Pramanicin induces apoptosis in Jurkat leukemia cells; a role for JNK, p38 and caspase activation

Pramanicin is a novel anti-fungal drug with a wide range of potential application against human diseases. It has been previously shown that pramanicin induces cell death and increases calcium levels in vascular endothelial cells. In the present study, we showed that pramanicin induced apoptosis in Jurkat T leukemia cells in a dose- and time-dependent manner. Our data reveal that pramanicin induced the release of cytochrome c and caspase-9 and caspase-3 activation, as evidenced by detection of active caspase fragments and fluorometric caspase assays. Pramanicin also activated c-jun N-terminal kinase (JNK), p38 and extracellular signal-regulated kinases (ERK 1/2) with different time and dose kinetics. Treatment of cells with specific MAP kinase and caspase inhibitors further confirmed the mechanistic involvement of these signalling cascades in pramanicin-induced apoptosis. JNK and p38 pathways acted as pro-apoptotic signalling pathways in pramanicin-induced apoptosis, in which they regulated release of cytochrome c and caspase activation. In contrast the ERK 1/2 pathway exerted a protective effect through inhibition of cytochrome c leakage from mitochondria and caspase activation, which were only observed when lower concentrations of pramanicin were used as apoptosis-inducing agent and which were masked by the intense apoptosis induction by higher concentrations of pramanicin. These results suggest pramanicin as a potential apoptosis-inducing small molecule, which acts through a well-defined JNK- and p38-dependent apoptosis signalling pathway in Jurkat T leukemia cells

Morphology, crystal structure and thermal properties of nano-sized amorphous colemanite synthesis

It is important to utilize the raw colemanite (RC) mineral, which has abundant reserves in the world, and to reduce its particles to smaller sizes for nanotechnology. However, not only the particle size of the produced colemanite powder but also its other properties need to be elucidated. By using the Taguchi design, the RC mineral was ground in a high-energy ball mill. From signal-to-noise (S/N) ratio, the smallest average particle size was found to be 3.10 µm for the experiment E04/nano-sized amorphous colemanite (NAC) powder. The characteristics of as-received RC mineral and synthesized NAC material were investigated using laser particle size analyzer, optical microscopes, SEM–EDS, XRD, TEM, HRTEM, and TGA–DTA devices. It was found that the NAC powder was not homogeneous, a small peak within the 300–20 nm range appeared, and d90, d50, d10, and dmin values were, respectively, 14.6 µm, 3.08 µm, 232 nm, and 26 nm. In the XRD analysis, the pure colemanite, calcite, and silica minerals were determined. The crystal structure of the NAC powder almost turned amorphous, and the crystallite size of (031) peak was reduced to 7.3 nm. It was deduced that the average particle size was 8.29 nm (R2 = 0.86), and the d-spacing value was 0.307 nm. This significant finding was attributed to the mobility of balls and moreover it was interpreted with an equation. An unknown transition in TGA–DTA was referred to the calcite mineral. Finally, it is believed that the synthesized NAC material will be beneficial to engineering studies as a natural/mineral additive

Essays on Risk Creation in the Banking Sector

This thesis consists of four essays exploring risk creation in the banking sector. The essays examine how conflicting interests can compromise the objectivity, judgment, and decision making of economic agents. Consequently, they may prioritize their personal or institutional interests over the best interests of others or the entire financial system. Chapter 2 delves into the conflict of interest that arises when a bank serves as an investor in the stock market. Chapter 3 revisits the discussion of the potential misalignment between sovereign incentives and the collective interests of the currency union, particularly in the bond market. Chapter 4 draws attention to a situation where regulations in the banking sector may be advantageous for a government in the sovereign bond market. Finally, Chapter 5 looks at the flip side of the coin, examining how banks may be susceptible to moral hazard concerns in their FX lending decisions, given that they do not fully bear the consequences of their actions

Influence of milling parameters on particle size of ulexite material

Commercial raw ulexite (U) materials were milled from 0 h to 8 h by using mechanical milling technique for var-ious initial powder size (−3mm;−75μm), ball to powder ratio (5:1; 10:1), and ball size (10 mm; 5 mm). Par-ticle size, morphology, elemental, and crystal structure measurements of the milled powders were performed. Inthe particle size distribution analysis, the smallestd50andd10values were respectively found as 8.846μmand790 nm for U_5m powder (obtained from that initial powder with−3 mm in size was milled by balls with5 mm in size) at 0.5 h. In the morphology analysis, the microstructure of the U_5m powder was observed tobe more homogeneous by means of milling process. In the elemental analysis, it was deduced that the U_5mpowder is not a pure compound. In the crystal structure analysis, it was determined that the crystal structureof the U_5m powder is exponentially deteriorated with increasing the milling time, and then it has become anamorphous structure at the end of 8 h. The crystalline size of the U_5m powder is reduced to 15.5 nm after 4 hof milling. The results of this study are considered to be useful for future nano studies and industrial applicationsof ceramic ulexite compound, which is a boron mineral.Scientific Research Projects Unit of Recep Tayyip Erdogan University: 2014.109.03.0

The Effect of Non-Performing Loans on Sector Profitability in the Turkish Banking Sector

The main purpose of this study is to determine the impact of non-performing loans (NPLs) on profitability of banking industry in Turkiye. In this study, in order to examine the basic indicators of profitability, non-performing receivables and consumer credit cards, non-performing housing and vehicle loans, non-performing consumer loans, consumer loans, loans and credit cards, net profit-loss and non-performing loans were compiled to generate a data set for the period between 2004 and 2018. Due to the different integration levels of the series obtained, models based on the autoregressive distributed lag (ARDL) approach, which is one of the time series regression methods, were established to analyze. Then, the effect of non-performing receivables on the banking sector profitability was examined. The initial findings reveal that the increase in non-performing receivables significantly reduced the profit of the banking sector.Bu çalışmanın amacı Türkiye’de bankaların takipteki alacaklarının sektör karlılığına etkisini belirlemektir. Bu çalışmada karlılığın temel göstergelerini incelemek amacıyla, takipteki ihtiyaç kredileri ve bireysel kredi kartları, takipteki konut ve taşıt kredileri, takipteki tüketici kredileri,  tüketici kredileri, krediler ve kredi kartları, dönem net kar-zararı ve takipteki alacakların 2004 - 2018 tarihleri arasındaki aylık bilançoları Bankacılık Düzenleme ve Denetleme Kurulu (BDDK) verileri ile derlenmiştir. Elde edilen serilerin farklı bütünleşme seviyeleri nedenle zaman serileri regresyonu yöntemlerinden ARDL yaklaşımı temel alınarak modeller kurulmuş ve banka karlılığı analiz edilmiş, takipteki alacakların bankacılık sektörü karlılığına etkisi incelenmiştir. Elde edilen ilk bulgulara göre, takipteki alacakların artışının, bankacılık sektörünün karını önemli ölçüde düşürdüğü ortaya çıkmaktadır

Pramanicin analog induces apoptosis in human colon cancer cells: critical roles for Bcl-2, Bim, and p38 MAPK signaling

Pramanicin (PMC) is an antifungal agent that was previously demonstrated to exhibit antiangiogenic and anticancer properties in a few in vitro studies. We initially screened a number of PMC analogs for their cytotoxic effects on HCT116 human colon cancer cells. PMC-A, the analog with the most potent antiproliferative effect was chosen to further interrogate the underlying mechanism of action. PMC-A led to apoptosis through activation of caspase-9 and -3. The apoptotic nature of cell death was confirmed by abrogation of cell death with pretreatment with specific caspase inhibitors. Stress-related MAPKs JNK and p38 were both activated concomittantly with the intrinsic apoptotic pathway. Moreover, pharmacological inhibition of p38 proved to attenuate the cell death induction while pretreatment with JNK inhibitor did not exhibit a protective effect. Resistance of Bax -/- cells and the protective nature of caspase-9 inhibition indicate that mitochondria play a central role in PMC-A induced apoptosis. Early post-exposure elevation of cellular Bim and Bax was followed by a marginal Bcl-2 depletion and Bid cleavage. Further analysis revealed that Bcl-2 downregulation occurs at the mRNA level and is critical to mediate PMC-A induced apoptosis, as ectopic Bcl-2 expression substantially spared the cells from death. Conversely, forced expression of Bim proved to significantly increase cell death. In addition, analyses of p53-/- cells demonstrated that Bcl-2/Bim/Bax modulation and MAPK activations take place independently of p53 expression. Taken together, p53-independent transcriptional Bcl-2 downregulation and p38 signaling appear to be the key modulatory events in PMC-A induced apoptosis

Topoloji Optimizasyonunda Eleman Silme Metodunun Uygulanmasi

Konferans Bildirisi -- Teorik ve Uygulamalı Mekanik Türk Milli Komitesi, 2008Conference Paper -- Theoretical and Applied Mechanical Turkish National Committee, 2008Makine parçalarında en iyi malzeme dağılımını sağlayabilmek için çeşitli optimizasyon yöntemleri geliştirilmiştir. Bu yöntemlerden birisi de topoloji optimizasyonudur. Topoloji optimizasyonunda en önemli sorun, çözüm için gereken uzun süredir. Bu çalışmada topoloji optimizasyonunda eleman silme metodu irdelenmiş ve metodun, topoloji optimizasyonunda uzun çözüm süresi için bir çıkış yolu olabileceği gösterilmiştir.To obtain the best material distribution in machine parts, some optimization techniques are developed by many researchers. Among these techniques topology optimization algorithms are discussed. These algorithms are useful for determining initial possible shape of structures. An important drawback of the topology optimization is time consumption. In this study, element deletion during topology optimization is discussed and it is shown that the method may be a solution to time consumption problem of topology optimization

The Effect of Sodium Chloride on Concretes Containing Milled Colemanite

Bu çalışmada, %0 (Referans), %1, %2, %3, %4 ve %5 oranlarında öğütülmüş kolemanit minerali çimento ile ikame edilerek beton karışımları hazırlanmıştır. Beton karışımlar 150 x 150 x 150 mm boyutlu küp kalıplara yerleştirilmiştir. Sertleşmiş beton numuneler 28 gün suda kür edilerek, sonrasında 90. güne kadar sodyum klorür (NaCI) çözeltisine maruz bırakılmıştır. Ayrıca aynı özelliklerde üretilen kontrol beton örnekleri ise 90. güne kadar su küründe bekletilmiştir. Kontrol ve NaCI çözeltisine maruz bırakılmış beton numuneler üzerinde Schmidt çekici, ultrases geçiş hızı ve basınç dayanımı deneyleri gerçekleştirilmiştir. Gerçekleştirilen deneyler üzerinden beton numunelerin NaCI çözeltisinin etkisi ile meydana gelen kayıplar hesaplanmıştır Sonuç olarak, çimentoya ikame edilen %5 kolemanit ikameli numunenin, kolemanit içermeyen numuneye göre basınç dayanımını azalttığı, ancak %4’ kadar ikame oranlarında ise dayanımı arttırdığı tespit edilmiştir. NaCI çözeltisi kürü sonucunda, en yüksek basınç dayanımı ve en az basınç dayanımı kaybının %3 kolemanit ikameli beton karışımına ait olduğu tespit edilmiştir.In this study, concrete mixtures were prepared by substituting milled colemanite mineral with cement in the ratio of 0% (Reference), 1%, 2%, 3%, 4% and 5%. The concrete mixtures are placed in 150 x 150 x 150 mm cube molds. Hardened concrete samples were cured in water for 28 days and then exposed to sodium chloride (NaCl) solution until day 90. In addition, the control concrete samples produced with the same characteristics were kept in the water cure until the 90th day. Schmidt hammer, ultrasonic pulse velocity and compressive strength tests were performed on concrete samples exposed to control and NaCl solution. The losses occuring by the effect of NaCl solution of concrete samples were calculated. As a result, it was found that the strength of the sample with 5% colemanite decreased compared to the sample without colemanite, but the strengthes of samples with up to 4% colemanite increased. As a result of cured to NaCl solution, the highest compressive strength and minimum compressive strength losses were determined to belong to the sample with 3% colemanite

Thermal properties of nanoparticle colemanite mineral and its advantages in application

Kolemanit minerali (C-3 mm) ve öğütülmüş kolemanit mineralleri (C-75 µm ile C-45 µm tozları) Eti Maden Bigadiç Bor İşletme Müdürlüğünden tedarik edildi. C-3 mm başlangıç malzemesi yüksek enerjili bilyalı değirmende öğütme işlemine tabi tutuldu. Akabinde bu malzeme mikronaltı boyutlu/nano boyutlu partiküller üretebilmek amacıyla ASTM standardındaki boyutu 25 μm olan bir elekten geçirildi (C-25 μm). C-3 mm mineralinin, C-75 µm tozunun, C-45 µm tozunun ve C-25 μm tozunun ısıl özellikleri TermoGravimetri (TG)/Diferansiyel Termal Analiz (DTA) cihazı ile belirlendi. DTA ölçümünde, ilk ayrışma sıcaklığı C-3 mm minerali için 406°C’de yüksek şiddete sahip endotermik bir pik ile gözükürken, C-25 μm tozu için 388°C’de endotermik bir pik ile ortaya çıktı. Diferansiyel TG ölçümünde, ilk ayrışma sıcaklığı C-3 mm minerali için 403°C’de yüksek şiddete sahip dar endotermik bir pik ile belirdi ve C-25 μm tozu için de 388°C’de endotermik bir pik ile ortaya çıktı. Önceki bir çalışmada, C-75 µm, C-45 µm ile C-25 μm tozları Portland çimentolu betona farklı oranlarda ilave edilmiştir. Çalışma sonunda betonun basınç dayanımında belirgin bir artış gözlemlendiği rapor edilmiştir. Bu bulguların nano boyutlu bor mineralleri ile alakalı mühendislik araştırmalarına ışık tutacağı düşünülmektedir

Öğütülmüş Kolemanit İçeren Betonlarda Sodyum Klorür Etkisi

Bu çalışmada, %0 (Referans), %1, %2, %3, %4 ve %5 oranlarında öğütülmüş kolemanit minerali çimento ile ikame edilerek beton karışımları hazırlanmıştır. Beton karışımlar 150 x 150 x 150 mm boyutlu küp kalıplara yerleştirilmiştir. Sertleşmiş beton numuneler 28 gün suda kür edilerek, sonrasında 90. güne kadar sodyum klorür (NaCI) çözeltisine maruz bırakılmıştır. Ayrıca aynı özelliklerde üretilen kontrol beton örnekleri ise 90. güne kadar su küründe bekletilmiştir. Kontrol ve NaCI çözeltisine maruz bırakılmış beton numuneler üzerinde Schmidt çekici, ultrases geçiş hızı ve basınç dayanımı deneyleri gerçekleştirilmiştir. Gerçekleştirilen deneyler üzerinden beton numunelerin NaCI çözeltisinin etkisi ile meydana gelen kayıplar hesaplanmıştır Sonuç olarak, çimentoya ikame edilen %5 kolemanit ikameli numunenin, kolemanit içermeyen numuneye göre basınç dayanımını azalttığı, ancak %4’ kadar ikame oranlarında ise dayanımı arttırdığı tespit edilmiştir. NaCI çözeltisi kürü sonucunda, en yüksek basınç dayanımı ve en az basınç dayanımı kaybının %3 kolemanit ikameli beton karışımına ait olduğu tespit edilmiştir