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Obscuri̇n ve tri̇o protei̇n ai̇leleri̇nde evri̇msel korunum ve yapısal anali̇z yoluyla varyant etki̇ tahmi̇ni̇
No full textObscurin and Trio protein families represent evolutionarily related proteins with crucial roles in muscle development and neuronal signalling, respectively. In this study, the evolutionary relationships between these protein families across vertebrate lineages were established through comprehensive phylogenetic analysis of four key domains – kinase, Dbl-homology (DH), CRAL/TRIO, and immunoglobulin domains. Findings support the hypothesis that ancestral Titin and Mcf2 proteins underwent homologous recombination to create the ancestral Obscurin and Trio protein families, with subsequent specialisation and lineage-specific adaptations. Sequence comparison of immunoglobulin domains revealed conserved N-terminal and C-terminal clusters across vertebrates, providing further evidence for this evolutionary model.
Building on these evolutionary insights, the focus was directed towards the N-terminal DH domain of Trio (TrioN), which harbours one-third of all reported pathogenic variants in human DH domains. Trio functions primarily in neuronal migration, axon guidance, and synapse formation, with mutations associated with neurodevelopmental disorders including intellectual disability and autism spectrum disorders.
TrioNsight was developed as a meta-predictor designed to assess mutation impacts for TrioN and 12 highly similar human DH domains. This tool exploits the naïve-Bayes algorithm and leverages structural, evolutionary, and physiochemical features of approximately 1500 TrioN-like DH domains from 294 species. TrioNsight outperforms existing predictors, including AlphaMissense, achieving a Matthews' Correlation Coefficient of 0.906. Additionally, a variant impact map detailing mutation effects at each position was provided, potentially valuable for clinical assessments. This approach establishes a standardised workflow adaptable for creating domain-specific variant predictors for other protein families, offering a template for improved variant interpretation.Obscurin ve Trio protein aileleri, kas gelişimi ve nöronal sinyalleşmede önemli rolleri olan evrimsel ilişkili proteinleri temsil eder. Bu çalışmada, kinaz, Dbl-homoloji (DH), CRAL/TRIO ve immünoglobulin olmak üzere dört temel yapısal alanın kapsamlı filogenetik analizi yoluyla, bu protein ailelerinin omurgalı soyları boyunca evrimsel ilişkileri belirlenmiştir. Bulgular, atasal Titin ve Mcf2 proteinlerinin atasal Obscurin ve Trio protein ailelerini oluşturmak için homolog rekombinasyona uğradığı ve sonradan türe özgü adaptasyonlar geçirdiği evrimsel modelini desteklemektedir. İmmünoglobulin alanlarının dizi karşılaştırması, omurgalılar genelinde korunmuş N-terminal ve C-terminal kümeler ortaya çıkarmış ve bu evrimsel model için daha fazla kanıt sağlamıştır.
Bu evrimsel bulgular üzerine, çalışmanın odağı, insan DH alanlarında bildirilen tüm patojenik varyantların üçte birini barındıran Trio N-terminal DH alanına (TrioN) yöneltilmiştir. Trio öncelikle nöronal göç, akson rehberliği ve sinaps oluşumunda işlev görür ve mutasyonları zihinsel engellilik ve otizm spektrum bozuklukları dahil olmak üzere nörogelişimsel bozukluklarla ilişkilidir.
TrioNsight, TrioN ve benzer 12 insan DH alanı için mutasyon etkilerini değerlendirmek üzere tasarlanmış bir meta-tahmin edici olarak geliştirilmiştir. Bu araç, naif-Bayes algoritmasını kullanır ve 294 türden yaklaşık 1500 TrioN benzeri DH alanının yapısal, evrimsel ve fizikokimyasal özelliklerinden yararlanır. TrioNsight, AlphaMissense dahil mevcut tahmin edicilerin performansını aşarak 0.906 Matthews Korelasyon Katsayısına ulaşmıştır. Ek olarak, her pozisyondaki mutasyon etkilerini detaylandıran, klinik değerlendirmeler için potansiyel olarak değerli bir varyant etki haritası sağlanmıştır. Bu yaklaşım, diğer protein aileleri için alana özgü varyant tahmin edicileri oluşturmak için uyarlanabilir standartlaştırılmış bir iş akışı oluşturarak, evrimsel tarih bağlamında gelişmiş varyant yorumlaması için bir şablon sunar.Ph.D. - Doctoral Progra
Tek-malzemeli ve katmanlar-arası hibrit kompozit laminatların hasar mekanizmalarının incelenmesi
No full textInterply hybrid composite laminates consist of plies reinforced with different fiber types to achieve enhanced properties compared to single-material laminates. Such laminates are used in high-performance applications, including helicopter tail rotor blade flexbeams and wind turbine blades, where high interlaminar stresses under operational loads make them susceptible to delamination. This study investigates the interlaminar properties and failure behaviors of hybrid laminates in comparison with carbon and glass laminates. An experimental program was conducted, including double cantilever beam (DCB) and end-notched flexure (ENF) experiments for Mode-I and Mode-II fracture toughness, short-beam shear (SBS) and curved beam strength (CBS) experiments for interlaminar shear strength (ILSS) and interlaminar tensile strength (ILTS). Shear-loaded curved beam experiments were also performed to further elucidate the failure mechanisms in the CBS experiments. DCB and ENF results indicated that the Mode-I and Mode-II fracture toughness of the hybrid laminates fell between those of carbon and glass laminates. Post-mortem fracture surface examinations revealed cracks propagating predominantly along ply interfaces, with occasional deflections into adjacent plies.
SBS and CBS experiments revealed that hybrid laminates exhibited ILSS comparable to carbon laminates, whereas ILTS was comparable to glass laminates. The sequence and mechanisms of failure were examined, revealing differences from the literature. Our observations challenge the conventional definition of delamination as interface separation between layers in unidirectional (UD) laminates. Particularly, in curved laminates under four-point bending, substantial intralaminar failure accompanied interlaminar failure at various layers. Consequently, ILTS calculated based on maximum radial stress location may not accurately represent ply interface strength. Furthermore, finite element analysis of curved beam laminates with only cohesive zone modeling is not sufficient to capture the experimentally observed failure process. A key contribution of this work is demonstrating that the failure mechanisms in advanced aerospace-grade UD composites studied in this program do not conform to the traditional concept of delamination. The absence of a consistent crack-propagation preference along ply interfaces underscores the need to reassess the use of interface strength values obtained from standard tests in UD laminates.Katmanlar arası hibrit kompozit laminatlar, tek malzemeli laminatlara kıyasla geliştirilmiş özellikler sağlamak amacıyla farklı elyaf türleriyle takviye edilmiş tabakalardan oluşur. Bu tür laminatlar, helikopter kuyruk rotor palinin esnek kirişleri (flexbeam) ve rüzgar türbini kanatları gibi yüksek performanslı uygulamalarda yaygın olarak kullanılır. Ancak operasyonel yükler altında oluşan yüksek katmanlar arası gerilmeler, delaminasyona yol açabilmektedir. Bu çalışma, hibrit laminatların katmanlar arası özelliklerini ve hasar davranışlarını, karbon ve cam laminatlarla karşılaştırmalı olarak incelemektedir. Deneysel program kapsamında; Mod I ve Mod II kırılma tokluğu için çift dirsekli kiriş (DCB) ve çentik uçlu eğme (ENF) deneyleri, katmanlar arası kayma dayanımı (ILSS) için kısa kiriş eğme (SBS) deneyleri ve katmanlar arası çekme dayanımı (ILTS) için eğri kiriş dayanım (CBS) deneyleri yapılmıştır. CBS deneylerinde gözlenen hasar mekanizmalarını daha iyi anlamak amacıyla kesme yüklemeli eğri kiriş deneyleri de gerçekleştirilmiştir. DCB ve ENF sonuçları, hibrit laminatların Mod I ve Mod II kırılma tokluğu değerlerinin karbon ve cam laminatlar arasında olduğunu göstermiştir. Kırılma yüzeyi incelemeleri, çatlakların çoğunlukla tabaka ara yüzeyleri boyunca ilerlediğini, ancak zaman zaman komşu tabakalara da saptığını göstermiştir.
SBS ve CBS deneyleri, hibrit laminatların ILSS değerlerinin karbon laminatlara, ILTS değerlerinin ise cam laminatlara yakın olduğunu göstermiştir. Hasarın oluşum sırası ve mekanizmaları incelenmiş, literatürde bildirilenlerden farklılıklar gözlenmiştir. Bulgular, tek yönlü (UD) laminatlarda tabakalar arası ayrılma olarak tanımlanan geleneksel delaminasyon kavramını sorgulamaktadır. Özellikle dört nokta eğilme altındaki eğri kirişlerde, farklı tabakalarda katmanlar arası hasara ek olarak belirgin katman içi hasar görülmüştür. Bu nedenle, maksimum radyal gerilme konumuna dayalı ILTS değeri, gerçek ara yüzey dayanımını tam olarak yansıtmayabilir. Ayrıca, yalnızca yapışkan arayüz modelleme (CZM) ile yapılan sonlu eleman analizleri, deneylerde gözlenen hasar sürecini tam olarak yansıtamamaktadır. Bu çalışma, incelenen ileri havacılık sınıfı UD kompozitlerdeki hasar mekanizmalarının geleneksel delaminasyon kavramına uymadığını ortaya koymaktadır. Çatlak ilerlemesinin tabaka ara yüzeylerinde tutarlı olmaması, standart testlerle elde edilen ara yüzey dayanım değerlerinin kullanımının yeniden değerlendirilmesi gerektiğini göstermektedir.Ph.D. - Doctoral Progra
Modeling a humanitarian-aid covering tour problem with location selection and vehicle assignment decisions
No full textIn post-disaster situations, time-critical decision-making is essential. Due to high demand and limited resources, visiting all affected locations is often infeasible. This study presents a novel variant of the covering tour problem that addresses these constraints by integrating location selection and vehicle assignment decisions. In the proposed problem, vehicles depart from selected relief centers, visit a subset of victim locations, and are allowed to complete their tours at any center. The demands of unvisited locations are satisfied through demand transfers from nearby visited nodes, with associated transfer times included in the total operation time. A mixed integer linear programming (MILP) model is formulated to minimize total operation time, incorporating both travel and demand transfer times. Scenario-based analyses are performed to evaluate the model's performance under various operational conditions, including transfer time sensitivity, route flexibility, demand coverage constraints, time-based covering radius, and partial fulfillment policies. To address scalability, a two-stage clustering-based heuristic is developed, offering a practical and computationally efficient solution method. From a humanitarian logistics perspective, the findings emphasize the importance of flexible routing, strategic placement of relief centers, and careful management of coverage thresholds. Additionally, the simplicity and adaptability of the proposed heuristic make it well suited for real-time decision-making in post-disaster response operations
Observation of Cosmic-Ray Anisotropy in the Southern Hemisphere with 12 yr of Data Collected by the IceCube Neutrino Observatory
Get PDFWe analyzed the 7.92 x 10(11) cosmic-ray-induced muon events collected by the IceCube Neutrino Observatory from 2011 May 13, when the fully constructed experiment started to take data, to 2023 May 12. This data set provides an up-to-date cosmic-ray arrival direction distribution in the Southern Hemisphere with unprecedented statistical accuracy covering more than a full period length of a solar cycle. Improvements in Monte Carlo event simulation and better handling of year-to-year differences in data processing significantly reduce systematic uncertainties below the level of statistical fluctuations compared to the previously published results. We confirm the observation of a change in the angular structure of the cosmic-ray anisotropy between 10 TeV and 1 PeV, more specifically in the 100-300 TeV energy range. For the first time, we analyzed the angular power spectrum at different energies. The observed variations of the power spectra with energy suggest relatively reduced large-scale features at high energy compared to those of medium and small scales. The large volume of data enhances the statistical significance at higher energies, up to the PeV scale, and smaller angular scales, down to approximately 6 degrees compared to previous findings
Ecological processes shaping abundant and rare nirK- and nirS-type denitrifying bacteria in Taihu lake sediments
No full textPurpose: Denitrifying bacteria perform a crucial ecological process regulating nitrogen cycling and greenhouse gas emissions. However, the community assembly mechanisms of nitric oxide producing denitrifying bacteria, particularly abundant and rare communities, are poorly understood. Materials and methods: In this study, nirK- and nirS marker genes were amplified following 16S rRNA sequencing, with the aim to identify the mechanisms shaping abundant and rare nirK- and nirS-type denitrifying bacteria in Taihu Lake sediments, particularly regarding the heterogeneity of a wide range of environmental factors. Results: Taihu Lake sediment showed low-pollution levels of heavy metals, but with significant differences of high nutrient status. The phylogenetic diversity of nirK- and nirS-type denitrifying bacteria, and beta-diversity of abundant and rare communities were affected by a combined stressor of heavy metals and nutrients. Our results revealed that rare denitrifying bacteria had significantly higher homogeneity of dispersal than that of abundant taxa. We found heterogeneous selection was the main process governing both abundant and rare nirK-type denitrifying bacteria, while the abundant nirS-type denitrifying bacteria were mainly governed by the dispersal limitation. Complex network interactions between abundant and rare nirK- and nirS-type denitrifying bacteria were detected, further the Mantel test showed strong significant correlations between keystone denitrifying bacteria with environmental factors. Conclusion: This study provides insights into the effects of nutrient pollution on denitrifying bacteria in lake sediment, and also enhances our understanding of community assembly mechanisms of abundant and rare nirK- and nirS-type denitrifying bacteria in lake ecosystems
Classification of Generalized Prejudice against Minorities in Türkiye: A Stereotype Content Model Approach in Two Samples
No full textPrevious research demonstrated that a context-specific (i.e., Türkiye) measure of generalized prejudice toward social minorities exhibits a factor structure consistent with the Dual Process Motivational Model of ideology (DPM). Building on this, the present study explored how the groups identified in this measure are classified within the framework of Stereotype Content Model (SCM). A student sample (N=291) and a general community sample (N=287) evaluated 29 target groups of prejudice in Turkey on warmth and competence dimensions according to the view of society. For each sample, we conducted an agglomerative hierarchical cluster analysis with Ward’s linkage method to determine the optimal number of clusters, followed by a k-means cluster analysis to view which groups are classified together. For the student sample, the final clusters mostly overlapped with the DPM structure with a few exceptions. Post-hoc tests indicated the three-cluster groups were significantly different from each other on both dimensions, supporting the prevalence of mixed combinations of stereotypes hypothesis put forward by the SCM (i.e., low on warmth, high on competence, and vice versa). On the other hand, hierarchical cluster analysis for the general community sample suggested a two-cluster solution as a better fit. Even though the clustering of groups differed compared to the student sample, warmth and competence rates indicated differences within and between clusters again where both clusters embodied ambivalent stereotypes. Paired t-tests further supported the ambivalent stereotypes hypothesis, showing that 29 groups in the student sample and 25 groups in the general community sample exhibited ambivalence at the group level. Differences in religiosity, conservatism, and political orientation between samples were discussed as potential explanations for the variation in cluster solutions. The results raise a methodological question suggesting that responses to the SCM’s traditional question about society’s view of groups may vary depending on the sample
İlkokul öğretmenlerinin siber dayanıklılıklarının siber seviyelerinin incelenmesi
No full textThis study aims to examine the cyber resilience levels of primary school teachers within the context of the National Institute of Standards and Technology (NIST) Cybersecurity Framework (CSF) and their relationship with demographic and behavioral traits such as experience, duration of daily internet use, and whether they had received previous cybersecurity training. A total of 192 primary school teachers were surveyed online, and a cross-sectional quantitative design was employed. The cyber resilience of the teachers was assessed through open-ended questions aligned with CSF in a cyber-attack scenario form. Using a rubric, qualitative data were converted into quantitative data. After measuring validity with Cohen's Kappa, data were analyzed using descriptive and non-parametric statistics.
The findings showed that teachers' cyber resilience skills need improvement in terms of the five functions of the NIST CSF. Separate analysis of the sub-factors confirmed that they also need improvements in the fields of maintaining a safe school environment, including recognizing risky data, identifying problems, resisting threats, and recovering from attacks. According to the distributions, they have the necessary knowledge and skills in protection functions, i.e., simple proactive security measures. There is a statistically significant difference in teachers’ cyber resilience with respect to gender. The use of digital tools has a slight positive correlation with the total cyber resilience scores. Neither the daily internet usage time factor nor the professional experience factor has any significant relationship with teachers' cyber resilience. On the other hand, the factor of receiving cybersecurity training has a significant impact on teachers' cyber resilience. This study contributes to the development of training programs for teachers to enhance their cyber resilience skills and thus to create a safer school environment.Bu çalışma, ilkokul öğretmenlerinin Ulusal Standartlar ve Teknoloji Enstitüsü (NIST) Siber Güvenlik Çerçevesi (CSF) bağlamındaki siber dayanıklılık düzeylerini ve bu düzeylerin deneyim, günlük internet kullanım süresi ve daha önce siber güvenlik eğitimi alıp almadıkları gibi demografik ve davranışsal özelliklerle ilişkisini incelemeyi amaçlamaktadır. Toplam 192 ilkokul öğretmeni çevrim içi anketle çalışmaya katılmış ve kesitsel nicel bir araştırma deseni uygulanmıştır. Öğretmenlerin siber dayanıklılıkları, bir siber saldırı senaryosu formunda CSF ile uyumlu açık uçlu sorular aracılığıyla değerlendirilmiştir. Nitel veriler, bir dereceli puanlama anahtarı (rubrik) kullanılarak nicel verilere dönüştürülmüştür. Cohen's Kappa ile geçerlik ölçümünün ardından veriler betimsel ve parametrik olmayan istatistiklerle analiz edilmiştir.
Bulgular, öğretmenlerin NIST CSF'nin beş işlevi bağlamında siber dayanıklılık becerilerinin geliştirilmesi gerektiğini göstermektedir. Alt faktörlerin ayrı ayrı analizinde, öğretmenlerin riskli verileri tanıma, sorunları belirleme, tehditlere karşı direnme ve saldırılardan kurtulma gibi alanlar da dahil olmak üzere güvenli bir okul ortamını sürdürme konusunda da gelişime ihtiyaç duydukları doğrulanmıştır. Dağılımlar incelendiğinde, koruma işlevleri yani basit önleyici güvenlik önlemleri konusunda gerekli bilgi ve becerilere sahip oldukları görülmektedir. Öğretmenlerin siber dayanıklılık düzeyleri cinsiyete göre istatistiksel olarak anlamlı bir farklılık göstermektedir. Dijital araç kullanımının, toplam siber dayanıklılık puanları ile hafif düzeyde pozitif korelasyonu bulunmaktadır. Günlük internet kullanım süresinin anlamlı bir farkı ya da mesleki deneyim faktörünün öğretmenlerin siber dayanıklılığı ile anlamlı bir ilişkisi bulunmamaktadır. Öte yandan, siber güvenlik eğitimi alma faktörü öğretmenlerin siber dayanıklılığı üzerinde anlamlı bir etkiye sahiptir. Bu çalışma, öğretmenlerin siber dayanıklılık becerilerini geliştirmeye yönelik eğitim programlarının oluşturulmasına ve dolayısıyla daha güvenli bir okul ortamı sağlanmasına katkıda bulunmaktadır.M.S. - Master of Scienc