IYTE GCRIS Database (Izmir Institute of Technology)
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Investigation of Biomarkers Using Lipidome-Based Research Analysis in Sialidosis
No full textNeuraminidase 1, also known as N-acetyl-α-neuraminidase, is an enzyme found in lysosomes and encoded by the NEU1 gene. This enzyme is responsible for eliminating terminal sialic acids from glycoproteins and oligosaccharides. When mutations occur in the NEU1 gene, it leads to a particular lysosomal storage disorder known as sialidosis. Sialidosis is a rare genetic disorder that is inherited in an autosomal recessive manner. Sialidosis is classified into two subtypes: Type I, which has a later onset and Type II, which presents with early onset. In previous studies, an increase in glycolipid levels in visceral organs, and accumulation of sialyloligosaccharides and sialoglycoproteins were reported. However, the effect of NEU1 sialidase on secondary lipid expression levels in sialidosis pathology remains unknown. The relationship between lipid expression levels and inflammation of human and mice sialidosis fibroblasts cell lines was analyzed for the first time in this study. To understand the connection between secondary lipid alterations and inflammation in sialidosis molecular biological approaches and shotgun lipidome analysis were followed. The link between the secondary lipid alterations and its association with sialidosis was determined in our research. We have concluded that the findings not only provide the elucidation of the lipidome characteristics in sialidosis models of mice and patients, but they also have the potential to establish a connection between the lipidome features and the occurrence of neuroinflammation in sialidosis. Grasping the correlation between the changes in secondary lipids and inflammation may offer therapeutic strategies for sialidosis patients by modulating the expression of secondary lipids.N-asetil-a-nöraminidaz olarak da bilinen Neuraminidaz 1, lizozomlarda bulunan ve NEU1 geni tarafından kodlanan bir enzimdir. Bu enzim, terminal sialik asitlerin glikoproteinlerden ve oligosakaritlerden elimine edilmesinden sorumludur. NEU1 geninde mutasyonlar meydana geldiğinde, sialidoz olarak bilinen özel bir lizozomal depo bozukluğuna yol açar. Sialidoz, otozomal resesif bir şekilde kalıtsal olan nadir bir genetik hastalıktır. Sialidoz iki alt tipe ayrılır: Daha geç başlayan Tip I ve erken başlayan Tip II. Önceki çalışmalarda iç organlarda glikolipid düzeylerinde artış ve sialiloligosakkaritler ile siyaloglikoproteinlerin birikimi rapor edilmiştir. Ancak NEU1 sialidazın sialidoz patolojisinde sekonder lipid ekspresyon seviyeleri üzerindeki etkisi bilinmemektedir. İnsan ve fare sialidosis fibroblast hücre dizilerinin lipit ekspresyon düzeyleri ile inflamasyonu arasındaki ilişki ilk kez bu çalışmada analiz edildi. Sialidozda ikincil lipid değişiklikleri ile inflamasyon arasındaki bağlantıyı anlamak için moleküler biyolojik yaklaşımlar ve Shotgun Lipidome analizi takip edildi. Araştırmamızda sekonder lipid değişiklikleri ile sialidoz arasındaki ilişki belirlendi. Bulguların, fare ve hastaların sialidoz modellerinde lipidom özelliklerinin aydınlatılmasının yanı sıra, lipidom özellikleri ile sialidozda nöroinflamasyon oluşumu arasında bağlantı kurma potansiyeline sahip olduğu sonucuna vardık. Sekonder lipitlerdeki değişiklikler ile inflamasyon arasındaki korelasyonun anlaşılması, sekonder lipitlerin ekspresyonunu modüle ederek sialidoz hastaları için terapötik stratejiler sunabilir
Soil Contamination by Metals/Metalloids Around an Industrial Region and Associated Human Health Risk Assessment
No full textIndustrial, agricultural, transportation, and waste management activities cause soil contamination by metals/metalloids. Soil contamination is an essential global concern since it poses a significant risk to human health. Particularly in areas near heavy industry, people are more prone to exposure. This study aims to determine current metal/metalloid contamination levels in soil from Aliağa industrial region and assess associated health risks. Five surface soil samples were collected from the region, representing residential, agricultural areas, and downwind of possible sources. Pollution indices were calculated to determine the metal(loid)s with anthropogenic inputs, and a human health risk assessment was conducted. As a result, significant to extreme enrichment of arsenic (As), moderate to significant enrichment of zinc (Zn) and manganese (Mn), and very high enrichment of lead (Pb) and cadmium (Cd) were observed in soil samples. Possible sources of contamination were iron and steel facilities with electric arc furnaces and oil combustion. Non-carcinogenic risk assessment revealed acceptable risks of exposure to Aliağa soils, while exposure scenarios had a great impact on estimated risks. Arsenic, chromium (Cr), and Pb appeared to be significant contributors to non-carcinogenic risk. Carcinogenic risks associated with exposure to As, Pb, Cr, cobalt (Co), and Cd in soils were evaluated to be at an acceptable level. This study only considered soil exposure pathways; hence, a comprehensive risk assessment is deemed necessary not to underestimate the risk of living around an industrial region. Nevertheless, the study provided crucial information for the current hot spots for metal(loid)s in the region and human exposure level
Epitranscriptomics M6a Analyses Reveal Distinct M6a Marks Under Tumor Necrosis Factor Α (tnf-Α) Apoptotic Conditions in Hela Cells
No full textTumor necrosis factor-alpha (TNF-alpha) is a ligand that induces both intrinsic and extrinsic apoptotic pathways in HeLa cells by modulating complex gene regulatory mechanisms. However, the full spectrum of TNF-alpha-modulated epitranscriptomic m(6)A marks is unknown. We employed a genomewide approach to examine the extent of m(6)A RNA modifications under TNF-alpha-modulated apoptotic conditions in HeLa cells. miCLIP-seq analyses revealed a plethora of m(6)A marks on 632 target mRNAs with an enrichment on 99 mRNAs associated with apoptosis. Interestingly, the m(6)A RNA modification patterns were quite different under cisplatin- and TNF-alpha-mediated apoptotic conditions. We then examined the abundance and translational efficiencies of several mRNAs under METTL3 knockdown and/or TNF-alpha treatment conditions. Our analyses showed changes in the translational efficiency of TP53INP1 mRNA based on the polysome profile analyses. Additionally, TP53INP1 protein amount was modulated by METTL3 knockdown upon TNF-alpha treatment but not CP treatment, suggesting the existence of a pathway-specific METTL3-TP53INP1 axis. Congruently, METLL3 knockdown sensitized HeLa cells to TNF-alpha-mediated apoptosis, which was also validated in a zebrafish larval xenograft model. These results suggest that apoptotic pathway-specific m(6)A methylation marks exist in cells and TNF-alpha-METTL3-TP53INP1 axis modulates TNF-alpha-mediated apoptosis in HeLa cells
Development of 3d Tumor Models for Investigating Drug Efficacy of Sapogenol Derivatives
No full textSon dönemin hastalığı olan kanser tedavisi çalışmalarında potansiyel ilaçların etkinliklerinin araştırılması için doku fizyolojisine yüksek benzerlik gösteren 3 boyutlu (3B) hücre kültürü modelleri dikkat çekmektedir. Bu modeller 2B hücre kültürü çalışmalarındaki birçok problemin aşılmasını sağlayarak ilaç geliştirme çalışmalarında tercih edilmektedir. Bu çalışmada yeni nesil manyetik levitasyon (MagLev) kullanılarak üretilmiş 3B tümör sferoid modelleri üzerinde sapogenol türevi potansiyel kanser ilaçları ve FDA onaylı antikanser ilacı Paklitaksel'in (Ptx) ilaç aktivite taramaları yapılmıştır. Manyetik levitasyon yöntemi doku iskelesinden bağımsız olup, iki mıknatıs tarafından yaratılmış manyetik alan içerisinde paramanyetik ajanların etkisiyle manyetize edilmiş hücrelerin yoğunlarına bağlı olarak kendilerine has bir yükseklikte (levitasyon yüksekliği) harici bir kuvvet gerektirmeden asılı kalmalarını sağlamaktadır. Bu yöntemle, levitasyon yükseklikleri aynı seviyede olan hücreler arası etkileşimler artarak 3B sferoid yapıları doku iskelesine ihtiyaç duyulmadan hızlıca elde edilebilmektedir. Tamamlanan çalışmada; tümör sferoid modelleri her hücre hattı için ayrı şekilde elde edilmiştir. MagLev yöntemine ek, kontrol amaçlı, aynı hücre hatlarıyla asılı damlacık yöntemi kullanılarak 3B sferoid modelleri elde edilmiştir. Oluşturulan sferoid modelleri üzerinde 2B hücre kültüründe ilaç etkinliği belirlenmiş sapogenol türevi ilaç moleküllerinin ve Ptx'in aktivitesi araştırılmıştır. Sferoid modelleri üzerinde beklenen toksik etki görülmüş, karşılaştırmalı sonuçlar paylaşılmıştır. Bu sonuçlarla birlikte, 2B hücre kültürü kullanılarak yapılan tümör fizyolojisi araştırmaları yerine bu modellerin dezavantajlarını geride bırakan, gerçek tümör fizyolojisini çok daha yakın seviyede taklit edebilen, klinik araştırmalar öncesinde ilaç taramalarında ve farklı moleküllerin etkilerinin araştırılmışında kolay, gerçekçi ve hızlı sonuçlar sağlayabilecek manyetik levitasyon temelli yeni bir ilaç aktivite tarama modeli geliştirilmiştirIn studies on the treatment of cancer, which is a common disease of the latest period, 3D cell culture models, which show high similarity to tissue physiology, attract attention in order to investigate the efficacy of potential drugs. These models are preferred in drug development studies by overcoming many problems in 2D cell culture studies. In the completed research, drug activity screenings of sapogenol-derived molecules and anticancer drug Ptx were performed on 3D tumor spheroid models produced using new generation magnetic levitation (MagLev) technology. The magnetic levitation is a scaffold free methodology which allows the cells magnetized by the effect of paramagnetic agents in the magnetic field created by two magnets to balance at a unique height (levitation height) depending on density, without requiring an external force. With this method, intercellular interactions with the same level of levitation heights can be increased and 3D spheroid structures can be obtained quickly without the need any scaffold. In the completed thesis; As a control group for MagLev spheroids, hanging drop methodology was preferred with the same cell lines. The activity of sapogenol-derived molecules and the Ptx were investigated. The expected toxic effect on spheroids was observed and comparative results were shared. MagLev based new drug activity screening model which overcomes the disadvantages of 2D cell culture studies, can imitate real tumor physiology much more closely, can provide easy, realistic and fast results in drug screenings and investigating the effects of different molecules before clinical studies has been devoloped
A Numerical Method Based on Legendre Wavelet and Quasilinearization Technique for Fractional Lane-Emden Type Equations
No full textIn this research, we study the numerical solution of fractional Lane-Emden type equations, which emerge mainly in astrophysics applications. We propose a numerical approach making use of Legendre wavelets and the quasilinearization technique. The nonlinear term in fractional Lane-Emden type equations is iteratively linearized using the quasilinearization technique. The linearized equations are then solved using the Legendre wavelet collocation method. The proposed method is quite effective to overcome the singularity in fractional Lane-Emden type equations. Convergence and error analysis of the proposed method are given. We solve some test problems to compare the effectiveness of the proposed method with some other numerical methods in the literature. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature
Optimization of Ir Reflective Automotive Topcoat Formulations To Reduce Vehicle Cooling Load by Using Design of Experiment
No full textBu tez kapsamında, kızılötesi yansıtıcı inorganik pigmentlerin akrilik ortamdaki dispersiyonları oluşturulmuştur. RAL 9010, RAL 7021 ve RAL 9011 renklerine yönelik renk eşleştirme çalışmaları, IR yansıtıcı pigmentlerle tasarlanan renk pastaları kullanılarak yapıldı. RAL 9010, 7021 ve 9011 renkleri için geleneksel pigmentlerle ve IR yansıtıcı inovatif pigmentlerle tasarlanmış formüllerin kızılötesi bölgede yansıtma kabiliyetleri karşılaştırılmış ve IR yansıtıcı pigmentlerin performansının iyi olduğu sıcaklık testi ile belirlenmiştir. Daha sonra IR yansıtıcı pigmentlerle tasarlanan formüllerin optimizasyon çalışmaları ele alınmıştır. Tasarlanan renk formüllerinde ön çalışmalar yapılarak, parametre olarak pigmentasyon ve kuru film kalınlığı; response olarak ise sıcaklık testi ve rub-out testi belirlenmiştir. Her renk için belirlenen matrislere göre panel uygulamaları yapılmıştır. Belirtilen formüllerle boya uygulanan paneller için sıcaklık test düzeneği oluşturularak analizleri yapılmıştır. Formülasyonların stabilite kontrolleri için rub-out testi yapılmıştır. Deney tasarımı matrisi, deneysel tasarım koşullarına uygun olacak şekilde hazırlanmıştır. Yapılan çalışmalar sonucu toplanan veriler Minitab 16 yazılımında deneysel tasarım yöntemi ile anliz edilmiştir. Yapılan çalışmalar sonucunda pigmentasyon ve kuru film kalınlığı olarak belirlenen parametrelerin response üzerindeki etkileri incelenmiştir. Kurulan modellemelerin performansı detaylı olarak incelenmiş olup ve elde edilen modellerin başarılı olduğu görülmüştür. Geleneksel pigmentlere göre kızılötesi bölgede daha iyi yansıtma performansı gösteren IR yansıtıcı pigmentlerin kullanıldığı formüller bu tez kapsamında optimize edilmiştir.This thesis involved creating dispersions of infrared-reflective inorganic pigments in acrylic medium. Color matching studies for RAL 9010, RAL 7021, and RAL 9011 colors were carried out using color pastes designed with IR-reflective pigments. For RAL 9010, 7021, and 9011 colors, the reflection abilities of formulas designed with traditional pigments and IR reflective innovative pigments in the infrared region were compared, and it was determined by the temperature test. Through a temperature test, it was established that the performance of the IR reflective pigments was satisfactory. Next, the discussion focused on optimization studies of the formulations that were designed using IR-reflective pigments. Preliminary studies were carried out on the designed color formulas, and pigmentation and dry film thickness were determined as parameters, and a temperature test and a rub-out test were determined as responses. Panel applications were made according to the matrices determined for each color. A temperature test apparatus was created and analysed for the panels on which paint was applied with the specified formulas. A rub-out test was performed for stability control of the formulations. The experimental design matrix was prepared to comply with the experimental design conditions. The data collected as a result of the studies was analysed using the experimental design method in Minitab 16 software. The studies examined the effects of determined parameters, such as pigmentation and dry film thickness, on the response. The performance of the established models was examined in detail and was found to be quite successful. Formulas using IR-reflective pigments, which show better reflecting performance in the infrared region compared to traditional pigments, have been optimized
The Future of Regional Inequalities: an Arima Forecast
No full textThe existing stream of empirical literature on regional inequalities has always adopted a retrospective look by analyzing the past evolution. We depart from the main stream by adopting a future perspective: Will regional inequalities shrink over time? How will the shape of income distribution evolve? Will spatial dependency increase? In the current paper, we forecast the long-term trajectory of per capita real personal income for U.S. states using the ARIMA model. We estimate the future of disparity level (for 2050 and 2090), the shape and spatial pattern of income distribution, convergence trend and spatial dependence by the help of inequality indexes (Atkinson, Coefficient of Variation, Theil) Kernel probability density distributions, explorative maps and Moran's I test. The dataset includes 48 coterminous U.S. states over the period 1929-2022. A set of important results appeared to emerge as an outcome of the empirical analyses: First, income disparities are expected to increase over the long-term period that implies a divergence pattern. Second, the forecasted shape of the income distribution is bi-modal and polarized, therefore, pointing to a widening of the inequalities. Third, the geography of the prosperity is projected to change in a way that the geographical position of high and low-income areas will change. Fourth, spatial dependence in per capita income is expected to fade away in the future. From a political stand point, additional resources should be devoted to the states that are expected to become backward (for some states in Northeast and Southwest) in order to maintain territorial cohesion
The Effect of Structural Retrofitting and Ventilation Scenarios on the Indoor Microclimate of a Historical Library: The Necip Pasa Library, Turkiye
No full textStructural retrofitting in buildings may result in changes in the indoor microclimate. Chemical, mechanical and biological deterioration can be seen in the cultural properties as a consequence of substrates and inappropriate microclimatic conditions such as high indoor temperature, relative humidity and fluctuations of them. The primary aim of the study is to evaluate the effect of the structural retrofitting, that the building underwent, on the chemical degradation risk of the library collection based on two different ventilation scenarios. One is natural ventilation which is an existing situation since the building is free-floating. The other one implementing a mechanical ventilation system into the building. To be able to compare the microclimate that affects the library collection pre- and post-retrofitting, two models are developed in DesginBuilder and simulated for both scenarios. According to the results of the post-retrofitting model, mechanical ventilation reduced the risk of chemical degradation by 38 %, while natural ventilation did not cause any effect. Natural ventilation gives a similar output in the pre-retrofitting model as in the post-retrofitting model. Mechanical ventilation in the pre-retrofitting model achieves a 33 % reduction in chemical degradation risk. Structural retrofitting only achieves a 1 % reduction in the chemical risk level for both ventilation scenarios. Thus, its effect on the indoor microclimate is insignificant. This study shows that creating simulation models effectively assesses potential risks pre-post-structural retrofitting or any retrofitting in historical buildings. Simulations reveal that mechanical ventilation is a better choice for decreasing chemical degradation risks for the library. © 2024 Elsevier Lt
Bioavailability Assessment of the Novel Gsh-Functionalized Feb Nanoparticles Via Oxidative Stress and Trace Element Metabolism in Vitro: Promising Tools for Biomedical Applications
No full textIron-based magnetic nanoparticles (NPs) have attracted significant attention in biomedical research, particularly for applications such as cancer detection and therapy, targeted drug delivery, magnetic resonance imaging (MRI), and hyperthermia. This study focuses on the synthesis and glutathione (GSH) functionalization of iron boride (FeB) nanoparticles (NPs) for prospective biomedical use. The GSH-functionalized FeB NPs (FeB@GSH) demonstrated ferromagnetic behavior, with a saturation magnetization (Ms) of 45.8 emu/g and low coercivity (Hc = 1000 Oe), indicating desirable magnetic properties for biomedical applications. Transmission electron microscopy (TEM) analysis of the FeB@GSH revealed well-dispersed nanoparticles with diameters smaller than 30 nm. Comprehensive nanotoxicity and biocompatibility assessments were performed using various healthy and cancer cell lines, including 293 T, HeLa, 3T3, MCF7, HCT116, and CFPAC-1. Cytotoxicity assays were conducted on FeB@GSH-treated cells over a dose range of 0-300 mu g/mL during 24-h incubations. Results indicated no significant differences in cell viability between treated and untreated control groups, confirming the biocompatibility of FeB@GSH. Further nanotoxicity evaluations were carried out on 3T3, 293 T, and CFPAC-1 cell lines, focusing on oxidative stress markers and cellular metabolism by measuring antioxidant enzyme activity. Additionally, ion release and mineral metabolism were assessed using inductively coupled plasma mass spectrometry (ICP-MS), revealing no notable variations between the treated and control groups. These findings suggest that FeB@GSH NPs exhibit excellent biocompatibility, making them promising candidates for diverse biomedical applications, including medical imaging, drug delivery systems, and therapeutic interventions
Local Citation Recommendation With Graph Convolutional Networks
No full textLocal Citation Recommendation is a task that finds the missing reference in the corresponding citation placeholder. It is mainly contextual since context identifies the citation. On the other hand, a context can be a descriptor for a set of papers. In other words, there can be more than one candidate citation for a context. Thus, a further matching of a context with candidate papers is beneficial. Titles and abstracts of candidate papers serve as a global context to match with the local one. This work proposes a state-of-the-art approach for the Local Citation Recommendation task that exploits the similarities between global and local contexts to generate citation predictions. By utilizing a Graph Convolutional Network (GCN) with BERT embeddings, our proposed model demonstrates superior performance over previous methods. It not only outperforms all prior approaches on the benchmark datasets of ACL-200, FullTextPeerRead, RefSeer, and arXiv but also strikes a balance between speed, memory, and computational requirements. Once deployed as a production-level Local Citation Recommendation, it is fast enough to enable real-time recommendations for researchers.Yerel atıf önerisi, ilgili atıf yer tutucusundaki eksik referansı bulma görevidir. Temel olarak bağlamsal olduğundan, bağlam atıfı yansıtır. Öte yandan, bir bağlam bir dizi makale için bir tanımlayıcı olabilir. Başka bir deyişle, bir bağlam için birden fazla atıf adayı olabilir. Bu nedenle, bir bağlamın aday makalelerle daha fazla eşleşmesi faydalıdır. Aday makalelerin başlıkları ve özetleri, küresel bir bağlam oluşturur ve yerel olanla eşleşmek için kullanılır. Bu çalışma, küresel ve yerel bağlamlar arasındaki benzerlikleri kullanarak atıf tahminleri üretmek için son teknoloji bir yaklaşım önermektedir. BERT özelliklerini Grafik Evrişimsel Ağlara gömerek kullanan modelimiz, önceki yöntemlere göre üstün performans sergilemektedir. ACL-200, FullTextPeerRead, RefSeer ve arXiv veri kümelerinde tüm önceki yaklaşımları aşmakla kalmaz, aynı zamanda hız, bellek ve hesaplama gereksinimleri arasında bir denge kurar. Bu yaklaşım bir ürün olarak son kullanıcıya sunulduğunda, araştırmacılar için gerçek zamanlı önerileri mümkün kılar