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Item Zinc supplementation prolongs the latency of hyperthermia-induced febrile seizures in rats(2016) Aydin, L.; Erdem, S.R.; Yazici, C.; 27030634Some studies have shown a relationship between febrile seizures and zinc levels. The lowest dose zinc supplementation in pentylenetetrazole seizure model has a protective effect. But, zinc pretreatment has no effect in maximal electroshock model. However, it is unclear how zinc supplementation affects hyperthermia-induced febrile seizures. The aim of the present study was to investigate the effects of zinc supplementation on febrile seizures in male Sprague-Dawley rats. The rats were randomly assigned to four groups. Zinc supplementation was commenced 5 days prior to febrile seizure induction by placing the animals in a water bath at 45 degrees C. We measured the rectal temperature and determined the febrile seizure latency, duration, and stage. In the zinc-supplemented group, both the seizure latency and the rectal temperature triggering seizure initiation were significantly higher than in the other groups. We suggest that zinc supplementation can positively modulate febrile seizure pathogenesis in rats.Item Three-dimensional finite element analysis of stress distribution in inlay-restored mandibular first molar under simultaneous thermomechanical loads(2016) Koycu, Berrak Celik; Imirzalioglu, Pervin; Oezden, Utku Ahmet; 27041006Functional occlusal loads and intraoral temperature changes create stress in teeth. The purpose of this study was to evaluate the impact of simultaneous thermomechanical loads on stress distribution related to inlay restored teeth by three-dimensional finite element analysis. A mandibular first molar was constructed with tooth structures, surrounding bone and inlays of Type II gold alloy, ceramic, and composite resin. Stress patterns on the restorative materials, adhesive resin, enamel and dentin were analyzed after simulated temperature changes from 36 degrees C to 4 or 60 degrees C for 2 s with 200-N oblique loading. The results showed that the three types of inlays had similar stress distribution in the tooth structures and restorative materials. Concerning the adhesive resin, the composite resin inlay model exhibited lower stresses than ceramic and gold alloy inlays. Simultaneous thermomechanical loads caused high stress patterns in inlay-restored teeth. Composite resin inlays may be the better choice to avoid adhesive failure.Item Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant(2016) Ali, Moazzam; Akin, Ayse; Bahamondes, Luis; Brache, Vivian; Habib, Ndema; Landoulsi, Sihem; Hubacher, David; 0000-0003-2379-3325; 27671673; AAK-1688-2021Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan-Meier (K-M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes. The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K-M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95% confidence interval (CI): 0.2-1.8] and 0.8 per 100 W-Y [95% CI: 0.2-2.3], respectively. Complaints of bleeding changes were similar; however, ENG-users were more likely than LNG-users to experience heavy bleeding (p < 0.05). The median duration of the implant removal procedure was 64 seconds shorter for the one-rod ENG-implant (inter-quartile range (IQR) = 30.5, 117.5) compared to the two-rod LNG product (IQR = 77.0, 180.0). The 2-year rate for pregnancy in the IUD group compared with the two implant groups combined was 4.1 per 100 W-Y [95% CI: 2.5-6.5]. Few women were a parts per thousand currency sign19 years old or nulligravida. Although there was no weight limit for enrolment in the study, the number of women a parts per thousand yen70 kg were few. The results from this study corroborate previous evidence showing high contraceptive efficacy through 4 years for the ENG-implant. Data through 5 years are a novel contribution and further proof of the product's capability to provide safe and effective contraception that rivals the current 5-year LNG-subdermal implant. The findings provide valuable information for policy makers, family planning programmers and clinicians that the ENG-releasing subdermal implant is still highly effective up to 5 years after insertion. Compared to previous efforts, our study population was geographically diverse and our study had the highest number of participants completing at least 5 years of use. The trial was registered as ISRCTN33378571. The contraceptive devices and funds for conduct of the study were provided by the United Nations Development Programme/United Nations Population Fund/World Health Organization (WHO)/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), WHO. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the WHO. All stated authors have no conflict of interest, except Dr Hubacher who reported grants from United States Agency for International Development, during the conduct of the study; other from Advisory Boards (Teva, Bayer, OCON), outside the submitted work.Item Can Computerized Adaptive Testing Work in Students' Admission to Higher Education Programs in Turkey?(2017) Berberoglu, Giray; Kalender, IlkerAdmission into university in Turkey is very competitive and features a number of practical problems regarding not only the test administration process itself, but also concerning the psychometric properties of test scores. Computerized adaptive testing (CAT) is seen as a possible alternative approach to solve these problems. In the first phase of the study, a series of CAT simulations based on real students' responses to science items were conducted in order to determine which test termination rule produced more comparable results with scores made on the paper and pencil version of the test. An average of 17 items was used to terminate the CAT administration for a reasonable reliability level as opposed to the normal 45 items. Moreover, CAT based science scores not only produced similar correlations when using mathematics subtest scores as an external criterion, but also ranked the students similarly to the paper and pencil test version. In the second phase, a live CAT administration was implemented using an item bank composed of 242 items with a group of students who had previously taken the exam the paper and pencil version of the test. A correlation of.76 was found between the CAT and paper and pencil scores for this group. The results seem to support the CAT version of the subtests as a feasible alternative approach in Turkey's university admission system.Item Protective effect of Nigella sativa oil on acoustic trauma induced hearing loss in rats(2017) Culhaoglu, Belde; Erbek, Selim S.; Erbek, Seyra; Hizal, Evren; 0000-0002-8453-6069; 0000-0003-4825-3499; 0000-0002-9699-6783; 28791082; AAJ-2445-2021; B-7604-2019; A-5853-2018Acoustic trauma is a common reason for hearing loss. Different agents are used to prevent the harmful effect of acoustic trauma on hearing. The aim of this study was to evaluate the potential preventive effect of Nigella sativa (black cumin) oil in acoustic trauma. Our experimental study was conducted with 20 Sprague Downey female rats (mean age, 12 months; mean weight 250 g). All of the procedures were held under general anesthesia. Following otoscopic examinations, baseline-hearing thresholds were obtained using auditory brainstem responses (ABR). To create acoustic trauma, the rats were then exposed to white band noise of 4 kHz with an intensity level of 107 dB in a soundproof testing room. On Day 1 following acoustic trauma, hearing threshold measurements were repeated. The rats were divided into two groups as the study group (n: 10) and the controls (n: 10). 2 mL/kg/day of Nigella sativa oil was given to the rats in the study group orally. On Day 4 following acoustic trauma, ABR measurements were repeated again. There was no difference between the baseline hearing thresholds of the rats before acoustic trauma (P>0.005). After the acoustic trauma, hearing thresholds were increased and there was no significant statistically difference between the hearing thresholds of the study and control groups (P=0.979). At the 4th day following acoustic trauma, hearing thresholds of the rats in control group were found to be higher than those in the study group (P=0.03). Our results suggest that Nigella sativa oil has a protective effect against acoustic trauma in early period. This finding should be supported with additional experimental and clinical studies, especially to determine the optimal dose, duration and frequency of potential Nigella sativa oil therapy.Item Prefrontal Brain Activation in Subtypes of Attention Deficit Hyperactivity Disorder: A Functional Near-Infrared Spectroscopy Study(2018) Dolu, Nazan; Altinkaynak, Miray; Guven, Aysegul; Izzetoglu, Meltem; Demirci, Esra; Ozmen, Sevgi; Pektas, Ferhat; 0000-0002-3104-7587; AAG-4494-2019According to clinical symptoms, attention deficit and hyperactivity disorder (ADHD) is categorized into three groups: the predominantly inattentive subtype (ADHD-I),the predominantly hyperactive-impulsive subtype (ADHD-HI), and the combined subtype (ADHD-C). Recent advances in neuroimaging have demonstrated new approaches for assessing the ADHD subtypes with underlying pathophysiology.This study aims to examine the hemodynamic response and reaction time (RT) in healthy children and the ADHD subtypes as measured by functional near-infrared spectroscopy (fNIRS) during an auditory oddball attention task. The sample was made up of 40 children divided into four groups: control group (n=14), ADHD-I group (n=9), ADHD-HI group (n=6), and ADHD-C group (n=11). The target responses were identified and were grand-averaged for each participant. Right prefrontal cortex hemodynamic responses and groups performances on RT were compared between subtypes and between controls and subtypes. Functional near-infrared spectroscopy indicated that while control subjects exhibited higher activation than all ADHD subtypes, the ADHD subtypes did not differ from one another. Relative to control subjects, a longer RT was observed in all ADHD subtypes. The ADHD-I group showed significantly longer RTs compared to the ADHD-HI and ADHD-C groups.This study can bring a new perspective to the continuing controversy about ADHD subtypes, and the findings may help in the evaluation of fNIRS, RT, and RT variability studies in ADHD.Item Tek taraflı periferik vestibüler bozukluğu olan hastalarda statokinesigram ve parametrelerinin video baş savurma testi ve otolitik reflekslerle olan korelasyonu(Başkent Üniversitesi Sağlık Bilimleri Enstitüsü, 2018) Çöpürgensli, Canan; Özlüoğlu, Levent NaciPeriferik vestibüler bozukluklar, vestibüler labirent ya da vestibüler sinirlerdeki patolojilerden kaynaklanır. Bu bozukluklarda, vertigo, postüral instablite ve denge kaybı gibi semptomlar görülmektedir. Vestibüler sistemin değerlendirilmesinde, detaylı öykü ve fizik muayenenin yanı sıra, sıklıkla kullanılan birkaç test bulunmaktadır. Literatürde bu testlerin birbiriyle ilişkisini inceleyen herhangi bir çalışma bulunmaması bizde bu araştırmayı yapma ihtiyacı doğurmuştur. Bu çalışmanın amacı, tek taraflı periferik vestibüler bozukluğu olan hastalarda, statokinesigramın ne ölçüde etkilendiğini incelemektir. Bu bağlamda, dinamik/ statik postürografi ile tek taraflı vestibüler bozukluğu tanısına katkıda bulunan video baş savurma testi (VHIT) ve vestibüler uyarılmış myojenik potansiyeller (VEMP) testlerinin ilişkisini incelemektir. Bu çalışma “tek taraflı periferik vestibüler bozukluk” tanısı almış, semptomları en az üç aydır devam eden ve yaşları 40 ile 82 yaş arasında değişen 30 hastanın katılımı ile gerçekleştirildi. Hastalara; statokinesigram (SKG), stabiliteninin limiti testi (limits of stability), öne-arkaya postüral stabilite, sağa-sola postüral stabilite alt parametrelerini içeren statik/dinamik sensoryal organizasyon testleri (dinamik postürografi); semisirküler kanalların VOR kazanç ve ortalama hız parametrelerini içeren VHIT ve servikal- oküler VEMP testleri uygulandı. Dinamik postürografi; farklı koşullardaki postüral stabiliteyi, VHIT; kanalların VOR kazanç ve fonksiyonlarını; VEMP testleri ise, otolit fonksiyonunu ölçmekteydi. Değişkenler arasındaki doğrusal ilişki pearson korelasyon analizi ile incelendi. Analizler sonucunda, arkaya stabilite limiti ile posterior kanal hız ölçümleri arasında negatif yönlü, orta derecede (r=-0,555; p=0,032); sola stabilite limiti ile anterior ve lateral kanal hızları arasında pozitif yönlü orta derecede (r=0,528; p=0,043 / r=0,549; p=0,034); anterior kanal kazancı ile servikal VEMP dalga latansları arasında negatif yönlü kuvvetli derecede (r=-0,807; p=0,015 / r=-767; p=0,026); gözler açık SKG alanı ile servikal VEMP N1 dalga amplitudu arasında pozitif yönlü, çok yüksek derecede (r=0,826; p=0,011); gözler açık ön-arka postüral stabilite ile posterior kanal hızı arasında negatif yönlü, yüksek derecede (r=- 0,643; p=0,010); gözler kapalı ön-arka postüral stabilite ile anterior kanal kazancı arasında, negatif yönlü, orta derecede (r=-0,580; p=0,024); gözler kapalı ön-arka postüral stabilite ile posterior kanal hızı arasında, negatif yönlü, yüksek derecede (r=-0,661;p=0,007); örümcek ön-arka postüral stabilite ile posterior kanal hızı arasında negatif yönlü, yüksek derecede (r=- 0,614; p=0,015); servikal VEMP P1 dalga amplitudu ile örümcek sağ-sol postüral stabilite ve laterak kanal hızları arasında negatif yönlü yüksek derecede (r=-0,772; p=0,025 / r=-0,843; p=0,009); stabilite limiti total alanı ile anterior kanal hızı arasında pozitif yönlü, orta derecede (r=0,574; p=0,025); lateral kanal kazancı ile servikal VEMP dalga latansları arasında negatif yönlü yüksek derecede (r=-0,780; p=0,022; r=-0,722; p=0,043); gözler açık SKG alanı ile lateral ve anterior kanal hızları arasında pozitif yönlü orta derecede (r=0,534; p=0,040; r=0,602;p=0,018); gözler kapalı ön-arka postüral stabilite ile lateral kanal hızı arasında pozitif yönlü orta derecede (r=0,520; p=0,047); gözler kapalı sağ-sol postüral stabilite ile servikal VEMP P1 latansı arasında negatif yönlü, çok yüksek derecede (r=-0,835; p=0,010); örümcek SKG alanı ile anterior kanal hızı arasında pozitif yönlü, orta derecede doğrusal ilişki bulunmuştur (r=0,614; p=0,015). Çalışmanın bulguları dikkate alındığında, tek taraflı periferik vestibüler bozukluğu olan hastalarda, dinamik postürografi alt parametrelerinden sitatokinesigramın, farklı ölçülerde etkilendiği ve VHIT ile VEMP testleri ile farklı kuvvetlerde ilişkili olduğu bulunmuştur. Bu sonuçların, vestibüler rehabilitasyon programlarının planlanması aşamasında dikkate alınmasını önermekteyiz. Peripheral vestibular disorders are resulted from vestibular labyrinth or vestibular nerve pathologies. In these disorders, it is also possible to observe symptoms such as vertigo, postural instability and poor balance. Some other tests exist for evaluating vestibular system as well as detailed medical history and physical examination. Not finding any studies investigating the relation between these tests in literature created a need to conduct this study. The aim of this study are to examine the level of effect that statokinesigram (SKG) has exposed on patients having Unilateral Peripheral Vestibular Disorder (UPVD), in this context, to investigate the relation between Video Head Impulse Test (VHIT) and Vestibular Evoked Myogenic Potential (VEMP) Test, which contributes diagnosis of UPVD and Static / Dynamic Posturography. This study has been conducted with 30 patients whose ages differ between 40-82 years and diagnosed UPVD, and their symptoms lasting at least 3 months. Static/ Dynamic Sensory Organization Test (SOT) including sub-parameters of SKG, Limits of Stability (LOS) Test, antero-posterior postural stability, medio-lateral postural stability, VHIT including VOR gains and head velocity and cervical-ocular VEMP tests were all administered to patients. Dynamic Posturography assesses postural stability in different conditions, VHIT assesses VOR gains and functions of canals, VEMP assesses otoliths functions. Linear correlation between variations was examined with Pearson Correlation Analysis. Regarding the analysis in this study shows that a negative correlation-moderate degree (r=-0.555; p=0.032) has been found between LOS posterior and posterior SSC peak head velocity, and a positive correlation-moderate degree (r=0.528; p=0.043 / r=0.549; p=0.034) between LOS left and Anterior/ Lateral SSC peak head velocity. In addition to this, a negative correlation-high degree (r=-0.807; p=0.015 / r=-767; p=0.026) between Anterior SSC VOR gain and cervical VEMP Latans, and a positive correlation-high degree (r=0.826; p=0.011) between eyes open SKG area and cervical VEMP N1 Amplitude, and a negative correlationhigh degree (r=-0.643; p=0.010) between eyes open antero-posterior postural stability and posterior SSC peak head velocity have been observed. In addition correlations were following; a negative correlation-moderate degree (r=-0.580; p=0.024) between eyes closed antero-posterior postural stability and Anterior SSC VOR gain, and a negaive correlation-high degree (r=-0.661;p=0.007) between eyes closed antero-posterior postural stability and posterior SSC peak head velocity, and a negative correlation-high degree (r=-0.614; p=0.015) between cobweb antero-posterior postural stability and posterior SSC peak head velocity, and a negative correlation-high degree (r=-0.772; p=0.025 / r=-0.843; p=0.009) cervical VEMP P1 amplitude and cobweb right-left postural stability / lateral SSC peak head velocity have been found. Additionally, a positive correlation-moderate degree (r=0.574; p=0.025) between LOS total area and anterior SSC peak head velocity, and a negative correlation-high degree (r=- 0.780; p=0.022; r=-0.722; p=0.043) between lateral SSC VOR gain and cervical VEMP latans, and a positive correlation-moderate degree (r=0.534; p=0.040; r=0.602; p=0.018) between eyes open SKG area and lateral/anterior SSC peak head velocity have been come by. Finally, this study has come up with a positive correlation-moderate degree (r=0.520; p=0.047) between eyes closed antero-posterior postural stability and lateak SSC peak head velocity, and a negative correlation-high degree (r=-0.835; p=0.010) between eyes closed medio-lateral postural stability and cervical VEMP P1 latans, and a positive correlationmoderate degree (r=0.614; p=0.015) between cobweb SKG area and anterior SSC peak head velocity. In line with these findings, this study presents that SKG being sub-parameters of Dynamic Posturography has been affected in various degrees in patients experiencing UPVD, and SKG has a correlation with VHIT and VEMP in various degrees. We strongly suggest these findings to be taken into consideration in planning of vestibular rehabilitation programs.Item Hareket korkusu nedenleri ölçeğinin (kinesiophopia causes scale) türkçe uyarlamasının geçerlik ve güvenilirliği(Başkent Üniversitesi Sağlık Bilimleri Enstitüsü, 2018) Çayır, Melis; Durutürk, NeslihanÇalışmanın amacı; Türkçe konuşan geriatrik bireylerde, HKNÖ’nin Türkçe uyarlaması ve kültürel adaptasyonunu sağlayarak, geçerlik ve güvenilirliğini ölçmektir. Çalışmamıza, 65-80 yaş arası, kooperasyon ve anlamaya engel olabilecek herhangi bir mental problemi olmayan ve araştırmaya gönüllü olarak katılan 103 sağlıklı geriatrik birey (yaş ortalaması:71.09±4.45 yıl, vücut kütle indeksi:27.08 ±4.4 kg/m2) dahil edildi. Bireylere Türkçe çevirisi yapılan HKNÖ ile kriter geçerliğini belirlemek amacıyla Tampa Kinezyofobi Ölçeği (TKÖ) uygulandı. Ölçeğin güvenilirliğinin göstergesi olan zamana göre değişmezliği test etmek için 48 saat sonra, HKNÖ ikinci kez uygulandı. Ankette yer alan tüm sorular arası iç tutarlılık değeri 0.863 olarak bulundu. Biyolojik alt boyutta yer alan sorular arası Cronbach’s α katsayısı 0.913, Psikolojik alt boyutta 0.797 olarak bulundu. Biyolojik parametre alt boyutlarının (morfolojik, harekete geçmek için bireysel ihtiyaç, enerji kaynakları, biyolojik dürtülerin gücü) Cronbach’s α 0.800 ve üstü iken, psikolojik parametre alt boyutlarının (kendini kabul etme, motor yatkınlığın öz değerlendirmesi, vücut bakımı) iç tutarlılık değeri sırasıyla 0.834, 0.790, 0.642 bulundu. TKÖ ve HKNÖ alt boyut puanları arasındaki korelasyonlar incelendiğinde TKÖ toplam puanı ile HKNÖ toplam puanı, biyolojik ve psikolojik alt boyutları arasında istatistiksel olarak anlamlı, pozitif yönde korelasyon belirlendi (p<0.05). Sonuç olarak, yetişkinde motor inaktivitenin ve hareket korkusunun sebeplerinin belirlenmesi amacıyla geliştirilmiş ve şimdiye kadar başka herhangi bir dilde adaptasyonu yapılmamış olan HKNÖ’nün, Türk geriatrik bireylerde geçerli ve güvenilir bir anket olduğunu ayrıca farklı hastalıklarda, daha büyük örneklemlerde ve yaş gruplarında incelenmesi gerektiğini düşünmekteyiz. The aim of this study is to provide the Turkish adaptation and cultural adaptation of KCS in Turkish-speaking geriatric individuals and to measure their reliability and validity. Our study included 103 healthy geriatric individuals (the average age: 71.09±4.45 years, body mass index: 27.08±4.4 kg/m2) the aged of 65-80 years, who had no mental problems that could interfere with cooperation and understanding and who volunteered to participate in the study. Tampa Scale of Kinesiophobia (TSK) was applied in order to determine the validity of the criterion with the KCS translated into Turkish. After 48 hours of testing for variability, which is an indicator of the reliability of the scale, KCS was applied for the second time. The internal consistency value of the questionnaire was 0.863. The Cronbach’s α coefficient was 0.913 among the questions in the biological sub-dimension, and 0.797 in the psychological sub-dimension. While the biological parameters sub-dimensions (morphologic, individual need for stimulation, energetic substrates, power of biological drives) have Cronbach's α coefficient of 0.800 and above, the internal consistency of psychological parameter sub-dimensions (self-acceptance, self-assessment of motor susceptibility, body care) is respectively 0.834, 0.790, 0.642. When the correlations between TSK and KCS subscale scores were examined, there was a statistically significant positive correlation between total score of TSK and total score of KCS biological and psychological subscales (p<0.05). As a result, we think that the KCS questionnaire, which has been developed in order to determine the causes of motor inactivity and fear of movement in adults, is a valid and reliable survey in Turkish geriatric individuals and should be examined in different diseases and age groups.Item HER2+ meme kanseri hücrelerinde pan-her inhibitörü dacomitinib'e hücre ölümü cevabının AVEN tarafından düzenlenmesi(Başkent Üniversitesi Sağlık Bilimleri Enstitüsü, 2018) Özcan, Sinejan; Kütük, ÖzgürMeme kanseri kadınlarda en sık görülen kanser tipidir ve geliştirilen yenilikçi tanı ve tedavi stratejilerine rağmen mortalite oranları halen yüksek seyretmektedir. Bu durumun en önemli nedenlerinden birisi hastanın tedavisinin başlangıcında varolan ya da tedavi sırasında ortaya çıkan terapi direncidir. HER reseptör ailesinin üyelerinin mutasyon ya da amplifikasyon ile aşırı aktif hale gelmesi birçok meme kanseri tipinde malign değişikliklerin nedenidir. HER2 amplifikasyonu meme kanseri hastalarının yaklaşık yüzde 20’sinde görülmektedir ve kötü prognozla ilişkilidir. Trastuzumab ve lapatinib gibi hedeflenmiş terapiler her ne kadar bu tümörlerde etkinlik gösterseler de terapi direnci önemli bir sorun olarak karşımıza çıkmaktadır. Bu nedenle tüm HER ailesi üyelerini eşzamanlı olarak hedefleyen panHER inhibitörleri (neratinib, dacomitinib, afatinib) geliştirilmiştir. Mitokondriyal apoptotik yolak gerek konvansiyonel gerekse hedeflenmiş terapilerin kanser hücreleri üzerindeki öncelikli etki yollarındandır. Mitokondriyal apoptotik yolak BCL-2 protein ailesi tarafından düzenlenir. BAX ve BAK proteinlerinin aktivatör BH3 proteinleri tarafından aktive edilmesi, mitokondriyal dış membran geçirgenliğinin artışı, sitokrom c’nin sitozole geçişi ve kaspaz aktivasyonu mitokondriyal apoptotik yolağın ana basamaklarıdır. AVEN, mitokondriyal apoptoz yolağının ve DNA hasar yanıtının düzenlenmesinde kritik rol oynayan sitozolik bir proteindir. BCL-xL proteinin anti-apoptotik aktivitesini destekleyerek ve Apaf-1 proteinin oligomerizasyonunu engelleyerek apoptoz yanıtnı inhibe etmektedir. Dahası sahip olduğu sinyal dizisi sayesinde nükleusa göç ederek ATM ve ATR proteinleri ile etkileşime girmekte ve hücre döngüsünün regülasyonunda rol oynamaktadır. AVEN’in ifadelenmesindeki ve/veya aktivasyonundaki artış kanserleşme ve ilaç direnciyle ilişkilendirilmektedir. Bu çalışmada amacımız AVEN’ın HER2+ meme kanseri hücrelerinde dacomitinib tarafından indüklenen hücre ölümü cevabını nasıl etkilediğini ortaya koymaktı. Bu amaç çerçevesinde HER2+ SKBR3 meme kanseri hücrelerinde AVEN ifadelenmesini arttırarak ya da azaltarak hücre ölümü cevabını değerlendirdik. AVEN’ın aşırı ifadelenmesi dacomitinib tarafından indüklenen mitokondriyal hücre ölümü cevabını azaltırken, RNAi yoluyla sustumu ise hücre ölümü cevabını arttırdı. Gerçekleştirdiğimiz çalışma literatürde HER2+ meme kanseri hücrelerinde AVEN’ın panHER baskılanmasına cevaben mitokondriyal hücre ölümünü nasıl etkilediğine dair ilk bulguları sağlamıştır. Breast cancer is the most common malignancy in women and the mortality rates are still high despite the development of novel diagnostic and therapeutic strategies. Resistance to therapy is among the leading causes of therapy failure, presenting either initially or emerges druing the course of the therapy. Overactivation of HER family of receptor kinases due to mutations or amplifications promotes malign transformation in various breast cancer cases. HER2 amplification is seen in 20% breast cancer patients and related to poor prognosis. Targeted therapies including trastuzumab and lapatinib exerted prominent antitumor effect in these breast cancer tumors, but therapy resistance significantly circumvents their activities. To cope with this issue, several panHER inhibitors (neratinib, dacomitinib, afatinib) have been developed. Mitochondrial apoptotic pathway is among the main mechanisms that modulates the effects of conventional and targeted therapies on cancer cells. BCL-2 proteins regulate mitochondrial apoptotic pathway. Activation of BAX and BAK by BH3-only proteins leads to mitochondrial outer membrane permeabilization, translocation of cytochrome c into cytosol and caspase activation are key steps of mitochondrial apoptotic signaling. AVEN is a cytosolic protein which regulates mitochondrial apoptotic pathway and DNA damage response. AVEN interferes with apoptotic signaling by enhancing the antiapoptotic activity of BCL-XL and by preventing Apaf-1 oligomerization. In addition, AVEN translocates to nucleus by means of its nuclear localization signal and interacts with ATM and ATR. These interactions regulate cell cycle response. Furthermore, increased AVEN activity or expression have been shown to trigger tumorigenesis and tumor maintenance. In this study, we aimed to identify how AVEN regulates dacomitinib-induced cell death response in HER2+ breast cancer cells. To explore these responses, we overexpressed or silenced AVEN in HER2+ SKBR3 breast cancer cells. AVEN overexpression led to attenuation of dacomitinib-induced mitochondrial apoptotic response and RNAi-mediated suppression of AVEN increased dacomitinib-induced apoptosis. Our results provided first findings in the literature regarding the modulation of panHER inhibition-induced apoptosis by AVEN.Item Analysis of Cryptocurrencies(Başkent Üniversitesi Fen Bilimleri Enstitüsü, 2018) Ulusoy, Görkem; Aktaş, Ahmet ZiyaDuring recent years Cryptocurrencies is one of the exciting discussion topics. Unfortunately, there is not yet a reliable reference on this topic. During this study cryptocurrencies will be investigated including their production techniques and operations. Existing cryptocurrency types will be compared; their strengths and weaknesses will be discussed as well. Security of cryptocurrencies are analyzed and their possible effects to the daily life and future of humanity will also be debated. Thus, the major objective of this study is to provide a road map to those who are working and researching in this field. Kripto paralar konusu son yıllarda çeşitli çevrelerde tartışma konusu yapılmaktadır. Ancak bu konuda yeterli ve geçerli bir kaynak henüz elimizde yoktur. Bu çalışma ile kripto paraların ne oldukları, nasıl üretildikleri incelenip, işleyiş yöntemleri karşılaştırılacaktır. Bunu yaparken piyasada mevcut olan kripto para örneklerinin güçlü ve zayıf yönleri tartışılacaktır. Çalışmada kripto paraların güvenilirlikleri ve güvenlik açıkları konusuna da ayrıca yer verilecek, kripto paraların insanlığı günümüzde ve gelecekte nasıl etkilediği ve etkileyeceği de kısaca irdelenecektir. Böylece bu konuda çalışma ve uygulama yapacak kişilere bir yol haritası oluşturulması tezin temel amacıdır.