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Molecular Analysis Of The Relationship Between Fatty Acid Metabolism Related Ampk And Mir-33a Expressions And Clinicopathological Parameters İn Clear Cell Renal Carcinoma İn The Tcga Data Set And Cell Lines
No full textDoktora tezi.Böbrek kaynaklı en sık izlenen kanser olan ve lipid metabolizması ile yakından ilişkili olduğu gösterilen berrak hücreli renal hücreli karsinom (BHRHK)' da yağ asidi metabolizmasının rolü, günümüzde prognozu tahmin etmek ve tedavi stratejilerini yönlendirebilmek amacıyla çok sayıda araştırmaya konu olmuş ve yeterli düzeyde kanıtlara ulaşmak için halen yeni çalışmalara konu olmaya devam etmektedir. Bu çalışmada, Kanser Genom Atlası (The Cancer Genome Atlas, TCGA) veri bankası üzerinden, yağ asit metabolizması ile ilişkili olan 5′-adenozin monofosfat (AMP) ile aktive edilmiş protein kinaz (AMPK) ve yağ asidi metabolizması ile ilişkisi en net açıklanan mikro RNA olan miR-33a ifadelerinin BHRHK olgularında klinikopatolojik verilerle ilişkisini araştırdık. Ardından, hücre hattı analizleriyle, AMPK ve miR-33a ifadelerinin primer ve metastatik BHRHK hücre hatlarında hücresel düzeyde ifadelerini ve miR-33a modulasyonlarının hücre içi lipid birikimi üzerine etkilerini değerlendirdik. TCGA veri bankasında kayıtlı BHRHK olgularına ait biyoinformatik veriler açık erişimli cBioPortal, UCSC Xena, UALCAN ve Linkedomics veri portalları kullanılarak elde edildi. Bu portallardaki yerleşik istatiksel metodlar ile AMPK 1 ve 2 genleri mRNA ifadeleri ile miR-33a ifade seviyelerinin BHRHK olgularında patolojik tümör derecesi, patolojik tümör T evresi, N evresi ve M evresi, ve sağkalım gibi klinikopatolojik parametrelerle olan ilişkileri irdelendi. Ayrıca, miR-33a ve AMPK1 ve 2 ifadeleri arasındaki korelasyonlar da analiz edildi. Takiben, primer BHRHK kaynaklı A-498 ve metastatik BHRHK kaynaklı Caki-1 hücre hatları ve kontrol hücre hattı olarak kullanılan HEK-293 hücre hatlarında immunoblotlama ile AMPK 1α alt ünitesi protein seviyeleri ve kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (Real-Time Quantitative Reverse Transcription PCR, qRT-PCR) ile miR-33a ifadeleri belirlendi. Son aşamada ise, miR-33a mimik ve anti-miR-33a trasnfeksiyonları sonrası miR-33a modülasyonlarının bu hücre hatlarında hücre içi lipid birikimleri üzerine etkileri BODIPY ve eş zamanlı DAPI floresan boyama yöntemiyle değerlendirildi. TCGA analiz sonuçlarına göre; BHRHK olgularında primer tümör dokularında AMPK 1 ve 2 mRNA ifadelerinin normal doku örneklerine kıyasla büyük oranda anlamlı azalma sergiledikleri izlendi. Tümör patolojik derecesi ve T evresi ilerledikçe bu azalmalar daha da belirginleşme eğilimindeydi. Benzer şekilde lenf nodu tutulumu ve metastazlı olgularda da anlamlı derecede daha az ifade edildikleri gözlendi. Ayrıca, azalmış AMPK 1 ve 2 mRNA ifadelerinin BHRHK olgularında daha kötü sağ kalım sonuçları ile ilişkili olduğu saptandı. Protein düzeyinde ise primer tümörlü dokularda AMPK 1 protein ifadesinin normal dokulara oranla anlamlı derecede yüksek, AMPK 2 protein ifadesinin ise anlamlı derecede düşük olduğu belirlendi. Artmış AMPK 1 protein ifadesi artan tümör T evresi ile birlikte daha da artma eğilimindeydi. miR33-a ifadeleri irdelendiğinde primer tümör dokularında normal doku örneklerine kıyasla anlamlı derecede azalmış miR-33a ifadesi izlenirken, BHRHK' ya ait primer tümör doku örneklerinde T evresi ilerledikçe miR-33a ifadesinin artma eğiliminde olduğu belirlendi. Bu dokularda, ayrıca, miR-33a ile AMPK 1 ve 2 mRNA ifadeleri arasındaki negatif yönde zayıf korelasyonların olduğu saptandı. Ancak, alt grup analizlerinde bu korelasyonların yüksek T evreli olgularda olmadığı belirlendi. Hücre hatları analizlerimizde ise; AMPK 1α protein ve miR-33a ifade düzeylerinin, daha agresif olan metastatik Caki-1 hücrelerinde A-498 primer tümör hücrelerine oranla anlamlı derecede daha yüksek olduğu belirlendi. miR-33a mimik transfeksiyonlarına bağlı olarak hücre içi lipid içeriğinde belirgin değişim olmadığı gözlemlenirken, anti-miR-33a transfeksiyonlarının A-498 ve Caki-1 hücrelerinde hücre içi doğal lipid oranında azalmaya sebep olduğu izlendi. Öte yandan, hücre içi lipid düzeyindeki azalma AMPK 1α protein seviyesi daha yüksek olan metastatik Caki-1 hücrelerinde daha fazlaydı. Bulgularımız, BHRHK patogenezinde yağ asit metabolizması ilişkili AMPK ve miR-33a' nın erken evre ve ileri evre hastalıkda farklı karmaşık rollleri olabileceğini düşündürecek kanıtlar olarak ele alınabilir. Hücre hatlarından elde ettiğimiz sonuçlara göre, AMPK 1α protein seviyesi daha yüksek olan metastatik hücrelerde anti-miR-33a ile müdahelenin hücre içi lipid birikimini önemli ölçüde azalttığı saptandı. Sonuç olarak bulgularımız, miR-33a' nın ileri evre BHRHK tedavisinde potansiyel bir hedef olabileceğini desteklemekle birlikte, bu konuda daha net sonuçlar için miR-33a' nın hücre sağkalımı üzerine etkilerinin de ayrıntı irdelenmesi gerekmektedir
Molecular Docking and Molecular Dynamics Studies of Glu-Glu-Arg, Glu-Pro-Arg, and Pro-Arg-Pro Tripeptides to Reveal Their Anticancer and Antiviral Potentials
No full textBioactive peptides have been emerging as drug candidates with increasing importance in the last few decades. In this study, to evaluate the anticancer and antiviral properties of EER (Glu-Glu-Arg), EPR (Glu-Pro-Arg), and PRP (Pro-Arg-Pro) tripeptides, firstly their conformation preferences were searched, and the most stable optimized structure of each tripeptide was determined, using the molecular mechanics force field (MMFF) method and the Spartan06 program. Afterwards, each tripeptide was docked to SARS-CoV-2 spike protein receptor-binding domain (6M0J), SARS-CoV-2 main protease (6M03, 6LU7), spike glycoprotein (6VXX), DNA (1BNA), integrins (4WK0, 3ZDX, 1JV2) and epidermal growth factor receptor tyrosine kinase (4HJO). Moreover, molecular dynamics (MD) simulations were performed to validate the stability of the EER, EPR and PRP tripeptides docked to SARS-CoV-2 main protease, MPro (6M03) and epidermal growth factor receptor tyrosine kinase (4HJO) within 100 ns time scale and ligand-receptor interactions were evaluated. The metrics root-mean-square deviation, root-mean-square fluctuation, intermolecular hydrogen bonding, and radius of gyration revealed that the EER, EPR, and PRP tripeptides form energetically stable complexes with the target proteins. The binding free energies were calculated by the combination of Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) methods (MM/PB(GB)SA). Principal Component Analysis on MD data was performed to evaluate the energy and structural information of the tripeptide-protein complexes. Additionally, in-silico structure-based pharmacological predictions were made and the anticancer and antibacterial activities of the tripeptides were predicted.Bilimsel Arastirma Projeleri Birimi, Istanbul Universites
10. Aile İşletmeleri Kongresi: İş Dünyasında Dönüşümler: Bildiriler Kitabı, 15-16 Mayıs
No full text▪️ Aile İşletmeleri hakkında pek çok bilgiyi içeren bu kaynak kitap, 15-16 Mayıs 2024 tarihinde gerçekleştirilen 10. Aile İşletmeleri Kongresi’nde sunulan bildirilerden oluşmaktadır
1st International conference on Mediterranean Geosciences Union, MedGU 2021, 25 November 2021through 28 November 2021
No full textThis study is fictionalized with the use of ANNs logic to estimate the compaction parameters of bentonite–sand mixtures. Totally 230 sets of tests were digitized from the nine well-accepted literature sources to specify the grain size, consistency, and compaction parameters of the bentonite–sand mixtures. Matlab R2018a software is used to perform the estimation process of the compaction parameters, and representative expressions were derived to ease the determination process of mixtures. Consequently, the applicability of the suggested expressions has been checked by the determination and comparison of well-known international metric measurements. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
Cognitive Control and Flexibility to Happiness: Distress Tolerance and Difficulties in Emotion Regulation as Serial Mediators
No full textHappiness is a positive construct that includes individual, interrelated cognitive and emotional components and is the pursuit of human nature. In this study, serial multiple mediation analysis was performed to test the hypothetical model that addresses distress tolerance and difficulties in emotion regulation as serial mediators in the relationship between cognitive control and flexibility, and happiness. The participants were 315 Turkish individuals from 34 cities in Turkiye. The structural equation modeling revealed that both distress tolerance and difficulties in emotion regulation have a full serial mediator role in the relationships between cognitive control and flexibility, and happiness. Limitations and future research suggestions are discussed
7th International Conference on Earthquake Engineering and Seismology, 7ICEES 2023
No full textIn this study, an adaptive modal pushover analysis procedure (VMPA-A) is implemented in the 20-story Los Angeles SAC Steel building. The method considers the changes in the dynamic characteristics and bi-directional ground motion effects simultaneously with the help of the hybrid-spectrum concept. Two different approaches are used to calculate displacement demands for each mode. The first one is equal displacement rule and the second is performing nonlinear time history analyses (NTHA) to modal single degree of freedom systems (SDOF). VMPA-A procedure is implemented by using a MATLAB-based computer program, DOC3D. The building is modeled with both SAP2000 and DOC3D programs. Cross-checks are done between two programs by performing eigenvalue and pushover analyses. As an accepted “exact solution”, NTHAs are used to check the accuracy of the VMPA-A procedure. Fourteen ground motion records, which were selected from the PEER NGA-West2 Database, are used in NTHAs by using SAP2000. The response parameters of storey shears, storey displacements, storey drifts, and column and beam curvatures are discussed by comparing the results of VMPA-A with nonlinear time history analyses. Good estimates are observed for storey displacements, storey shears, and storey drifts. Although the second approach in the calculation of displacement demands gives closer results to NTHA, the obtained demand parameters from the equal displacement rule are conservative. Storey drift and beam curvature distributions seem to be in a similar trend. Larger values for lower stories and smaller values for the upper stories are obtained with respect to the average of NTHAs. However, beam curvature distribution can not be predicted by VMPA-A, especially for the upper stories of the building. The column curvature results are in good agreement with NTHA results. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
EU External Governance in Policy Area Under "Embedded Stalemate": Navigating the Dynamic Networks of Turkish Transport
No full textThis paper offers a nuanced examination of EU external governance within the challenging terrain of ‘embedded stalemate’, utilizing a network governance lens. Focusing on the Turkish transport sector as a case study, the research seeks to unravel the determinants of EU compliance in areas characterized by a protracted political impasse. By investigating the intricate dynamics of this ‘embedded stalemate’, the paper explores the question: ‘How do various factors influence the compliance with the EU in the Turkish transport sector amid a prolonged stalemate characterized by the absence of benchmarks and deadlines?’ Through 11 semi-structured interviews with key stakeholders, ranging from Turkish Ministry officials to private transport advisors, the study identifies variables such as incentives, actor capacities, asymmetry of interdependence, socialization, and politicization as crucial forces influencing the trajectory of compliance. The conceptual framework of network governance is introduced, providing a theoretical lens to understand the complex web of actors and preferences in this dynamic landscape. Therefore, the study concludes that as a result of ‘embedded stalemate’, patchy compliance is achieved through prolonged and dynamically evolving network governance involving a diverse array of actors from both the EU and Turkey sides
Hydrogen-Atom-Assisted Tautomerization on Solid Surfaces-The Case Study of Thioacetamide
No full textAmorphous thioacetamide (TA) ice was prepared by deposition on a low-temperature substrate in an ultrahigh-vacuum simulation chamber, exposing the sample to a beam of hydrogen atoms. The structural changes were monitored by reflection-absorption FT-IR spectroscopy. The spectral data unambiguously evidence the formation of the higher-energy thiol tautomeric forms of TA upon interaction with H atoms, resulting from the more stable thione tautomer, which is otherwise exclusively present in unprocessed ice. The regeneration of the thione species from the thiol tautomeric forms occurs upon heating the sample above 100 K. Quantum-chemical computations were conducted to confirm the conclusions drawn from the experimental results. According to the theoretical findings, the thiol molecules, formed on the surface of amorphous ice upon H-atom-assisted thione -> thiol tautomerization, cannot survive in the crystalline material. A mechanism for the process at the molecular level is also proposed. This work provides the first example of H-atom-assisted tautomerization occurring on the surface of amorphous ice without the action of UV light as the source of energy.Fundacao para a Ciencia e a Tecnologia (FCT)
Hungarian Academy of Sciences
Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA)
Thematic Excellence Program of the Eotvos Lorand University
National Research, Development & Innovation Office (NRDIO) - Hungary
Bolyai" scholarship of MTA
New National Excellence Program" of the Ministry for Culture and Innovation from the source of NKFIH
Fundacao para a Ciencia e a Tecnologia (FCT)
Chemical Engineering and Renewable Resources for Sustainability (CERES
International Symposium for Production Research, ISPR 2023
No full textThe urgent need for Value Engineering has arisen due to the enormous expenditure in the construction industry, which could be reduced by up to 25%. This substantial spending is often accompanied by poor quality, leading to a constant need for reconstruction and maintenance. The methods and concepts of Value Engineering can be applied to address this issue. By using Value Engineering, solutions can be created that fulfil the same functional purpose at a lower cost while maintaining high quality. This can be achieved through an analytical study using a specific approach conducted by a multidisciplinary team to identify and classify the functions that the project performs. Profound methods can then be utilized to find innovative alternatives without compromising the basic requirements and quality. This research is dedicated to demonstrating the methodology of Value Engineering while highlighting its impact on construction projects through a case study: Magrabi Offices in Saudi Arabia. This paper used an organized multidisciplinary methodology to identify the project’s main and secondary functions, then utilized Pareto’s law to identify higher-cost materials. It was proven that finding low-cost equivalent materials could reduce the total price by 23.13%. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
Content Analysis of the "Arkitekt" Journal From Housing Perspective: A Discussion About Social Aspects of Housing in Turkey
No full textThe shared spaces in residential areas identify the medium for private/domestic and public/social life interaction of the individual-society-space and create potentials for developing more sustainable residential areas. Accordingly, the housing problem is a social phenomenon, which is related to both individual and societal requirements about finding the adequate dwelling opportunities. This research creates a discussion about social aspects of housing and analysis of Turkish housing history from this perspective. The conceptual background includes the subjects about spatial characteristics of individual and society interaction according to daily life routines and the public-domestic space hierarchy in residential areas. This research has two analysis phases: content analysis and spatial analysis. Firstly, the changes in the housing development in Turkey is explained in the historical context via the content analysis of the Arkitekt Journal. In the second phase of analysis, Turkish housing examples which were selected according to the content analysis are spatially analyzed with general features and public-private space hierarchy. The spatial characteristics of examples are evaluated according to social and built environment characteristics in order to explain the impact of shared spaces in residential areas. The main discussion is developed according to the changes in shared space use of different periods in relation to housing decisions of their era. In order to examine the housing developments in Turkey, the term social aspects of housing provides the opportunities to identify the different factors, which have effects on social and built environment characteristics of the residential areas and the relevance to socially sustainable housing developments