Exploring nanobodies interrupting the interaction between p53 and MDM4

The p53 protein is considered as the guardian of the genome thanks to its important tumor suppressor roles such as cell-cycle arrest, apoptosis and senescence. Because these roles are extremely vital, the p53 pathway is strictly regulated. During unstressed conditions, p53 protein levels are kept in control by both ubiquitination of the p53 protein and inhibition of its transcriptional activity through the MDM2 and MDM4 proteins, respectively. Although MDM2 is the main modulator of p53 activity, there is a collaboration between MDM2 and MDM4 proteins to enable the control of p53. Thus, MDM4 is as important as MDM2 in this mechanism. In most human cancers, there is either a mutation in the Tp53 gene or an overexpression of its negative regulators. Thus, targeting the p53-MDM2-MDM4 interplay is one of the main aims of cancer therapeutics. Also, in some cancers, where there is overexpression of negative regulators, the use of inhibitors for only MDM2 is not enough to activate the p53 protein. For this reason, exploring inhibitors for MDM4 are vital for therapy. In this study, we aimed to optimize the purification of in silico designed nanobodies targeting the MDM4-p53 interaction and test their affinity and effectiveness by surface plasmon resonance (SPR) and a fluorescent two-hybrid (F2H) assay

Media narratives, politics and the Cyprus problem

Media, politics and the Cyprus Problem are the main themes of the present study. Through analysis of Greek and Turkish Cypriot television news bulletins and newspaper editorials and leading articles, the study seeks to establish media approaches and positions on important issues so as to better understand their work, role and functions. The study analyses practices and positions related to the Cyprus Problem, the solution, matters of identity, the ‘others’ and the European Union, the authorities and the political forces. This attempt to ascertain the underlying values that guide news selection and content will provide a clearer picture of how the media interacts with or influences society

The effect of the smoking on the oxidative stress and serum mineral element levels

Bu çalışmada, sigara kullanımının oksidatif stres ve serum mineral madde düzeyleri üzerine etkisi incelendi. Bu amaçla hiçbir sağlık problemi olmayan, sigara dışında herhangi bir ilaç, vitamin, alkol ve benzeri madde kullanmayan, sigara kullanım süreleri 5-10 yıl arasında, günlük sigara içme adedi 15-30 adet arasında değişen, yaşları 25-45 yaş arasında 25 erkek ile çalışmanın deneme grubunu, hayatı boyunca hiç sigara ve alkol kullanmamış aynı zamanda ev ve iş ortamlarında pasif içici olmayan yaşları 25-45 yaş arasında değişen 23 erkek ise kontrol grubunu oluşturdu. Deneme ve kontrol grubunu oluşturan kişilerden tüm kan örnekleri, 12 saatlik açlığı takiben ve kan örneklerinin standardizasyonunun sağlanması amacı ile bireyler oturur pozisyondayken alındı. Kanlar 3000 rpm'de 10 dakika santrifüj edilerek serum ve plazmaları ayrıldı. Ayrılan serumlarda demir (Fe) ve magnezyum (Mg) düzeyleri aynı gün içinde bakılırken, bakır (Cu) ve çinko (Zn) analizleri için kalan serum örnekleri ependorf tüplerine aktarılarak -20oC' de analizin yapılacağı tarihe kadar saklandı. Elde edilen plazmalardan askorbik asit (Vit C) ve malondialdehit (MDA) ölçümü aynı gün içinde yapıldı. Süperoksit dismutaz (SOD) analizi için eritrosit hemolizatları hazırlanarak analiz gününe kadar -20 oC' de saklandı. Plazma MDA düzeyleri, sigara içmeyen ve sigara içen kişilerde sırasıyla 6,14 ± 0,46 µmol/L ve 11,99 ± 0,39 µmol/L olarak, plazma vitamin C düzeyleri ise sırasıyla 0,384 ± 0,062 mg/dL ve 0,217 ± 0,027 mg/dL olarak bulundu. Eritrosit hemolizatlarında SOD enzim aktiviteleri, sigara içmeyen ve sigara içen kişilerde sırasıyla 30,96 ± 2,96 U/mgHgb ve 39,19 ± 2,76 U/mgHgb olarak ölçüldü. Serum bakır seviyeleri sigara içmeyen ve sigara içen kişilerde sırasıyla 49,48 ± 2,30 µg/dL ve 86,73 ± 5,05 µg/dL olarak ölçülürken, serum çinko seviyeleri sigara içmeyen ve sigara içen kişilerde sırasıyla 27,45± 0,77 µmol/L ve 23,44 ± 0,62 µmol/L olarak saptandı. Serum magnezyum miktarları ise sigara içmeyen ve sigara içen kişilerde sırasıyla 2,12 ± 0,12 mg/dL ve 3,14 ± 0,53 mg/dL olarak tespit edildi. Elde edilen bulgular sonucunda, uzun süreli sigara içiminin antioksidan sistem ve bu sistemle ilişkili serum mineral madde düzeylerinde değişikliklere neden olduğu ve sigara içenlerin diyetlerinin askorbik asit ve aynı zamanda antioksidan enzimlerin kofaktörleri de olan eser elementler yönünden takviye edilmesinin yararlı olacağı sonucuna varıldı. In this study, it is examined that the effect of the smoking on the oxidative stress and serum mineral element levels. With this aim, between 25 and 45 years old 25 men who haven?t got any healty problem, who are not using a drug, vitamine, alcohol or same materials except cigarette, smoking years between 5 or 10 years, daily smoking members changing between 15- 30 unit are the test grup of this study. 23 men who haven?t used cigarette or alcohol, in the same time who are not passive smokers at home or at work and changing their ages between 25 and 45 years olda re the control group of this study. Blood somples from control and test groups? members are taken for the aim of providing standarization of the blood samples, these are taken after 12 hours hunger and on the sittin position. Blood samples on 3000 rpm bye making centrifuge in ten minutes, serum and plasmas are seperated. On seperated serums iron (Fe) and magnesium (Mg) levels are examined in the same day but serum samples fort he analysis of the copper (Cu) and zinc (Zn), by transferring eppendorf tubes in -20oC were hidden till the analysis day. From the plasmas that we have, ascorbic asid (Vit C) and malondialdehid ( MDA) measuring were done in the same time. For the superoxide dismutase (SOD) analysis, by preparing hemolysates of erythrocytes they were hidden till the analysis day in -20 oC degree. It is established that plasma MDA levels between non-smokers and smokers people one by one as 6,14 ± 0,46 µmol/L and 11,99 ± 0,39 µmol/L, plasma Vit C levels are also one by one as 0,384 ± 0,062 mg/dL and 0,217 ± 0,027 mg/dL. In erythrocyte hemolysates SOD enzyme activities were measured between non-smokers and smokers people one by one as 30,96 ± 2,96 U/mgHgb and 39,19 ± 2,76 U/mgHgb. Serum copper levels were measured between non-smokers and smokers people one by one as 49,48 ± 2,30 µg/dL ve 86,73 ± 5,05 µg/d Land serum zinc levels were fixed between non-smokers people one by one as 27,45± 0,77 µmol/L and 23,44 ± 0,62 µmol/L. Serum magnesium quantities were established between non-smokers and smokers people one by one as 2,12 ± 0,12 mg/dL ve 3,14 ± 0,53 mg/dL. In the result of the evaluated findings, it was come to a conclusion that long time smoking causes changes on antioxidane system and serum mineral substance level that with this system and it will be useful to reinforcement on trace elements which are the cofactors of the antioxidane enzymes in the same time and ascorbic asid of the smoker diets

Encountering the Indeterminacy of the Self

In recent decades, phenomenology and hermeneutical phenomenology have taken the lead in addressing the question of personal identity through the inquiry of “who are you?”. However, this lead has questionable aspects in capturing the relationality between self, others, and the surrounding world, characterized by its ever-changing state. To understand personal identity in its ever-changing state of becoming, the primary focus of this paper is twofold: firstly, exploring how to reconcile these complex relations into a unified conception of personal identity by following Husserl’s notion of “indeterminate determinacy” and his theory of variation, and secondly, considering the limitations of defining this unity as an “autobiography or biography" in accordance with Arendt’s notion of a "life-story". In the final analyses the notion of life-story will be revised together with Waldenfels’s analyses on “radical alien” and Sözer’s “in-between”.  This will prompt a reconsideration of personal identity as a process, leading to a genetic phenomenological perspective that recognizes the “indeterminacy of the self”

A new approach when comprehending the order of operations in mathematics instruction: Mnemoni

Araştırmanın amacı, İlköğretim 6. sınıf öğrencilerinin 'Matematik Öğretiminde İşlem Sırası' konusunda Öksüz (2009) tarafından geliştirilen bellek destekleyici ipucunun (Parayı Bulan Çabucak Tatile Çıkar) öğrencilerin başarılarına etkisi ve öğrencilerin bu kuralı gerektiren problemlerdeki çözüm stratejilerinin belirlenmesidir. Araştırmanın modeli nitel ve nicel karma araştırma modeli olarak yapılandırılmıştır. Öğrencilerin işlem sırası kuralına yönelik başarılarının yarı deneysel araştırma modeli kullanılarak araştırıldığı nicel araştırma metodu ile öğrencilerin işlem sırası kuralı gerektiren problemlerdeki çözüm stratejilerinin detaylı olarak ele alındığı klinik görüşmelerin kullanıldığı nitel araştırma metodu birlikte kullanılmıştır. Araştırmada ilköğretim 6.sınıf öğrencilerinin işlem sırası konusuna yönelik başarılarını belirleyebilmek amacıyla gerekli nicel verilerin toplanmasında veri aracı olarak araştırmacı tarafından yine bu çalışma kapsamında geliştirilmiş olan bir başarı testi kullanılmış, verilerin analizi ve yorumlanması nicel araştırma metoduna uygun olarak gerçekleştirilmiştir. Aynı amaçlı olarak nitel verilerin toplanmasında araştırmacı notları, öğrenci notları ve video kayıtları birlikte incelenmiş ve bu doğrultuda veri çeşitlemesi-triangulation yöntemi kullanılmıştır. Nitel verilerin analizi ve yorumlanması nitel araştırma metoda uygun olarak gerçekleştirilmiştir. Araştırmada ilköğretim 6.sınıf öğrencilerinin işlem sırası konusuna yönelik başarılarını belirleyebilmek amacıyla 'İşlem Sırası Başarı Testi' geliştirilmiş ve başarı testinin madde analizleri, geçerlilik ve güvenirlik analizleri yapılmıştır. Geliştirilen başarı testinin Cronabach Alfa güvenirlik katsayısı .82 olarak hesaplanmıştır. Yapılan madde analizleri, geçerlik- güvenirlik analizleri sonucunda 25 maddeden ve altı soru türünden (sembolik ifadeler, doğrulayıcı ifadeler, doğru-yanlış soruları, açık uçlu sorular, sembolik ifadeyi sözel ifadeye çevirme, sözel ifadeler) oluşan 'İşlem Sırası Başarı Testi'ne son hali verilmiştir. Araştırmanın nicel boyutu kapsamında 'İşlem Sırası Başarı Testi' 2009-2010 öğretim yılında Aydın ili merkez ilçede öğrenim görmekte olan 156 öğrenciye uygulanmıştır. Araştırmanın evrenini Aydın ili merkez ilçede yer alan ilköğretim 6.sınıf öğrencileri oluşturmakta, örneklemi ise; seçkisiz örnekleme yöntemi ile belirlenmiş üç okulun 6.sınıflarında okuyan 156 öğrenci oluşturmaktadır. Her üç okulda başarı düzeyleri birbirine yakın deney (n= 78) ve (ve kontrol (n= 78) grupları belirlenmiştir. Araştırmanın nicel boyutunda geliştirilen 'İşlem Sırası Başarı Testi' uygulama sonrası sontest ve uygulamadan 8 hafta sonra kalıcılık testi olarak öğrencilere uygulanmıştır. Elde edilen nicel verilerin analizi SPSS 11.5 programında deney ve kontrol grupların karşılaştırılmasında bağımsız gruplar ve deney ve kontrol gruplarının kendi içerisindeki karşılaştırılmasında bağımlı gruplar t-testi teknikleri kullanılarak analiz edilmiştir. Araştırmanın nitel boyutunda, deney (n=3) ve kontrol (n= 3) gruplarından belirlenen toplam 6 öğrenci ile öğretim süreci öncesinde ön klinik ve uygulama sonrasında son klinik görüşmeler yapılmıştır. Öğrencilere klinik görüşmelerde 'İşlem Sırası Başarı Testi' uygulanmıştır. Uygulamada bu test geliştirilirken göz önünde bulundurulan esaslar doğrultusunda işlemlerin önceliğinin etkili olduğu problem durumları oluşturulmuş ve çocuklara bu problem durumları ile nasıl baş ettikleri gözlemlenmiştir. Çocukların işlem sırası kuralı gerektiren problem durumları ile karşılaştıklarında verdikleri tepkiler, probleme yönelik geliştirdikleri çözüm stratejileri tamamıyla video kayıt altına alınmıştır. Araştırmanın sonucunda; başarı testi göz önüne alındığında; matematik öğretiminde aritmetik işlemlerde işlem sırası konusunda bellek destekleyici ipucunun kullanıldığı bir ortamın, ipucunun kullanılmadığı bir öğrenme ortamına göre başarıyı önemli ölçüde yükselttiği tespit edilmiştir. Ayrıca konunun hatırda kalma ve kalıcılık düzeyi, bellek destekleyici ipucunun kullanıldığı öğrencilerde anlamlı bir seviyede farklılık göstermiştir. Araştırmanın nitel sonuçları göz önüne alındığında; öğrencilerin işlem sırası gerektiren problemlerdeki çözüm stratejilerin uygulama sonrasında farklılık gösterdiği görülmüştür. Bellek destekleyici ipucunun kullanıldığı deney grubunda yer alan öğrencilerin işlem sırası gerektiren problemlerdeki çözüm stratejilerinde bellek destekleyici ipucundan yararlandıkları, bunun yanı sıra kontrol grubunda ise sadece işlem sırası kuralından yararlandıkları belirlenmiştir. Araştırmanın nicel ve nitel verileri ile karşılaştırmalı bir analiz yapılmıştır. Yapılan analiz sonuçları değerlendirildiğinde, araştırmanın nicel boyutundan elde edilen bulgular ile nitel verilerden elde edilen bulguların birbirini destekler doğrultuda olduğu belirlenmiştir.The aim of this research is to investigate the effect of the mnemonic device (When You Get Money You Can Quickly Go On a Vacation), which was developed by Oksuz (2009) over students' success and to find out students' solution strategies when solving problems requiring the use of order of operations rule. This research has been structured as a mixed research model including both qualitative and quantitative research methods. This model mixes the results from both quantitative study, which was modeled as a quasi-experimental pretest-posttest design with a control group and qualitative study, which was carried out through using clinical interviews to find out students` solution strategies when solving problems requiring the use of order of operation rules. To find out students` success on problems consisting of order of operationions, a success test was used as data collection instrument, which was developed by the author of this research, and data collection and data analysing procedures have been done congruent to the quantitative model. For the same purpose, while collecting qualitative data, researcher`s notes, students` notes and video recording transcripts have been examined thoroughly and triangulation method has been utilized in this way. The analysis and interpretation of qualitative data have been done following qualitative research analysis method. To figure out 6th grade students` success on the order of operations topic 'Success test for the order of operations' was developed and item analysis was used to build validity and reliability of the test. Cronbach alpha values of the success test was found as .82. After completing item, validity and reliability analyses, a 25 item test, which was categorized under 6 problem types (Symbolic expressions, confirmatory expressions, true-false questions, open-ended questions, symbolic to verbal translational questions, and verbal expressions) was finalized. For the quantitative dimension of this research, data was collected with156 sixth grade students in the downtown area of the city of Aydin during 2009-2010 academic year. Three schools were randomly chosen to conduct this study. Two groups were randomly assigned to an experimental and control group among these 3 schools. Thus 3 experşmental and 3 control groups were formed. Both groups were identified as equivalent in respect to pretest results about their success on the order of operations. While in the experimental group, mnemonic device assissted instruction was utilized through using 'Parayı Bulan Çabucak Tatile Çıkar' expression, in the control group lesson plans that were designed by the teacher based on 6th grade teacher book have been utilized during the 3 hours of the study. While teaching activity in the experimental groups were carried out by researcher, classrooms` own teachers were in charge in the control group. Experimental and control groups were subjected to; pretest simultaneously a week before the study begins, posttest right after the study completes and a retention test 8 weeks after the study completes regarding the students` success. Quantative analysis of this research was obtained from calculating independent t-test and paired T-test using SPSS 11.5 statistics program. For the qualitative dimension of this research 3 students were assigned to experimental and 3 students were assigned to control group. Clinical interviews were conducted with these students before and after the experiment to gather their problem solving strategies on the order of operations. While conducting clinical interviews 'Success Test for Order of Operations' was utilized. In these interviews, students were faced with some question types regarding with the order of operations and observed how did they deal with these problems when solving them. Their reactions to the problems and their solution strategies were fully videorecorded. Results from the quantitative dimension of this study illustrated that using Mnemonic Device in instruction is more effective on students' success on the order of operations subject comparing to the regular classrooom activities in which Mnemonic Device use is not present. Moreover the level of retention is found more significant when using the Mnemonic Device in instruction. Examining the qualitative results of this study, students` solution strategies on the order of operation problems were found different and varied at the end of the study. While experimental group mostly used Mnemonic Device when solving order of operation problems, control group mostly used order of operation rules. Moreover, their success on their solutions were found in favor of the experimental group. Comprehensive analysis was carried out by comparing qualitative and quantitative results. At the end of the analysis, it was found that both dimension of the study support each other

Structure, Reactivity and Solution Dynamics of the Sn94- Ion

In this thesis, the nature of the Sn94- in solution and its reactivity with transition metal atoms and electrophiles have been studied. The Sn94- ion is a very strong Brønsted base that deprotonates en to form the Sn9H3- ion and is a potent ion sequestering agent that competes with 2,2,2-crypt for binding K+. The Sn9H3- ion has a pKa in a range of 32.2– 44 in dmso and can be reversibly interconverted to K3Sn9- through addition of K+ and base. Addition of K+ to Sn9H3- in the absence of base gives the proposed coupled Sn9–Sn96- dimer. The diamagnetic Sn9H3- ion was mischaracterized as the Sn93- paramagnetic radical in numerous publications since 1983. The Sn9H3- ion reacts with Ni(cod)2 and Pd(PPh3)4 complexes and give the M@Sn9H3- clusters (M= Ni, Pd). The Ni@Sn9H3- ion reacts with (arene)M(CO)3 complexes to form is the Ni@Sn9M(CO)34- ion. Endohedral d–10 atoms do not affect the pKa's of the hydrido clusters, whereas coordination of M(CO)3 group (M= Cr, Mo) significantly increases the acidity. The M@Sn9SnCy33- ions, where M= Ni and Pd, have been prepared with two different synthetic routes from Ni@Sn9H3- and Sn9SnCy33- ions, respectively. The Ni@Sn9H3- ion reacts with Cy3SnCl and gives the Ni@Sn9SnCy33- ion. The Sn9SnCy33- ion reacts with Pd(PPh3)4 and gives the Pd@Sn9SnCy33- cluster. The Pd@Sn9PdSnCy33- ion has been prepared from a new type of reaction, where the Pd metal is oxidatively inserted into the exo-bond of Pd@Sn9—SnCy33-. Two new fused deltahedral clusters have been prepared from Sn94-, Ge94-, Pd(PPh3)4, and Ni(cod)2 precursors to give the Pd2@Sn184-, the largest-known deltahedral cluster to-date, and Ni@Sn8(μ–Ge)Ni@Sn84-, the first example of an endohedral heteroatom cluster. 119Sn, 1H, 13C NMR studies show these clusters to be highly dynamic. The Sn9SnR33- ions (R= Cy and nBu) and M@Sn9R3- ions (M= Ni, Pd and R= H, SnCy3) exhibit fast intramolecular exchange of the all 9-Sn atoms, while the exo-substituent groups scramble around the clusters. The Sn9–iPr3- ion has non-mobile alkyl substituent, which removes the exo-bonded Sn atom from exchanging with the remaining 8-Sn atoms of the cluster

THE RELATIONSHIP BETWEEN THE STAR SYSTEM AND THE POPULAR CULTURE

This study includes an examination of the relationship between the popular culture and the star system. The main purpose of the study is to examine the interconnected relationship between popular culture and stars, in other words to examine and clarify the relation of the star system to the economic and cultural field. The star phenomenon has emerged in America at the end of the eighteenth century, when the middle class, who chose the theatre, ended up thinking of filming. The producers tried to make attractive theatrical actors play in movies and to make the audience close to the cinemas. The star system’s foundation has been laid, given the role of a goddess of love or idol to the actors or actresses (Yüksel, 2001, p.23-24). Popular culture is a usage and consumption culture. Other popular are used to create popular such as popular sports, athletes, artists, popular ideas and ideologies, behaviours, magazine heroes. Popular is packaged, and consumers take part in the popular popularization process by applying them to their lives (Erdoğan, 1999, p.3). A material or materialism is sold directly. It is indirect marketing through the media. Non-materials (ideologies) are also sold. Sales are legitimized by production relations. The star, a product of the consumer society, catches basic expectations. This is the inevitable meeting of commerce, art, goddess and merchandise. The star is convincing, makes people buy, and challenges time. It has an important feature of communication which is the "attraction". What is applicable to brands, also applies to stars (Seguêla, 1991, p. 55-58).  Stars can be regarded as a popular product because they offer a combination of continuity, permanence and change. The stars can be related to the popular culture industry, with their own styles and the looks they follow, with the changes they make. This research is in the screening model. "The screening model is an approach aimed at describing the situation existed before or still existing as the way it is" (Karasar, 1995, p.77). This research aims to reveal the relationship between the concepts of star and popular culture. The information that will emerge as a result of this research can be enlightening for the studies in this area, as the concepts of "popular culture" and "star" can be important clues in the search for cultural, economic and social characteristics of societies

Significance of early diagnosis and early intervention in early childhood hearing loss

Hearing loss is an important problem interfering with the propagation of acoustic signal starting from the external ear to the primary auditory center of the brain. The congenital hearing loss is an important and common disorder that can lead to many consecutive negative conditions when it is not diagnosed and treated within the first few months of life. Early Hearing Diagnosis and Intervention programs becoming more increasingly popular in recent years aim to avoid the negative effects of hearing loss. The main goal of these programs is to maximize the linguistic proficiency and literacy development of children with hearing loss. Children who are not given the appropriate opportunities for learning language fall behind their peers with normal hearing in communication, reading, cognitive and socio-emotional development. Delays occurring in these fields manifest as a lower educational status and vocational employment problem in adulthood. Therefore, diagnosing and treating hearing loss as early as possible is extremely important