Browsing by Subject "Urea"
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Item Open Access Data mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial: ‘exposing the invisible’(Oxford University Press, 2016) Okutucu, S.; Katircioglu-Öztürk, D.; Oto, E.; Güvenir, H. A.; Karaagaoglu, E.; Oto, A.; Meinertz, T.; Goette, A.Aims: The aims of this study include (i) pursuing data-mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial dataset containing atrial fibrillation (AF) burden scores of patients with many clinical parameters and (ii) revealing possible correlations between the estimated risk factors of AF and other clinical findings or measurements provided in the dataset. Methods: Ranking Instances by Maximizing the Area under a Receiver Operating Characteristics (ROC) Curve (RIMARC) is used to determine the predictive weights (Pw) of baseline variables on the primary endpoint. Chi-square automatic interaction detector algorithm is performed for comparing the results of RIMARC. The primary endpoint of the ANTIPAF-AFNET 2 trial was the percentage of days with documented episodes of paroxysmal AF or with suspected persistent AF. Results: By means of the RIMARC analysis algorithm, baseline SF-12 mental component score (Pw = 0.3597), age (Pw = 0.2865), blood urea nitrogen (BUN) (Pw = 0.2719), systolic blood pressure (Pw = 0.2240), and creatinine level (Pw = 0.1570) of the patients were found to be predictors of AF burden. Atrial fibrillation burden increases as baseline SF-12 mental component score gets lower; systolic blood pressure, BUN and creatinine levels become higher; and the patient gets older. The AF burden increased significantly at age >76. Conclusions: With the ANTIPAF-AFNET 2 dataset, the present data-mining analyses suggest that a baseline SF-12 mental component score, age, systolic blood pressure, BUN, and creatinine level of the patients are predictors of AF burden. Additional studies are necessary to understand the distinct kidney-specific pathophysiological pathways that contribute to AF burden. Published on behalf of the European Society of Cardiology.Item Open Access Electrospinning of polymer-free nanofibers from cyclodextrin inclusion complexes(American Chemical Society, 2011) Çelebioğlu, Aslı; Uyar, TamerThe electrospinning of polymer-free nanofibers from highly concentrated (160%, w/v) aqueous solutions of hydroxypropyl-β-cyclodextrin (HPβCD) and its inclusion complexes with triclosan (HPβCD/triclosan-IC) was achieved successfully. The dynamic light scattering (DLS) and rheology measurements indicated that the presence of considerable HPβCD aggregates and the high solution viscosity were the key factors in obtaining electrospun HPβCD and HPβCD/ triclosan-IC nanofibers without the use of any polymeric carrier. The HPβCD and HPβCD/triclosan-IC solutions containing 20% (w/w) urea yielded no fibers but only beads and splashes because of the depression of the self-aggregation of the HPβCD. The inclusion complexation of triclosan with HPβCD was studied by isothermal titration calorimetry (ITC) and turbidity measurements. The characteristics of the HPβCD and HPβCD/triclosan-IC nanofibers were investigated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). It was found that the electrospinning of HPβCD/triclosan-IC solution having a 1:1 molar ratio was optimal for obtaining nanofibers without any uncomplexed guest molecules.Item Open Access Elucidation of the denaturation mechanism of urea on macromolecules in aqueous medium(2022-09) Mutlu, FerhatThe urea molecule is a well-known denaturant for a wide range of macromolecules. To date, there is no unified molecular-level explanation for urea-induced denaturation of all macromolecules. As a result, considerable effort has been directed toward this subject in recent years, because osmolyte protein interactions are of central interest and have implications ranging from polymer physics to cell biology. Detailed urea denaturation mechanisms, focusing on the entropically driven formation of urea clouds, urea induced cross-linking mechanism, and osmolyte clouding around macromolecules, have been proposed in the literature. However, no agreement has been reached on the molecular machinery of urea denaturation. In this thesis, the urea-induced solubility changes of macromolecules in aqueous solutions were investigated by utilizing the lower critical solution temperature (LCST) of poly (N - isopropylacrylamide) (PNIPAM) and poly (N,N-diethylacrylamide) (PDEA) as a function of urea concentration up to 6.0 M. Due to the lack of suitable probing methods for the collapsed state of interested macromolecules, a temperature-controlled ATR – FTIR spectroscopy based method was developed to explore the interaction between urea and the collapsed state of macromolecule. LCST measurements revealed that the solubility of PDEA increases with increasing urea concentrations, whereas PNIPAM salts-out from the solution monotonically, despite the fact that both polymers have similar molecular structures. Temperature gradient ATR-FTIR measurements were carried out to further investigate this discrepancy. First, no favourable urea accumulation towards the collapsed form of macromolecules was observed up to 6.0 M urea, which puts doubt on the urea clouding mechanism. Moreover, at elevated (> 3.0 M) urea concentrations, the collapsed form of the PNIPAM and PDEA accumulated towards the cooler parts of temperature gradient in solution, indicating the preferred form of the macromolecule is the soluble (uncollapsed) form. These surprising results indicate that both PNIPAM and PDEA prefers the soluble form at elevated urea concentrations above the LCST. As a molecular mechanism, the urea molecules act as a "glue" between the amide groups of PNIPAM, bringing intra- and inter-molecular parts of the macromolecule into close proximity, and act as a collapsed form of macromolecules. Apparently, such a mechanism is not valid for the PDEA. Our findings shed new light not only on aqueous phase phenomena, but also on the aggregated (collapsed) phase of macromolecules in aqueous medium.Item Open Access Multiplexed cell-based diagnostic devices for detection of renal biomarkers(Elsevier, 2022-12-24) Köse, Sıla; Ahan, Recep Erdem; Köksaldı, İlkay Çisil; Olgaç, A.; Kasapkara, Çiğdem S.; Şeker, Urartu Özgür ŞafakThe number of synthetic biology-based solutions employed in the medical industry is growing every year. The whole cell biosensors being one of them, have been proven valuable tools for developing low-cost, portable, personalized medicine alternatives to conventional techniques. Based on this concept, we targeted one of the major health problems in the world, Chronic Kidney Disease (CKD). To do so, we developed two novel biosensors for the detection of two important renal biomarkers: urea and uric acid. Using advanced gene expression control strategies, we improved the operational range and the response profiles of each biosensor to meet clinical specifications. We further engineered these systems to enable multiplexed detection as well as an AND-logic gate operating system. Finally, we tested the applicability of these systems and optimized their working dynamics inside complex medium human blood serum. This study could help the efforts to transition from labor-intensive and expensive laboratory techniques to widely available, portable, low-cost diagnostic options.