Biyomühendislik / Bioengineering
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Article Computational Prediction of Functional MicroRNA-mRNA Interactions(HUMANA PRESS INC, 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA, 01.01.2019) Demirci, Muserref Duygu Sacar; Yousef, Malik; Allmer, Jens; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüProteins have a strong influence on the phenotype and their aberrant expression leads to diseases. MicroRNAs (miRNAs) are short RNA sequences which posttranscriptionally regulate protein expression. This regulation is driven by miRNAs acting as recognition sequences for their target mRNAs within a larger regulatory machinery. A miRNA can have many target mRNAs and an mRNA can be targeted by many miRNAs which makes it difficult to experimentally discover all miRNA-mRNA interactions. Therefore, computational methods have been developed for miRNA detection and miRNA target prediction. An abundance of available computational tools makes selection difficult. Additionally, interactions are not currently the focus of investigation although they more accurately define the regulation than pre-miRNA detection or target prediction could perform alone. We define an interaction including the miRNA source and the mRNA target. We present computational methods allowing the investigation of these interactions as well as how they can be used to extend regulatory pathways. Finally, we present a list of points that should be taken into account when investigating miRNA-mRNA interactions. In the future, this may lead to better understanding of functional interactions which may pave the way for disease marker discovery and design of miRNA-based drugs.Article RAFT-mediated synthesis of poly(N-(2-hydroxypropyl)methacrylamide-b-4-vinylpyridine) by conventional and microwave heating(SPRINGERONE NEW YORK PLAZA, SUITE 4600 , NEW YORK, NY 10004, UNITED STATES, 2013) Ozdemir, Zeynep; Topuzogullari, Murat; İsoglu, Ismail Alper; Dincer, Sevil; 0000-0003-4435-7776; 0000-0001-5085-5814; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; İsoglu, Ismail Alper; Dincer, SevilWe report the synthesis of N-(2-hydroxypropyl)methacrylamide (HPMA) macroCTA and HPMA-b-4-Vinylpyridine block copolymers via reversible addition-fragmentation chain transfer (RAFT) reaction. Polymerization was carried out in dimethylformamide (DMF) at 70 C using 4-Cyano-4(thiobenzoylthio) pentanoic acid as chain transfer agent and AIBN as an initiator. Control over molecular weight and composition was achieved by altering the CTA, monomer and initiator feed ratio. The controlled living character of the polymerization was verified with pseudo-first-order kinetic plots, a linear increase of the molecular weight with conversion, and low polydispersities (PDIs B 1.2). Effect of microwave heating on the homo- and copolymer formation was investigated and the rates were significantly higher than those observed under conventional heating conditions. These polymerization reactions were in controlled fashion resulting in polymers with low PDIs, too. These polymers have a great potential to be used in developing delivery vehicles and conjugates for further drug or gene delivery applicationsArticle Liver fibrosis staging using CT image texture analysis and soft computing(ELSEVIER, 2014) Kayaalti, Omer; Aksebzeci, Bekir Hakan; Karahan, Ibrahim Okkes; Deniz, Kemal; Ozturk, Mehmet; Yilmaz, Bulent; Kara, Sadik; Asyali, Musa Hakan; 0000-0001-7476-8141; 0000-0003-2954-1217; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü; Yilmaz, Bulent; Aksebzeci, Bekir HakanLiver biopsy is considered to be the gold standard for analyzing chronic hepatitis and fibrosis; however, it is an invasive and expensive approach, which is also difficult to standardize. Medical imaging techniques such as ultrasonography, computed tomography (CT), and magnetic resonance imaging are non-invasive and helpful methods to interpret liver texture, and may be good alternatives to needle biopsy. Recently, instead of visual inspection of these images, computer-aided image analysis based approaches have become more popular. In this study, a non-invasive, low-cost and relatively accurate method was developed to determine liver fibrosis stage by analyzing some texture features of liver CT images. In this approach, some suitable regions of interests were selected on CT images and a comprehensive set of texture features were obtained from these regions using different methods, such as Gray Level Co-occurrence matrix (GLCM), Laws’ method, Discrete Wavelet Transform (DWT), and Gabor filters. Afterwards, sequential floating forward selection and exhaustive search methods were used in various combinations for the selection of most discriminating features. Finally, those selected texture features were classified using two methods, namely, Support Vector Machines (SVM) and k-nearest neighbors (k-NN). The mean classification accuracy in pairwise group comparisons was approximately 95% for both classification methods using only 5 features. Also, performance of our approach in classifying liver fibrosis stage of subjects in the test set into 7 possible stages was investigated. In this case, both SVM and k-NN methods have returned relatively low classification accuracies. Our pairwise group classification results showed that DWT, Gabor, GLCM, and Laws’ texture features were more successful than the others; as such features extracted from these methods were used in the feature fusion process. Fusing features from these better performing families further improved the classification performance. The results show that our approach can be used as a decision support system in especially pairwise fibrosis stage comparisons.Article Polyethylenimine Modified and Non-Modified Polymeric Micelles Used for Nasal Administration of Carvedilol(AMER SCIENTIFIC PUBLISHERS, 2015) Kahraman, Emine; Karagoz, Ayse; Dinçer, Sevil; Ozsoy, Yildiz; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Dinçer, SevilThis 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 TACTILE SENSITIVITY and CAPABILITY OF SOFT-SOLID TEXTURE DISCRIMINATION(WILEY, 2015) Aktar, Tugba; Ettelaie, Rammile; Chen, Jianshe; Holmes, Melvin; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Aktar, TugbaThe sensation and perception of food texture is regulated by tactile-dominated mechanisms and therefore, it is believed that one’s capability in discriminating food textural properties could be related to one’s tactile sensitivity. However, evidence to support this hypothesis is currently not available. This work aims to test this hypothesis by examining tactile sensitivity of individuals’ (touch detection threshold and two-point discrimination threshold) and texture discrimination capability. A range of soft-solid food samples with controlled firmness and elastic moduli were designed for textural discrimination tests. A total of 32 healthy subjects threshold of touch detection was found to be 0.028 g for the fingertip and 0.013 g for the tongue. Similarly, the mean threshold of two-point discrimination was 1.42 mm and 0.62 mm for the fingertip and tongue, respectively. Threshold for firmness discrimination (compressing until yielding) of the gel samples was 13.3% for the fingertip and 11.1% for the tongue. However, the elasticity discrimination threshold (by gentle pressing) of the population was found to be much smaller at 2.3% and 1.2% for the fingertip and the tongue respectively. Results show that tongue is slightly more sensitive than the fingertip in discriminating food texture (P < 0.05). An expected correlation between individual’s capability of texture discrimination and their tactile sensitivity was not observed.Article Combination of the Simple Additive (SAW) Approach and Mixture Design to Determine Optimum Cocoa Combination of the Hot Chocolate Beverage(TAYLOR & FRANCIS INC, 2015) DOGAN, Mahmut; Aktar, Tugba; Toker, Omer Said; Tatlisu, Nevruz Berna; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Aktar, TugbaPhysicochemical (pH, brix, and color), sensory (color, taste, odor, mouthfeeling, consistency, bitter flavor, and general acceptability), and rheological properties of the hot chocolate beverages including different cocoa combinations were investigated in the present study. Cocoa type significantly affected all of the properties. Simple additive weighting approach was applied to obtain one score from seven different sensory parameters and simple additive weighting score was used in mixture design to determine optimum cocoa type or cocoa combination. Ostwald de Waele model described the flow behavior of the hot chocolate beverage samples with R2 values ranged between 0.818 and 0.999. The consistency coefficient (K) and apparent viscosity at shear rate 50 s−1 (η50) were significantly affected by cocoa type found in the formulation of the beverage. The mixture design approach was performed in order to determine variation of the responses (physicochemical, sensory, and rheological parameters) as a function of cocoa concentration. Simple additive weighting scores were satisfactorily described by established equation as a function of cocoa concentration to be used in the formulation of the hot chocolate beverage (R2 = 0.8645).Article EVALUATION OF THE SENSORY CORRELATION BETWEEN TOUCH SENSITIVITY AND THE CAPACITY TO DISCRIMINATE VISCOSITY(WILEY, 2015) Aktar, Tugba; Chen, Jianshe; Ettelaie, Rammile; Holmes, Melvin; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüThe capacity to discriminate the viscous nature of food materials is critically important in the sensory evaluation and subsequent perception of food texture and acceptability. It is generally assumed that this capability is closely linked to individual's tactile sensitivity, which in itself is a function of the individual's specific capabilities due to experience, age, lifestyle and health status for example. However, no experimental evidence is yet available to validate or disprove this assumption. By comparing the touch sensitivity and the capability of viscosity discrimination among individuals (using finger and tongue sensory perception), this work aims to establish if a correlation exists. Semmes-Weinstein monofilaments were used for touch sensitivity tests of the index fingers and tongue surfaces. A series of syrup solutions were prepared to give a wide range of viscosities with a viscosity scale factor of 1.20.009. A total of 30 healthy subjects (16 female and 14 male; mean age 29.9 +/- 9 years; mean body mass index 22.5 +/- 2.9kg/m(2)) participated in this study. A similar touch sensitivity threshold, 0.023 and 0.021g, was observed for the index fingertip and for the tongue, respectively. However, the tongue appears to be more sensitive to touch than the fingertips when the force range they cover was compared. The viscosity discrimination threshold was found to be approximately 53% for the index fingertip and around 47% for the tongue. By comparing individual capabilities of viscosity discrimination against touch sensitivity, no significant correlation was observed between the two factors. The results from this work suggest that the capability to discriminate viscosity differences is more likely attributed to experience and is little influenced by one's physiological capability of tactile sensation, e.g., the touch sensitivity. Practical ApplicationsThe capability to discriminate differences in viscosity and the subsequent perception is an important factor for food texture appreciation. Establishment of the underlying factors that characterize the variation in the ability for such discrimination across individuals is not only critically important for our fundamental understanding of the viscosity perception but is also hugely important for the food industry in development of new food products, and in particular for specific food design for individuals with special needs, e.g., elderly, dysphagia patients, etc. Differential threshold for certain tastes and aroma compounds has been investigated. However, little has been reported in the literature about the tactile interpretation of viscosity sensation and perception. Findings from this work could provide new insight for researchers in the food industry and in food development by giving them flexibility to redesign their ingredients especially the one that has thickening effect on the product viscosity. Methodologies used in this experiment could also be applied for general food sensory studies in establishing relationships between sensory psychology and sensory physiology and especially the threshold studies with a similar approach of finding just noticeable difference values of any stimuli. The method could also be applicable to sensory capability studies of some particular groups such as elderly people to assess how weakened physiology affects their sensory capability.Article Biodiversity, drug discovery, and the future of global health: Introducing the biodiversity to biomedicine consortium, a call to action(UNIV EDINBURGH, GLOBAL HEALTH SOC, CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, SCOTLAND, 2017) Neergheen-Bhujun, Vidushi; Awan, Almas Taj; Baran, Yusuf; Bunnefeld, Nils; Chan, Kit; Edison Dela Cruz, Thomas; Egamberdieva, Dilfuza; Elsasser, Simon; Johnson, Mari-Vaughn V.; Komai, Shoji; Konevega, Andrey L.; Malone, John H.; Mason, Paul; Nguon, Rothsophal; Piper, Ross; Shrestha, Uttam Babu; Pesic, Milica; Kagansky, Alexander; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;[Özet Yok]conferenceobject.listelement.badge Computer-Aided Classification of Breast Cancer Histopathological Images(IEEE345 E 47TH ST, NEW YORK, NY 10017 USA, 2017) Aksebzeci, Bekir Hakan; Kayaalti, Omer; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüNowadays, one of the most common types of cancer is breast cancer. The early and accurate diagnosis of breast cancer has great importance in the treatment of the disease. In the diagnosis of breast cancer, histopathological analysis of cell and tissue specimens taken by biopsy is considered as the gold standard. Histopathological analysis is a tedious process that is highly dependent on the knowledge and experience of the pathologists. In this study; it is aimed to develop a computer-aided system that can reduce the workload of pathologists and help them in their diagnosis. An image set containing benign and malignant tumor images of breast cancer has been studied. To perform texture analysis on tumor images; first order statistics, Gabor and gray-level co-occurrence matrix (GLCM) feature extraction methods have been applied. Then, various classifiers were applied to the obtained feature matrices and their performances were compared. The highest classification accuracy was achieved 82.06% by Random Forests classifier with feature combination of Gabor and GLCM methods. The results presented here show that computer-assisted diagnosis of breast cancer is a promising field.Review Advances in Micelle-based Drug Delivery: Cross-linked Systems(BENTHAM SCIENCE PUBL LTDEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüThere are several barriers that drug molecules encounter in body beginning from kidney filtration and reticulo-endothelial system (RES) clearance to cellular trafficking. Multifunctional nanocarriers have a great potential for the delivery of drugs by enhancing therapeutic activity of existing methodologies. A variety of nanocarriers are constructed by different material types, which have unique physicochemical properties for drug delivery applications. Micelles formed by amphiphilic polymers are one of the most important drug/nanocarrier formulation products, in which the core part is suitable for encapsulation of hydrophobic agent whereas the outer shell can be utilized for targeting the drug to the disease area. Micelles as self-assembled nanostructures may encounter difficulties in biodistribution of encapsulated drugs because they have a tendency to be dissociated in dilution or high ionic strength. Therefore, therapeutic efficiency is decreased and it requires high amount of drug to be administered to achieve more efficient result. To overcome this problem, covalently stabilized structures produced by cross-linking in core or shell part, which can prevent the micelle dissociation and regulate drug release, have been proposed. These systems can be designed as responsive systems in which cross-links are degradable or hydrolysable under specific conditions such as low pH or reductive environment. These are enhancing characteristics in drug delivery because their cleavage allows the release of bioactive agent encapsulated in the carrier at a certain site or time. This review describes the chemical methodologies for the preparation of cross-linked micelles, and reports an update of latest studies in literature.Article Thermo-Responsive Complexes of c-Myc Antisense Oligonucleotide with Block Copolymer of Poly(OEGMA) and Quaternized Poly(4-Vinylpyridine)(WILEY-V C H VERLAG GMBHPOSTFACH 101161, 69451 WEINHEIM, GERMANY, 2017) Topuzogullari, Murat; Elalmis, Yeliz Basaran; Isoglu, Sevil Dincer; 0000-0002-6871-2202; 0000-0003-4435-7776; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüSolution behavior of thermo-responsive polymers and their complexes with biological macromolecules may be affected by environmental conditions, such as the concentration of macromolecular components, pH, ion concentration, etc. Therefore, a thermo-responsive polymer and its complexes should be characterized in detail to observe their responses against possible environments under physiological conditions before biological applications. To briefly indicate this important issue, thermo-responsive block copolymer of quaternized poly(4-vinylpyridine) and poly(oligoethyleneglycol methyl ether methacrylate) as a potential nonviral vector has been synthesized. Polyelectrolyte complexes of this copolymer with the antisense oligonucleotide of c-Myc oncogene are also thermo-responsive but, have lower LCST (lower critical solution temperature) values compared to individual copolymer. LCST values of complexes decrease with molar ratio of macromolecular components and presence of salt. Dilution of solutions also affects solution behavior of complexes and causes a significant decrease in size and an increase in LCST, which indicates possible effects of severe dilutions in the blood stream.Article Environmental responsiveness of tubulin glutamylation in sensory cilia is regulated by the p38 MAPK pathway(NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, 2018) Kimura, Yoshishige; Tsutsumi, Koji; Konno, Alu; Ikegami, Koji; Hameed, Saira; Kaneko, Tomomi; Kaplan, Oktay Ismail; Teramoto, Takayuki; Fujiwara, Manabi; Ishihara, Takeshi; Blacque, Oliver E.; Setou, Mitsutoshi; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;Glutamylation is a post-translational modification found on tubulin that can alter the interaction between microtubules (MTs) and associated proteins. The molecular mechanisms regulating tubulin glutamylation in response to the environment are not well understood. Here, we show that in the sensory cilia of Caenorhabditis elegans, tubulin glutamylation is upregulated in response to various signals such as temperature, osmolality, and dietary conditions. Similarly, tubulin glutamylation is modified in mammalian photoreceptor cells following light adaptation. A tubulin glutamate ligase gene ttll-4, which is essential for tubulin glutamylation of axonemal MTs in sensory cilia, is activated by p38 MAPK. Amino acid substitution of TTLL-4 has revealed that a Thr residue (a putative MAPKphosphorylation site) is required for enhancement of tubulin glutamylation. Intraflagellar transport (IFT), a bidirectional trafficking system specifically observed along axonemal MTs, is required for the formation, maintenance, and function of sensory cilia. Measurement of the velocity of IFT particles revealed that starvation accelerates IFT, which was also dependent on the Thr residue of TTLL-4. Similarly, starvation-induced attenuation of avoidance behaviour from high osmolality conditions was also dependent on ttll-4. Our data suggest that a novel evolutionarily conserved regulatory system exists for tubulin glutamylation in sensory cilia in response to the environment.Article Antibacterial Bilayered Skin Patches Made of HPMA and Quaternary Poly(4-vinyl pyridine)(KOREAN FIBER SOC, KOREA SCIENCE TECHNOLOGY CTR #501 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA, 2018) Isoglu, I. Alper; Demirkan, Cemre; Seker, Mine Gul; uzlakoglu, Kadriye; Isoglu, Sevil Dincer; 0000-0002-6887-6549; 0000-0002-6226-7507; 0000-0002-7564-9213; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüThis study aimed to produce poly(4-vinyl pyridine) and hydroxypropyl methacrylamide (HPMA)-based bilayer wound dressings materials enhancing healing mechanism for the wounds which have self-healing problem and high infection risk. These materials were designed to protect wound from secondary traumas caused microorganism invasion and do not have toxic substance release problem. Synthesis of quaternary poly(4-vinyl pyridine) (poly(Q4-VP)) which is the antibacterial layer of wound dressing material was carried out in two stages. At first stage, poly(4-vinyl pyridine) polymer was synthesized from 4-vinyl pyridine monomer by free radical polymerization. Then, poly(Q4-VP) was synthesized from poly(4-VP) by alkylation reaction with 6-bromocaproic acid. Resulted polymer was structurally characterized by FT-IR. The macroporous spongy structure, as the lower layer of wound dressing material, was prepared by cryogelation of HPMA. Then, the antibacterial polymer was electrospun onto the cryogel structure and bilayered material was obtained. Cryogel structure, fiber morphology and layer integration was examined by SEM. In order to enhance wound healing process, ascorbic acid (vitamin C) was loaded to cryogel layer and release was followed by spectrophotometrically. The antimicrobial properties of the materials were examined against Escherichia coli, Staphylococcus aureus and Candida albicans, respectively. According to the results, bilayered, antibacterial and antifungal against Staphylococcus aureus and Candida albicans, temporary wound dressings which can stimulate wound healing and have high swelling capacity were obtained successfully.conferenceobject.listelement.badge Poly(OEGMA)-b-Poly(4-VP) block copolymer nanocarriers for anticancer agent release(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2018) Aksit, N. N.; Topuzogullari, M.; Isoglu, I. A.; El Khatib, M.; Isoglu, S. Dincer; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;Today, the most common approach to treating cancer is to transport the active substances with nanocarriers, which is more advantageous than systemic administration. One of the major advantages of nanocarriers is that they can be transferred to tumors (EPR effect) through passive targeting due to their small size and with lower toxicity than systemic administration for higher drug concentration in the tumor locus. For this purpose, micelles have been widely studied because of the advantages such as increasing the solubility of the active substance or masking its toxicity. In our study, we have synthesized a block copolymer based on PEG and 4VP by RAFT polymerization in order to obtain uniform polymer chains that will allow forming micelles in better characteristics. Block copolymers were characterized by FTIR and 1H NMR. We confirmed RAFTmediated polymer formation by following molecular weight with GPC. Following that, polymers were tested on SKBR3 breast cancer cells in terms of toxicity by MTS using Cell Titer 96® Aqueous One Solution Cell Proliferation Assay. Polymers which are not loaded with drug revealed good cell viability (above %80). Then, micelles containing DOX as a model drug were prepared by the emulsionsolvent evaporation method. Micelles were characterized by Zeta Sizer in terms of size and size distribution. Afterward, resulted drugloaded micelles were applied to breast cancer cells and toxicity was evaluated by MTS.Article Akut Böbrek Hasarında Nötrofil Jelatinaz İlişkili Lipokalin ile Mortalite İlişkisi(GALENOS YAYINCILIK, ERKAN MOR, MOLLA GURANI CAD 21-1, FINDIKZADE, ISTANBUL 34093, TURKEY, 2018) Aksebzeci, Bekir Hakan; Kayaaltı, Seda; Kayaaltı, Ömer; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;Objective: Almost half of intensive care patients are affected by acute kidney injury (AKI). The purpose of this study is to determine parameters that can be used for predicting of early (within 28 days) and late (within 90 days) mortality in patients who are followed-up with AKI in intensive care units. Materials and Methods: In this study, a dataset that contains 50 patients with AKI in intensive care units was used. This dataset contains blood urea nitrogen, creatinine, plasma and urinary neutrophil gelatinase-associated hpocalin (NGAL), lactate dehydrogenase, alkaline phosphatase and gammaglutamyl transpeptidase values of patients who were admitted to intensive care for various reasons and who developed AKI on the days 1, 3 and 7. In addition to these values, laboratory results such as serum electrolytes on day 1, blood gas; vital signs such as mean arterial pressure, central venous pressure; and demographic data were also recorded. Data mining techniques were applied to determine correlation between all of these data and mortality. Results: The threshold level of urinary NGAL on day 7 was determined to be 69 ng/mL, and strong correlation was found between this threshold level and early mortality. Similarly, the threshold level of plasma NGAL on day 7 was determined to be 150 ng/mL, and this was highly correlated with early mortality. Besides, strong correlation was also found between the difference in the urinary NGAL levels on day 1 and 7, and early mortality. Conclusion: In this study, plasma and urinary NGAL levels were found to be closely related to early mortality in patients who were followed-up with AKI in intensive care units. On the other hand, any parameter associated with late mortality was not found.Article Stem cells combined 3D electrospun nanofibrous and macrochannelled matrices: a preliminary approach in repair of rat cranial bones(Taylor & Francis Group, 2019) İşoğlu, İsmail Alper; Bölgen, Nimet; Korkusuz, Petek; Vargel, İbrahim; Çelik, Hakan Hamdi; Kılıç, Emine; Güzel, Elif; Çavuşoğlu, Tarık; Uçkan, Duygu; Pişkin, Erhan; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;Repair of cranial bone defects is an important problem in the clinical area. The use of scaffolds combined with stem cells has become a focus in the reconstruction of critical-sized bone defects. Electrospinning became a very attracting method in the preparation of tissue engineering scaffolds in the last decade, due to the unique nanofibrous structure of the electrospun matrices. However, they have a limitation for three dimensional (3D) applications, due to their two-dimensional structure and pore size which is smaller than a cellular diameter which cannot allow cell migration within the structure. In this study, electrospun poly(e-caprolactone) (PCL) membranes were spirally wounded to prepare 3D matrices composed of nanofibers and macrochannels. Mesenchymal stromal/stem cells were injected inside the scaffolds after the constructs were implanted in the cranial bone defects in rats. New bone formation, vascularisation and intramembranous ossification of the critical size calvarial defect were accelerated by using mesenchymal stem cells combined 3D spiral-wounded electrospun matrices.Article Core-crosslinking as a pathway to develop inherently antibacterial polymeric micelles(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2019) Kadayifci, Melike Seyma; Gokkaya, Damla; Topuzogullari, Murat; Isoglu, Sevil Dincer; Atabey, Tugba; Arasoglu, Tulin; Ozmen, Mehmet Murat; 0000-0002-6887-6549; 0000-0002-9330-5107; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüPositively charged polymeric materials have been an alternative to combat bacteria as they exhibit inherently antibacterial potency via bacteria membrane disruption. In this study, we report facile preparation of positively charged core-crosslinked polymeric micelles with inherent antibacterial properties. Spherical micelles were prepared by self-assembling of poly(4-vinylpyridine)-b-(oligoethylene glycol methyl ether methacrylate) copolymer in aqueous solution. Herein, quaternization reaction was utilized for the first time to core crosslink the micelles through the pyridine rings utilizing their hydrophobic core and thus resulting positively charged nanostructures. Dynamic light scattering (DLS) results identified that the micelles have an average hydrodynamic diameter of 114 nm with a polydispersity index ranging between 0.105 and 0.114. The electrophoretic light scattering (ELS) measurements demonstrated that the micelles have zeta potential values ranging from +38 to +63 mV. It was evident from both ELS and DLS results that the micelles in solution exhibit long-term stability as the samples were able to maintain their size and charge even after a year of storage. Further, the micelles exhibited inherently antibacterial activity against Escherichia coli and furthermore, this antibacterial efficacy was sustained over a period of 1 year. These stable core-crosslinked micelles are proposed to have great potential as antibacterial materials for long-term applications. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48393.Article 3-Sulfopropyl methacrylate based cryogels as potential tissue engineering scaffolds(TAYLOR & FRANCIS LTD, 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND, 2019) Durukan, Adile Yuruk; Isoglu, Ismail Alper; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüIn this study, we developed cryogels containing 3-sulfopropyl methacrylate (SPMA) and 4-vinyl pyridine (4-VP) as a potential scaffold for tissue engineering applications. Cryogels with varying monomer ratios were synthesised by chemical cross-linking under cryogelation conditions. Effect of initiators and cross-linker amount (0.025-0.15 g MBA; 0.012-0.05 g APS; 2.5-12.5 mu l TEMED) and also freezing temperature (-20 and -80oC) were investigated, and the conditions were optimised according to the morphological structures examined by SEM. The functional groups of the materials were characterised by FT-IR. Compression test and swelling were applied to investigate mechanical properties and water absorption ability, respectively. As a preliminary study, selected materials were tested for cell cytotoxicity with MTT. According to our results, the ionic and biocompatible cryogels prepared in this study possessing a highly porous and interconnective structure with good mechanical characteristics and swelling properties can be suitable as tissue scaffolds for many applications.Article On the detailed mechanical response investigation of PHBV/PCL and PHBV/PLGA electrospun mats(IOP PUBLISHING LTD, TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND, 2019) Bal, Burak; Tugluca, Ibrahim Burkay; Koc, Nuray; Isoglu, Ismail Alper; 0000-0002-7389-9155; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik BölümüIn this study, electrospun mats of pristine poly(epsilon-caprolactone) (PCL), Poly(D, L-lactide-co-glycolide) (PLGA), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), as well as PHBV/PCL blends and PHBV/PLGA blends in different ratios (80:20, 75:25, 50:50, 25:75, 20:80, 10:90, 5:95%, w/w) and Centella Asiatica (CA) loaded (1, 5, 10%, w/v) PHBV/PCL and PHBV/PLGA polyester blends were prepared. Electrospun mats were characterized by scanning electron microscopy (SEM) in order to show uniform and bead and defect-free fiber structure with average diameter. The blend ratio and strain rate dependencies of mechanical behavior of these electrospun membranes were investigated under tensile loading. The tensile tests were conducted at an initial strain rates of 10(-1) s(-1), 10(-2) s(-1), 10(-3) s(-1) and 10(-4) s(-1) at room temperature and the best and worst combinations of PHBV/PLGA, PHBV/PCL blend ratios for both stress and ductility required applications were specified for each strain rate. The effects of blend ratios on the tensile strength and Young's modulus were also investigated. Moreover, the effects of Centella Asiatica on the electrospun membranes' mechanical behavior were demonstrated at different strain rates. Consequently, this study constitutes an important guideline for the selection and usage of the aforementioned electrospun membranes as a wound dressing material in terms of mechanical response at different loading scenarios.Article MicroRNA prediction based on 3D graphical representation of RNA secondary structures(TUBITAK SCIENTIFIC & TECHNICAL RESEARCH COUNCIL TURKEY, ATATURK BULVARI NO 221, KAVAKLIDERE, ANKARA, 00000, TURKEY, 2019) Müşerref Duygu, SAÇAR DEMİRCİ; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Müşerref Duygu, SAÇAR DEMİRCİMicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. While a miRNA can target hundreds of messenger RNA (mRNAs), an mRNA can be targeted by different miRNAs, not to mention that a single miRNA might have various binding sites in an mRNA sequence. Therefore, it is quite involved to investigate miRNAs experimentally. Thus, machine learning (ML) is frequently used to overcome such challenges. The key parts of a ML analysis largely depend on the quality of input data and the capacity of the features describing the data. Previously, more than 1000 features were suggested for miRNAs. Here, it is shown that using 36 features representing the RNA secondary structure and its dynamic 3D graphical representation provides up to 98% accuracy values. In this study, a new approach for ML-based miRNA prediction is proposed. Thousands of models are generated through classification of known human miRNAs and pseudohairpins with 3 classifiers: decision tree, naive Bayes, and random forest. Although the method is based on human data, the best model was able to correctly assign 96% of nonhuman hairpins from MirGeneDB, suggesting that this approach might be useful for the analysis of miRNAs from other species.