PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Thermal Stresses in SOFC Stacks: The Role of Mismatch Among Thermal Conductivity of Adjacent Components(Tubitak Scientific & Technological Research Council Turkey, 2021-06-30) Aydin, Ozgur; Matsumoto, Go; Shiratori, YusukeGenerating power from renewable biogas in solid oxide fuel cells (SOFCs) is an environment-friendly, efficient, and promising energy conversion process. Biogas can be used in SOFCs via a reforming process for which dry reforming is more suitable as the reforming agent exists in the biogas mixture. Biogas can be directly reformed to H-2 -rich fuel stream in the anode chamber of a SOFC by the heat released during power generation. Exploiting the heat and water produced in the SOFC for internal reforming of biogas makes the energy conversion process very efficient; however, various challenges are reported. Thus, indirect internal reforming is opted for which a separate reforming domain is required. In an indirect internal reformer operating at usual conditions, dry reforming rate is quite high in the inlet and it decreases steeply toward the fuel outlet. Great temperature gradients develop over the reformer, since the dry reforming reaction is strongly endothermic. The abruptly varying rate of the reforming reaction affects the temperature fields in the adjacent components of SOFC and hence intolerable thermal stresses emerge on the SOFC components. In our preceding study, we graded the reforming domain, homogenized the temperature profile over the reforming domain, and executed performance and durability experiments. However, most of the experiments failed due to fracturing SOFC components hinting at existence of thermal stresses. In that study, we focused on minimizing the temperature gradients within the reforming domain; namely, we neglected the other processes. To eliminate the thermal stresses, we modeled the entire module of SOFC equipped with a reformer featuring a graded reforming domain. We found that the mismatch between the thermal conductivities of the adjacent module components is the major reason for the thermal stresses. When the mismatch is eliminated, thermal stresses disappear even if the reforming domain is not graded.Article Citation - WoS: 6Citation - Scopus: 7Therapeutic Potential of Nitrogen-Substituted Oleanolic Acid Derivatives in Neuroinflammatory and Cytokine Pathways: Insights From Cell-Based and Computational Models(Wiley-VCH Verlag GmbH, 2025-04-22) Turgut, Gurbet Celik; Pepe, Nihan Aktas; Ekiz, Yagmur Ceylan; Senol, Halil; Sen, AlaattinThis study was conducted to investigate the mechanism of the potential and anti-inflammatory properties of nitrogen-substituted oleanolic acid derivatives that can be used to treat neuroinflammatory diseases. Nitrogen-containing oleanolic acid derivatives have been evaluated for their anti-neuroinflammatory effects in vitro in neuronal and monocytic cell lines at nontoxic doses, and the production of cytokines (TNF-alpha, IL-6 and IL-17), the inflammatory enzyme induced nitric oxide synthase (iNOS) and NF-kappa B signalling under LPS-stimulated conditions, and the expression of genes associated with Alzheimer's disease have been assessed. In addition, molecular docking and molecular dynamics simulation assessments are conducted in silico. Key protein markers of neurodegenerative diseases, especially Alzheimer's disease and neuroinflammation, TAU protein levels, and microglial activation, as well as ionised calcium-binding adaptor protein-1 (IBA1) levels, were significantly reduced with the addition of oleanolic acid derivatives. LPS-induced NF-kappa B luciferase reporter activity and iNOS activity were significantly inhibited, approaching the levels in uninduced controls. The mRNA expression of proinflammatory cytokines critical for neuroinflammation, such as TNF-alpha, NF-kappa B, IL-6 and IL-17, was reduced twofold to sevenfold. Furthermore, the molecular docking and MD simulation analyses revealed potential interactions with the TNF-alpha and NF-kappa B proteins. These findings underscore the potential of oleanolic acid derivatives, particularly compound 16, as candidates for further development as therapeutic agents for neurodegenerative diseases associated with chronic inflammation.Article Citation - WoS: 9Citation - Scopus: 13The Impact and Future of Artificial Intelligence in Medical Genetics and Molecular Medicine: An Ongoing Revolution(Springer Heidelberg, 2024-08) Ozcelik, Firat; Dundar, Mehmet Sait; Yildirim, A. Baki; Henehan, Gary; Vicente, Oscar; Sanchez-Alcazar, Jose A.; Dundar, MunisArtificial intelligence (AI) platforms have emerged as pivotal tools in genetics and molecular medicine, as in many other fields. The growth in patient data, identification of new diseases and phenotypes, discovery of new intracellular pathways, availability of greater sets of omics data, and the need to continuously analyse them have led to the development of new AI platforms. AI continues to weave its way into the fabric of genetics with the potential to unlock new discoveries and enhance patient care. This technology is setting the stage for breakthroughs across various domains, including dysmorphology, rare hereditary diseases, cancers, clinical microbiomics, the investigation of zoonotic diseases, omics studies in all medical disciplines. AI's role in facilitating a deeper understanding of these areas heralds a new era of personalised medicine, where treatments and diagnoses are tailored to the individual's molecular features, offering a more precise approach to combating genetic or acquired disorders. The significance of these AI platforms is growing as they assist healthcare professionals in the diagnostic and treatment processes, marking a pivotal shift towards more informed, efficient, and effective medical practice. In this review, we will explore the range of AI tools available and show how they have become vital in various sectors of genomic research supporting clinical decisions.Article Citation - WoS: 3Citation - Scopus: 4Prediction of Biomechanical Properties of Ex Vivo Human Femoral Cortical Bone Using Raman Spectroscopy and Machine Learning Algorithms(Elsevier, 2025-09) Unal, Mustafa; Unlu, Ramazan; Uppuganti, Sasidhar; Nyman, Jeffry S.This study applied Raman spectroscopy (RS) to ex vivo human cadaveric femoral mid-diaphysis cortical bone specimens (n = 118 donors; age range 21-101 years) to predict fracture toughness properties via machine learning (ML) models. Spectral features, together with demographic variables (age, sex) and structural parameters (cortical porosity, volumetric bone mineral density), were fed into support vector regression (SVR), extreme tree regression (ETR), extreme gradient boosting (XGB), and ensemble models to predict fracture-toughness metrics such as crack-initiation toughness (Kinit) and energy-to-fracture (J-integral). Feature selection was based on Raman-derived mineral and organic matrix parameters, such as nu 1Phosphate (PO4)/CH2-wag, nu 1PO4/ Amide I, and others, to capture the complex composition of bone. Our results indicate that ensemble models consistently outperformed individual models, with the best performance for crack initiation toughness (Kinit) prediction being achieved using the ensemble approach. This yielded a coefficient of determination (R2) of 0.623, root-mean squared error (RMSE) of 1.320, mean absolute error (MAE) of 1.015, and mean percentage absolute error (MAPE) of 0.134. For prediction of the overall energy to propagate a crack (J-integral), the XGB model achieved an R2 of 0.737, RMSE of 2.634, MAE of 2.283, and MAPE of 0.240. This study highlights the importance of incorporating mineral quality properties (MP) and organic matrix properties (OMP) for enhanced prediction accuracy. This work represents the first-ever study combining Raman spectroscopy with other clinical and structural features to predict fracture toughness of human cortical bone, demonstrating the potential of artificial intelligence (AI) and ML in advancing bone research. Future studies could focus on larger datasets and more advanced modeling techniques to further improve predictive capabilities.Article Citation - Scopus: 1Possible Drug-Drug Interactions Between Mesalamine and Tricyclic Antidepressants Through CYP2D6 Metabolism - in Silico and in Vitro Analyses(Georg Thieme Verlag, 2025-04-01) Ozen, Melek B.; Gazioğlu, Işil; Ozgun-Acar, Özden; Guner, Hüseyin; Semiz, Gürkan; Sen, Alaattin; Ozgun Acar, OzdenMesalamine (mesalazine, 5-aminosalicylic acid, 5-ASA) is an essential anti-inflammatory agent both used for therapy and as a remission control in patients with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). Tricyclic antidepressants (TCAs) are used to alleviate remaining symptoms in patients already receiving IBD therapy or with quiescent inflammation. The cytochrome P4502D6 enzyme is involved in the metabolism of TCAs. Hence, it is crucial to investigate the role of CYP2D6 in 5-ASA metabolism. Initially, in silico analysis involving the docking of 5-ASA to CYP2D6 and molecular dynamics simulations was conducted. Next, the rate of O-demethylation of a nonfluorescent probe 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin (AMMC) into a fluorescent metabolite AMHC (3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) was optimized with baculosomes co-expressing human CYP2D6 and human P450 oxidoreductase (hCPR) to monitor CYP2D6 activity in a microtiter plate assay. The apparent Km and Vmax were found to be 1.30 μM and 32.68 pmol/min/mg of protein for the O-demethylation of AMMC to AMHC, and the reaction was linear for 40 min. Then, nonselective inhibition of CYP2D6 activity with various concentrations of 5-ASA was detected. Finally, the conversion of AMMC to metabolites was analyzed by HPLC-ESI-MS/MS spectrometry, and none were identified. Thus, this study suggests that concurrent use of mesalamine with TCA may lead to adverse effects, and CYP2D6 genotyping should be routinely performed on these patients to eliminate possible threats. © 2025 Elsevier B.V., All rights reserved.Article Citation - WoS: 21Citation - Scopus: 21Polyethylenimine Modified and Non-Modified Polymeric Micelles Used for Nasal Administration of Carvedilol(Amer Scientific Publishers, 2015-05-01) Kahraman, Emine; Karagoz, Ayse; Dincer, Sevil; Ozsoy, YildizThis study evaluates the ability of polyethylenimine-modified and non-modified polymeric micelles to enhance permeation through the nasal mucosa for a highly hydrophobic model drug. Carvedilol was loaded into polyethylenimine-modified and non-modified micelles by direct dissolution. Formulations were characterised by critical micelle concentration, micelle particle size and distribution, zeta potential, morphological structure and entrapment efficiency. The drug entrapment efficiency was determined to be as high as 77.14%, while micelle particle sizes and zeta potentials were within the range of 140.0-279.9 nm and (-40.6)-(+25.9) mV, respectively. In vitro studies showed 100% release of carvedilol from micelles in 120 hours. Ex vivo permeation studies showed that the drug in polyethylenimine non-modified micelles passed more efficiently than the drug in polyethylenimine modified micelles. These results demonstrated that polyethylenimine modified micelles did not significantly affect the permeation of the drug when compared to polyethylenimine non-modified micelles. On the contrary, the drug in poly(L-lactide)-block-methoxy poly(ethylene glycol) 5000 micelles, the polyethylenimine non-modified micelles, showed the highest permeation rate through bovine nasal mucosa. In conclusion, poly(L-lactide)-block-methoxy poly(ethylene glycol) 5000 polymeric micelles maybe useful as novel drug carriers that increase the permeation through the nasal mucosa.Article Citation - WoS: 4Citation - Scopus: 5Novel Insights Into Bacillus Thuringiensis: Beyond Its Role as a Bioinsecticide(Elsevier, 2025-03) Jouzani, Gholamreza Salehi; Sharafi, Reza; Argentel-Martinez, Leandris; Penuelas-Rubio, Ofelda; Ozkan, Ceyda; Incegul, Bengisu; Azizoglu, Ugur; Salehi Jouzani, GholamrezaThis review explores the diverse applications of Bacillus thuringiensis (Bt) beyond its traditional role as a bioinsecticide. Bt produces a variety of compounds with distinct chemical structures and biological activities. These include antimicrobial agents effective against plant pathogens and bioactive compounds that promote plant growth through the production of siderophores, hormones, and enzymes. Additionally, Bt's industrial potential is highlighted, encompassing biofuel production, bioplastics, nanoparticle synthesis, food preservation, anticancer therapies, and heavy metal bioremediation. This critical analysis emphasizes recent advancements and applications, providing insights into Bt's role in sustainable agriculture, biotechnology, and environmental management.Article Citation - WoS: 2Citation - Scopus: 2Membrane Binding and Lipid-Protein Interaction of the C2 Domain From Coagulation Factor V(Elsevier, 2024) Ohkubo, Y. Zenmei; Radulovic, Peter W.; Kahira, Albert N.; Madsen, Jesper J.Anchoring of coagulation factors to anionic regions of the membrane involves the C2 domain as a key player. The rate of enzymatic reactions of the coagulation factors is increased by several orders of magnitude upon membrane binding. However, the precise mechanisms behind the rate acceleration remain unclear, primarily because of a lack of understanding of the conformational dynamics of the C2-containing factors and corresponding complexes. We elucidate the membrane-bound form of the C2 domain from human coagulation factor V (FV-C2) by characterizing its membrane binding the specific lipid -protein interactions. Employing all-atom molecular dynamics simulations and leveraging the highly mobile membrane-mimetic (HMMM) model, we observed spontaneous binding of FV-C2 to a phosphatidylserine (PS)-containing membrane within 2-25 ns across twelve independent simulations. FV-C2 interacted with the membrane through three loops (spikes 1-3), achieving a converged, stable orientation. Multiple HMMM trajectories of the spontaneous membrane binding provided extensive sampling and ample data to examine the membrane-induced effects on the conformational dynamics of C2 as well as specific lipid -protein interactions. Despite existing crystal structures representing presumed "open" and "closed" states of FV-C2, our results revealed a continuous distribution of structures between these states, with the most populated structures differing from both "open" and "closed" states observed in crystal environments. Lastly, we characterized a putative PS-specific binding site formed by K23, Q48, and S78 located in the groove enclosed by spikes 1-3 (PS-specificity pocket), suggesting a different orientation of a bound headgroup moiety compared to previous proposals based upon analysis of static crystal structures.Article Citation - WoS: 5Citation - Scopus: 5Linear Variable Optical Attenuators With Shaped-Finger Comb-Drive Actuators(Optical Soc Amer, 2020-01-06) Hah, DooyoungA design method is proposed for variable optical attenuators (VOAs), aiming at linear attenuation-voltage characteristics, and verified by finite element analysis. Devices of interest are planar VOAs based on microelectromechanical systems technology, with either a knife-edge shutter or a reflector. The proposed method calculates the shape of the fingers of the comb-drive actuators that are used to move the optical component (shutter or reflector) to change the attenuation level. The calculation is, in effect, tantamount to solving a differential equation that encompasses the optical model of the device, electromechanical behavior of the actuators, and the objective of the design, i.e., linear attenuation-voltage characteristics. The design method is almost all-analytical with minimum usage of numerical analysis. The obtained designs are further examined by three-dimensional finite element analysis to understand their effectiveness and to probe the validity of the approximations used. The best linearity factor (defined as % deviation from the ideal case) obtained is 1.34% for both shutter- and reflection-type devices when the conditions are set as 1-dB insertion loss and 50-dB maximum attenuation. (C) 2020 Optical Society of AmericaArticle Identification of Nonsense Variants in the ATM Gene Mimicking SCID Phenotype: A Brief Report(Springer, 2025-05-16) Firtina, Sinem; Saritas, Merve; Ng, Yuk Yin; Nepesov, Serdar; Kiykim, Ayca; Bozkurt, Selcen; Sayitoglu, MugeSevere combined immunodeficiency (SCID) represents a life-threatening inborn error of immunity, necessitating rapid diagnosis and intervention to prevent fatal outcomes. While SCID is characterized by profound T-cell lymphopenia, it may overlap with other conditions like ataxia-telangiectasia (AT), which also presents with T-cell deficiencies. This study examines two cases of suspected SCID in infants, later identified as AT due to pathogenic variants in the ATM gene. Despite initial negative results from SCID-targeted gene panels, further genetic testing revealed nonsense mutations (p.Y2036X and p.E1996X) in the FAT domain of the ATM gene, confirmed by Sanger sequencing. The patients exhibited significant T-cell lymphopenia and reduced ATM protein activity, indicative of AT. These findings highlight the importance of comprehensive genetic screening beyond common SCID-associated genes, especially in patients with atypical presentations. Early and accurate diagnosis can prevent mismanagement and guide appropriate therapies, improving patient outcomes.