and actions at the command of the author of the play. The still existent Moscow Art Theatre had been a base for him not only to improve this then new acting theory, but also an arena where he could see the reflections of his technique whilst directing. Stanislavski, who had never seen his system as a completed solid structure, advised that in this particular field of art, which is performed by and with human beings, one had to be always open to changing and researching. As a director apart from his directing practice, by the help of his acting system, he offered many different tools for the directors in order to reach the actors. In this thesis, through all the way from the director's first connection with the project to forming communication with the designers, from casting process, to preparation rehearsals without the text and finally to stage rehearsals, as the search for ways of reaching a co-creation as indicated above continues, the importance of creating an ensemble is also emphasized. In the play-world's atmosphere created by the director, the idea of reaching a more polyphonic, multifocal result by pursuing the paths formed from the actors' points of view is the guiding spirit of this work. As a co-creator of a play in which the through line of actions are drawn in orientation of actors' individual decisions, the director wouldn't be the all knowing authoritarian figure, but a contributor of an organic work of art
The role of metabolic rewiring in endocrine resistance
No full textBreast cancer is the most common cancer type in women population affecting a large number of women worldwide. Due to its highly heterogenous molecular characteristics, there is not a default treatment strategy for breast cancer. Almost two third of breast cancer cases are estrogen receptor positive ER (+). Majority of breast cancer specific deaths in women with ERα (+) tumor occur due to metastases that are resistant to endocrine therapy. There is a critical need for novel therapeutic approaches to prevent or delay recurrence of ERα (+) tumors. The overall objective of this dissertation project is to define the interaction among endocrine resistance, nuclear export system, and cellular metabolic pathways, and to evaluate the metabolic impact of combinational ER and XPO1 targeting by using combination of endocrine therapy agents and a XPO1-specific small molecule inhibitor (Selinexor-SEL) in different endocrine resistant ER (+) breast cancer cell lines. The long term goal is to develop effective treatment strategies to overcome endocrine resistance in ER (+) breast cancer.
In the first part of this project, we focused on the characterization of XPO1 protein in tamoxifen resistance. In this part, we used endocrine-sensitive and -resistant breast cancer cell lines (in vitro) and tumor xenograft models (in vivo) to test our hypothesis. Our results showed that expression profile of XPO1 protein has a pivotal role in the progression of tamoxifen resistance in ER (+) breast cancer cell models. We found out that XPO1 protein modulates tamoxifen resistance due to its function to determine subcellular localization of important kinases.
In the second part of the project, we investigated how nuclear export system contribute to tamoxifen resistance development by testing with a novel combinational targeting strategy using 4-OHT and SEL in Luminal B type breast cancer cell lines, and to investigate the metabolic outcomes of this novel therapy. To test our hypotheses, we used actual patient tumor samples and endocrine-sensitive and -resistant breast cancer cell lines (in vitro). Our findings indicated that XPO1 expression is significantly higher in Luminal B subtype compared to other molecular subtypes. We demonstrated that combined targeting of XPO1 and ERα rewires metabolic pathways (e.g. Akt pathway), and shuts down both glycolytic and mitochondrial pathways that would eventually lead to autophagy.
Lastly, we assessed the impact of other endocrine therapy options alone or in combination with Selinexor on metabolism in different endocrine resistant breast cancer cell lines and possible metastatic organ sites. We used 3-D cell culture models and endocrine-sensitive and -resistant breast cancer cell lines (in vitro). Using a combination of transcriptomics, kinase arrays, metabolomics and metabolic flux experiments, we identified glutamine metabolism pathways to be rewired during endocrine resistance. In limited media conditions mimicking nutrient deprived tumor microenvironment, endocrine resistant cells were more dependent on mitochondria for energy production. Their glucose and fatty acid dependency decreased in the presence of SEL and cells were more dependent on glutamine. The effect of glutamine was dependent on conversion of the glutamine to glutamate and mitochondrial complex 1 activity. In order to examine metabolites that might result in the observed phenotype we performed GC/MS whole metabolite profiling and identified amino acid metabolism pathways to be upregulated when cells were treated with SEL.
In conclusion, our study indicated that remodeling metabolic pathways to regenerate new vulnerabilities in endocrine resistant breast tumors is novel, and given the need for better strategies for improving therapy response of relapsed ERα(+) tumors, our findings show great promise for uncovering the role ERα-XPO1 crosstalk plays in reducing cancer recurrences.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2021-08-01The student, Eylem Kulkoyluoglu Cotul, accepted the attached license on 2019-06-10 at 19:00.The student, Eylem Kulkoyluoglu Cotul, submitted this Dissertation for approval on 2019-06-10 at 19:02.This Dissertation was approved for publication on 2019-07-09 at 11:23.DSpace SAF Submission Ingestion Package generated from Vireo submission #14020 on 2019-11-26 at 13:59:38Made available in DSpace on 2019-11-26T20:58:27Z (GMT). No. of bitstreams: 8
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Munzur Üniversitesi öğrenci memnuniyeti örnek olay incelemesi
No full textÖnder, Eylem Yalçınkaya (Munzur Author)The aim of this study is to get views of 4th year undergraduate students (including students in extending section) studying at engineering faculty about the University and the program they enrolled. The sample of the study is 232 students attending the final year of engineering faculty at 2015-2016 fall semesters. 23 of these students were studying in Chemical Engineering, 20 of these students were studying in Food Engineering, 29 of these students were studying in Mechanical Engineering, 54 of these students were studying in Computer Engineering, 36 of these students were studying in Civil Engineering, 67 of these students were studying in Electrical-Electronics Engineering, 3 of these students were studying in Environmental Engineering. In order to get students’ views on university and the program they enrolled, the survey questionnaire consisting of 50 multiple-choice questions was developed by last year chemical engineering student. This questionnaire survey was prepared taking into consideration the student satisfaction survey of other universities. The content analysis of the developed survey questionnaire was made conducted by five faculty members and necessary arrangements were made in accordance with the recommendations of the faculty members. The findings are expected to be a useful guide for the academic institution.Bu çalışmanın amacı Munzur Üniversitesi mühendislik fakültesinde okuyan son sınıf lisans öğrencilerinin (bölümü uzatan öğrenciler de dahil) öğrenim gördükleri üniversite ve program hakkındaki görüşlerini almaktır. Bu çalışmanın örneklemini 2015-2016 güz döneminde mühendislik fakültesine devam eden son sınıf 232 öğrenci oluşturmaktadır. Bu öğrencilerin 23’ü Kimya Mühendisliği, 20’si Gıda Mühendisliği, 29’u Makine Mühendisliği, 54’ü Bilgisayar Mühendisliği, 36’sı İnşaat Mühendisliği, 67’si Elektrik-Elektronik Mühendisliği, 3’ü ise Çevre Mühendisliği’nde öğrenim görmektedir. Öğrencilerin okudukları üniversite ve okudukları program hakkındaki görüşlerini almak amacıyla Kimya Mühendisliği son sınıf öğrencisi tarafından 50 soruluk çoktan seçmeli sorudan oluşan bir anket geliştirilmiştir. Bu anket diğer üniversitelerin öğrenci memnuniyeti anketleri dikkate alınarak hazırlanmıştır. Geliştirilen anketin içerik analizi 5 öğretim üyesi tarafından yapılmış olup, öğretim üyelerinin önerileri doğrultusunda gerekli düzenlemeler yapılmıştır. Bulguların akademik kurum için faydalı bir kılavuz olması beklenmektedir
The image of the girl child in Raymond Queneau’s Zazie in the Metro
No full textRaymond Queneau, one of the pioneers of the Oulipo literary group and the author of Exercises in Style (French version: 1947, English version: 1958), became more widely known with Zazie in the Metro, original version in French published in 1959. Known for his sensitivity to style, in this work, which he wrote mostly in the form of dialogue, the author tries to put forward a new way of writing by approaching the daily spoken language. In order to better reflect his linguistic and stylistic quest as a result of modernity, the author chose Zazie as the lead character, a girl who grew up at an early age and whose childhood was stolen due to the negativities she experienced. The author also made an effort to narrate the events with the purified language of Zazie. In his story, which he built on the character of Zazie, Queneau tries to reveal a new world and a way of perception through Zazie's point of view and frankness. Zazie puts adults in trouble with her disturbing questions, pushes their limits. By refusing to accept the world as it is, she also contributes to the questioning of all topics by characters of the novel as well as its readers. In these respects, the character of Zazie reminds us of the concept of "becoming a girl child", which is the most fundamental of the minoritaire conditions necessary for the realization of the concept of "becoming" put forward by Gilles Deleuze and Félix Guattari, and has a great importance in how the world is perceived. This article will evaluate how "becoming", a philosophical and theoretical concept, is reflected in Raymond Queneau's literary work Zazie in the Metro within the framework of Deleuze and Guattari's philosophical theory, and will try to reveal the different meanings added by the image of girl child.</jats:p
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