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Publication Metadata only Antitumor efficacy of ceranib-2 with nano-formulation of PEG and rosin esters(Humana Press Inc, 2021) Ben Taleb, Ali; Karakus, Selcan; Tan, Ezgi; Ilgar, Merve; Kutlu, Ozlem; Kutlu, Hatice Mehtap; Kilislioglu, Ayben; N/A; Gözüaçık, Devrim; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 40248Ceranib-2 is a recently discovered, poorly water-soluble potent ceramidase inhibitor, with the ability to suppress cancer cell proliferation and delay tumor growth. However, its poor water solubility and weak cellular bioavailability hinder its use as a therapeutic agent for cancer. PEGylated rosin esters are an excellent platform as a natural polymer for drug delivery applications, especially for controlling drug release due to their degradability, biocompatibility, capability to improve solubility, and pharmacokinetics of potent drugs. In this study, stable aqueous amphiphilic submicron-sized PEG400-rosin ester-ceranib-2 (PREC-2) particles, ranging between 100 and 350 nm in a 1:1 mixture, were successfully synthesized by solvent evaporation mediated by sonication. Conclusion: Stable aqueous PEGylated rosin ester nanocarriers might present a significant solution to improve solubility, pharmacokinetic, and bioavailability of ceranib-2, and hold promises for use as an anticancer adjacent drug after further investigations.Publication Open Access Applications of augmented reality in ophthalmology [invited](Optical Society of America (OSA), 2021) Artal, Pablo; Department of Physics; Department of Electrical and Electronics Engineering; Aydındoğan, Güneş; Kavaklı, Koray; Ürey, Hakan; Şahin, Afsun; Faculty Member; Faculty Member; Department of Physics; Department of Electrical and Electronics Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; N/A; 8579; 171267Throughout the last decade, augmented reality (AR) head-mounted displays (HMDs) have gradually become a substantial part of modern life, with increasing applications ranging from gaming and driver assistance to medical training. Owing to the tremendous progress in miniaturized displays, cameras, and sensors, HMDs are now used for the diagnosis, treatment, and follow-up of several eye diseases. In this review, we discuss the current state-of-the-art as well as potential uses of AR in ophthalmology. This review includes the following topics: (i) underlying optical technologies, displays and trackers, holography, and adaptive optics; (ii) accommodation, 3D vision, and related problems such as presbyopia, amblyopia, strabismus, and refractive errors; (iii) AR technologies in lens and corneal disorders, in particular cataract and keratoconus; (iv) AR technologies in retinal disorders including age-related macular degeneration (AMD), glaucoma, color blindness, and vision simulators developed for other types of low-vision patients.Publication Metadata only Embedding alternative conformations of proteins in protein–protein interaction networks(Humana Press inc, 2020) N/A; N/A; Department of Computer Engineering; Department of Chemical and Biological Engineering; Halakou, Farideh; Gürsoy, Attila; Keskin, Özlem; PhD Student; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 8745; 26605While many proteins act alone, the majority of them interact with others and form molecular complexes to undertake biological functions at both cellular and systems levels. Two proteins should have complementary shapes to physically connect to each other. As proteins are dynamic and changing their conformations, it is vital to track in which conformation a specific interaction can happen. Here, we present a step-by-step guide to embedding the protein alternative conformations in each protein–protein interaction in a systems level. All external tools/websites used in each step are explained, and some notes and suggestions are provided to clear any ambiguous point.Publication Metadata only Hemodynamic flow visualization of early embryonic great vessels using μPIV(Humana Press Inc, 2015) Chen, Chia-Yuan; Kowalski, William J.; Pekkan, Kerem; N/A; Göktaş, Selda; Researcher; N/A; N/AMicroparticle image velocimetry (mu PIV) is an evolving quantitative methodology to closely and accurately monitor the cardiac flow dynamics and mechanotransduction during vascular morphogenesis. While PIV technique has a long history, contemporary developments in advanced microscopy have significantly expanded its power. This chapter includes three new methods for mu PIV acquisition in selected embryonic structures achieved through advanced optical imaging: (1) high-speed confocal scanning of transgenic zebrafish embryos, where the transgenic erythrocytes act as the tracing particles; (2) microinjection of artificial seeding particles in chick embryos visualized with stereomicroscopy; and (3) real-time, timeresolved optical coherence tomography acquisition of vitelline vessel flow profiles in chick embryos, tracking the erythrocytes.Publication Open Access Machine learning helps identify CHRONO as a circadian clock component(Public Library of Science, 2014) Anafi, Ron C.; Lee, Yoo; Sato, Trey K.; Venkataraman, Anand; Ramanathan, Chidambaram; Hughes, Michael E.; Baggs, Julie E.; Growe, Jacqueline; Liu, Andrew C.; Kim, Junhyong; Hogenesch, John B.; Kavaklı, İbrahim Halil; Faculty Member; College of Engineering; 40319Over the last decades, researchers have characterized a set of ‘‘clock genes’’ that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3). One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator). Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics.Publication Metadata only SYBR green dye-based probe-free SNP genotyping: Introduction of T-Plex real-time PCR assay(Elsevier, 2013) Etlik, Ozdal; Koksal, Vedat; Ocak, Zeynep; Baris, Saniye Tugba; Department of Molecular Biology and Genetics; Barış, İbrahim; Teaching Faculty; Department of Molecular Biology and Genetics; College of Sciences; 111629Single-nucleotide polymorphism (SNP) genotyping is widely used in genetic association studies to characterize genetic factors underlying inherited traits. Despite many recent advances in high-throughput SNP genotyping, inexpensive and flexible methods with reasonable throughput levels are still needed. Real-time PCR methods for discovering and genotyping SNPs are becoming increasingly important in various fields of biology. In this study, we introduce a new, single-tube strategy that combines the tetra-primer ARMS PCR assay, SYBR Green I-based real-time PCR, and melting-point analysis with primer design strategies to detect the SNP of interest. This assay, T-Plex real-time PCR, is based on the T. discrimination of the amplified allele-specific amplicons in a single tube. The specificity, sensitivity, and robustness of the assay were evaluated for common mutations in the FV, PII, MTHFR, and FGFR3 genes. We believe that T-Plex real-time PCR would be a useful alternative for either individual genotyping requests or large epidemiological studies.Publication Metadata only Transgene-free disease-specific iPSC generation from fibroblasts and peripheral blood mononuclear cells(Humana Press Inc, 2016) Ebrahimi, Ayyub; N/A; N/A; N/A; N/A; Fidan, Kerem; Bozlak, Özlem Hilal Çağlayan; Özçimen, Burcu; Önder, Tamer Tevfik; Master Student; Undergraduate Student; Phd Student; Faculty Member; Graduate School of Sciences and Engineering; School of Medicine; Graduate School of Sciences and Engineering; School of Medicine; N/A; 296433; 316273; 42946Induced pluripotent stem cells (iPSCs) offer great promise as tools for basic biomedical research, disease modeling, and drug screening. In this chapter, we describe the generation of patient-specific, transgene-free iPSCs from skin biopsies and peripheral blood mononuclear cells through electroporation of episomal vectors and growth under two different culture conditions. The resulting iPSC lines are characterized with respect to pluripotency marker expression through immunostaining, tested for transgene integration by PCR, and assayed for differentiation capacity via teratoma formation.