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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6

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    PublicationOpen Access
    Transition from the fetal to neonatal circulation: Modeling the effects of umbilical cord clamping
    (Elsevier, 2015) Yiğit, Mehmet B.; Kowalski, William J.; Hutchon, David J.R.; Department of Mechanical Engineering; Pekkan, Kerem; Faculty Member; Department of Mechanical Engineering; College of Engineering; 161845
    Hemodynamics of the fetal to neonatal transition are orchestrated through complex physiological changes and results in cardiovascular adaptation to the adult biventricular circulation. Clinical practice during this critical period can influence vital organ physiology for normal newborns, premature babies and congenital heart defect patients. Particularly, the timing of the cord clamping procedure, immediate (ICC) vs. delayed cord clamping (DCC), is hypothesized to be an important factor for the transitory fetal hemodynamics. The clinical need for a quantitative understanding of this physiology motivated the development of a lumped parameter model (LPM) of the fetal cardio-respiratory system covering the late-gestation to neonatal period. The LPM was validated with in vivo clinical data and then used to predict the effects of cord clamping procedures on hemodynamics and vital gases. Clinical time-dependent resistance functions to simulate the vascular changes were introduced. For DCC, placental transfusion (31.3ml) increased neonatal blood volume by 11.7%. This increased blood volume is reflected in an increase in preload pressures by ~20% compared to ICC, which in turn increased the cardiac output (CO) by 20% (CO.sub.ICC =993ml/min; CO.sub.DCC =1197ml/min). Our model accurately predicted dynamic flow patterns in vivo. DCC was shown to maintain oxygenation if the onset of pulmonary respiration was delayed or impaired. On the other hand, a significant 25% decrease in oxygen saturations was observed when applying ICC under the same physiological conditions. We conclude that DCC has a significant impact on newborn hemodynamics, mainly because of the improved blood volume and the sustained placental respiration.
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    PublicationOpen Access
    Gaussian network model revisited: effects of mutation and ligand binding on protein behavior
    (Institute of Physics (IOP) Publishing, 2022) Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997
    The coarse-grained Gaussian network model (GNM), considers only the alpha carbons of the folded protein. Therefore it is not directly applicable to the study of mutation or ligand binding problems where atomic detail is required. This shortcoming is improved by including all atom pairs within the coordination shell of each other into the Kirchoff adjacency matrix. Counting all contacts rather than only alpha carbon contacts diminishes the magnitude of fluctuations in the system. But more importantly, it changes the graph-like connectivity structure, i.e., the Kirchoff adjacency matrix of the protein. This change depends on amino acid type which introduces amino acid specific and position specific information into the classical coarse-grained GNM which was originally modeled in analogy with the phantom network model of rubber elasticity. With this modification, it is now possible to explain the consequences of mutation and ligand binding on residue fluctuations, their pair-correlations and mutual information shared by each pair. We refer to the new model as 'all-atom GNM'. Using examples from published data we show that the all-atom GNM gives B-factors that are in better agreement with experiment, can explain effects of mutation on long range communication in PDZ domains and can predict effects of GDP and GTP binding on the dimerization of KRAS.
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    PublicationOpen Access
    Mode coupling points to functionally important residues in myosin II
    (Wiley, 2014) Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Physics; Varol, Onur; Yüret, Deniz; Erman, Burak; Kabakçıoğlu, Alkan; Faculty Member; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Physics; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; 179996; 179997; 49854
    Relevance of mode coupling to energy/information transfer during protein function, particularly in the context of allosteric interactions is widely accepted. However, existing evidence in favor of this hypothesis comes essentially from model systems. We here report a novel formal analysis of the near-native dynamics of myosin II, which allows us to explore the impact of the interaction between possibly non-Gaussian vibrational modes on fluctutational dynamics. We show that an information-theoretic measure based on mode coupling alone yields a ranking of residues with a statistically significant bias favoring the functionally critical locations identified by experiments on myosin II.