Publications with Fulltext
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
Browse
15 results
Search Results
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 Modelling and analysis of the impact of correlated inter-event data on production control using Markovian arrival processes(Springer, 2019) Department of Business Administration; Department of Industrial Engineering; N/A; Tan, Barış; Dizbin, Nima Manafzadeh; Faculty Member; Department of Business Administration; Department of Industrial Engineering; College of Administrative Sciences and Economics; College of Engineering; Graduate School of Business; 28600; N/AEmpirical studies show that the inter-event times of a production system are correlated. However, most of the analytical studies for the analysis and control of production systems ignore correlation. In this study, we show that real-time data collected from a manufacturing system can be used to build a Markovian arrival processes (MAP) model that captures correlation in inter-event times. The obtained MAP model can then be used to control production in an effective way. We first present a comprehensive review on MAP modeling and MAP fitting methods applicable to manufacturing systems. Then we present results on the effectiveness of these fitting methods and discuss how the collected inter-event data can be used to represent the flow dynamics of a production system accurately. In order to study the impact of capturing the flow dynamics accurately on the performance of a production control system, we analyze a manufacturing system that is controlled by using a base-stock policy. We study the impact of correlation in inter-event times on the optimal base-stock level of the system numerically by employing the structural properties of the MAP. We show that ignoring correlated arrival or service process can lead to overestimation of the optimal base-stock level for negatively correlated processes, and underestimation for the positively correlated processes. We conclude that MAPs can be used to develop data-driven models and control manufacturing systems more effectively by using shop-floor inter-event data.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 Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice(Nature Portfolio, 2022) Akyel, Yasemin Kübra; Korkmaz, Tuba; Selvi, Saba; Danış, İbrahim; İpek, Özgecan Savluğ; Aygenli, Fatih; Öztürk, Nuri; Öztürk, Narin; Ünal, Durişehvar Özer; Güzel, Mustafa; Okyar, Alper; N/A; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Gül, Şeref; Gül, Zeynep Melis; Işın, Şafak; Özcan, Onur; Akarlar, Büşra; Taşkın, Ali Cihan; Türkay, Metin; Kavaklı, İbrahim Halil; Researcher; Other; Faculty Member; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; N/A; N/A; N/A; N/A; N/A; 291296; 105301; 24956; 40319Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53(-/-) mice by similar to 25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation.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 Modelling data for predicting new iron garnet thin films with perpendicular magnetic anisotropy(Elsevier, 2020) Department of Electrical and Electronics Engineering; N/A; Onbaşlı, Mehmet Cengiz; Zanjani, Saeedeh Mokarian; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering; Graduate School of Sciences and Engineering; 258783; N/AThese data include detailed calculations and graphs based on our manuscript submitted to Journal of Magnetism and Magnetic Materials, entitled “Predicting New Iron Garnet Thin Films with Perpendicular Magnetic Anisotropy”. These data are organized in two parts; first, we present the calculated plots of sensitivity of magnetic anisotropy field and anisotropy energy density for 49 epitaxial rare earth iron garnet (REIG) film/substrate pairs (a total of 98 plots, Figs. 1–15). In the second part, we present in Table 1 the complete details on the calculations for total magnetic anisotropy and all material constants used for each of 50 film/substrate pairs. The comparison with the previous experimental demonstrations is also shown in Table 1 (last column) and 2 with an accompanying discussion confirming the reliability of our model.Publication Open Access De novo mutations in Plxnd1 and Rev3l cause mobius syndrome(Nature Publishing Group (NPG), 2015) Tomas-Roca, Laura; Tsaalbi-Shtylik, Anastasia; Jansen, Jacob G.; Singh, Manvendra K.; Epstein, Jonathan A.; Altunoglu, Umut; Verzijl, Harriette; Soria, Laura; van Beusekom, Ellen; Roscioli, Tony; Iqbal, Zafar; Gilissen, Christian; Hoischen, Alexander; de Brouwer,Arjan P. M.; Erasmus, Corrie; Schubert, Dirk; Brunner, Han; Aytes, Antonio Perez; Marin, Faustino; Aroca, Pilar; Carta, Arturo; de Wind, Niels; Padberg, George W.; van Bokhoven, Hans; N/A; Kayserili, Hülya; Other; School of Medicine; 7945Mobius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The aetiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Mobius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology. Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients.Publication Open Access Serum uric acid and acute kidney injury: a mini review(Elsevier, 2017) Hahn, Kai; Lanaspa, Miguel A.; Johnson, Richard J.; Ejaz, A. Ahsan; N/A; Kanbay, Mehmet; Faculty Member; School of Medicine; 110580Acute kidney injury causes great morbidity and mortality in both the community and hospital settings. Understanding the etiological factors and the pathophysiological principles resulting in acute kidney injury is essential in prompting appropriate therapies. Recently hyperuricemia has been recognized as a potentially modifiable risk factor for acute kidney injury, including that associated with cardiovascular surgery, radiocontrast administration, rhabdomyolysis, and associated with heat stress. This review discussed the evidence that repeated episodes of acute kidney injury from heat stress and dehydration may also underlie the pathogenesis of the chronic kidney disease epidemic that is occurring in Central America (Mesoamerican nephropathy). Potential mechanisms for how uric acid might contribute to acute kidney injury are also discussed, including systemic effects on renal microvasculature and hemodynamics, and local crystalline and noncrystalline effects on the renal tubules. Pilot clinical trials also show potential benefits of lowering uric acid on acute kidney injury associated with a variety of insults. In summary, there is mounting evidence that hyperuricemia may have a significant role in the development of acute kidney injury. Prospective, placebo controlled, randomized trials are needed to determine the potential benefit of uric acid lowering therapy on kidney and cardio-metabolic diseases.Publication Open Access Transport of gold nanoparticles by vascular endothelium from different human tissues(Public Library of Science, 2016) Gromnicova, Radka; Romero, Ignacio A.; Williams, Phil; Satchell, Simon; Sharrack, Basil; Male, David; N/A; Kaya, Mehmet; Faculty Member; School of Medicine; 10486The selective entry of nanoparticles into target tissues is the key factor which determines their tissue distribution. Entry is primarily controlled by microvascular endothelial cells, which have tissue-specific properties. This study investigated the cellular properties involved in selective transport of gold nanoparticles (<5 nm) coated with PEG-amine/galactose in two different human vascular endothelia. Kidney endothelium (ciGENC) showed higher uptake of these nanoparticles than brain endothelium (hCMEC/D3), reflecting their biodistribution in vivo. Nanoparticle uptake and subcellular localisation was quantified by transmission electron microscopy. The rate of internalisation was approximately 4x higher in kidney endothelium than brain endothelium. Vesicular endocytosis was approximately 4x greater than cytosolic uptake in both cell types, and endocytosis was blocked by metabolic inhibition, whereas cytosolic uptake was energy-independent. The cellular basis for the different rates of internalisation was investigated. Morphologically, both endothelia had similar profiles of vesicles and cell volumes. However, the rate of endocytosis was higher in kidney endothelium. Moreover, the glycocalyces of the endothelia differed, as determined by lectin-binding, and partial removal of the glycocalyx reduced nanoparticle uptake by kidney endothelium, but not brain endothelium. This study identifies tissue-specific properties of vascular endothelium that affects their interaction with nanoparticles and rate of transport.Publication Open Access 3D-printed microrobots from design to translation(Nature Portfolio, 2022) Department of Mechanical Engineering; N/A; Dabbagh, Sajjad Rahmani; Sarabi, Misagh Rezapour; Birtek, Mehmet Tuğrul; Sitti, Metin; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; 297104; 291971Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility.