Regulation of protein kinase B (PKB/Akt) by DNA-dependent protein kinase (DNA-PK) under physiological conditions

The serine/threonine protein kinase B (PKB/Akt) is a downstream effector of phosphatidylinositol 3-kinase (PI3K) and a major regulator of a variety of cellular processes, including metabolism, transcription, survival, proliferation, and growth. PKB is activated by several stimuli, including hormones, growth factors, cytokines and, as recently reported, also by DNA damage. Activation of PKB requires phosphorylation at two key regulatory sites: Thr308 and Ser473 (of PKBa). Phosphorylation by 3-phosphoinositide-dependent kinase-1 (PDK1) occurs on Thr308 in the activation loop of PKB. The phosphorylation on Ser473 within a C-terminal hydrophobic motif leads to full activation of PKB and mediated by two members of the PI3K-related kinase (PIKK) family, mTOR/rictor complex (mTORC2) or DNA-dependent protein kinase (DNA-PK) in a stimulus specific manner. Insulin or growth factor induced PKB Ser473 phosphorylation is regulated by mTORC2. In contrast, DNA damage-induced phosphorylation of PKB Ser473 is mediated by DNA-PK. The present study made use of genetically modified mouse models to investigate PKB regulation by DNA-PK, as phosphorylation of Ser473 may be stimulus-, signalling pathway- and/or cell type-specific. In this study, we investigated the role of DNA-PK in basal, insulin-induced, and DNA damage-induced phosphorylation of PKB Ser473 under physiological conditions. We report that DNA-PK phosphorylated PKB on Ser473 upon DNA damage induced by γ-irradiation in vivo. In contrast, DNA-PK was dispensable for insulin and growth factor-induced PKB activation. Interestingly, analysis of basal PKB Ser473 phosphorylation in DNA-PKcs−/− mice showed tissue-specific deregulation of the PKB/FoxO pathway. In particular, we provide evidence that persistent PKB hyperactivity in the thymus apparently contributes to spontaneous tumourigenesis in DNA-PKcs−/− mice. Lymphomagenesis could be prevented by the deletion of PKBa and implies deregulation of PKB in DNA-PKcs−/− thymi. Deregulation of PKB is implicated in various types of cancer and PI3K/PKB pathway is one of the most deregulated pathways in human malignancies. Therefore PI3K/PKB pathway is a major focus of current efforts for the treatment of cancer. In the second part of the study we made use of differential activation of PKB by upstream kinases in response to specific stimuli as a tool to dissect the mode of action of a small molecule inhibitor BBD130

The investigation of electronic, anisotropic elastic and lattice dynamical properties of MAB phase nanolaminated ternary borides: M2AlB2 (M ¼ Mn, Fe and Co) under spin effects

In the present study, the structural, electronic, magnetic, anisotropic elastic and lattice dynamic properties of the ternary metal borides M2AlB2 (M=Mn, Fe and Co) known as MAB phases have been investigated by density functional theory. The obtained results from the structural optimizations show that all these compounds have negative formation enthalpy implying the thermodynamic stability and synthesizability. The spin effects on the M2AlB2 phases have been studied with the plotted energy-volume curves for different magnetic phases (antiferromagnetic (AFM), ferromagnetic (FM), and paramagnetic (PM)) of these compounds. The stable magnetic phase for the Mn2AlB2 compound is found to be AFM while the magnetic nature of Fe2AlB2 and Co2AlB2 compounds are FM. The calculated electronic band structures with the total and orbital projected partial density of electronic states imply that these ternary metal borides have metallic behavior. Also, the mentioned compounds have mechanical and dynamic stability due to the calculated elastic constants and the observed phonon dispersion curves. Some thermodynamic properties have been investigated by means of phonon dispersion curves. Furthermore, the anisotropic elastic properties have been visualized in three dimensions (3D) for Young's modulus, linear compressibility, shear modulus, Poisson's ratio, and sound wave velocities. © 2020 Elsevier B.V

The impact of time limitation: insights from a queueing experiment

We experimentally explore the effects of time limitation on decision making. Under different time allowance conditions, subjects are presented with a queueing situation and asked to join one of the two given queues. The results can be grouped under two main categories. The first one concerns the factors driving decisions in a queueing system. Only some subjects behave consistently with rationality principles and use the relevant information efficiently. The rest of the subjects seem to adopt a simpler strategy that does not incorporate some information into their decision. The second category is related to the effects of time limitation on decision performance. A substantial proportion of the population is not affected by time limitations and shows consistent behavior throughout the treatments. On the other hand, some subjects’ performance is impaired by time limitations. More importantly, this impairment is not due to the stringency of the limitation but rather to being exposed to a time constraint

A study on destination image perceptions of domestic tourists

The concept of destination image has turned into a widely researched concept to revitalize local regions. As various regions develop in tourism, they give tourists or potential tourists more choice rights, and individuals' decision process is affected via different destination options. The destination image reflects the satisfaction levels, perceptions, and experiences of tourists cognitively and emotionally. Within the scope of the research, a face-to-face survey was conducted by applying the convenience sampling method to collect the data of 497 local tourists who visited Bartın Amasra, an urban tourism destination in Turkey founded in the 3000s BC and with a unique history of 5000 years. The “Destination Image Scale” was benefited through the quantitative research technique in the study. Besides, open-ended questions were asked to determine the travel behavior of tourists. Based on the findings, it is evident that domestic tourists who come to Amasra primarily attach importance to “the sea, nature, and cultural structure”. It was also found that tourists act according to their family and friends' advice the most as a source of information in their preference for Amasra. Also, the emotional states tourists feel throughout their destination visits have come to the forefront as “Peaceful, Happy, Good and Comfortable”. While there is a significant difference in the level of participation of tourists in the dimension of the affective image in favor of women at the gender level, there is a significant difference in the dimension of the cognitive image in favor of those with higher education levels. Within the scope of the study, the elements that may come to the forefront in promoting the relevant region as a desirable travel destination have been disclosed. As a result, it is clear that the perceptions of domestic tourists visiting Amasra regarding the image of the destination are high

The Influence of Transformational Leadership on Employees\u27 Innovative Behaviour in the Hospitality Industry: The Mediating Role of Leader Member Exchange

The purpose of this research is to contribute to improving the quality of service in the hospitality industry by helping to understand profoundly the premises of innovative behaviour. For this purpose, a conceptual model including transformational leadership, leader member exchange and innovative behaviour is proposed. To test the research model, data were obtained from the employees of 5-star hotels in Muğla, Turkey (n = 281). The data were analysed with the IBM SPSS 23 program. As a result of the Process Macro analysis, it was discovered that the transformational leader positively influenced innovative behaviour and leader member exchange had a mediating role in this relationship. Our research helps us to understand profoundly the pioneers of innovative behaviour, and will increase managers\u27 awareness by making managerial suggestions to improve service quality in hotels

An ab initio Study of Cr and Mn Doped MAX Phase TiMSiB

MAX phases, which are widely studied experimentally and theoretically, have general formula of M(n1)AXn, where M is transition metals, A is A group element and X is C and N. In this study, the structural, mechanical and electronic properties have been researched for hypothetical MAX phase TiMSiB, where M is Cr and Mn by applying ab initio calculations. Initially, structural optimizations have been completed and the outcomes crosschecked with the studies of Ti2SiB in literatures [1]. After optimization process have been achieved, the mechanical stability has been proved. Moreover, Young, Bulk, Shear modules and Poisson ratio for the compounds have been estimated by using elastic constants. Also, to understand the anisotropic behavior of the materials, directional dependent two and three-dimensional mechanical properties have been plotted. Finally, electronic band structures and corresponding density of state (DOS) have been plotted. © 2019 IEEE

Okul-Çevre ilişkilerinin okul yönetimine etkileri

Yüksek Lisans TeziBu çalışmanın amacı, ilköğretim ve ortaöğretim okullarında okul-çevre ilişkilerinin okul yönetimine etkilerini, teorik ve uygulamalı olarak geniş bir çerçevede incelemek ve bu kapsamda yapılması gerekenler konusunda öneriler geliştirmektir. Araştırma olgubilim modelindedir. Veri toplama aracı olarak, araştırmacı tarafından geliştirilen “Okul-Çevre İlişkilerinin Okul Yönetimine Etkileri” görüşme formları kullanılmıştır. Araştırma verileri 2010-2011 eğitim-öğretim yılında Kırklareli ili Lüleburgaz ilçesi ilköğretim ve ortaöğretim okullarında görev yapan yöneticilerden 62 kişiyle görüşülerek elde edilmiştir. Verilerin yüzde ve frekans dağılım tabloları hazırlanmıştır. Araştırmanın sonucunda aşağıda yazılı olan bulgular saptanmıştır: Bulgulardan ilki, yöneticilerin çoğunun veliler tarafından etki altına alındığı ve okul aile birliği temsilcisinin yöneticilerin yarısının alacakları kararları etkilediğidir. Diğer taraftan, velilerin büyük çoğunluğunun kısmen de olsa okula karşı duyarlı davrandığı ve ilköğretim okullarında ticari kuruluşların ağırlıklı olarak sınıfların tadilatını üstlendiği görülmüştür. Ortaöğretim okullarında ise ticari kuruluşların okula olan katkıları çeşitlilik göstermektedir. İl ve ilçe parti başkanlarının öğrencileri okutacak öğretmenlerin seçimi konusunda yöneticilere müdahale etmedikleri ve bürokratik yazışmaların yöneticilerin çok az bir kısmının iş verimini etkilemediği görülmüştür. Son olarak, yöneticilerin yarısının müdür ve müdür yardımcılarını kendilerinin seçmek istediği saptanmıştır.AbstractThe purpose of this study is to analyse theoretically and practically with a large frame that the effects of school-enviroment relations to school management at elemantary and high schools and in this context to develop suggestions about dues. Research is in fact science form. Data collection tool is developed by researcher as "The Effects of School-Enviroment Relations to School Management" interview forms are used. Datas of inquiry were carried by interviewing with 62 managers who are work in 2010-2011 training-education year at Kırklareli Lüleburgaz elemantary and high schools. Percentage and frequency distribution tables of datas were prepared. By reason of this research the inventions as below were determined: Firstly, most of managers are taken under influnce by guardians and the delegate of parent-teacher association is effected half of managers’ decisions. On the other hand, most of guardians are partially acting sensitive for school and as it seen that in elemantary schools commercial enterprises are predominantly undertake the modification of classrooms. At high school however, the contributions to school by commercial enterprises are in diversity. The chiefs of province and borough political parties don’t intermeddle the school managers about choosing teachers who are teaching the students and bureaucratic correspondences aren’t effected the job effiencies of exiguous managers. Finally as determined that half of managers want to choose director and deputy manager by themselves

Identification of genes involved in hepatocellular carcinoma : evaluation of hCdc4 and B-Raf genes

Cataloged from PDF version of article.Hepatocellular carcinoma (HCC), the major type of primary liver cancer, is one of the most common cancers worldwide. Development and progression of HCC occur as a multistep process, requiring the activation of oncogenes and the inactivation of several tumor suppressor genes. Although, inactivation of tumor suppressor genes, including p53, Axin and activation of oncogene β-catenin, have been shown to be involved in HCC development, the molecular mechanism of hepatocarcinogenesis is still unclear. The identification of additional genes that are involved in hepatocarcinogenesis is, not only, an important task to understand this process, but also for development of novel strategies for prevention or therapy. The aim of this study was to elucidate a possible function of hCdc4 and B-Raf genes in HCCs. A gene or genes on chromosome 4q have been implicated in hepatocarcinogenesis by the observation of frequent deletions of this region in HCCs. More recently, hCdc4, a gene in this region has been proposed as a candidate tumor suppressor gene. hCdc4 is an F-box protein which is shown to be involved in ubiquitination of cyclin E, thus targeting it for destruction. Cyclin E overexpression, is reported to be a frequent event in different cancers including HCC suggesting a problem in its destruction. 15 HCC cell lines were analysed for expression and mutation of hCdc4 gene by RT-PCR and direct sequencing of PCR products. No abnormal transcript and mutation observed in HCC cell lines tested. Our findings suggest that alteration of this gene is not a frequent event in hepatocarcinogenesis. iv B-Raf, which is one of the human isoforms of RAF, is activated by oncogenic Ras (leading to cooperative effects in cells responding to growth factor signals). B-Raf mutations are found in a wide range of cancers. Eventhough, mutational activation of Ras is not a frequent event in human hepatocarcinogenesis, few Ras mutations were reported in HCC cases. Thus activation of oncogenic MAP kinase pathway by another component of this pathway such as BRAF is worth to analyze. HCC cell lines and tumours were searched for B-Raf mutations. Activating BRAF missense mutations were identified in 2/72 HCCs (3%). Our results suggest that B-Raf may be occasionally involved in hepatocarcinogenesis. Thus MAP kinase pathway might be involved in hepatocarcinogenesis but neither B-Raf nor Ras are the major players of this pathway in this event. For this reason, other members of this pathway should be evaluated for mutations in HCC.Sürücü, BanuM.S

The effect of trust and personalization in programmatic advertising on consumers’ purchase intention

Akıllı telefon ve bilgisayar kullanımının artması sonucu tüketiciler / kullanıcılar internette aşırı miktarda veri oluşturmaktadırlar. Kişisel ve davranışsal veriler dijital ortamda kolaylıkla toplanabilmektedir. Yapay zeka uygulamalarından biri olan programatik reklamlar da bu verileri pazarlama açısından faydalı şekilde kullanmaya çalışmaktadır. Yapay zeka teknolojileri, sağlanan genel hizmeti geliştirmek için programatik reklam uygulamalarına uyarlanmaktadır. Programatik reklam uygulamaları sayesinde tüketicilere kişiselleştirilmiş mesajlar gösterilmektedir. Programatik reklamcılık,akademik literatürde yakın zamanda önemli bir konu haline gelmesine rağmen tüketici davranışına etkisi bakımından yavaş ilerleyen bir araştırma alanıdır. Bu çalışmada, programatik reklamcılığın tüketicilerin satın alma niyetine etkileri incelenirken aynı zamanda programatik reklamcılıktaki iki faktörün –güven ve kişiselleştirme-satın alma niyetine etkisi de incelenmiştir. Ayrıca, demografik verilere ve diğer değişkenlere göre satın alma niyetlerinde farklılaşma olup olmadığı da incelenmiştir. Veriler 388 katılımcıdan online anket yöntemi kullanılarak elde edilmiştir ve toplanan verilerin analizinde SPSS ve AMOS programları kullanılmıştır. Yapılan analizler sonucunda, programatik reklamcılıkta güven faktörünün satın alma niyeti üzerinde anlamlı etkisi olduğu bulunmuştur. Öte yandan, programatik reklamcılıkta kişiselleştirme faktörünün satın alma niyeti üzerinde anlamlı bir etkisi olmadığı tespit edilmiştir. İlave analizler, demografik değişkenler ve programatik reklamcılığa dair algıların satın alma niyetinde ne tür farklılıklara sebep olduğunu ortaya koymuştur. Elde edilen bulguların hem teorik literatüre katkı sağlayacağı hem de programatik reklamcılık uygulamalarını pazarlamada kullanan işletmelere öngörü kazandıracağına inanılmaktadır.As a result of increased use of smartphones and computers, consumers / users create an excessive amount of data on the internet. Personal and behavioral data can be easily collected in the digital environment. Programmatic advertising, one of the artificial intelligence applications, also try to use this data in a useful way for marketing. Artificial intelligence technologies are adapted to programmatic advertising applications to improve the overall service provided. Thanks to programmatic advertising applications, personalized messages are shown to consumers. Although programmatic advertising has become an important subject in academic literature recently, it is a slowly progressing research area in terms of its effects on consumer behavior. In this study, the effects of programmatic advertising on consumers’ purchase intention is examined as well as the effects of two factors in programmatic advertising –trust and personalization– on purchase intention. Furthermore, the differences in purchase intentions according to the demographic variables and other variables are also investigated. The data is obtained from 388 participants using an online questionnaire and SPSS and AMOS programs are used in the analysis of the collected data. As a result of the analyses, it is found that trust in programmatic advertising has a significant effect on purchase intention. On the other hand, it is determined that personalization in programmatic advertising does not have a significant effect on purchase intention. Additional analyses revealed different effects of demographic variables and perceptions of programmatic advertising practices on purchase intention. It is believed that the findings will both contribute to theoretical literature and provide insight to businesses that use programmatic advertising applications in marketing

The Mediating Role of Organizational Commitment in the Effect of Authentic Leadership on Employee Performance

In today's competitive environment, employees' individual performances are considered to be an important determining factor in achieving sustainable competitive advantage of organizations. Therefore, managers are in the interest of increasing the performance of their employees. Many studies have been conducted by researchers to identify the antecedents of employee performance. In the researches, leadership is the most remarkable research topic. The literature supports the view that the leader positively affects employee performance. Although it has been documented in the literature that different leadership styles are effective on employee performance, research on authentic leadership is limited. For this reason, studies are needed in the literature to determine the effect of the authentic leader on employee performance. An authentic leader is a leadership approach that motivates employees to perform beyond expectations by identifying them with organizational goals and interests. Also, the authentic leader plays an important role in the formation of organizational commitment in employees as well as affecting employee performance. Based on this reasoning in the research; A conceptual model including the authentic leader, employee performance, and organizational commitment is proposed. To test the proposed model, 317 survey data were obtained from the garment manufacturing employees in Istanbul. The survey data were analyzed with the help of SSPS-24 and AMOS-18 software. The results of the analysis showed that the authentic leadership positively affected employee performance and organizational commitment. In addition to these findings, it was determined that organizational commitment has a mediating role in the effect of the authentic leader on employee performance. In addition to contributing to the literature, the research findings have results that will attract the attention of researchers and practitioners