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Title: Mechanisms of adaptation and speciation : an experimental study using artificial life
Creator: Anderson, Carlos Jesus
Date: 2013
Collection: Electronic Theses & Dissertations
Description: Detailed experimental studies in evolutionary biology are sometimes difficult--even with model organisms. Theoretical models alleviate some of these difficulties and often provide clean results, but they cannot always capture the complexity of dynamic evolutionary processes. Artificial life systems are tools that fall somewhere between model organisms and theoretical models that have been successfully used to study evolutionary biology. These systems simulate simple organisms that replicate,...
Show moreDetailed experimental studies in evolutionary biology are sometimes difficult--even with model organisms. Theoretical models alleviate some of these difficulties and often provide clean results, but they cannot always capture the complexity of dynamic evolutionary processes. Artificial life systems are tools that fall somewhere between model organisms and theoretical models that have been successfully used to study evolutionary biology. These systems simulate simple organisms that replicate, acquire random mutations, and reproduce differentially; as a consequence, they evolve naturally (i.e., evolution itself is not simulated). Here I use the software Avida to study several open questions on the genetic mechanisms of adaptation and speciation.In Chapter 1 (p. 13), I investigated whether beneficial alleles during adaptation came from new mutations or standing genetic variation--alleles already present in the population. I found that most beneficial alleles came from standing genetic variation, but new mutations were necessary for long-term evolution. I also found that adaptation from standing genetic variation was faster than from new mutations. Finally, I found that recombination brought together beneficial combinations of alleles from standing genetic variation.In Chapter 2 (p. 31), I investigated the probability of compensatory adaptation vs. reversion. Compensatory adaptation is the fixation of mutations that ameliorate the effects of deleterious mutations while the original deleterious mutations remain fixed. I found that compensatory adaptation was very common, but the window of opportunity for reversion was increased when the initial fitness of the population was high, the population size was large, and the mutation rate was high. The reason that the window of opportunity for reversion was constrained was that negative epistatic interactions with compensatory mutations prevented the revertant from being beneficial to the population.In Chapter 3 (p. 58), I showed experimentally that compensatory adaptation can lead to reproductive isolation (specifically, postzygotic isolation). In addition, I found that the strength of this isolation was independent of the effect size of the original deleterious mutations. Finally, I found that both deleterious and compensatory mutations contribute equally to reproductive isolation.Reproductive isolation between populations often evolves as a byproduct of independent adaptation to new environments, but the selective pressures of these environments may be divergent (`ecological speciation') or uniform (`mutation-order speciation'). In Chapter 4 (p. 75), I compared directly the strength of postzygotic isolation generated by ecological and mutation-order processes with and without migration. I found that ecological speciation generally formed stronger isolation than mutation-order speciation and that mutation-order speciation was more sensitive to migration than ecological speciation.Under the Dobzhansky-Muller model of speciation, hybrid inviability or sterility results from the evolution of genetic incompatibilities (DMIs) between species-specific alleles. This model predicts that the number of pairwise DMIs between species should increase quadratically through time, but the few tests of this `snowball effect' have had conflicting results. In Chapter 5 (p. 101), I show that pairwise DMIs accumulated quadratically, supporting the snowball effect. I found that more complex genetic interactions involved alleles that rescued pairwise incompatibilities, explaining the discrepancy between the expected accumulations of DMIs and observation.
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Title: Logic simulation on massively parallel SIMD machines
Creator: Chung, Yunmo
Date: 1991
Collection: Electronic Theses & Dissertations

Title: Investigating the impact of manmade reservoirs on large-scale hydrology and water resources using high-resolution modeling
Creator: Shin, Sanghoon
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Manmade reservoirs are important components of the terrestrial hydrologic system. Dam installments fragment river systems, and reservoir operations alter flow regimes. The total storage capacity of existing global reservoirs is large enough to hold one sixth of annual continental discharge to global oceans. Due to growing energy demands, hundreds of large dams are being built and planned around the world, especially in the developing countries. Therefore, there is an urgent need to develop a...
Show moreManmade reservoirs are important components of the terrestrial hydrologic system. Dam installments fragment river systems, and reservoir operations alter flow regimes. The total storage capacity of existing global reservoirs is large enough to hold one sixth of annual continental discharge to global oceans. Due to growing energy demands, hundreds of large dams are being built and planned around the world, especially in the developing countries. Therefore, there is an urgent need to develop a better understanding of the impact of the existing and new dams on hydrological, ecological, agricultural, and socio-economic systems. Owing to increasing computational power and needs to understand and simulate processes in small-scale, hydrological models are advancing towards hyper-resolution global hydrological models. One of benefits of the increased spatial resolution is that the dynamics of surface water inundation over natural river-floodplain systems and manmade reservoirs can be explicitly represented; however, existing global models are not capable of simulating the river-floodplain-reservoir inundation dynamics in an integrated manner. This dissertation addresses this important standing issue by developing a high-resolution, continental-scale model to simulate the spatial and temporal dynamics of reservoir storage and release, thus paving pathways toward hyper-resolution surface water modeling in continental- to global-scale hydrological and climate models. The newly developed model is applied to simulate reservoirs within the contiguous United States (CONUS) and the Mekong River Basin (MRB) in Southeast Asia. With respect to the model development, the following advances are made over the previous global reservoir modeling studies: (1) an existing algorithm for reservoir operation is improved by conducting analytical analysis and numerical experiments and by introducing new calibration features for reservoir operation; (2) the spatial extent and its seasonal dynamics of reservoirs are explicitly simulated and reservoirs are treated as an integral part of river-floodplain routing, thus reservoir storage is no longer isolated from river and floodplain storages; and (3) a novel approach for processing and integrating high-resolution digital elevation models (DEMs) in river-floodplain-reservoir routing is introduced. The newly developed reservoir scheme is integrated within the river-floodplain routing scheme of a continental hydrological model, LEAF-Hydro-Flood, which is set for the CONUS, where abundant data are available for model validation. Then, the reservoir scheme is integrated into a global hydrodynamics model, CaMa-Flood, to investigate the historical impact of manmade reservoirs in the MRB that is experiencing an unprecedented boom in hydropower dam construction. Using the new scheme, the role of flood dynamics in modulating the hydrology of the MRB and the potential impact of flow regulation by the dams on the inundation dynamics are investigated. The significance of hydrologic effect of increasing dams is compared with that of climate variability. The fully coupled river-reservoir-floodplain storage simulation approach presented in this dissertation provides an advancement in hydrological modeling in terms of the representation of surface water dynamics, which is indispensable for better attribution of the observed changes in the water cycle, prediction of changes in water resources, and the understanding of the continually changing environmental and ecological systems.
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Title: Integration of topological data analysis and machine learning for small molecule property predictions
Creator: Wu, Kedi
Date: 2018
Collection: Electronic Theses & Dissertations
Description: Accurate prediction of small molecule properties is of paramount importance to drug design and discovery. A variety of quantitative properties of small molecules has been studied in this thesis. These properties include solvation free energy, partition coefficient, aqueous solubility, and toxicity endpoints. The highlight of this thesis is to introduce an algebraic topology based method, called element specific persistent homology (ESPH), to predict small molecule properties. Essentially ESPH...
Show moreAccurate prediction of small molecule properties is of paramount importance to drug design and discovery. A variety of quantitative properties of small molecules has been studied in this thesis. These properties include solvation free energy, partition coefficient, aqueous solubility, and toxicity endpoints. The highlight of this thesis is to introduce an algebraic topology based method, called element specific persistent homology (ESPH), to predict small molecule properties. Essentially ESPH describes molecular properties in terms of multiscale and multicomponent topological invariants and is different from conventional chemical and physical representations. Based on ESPH and its modified version, element-specific topological descriptors (ESTDs) are constructed. The advantage of ESTDs is that they are systematical, comprehensive, and scalable with respect to molecular size and composition variations, and are readily suitable for machine learning methods, rendering topological learning algorithms. Due to the inherent correlation between different small molecule properties, multi-task frameworks are further employed to simultaneously predict related properties. Deep neural networks, along with ensemble methods such as random forest and gradient boosting trees, are used to develop quantitative predictive models. Physical based molecular descriptors and auxiliary descriptors are also used in addition to ESTDs. As a result, we obtain state-of-the-art results for various benchmark data sets of small molecule properties. We have also developed two online servers for predicting properties of small molecules, TopP-S and TopTox. TopP-S is a software for topological learning predictions of partition coefficient and aqueous solubility, and TopTox is a software for computing element-specific tological descriptors (ESTDs) for toxicity endpoint predictions. They are available at http://weilab.math.msu.edu/TopP-S/ and http://weilab.math.msu.edu/TopTox/, respectively.
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Title: Improving the representation of irrigation and groundwater in global land surface models to advance the understanding of hydrology-human-climate interactions
Creator: Felfelani, Farshid
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Hydrological models and satellite observations have been widely used to study the variations in the Earth's hydrology and climate over multitude of scales, especially in relation to natural and human-induced changes in the terrestrial water cycle. Yet, both satellite products and model results suffer from inherent uncertainties, calling for the need to improve the representation of critical processes in the models and to make a combined use of satellite data and models to examine the...
Show moreHydrological models and satellite observations have been widely used to study the variations in the Earth's hydrology and climate over multitude of scales, especially in relation to natural and human-induced changes in the terrestrial water cycle. Yet, both satellite products and model results suffer from inherent uncertainties, calling for the need to improve the representation of critical processes in the models and to make a combined use of satellite data and models to examine the variations in the terrestrial hydrology. The representation of irrigation and groundwater-two major hydrologic processes with complex reciprocal interplay-in large-scale hydrological models is rather poorly parameterized and heavily simplified, hindering our ability to realistically simulate groundwater-human-climate interactions. This dissertation advances the physical basis for irrigation and groundwater parameterizations in global land surface models, leveraging the potential of emerging satellite data (i.e., data from GRACE and SMAP satellite missions) toward a more realistic quantification of the impacts of human activities on the hydrological cycle. A comprehensive global analysis is developed to examine the historical spatial patterns and long-term temporal response, i.e., the terrestrial water storage (TWS), of two models to natural and human-induced drivers. Human-induced changes in TWS are then quantified in the highly managed global regions to identify the uncertainties arising from a simplistic representation of irrigation and groundwater. The potential of improving irrigation representation in the Community Land Model version 4.5 (CLM4.5) is then investigated by assimilating the soil moisture data from SMAP satellite mission using 1-D Kalman Filter assimilation approach. The new irrigation scheme is then tested over the heavily irrigated central U.S. Next, the existing groundwater module of CLM5 is broadly evaluated over conterminous U.S. and a new prognostic groundwater module is implemented in CLM5 to account for lateral groundwater flow, pumping, and conjunctive water use for irrigation. In particular, an explicit parameterization for the steady-state well equation is introduced for the first time in large-scale hydrological modeling. Finally, the impacts of climate change on global TWS variabilities and the implications on sea level change are examined for the entire 21st century using multi-model hydrological simulations. The key findings and conclusions from the aforementioned multi-scale analysis and model developments are: (1) in terms of TWS, notable differences exist not only between simulations of hydrological models and GRACE but also among different GRACE products, therefore, TWS variations from a single model cannot be reliably used for global analyses; (2) these differences significantly increase in projections of TWS under climate change, however, models agree in sign of change for most global areas; (3) TWS is expected to decline in many regions in southern hemisphere, but increase in northern high latitudes, projected to accelerate sea level rise by the mid- and late-21st century; (4) constraining the target soil moisture in CLM4.5 using SMAP data assimilation with 1-D Kalman Filter reduces the bias in the simulated irrigation water by up to 60% on average, improving irrigation and soil moisture simulations in CLM4.5; (5) the new groundwater model significantly improves the simulation of groundwater level change and promisingly captures most of the hotspots of groundwater depletion across the U.S. overexploited aquifers; and (6) the simulation with the lateral groundwater flow substantially enhances the TWS trends relative to the default CLM5. These results and findings could provide a basis for improved large-scale irrigation and groundwater modeling and improve our understanding of hydrology-human-climate interactions.
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Title: IFLMAPS : an interactive farm level marketing and production simulator intended for research, teaching and extension applications
Creator: Rister, M. Edward (Milton Edward)
Date: 1981
Collection: Electronic Theses & Dissertations

Title: Experiments and model development of a dual mode, turbulent jet ignition engine
Creator: Tolou, Sedigheh
Date: 2019
Collection: Electronic Theses & Dissertations
Description: "The number of vehicles powered by a source of energy other than traditional petroleum fuels will increase as time passes. However, based on current predictions, vehicles run on liquid fuels will be the major source of transportation for decades to come. Advanced combustion technologies can improve fuel economy of internal combustion (IC) engines and reduce exhaust emissions. The Dual Mode, Turbulent Jet Ignition (DM-TJI) system is an advanced, distributed combustion technology which can...
Show more"The number of vehicles powered by a source of energy other than traditional petroleum fuels will increase as time passes. However, based on current predictions, vehicles run on liquid fuels will be the major source of transportation for decades to come. Advanced combustion technologies can improve fuel economy of internal combustion (IC) engines and reduce exhaust emissions. The Dual Mode, Turbulent Jet Ignition (DM-TJI) system is an advanced, distributed combustion technology which can achieve high diesel-like thermal efficiencies at medium to high loads and potentially exceed diesel efficiencies at low-load operating conditions. The DM-TJI strategy extends the mixture flammability limits by igniting lean and/or highly dilute mixtures, leading to low-temperature combustion (LTC) modes in spark ignition (SI) engines. A novel, reduced order, and physics-based model was developed to predict the behavior of a DM-TJI engine with a pre-chamber air valve assembly. The engine model developed was calibrated based on experimental data from a Prototype II DM-TJI engine. This engine was designed, built, and tested at the MSU Energy and Automotive Research Laboratory (EARL). A predictive, generalized model was introduced to obtain a complete engine fuel map for the DM-TJI engine. The engine fuel map was generated in a four-cylinder boosted configuration under highly dilute conditions, up to 40% external exhaust gas recirculation (EGR). A vehicle simulation was then performed to further explore fuel economy gains using the fuel map generated for the DM-TJI engine. The DM-TJI engine was embodied in an industry-based vehicle to examine the behavior of the engine over the U.S. Environmental Protection Agency (EPA) driving schedules. The results obtained from the drive cycle analysis of the DM-TJI engine in an industry-based vehicle were compared to the results of the same vehicle with its original engine. The vehicle equipped with the DM-TJI system was observed to benefit from 103033% improvement in fuel economy and 103031% reduction in CO2 emission over the EPA combined city/high driving schedules. Potential improvements were discussed, as these results of the drive cycle analysis are the first-ever reported results for a DM-TJI engine embodied in an industry-based vehicle. The resulting fuel economy and CO2 emission were used to conduct a cost-benefit analysis of a DM-TJI engine. The cost-benefit analysis followed the economic and key inputs used by the U.S. EPA in a Proposed Determination prepared by that agency. The outcomes of the cost-benefit analysis for the vehicle equipped with the DM-TJI system were reported in comparison with the same vehicle with its base engine. The extra costs of a DM-TJI engine were observed to be compensated over the first three years of the vehicle's life time. The results projected maximum savings of approximately 2400 in 2019 dollars. This includes the lifetime-discounted present value of the net benefits of the DM-TJI technology, compared to the base engine examined. In this dollar saving estimate, the societal effects of CO2 emission were calculated based on values by the interagency working group (IWG) at 3% discount rate."--Pages ii-iii.
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Title: Evolutionary dynamics of digitized organizational routines
Creator: Liu, Peng
Date: 2013
Collection: Electronic Theses & Dissertations
Description: This dissertation explores the effects of increased digitization on the evolutionary dynamics of organizational routines. Do routines become more flexible, or more rigid, as the mix of digital technologies and human actors changes? What are the mechanisms that govern the evolution of routines? The dissertation theorizes about the effects of increased digitization on path dependence and interdependence mechanisms, and therefore extends current theory on the evolutionary dynamics of...
Show moreThis dissertation explores the effects of increased digitization on the evolutionary dynamics of organizational routines. Do routines become more flexible, or more rigid, as the mix of digital technologies and human actors changes? What are the mechanisms that govern the evolution of routines? The dissertation theorizes about the effects of increased digitization on path dependence and interdependence mechanisms, and therefore extends current theory on the evolutionary dynamics of organizational routines by taking into account the effects of three basic phenomena: digitization, path dependence and interdependence.In this dissertation, I use computer-based simulation, grounded with data collected in field interviews, to model the evolution of routines. More specifically, this dissertation models routines as networks of action that are subject to an evolutionary process of random variation and selective retention. To assess the evolution of routine, I introduce the idea of evolutionary trajectory, which is defined as the product of the magnitude of change and the direction of change in the networks of action.The dissertation also addresses a foundational issue in the literature on organizational routines. Routines are generally believed to remain stable due to path dependence. An alternative explanation is that routines may be stable due to interdependence among actions, which tends to constrain the sequence in which actions can occur. I have developed a simulation that allows meto test the relative importance of these factors, a question that has never been addressed. By addressing this fundamental issue, I provide a deeper, theory driven explanation of the effects of digitization.
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Title: Evaluation of the impacts of a simulated irrigation withdrawal on the habitat and populations of brook trout and benthic macroinvertebrates in Hunt Creek, Michigan
Creator: Baker, Edward Allen
Date: 1995
Collection: Electronic Theses & Dissertations

Title: Evaluation of calibration for optical see-through augmented reality systems
Creator: McGarrity, Erin Scott
Date: 2001
Collection: Electronic Theses & Dissertations

Title: Energy utilization modeling of animal draft power (EUMDAP) for Kenyan small-holder semi-arid agriculture
Creator: Mungai, George S. N.
Date: 1998
Collection: Electronic Theses & Dissertations

Title: Empirical analysis of the effects of decision type and control over data access and model access on user preference for modeling environments
Creator: Dawson, Margaret (Margaret Leigh)
Date: 1988
Collection: Electronic Theses & Dissertations

Title: Elucidating the evolutionary origins of collective animal behavior
Creator: Olson, Randal S.
Date: 2015
Collection: Electronic Theses & Dissertations
Description: Despite over a century of research, the evolutionary origins of collective animal behavior remain unclear. Dozens of hypotheses explaining the evolution of collective behavior have risen and fallen in the past century, but until recently it has been difficult to perform controlled behavioral evolution experiments to isolate these various hypotheses and test their individual effects. In this dissertation, I outline a relatively new method using digital models of evolution to perform controlled...
Show moreDespite over a century of research, the evolutionary origins of collective animal behavior remain unclear. Dozens of hypotheses explaining the evolution of collective behavior have risen and fallen in the past century, but until recently it has been difficult to perform controlled behavioral evolution experiments to isolate these various hypotheses and test their individual effects. In this dissertation, I outline a relatively new method using digital models of evolution to perform controlled behavioral evolution experiments. In particular, I use these models to directly explore the evolutionary consequence of the selfish herd, predator confusion, and the many eyes hypotheses, and demonstrate how the models can lend key insights useful to behavioral biologists, computer scientists, and robotics researchers. This dissertation lays the groundwork for the experimental study of the hypotheses surrounding the evolution of collective animal behavior, and establishes a path for future experiments to explore and disentangle how the various hypothesized benefits of collective behavior interact over evolutionary time.
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Title: Dynamic simulation of the electrorheological effect in a uniformly distributed electric field
Creator: Cristescu, Nicolae
Date: 2000
Collection: Electronic Theses & Dissertations

Title: Diverse platform modeling of dynamical systems
Creator: Mitchell, Robert Alex
Date: 1991
Collection: Electronic Theses & Dissertations

Title: Designing a package for pharmaceutical tablets in relation to moisture and dissolution
Creator: Yoon, Seungyil
Date: 2003
Collection: Electronic Theses & Dissertations

Title: Design and simulation of single-crystal diamond diodes for high voltage, high power and high temperature applications
Creator: Suwanmonkha, Nutthamon
Date: 2016
Collection: Electronic Theses & Dissertations
Description: ABSTRACTDESIGN AND SIMULATION OF SINGLE-CRYSTAL DIAMOND DIODES FOR HIGH VOLTAGE, HIGH POWER AND HIGH TEMPERATURE APPLICATIONSByNutthamon SuwanmonkhaDiamond has exceptional properties and great potentials for making high-power semiconducting electronic devices that surpass the capabilities of other common semiconductors including silicon. The superior properties of diamond include wide bandgap, high thermal conductivity, large electric breakdown field and fast carrier mobilities. All of these...
Show moreABSTRACTDESIGN AND SIMULATION OF SINGLE-CRYSTAL DIAMOND DIODES FOR HIGH VOLTAGE, HIGH POWER AND HIGH TEMPERATURE APPLICATIONSByNutthamon SuwanmonkhaDiamond has exceptional properties and great potentials for making high-power semiconducting electronic devices that surpass the capabilities of other common semiconductors including silicon. The superior properties of diamond include wide bandgap, high thermal conductivity, large electric breakdown field and fast carrier mobilities. All of these properties are crucial for a semiconductor that is used to make electronic devices that can operate at high power levels, high voltage and high temperature.Two-dimensional semiconductor device simulation software such as Medici assists engineers to design device structures that allow the performance requirements of device applications to be met. Most physical material parameters of the well-known semiconductors are already compiled and embedded in Medici. However, diamond is not one of them. Material parameters of diamond, which include the models for incomplete ionization, temperature-and-impurity-dependent mobility, and impact ionization, are not readily available in software such as Medici. Models and data for diamond semiconductor material have been developed for Medici in the work based on results measured in the research literature and in the experimental work at Michigan State University. After equipping Medici with diamond material parameters, simulations of various diamond diodes including Schottky, PN-junction and merged Schottky/PN-junction diode structures are reported. Diodes are simulated versus changes in doping concentration, drift layer thickness and operating temperature. In particular, the diode performance metrics studied include the breakdown voltage, turn-on voltage, and specific on-resistance. The goal is to find the designs which yield low power loss and provide high voltage blocking capability. Simulation results are presented that provide insight for the design of diamond diodes using the various diode structures. Results are also reported on the use of field plate structures in the simulations to control the electric field and increase the breakdown voltage.
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Title: Data-driven and task-specific scoring functions for predicting ligand binding poses and affinity and for screening enrichment
Creator: Ashtawy, Hossam Mohamed Farg
Date: 2017
Collection: Electronic Theses & Dissertations
Description: Molecular modeling has become an essential tool to assist in early stages of drug discovery and development. Molecular docking, scoring, and virtual screening are three such modeling tasks of particular importance in computer-aided drug discovery. They are used to computationally simulate the interaction between small drug-like molecules, known as ligands, and a target protein whose activity is to be altered. Scoring functions (SF) are typically employed to predict the binding conformation ...
Show moreMolecular modeling has become an essential tool to assist in early stages of drug discovery and development. Molecular docking, scoring, and virtual screening are three such modeling tasks of particular importance in computer-aided drug discovery. They are used to computationally simulate the interaction between small drug-like molecules, known as ligands, and a target protein whose activity is to be altered. Scoring functions (SF) are typically employed to predict the binding conformation (docking task), binary activity label (screening task), and binding affinity (scoring task) of ligands against a critical protein in the disease's pathway. In most molecular docking software packages available today, a generic binding affinity-based (BA-based) SF is invoked for the three tasks to solve three different, but related, prediction problems. The vast majority of these predictive models are knowledge-based, empirical, or force-field scoring functions. The fourth family of SFs that has gained popularity recently and showed potential of improved accuracy is based on machine-learning (ML) approaches. Despite intense efforts in developing conventional and current ML SFs, their limited predictive accuracies in these three tasks have been a major roadblock toward cost-effective drug discovery. Therefore, in this work we present (i) novel task- specific and multi-task SFs employing large ensembles of deep neural networks (NN) and other state-of-the-art ML algorithms in conjunction with (ii) data-driven multi-perspective descriptors (features) for accurate characterization of protein-ligand complexes (PLCs) extracted using our Descriptor Data Bank (DDB) platform.We assess the docking, screening, scoring, and ranking accuracies of the proposed task-specific SFs with DDB descriptors as well as several conventional approaches in the context of the 2007 and 2014 PDBbind benchmark that encompasses a diverse set of high-quality PLCs. Our approaches substantially outperform conventional SFs based on BA and single-perspective descriptors in all tests. In terms of scoring accuracy, we find that the ensemble NN SFs, BsN-Score and BgN-Score, have more than 34% better correlation (0.844 and 0.840 vs. 0.627) between predicted and measured BAs compared to that achieved by X-Score, a top performing conventional SF. We further find that ensemble NN models surpass SFs based on other state-of-the-art ML algorithms. Similar results have been obtained for the ranking task. Within clusters of PLCs with different ligands bound to the same target protein, we find that the best ensemble NN SF is able to rank the ligands correctly 64.6% of the time compared to 57.8% obtained by X-Score. A substantial improvement in the docking task has also been achieved by our proposed docking-specific SFs. We find that the docking NN SF, BsN-Dock, has a success rate of 95% in identifying poses that are within 2 Å RMSD from the native poses of 65 different protein families. This is in comparison to a success rate of only 82% achieved by the best conventional SF, ChemPLP, employed in the commercial docking software GOLD. As for the ability to distinguish active molecules from inactives, our screening-specific SFs showed excellent improvements over the conventional approaches. The proposed SF BsN-Screen achieved a screening enrichment factor of 33.90 as opposed to 19.54 obtained from the best conventional SF, GlideScore, employed in the docking software Glide. For all tasks, we observed that the proposed task-specific SFs benefit more than their conventional counterparts from increases in the number of descriptors and training PLCs. They also perform better on novel proteins that they were never trained on before. In addition to the three task-specific SFs, we propose a novel multi-task deep neural network (MT-Net) that is trained on data from three tasks to simultaneously predict binding poses, affinities, and activity labels. MT-Net is composed of shared hidden layers for the three tasks to learn common features, task-specific hidden layers for higher feature representation, and three outputs for the three tasks. We show that the performance of MT-Net is superior to conventional SFs and competitive with other ML approaches. Based on current results and potential improvements, we believe our proposed ideas will have a transformative impact on the accuracy and outcomes of molecular docking and virtual screening.
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Title: Computer simulations of high-energy heavy ion collisions
Creator: Kortemeyer, Gerd
Date: 1997
Collection: Electronic Theses & Dissertations

Title: Computational modeling of cardiac mechanics : microstructual modeling & pulmonary arterial hypertension
Creator: Xi, Ce
Date: 2019
Collection: Electronic Theses & Dissertations
Description: Heart diseases, which approximately account for 31% of all human mortality every year, are the leading cause of death worldwide. Computational cardiac models have gained increasing popularity and become an indispensable and powerful tool in elucidating the pathological process of different heart diseases. They can be used to estimate important physiological and clinically relevant quantities that are difficult to directly measure in experiments. The broad goals of this thesis were to develop...
Show moreHeart diseases, which approximately account for 31% of all human mortality every year, are the leading cause of death worldwide. Computational cardiac models have gained increasing popularity and become an indispensable and powerful tool in elucidating the pathological process of different heart diseases. They can be used to estimate important physiological and clinically relevant quantities that are difficult to directly measure in experiments. The broad goals of this thesis were to develop 1) a microstructure-based constitutive model of the heart and 2) patient-specific computational models that would ultimately help medical scientists to diagnose and treat heart diseases.Heart diseases such as heart failure with preserved ejection fraction (HFpEF) are characterized by abnormalities of ventricular function that can be attributed to, changes in geometry, impaired myocyte (LV) relaxation, cardiac fibrosis and myocyte passive stiffening. Understanding how LV filling is affected by each of the many microstructural pathological features in heart diseases is very important and may help in the development of appropriate treatments. To address this need, we have developed and validated a microstructure-based computational model of the myocardium to investigate the role of tissue constituents and their ultrastructure in affecting the heart function. The model predicted that the LV filling function is sensitive to the collagen ultrastructure and the load taken up by the tissue constituents varies depending on the LV transmural location. This finding may have implications in the development of new pharmaceutical treatments targeting individual cardiac tissue constituents to normalize LV filling function in HFpEF.Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by elevated pulmonary artery pressure (PAP) and pulmonary artery vascular resistance, with limited survival rate and can affect patients of all ages. The increased pressure or afterload in the right ventricle (RV) can result in pathological changes in RV mechanics, which are currently not well-understood. To FB01ll this void, we have developed patient-specific computational models to investigate effects of PAH on ventricular mechanics. SpeciFB01cally, we have quantified regional ventricular myoFB01ber stress, myoFB01ber strain, contractility, and passive tissue stiffness in PAH patients, and compare them to those found in age- and gender-matched normal controls. Our results showed that RV longitudinal, circumferential and radial strain were depressed in PAH patients compared with controls; RV passive stiffness increased progressively with the degree of remodeling as indexed by the RV and LV end-diastolic volume ratio (RVEDV/LVEDV); Peak contractility of the RV was found to be strongly correlated, and had an inverse relationship with RVEDV/LVEDV. These results provide the mechanical basis of using RVEDV/LVEDV as a clinical index for delineating disease severity and estimating RVFW contractility in PAH patients.
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