The thermodynamics and statistical mechanics of protein folding

The physics of self-organization and complexity is manifested on a variety of biological scales, from large ecosystems to the molecular level. Protein molecules exhibit characteristics of complex systems in terms of their structure, dynamics, and function. Proteins have the extraordinary ability to fold to a specific functional three-dimensional shape, starting from a random coil, in a biologically relevant time. How they accomplish this is one of the secrets of life. In this work, theoretical research into understanding this remarkable behavior is discussed. Thermodynamic and statistical mechanical tools are used in order to investigate the protein folding dynamics and stability. Theoretical analyses of the results from computer simulation of the dynamics of a four-helix bundle show that the excluded volume entropic effects are very important in protein dynamics and crucial for protein stability. The dramatic effects of changing the size of sidechains imply that a strategic placement of amino acid residues with a particular size may be an important consideration in protein engineering. Another investigation deals with modeling protein structural transitions as a phase transition. Using finite size scaling theory, the nature of unfolding transition of a four-helix bundle protein was investigated and critical exponents for the transition were calculated for various hydrophobic strengths in the core. It is found that the order of the transition changes from first to higher order as the strength of the hydrophobic interaction in the core region is significantly increased. Finally, a detailed kinetic and thermodynamic analysis was carried out in a model two-helix bundle. The connection between the structural free-energy landscape and folding kinetics was quantified. I show how simple protein engineering, by changing the hydropathy of a small number of amino acids, can enhance protein folding by significantly changing the free energy landscape so that kinetic traps are removed. The results have general applicability in protein engineering as well as understanding the underlying physical mechanisms of protein folding. ^

Lattice Boltzmann modeling of fluid flow and solute transport in karst aquifers

A novel modeling approach is applied to karst hydrology. Long-standing problems in karst hydrology and solute transport are addressed using Lattice Boltzmann methods (LBMs). These methods contrast with other modeling approaches that have been applied to karst hydrology. The motivation of this dissertation is to develop new computational models for solving ground water hydraulics and transport problems in karst aquifers, which are widespread around the globe. This research tests the viability of the LBM as a robust alternative numerical technique for solving large-scale hydrological problems. The LB models applied in this research are briefly reviewed and there is a discussion of implementation issues. The dissertation focuses on testing the LB models. The LBM is tested for two different types of inlet boundary conditions for solute transport in finite and effectively semi-infinite domains. The LBM solutions are verified against analytical solutions. Zero-diffusion transport and Taylor dispersion in slits are also simulated and compared against analytical solutions. These results demonstrate the LBM’s flexibility as a solute transport solver. The LBM is applied to simulate solute transport and fluid flow in porous media traversed by larger conduits. A LBM-based macroscopic flow solver (Darcy’s law-based) is linked with an anisotropic dispersion solver. Spatial breakthrough curves in one and two dimensions are fitted against the available analytical solutions. This provides a steady flow model with capabilities routinely found in ground water flow and transport models (e.g., the combination of MODFLOW and MT3D). However the new LBM-based model retains the ability to solve inertial flows that are characteristic of karst aquifer conduits. Transient flows in a confined aquifer are solved using two different LBM approaches. The analogy between Fick’s second law (diffusion equation) and the transient ground water flow equation is used to solve the transient head distribution. An altered-velocity flow solver with source/sink term is applied to simulate a drawdown curve. Hydraulic parameters like transmissivity and storage coefficient are linked with LB parameters. These capabilities complete the LBM’s effective treatment of the types of processes that are simulated by standard ground water models. The LB model is verified against field data for drawdown in a confined aquifer.

Lattice Boltzmann Modeling of Fluid Flow and Solute Transport in Karst Aquifers

A novel modeling approach is applied to karst hydrology. Long-standing problems in karst hydrology and solute transport are addressed using Lattice Boltzmann methods (LBMs). These methods contrast with other modeling approaches that have been applied to karst hydrology. The motivation of this dissertation is to develop new computational models for solving ground water hydraulics and transport problems in karst aquifers, which are widespread around the globe. This research tests the viability of the LBM as a robust alternative numerical technique for solving large-scale hydrological problems. The LB models applied in this research are briefly reviewed and there is a discussion of implementation issues. The dissertation focuses on testing the LB models. The LBM is tested for two different types of inlet boundary conditions for solute transport in finite and effectively semi-infinite domains. The LBM solutions are verified against analytical solutions. Zero-diffusion transport and Taylor dispersion in slits are also simulated and compared against analytical solutions. These results demonstrate the LBM’s flexibility as a solute transport solver. The LBM is applied to simulate solute transport and fluid flow in porous media traversed by larger conduits. A LBM-based macroscopic flow solver (Darcy’s law-based) is linked with an anisotropic dispersion solver. Spatial breakthrough curves in one and two dimensions are fitted against the available analytical solutions. This provides a steady flow model with capabilities routinely found in ground water flow and transport models (e.g., the combination of MODFLOW and MT3D). However the new LBM-based model retains the ability to solve inertial flows that are characteristic of karst aquifer conduits. Transient flows in a confined aquifer are solved using two different LBM approaches. The analogy between Fick’s second law (diffusion equation) and the transient ground water flow equation is used to solve the transient head distribution. An altered-velocity flow solver with source/sink term is applied to simulate a drawdown curve. Hydraulic parameters like transmissivity and storage coefficient are linked with LB parameters. These capabilities complete the LBM’s effective treatment of the types of processes that are simulated by standard ground water models. The LB model is verified against field data for drawdown in a confined aquifer.

The Expression of Rap6 in the Adult Mouse Brain and Early Mouse Embryonic Development

The previously identified RAP6 (Rab5 activating protein 6) was associated with plasma membrane mediated endocytosis and contains a Rab5 guanine nucleotide exchange factor (GEF) domain. RAP6 has been shown to act a Ras activating protein (GAP) domain. The identification of RAP6 and its crucial role in both receptors mediated endocytosis and fluid phase endocytosis presents the opportunity to investigate its role in murine embryonic development and in the adult brain. To confirm and characterize the presence of RAP6 during embryonic development and in the adult brain, the current study examined the expression of both the RGD and the Vps9 domains of RAP6 through in situ hybridization. We present an extensive evaluation of the expression for both RAP6 domains through in situ hybridization of 12.5 and 14.5 weeks old C67 mouse embryos and adult C67 mouse brain. The current study confirms the presence of both RAP6 domains and presents an extensive evaluation its expression in embryonic development and the adult brain. These data together support the role of RAP6 in receptor mediated endocytosis and fluid phase endocytosis relevant active during murine embryonic development and adult brain processes.

Exergoeconomic analysis of solar organic rankine cycle for geothermal air conditioned net zero energy buildings

This study is an attempt at achieving Net Zero Energy Building (NZEB) using a solar Organic Rankine Cycle (ORC) based on exergetic and economic measures. The working fluid, working conditions of the cycle, cycle configuration, and solar collector type are considered the optimization parameters for the solar ORC system. In the first section, a procedure is developed to compare ORC working fluids based on their molecular components, temperature-entropy diagram and fluid effects on the thermal efficiency, net power generated, vapor expansion ratio, and exergy efficiency of the Rankine cycle. Fluids with the best cycle performance are recognized in two different temperature levels within two different categories of fluids: refrigerants and non-refrigerants. Important factors that could lead to irreversibility reduction of the solar ORC are also investigated in this study. In the next section, the system requirements needed to maintain the electricity demand of a geothermal air-conditioned commercial building located in Pensacola of Florida is considered as the criteria to select the optimal components and optimal working condition of the system. The solar collector loop, building, and geothermal air conditioning system are modeled using TRNSYS. Available electricity bills of the building and the 3-week monitoring data on the performance of the geothermal system are employed to calibrate the simulation. The simulation is repeated for Miami and Houston in order to evaluate the effect of the different solar radiations on the system requirements. The final section discusses the exergoeconomic analysis of the ORC system with the optimum performance. Exergoeconomics rests on the philosophy that exergy is the only rational basis for assigning monetary costs to a system’s interactions with its surroundings and to the sources of thermodynamic inefficiencies within it. Exergoeconomic analysis of the optimal ORC system shows that the ratio Rex of the annual exergy loss to the capital cost can be considered a key parameter in optimizing a solar ORC system from the thermodynamic and economic point of view. It also shows that there is a systematic correlation between the exergy loss and capital cost for the investigated solar ORC system.

Does Obesity Affect Outcomes in Children Admitted from Trauma Centers?

Introduction and Research Objectives: Pediatric obesity has reached epidemic proportions in the United States. In the critical care setting, obesity has yet to be fully studied. We sought to evaluate the effects of obesity in children who are admitted to a hospital from trauma centers using Kid's Inpatient Database (KID) during 2009. Methods: The study examined inpatient admissions from pediatric trauma patients in 2009 using the Kids´ Inpatient Database (KID). Patients (n=27599) were selected from the KID based on Age (AGE>1) and Admission Type (ATYPE=5) and assessed on Race, Sex, Length of Stay (LOS), Number of Diagnoses and Procedures, Severity of Illness (SOI), Risk of Mortality (ROM), Co-morbidities, and Intubation by comparing obese and non-obese cohorts. Chi-square test and student t-test were used to analyze the data. All variables were weighted to get national estimates. Results: The overall prevalence of obesity (those coded as having obesity as co-morbidity) was 1.6% with significantly higher prevalence among Blacks (1.8%), Hispanics (2.3%), and Native Americans (4.1%; p<0.001). Obesity was more prevalent among females (2.4% vs 1.2%; p<.001). Overall mortality in the cohort was 4.8%. Obesity was significantly lower among children who died during hospitalization (0.5% vs 1.6%; p<0.002). However, obese children had significantly longer LOS, greater number of diagnoses, more procedures and greater than expected loss of function due to SOI when compared with nonobese cohort (p<.001). Deficiency anemia, diabetes, hypertension, liver disease, and fluid and electrolyte disorders are all strongly associated with the presence of obesity (p<.005). The rate of intubation is similar between obese and non-obese cohorts. Conclusion: Our study using KID national database found that obese children who are admitted from trauma centers have a higher morbidity and LOS but lower mortality. Racial and gender inequalities of obesity prevalence is consistent with previous reports.