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Publication Metadata only Anomalies in the transcriptional regulatory network of the Yeast Saccharomyces cerevisiae(Elsevier, 2010) N/A; Department of Physics; Tuğrul, Murat; Kabakçıoğlu, Alkan; N/A; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 49854We investigate the structural and dynamical properties of the transcriptional regulatory network of the Yeast Saccharomyces cerevisiae and compare it with two "unbiased" ensembles: one obtained by reshuffling the edges and the other generated by mimicking the transcriptional regulation mechanism within the cell. Both ensembles reproduce the degree distributions (the first-by construction-exactly and the second approximately), degree-degree correlations and the k-core structure observed in Yeast. An exceptionally large dynamically relevant core network found in Yeast in comparison with the second ensemble points to a strong bias towards a collective organization which is achieved by subtle modifications in the network's degree distributions. We use a Boolean model of regulatory dynamics with various classes of update functions to represent in vivo regulatory interactions. We find that the Yeast's core network has a qualitatively different behavior, accommodating on average multiple attractors unlike typical members of both reference ensembles which converge to a single dominant attractor. Finally, we investigate the robustness of the networks and find that the stability depends strongly on the used function class. The robustness measure is squeezed into a narrower band around the order-chaos boundary when Boolean inputs are required to be nonredundant on each node. However, the difference between the reference models and the Yeast's core is marginal, suggesting that the dynamically stable network elements are located mostly on the peripherals of the regulatory network. Consistently, the statistically significant three-node motifs in the dynamical core of Yeast turn out to be different from and less stable than those found in the full transcriptional regulatory network.Publication Metadata only Bias, Type I error rates, and statistical power of a latent mediation model in the presence of violations of invariance(Sage, 2018) Olivera-Aguilar, Margarita; Rikoon, Samuel H.; Gonzalez Oskar; MacKinnon David P.; Department of Psychology; Sakarya, Yasemin Kisbu; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 219275When testing a statistical mediation model, it is assumed that factorial measurement invariance holds for the mediating construct across levels of the independent variable X. The consequences of failing to address the violations of measurement invariance in mediation models are largely unknown. The purpose of the present study was to systematically examine the impact of mediator noninvariance on the Type I error rates, statistical power, and relative bias in parameter estimates of the mediated effect in the single mediator model. The results of a large simulation study indicated that, in general, the mediated effect was robust to violations of invariance in loadings. In contrast, most conditions with violations of intercept invariance exhibited severely positively biased mediated effects, Type I error rates above acceptable levels, and statistical power larger than in the invariant conditions. The implications of these results are discussed and recommendations are offered.Publication Open Access Censoring distances based on labeled cortical distance maps in cortical morphometry(Frontiers, 2013) Nishino, Tomoyuki; Alexopolous, Dimitrios; Todd, Richard D.; Botteron, Kelly N.; Miller, Michael I.; Ratnanather, J. Tilak; Department of Mathematics; Ceyhan, Elvan; Undergraduate Student; Faculty Member; Department of Mathematics; College of SciencesIt has been demonstrated that shape differences in cortical structures may be manifested in neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM) voxels with respect to GM/white matter (VW) surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.Publication Metadata only Exploring a diverse world of effector domains and amyloid signaling motifs in fungal NLR proteins(Public Library Science, 2022) Wojciechowski, Jakub W.; Gasior-Glogowska, Marlena; Coustou, Virginie; Szulc, Natalia; Szefczyk, Monika; Kopaczynska, Marta; Saupe, Sven J.; Dyrka, Witold; Tekoğlu, Tahsin Emirhan; PhD Student; Graduate School of Sciences and Engineering; N/ANLR proteins are intracellular receptors constituting a conserved component of the innate immune system of cellular organisms. In fungi, NLRs are characterized by high diversity of architectures and presence of amyloid signaling. Here, we explore the diverse world of effector and signaling domains of fungal NLRs using state-of-the-art bioinformatic methods including MMseqs2 for fast clustering, probabilistic context-free grammars for sequence analysis, and AlphaFold2 deep neural networks for structure prediction. In addition to substantially improving the overall annotation, especially in basidiomycetes, the study identifies novel domains and reveals the structural similarity of MLKL-related HeLo- and Goodbye-like domains forming the most abundant superfamily of fungal NLR effectors. Moreover, compared to previous studies, we found several times more amyloid motif instances, including novel families, and validated aggregating and prion-forming properties of the most abundant of them in vitro and in vivo. Also, through an extensive in silico search, the NLR-associated amyloid signaling was identified in basidiomycetes. The emerging picture highlights similarities and differences in the NLR architectures and amyloid signaling in ascomycetes, basidiomycetes and other branches of life.Publication Open Access HMI-PRED 2.0: a biologist-oriented web application for prediction of host-microbe protein-protein interaction by interface mimicry(Oxford University Press (OUP), 2022) Lim, H., Tsai, C.J.; Nussinov, R.; Department of Computer Engineering; Department of Chemical and Biological Engineering; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; College of Engineering; 26605; 8745HMI-PRED 2.0 is a publicly available web service for the prediction of host-microbe protein-protein interaction by interface mimicry that is intended to be used without extensive computational experience. A microbial protein structure is screened against a database covering the entire available structural space of complexes of known human proteins.Publication Open Access Modeling the interplay between HDV and HBV in chronic HDV/HBV patients(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Mhlanga, A.; Zakh, R.; Churkin, A.; Reinharz, V.; Glenn, J.S.; Etzion, O.; Cotler, S.J.; Barash, D.; Dahari H.; Yurtaydın, Süleyman Cihan; Faculty Member; School of Medicine; 189330Hepatitis D virus is an infectious subviral agent that can only propagate in people infected with hepatitis B virus. In this study, we modified and further developed a recent model for early hepatitis D virus and hepatitis B virus kinetics to better reproduce hepatitis D virus and hepatitis B virus kinetics measured in infected patients during anti-hepatitis D virus treatment. The analytical solutions were provided to highlight the new features of the modified model. The improved model offered significantly better prospects for modeling hepatitis D virus and hepatitis B virus interactions.Publication Open Access Nonlinear spectral singularities for confined nonlinearities(American Physical Society (APS), 2013) Department of Mathematics; Mostafazadeh, Ali; Faculty Member; Department of Mathematics; College of Sciences; 4231We introduce a notion of spectral singularity that applies for a general class of nonlinear Schrodinger operators involving a confined nonlinearity. The presence of the nonlinearity does not break the parity-reflection symmetry of spectral singularities but makes them amplitude dependent. Nonlinear spectral singularities are, therefore, associated with a resonance effect that produces amplified waves with a specific amplitude-wavelength profile. We explore the consequences of this phenomenon for a complex delta-function potential that is subject to a general confined nonlinearity.Publication Metadata only Stratified partial likelihood estimation(Elsevier, 1999) Ridder, Gert; Department of Economics; Tunalı, Fehmi İnsan; Faculty Member; Department of Economics; College of Administrative Sciences and Economics; 105635When multiple durations are generated by a single unit, they may be related in a way that is not fully captured by the regressors. The omitted unit-specific variables might vary over the durations, They might also be correlated with the variables in the regression component. We propose an estimator that responds to these concerns and develop a specification test for detecting unobserved unit-specific effects, Data from Malaysia reveal that concentration of child mortality in some families is imperfectly explained by observed explanatory variables, and that failure to control for unobserved heterogeneity seriously biases the parameter estimates.Publication Open Access Testing spatial symmetry using contingency tables based on nearest neighbor relations(Hindawi, 2014) Department of Mathematics; Ceyhan, Elvan; Undergraduate Student; Faculty Member; Department of Mathematics; College of SciencesWe consider two types of spatial symmetry, namely, symmetry in the mixed or shared nearest neighbor (NN) structures. We use Pielou’s and Dixon’s symmetry tests which are defined using contingency tables based on the NN relationships between the data points. We generalize these tests to multiple classes and demonstrate that both the asymptotic and exact versions of Pielou’s first type of symmetry test are extremely conservative in rejecting symmetry in the mixed NN structure and hence should be avoided or only the Monte Carlo randomized version should be used. Under RL, we derive the asymptotic distribution for Dixon’s symmetry test and also observe that the usual independence test seems to be appropriate for Pielou’s second type of test. Moreover, we apply variants of Fisher’s exact test on the shared NN contingency table for Pielou’s second test and determine the most appropriate version for our setting. We also consider pairwise and one-versus-rest type tests in post hoc analysis after a significant overall symmetry test. We investigate the asymptotic properties of the tests, prove their consistency under appropriate null hypotheses, and investigate finite sample performance of them by extensive Monte Carlo simulations. The methods are illustrated on a real-life ecological data set.