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In Silico Screening of Drug Candidates Against Misfolding and Aggregation of Mutant and Wild Type SOD1 Enzymes for the Treatment of Familial ALS
No full textAmyotrofik Lateral Skleroz (ALS), genellikle süperoksit dismutaz 1 (SOD1) enzimindeki anormalliklerle bağlantılı nörodejeneratif bir durumdur. Bu tez, vahşi tip (WT) ve terapötik olabilecek üç SOD1 mutantının hem aktif bölgesini hem de dimer arayüzlerini hedefleyen yeni modülatörleri keşfetmeyi amaçlayan kapsamlı bir in silico analizi açıklamaktadır. Her biri yaklaşık 100.000 ligand içeren protein bölgesi kombinasyonu için bir tane olmak üzere sekiz Yapı Tabanlı Sanal Tarama (SBVS) gerçekleştirildi. Kalıntı düzeyinde yapısal çalışmalara dayalı olarak eş zamanlı olarak on iki özel tasarlanmış tripeptit taklit eden iskele oluşturuldu. Bu ligandlar çizildi, BioVia Discovery Studio ile enerji en aza indirildi ve sekiz protein modelinin tümünde hedeflendi. On altı taramanın her birinden, en iyi performans gösteren ligand-protein kombinasyonu, 100 nanosaniye moleküler dinamik (MD) simülasyonları için apo muadili ile birlikte toplam yirmi simülasyon için seçildi. Simülasyon çıktısı RMSD, RMSF ve Rg metrikleri kullanılarak yapısal ve işlevsel kararlılık açısından değerlendirildi. Ligand'a bağlı sistemler, konformasyonel etkileri belirlemek için apo formlarıyla karşılaştırıldı. Rasyonel ligand tasarımı, yüksek verimli sanal tarama ve MD simülasyonlarını içeren bu bütünleştirici strateji, çok sayıda ilginç adayın keşfedilmesiyle sonuçlandı. Bu bileşikler, olası fonksiyonel inhibisyon ile uyumlu bağlanma ve dinamik davranış gösterir ve hücresel modellerde daha fazla doğrulama için mükemmel adaylardır. Çalışma, ALS ortamında SOD1'i hedefleyen tedavi ipuçlarını rasyonel olarak belirlemeye yardımcı olur. Anahtar Sözcükler: Nörodejeneratif hastalıklar, ALS, SOD1, Yapı Tabanlı Sanal Tarama, Moleküler Yerleştirme, Moleküler Dinamik SimülasyonlarAmyotrophic Lateral Sclerosis (ALS) is a neurodegenerative condition that is usually linked to abnormalities in the superoxide dismutase 1 enzyme. This thesis describes a thorough in silico analysis aiming at discovering new modulators that target both the active site and dimer interfaces of wild-type (WT) and three therapeutically relevant SOD1 mutants. Eight Structure-Based Virtual Screenings (SBVS) were carried out, one for each protein-region combination, with each including roughly 100,000 ligands. Twelve custom-designed tripeptide-mimicking scaffolds were created concurrently based on residue-level structural studies. These ligands were drawn, energy-minimized with BioVia Discovery Studio, and targeted-screened across all eight protein models. From each of the sixteen screens (8 active site, 8 interface), the best-performing ligand-protein combination was chosen for 100-nanosecond molecular dynamics (MD) simulations, along with its apo counterpart, for a total of twenty simulations. The trajectories were evaluated for structural and functional stability using the RMSD, RMSF, and Rg metrics. Ligand-bound systems were compared to their apo forms to determine conformational effects. This integrative strategy, which included rational ligand design, high-throughput virtual screening, and MD simulations, resulted in the discovery of numerous interesting candidates. These compounds show binding and dynamic behavior compatible with possible functional inhibition, and they are excellent candidates for further validation in cellular models. This work helps to rationally identify treatment leads that target SOD1 in the setting of ALS. Keywords: Neurodegenerative diseases, ALS, SOD1, Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamic Simulation
Analysis of the Impact of Factors on Attitudes and Intentions Towards Reducing Food Waste: Sustainability Marketing Perspective
No full textBu araştırma, bireylerin gıda israfını azaltmaya yönelik tutum ve niyetlerini etkileyen faktörleri, medya bağlamında içsel ve dışsal unsurları inceleyerek sürdürülebilirlik pazarlama iletişimleri perspektifinden anlamayı amaçlamaktadır. Literatürde yer alan Planlanmış Davranış Teorisi (PDT), Gündem Belirleme Teorisi (GBT) ve Yetiştirme Teorisi (YT) çerçevesinde doğrudan ve dolaylı faktörlerin etkileri incelenmiştir. Ayrıca, PDT, GBT, YT'ye ek olarak ve Beklenti Teorisi'ne (BT) dayalı faktörler de ortaya konmuştur. Araştırmada karma yöntem kullanılmıştır: Öncelikle kavramsal modeli son hâline getirmek amacıyla nitel çalışmalar (uzman görüşmeleri ve ardından odak grup tartışmaları) yürütülmüş, ardından önerilen hipotezleri test etmek için nicel araştırma kapsamında anketler ile birlikte Açıklayıcı Faktör Analizi (AFA), Doğrulayıcı Faktör Analizi (DFA) ve Yapısal Eşitlik Modellemesi (YEM) kullanılmıştır. Araştırma bulgularına göre, medya maruziyeti (çeşitlilik) sürdürülebilirlik bilinci ve medya etkisi üzerinde anlamlı bir etkiye sahiptir; ancak medya maruziyeti (süre) bu değişkenler üzerinde anlamlı bir etki göstermemektedir. YouTube'un, sürdürülebilirlik bilincini etkileyen güçlü bir medya kanalı olduğu tespit edilmiş olup, sürdürülebilirlik bilinci, gıda israfına yönelik tutum ve niyetlerde PDT değişkenlerini olumlu yönde etkilemede önemli bir rol oynamaktadır. Medya kullanımı sırasında, hem mesajın özgüllüğü hem de kazanç odaklı pozitif mesaj çerçevesi, sürdürülebilirlik bilinci ile gıda israfına yönelik tutum arasındaki ilişkiyi güçlendiren ayrı moderatör değişkenler olarak işlev görmektedir. Öte yandan, çocuklukta edinilen israf etmeme öğretilerinden beslenen otobiyografik bellek, sürdürülebilirlik bilinci ile tutum arasındaki ilişkiyi güçlendirme açısından anlamlı bir moderatör etkisi göstermemektedir. Anahtar Sözcükler: İletişim kampanyaları, medya, sürdürülebilirlik bilinci, gıda israfını azaltmaya yönelik tutum, niyet, mesajın özgüllüğü, mesaj çerçevesi, otobiyografik bellek, yapısal eşitlik modellemesi, pazarlama iletişimiThis research seeks to understand the factors that affect individuals' attitudes and intentions to reduce food waste from a sustainability perspective by exploring external and intrinsic factors related to communication through the media context. It examines the effects of direct and indirect factors, mainly within the Theory of Planned Behaviour (TPB), Agenda-Setting Theory (AST) and Cultivation Theory (CT) in the literature. Additional factors based on the TPB, AST, and CT, Prospect Theory have also been discovered. A mixed-method design was used with qualitative studies (expert interviews followed by focus group discussions) to adjust and finalize the conceptual model, and then a quantitative study using questionnaires and experimental factor analysis (EFA), confirmatory factor analysis (CFA) and finally structural equation modelling (SEM) to test the proposed hypothesis. Findings show that media exposure (diversity) impacts sustainability consciousness and media impact, while media exposure (duration) has no significant effect on them. YouTube is an impactful medium to affect sustainability consciousness, which is, in turn, essential in influencing TPB variables in food waste attitude and intention. During media use, both claim specificity and the frame of a gain message function as distinct moderators, enhancing the relationship between sustainability consciousness and attitude toward food waste. On the other hand, autobiographic memory that is powered by childhood teachings to waste less has no significant effect on moderating the same relationship to foster the link between sustainability consciousness and attitude. Keywords: Communication campaigns, media, sustainability consciousness, food waste reduction attitude, intention, claim specificity, message frame, autobiographical memory, structural equation modelling, marketing communicatio
Exploring Isis’ Takfir Discourse: A BERT-Based Entity Level Sentiment Analysis Approach
No full textThe Islamic State of Iraq and Syria (ISIS) significantly influenced the lives of many people during and after the Syrian civil conflict, especially civilians. Analyzing social media discussions about ISIS can provide valuable insights into the group’s beliefs and attitudes. In this paper, we examine ISIS’s takfir discourse—their practice of labeling other Muslims as unbelievers to justify exclusion or violence—in Telegram groups. We collected 14,500 Telegram messages (2015–2017) using snowball sampling, API-based crawling, language filtering, and time-window selection. We then integrated a BERT-based Named Entity Recognition (NER) model with two layers of the Span ASTE (Aspect-Based Sentiment Analysis) model. We also used the Span ASTE as an end-to-end baseline for comparison. Based on Precision, Recall, and F1-scores, our hybrid model outperformed the baselines, demonstrating its effectiveness in sentiment analysis of extracted named entities. © 2025 Elsevier B.V., All rights reserved
Framework Genesis: A Novel Root Framework of Management Frameworks and Management System Standards
No full textBirbirinden farklı yönetim çerçevelerinin (YÇ), sistem standartlarının (YSS) ve kurumsal mimarilerin (KM) yaygınlaşması, operasyonel verimsizliklere, stratejik uyum eksikliğine ve kafa karıştırıcı bir 'Paradoks Sözlüğü'ne yol açan parçalanmış bir yapı oluşturmaktadır. Bu tez, organizasyonel yönetime birleştirme ve sistemik netlik getirmek üzere tasarlanmış yenilikçi bir kök çerçeve olan Framework Genesis'in (FG) geliştirilmesi ve keşifsel doğrulaması yoluyla bu kritik boşluğu ele almaktadır. Araştırmada, özel olarak geliştirilmiş yedi fazlı Geliştirilmiş Sezgisel Araştırma Yöntemi (EHRM) tarafından yönlendirilen bir tasarım bilimi yaklaşımı kullanılmıştır. Bu metodoloji, iki temel bileşenin geliştirilmesini sağlamıştır. Birincisi, mevcut YÇ'lerin ve YSS'lerin kapsamlı bir analizinden türetilen 48 temel bileşenden oluşan doğrulanmış bir taksonomi olan Bütünlüklü Yapı Taşı Taksonomisi (CBBT), ortak bir içerik sözlüğü sunmaktadır. İkincisi, sistemik bir meta-model olan Birleşik Mimari Çerçevesi (UAF), mimari yapıyı sağlamaktadır. Framework Genesis, bu bileşenleri entegre ederek organizasyonu, ideal bir mimari tasarım (EidosTwin) ve onun somut operasyonel gerçekliği (OusiaTwin) arasında felsefi temelli bir ikilik aracılığıyla kavramsallaştırmaktadır. Çerçeve ve amaca yönelik geliştirilmiş doğrulama araçları (FGMAPM, FGGIS, FGCMAM), kapsamlı ve karma yöntemli bir doğrulama stratejisine (FGVAL) tabi tutulmuştur. Bu strateji, mevcut standartlara karşı nicel bir boşluk analizi, 209 firmanın katıldığı bir olgunluk değerlendirme çalışması ve üç derinlemesine boylamsal vaka çalışmasını içermiştir. Bulgular, FG'nin kavramsal sağlamlığını teyit etmiş ve sistemik sorunları teşhis etme ile organizasyonel dönüşüme rehberlik etmedeki pratik faydasını göstermiş, müdahale sonrası olgunluk skorlarında ölçülebilir iyileşmeler ortaya koymuştur. Bu tez, yönetim çerçevesi teorisi için yeni bir mimari ve üretken paradigma sunmaktadır. Organizasyonların karmaşıklıkta yol bulmalarını, birbirinden farklı sistemleri entegre etmelerini ve daha fazla stratejik uyum elde etmelerini sağlayan, doğrulanmış ve bütünsel bir meta-çerçeve sağlamaktadır. Anahtar Sözcükler: yönetim çerçeveleri, yönetim sistemi standartları, Entegre Yönetim Sistemi, bilgide birlik teorisi, ISO standartları, yönetim sistemi, sistem teorisi, sistem düşüncesi, Bütünlüklü Yapı Taşı Taksonomisi, Bütünlüklü Kök Yönetim ÇerçevesiThe proliferation of disparate management frameworks (MFs), system standards (MSSs), and enterprise architectures (EAFs) creates a fragmented landscape, leading to operational inefficiencies, a lack of strategic coherence, and a confusing 'Vocabulary of Paradox.' This thesis addresses this critical gap through the development and exploratory validation of Framework Genesis (FG), a novel root framework designed to bring unification and systemic clarity to organisational management. The research employed a design science approach, guided by a bespoke seven-phase Enhanced Heuristic Research Method (EHRM). This methodology facilitated the development of two core components. First, the Consilient Building Block Taxonomy (CBBT), a validated taxonomy of 48 fundamental components derived from an extensive analysis of existing MFs and MSSs, provides a common content lexicon. Second, the Unified Architecture Framework (UAF), a systemic meta-model, provides the architectural structure. Framework Genesis integrates these components, conceptualising the organisation through a philosophically-grounded dualism of an ideal architectural blueprint (the EidosTwin) and its tangible operational reality (the OusiaTwin). The framework and its purpose-built validation instruments were subjected to a comprehensive, mixed-methods validation strategy (FGVAL). This included a quantitative gap analysis against existing standards, a maturity assessment with an empirical study (209 firms, and three case in-depth longitudinal case studies). The findings confirmed FG's conceptual soundness and demonstrated its practical utility in diagnosing systemic issues and guiding organisational transformation, showing measurable improvements in maturity scores post-intervention. This thesis contributes a new architectural, generative paradigm for management framework theory. It provides a validated, holistic meta-framework that enables organisations to navigate complexity, integrate disparate systems, and achieve greater strategic coherence. Keywords: management frameworks (MFs), management system standards (MSSs), Integrated Management System (IMS), consilience theory, ISO standards, management system (MS), systems theory, systems thinking, Consilient Building Block Taxonomy (CBBT), Consilient Root Management Framework (CRMF
Computational Assessment of Hemodynamics in Asymmetric-Type Lesion of Idealized Coronary Stenoses
No full textPurpose: Coronary artery stenosis, characterized by the narrowing of the arterial lumen, significantly alters blood flow and contributes to the progression of cardiovascular diseases. This study investigates the hemodynamic effects of different stenosis morphologies, all maintaining an 80% lumen reduction, to determine how variations in shape influence flow behavior and mechanical stresses. Methods: We employed computational fluid dynamics (CFD) to analyze five idealized stenosis geometries with the following asymmetric and symmetric configurations: C1 (10% and 70%), C2 (20% and 60%), C3 (30% and 50%), C4 (40% and 40%), and C5 (0% and 80%). Using physiological pulsatile flow conditions, we evaluated key hemodynamic parameters, including velocity profiles, wall shear stress, and pressure distribution. Results: Despite having the same degree of lumen reduction, each stenosis configuration produced distinct hemodynamic profiles. Asymmetric stenoses, particularly the C1 and C2 cases, exhibited pronounced flow disturbances, higher wall shear stress at the stenosis throat, and increased post-stenotic turbulence. In contrast, symmetric stenoses, such as C4, demonstrated more uniform flow and reduced vortex formation. These findings suggest that stenosis morphology plays a crucial role in determining local flow dynamics. Conclusion: Our findings challenge the common practice of generalizing results across stenosis configurations without considering morphological variations, which is prevalent in many CFD studies using idealized models. This study emphasizes the need for stenosis-specific assessments in CFD analyses and clinical interpretations to improve the accuracy of diagnostic tools, optimize personalized treatment strategies, and guide the design of medical devices such as stents. © The Author(s), under exclusive licence to The Brazilian Society of Biomedical Engineering 2025
Understanding Customer Conversations in Social Media Support Interactions: Divergent Sentiments in Material and Experiential Brands
No full textPurpose – This study aims to investigate how customer sentiments differ in social media interactions with customer support accounts of material and experiential brands. It seeks to understand the impact of these interactions on customer sentiment dynamics and their implications for customer support strategies. Design/methodology/approach – Drawing on experiential recommendation literature, this study employs a sentiment analysis approach to analyze 60, 000 tweets directed at customer support accounts of three experiential and three material brands on X (formerly known as Twitter). Regression analysis is also applied to investigate the influence of post characteristics and content types (e.g. emojis) on sentiment. Findings – Results reveal significant differences between material and experiential brands in both overall sentiment and sentiment evolution during customer support interactions. Conversations with experiential brands exhibit more positive overall sentiments; whereas interactions with material brands demonstrate a greater positive sentiment shift despite initially exhibiting more negative sentiments. The findings also show that tweet length is a strong predictor of customer sentiment. Originality/value – This research underscores the unique roles of material and experiential brands in shaping customer sentiment during social media interactions. The study provides novel insights into online customer support dynamics and offers actionable recommendations for improving after-sales management strategies in social media contexts. © 2025 Emerald Publishing Limite
The Dead Are Alive: The Exotic Non-Place of the Bondian Runaway Production
No full textThis chapter dissects the opening sequences of Skyfall (2012) in Istanbul and Spectre (2015) in Mexico City in order to argue that Eon’s predilection for runaway productions has begun began to influence the textual composition of the James Bond film series. Eon Productions often modifies the narratives and settings of its Bond features in order to exploit the increasingly global availability of funding schemes, tax incentives, and cheap labor, and to secure, on a global scale, profitable distribution deals, enhanced visibility, and greater revenues from merchandizing. In the process, the Bondian runaway production fashions a colonial imaginary of exotic non-places, which has since long been a staple of the brand of Bond. © The authors/Taylor & Francis Group 2020
Estimation of the Probability of Informed Trading Models Via an Expectation-Conditional Maximization Algorithm
No full textThe estimation of the probability of informed trading (PIN) model and its extensions poses significant challenges owing to various computational problems. To address these issues, we propose a novel estimation method called the expectation-conditional-maximization (ECM) algorithm, which can serve as an alternative to the existing methods for estimating PIN models. Our method provides optimal estimates for the original PIN model as well as two of its extensions: the multilayer PIN model and the adjusted PIN model, along with its restricted versions. Our results indicate that estimations using the ECM algorithm are generally faster, more accurate, and more memory-efficient than the standard methods used in the literature, making it a robust alternative. More importantly, the ECM algorithm is not limited to the models discussed and can be easily adapted to estimate future extensions of the PIN model. © The Author(s) 2025.Hakan Bugra Erentug; Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTAK, (122K637)Social Science Citation Inde
Splitout: Out-Of Training-Hijacking Detection in Split Learning Via Outlier Detection
No full textSplit learning enables efficient and privacy-aware training of a deep neural network by splitting a neural network so that the clients (data holders) compute the first layers and only share the intermediate output with the central compute-heavy server. This paradigm introduces a new attack medium in which the server has full control over what the client models learn, which has already been exploited to infer the private data of clients and to implement backdoors in the client models. Although previous work has shown that clients can successfully detect such training-hijacking attacks, the proposed methods rely on heuristics, require tuning of many hyperparameters, and do not fully utilize the clients' capabilities. In this work, we show that given modest assumptions regarding the clients' compute capabilities, an out-of-the-box outlier detection method can be used to detect existing training-hijacking attacks with almost-zero false positive rates. We conclude through experiments on different tasks that the simplicity of our approach we name SplitOut makes it a more viable and reliable alternative compared to the earlier detection methods.Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTAK, (119E088)Scientific and Technological Research Council of Turkey (TUBITAK) [119E088]We acknowledge the Scientific and Technological Research Council of Turkey (TUBITAK) project 119E088.Conference Proceedings Citation Index - Scienc