EPR studies of intermolecular interactions and competitive binding of drugs in a drug-BSA binding model

Understanding intermolecular interactions between drugs and proteins is very important in drug delivery studies. Here, we studied different binding interactions between salicylic acid and bovine serum albumin (BSA) using electron paramagnetic resonance (EPR) spectroscopy. Salicylic acid was labeled with a stable radical (spin label) in order to monitor its mobilized (free) or immobilized (bound to BSA) states. In addition to spin labeled salicylic acid (SL-salicylic acid), its derivatives including SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane and SL-hexane were synthesized to reveal the effects of various drug binding interactions. EPR results of these SL-molecules showed that hydrophobic interaction is the main driving force. Whereas each of the two functional groups (-COOH and -OH) on the benzene ring has a minute but detectable effect on the drug-protein complex formation. In order to investigate the effect of electrostatic interaction on drug binding, cationic BSA (cBSA) was synthesized, altering the negative net charge of BSA to positive. The salicylic acid loading capacity of cBSA is significantly higher compared to that of BSA, indicating the importance of electrostatic interaction in drug binding. Moreover, the competitive binding properties of salicylic acid, ibuprofen and aspirin to BSA were studied. The combined EPR results of SL-salicylic acid/ibuprofen and SL-ibuprofen/salicylic acid showed that ibuprofen is able to replace up to ∼83% of bound SL-salicylic acid, and salicylic acid can replace only ∼14% of the bound SL-ibuprofen. This indicates that ∼97% of all salicylic acid and ibuprofen binding sites are shared. On the other hand, aspirin replaces only ∼23% of bound SL-salicylic acid, and salicylic acid replaces ∼50% of bound SL-aspirin, indicating that ∼73% of all salicylic acid and aspirin binding sites are shared. These results show that EPR spectroscopy in combination with the spin labeling technique is a very powerful method to investigate drug binding dynamics in detail.Turkish Scientific and Technological Research Council (2232-114C082

Comparison of implant versus tooth-supported zirconia-based single crowns in a split-mouth design: A 4-year clinical follow-up study

WOS: 000388957000017PubMed ID: 26924133This study aims to evaluate the 4-year clinical performance of tooth versus implant-supported single-unit zirconia crowns (LAVA (TM)) placed on posterior region. Twenty-four patients (10 men and 14 women) who had received 48 single crowns (24 implant-supported and 24 tooth-supported) from January 2007 to December 2009, were included. California Dental Association (CDA) quality assessment system, plaque and gingival index scores were used to evaluate the performance of the crowns at baseline and at all follow-up examinations. During the follow-up period, no fracture of zirconia coping has occurred. Major complication was chipping in three patients that required a new crown fabrication. Except for the failure ones, all crowns in both groups were rated as satisfactory at the follow-up examinations based on the CDA quality assessment criteria. There were no statistically significant differences between tooth and implant-supported crowns in terms of periodontal parameters. The present 4-year follow-up clinical study demonstrates that single-unit tooth- and implant-supported zirconia crowns have similar prosthetic and periodontal outcomes. Single-unit implant or tooth-supported zirconia crowns may be considered acceptable treatment modalities for restoration of either missing or compromised posterior teeth

Effect of shading devices on external pressure coefficients' of windvard surfaces of buildings

Binaların pasif olarak en etkin biçimde soğutulması amaçlandığında; güneş ışınımı engeli olarak tasarlanacak kontrol elemanlarının (GE), tasarım aşamasında rüzgar etkileri bakımından irdelenerek performanslarının optimize edilmesi zorunludur. Yukarıdaki gerekçeye dayanarak yapılacak çalışmanın amacı; özellikle rüzgar konusunda sayısal yöntemler yeterli olamayacağından, GE’lerin basınç ve taşınım katsayıları üzerindeki etkilerinin rüzgar tünelinde deneysel yolla ortaya konmasıdır. GE’lerin cepheye paralel, dikey ve 45 derece açılı konumlandırılışlarıyla ana üç seçenek, kanatlarının 0 – 45 - 90' kanat açılarıyla oluşturulmuş almaşıklar ve referans (BOŞ) durum da dahil olmak üzere toplam 19 adet farklı durum üretilmiştir. Seçenek ve almaşıkların her birinde tünel içi hızı (GH) 2.5 ms-1, 5.0 ms-1 ve 8.3 ms-1’de rüzgar üstü yüzeyde basınç ölçümleri yapılmıştır. Bina yüzeyinde oluşan basınç katsayılarının (Cp) GE seçeneklerine bağlı olarak referans duruma (BOŞ) göre ne kadar farklılık gösterdiği incelendiğinde; % 95 güven aralığında, en dikkate değer fark referans durum ile (GE- CP- YK 0) yatay kanatlardan oluşan gölgeleme elemanının cepheye paralel konumlandırıldığı, 0 derece kanat açısında (t = 4.745, p =.0000 düzeyinde) ortaya çıkmıştır. Yapılan çalışmanın sonuçları pasif soğutma sisteminde rüzgar basıncıyla iç mekanlardaki hava hareketi hızının uygun düzeylerde sağlanıp sağlanamayacağının kestirilebilmesinde kullanılabilecektir. BOŞ durumda orta aksta cephenin tümünde Cp ort = ~ 0.80 düzeyinde elde edilen basınç katsayısı (Cp) değeri birçok ülkenin rüzgar yüklerine ilişkin yönetmeliklerine uyum göstermesine rağmen zemine yakın noktalarda mevcut benzer çalışmalardan ~ %10 daha büyük miktarlar ortaya koymuştur. Anahtar Kelimeler: Gölgeleme elemanları, basınç katsayısı dağılımı, doğal havalandırma, pasif soğutma.Solar shading devices prohibit the passage of direct component of solar radiation at the same time decrease the chilling effect of winds on buildings by forming insulative air pockets in summer season. External solar shading devices vary as a function building crust orientation.  In other words they should be designed as auxiliary architectural parts. These parts may be manufactured from materials such as glass, wood, plastic, concrete or metal. Typologically their form resembles shield forms which are either parallel or perpendicular to the building façade. Wind imposed pressure variations have major influence on building thermal comfort through temperature, humidity and air circulation speed.  These entities vary as a function of wind direction, wind speed, building orientation, roof and façade shapes, building height and openings on winward and leeward façades.  Air mass flow rate that passes through the building may be calculated as a function of average inlet and outlet pressures. In order to obtain the effect of solar shading devices on the wind pressure field over the building surface, an experimental campaign is conducted in a wind tunnel which has a test cross section of 1x1 meter. The 4 mm thick Plexiglas building model which is 50 cm. in width, 30 cm in height and 50 cm in depth simulates 5x3x5 m full scale building forming one zone. Solar shading devices are made of aluminum and of two type wings that are placed parallel to border longitudinal or transversal. The wings make 0, 45 and 90 degrees with the device plane. The position of the shading devices that holds the wings together also makes 0, 45 and 90 degrees with respect to the vertical windward façade of the model.  Thus, including the baseline - situation unless shading device is mounted - case, 19 different configurations;   are investigated throughout the campaign. There are a total number of 105 pressure measurement points clustered around the edges on the windward face of the model. The measurements were made at 2.5 m/s, 5 m/s and 8.3 m/s average wind speeds. For the case in which solar shading devices are not attached to the façade, the Cp distributions stay in a very narrow band no matter what the wind tunnel speed is.  The minimum Cp values are recorded as 0.42, 0.38 and 0.40 for the three speeds: 2.5, 5.0 and 8.3 m/s respectively. The maximum difference between the Cp values happens to be 0.04. The pressure coefficients (Cp) data obtained for different configurations of shading devices   are compared with the baseline configuration by Paired Samples Test. They are found  significant difference in 95% confidence level, between basline case (BOS ) and  configuration  that is the shading device parallel to building surface and its wings closed (they make 0 degree with respect to the self plane ) (GE-CP-YK 0  ). The average Cp value along the central axis (Cpave ~ 0.80) obtained for basline case (BOS) is in good agreement with wind load regulations of many other countries. According to the positioning and shading intensity of opaque shading devices on the windward face, the Cp values vary between 130 % and 40% with the respect to baseline case. The correlation coefficients obtained along the C1 axis are calculated as 0.74 and 0.84 for the horizontal and vertical wing configurations respectively. The measurement points corresponding to the opening on the windward face give an average correlation coefficient of 0.73 for all configurations. The effect of Solar shading devices on building façade pressure coefficient distribution has been considered only by a few numbers of researchers in the field.  Therefore, excluding the baseline case, the results obtained in the present investigation are original data introduced to the building aerodynamics field. Air mass flow rate that passes through the building may be calculated as a function of average inlet and outlet pressures. In order to assess the usage of the results in the design of natural ventilation systems and cooling load calculations, different pressure and velocity measurement programs are being undertaken.  Keywords: Shading devices, forced convection heat transfer, wind pressure distribution, natural ventilation, passive cooling, natural  climatisation.

Relationship between Pollen Counts and Weather Variables in East-Mediterranean Coast of Turkey

Background: Aeroallergen sampling provides information regarding the onset, duration and severity of the pollen season that clinicians use to guide allergen selection for skin testing and treatment

Effect of Fluid Supplementation on Serum Bilirubin Level During Phototherapy of Exclusively Breastfed Term Infants with Hyperbilirubinemia

Aim:This study compared the rates of decrease in serum bilirubin levels in severely jaundiced healthy term infants given oral or intravenous fluid supplementation during phototherapy.Materials and Methods:A randomized controlled study was carried out in the neonatal intensive care unit of Zeynep Kamil Maternity and Children Training and Research Hospital (Istanbul, Turkey) over a 4-month period. Fifty healthy term infants with hyperbilirubinemia were randomized to receive either solely breastmilk (n=25) or both breastmilk and intravenous fluid (n=25) during phototherapy.Results:There were no significant differences (p>0.05) in the mean birth weight, mean gestastional age, modes of delivery, mean time of admission age, mean serum osmolality, and hematocrit and reticulocyte count between the two groups. Similarly, there was no significant difference (p>0.05) in the mean indirect serum bilirubin level at the time of admission to the neonatal intensive care unit and at 4, 8, 12, 24, and 48 hours after commencement of phototherapy between the two groups. There was no significant difference (p>0.05) in the mean duration of phototherapy or in the median duration of hospitalization between the two groups.Conclusion:Based on our results, intravenous fluid support has no effect on the rate of decrease in serum bilirubin and decrease in duration of phototherapy in healthy term newborns with no dehydration. However, using the oral route avoided the need for intravenous cannula and their attendant complications. Insensible fluid loss is increased during phototherapy, so protection of hydration status with oral feeding is important for newborns

Metastatik safra yolu kanseri olan yaşlı hastalarda optimal tedavi yaklaşımları ve prognostik faktörler

Introduction: There is a lack of evidence of the outcomes in elderly patients advanced stage biliary tract cancer due to the patients aged over 65 years are less than 25% in many prospective trials. We designed a retrospective multicenter study to evaluate the factors affecting treatment and survival in elderly patients with advanced-stage biliary tract cancer. Materials and methods: A total of 116 patients with advanced stage biliary tract cancer aged ≥65 years were included, and the treatment responses, survival, and toxicity rates were evaluated with respect to age groups Results: There was no significant difference between age and response to treatment, survival, or toxicity. The median progression-free survival and overall survival were 5.3, and 11.8 months respectively. Multivariate analysis indicated that ECOG PS (p<0.001 CI95% 1.5-3.7) and PNI (p<0.001 CI 95% 0.14-0.41) were significant independent prognostic factors for PFS. The independent prognostic factors for OS were choice of frontline regimen, NLR and PNI (p=0.007 CI 95% 0.71 – 0.94, p=0.006 CI 95% 1.2 – 3.1, p=0.001 CI 95% 0.35 – 0.91, respectively). Discussion: This study confirms the general prognostic relevance of inflammatory parameters and the importance of frontline treatment in elderly patients with advanced-stage biliary tract tumors. Additionally, getting older does not indicate that treatment will be avoided or that they will have a worse prognosis and suffer from more toxicities.Giriş: 65 yaş üzeri hastaların klinik çalışmaların %25’inden daha azını oluşturması nedeniyle biliyer sistem kanseri olan ileri yaş hastaların yönetimi konusunda kanıt eksiği bulunmaktadır. Bu amaçla, metastatik safra yolu kanseri tanılı yaşlı hastalarda tedaviyi ve sağkalımı etkileyen faktörleri değerlendirmek için retrospektif çok merkezli bir çalışma tasarladık. Gereç ve yöntemler: Çalışmaya 65 yaş ve üzeri, ileri evre safra yolu kanseri tanısı almış, 116 hasta dahil edildi ve yaş gruplarına göre tedavi yanıtları, sağkalım ve toksisite oranları değerlendirildi. Bulgular: Median yaşa göre gruplandırılıdğında; yaş ile tedaviye yanıt, sağkalım, toksisite arasında anlamlı bir fark bulunmadı. Tüm populasyonda medyan progresyonsuz sağkalım (PSK) ve genel sağkalım (GSK) sırasıyla 5.3, 11.8 aydı. Multivariate analizde, PSK için bağımsız prognostik faktörler preformans durumu(ECOG PS) (p<0.001 CI95% 1.5-3.7) ve Prognostik nutrisyonel indek (PNI) (p<0.001 CI 95% 0.14-0.41) olarak bulundu. GSK için ise bağımsız prognostik faktörler, birinci sıra tedavi seçimi, Notrofil Lenfosit oranı (p=0,007 CI %95 0,71 – 0,94) ve PNI (p=0,001 CI %95 0,35 – 0,91) olarak bulundu. Tartışma: Metastatik safra yolu kanseri olan yaşlı hastalarda prognozu etkileyen temel faktöreler inflamatuar parametreler ve birinci basamakta seçilen kemoterapi rejimidir. İleri yaş ile sağkalım, toksiste profili ve tedavi toleransı farklılık göstermemektedir

A genomic snapshot of demographic and cultural dynamism in Upper Mesopotamia during the Neolithic Transition

Upper Mesopotamia played a key role in the Neolithic Transition in Southwest Asia through marked innovations in symbolism, technology, and foodways. We present thirteen ancient genomes (c.8500-7500 calBCE) from Pre-Pottery Neolithic Çayönü in the Tigris basin together with bioarchaeological and material culture data. Our findings reveal that Çayönü was a genetically diverse population, carrying a mixed ancestry from western and eastern Fertile Crescent, and that the community received immigrants. Our results further suggest that the community was organised along biological family lines. We document bodily interventions such as head-shaping and cauterization among the individuals examined, reflecting Çayönü's cultural ingenuity. Finally, we identify Upper Mesopotamia as the likely source of eastern gene flow into Neolithic Anatolia, in line with material culture evidence. We hypothesise that Upper Mesopotamia's cultural dynamism during the Neolithic Transition was the product not only of its fertile lands but also of its interregional demographic connections

Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication

Yurtman, ozer, Yuncu et al. provide an ancient DNA data set to demonstrate the impact of human activity on the demographic history of domestic sheep. The authors demonstrate that there may have been multiple domestication events with notable changes to the gene pool of European and Anatolian sheep since the Neolithic. Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic

Proceedings of the 24th Paediatric Rheumatology European Society Congress: Part three

From Springer Nature via Jisc Publications Router.Publication status: PublishedHistory: collection 2017-09, epub 2017-09-0

Oyunlaştırma yoluyla toplumsal bilincin geliştirilmesi

Günümüzde iletişim ve bilgi teknolojilerinin baş döndürücü bir hızla ilerlermesi, geçmişte video oyunları olarak adlandırılan dijital oyunların da gelişmesine ve farklılaşmasına neden olmuştur. Özellikle bu oyunlar ile birlikte büyümekte olan ve G-nesli olarak adlandırılan yeni neslin toplumsal olaylara karşı hassasiyetlerinin giderek azalmakta olduğu görülmüştür. Genel olarak, bireylerin toplumda cari olan problemlere çözüm getirilmesi konusunda salt seçtikleri temsilciler vasıtası ile değil, doğrudan ve bizzat katılım gerçekleştirme eğiliminde olmaları beklenir. Buna karşılık, iletişim ve bilgi teknolojilerinin gelişmesi ile oluşan yeni sosyal ortamların bireyleri sosyal katılım konusunda miskinliğe itmekte olduğu da yadsınamaz bir gerçektir. Bu çerçevede, oyunlaştırma uygulamalarının günümüz sosyal problemlerine katılımın arttırılmasında oldukça olumlu katkılar sunacağı değerlendirilmektedir. Son yıllarda, söz konusu neslin ve toplumun diğer tüm fertlerinin toplumsal olaylara karşı farkındalıklarının arttırılması, sivil katılımlarının sağlanması ve toplumsal bilinçlerinin geliştirilmesi maksadı ile oyunlaştırma uygulamalarının eğitimden sağlığa, pazarlamadan spora vs. varıncaya kadar birçok alanda oldukça verimli şekilde uygulanmış olduğu ve görülmüştür. Bu çalışmada, öncelikle toplumsal bilinç kavramı incelenmiş olup daha sonra oyunlaştırma uygulamalarına ait tasarım unsurları incelenmiştir. Ayrıca, oyunlaştırmanın bireylerin davranışına olan etkileri ile oyunlaştırma tasarımı unsurlarının toplumsal bilincin arttırılmasına yönelik olarak değerlendirilmesi ele alınmıştır. Oyunlaştırmanın avantajlı yönleri ile oyunlaştırma uygulamalarının tasarlanması ve geliştirilmesi konusunda karşılaşılan zorluklar ele alınmış ve toplumsal bilincin arttırılmasına yönelik olarak son yıllarda gerçekleştirilen birçok başarılı çalışma incelenmiştir. -------------------- Today, the tremendous advancements of data and communication technologies give rise to the advancements and proliferation of digital games, which were once called as video games. Specifically, the new generation, which is dubbed as Generation-G, grows up with playing such games intensively that, it is stated to be the most eminent reason for their reluctance to the social problems. Generally, the individuals of the society are expected to be directly involved in such problems, instead of passing them to the selected representatives or proxies. Nevertheless, it is accepted that the novel social means, which are the consequences of the aforementioned improvements in technology, drives the individuals to a kind of digital slackness. In this sense, gamification applications may be exploited to guide the individuals to actively involve in today’s social problems. Nowadays, it can be seen that the gamification applications are becoming prevalent to be utilized in areas ranging from education, health, marketing, sports etc., in order to fortify the consciousness for the social problems and civic engagement. In this study, firstly, the individual consciousness and social consciousness concepts, the gamification concept and gamification design guidelines are explained. In addition, the behavioral influences of the gamification applications are analyzed and gamification design elements are explained through enhancement of social consciousness issues. Lastly, the advantages and challenges of gamification deployment and design issues are handled and various real world gamification applications which are designed for social consciousness enhancement are illustrated