Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution

Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations' resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics

Grafen ve au arayüzleri arasındaki sürtünme kuvvetinin katman sayısı ve yüke bağlı değişiminin yük yoğunluğu fonksiyoneli teorisi ile incelenmesi.

As the investigation of materials at nano scale become possible with today's technology it is observed that some physical phenomenons have different characteristics at atomistic scale than macroscopic one because of the quantum mechanical effects. One of these physical processes that differs at nano scale is the friction force. While it is expected that the friction force to be independent of contact area and velocity according to Amontos-Coulomb laws, it was observed that it changes by the effect of some parameters such as contact area, velocity, load and temperature at smaller scales. This study will include nanotribological calculations which analyzes the friction force between objects at atomic level. The lateral friction force that arises from the relative sliding motion of materials can be investigated in experimental manner using the Friction Force Microscopy (FFM) which is modified version of the Atomic Force Microscopy (AFM). It is also possible to obtain a detailed understanding of friction in atomic scale by modelling the mechanism of FFM using computational methods. The ab initio Density Functional Theory (DFT) is one of these methods that one can perform accurate calculations for the relative sliding motion of FFM probe tip and the surface. The importance of these kind of numerical methods is the convenience of investigating the wide range of material interactions that are not achievable with experimental methods. As it was observed that the two dimensional materials such as graphene, hexagonal boron nitride(h-BN) , $MoS_2$ provides good performance as dry lubricants, the scope of the nanotribology studies shifted into the frictional behaviors of these systems and their effects on other type of materials. In this thesis, we focus on the lateral friction force between two dimensional graphene sheets and three high-symmetry surfaces of gold. Our aim is to understand the results of FFM experiments by modelling the friction mechanism between Au coated probe-tip and graphene surface by implementing static calculations based on Density Functional Theory. As the Au coated probe slides over graphene, Au surfaces with different orientations would interact with graphene surface and three of them namely Au(100), Au(110) and Au(111) are reviewed as the subjects of this study. The effects of physical variables such as an external load applied to structures and increasing the thickness of the surfaces were interpreted. Results of this thesis can provide useful informations about minimizing the friction between objects with the help of different parameters which would be beneficial in industrial manner about reducing the loss of energy arises due to friction.M.S. - Master of Scienc

Retinoic acid signaling and bladder cancer: Epigenetic deregulation, therapy and beyond

Retinoic acid (RA) signaling is a crucial developmental pathway involved in urothelium development, differentiation and regeneration. Deregulation of the RA signaling is highly implicated in several cancers, including bladder cancer, underlying the need to unravel the complete regulatory aspects of the retinoids in bladder tumorigenesis. Given the fact that RA receptors are transcription factors functioning at the chromatin level and act in close cooperation with chromatin modifiers, it is known that retinoids show their efficacy by changing the epigenome. Bladder cancer can be defined as a "disease of chromatin" with mutations identified in the genes involved in chromatin regulation in 80% of the patients. Therefore, a careful examination of the epigenetic backgrounds and the breakdown of the emerging and highly underexplored field of RA dependent regulation of the epigenome is essential to fully understand the retinoid-dependent effects on bladder cancer. With this motivation, in this review, we evaluate the role of RA signaling in bladder cancer with a focus on the regulatory and mutational aspects, emphasizing the deregulatory characteristics in bladder cancer and highlighting the potential treatment opportunities with the RA and derivatives alone or in combination with epigenetic drugs

Nazım Hikmet ve Bursa Cezaevi

Ankara : İhsan Doğramacı Bilkent Üniversitesi İktisadi, İdari ve Sosyal Bilimler Fakültesi, Tarih Bölümü, 2012.This work is a student project of the The Department of History, Faculty of Economics, Administrative and Social Sciences, İhsan Doğramacı Bilkent University.by Erdem Sönmez.Sönmez, Erdem. HIST 200-14SÖNMEZ HIST 200-14/E 2011-1

Association between Plasma Fibrinogen Level and Saphenous Vein Graft Patency

BACKGROUND: Fibrinogen is related to the pathogenesis of atherosclerosis. The inflammatory process in atherosclerosis may cause an increase in plasma fibrinogen level. Therefore, in this study we proposed to investigate whether plasma fibrinogen is associated with the patency of saphenous vein graft in patients at least 1 year after coronary artery bypass graft (CABG) surgery. METHODS: Patients who had undergone CABG surgery at least 1 year previously with at least one saphenous vein graft were included in the study. Patients were directed to cardiac catheterization for stable anginal symptoms or positive stress test results. Before coronary angiography, all patients underwent routine blood tests including assessment of plasma fibrinogen levels. RESULTS: Saphenous vein grafts were found to be patent in 199 patients and occluded in 132 patients. Plasma fibrinogen levels were significantly different between the two groups (2.85 ± 0.49 g/L vs. 3.62 ± 0.82 g/L, p < 0.001, respectively). Although the time duration after CABG operation differs significantly between the two groups (p = 0.004), multiple logistic regression analysis showed that plasma fibrinogen levels were found to be significantly associated with the patency of vein graft (odds ratio = 0.27, 95% confidence internal: 0.16-0.48, p < 0.001). CONCLUSIONS: Our results demonstrated that plasma fibrinogen levels were higher in patients with an occluded saphenous vein graft. To conclusively prove the relationship between plasma fibrinogen values and saphenous vein graft patency, additional investigation would be necessary