Synthesis of novel oxadiazole derivatives and their cytotoxic activity against various cancer cell lines

Caffeic acid (CA), ferulic acid (FA) and caffeic acid phenethyl ester (CAPE) have a broad anticancer effect on various cell lines. In this study, nine ferulic and caffeic acid-based 1,2,4 and 1,3,4 oxadiazole molecular hybrids were synthesized and their cytotoxic activity was evaluated mainly against Glioblastoma (GBM) cell lines. Compounds 1 and 5 exhibited the highest inhibitory activity against three different GBM cell lines (LN229, T98G, and U87), without toxicity to healthy human mesenchymal stem cells (hMSC). In addition, their cytotoxicity was also evaluated against three additional cancer cell lines and more inhibitory results were found than GBM cell lines. The IC50 values of compound 5 in U87, T98G, LN229, SKOV3, MCF7, and A549 cells were determined as 35.1, 34.4, 37.9, 14.2, 30.9, and 18.3 µM. In the light of biological activity studies, the developed compounds have a high potential to lead studies for the development of new drug candidates for the treatment of cancer

Fiyat Artış Hızının Tüketicilerin Fiyat Algısı, Panik Satın Alma, Stoklama Niyeti ve Düşük Fiyat Bekleme Üzerine Etkisi

Pazarlama literatüründe fiyat indirimleri üzerine çok sayıda araştırma olmasına rağmen, fiyat artışlarının etkisini araştırmak için sınırlı sayıda çalışma yapılmıştır. Özellikle fiyat artış hızının tüketici davranışları üzerindeki etkisine yönelik çalışmalara ihtiyaç duyulmaktadır. Bu çalışma, fiyat artış hızının, fiyat algısı, panik satın alma davranışı, stoklama niyeti ve düşük fiyat bekleme üzerindeki etkisini incelemeyi amaçlamaktadır. Bu doğrultuda, farklı fiyat artış hızlarına sahip ürün görsellerini içeren iki senaryo 204 tüketiciden oluşan iki farklı katılımcı grubuna gösterilmiş ve araştırma değişkenlerini ölçmek amacıyla anketler uygulanmıştır. Araştırmada elde edilen verilere uygulanan analiz sonuçları, incelenen gruplar arasında düşük fiyat beklentisi, stoklama niyeti ve fiyat algısı açısından istatistiksel olarak anlamlı farklılıklar olduğunu göstermiştir. Araştırmanın sonucunda hem fiyatlandırma ile ilgilenen uygulayıcılar hem de pazarlama alanında çalışan araştırmacılar için çıkarımlarda bulunulmuştur

Effect of sowing methods on silage yield and quality of some corn cultivars grown in second crop season under irrigated condition of Central Anatolia, Turkey

Silage corn has an important potential as second crop under irrigated lands of semi-arid regions. This research was conducted to determine silage yield and quality of some corn cultivars (Ada, Cadiz, Donana, Sagunto and Sakarya) grown after barley harvest using different sowing methods (direct and conventional) in 2014 and 2015 years in Eskisehir Plain. Investigated parameters were significantly different between years except for leaf ratio and neutral detergent fiber (NDF) content. In the first year, plant height, fresh forage yield, and Fleig point were higher than the second year but dry matter, crude protein, acid detergent fiber (ADF) content, cob ratio and pH were contrarily higher in the second year. Sowing method significantly affected all parameters except leaf ratio. Using direct sowing method increased cob ratio (40.3 %), dry matter (22.93 %), crude protein content (7.56 %), pH (3,76) and Fleig score (85.82) compared to conventional sowing method. Cultivars significantly varied in terms of plant height, cob ratio, dry matter, crude protein, neutral detergent fiber, acid detergent fiber, pH, and Fleig point. Considering the total silage yield and quality the domestic cultivar Ada, which seeds are common in the market, could be suggested after barley harvest for second crop production as long as sown conventionally in irrigated lands of Central Anatolia

Adsorption challenge in the PDMS-based microfluidic systems for drug screening application

Drug screening is one of the demand areas due to close and direct dependency on human health. On the other hand, recently microfluidic systems have been increasingly used for drug development and screening purposes. However, this system has some challenges such as adsorption issue which can effect pharmacokinetic-pharmacodynamic (PK-PD) of the drugs. Thus, in this research, the issue was characterized and evaluated by UV-Vis spectrophotometry and FTIR spectroscopy devices as a model drug of cisplatin. Despite of strong relationship between logP and adsorption, and the very low value of logP in the drug candidate, the results for both apical and basal planes of the microfluidic chip confirmed the adsorption. In the UV-Vis spectrophotometry, the basal plane show 5%, and 10% higher adsorption compared to apical and control polydimethylsiloxane (PDMS)-based microfluidic. Additionally, the FTIR patterns were a good coincide with UV-Vis results

Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria

BackgroundMigraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert.MethodsIn this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis.ResultsLonger headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone.ConclusionLonger headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs

Numerical analysis of rock mass falls using PFC3D : a comparison of two cases: Thurwieser Rock Avalanche and Frank Slide

Rock mass falls, especially in mountain ranges like the Alps, belong to natural morphological phenomena. If they occur near population areas, they comprise great hazard to human life and to the nearby infrastructure. Thus it is very important to predict any possible occurrence and foresee the likely pathway of rock avalanches, so that precautions could be taken just in time.In order to evaluate the qualification of the numerical program PFC modified for run out modeling two cases were selected for comparing reality and simulation: Punta Thurwieser rock avalanche with a steep Fahrböschung and Frank Slide showing a gentle Fahrböschung.PFC3D (Particle Flow Code in 3 Dimensions) is a discontinuum mechanics program developed by ITASCA CONSULTING GROUP. PFC models the movements and interactions of stressed assemblies of spherical particles either in or getting contact with wall elements. The particles may be bonded together at their contact points to represent a solid that may fracture due to progressive bond breakage. Every particle is checked on contact with every other particle at every timestep. Thus PFC can simulate not only failure mechanisms of rock slopes but also the run out of a detached and fractured rock mass. The run out model using PFC consists of two basic elements: two dimensional wall elements which represent the non moved ground and spherical elements representing the rock mass particles in motion.Parameter variations showed that the parameters necessary to get results coinciding with observations in nature in the particular cases are completely different. The diagrams of mean particle velocities and kinetic energy over time clearly point out that some 30 percent of total kinetic energy is rotational kinetic energy in Thurwieser, whereas the contribution of rotational kinetic energy in Frank Slide is zero. Thus Frank run out is a real "slide" of a coherent mass, whilst Punta Thurwieser run out is a rock mass fall with much internal movement.Therefore, the prediction of the run out kinematics and the fixing of the parameters is a demanding task in each case when modeling run outs.10

Rekombinant İnsan Hyaluronidazının (rHuPH20) Post Travmatik Ödeme Etkisinin Deksametazonla Karşılaştırmalı Olarak İncelenmesi

Edema is a complication which may cause non-healing of epithelium lines, lessen the function and failing at the surgical operation. Today there are so many medications and ways to prevent edema due to surgical operations. But non of these ways and medications supresses the surgical edema at the desired level. At our study we aimed to reduce the operative edema which is named exudates of intercellular substance, by hyaluronidase enzyme which fasten the pass of the fluids from intercellular substance to systemic circulation. That activity of hyaluronidase enzyme is compared with deksamethasone’s which has the highest antiinflamatuar potency between glucocorticoids. As hyaluronidase enzyme, recombinant human hyaluronidase (rHuPH20) is used because of avoiding allergic reactions due to animal derived hyaluronidase preparats. 40 Sprague-Dawley albino rats divided randomly 5 equal groups. At 1. group just traumatic edema was made on 8 rats. At 2. group traumatic edema was made and 0.4 ml SF injected to the right hind paws of the rats. At 3. group 0.4 ml hyaluronidase injected to the right hind paws of the rats. At 4. group 0.4 ml deksamethasone injected to the right hind paws of the rats in the same way. At 5. group 0.4 ml deksamethasone-hyaluronidase combine injected to the right hind paws of the rats. The dosage of the medicines calculated according to weights of the rats. Because all fluids which are injected to the paws of the rats must be at the same volume, all medicines are completed to 0.4 ml by SF. All the rats’ right hind paws volume evaluated by plethysmometer before starting the traumatic edema formation and after it at the 3., 6., 12., 24., 48., 72., hours. As a result of statistical analysis deksamethasone didn’t significantly diminished the edema according to group 1, but significantly diminished the edema according to SF applicated group 2. Besides this, hyaluronidase significantly reduced the edema according to group 1 and 2. When hyaluronidase compared with dexamethasone, it had been shown hyaluronidase significantly reduces edema according to dexamethasone. Hyaluronidase-dexamethasone’s combine application provides less edema with regard to alone hyaluronidase application, but this difference isn’t significant. As a result of this study hyaluronidase enzyme may provide more better edema control than deksamethasone which is widely using effective agent for managing edema.ONAY SAYFASI iii YAYIMLAMA VE FİKRİ MÜLKİYET HAKLARI BEYANI iv ETIK BEYAN SAYFASI v TEŞEKKÜR vi ÖZET vii ABSTRACT viii İÇİNDEKİLER ix SİMGELER VE KISALTMALAR xi ŞEKİLLER xiv TABLOLAR xv 1. GİRİŞ 1 2. GENEL BİLGİLER 3 2.1. Yara İyileşmesi 3 2.1.1. İnflamatuar Faz 3 2.1.2. Proliferatif Faz 4 2.1.3. Remodelasyon Fazı 5 2.2. İnflamasyon 5 2.2.1. Akut İnflamasyon 7 2.2.2. Kronik İnflamasyon 8 2.2.3. İnflamasyonda Rol Alan Mediatörler 8 2.2.4. Post Travmatik ve Post Operatif Ödemi Giderme Amacıyla Kullanılan Ajanlar ve Yöntemler 22 2.2.5. Ödem Oluşturma Modelleri ve Hacmini Hesaplama Yöntemleri 40 3. GEREÇ ve YÖNTEM 46 3.1. Deney Hayvanları 46 3.2. Kullanılan Kimyasallar ve Ajanlar 48 3.3. Araç ve Gereçler 48 3.4. Deney Grupları ve Yöntem 49 3.4.1. Deney Grupları 49 3.4.2. Deneysel Ödem Oluşturma Modeli 51 3.4.3. Ödemi Değerlendirme Yöntemi 53 3.5. İstatistiksel Analiz 56 4. BULGULAR 58 5. TARTIŞMA 73 6. SONUÇ 81 7. KAYNAKLAR 83 8. EKLER 98 9. ÖZGEÇMİŞ 99Ödem, cerrahi operasyonlar sonrasında yara dudaklarının açılmasına sebep olabilen, fonksiyonda kısıtlılık yaratan ve işlemin başarısızlıkla sonuçlanmasına yol açabilen bir komplikasyondur. Günümüzde cerrahi işlemler sonrasında ödem oluşumunun önüne geçmek amacıyla kullanılmakta olan birçok ajan ve yöntem bulunmaktadır. Ancak bu ajan ve yöntemlerin hiçbiriyle istenilen kontrol sağlanamamıştır. Çalışmamızda dokulararası sıvıların sistemik dolaşıma çok daha hızlı bir şekilde geçmesini sağlayan hyaluronidaz enzimi ile dokulararası boşlukta eksuda birikimi olarak tanımlanan ödemin sistemik dolaşıma hızlı geçişinin sağlanmasıyla önlenmesi hedeflenmektedir. Çalışmamızda hyaluronidaz enziminin bu etkinliği, en yüksek antiinflamatuar potense sahip glukokortikoid olan deksametazonunkiyle karşılaştırıldı. Hyaluronidaz enzimi olarak hayvansal hyaluronidazlar kullanıldığında hastalarda yaşanan allerjik reaksiyon gelişme komplikasyonunu mimimuma indirmek amacıyla rekombinant teknolojiyle üretilmiş insan hyaluronidazı (rHuPH20) kullanıldı. 40 adet Sprague-Dawley cinsi albino rat, rastgele 5 eşit gruba ayrıldı. 1. gruptaki 8 ratta sadece travmatik ödem oluşturuldu. 2. gruptaki ratlarda travmatik ödem oluşturularak sağ arka pençelerine 0.4 ml SF uygulandı. 3. gruptaki ratların sağ arka pençelerine 0.4 ml hyaluronidaz uygulandı. 4. gruptaki ratlara 0.4 ml deksametazon aynı şekilde uygulandı. 5. gruptaki ratların pençelerine 0.4 ml deksametazon-hyaluronidaz kombine verildi. İlaç dozları ratların kilolarına göre hesaplandı. Eşit hacimde olmaları için SF ile seyreltilip 0.4 ml’ye tamamlanarak hayvanlara uygulandı. Ratların ilk pençe hacimleriyle, 3., 6., 12., 24., 48. ve 72. saatlerdeki pençe hacmi değişimleri pletismometreyle ölçüldü. Yapılan istatistiksel analizler sonucunda deksametazonun hiçbir sıvı verilmeyen gruptan anlamlı düzeyde ödemi azaltmayıp, aynı hacimde serum verilen gruba göre anlamlı olarak ödemi azalttığı görülmüştür. Bunun yanında hyaluronidaz enziminin, hiçbir sıvı uygulanmayan ve serum uygulanan gruplardan anlamlı düzeyde ödemi azalttığı gözlenmiştir. Deksametazonla hyaluronidaz enzimi karşılaştırıldığında enzimin, deksametazona göre anlamlı düzeyde daha düşük ödem oluşumu sağladığı gösterilmiş, deksametazon-hyaluronidaz’ın kombine uygulanışının sadece hyaluronidaz uygulamadan anlamlı olmayacak düzeyde daha düşük ödem oluşumu sağladığı görülmüştür. Bu çalışmadan çıkarıldığı üzere hyaluronidaz enzimi, ödem kontrolü için en etkili ajanlardan biri olarak kullanılan deksametazondan çok daha iyi bir ödem kontrolü sağlayabilir

Evaluation of the Relationship between Breast Duct Diameter Measured by Ultrasonography and Mastalgia in Postmenopausal Patients

Objectives: The aim of this study was to determine the relationship between mastalgia, which is an important health problem in women, and breast duct diameter using ultrasonography (US). Methods: The study was planned prospectively. A total of 40 postmenopausal patients who were referred to our clinic due to unilateral breast pain were included in the study. Before the US examination, the patients were asked to score pain levels from 0 (no pain) to 100 (worst pain) according to the Visual Analog Scale (VAS). Results: The mean age of the patients was 56 (range 40-77) years. The mean diameter of the duct was 1.77±0.59 mm for the side with pain and 1.08±0.36 mm for the other side. There was a statistically significant difference between the two groups (p<0.001). There were a statistically significant positive correlation between both the duct diameter and symptom duration (r=0.514, p=0.007) and between the duct diameter and VAS score (r=0.684, p<0.001). Conclusion: In this study, the relationship between mastalgia and duct diameter was shown, but more comprehensive studies on this subject can shed further light on the etiopathogenesis of mastalgia

Trace-Driven Cache Attacks on AES

Abstract. Cache based side-channel attacks have recently been attracted significant attention due to the new developments in the field. In this paper, we present efficient trace-driven cache attacks on a widely used implementation of the AES cryptosystem. We also evaluate the cost of the proposed attacks in detail under the assumption of a noiseless environment. We develop an accurate mathematical model that we use in the cost analysis of our attacks. We use two different metrics, specifically, the expected number of necessary traces and the cost of the analysis phase, for the cost evaluation purposes. Each of these metrics represents the cost of a different phase of the attack

Trace-Driven Cache Attacks on AES (Short Paper)

Abstract. Cache based side-channel attacks have recently been attracted significant attention due to the new developments in the field. In this paper, we present an efficient trace-driven cache attack on a widely used implementation of the AES cryptosystem. We also evaluate the cost of the proposed attack in detail under the assumption of a noiseless environment. We develop an accurate mathematical model that we use in the cost analysis of our attack. We use two different metrics, specifically, the expected number of necessary traces and the cost of the analysis phase, for the cost evaluation purposes. Each of these metrics represents the cost of a different phase of the attack. Keywords: Side-channel Analysis, cache attacks, trace-driven attacks, AES