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Publication Open Access The after-hours circadian mutant has reduced phenotypic plasticity in behaviors at multiple timescales and in sleep homeostasis(Nature Publishing Group (NPG), 2017) Maggi, Silvia; Balzani, Edoardo; Lassi, Glenda; Garcia-Garcia, Celina; Plano, Andrea; Espinoza, Stefano; Mus, Liudmila; Tinarelli, Federico; Nolan, Patrick M.; Gainetdinov, Raul R.; Nieus, Thierry; Tucci, Valter; Department of Psychology; Balcı, Fuat; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 51269Circadian clock is known to adapt to environmental changes and can significantly influence cognitive and physiological functions. In this work, we report specific behavioral, cognitive, and sleep homeostatic defects in the after hours (Afh) circadian mouse mutant, which is characterized by lengthened circadian period. We found that the circadian timing irregularities in Afh mice resulted in higher interval timing uncertainty and suboptimal decisions due to incapability of processing probabilities. Our phenotypic observations further suggested that Afh mutants failed to exhibit the necessary phenotypic plasticity for adapting to temporal changes at multiple time scales (seconds-to-minutes to circadian). These behavioral effects of Afh mutation were complemented by the specific disruption of the Per/Cry circadian regulatory complex in brain regions that govern food anticipatory behaviors, sleep, and timing. We derive statistical predictions, which indicate that circadian clock and sleep are complementary processes in controlling behavioral/cognitive performance during 24 hrs. The results of this study have pivotal implications for understanding how the circadian clock modulates sleep and behavior.Publication Open Access Effect of reaction solvent on hydroxyapatite synthesis in sol-gel process(The Royal Society, 2017) Department of Chemistry; Nazeer, Muhammad Anwaar; Yılgör, Emel; Yağcı, Mustafa Barış; Ünal, Uğur; Yılgör, İskender; PhD Student; Researcher; Researcher; Faculty Member; Faculty Member; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); College of Sciences; Graduate School of Sciences and Engineering; N/A; 40527; N/A; N/A; 24181Synthesis of hydroxyapatite (HA) through sol-gel process in different solvent systems is reported. Calcium nitrate tetrahydrate (CNTH) and diammonium hydrogen phosphate (DAHP) were used as calcium and phosphorus precursors, respectively. Three different synthesis reactions were carried out by changing the solvent media, while keeping all other process parameters constant. A measure of 0.5 M aqueous DAHP solution was used in all reactions while CNTH was dissolved in distilled water, tetrahydrofuran (THF) and N, N-dimethylformamide (DMF) at a concentration of 0.5 M. Ammonia solution (28-30%) was used to maintain the pH of the reaction mixtures in the 10-12 range. All reactions were carried out at 40 +/- 2 degrees C for 4 h. Upon completion of the reactions, products were filtered, washed and calcined at 500 degrees C for 2 h. It was clearly demonstrated through various techniques that the dielectric constant and polarity of the solvent mixture strongly influence the chemical structure and morphological properties of calcium phosphate synthesized. Water-based reaction medium, with highest dielectric constant, mainly produced beta-calcium pyrophosphate (beta-CPF) with a minor amount of HA. DMF/water system yielded HA as the major phase with a very minor amount of beta-CPF. THF/water solvent system with the lowest dielectric constant resulted in the formation of pure HA.Publication Open Access Increased srum uric acid over five years is a risk factor for developing fatty liver(Nature Publishing Group (NPG), 2017) Jensen, Thomas; Niwa, Koichiro; Hisatome, Ichiro; Andres-Hernando, Ana; Roncal-Jimenez, Carlos A.; Sato, Yuka; Garcia, Gabriela; Ohno, Minoru; Lanaspa, Miguel A.; Johnson, Richard J.; Kuwabara, Masanari; N/A; Kanbay, Mehmet; Faculty Member; School of Medicine; 110580The prevalence of fatty liver disease (FLD) is increasing. To clarify risk factors for developing FLD, we analyzed a database from healthy Japanese adults who had annual medical check-ups in 2004 and reexamined in 2009. We used the fatty liver index (FLI) to classify participants as FLD (FLI >= 60), borderline FLD (30 <= FLI < 60), and normal liver (FLI < 30). Subjects with hepatitis B or C virus infection and subjects with FLD at the baseline were excluded. The cumulative incidence of FLD from normal liver and from borderline FLD over five years were 0.65% (52/8,025) and 12.9% (244/1,888), respectively. After multiple adjustments, higher serum uric acid (SUA) (OR:1.92; 95% CI:1.40-2.63) and increased SUA change (OR:3.734; 95% CI:2.57-5.42) became risk factors for developing FLD from normal liver, as well as younger age and higher body mass index. The risk factors for developing FLD from borderline FLD were similar. Not only higher baseline SUA but also increased SUA change became independent risks for developing FLD.Publication Open Access A common genetic variation of melanoma inhibitory activity-2 labels a subtype of pancreatic adenocarcinoma with high endoplasmic reticulum stress levels.(Nature Publishing Group (NPG), 2015) Kong, Bo; Wu, Weiwei; Valkovska, Nataliya; Jager, Carsten; Hong, Xin; Nitsche, Ulrich; Friess, Helmut; Esposito, Irene; Kleeff, Joerg; Michalski, Christoph W.; N/A; Erkan, Murat Mert; Faculty Member; School of Medicine; 214689HNF1 homeoboxA(HNF1A)-mediated gene expression constitutes an essential component of the secretory pathway in the exocrine pancreas. Melanoma inhibitory activity 2 (MIA2), a protein facilitating protein secretion, is an HNF1A target. Protein secretion is precisely coordinated by the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) system. Here, we demonstrate that HNFA and MIA2 are expressed in a subset of human PDAC tissues and that HNF1A induced MIA2 in vitro. We identified a common germline variant of MIA2 (c.A617G:p.I141M) associated with a secretory defect of the MIA2 protein in PDAC cells. Patients carrying MIA2(I141M) survived longer after tumor resection but the survival benefit was restricted to those patients who received adjuvant chemotherapy. The MIA2(I141M) variant was associated with high expression of ER stress/UPR genes - in particular those of the ERN1/XBP arm - in human PDAC samples. Accordingly, PDAC cell lines expressing the MIA2(I141M) variant expressed high levels of ERN1 and were more sensitive to gemcitabine. These findings define an interaction between the common MIA2(I141M) variant and the ER stress/UPR system and specify a subgroup of PDAC patients who are more likely to benefit from adjuvant chemotherapy.Publication Open Access Singularity links with exotic Stein fillings(Worldwide Center of Mathematics, 2014) Akhmedov, Anar; Department of Mathematics; Özbağcı, Burak; Faculty Member; Department of Mathematics; College of Sciences; 29746In [4], it was shown that there exist infinitely many contact Seifert fibered 3-manifolds each of which admits infinitely many exotic (homeomorphic but pairwise non-diffeomorphic) simply-connected Stein fillings. Here we extend this result to a larger set of contact Seifert fibered 3-manifolds with many singular fibers and observe that these 3-manifolds are singularity links. In addition, we prove that the contact structures induced by the Stein fillings are the canonical contact structures on these singularity links. As a consequence, we verify a prediction of András Némethi by providing examples of isolated complex surface singularities whose links with their canonical contact structures admitting infinitely many exotic simply-connected Stein fillings. Moreover, for infinitely many of these contact singularity links and for each positive integer n, we also construct an infinite family of exotic Stein fillings with fixed fundamental group ? ? ?n.Publication Open Access Comparison of the trifecta outcomes of robotic and open nephron-sparing surgeries performed in the robotic era of a single institution(SpringerOpen, 2015) Isik, Esin Ozturk; Mut, Tuna; Saglican, Yesim; Vural, Metin; Musaoğlu, Ahmet; N/A; N/A; Acar, Ömer; Onay, Aslıhan; Esen, Tarık; Faculty Member; Faculty Member; School of Medicine; 237530; N/A; 50536Purpose: In this study we aimed to report a comparative analysis between open and robotic nephron sparing surgeries (NSS) from a single institutional database. Methods: Patients who have undergone NSS during the robotic era of our institution were included in this study. Open (n = 74) and robotic (n = 59) groups were compared regarding trifecta outcome. Trifecta was defined as; warm ischemia time (WIT) <25 min, negative surgical margins and the absence of perioperative complications. Results: A total of 57 (77 %) and 45 (76 %) patients in the open and robotic groups, respectively achieved the trifecta outcome. Overall trifecta rate was 77 % (n = 102/133). The only statistically significant difference between trifecta positive and trifecta negative patients was the length of hospitalization (LOH). Except LOH; none of the tested parameters were shown to be predictive of trifecta outcome on univariate and multivariate analyses. Concerning trifecta positive patients; those in the open surgery group had larger tumors with a higher degree of morphometric complexity and were hospitalized for a longer period of time. Additionally, operative duration was significantly higher in the robotic group. Conclusions: In our cohort, no significant difference in achieving the trifecta outcome was reported after open and robotic NSS. Length of hospitalization was the only parameter that differed significantly between trifecta positive and trifecta negative patients. Surgical approach was not a significant predictor of simultaneous achievement of trifecta outcomes. Irrespective of the trifecta definition; larger and more complicated tumors were handled via open NSS.Publication Open Access The confidence database(Nature Publishing Group (NPG), 2020) Rahnev, Dobromir; Desender, Kobe; Lee, Alan L. F.; Adler, William T.; Aguilar-Lleyda, David; Akdoğan, Başak; Arbuzova, Polina; Atlas, Lauren Y.; Bang, Ji Won; Bègue, Indrit; Birney, Damian P; Brady, Timothy F.; Calder-Travis, Joshua; Chetverikov, Andrey; Clark, Torin K.; Davranche, Karen; Denison, Rachel N.; Dildine, Troy C.; Double, Kit S.; Faivre, Nathan; Fallow, Kaitlyn; Filevich, Elisa; Gajdos, Thibault; Gallagher, Regan M.; de Gardelle, Vincent; Gherman, Sabina; Haddara, Nadia; Hainguerlot, Marine; Hsu, Tzu-Yu; Hu, Xiao; Iturrate, Iñaki; Jaquiery, Matt; Kantner, Justin; Koculak, Marcin; Konishi, Mahiko; Koß, Christina; Kwok, Sze Chai; Lebreton, Maël; Lempert, Karolina M.; Ming Lo, Chien; Luo, Liang; Maniscalco, Brian; Martin, Antonio; Massoni, Sébastien; Matthews, Julian; Mazancieux, Audrey; Merfeld, Daniel M.; O’Hora, Denis; Palser, Eleanor R.; Paulewicz, Borysław; Pereira, Michael; Peters, Caroline; Philiastides, Marios G.; Pfuhl, Gerit; Prieto, Fernanda; Rausch, Manuel; Recht, Samuel, Reyes, Gabriel; Rouault, Marion; Sackur, Jérôme; Sadeghi, Saeedeh; Samaha, Jason; Seow, Tricia X. F.; Shekhar, Medha, Sherman, Maxine T.; Siedlecka, Marta; Skóra, Zuzanna; Song, Chen; Soto, David; Sun, Sai; van Boxtel, Jeroen J. A.; Wang, Shuo; Weidemann, Christoph T.; Weindel, Gabriel; Wierzchoń, Michał; Xu, Xinming; Ye, Qun; Yeon, Jiwon; Zou, Futing; Zylberberg, Ariel; Department of Psychology; Balcı, Fuat; Duyan, Yalçın Akın; Faculty Member; PhD Student; Department of Psychology; College of Social Sciences and Humanities; 51269; N/A; N/AUnderstanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at ) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects.Publication Open Access Prediction of optimal folding routes of proteins that satisfy the principle of lowest entropy loss: dynamic contact maps and optimal control(Public Library of Science, 2010) Department of Computer Engineering; Department of Chemical and Biological Engineering; Arkun, Yaman; Erman, Burak; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; College of Engineering; 108526; 179997An optimization model is introduced in which proteins try to evade high energy regions of the folding landscape, and prefer low entropy loss routes during folding. We make use of the framework of optimal control whose convenient solution provides practical and useful insight into the sequence of events during folding. We assume that the native state is available. As the protein folds, it makes different set of contacts at different folding steps. The dynamic contact map is constructed from these contacts. The topology of the dynamic contact map changes during the course of folding and this information is utilized in the dynamic optimization model. The solution is obtained using the optimal control theory. We show that the optimal solution can be cast into the form of a Gaussian Network that governs the optimal folding dynamics. Simulation results on three examples (CI2, Sso7d and Villin) show that folding starts by the formation of local clusters. Non-local clusters generally require the formation of several local clusters. Non-local clusters form cooperatively and not sequentially. We also observe that the optimal controller prefers "zipping" or small loop closure steps during folding. The folding routes predicted by the proposed method bear strong resemblance to the results in the literature.Publication Open Access Automated, quantitative cognitive/behavioral screening of mice: for genetics, pharmacology, animal cognition and undergraduate instruction(Journal of Visualized Experiments (JoVE), 2014) Gallistel, C. R.; Freestone, David; Kheifets, Aaron; King, Adam; Department of Psychology; Balcı, Fuat; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 51269We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be controlled by one computer.Publication Open Access Distinct chemical composition and enzymatic treatment induced human endothelial cells survival in acellular ovine aortae(BioMed Central, 2021) Rahbarghazi, Reza; Saberianpour, Shirin; Delkhosh, Aref; Amini, Hassan; Hassanpour, Mehdi; Heidarzadeh, Morteza; Sokullu, Emel; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 163024Objective: the current experiment aimed to assess the impact of detergents such as 3% Triton X-100, 1% peracetic acid, 1% Tween-20, and 1% SDS in combination with Trypsin–EDTA on acellularization of ovine aortae after 7 days. Results: Hematoxylin–Eosin staining showed an appropriate acellularization rate in ovine aortae, indicated by a lack of cell nuclei in the tunica media layer. DAPI staining confirmed the lack of nuclei in the vascular wall after being exposed to the combination of chemical and enzymatic solutions. Verhoeff-Van Gieson staining showed that elastin fibers were diminished in acellular samples compared to the control group while collagen stands were unchanged. CCK-8 survival assay showed enhanced viability in human umbilical vein endothelial cells 5 days after being cultured on decellularized samples compared to the cells cultured on a plastic surface (p < 0.05). SEM imaging showed flattening of endothelial cells on the acellular surface.