Search results for: Serap Doğan
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 72

Search results for: Serap Doğan

12 2D Numerical Analysis for Determination of the Effect of Bored Piles Constructed against the Landslide near Karabuk University Stadium

Authors: Dogan Cetin, Burak Turk, Mahmut Candan

Abstract:

Landslides cause remarkable damage and loss of human life every year around the world. They may be made more likely by factors such as earthquakes, heavy precipitation, and incorrect construction activities near or on slopes. The stadium of Karabük University is located at the bottom of a very high slope. After construction of the stadium, severe deformations were observed on the social activity area surrounding the stadium. Some inclinometers were placed behind the stadium to detect the possible landslide activity. According to measurements of the inclinometers, irregular soil movements were detected at depths between 20 m and 45 m. Also, significant heaves and settlements were observed behind the stadium walls located at the toe of the slope. The heaves indicate that the stadium walls were under threat of a significant landslide. After inclinometer readings and field observations, the potential failure geometry was estimated. The protection system was designed based on numerous numerical analysis performed by 2-D Plaxis software. After the design was completed, protective geotechnical work was started. Before the geotechnical work began, new inclinometers were installed to monitor earth movement during the work and afterward. The total horizontal length of the possible failure surface is 220 m. Geotechnical work included two-row-pile construction and three-row-pile construction on the slope. The bored piles were 120 cm in diameter for two-row-pile construction, and 150 cm in diameter for three-row-pile construction. Pile length is 31.30 m for two-row-pile construction and 31.40 m for three-row-pile construction. The distance between two-row-pile and three-row-pile construction is 60 m. With these bored piles, the landslide was divided into three parts. In this way, the earth's pressure was reduced. After a number of inclinometer readings, it was seen that deformation continued during the work, but after the work was done, the movement reversed, and total deformation stayed in mm dimension. It can be said that the protection work eliminated the possible landslide.

Keywords: landslide, landslide protection, inclinometer measurement, bored piles

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11 The Effect of Organizational Justice on Management by Values Perception and Intention to Leave: A Study among Nurses

Authors: Arzu K. Harmanci Seren, Burcu Alacam, Serap Altuntas, Ulku Baykal

Abstract:

Organizational justice has been evaluated as a concept related to rules developed with regards to distributing gains and making decisions of distribution such as duty, goods, service, reward, punishment, fee, organizational position, opportunity or role among those working in that organization, and to social norms on which these rules are based. Studies of organizational justice are crucial for analyzing the organizational life. It is considered that organization justice will be positively influential upon organizational behaviours such as employees’ level of work satisfaction, their performance, and behaviours of organization citizenship, management by values perception, tendency towards cooperation, and towards quitting their jobs. However, when the literature related to health and nurse management is examined, authors could not reach enough findings related to the influence of nurses’ perception of organizational justice upon the perception of management and the intention of quitting in accordance with the values. For that reason, this study has been carried out with the purpose of determining the influence of nurses’ perception of organizational justice upon the perception of management and the intention of quitting in accordance with the values. The study has been carried out with 176 nurses working in a university hospital in Istanbul and a private hospital who accepted to take part in the study, and it is definitive and relation-seeking. Before the data has been collected, ethics committee approval and institutional permissions have been taken, Organizational Justice Scale, Management by Values, Intention to Leave Scale with a questionnaire including 8 questions that aims at defining the personal and professional characteristics of the nurses have been used as a means of data collection. The data collected between 1 May and 20 June 2016 have been evaluated by the researchers in a computer via definitive, relation-seeking and psychometric statistic. As a result of the study, it has been determined that most of the nurses are working in a university hospital (70.5%), that they are 30 and over (49.4%), women (91.5%), single (52.8%) and have a Bachelor’s Degree (48.3%), working in a surgery unit (17.6), have 5 year or less institutional experience (44.9%), 11 year or more professional experience. Cronbach alpha values of the scales used in this study are .94, .95 and .56. Nurses’ average scores of Organizational Justice Scale is M= 3.35±.96, Management by Values Scale is M=3.30±.74, Intention to Leave Scale is M=8.36±3.14. As a result of the analysis carried out in order to determine the influence of nurses’ perception of organizational justice upon the perception of management and the intention of quitting in accordance with the values, it has been pointed out that the Perception of Organizational Justice influenced the perception of Management by Values positively, Intention to Leave negatively.

Keywords: intention to leave, management by values, nursing, organizational justice

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10 Expression of Micro RNAs in the Liver Tissue of Mice Generated through in vitro Embryo Culture and Embryo Transfer

Authors: Göksel Doğan, Murat Öztürk, Didar Tuğçe Karakulak, Mehmet Nurullah Orman, Nicolas Sylvius, Matthew Blades, Mustafa Sandıkçı, Cengiz Ünsal, Mehtap Kılıç Eren, Funda Kıral, Levent Karagenç

Abstract:

Assisted reproduction is associated with impaired glucose metabolism in adulthood. miRNAs are key regulators of glucose metabolism. Whether embryo culture and/or transfer alters the expression of miRNAs and to what extent this process affects glucose metabolism remain largely unknown. The purpose of the present study was to examine the expression of miRNAs in the liver in mice obtained by the transfer of blastocysts. The study was comprised of an experimental (EG) and a control group (CG). EG was generated by embryo transfer to pseudo-pregnant females. Mice born from naturally ovulating females were used as the CG. Differential expression of miRNAs, blood glucose, plasma insulin, liver glycogen, and activities of some of the rate-limiting enzymes involved in glucose metabolism were determined at ten weeks of age. Blood glucose, plasma insulin, and glycogen concentrations were similar between the groups in both sexes. Activities of enzymes were similar among females. EG males had significantly less glucokinase and phosphofructokinase activity compared to CG males. None of the miRNAs were differentially expressed in males. On the other hand, miR-143-3p expression was upregulated in EG females. Expression of none of the genes targeted by miR143-3p differed between the groups. These results demonstrate that miR143-3p, a novel regulator of type 2 diabetes, is upregulated in mice generated by assisted reproduction in a sexually-dimorphic manner with no apparent effect on glucose and insulin levels at ten weeks of age. It remains to be determined if this process is associated with impaired glucose homeostasis in the long term.

Keywords: assisted reproduction, blastocyst, embryo culture, glucose metabolism, miR143-3p, oxygen

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9 From Makers to Maker Communities: A Survey on Turkish Makerspaces

Authors: Dogan Can Hatunoglu, Cengiz Hakan Gurkanlı, Hatice Merve Demirci

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Today, the maker movement is regarded as a socio-cultural movement that represents designing and building objects for innovations. In these creativity-based activities of the movement, individuals from different backgrounds such as; inventors, programmers, craftspeople, DIY’ers, tinkerers, engineers, designers, and hackers, form a community and work collaboratively for mutual, open-source innovations. Today, with the accessibility of recently emerged technologies and digital fabrication tools, the Maker Movement is continuously expanding its scope and has evolved into a new experience, and for many, it is now considered as new kind of industrial revolution. In this new experience, makers create new things within their community by using new digital tools and technologies in spots called makerspaces. In these makerspaces, activities of learning, experience sharing, and mentoring are evolved into maker events. Makers who share common interests in making benefit from makerspaces as meeting and working spots. In literature, there are many sources on Maker Movement, maker communities, and their activities, especially in the field of business administration. However, there is a gap in the literature about the maker communities in Turkey. This research aims to be an information source on the dynamics and process design of “making” activities in Turkish maker communities and also aims to provide insights to sustain and enhance local maker communities in the future. Within this aim, semi-structured interviews were conducted with founders and facilitators from selected Turkish maker communities. (1) The perception towards Maker Movement, makers, activity of making, and current situation of maker communities, (2) motivations of individuals who participate the maker communities, and (3) key drivers (collaboration and decision-making in design processes) of maker activities from the perspectives of main actors (founders, facilitators) are all examined deeply with question on personal experiences and perspectives. After a qualitative approached data analysis concerning the maker communities in Turkey, this research reveals that there are two main conclusions regarding (1) the foundation of the Turkish maker mindset and (2) emergence of self-sustaining communities.

Keywords: Maker Movement, maker community, makerspaces, open-source design, sustainability

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8 Effects of Learner-Content Interaction Activities on the Context of Verbal Learning Outcomes in Interactive Courses

Authors: Alper Tolga Kumtepe, Erdem Erdogdu, M. Recep Okur, Eda Kaypak, Ozlem Kaya, Serap Ugur, Deniz Dincer, Hakan Yildirim

Abstract:

Interaction is one of the most important components of open and distance learning. According to Moore, who proposed one of the keystones on interaction types, there are three basic types of interaction: learner-teacher, learner-content, and learner-learner. From these interaction types, learner-content interaction, without doubt, can be identified as the most fundamental one on which all education is based. Efficacy, efficiency, and attraction of open and distance learning systems can be achieved by the practice of effective learner-content interaction. With the development of new technologies, interactive e-learning materials have been commonly used as a resource in open and distance learning, along with the printed books. The intellectual engagement of the learners with the content that is course materials may also affect their satisfaction for the open and distance learning practices in general. Learner satisfaction holds an important place in open and distance learning since it will eventually contribute to the achievement of learning outcomes. Using the learner-content interaction activities in course materials, Anadolu University, by its Open Education system, tries to involve learners in deep and meaningful learning practices. Especially, during the e-learning material design and production processes, identifying appropriate learner-content interaction activities within the context of learning outcomes holds a big importance. Considering the lack of studies adopting this approach, as well as its being a study on the use of e-learning materials in Open Education system, this research holds a big value in open and distance learning literature. In this respect, the present study aimed to investigate a) which learner-content interaction activities included in interactive courses are the most effective in learners’ achievement of verbal information learning outcomes and b) to what extent distance learners are satisfied with these learner-content interaction activities. For this study, the quasi-experimental research design was adopted. The 120 participants of the study were from Anadolu University Open Education Faculty students living in Eskişehir. The students were divided into 6 groups randomly. While 5 of these groups received different learner-content interaction activities as a part of the experiment, the other group served as the control group. The data were collected mainly through two instruments: pre-test and post-test. In addition to those tests, learners’ perceived learning was assessed with an item at the end of the program. The data collected from pre-test and post-test were analyzed by ANOVA, and in the light of the findings of this approximately 24-month study, suggestions for the further design of e-learning materials within the context of learner-content interaction activities will be provided at the conference. The current study is planned to be an antecedent for the following studies that will examine the effects of activities on other learning domains.

Keywords: interaction, distance education, interactivity, online courses

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7 First Step into a Smoke-Free Life: The Effectivity of Peer Education Programme of Midwifery Students

Authors: Rabia Genc, Aysun Eksioglu, Emine Serap Sarican, Sibel Icke

Abstract:

Today the habit of cigarette smoking is among one of the most important public health concerns because of the health problems it leads to. The most important and hazardous group to use tobacco and tobacco products is adolescents and teenagers. And one of the most effective ways to prevent them from starting to smoke is education. This research is a kind of educational intervention study which was carried out in order to evaluate the effect of peer education on the teenagers' knowledge about smoking. The research was carried out between October 15, 2013 and September 9, 2015 at Ege University Ataturk Vocational Health School. The population of the research comprised of the students that have been studying at Ege University Atatürk Vocational Health School, Midwifery Department (N=390). The peer educator group that would give training on smoking consisted of 10 people, and the peer groups that would be trained were divided into two groups via simple randomization as experimental group (n=185) and control group (n=185). Questionnaire, information evaluation form, and informed consent forms were used as date collection tools. The analysis of the data which were collected in the study was carried out on Statistical Package for Social Science (SPSS 15.0). It was found out that 62.5 % of the students who were in peer educator group had smoked in some period of their lives; however, none of them continued to smoke. When they were asked about their reasons to start smoking, 25% said they just wanted to try it, and 25% of them answered that it was because of their friend groups. When the pre-peer education and post-peer education point averages of peer educator group were evaluated, the results showed that there was a significant difference between the point averages (p < 0.05). When the cigarette use of experimental group and the control group were evaluated, it was clear that 18.2% of the experimental group and 24.2%of the control group still smokes. 9.1% of the experimental group and 14.8% of control group stated that they started smoking because of their friend groups. Among the students who smoke 15.9% of the ones who belongs to the experimental group and 21.9% of the ones who belong to the control group stated they are thinking of quitting smoking. It was clear that there is a significant difference between the pre-education and post-education point averages of experimental group statistically (p ≤ 0.05); however, in terms of control group, there were no significant differences between the pre-test post-test averages statistically. Between the pre-test post-test averages of experimental and control groups there were not any statistically significant differences (p > 0.05). It was found out in the study that the peer education programme is not effective on the smoking habit of Vocational Health School students. When the future studies are being planned in order to evaluate the peer education activity, it can be taken into consideration that the peer education takes a long term and the students in the educator group will be more enthusiastic and a kind of leader in their environment.

Keywords: midwifery, peer, peer education, smoking

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6 Microbial and SARS-CoV-2 Efficiency Analysis of Froumann HEPA Filter Air Cleaner Brand

Authors: Serap Gedikli, Hakan Çakmak, M. Buğra Güldiken, Duygu Yalnızoğlu

Abstract:

Air, which is necessary for living things to survive; while it carries some useful substances in it, it can also carry foreign particles of different sizes that may be harmful to the health. All airborne organic substances of biological origin, including bacteria, fungi, fungal spores, viruses, pollen, and their components, are called "bioaerosols". Nowadays, everyone spends most of their time in closed areas such as home, workplace, school, etc. Although it is known that outdoor air pollution affects health, it is not known that indoor air pollution has harmful effects in terms of health. In this study, indoor air microbial load and SARS-CoV-2 virus cleaning efficiency of Froumann brand air cleaners were studied. This work in 300 m³, 600 m³, and 1000 m³ completely closed areas without any air circulation with Froumann N80, N90, and N100 air-cleaning devices. Analyzes were performed for both areas at 60 minutes before and after the device was operated using a particle measuring device (Particles Plus 7302) and an air sampler (Mas-100 ECO). The measurements were taken by placing the test equipment 1.5-2 m away from the air cleaner. At the same time, the efficiency of the HEPA filter was evaluated by taking samples from the air outlet point of the HEPA filter using the air sampling device (Mas-100 ECO) after the device was started. Nutrient agar and malt agar are used as total mesophilic bacteria and total fungi. The number of colony-forming units per m³ (cfu/m³) was calculated by counting colonies in Petri dishes after incubation for 48 hours at 37°C for bacteria and 72 hours at 30°C for fungi. The change in the number of colonies and the decrease in the microbial load was calculated as a percentage value. SARS-CoV-2 activity analysis studies were carried out by İnönü University Microbiology Department in accordance with the World Health Organization regulations. Finally, the HEPA filter in the devices used was taken and kept under a certain temperature and humidity, and the change in the microbial load on it was monitored over a 6-month period. At the end of the studies, a 91%-94% reduction was determined in the total mesophilic bacteria count of Frouman brand N80, N90, and N100 model air cleaners. A decrease of 94%-96% was detected in the total number of yeast/molds. HEPA filter efficiency was evaluated, and at the end of the analysis, 98% of the bacterial load and approximately 100% of yeast/mold load at the HEPA filter air outlet point were decreased. According to the SARS- CoV-2 analysis results, when the device is operating at the medium airflow level 3, it can filter virus-carrying aerosols by 99%. As a result, it was determined that the Froumann model air cleaner was effective in controlling and reducing the microbial load in the indoor air.

Keywords: HEPA filter, indoor air quality, microbial load, SARS-CoV-2

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5 Is Electricity Consumption Stationary in Turkey?

Authors: Eyup Dogan

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The number of research articles analyzing the integration properties of energy variables has rapidly increased in the energy literature for about a decade. The stochastic behaviors of energy variables are worth knowing due to several reasons. For instance, national policies to conserve or promote energy consumption, which should be taken as shocks to energy consumption, will have transitory effects in energy consumption if energy consumption is found to be stationary in one country. Furthermore, it is also important to know the order of integration to employ an appropriate econometric model. Despite being an important subject for applied energy (economics) and having a huge volume of studies, several known limitations still exist with the existing literature. For example, many of the studies use aggregate energy consumption and national level data. In addition, a huge part of the literature is either multi-country studies or solely focusing on the U.S. This is the first study in the literature that considers a form of energy consumption by sectors at sub-national level. This research study aims at investigating unit root properties of electricity consumption for 12 regions of Turkey by four sectors in addition to total electricity consumption for the purpose of filling the mentioned limits in the literature. In this regard, we analyze stationarity properties of 60 cases . Because the use of multiple unit root tests make the results robust and consistent, we apply Dickey-Fuller unit root test based on Generalized Least Squares regression (DFGLS), Phillips-Perron unit root test (PP) and Zivot-Andrews unit root test with one endogenous structural break (ZA). The main finding of this study is that electricity consumption is trend stationary in 7 cases according to DFGLS and PP, whereas it is stationary process in 12 cases when we take into account the structural change by applying ZA. Thus, shocks to electricity consumption have transitory effects in those cases; namely, agriculture in region 1, region 4 and region 7, industrial in region 5, region 8, region 9, region 10 and region 11, business in region 4, region 7 and region 9, total electricity consumption in region 11. Regarding policy implications, policies to decrease or stimulate the use of electricity have a long-run impact on electricity consumption in 80% of cases in Turkey given that 48 cases are non-stationary process. On the other hand, the past behavior of electricity consumption can be used to predict the future behavior of that in 12 cases only.

Keywords: unit root, electricity consumption, sectoral data, subnational data

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4 Robust Inference with a Skew T Distribution

Authors: M. Qamarul Islam, Ergun Dogan, Mehmet Yazici

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There is a growing body of evidence that non-normal data is more prevalent in nature than the normal one. Examples can be quoted from, but not restricted to, the areas of Economics, Finance and Actuarial Science. The non-normality considered here is expressed in terms of fat-tailedness and asymmetry of the relevant distribution. In this study a skew t distribution that can be used to model a data that exhibit inherent non-normal behavior is considered. This distribution has tails fatter than a normal distribution and it also exhibits skewness. Although maximum likelihood estimates can be obtained by solving iteratively the likelihood equations that are non-linear in form, this can be problematic in terms of convergence and in many other respects as well. Therefore, it is preferred to use the method of modified maximum likelihood in which the likelihood estimates are derived by expressing the intractable non-linear likelihood equations in terms of standardized ordered variates and replacing the intractable terms by their linear approximations obtained from the first two terms of a Taylor series expansion about the quantiles of the distribution. These estimates, called modified maximum likelihood estimates, are obtained in closed form. Hence, they are easy to compute and to manipulate analytically. In fact the modified maximum likelihood estimates are equivalent to maximum likelihood estimates, asymptotically. Even in small samples the modified maximum likelihood estimates are found to be approximately the same as maximum likelihood estimates that are obtained iteratively. It is shown in this study that the modified maximum likelihood estimates are not only unbiased but substantially more efficient than the commonly used moment estimates or the least square estimates that are known to be biased and inefficient in such cases. Furthermore, in conventional regression analysis, it is assumed that the error terms are distributed normally and, hence, the well-known least square method is considered to be a suitable and preferred method for making the relevant statistical inferences. However, a number of empirical researches have shown that non-normal errors are more prevalent. Even transforming and/or filtering techniques may not produce normally distributed residuals. Here, a study is done for multiple linear regression models with random error having non-normal pattern. Through an extensive simulation it is shown that the modified maximum likelihood estimates of regression parameters are plausibly robust to the distributional assumptions and to various data anomalies as compared to the widely used least square estimates. Relevant tests of hypothesis are developed and are explored for desirable properties in terms of their size and power. The tests based upon modified maximum likelihood estimates are found to be substantially more powerful than the tests based upon least square estimates. Several examples are provided from the areas of Economics and Finance where such distributions are interpretable in terms of efficient market hypothesis with respect to asset pricing, portfolio selection, risk measurement and capital allocation, etc.

Keywords: least square estimates, linear regression, maximum likelihood estimates, modified maximum likelihood method, non-normality, robustness

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3 Rheological Properties of Thermoresponsive Poly(N-Vinylcaprolactam)-g-Collagen Hydrogel

Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

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Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

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2 Relevance of Dosing Time for Everolimus Toxicity on Thyroid Gland and Hormones in Mice

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

Abstract:

Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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1 The Effects of Bisphosphonates on Osteonecrosis of Jaw Bone: A Stem Cell Perspective

Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

Abstract:

Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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