Inhibition of mutant RAS-RAF interaction by mimicking structural and dynamic properties of phosphorylated RAS

Undruggability of RAS proteins has necessitated alternative strategies for the development of effective inhibitors. In this respect, phosphorylation has recently come into prominence as this reversible post-translational modification attenuates sensitivity of RAS towards RAF. As such, in this study, we set out to unveil the impact of phosphorylation on dynamics of HRASWT and aim to invoke similar behavior in HRASG12D mutant by means of small therapeutic molecules. To this end, we performed molecular dynamics (MD) simulations using phosphorylated HRAS and showed that phosphorylation of Y32 distorted Switch I, hence the RAS/RAF interface. Consequently, we targeted Switch I in HRASG12D by means of approved therapeutic molecules and showed that the ligands enabled detachment of Switch I from the nucleotide-binding pocket. Moreover, we demonstrated that displacement of Switch I from the nucleotide-binding pocket was energetically more favorable in the presence of the ligand. Importantly, we verified computational findings in vitro where HRASG12D/RAF interaction was prevented by the ligand in HEK293T cells that expressed HRASG12D mutant protein. Therefore, these findings suggest that targeting Switch I, hence making Y32 accessible might open up new avenues in future drug discovery strategies that target mutant RAS proteins

Kadınlarda Yeme Stili ve İpucu Etkisi Arasındaki İlişkinin İncelenmesi, ve Obezite Sorununda Maruz Bırakma ve Tepki Önlemeye Dayalı Psikoeğitim Programının Etkinliğinin Araştırılması (Pilot Çalışma)

The aim of the first stage is to investigate the prevalence of binge eating among women, and also by exposing the overweight obese and normal-weight women, who got the highest scores on eating subscales, to the cues (sight and smell) of chocolate it is aimed to inquire whether or not there is a difference in terms of the craving scores and galvanic skin responses. The purpose of the second stage is to use the cue exposure and response prevention technique (Jansen, 2010) in order to assist obese adults to eliminate the effects of the environmental cues.Araştırmanın birinci aşamasının amacı kadınlarda bulimiya belirti düzeylerinin dağılımını; duygusal, kısıtlayıcı ve dışsal yeme stillerinden yüksek düzey elde eden normal kilolu ve aşırı kilo obezite sorunu olan kadınların çikolata ile ilişkili ipuçlarına (görüntü ve koku) maruz kalmaları durumunda aşerme düzeyleri ve galvanik deri tepkisi ölçümlerinin farklılaşıp farklılaşmadığını araştırmaktır. İkinci aşamasının amacı obeziteye yol açabilecek çevresel ipuçlarının etkisini maruz bırakma ve tepki önleme tekniğini (Jansen, 2010) kullanarak ortadan kaldırmaya yardımcı olmaktır

Öğretmenlerin ingilizce yazma dersi ile ilgili inançları ve bunların öğrenci inançları ve sınıf içi yazma dersi uygulamaları ile karşılaştırılması

KISA Öğretmenlerin İngilizce Yazma Dersi ile İlgili İnançları ve Bunların Öğrenci İnançları ve Sınıf içi Yazma Dersi Uygulamaları ile Karşılaştırılması Hem nicel hem nitel araştırma tekniklerinin kullanıldığı bu çalışma, öğretmenlerin ingilizce yazma dersi ile ilgili inançlarını ve bunların öğrenci inançları ve sınıf içi uygulamaları ile karşılaştırılmasını amaçlamıştır. Bu çalışma, öğretmenlerin yazma dersinde öğrenci ihtiyaçları, öğretim, geribildirim ve değerlendirme hususlarında bildirdiği inanç ve uygulamaları araştırmayı, öğretmenlerin bildirdiği inançların cinsiyet, yaş, öğretmenlik deneyimi, profesyonel/eğitim geçmişi, lisans eğitimi, hizmetiçi eğitim ve dil öğrenme deneyimi gibi değişkenlere göre farklılık gösterip göstermediğini, öğrencilerin yazma dersine yönelik ihtiyaçları ve motivasyonu, öğretmenleri tarafından kullanılan teknikler, hata düzeltme ve geribildirim hususlarındaki inançlarını ortaya çıkarmayı ve öğretmenlerin yazma dersi ile ilgili inançları ile öğrencilerin yazma dersi ile ilgili inançları arasında uyum olup olmadığını bulmayı amaçlamıştır. Bu çalışma ayrıca, öğretmenlerin sınıf içi uygulamalarının izlendiği yazma derslerinin genel özellikleri araştırmayı ve öğretmenlerin yazma dersine yönelik bildirdiği inançlar ile sınıf içi uygulamaları arasında nasıl bir ilişki olduğunu ortaya çıkarmayı amaçlamıştır. Son olarak, bu çalışma öğretmenlerin sınıf içi uygulamalarının dil öğrenme deneyimleri, lisans eğitimi, hizmetiçi eğitim, öğretmenlik deneyimleri ve bağlamsal faktörlerden nasıl etkilendiğini bulmayı amaçlamıştır. Bu çalışmanın katılımcıları, Marmara Üniversitesi Yabancı Diller Yüksekokulu’ndan 40 yazma öğretmeni ve 358 öğrencidir. Çalışma için gerekli olan veriler, Öğretmenler için Yazma Dersi ile ilgili İnanç Anketi (TBQ), Öğrenciler için Yazma Dersi ile ilgili İnançlar Anketi (SBQ), gözlemler ve öğretmenlerle yapılan yüz yüze görüşmelerden elde edilmiştir. Anketlerden elde edilen veriler SPSS 15 ile analiz edilirken, gözlem ve görüşmelerden elde edilen veriler için içerik analizi tekniği kullanılmıştır. Elde edilen bulgular, derste kullanılan materyal ile öğrenci ihtiyaçları arasında uyum olmadığını ve bu sebeple öğretmenlerin materyalin içeriğinde ve yapısında değişiklikler yapmak istediğini ortaya çıkarmıştır. Çalışmada yer alan öğretmenlerin, çoğu zaman yazılı, sözlü ve direk geribildirim verdiğini ve onların içerikten çok dilsel kullanıma önem verdiği bulunmuştur. Sonuçlar, deneyimsiz öğretmenler ile deneyimli öğretmenler arasında dersi planlama, dersten once hazırlık yapma, öğrencileri motive eden davranışlar sergileme ve süreç odaklı yazma teknikleri kullanma bakımından anlamlı farklılık ortaya çıkarmıştır. 0-3 yıllık deneyimsiz öğretmenler, deneyimli öğretmenlere göre daha fazla plan ve hazırlık yapmakta, daha çok öğrencileri motive eden davranışlar sergilemekte ve süreç odaklı yazma teknikleri uygulamaktadır. Diğer bir anlamlı farklılık ise lisans eğitiminde yazma dersi alanlar ile almayanlar arasında ortaya çıkmıştır. Lisans eğitiminde yazma dersi alan öğretmenlerin daha fazla plan ve hazırlık yaptığı, daha çok öğrencileri motive eden davranışlar sergilediği ve süreç odaklı yazma teknikleri kullandıkları ortaya çıkmıştır. Ayrıca, bulgular hizmet içi eğitimde yazma dersi ile ilgili eğitim almış öğretmenlerin almayan öğretmenlere göre ölçme ve değerlendirmeye daha fazla vakit ayırdığını ortaya koymuştur. Bu çalışma aynı zamanda yazma öğretimi konusunda öğretmen inançları ile öğrenci ihtiyaçları arasında uyum olduğunu ortaya koymuştur. Bunun yanı sıra, öğretmen inançları ile sınıf içi uygulamalarının çoğu zaman uyum içinde olduğu sonucuna varılmıştır. Öte yandan, öğretmenlerin müfredat ve sınavlar gibi faktörler tarafından kısıtlandığı takdirde, inançları ve sınıf içi uygulamaları arasında uyumsuzluk ortaya çıkarmıştır. Son olarak, bu çalışma dil öğrenim deneyimlerinin, lisans eğitiminin, hizmetiçi eğitimin ve öğretmenlik deneyimlerinin öğretmenlerin sınıf içi uygulamalarını etkilediğini göstermiştir. Anahtar Kelimeler: Yazma Öğretimi, Öğretmen İnançları, Sınıf Gözlemi ABSTRACT Teachers’ Beliefs about English Writing Instruction and Their Relevance to Their Learners’ Beliefs and Classroom Practices The present study, which was based on a mixed methods approach, attempted to investigate the relevance of English writing teachers’ beliefs about writing instruction to to their students’ beliefs and to their classroom practices. This study aims to explore writing teachers’ beliefs regarding writing instruction in terms of needs and planning, instructional phase, feedback and assessment in writing courses. Secondly, it aims to investigate if teachers’ self-reported beliefs about teaching writing change according to their gender, their age, years of teaching experience, professional/educational background, their background in pre-service training, in service training, and their language learning experience. Thirdly, it tries to examine students’ beliefs about writing instruction in terms of their needs and their motivation, techniques used by their teachers, error correction and feedback. Fourthly, it aims to find out the relevance of writing teachers’ beliefs to their students’ beliefs about writing instruction. Then, it aims to explore the general characteristics of writing instruction in teachers’ observed teaching practices and to discuss the relationships between teachers’ self-reported beliefs about teaching writing and their instructional practices. Finally, it aims to find out how writing teachers’ practices are affected by language learning experience, pre-service training, in-service training, teaching experience and contextual factors. The participants of the study were 40 writing teachers and 358 students at Marmara University, School of Foreign Languages. The data were collected through Writing Teachers’ Beliefs Questionnaire (TBQ), Students’ Beliefs Questionnaire (SBQ), classroom observations and interviews. The data gathered from the questionnaires were analysed through SPSS 15 using frequency distribution and t-tests. The data gathered from the observations and interviews were analysed through content analysis. The findings revealed that there was not a match between the material and students’ needs and so teachers wanted to make some changes in the content and the organization of the materials. It was found that teachers used written and verbal feedback most of the time, gave direct feedback and focused more on local issues such as grammar and mechanics. The results indicated that there was a significant difference between experienced and inexperienced teachers in terms of planning instruction, getting prepared, motivating students and using process approach techniques. Inexperienced teachers with 0-3 years experience plan instruction, make preparations, perform motivating behaviours and use process writing techniques more than the teachers with over 3 years experience. Another significant difference was found between teachers who had pre-service training and teachers who did not have pre-service training in writing. It was also found that teachers with pre-service training plan instruction, make preparations, perform motivating behaviours and use process writing techniques more than the teachers without pre-service training. Moreover, findings revealed that teachers with in-service training in writing spend more time on assessment. The study indicated that there was a match between teachers’ beliefs and students’ beliefs regarding writing instruction. Futhermore, it was concluded that teachers’ beliefs were most of the time consistent with their practices. However, some inconsistencies occurred when teachers were constrained by contextual factors such as curriculum and exams. Finally, the study revealed that prior language learning experiences, pre-service training, in-service training and teaching experiences influence teachers’ classroom practices. Key Words: Writing Instruction, Teachers’ Beliefs, Classroom Observatio

Examination of Students’ View about Usage of Comparative Advance Organizer Concerning Chemical Change Unit

An advance organizer is a teaching and learning tool that is presented prior to the subject to be learned, and that helps learners to organize and interpret new incoming information. The advance organizers are divided into two according to their purpose of preparation, comparative and expository. At the same time, they can be prepared in different forms such as verbal, pictorial and auditory. In this study, a concept map used as a comparative advance organizer concerning chemical change unit was prepared firstly. Then this advance organizer has been implemented in a 9th class. The sample of the study consisted of 26 students, 16 girls, and 10 boys, who attend school a state school in Balıkesir. After the application, the opinions of the students concerning the concept map were taken. It was concluded that the students had positive views about concept map that was used as a comparative advance organizer. At the end of the study, some recommendations for incorporating advance organizers in chemistry classes were presented

Assessments on the stability of natural slopes prone to toe erosion, and man-made historical semi-underground openings carved in soft tuffs at Zelve Open-Air Museum (Cappadocia, Turkey)

The Zelve Open-Air Museum, consisting of three valleys, is one of the oldest historical semi-underground settlements in the Cappadocia Region of Turkey which was designated as a World Heritage Site in 1985 by UNESCO. Particularly in the first valley, there are a lot of underground openings of different sizes carved in a soft tuff next to the valley cliffs used for cliff settlement in the past and several antique churches with some geo-engineering problems. In addition, steep natural slopes in this valley are prone to toe erosion resulting in stability problems. In this study, it is aimed to investigate engineering characteristics of the surrounding tuff and factors affecting them, and to assess the effect of rate of toe erosion on the stability of steep valley slopes and structural stability of some selected typical underground openings with large spans subjected to spalling. For these purposes, some observational, experimental and numerical modelling studies were conducted. Experimental results indicate that strength and deformability properties of the weak tuff surrounding the openings drastically reduce when it becomes wet or saturated. This situation suggests that possibility of occurrence of failures is expected to be higher in rainy seasons due to increase in water content of the tuff. Experimental results also suggest that spalling commonly observed in the valley is related with freezing-thawing and wetting-drying cycles in nature and that the process of freezing and thawing accelerates further the degradation of the rock. The long-term measurements at selected locations suggest that erosion in the tuff is important, which increases particularly in winter and spring seasons and results in the loss of support accelerating the occurrence of further slope failures. The 2-D numerical solutions indicate that no significant change in shear and tensile stresses in steep valley slopes prone to toe erosion would be expected after 100. years. However, the solutions obtained from the 500- and 1000-year scenarios suggest that failure zones due to the tensile stresses would develop in the form of slabs with thicknesses of 50-60. cm and 90-100. cm, respectively, which would break off from the slope and fall down. The results from 3-D numerical solutions indicate that failure (yield) zone resulting from tensile stresses around the semi-underground openings will develop parallel to the sidewalls. These results confirm the observed spalling of the tuff in the form of slabs parallel to the walls of the openings. © 2013 Elsevier B.V

Assessment of geoengineering and environmental problems for the possible use of abandoned rock hewn settlement area in Ürgüp Cappadocia Turkey

The Cappadocia Region of Central Anatolia having a very distinct culture is one of the attractive touristic sites of Turkey due to its spectacular and unique landforms and historical heritages. In this region, the structures carved into thick to massive tuffs survived and kept their original integrity for a number of centuries. Environmental and anthropological factors at the Cappadocia Region have been the main reasons for extensive subsurface and multi-purpose use in the past and present. In addition, thermal insulation properties of the tuffs make these rocks suitable for use in underground openings. The Kayakapi Neighborhood, located in the town of Urgup, is one of the famous historical sites. This site is situated within the "Goreme National Park and the Rock Sites of Cappadocia" which was inscribed on the World Heritage List in 1985. In order to develop the tourism potential of this abandoned site while preserving its cultural and natural values, a natural environmental conservation and revitalization project was initiated. As an integral part of this project, in this study, environmental and engineering geological problems, including rock fall potential and stability of about 1,200 rock-hewn structures, were investigated and an inventory was prepared for the possible re-use of the underground openings and other structures at the site, and remedial measures were recommended. The assessments based on observations and experimental studies indicated that the tuffs do not show significant changes both perpendicular and parallel to layering, and discontinuities and rock weathering seem to be more important factors controlling the stability of rock-hewn structures. The major stability problems threatening the re-use of the openings are structurally-controlled block instabilities, overbreaks, and erosion and shearing of the pillars made of tuff. On the other hand, the area at the entrance of the site requires some protection measures such as the construction of a retaining wall, systematic bolting of rock slabs and removal of some blocks having rock fall potential. The inventory for the openings suggests that there are a number of openings that can be re-used after necessary remedial measures