VictorJuiz/thesis huggingface dataset:
Examination of the TALE homeodomain protein Pbx1 as a potential co-factor for the caudal homeodomain protein Cdx-2 in regulating proglucagon gene expression

The homeodomain protein Cdx-2 may serve as a transactivator for proglucagon and other genes. Based on the fact that many Hox and Hox-like proteins utilize Pbx1 as a co-factor and Cdx-2 possesses the penta-peptide binding motif for Pbx1, it is proposed that Pbx1 is a co-factor for Cdx-2. It is demonstrated here that Pbx1 co-transfection enhances the activation on proglucagon promoter expression by Cdx-2, and mutating the penta-peptide motif attenuates the effect of Cdx-2 on proglucagon promoter expression. Physical interaction between Cdx-2 and Pbx1 was detected by co-immunoprecipitation and GST-fusion protein pull-down assays. Interestingly, mutating or deleting the penta-peptide motif did not disrupt this interaction. Finally, my preliminary results show that Pbx1 antisense-molecule repressed Pbx1 protein expression, associated with repressed proglucagon mRNA expression. These observations support our hypothesis that Pbx1 serves as a co-factor for Cdx-2 in exerting its biological functions including activating proglucagon gene expression.
Regulation of glutamate-mediated synaptic responses by protein tyrosine phosphatase alpha (PTP[alpha])

N-methyl-D-aspartate receptor (NMDAR) is a principle subtype of ionotropic glutamate receptors mediating excitatory neurotransmissions in the central nervous system (CNS). Here we report that synaptic NMDAR was down-regulated by application of a specific protein tyrosine phosphatase alpha (PTPα) antibody, and up-regulated by PTPα functional domain (D1 + D2), and the latter could be blocked by removal of intracellular ATPs or inhibition of Src family kinases. Further studies showed that application of either PTPα D1 or D2 domain alone had no such effect, neither did mutant (D1 + D2) − C433A. Interestingly, mutant (D1 + D2) − Y789F was found to down-regulate synaptic NMDAR, which could be blocked by inhibition of Src family kinases. The double-mutant, (D1 + D2) − (C433A + Y789F), produced no such effects. Thus, I propose that PTPα may up-regulate NMDAR-mediated synaptic responses through Src family kinases, and this regulation requires both D1 and D2 phosphatase domains, in which the catalytic activity of PTPα and a C-terminal tyrosine residue, Y789, play critical roles.
Comparison of optimization algorithms applied to aerodynamic design

This thesis investigates the performance and robustness of three gradient-based optimization algorithms. The algorithms are the BFGS quasi-Newton algorithm, which uses the quadratic penalty approach for constraints, the KSOPT algorithm, which uses the Kreisselmeier-Steinhauser function to combine the objective function and constraints, and the SNOPT algorithm, which implements a sequential quadratic programming method for solving constrained optimization problems. These approaches are applied to the two-dimensional Navier-Stokes aerodynamic shape optimization problem. Accurate gradients are computed using the discrete adjoint method. The performance of the optimizers is demonstrated for several design examples, including inverse design, maximization of lift-to-drag ratio, maximization of endurance factor, lift-constrained drag-minimization, and multi-point optimization. The SNOPT optimizer is more robust and efficient than the BFGS and KSOPT optimizers for the majority of test cases presented.

Keywords: Aerodynamics, Mathematical models
Fluid dynamics, Mathematics
Mathematical optimization
Rational design of block copolymer micelles as a parenteral formulation strategy for hydrophobic agents

In the last decade several drug formulations relying on block copolymer micelles (BCMs) have entered clinical trial development. Yet in most cases, the BCMs act as solubilizers rather than true carriers of the drug. This may be attributed to a limited understanding of the relationship between copolymer properties and biological performance of micelles as delivery systems. Therefore, this thesis focused on gaining an understanding of the influence of polymer-drug compatibility as well as the physicochemical properties of the micelles on their biological behavior as delivery vehicles. In these studies, a reliable method was established for prediction of polymer-drug compatibility that relied on calculation and consideration of the partial and total solubility parameters of polymer and drug as well as physicochemical analyses of polymer-drug pairs. Polymers identified to be compatible with the anti-cancer drug ellipticine were used as the core-forming blocks of the micelle. Formulations obtained wherein the degree of polymer-drug compatibility was maximized were found to have high drug to material ratios and sustained drug release profiles. In addition, the adsorption of proteins to BCM systems and the influence of protein on drug retention in these systems were also evaluated. It was demonstrated that significant protein adsorption onto the micelle system may be avoided by employing the optimal block length of PEG that provides sufficient coverage of the core. However, protein-drug interaction was identified as a critical factor that may result in rapid drug release profile from the micelles. Furthermore, optimization of material properties, including the degree of hydrophobicity, molecular weight, polydispersity and ratio of hydrophilic to hydrophobic block, were found to result in BCM systems with superior in vitro stability and consequently an extended circulation half-life in vivo. Overall, this research clearly demonstrates that optimization of material properties and maximization of polymer-drug compatibility results in BCM formulations with enhanced biological performance.
Functional properties of double-zero oriental mustard protein products

The Food Engineering Group in the Department of Chemical Engineering and Applied Chemistry developed a process for the production of protein isolates and concentrates from Brassica oilseeds, specifically mustard and canola seeds. Double-zero oriental mustard protein products were produced with our process by the pilot-scale tests in the Protein Research Centre of Texas A M University, College Station, Texas in 2005. In this study, the functionality of double-zero oriental mustard protein products were determined and compared to that of soybean protein isolate Supro 500E and other pilot yellow mustard products. Double-zero oriental mustard isolates have good nutritional values: precipitated protein isolate contained 84.4% [Nx6.25] db, soluble protein isolate contained 76.2% [Nx6.25] db. Double-zero oriental mustard protein products proved to be promising functional components for food applications and can be tailored to meet food product needs in competition with widely used commercial soy isolate products.
Acute effects of controlled exposure to concentrated particles with/without added ozone on heart rate variability

Epidemiological studies have shown that exposures to air pollution are associated with increased cardiorespiratory morbidity and mortality in susceptible people. The exact mechanism is poorly understood. Independent of exposure type for SDNN and WBF there were trends to decrease at the beginning of the exposure, between the 10-min and 20-min time points, and a tendency to increase towards the last 20 min of the exposure. Analysis of variance associated with the split-plot design, used to assess the size of the CAP effect, the O3 effect and their interaction, showed no significant differences for any HRV domain (p> 0.28). The effects of concentrated ambient particles (CAP) with/without added ozone (O3) on heart rate variability (HRV) were studied in six healthy non-asthmatics and four mild asthmatics, aged 21--34 years. Each subject was exposed to: (1) HEPA-filtered air (FA); (2) low CAP (60 mug/m3); and (3) high CAP (150 mug/m3), on three separate occasions. The responses observed in 6 young healthy subjects and 4 mild asthmatics at levels up to 185 mug/m3 CAP and 132 ppb O3 suggest no significant acute effects on analyzed domains of HRV. (Abstract shortened by UMI.).
Identification of interacting proteins to the K15 protein of Kaposi's sarcoma-associated herpesvirus

Kaposi's sarcoma-associated herpesvirus, also known as human herpervirus 8, is closely associated with several cancers including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. The rightmost end of the KSHV genome encodes a protein, K15, with multiple membrane-spanning segments and an intracellular carboxy-terminal tail that contains several conserved motifs with the potential to recruit interaction domains (i.e. SH2, SH3, TRAF) of host cell proteins. K15 has been implicated in downregulating B cell receptor (BCR) signaling through its conserved motifs, and may thereby play a role in maintaining viral latency and/or preventing apoptosis of the infected B cells. However, K15's mode of action is largely unknown. We have used mass spectrometry, domain and peptide arrays, and surface plasmon resonance, to identify binding partners to the conserved proline-rich sequence (PPLP) in the K15 cytoplasmic tail. We show that the PPLP motif selectively binds the third SH3 domain of an endocytic adaptor protein, Intersectin 2 (ITSN2). This interaction can be observed both in vitro and in cells, where K15 and ITSN2 co-localize to discrete compartments within the B cell. The ability of K15 to associate with ITSN2 suggests a new role for the K15 viral protein in intracellular protein trafficking.
Limnology and diatom paleoecology of lakes and ponds on Banks Island, N.W.T. and Devon Island, Nunavut, Canadian Arctic

The Canadian Arctic Archipelago is an important reference region for climate change studies, however a paucity of environmental data exists for this area. With the aim to document and characterize the effects of climate change in this high-latitude region, this thesis establishes baseline environmental conditions and investigates long-term climate trends on Banks Island, NWT. and Devon Island, Nunavut through the use of limnological and paleolimnological techniques. Both islands were previously unsurveyed limnologically, and in the case of Banks Island, no previous paleolimnological study had been conducted on this island. A diatom-based TN transfer function for Banks Island was developed for application to three recovered sediment cores. A general increase in species diversity was documented in all stratigraphies, although to a lesser degree in the lake than in the ponds. Meteorological data for Banks Island from the last 50 years also showed an increase in both total annual precipitation and annual mean July temperatures. Mean total nitrogen (TN) and total phosphorus (TP) concentrations on Banks Island were demonstrably higher than those reported by previous Arctic island limnological surveys. Furthermore, Banks Island provided an opportunity to observe limnological trends across three ecozones (Low, Mid and High Arctic), as each study site could each be classified into one of these three ecozonal designations based on their nutrient and dissolved organic carbon concentrations. The limnological characterization of Devon Island revealed that its inland water bodies are generally homogeneous, being ultra-oligotrophic and dilute. The exceptions were those water bodies associated with the impact-generated carbonate melt sheets found within the boundaries of Haughton Crater in the northwestern region of Devon Island. The diatom autecology of the inland lakes and ponds on Devon Island was also characterized, resulting in the development of a diatom-based soluble reactive phosphorus transfer function, and its application to a lake sediment core. This study demonstrated both the homogeneity of the inland water bodies on this island, and their differences from the coastal lakes and ponds. Interestingly, the diatom stratigraphy did not reflect the species assemblage shifts seen in other Arctic Island paleolimnological and ice core reconstructions.
The reductive amination chemistry of aziridine aldehydes

Amino aldehydes without N-protecting groups are subject to self-condensation, since the amine is able to react with an aldehyde to form an imine/enamine system. As a result, the aldehyde functional group is prematurely destroyed. In order to make it behave as an aldehyde, protection is unavoidable. Even if the unprotected amine and aldehyde groups can co-exist under special conditions, the aldehyde or amine function is unable to react independently. Our recent interest in amphoteric molecules has led to the discovery of stable compounds that contain unprotected amine and aldehyde functionalities. The so-called kinetic amphoterism has been coined in order to describe the co-existence of a secondary amine and aldehyde in such molecules. Amphoteric aziridine aldehydes exhibit different properties from normal aminoaldehydes and have great potential for the construction of peptidomimetic conjugates.
Rational design on controlled release ion-exchange polymeric microspheres and polymer-lipid hybrid nanoparticles for the delivery of water-soluble drugs through a multidisciplinary approach

Sulfopropyl dextran sulfate (SP-DS) microspheres and polymer-lipid hybrid nanoparticles (PLN) for the delivery of water-soluble anticancer drugs and P-glycoprotein inhibitors were developed by our group recently and demonstrated effectiveness in local chemotherapy. To optimize the delivery performance of these particulate systems, particularly PLN, an integrated multidisciplinary approach was developed, based on an in-depth understanding of drug-excipient interactions, internal structure, drug loading and release mechanisms, and application of advanced modeling/optimization techniques. An artificial neural networks (ANN) simulator capable of formulation optimization and drug release prediction was developed. In vitro drug release kinetics of SP-DS microspheres, with various drug loading and in different release media, were predicted by ANN. The effects of independent variables on drug release were evaluated. Good modeling performance suggested that ANN is a useful tool to predict drug release from ion-exchange microspheres. In summary, this thesis demonstrates that an integrated multidisciplinary strategy ranging from preformulation to formulation to optimization is suitable for the rational design of SP-DS microspheres and PLN with desired properties. Based upon the optimized drug-polymer-lipid interactions, PLN with high drug loading capacity (36%, w/w) and sustained release without initial burst release were achieved. VRP remained amorphous and was molecularly dispersed within PLN. H-bonding contributed to the miscibility between the VRP-DS complex and DA. Drug release from PLN was mainly controlled by diffusion and ion-exchange processes. Drug loading capacity and particle size of PLN depend on the formulation factors of the weight ratio of drug to lipid and concentrations of surfactants applied. A three-factor spherical composite experimental design was used to map the cause-and-effect relationship. PLN with high drug loading efficiency (92%) and small particle size (100 nm) were predicted by ANN and confirmed by experiment. The roles of various factors on the properties of PLN were also investigated. To further improve the performance of PLN, drug-polymer-lipid interactions were characterized theoretically and experimentally using verapamil hydrochloride (VRP) as a model drug and dextran sulfate sodium (DS) as a counter-ion polymer. VRP-DS complexation followed a stoichiometric rule and solid-state transformation of VRP were observed. Dodecanoic acid (DA) was identified as the lead lipid carrier material.
Time optimal control of fluid catalytic cracking unit

Due to the high nonlinearity and complex reactions occurring in fluid catalytic cracking unit (FCCU), solving the time optimal control problem is especially challenging. Also constraints on the state variables make the problem even more difficult. However, the large throughput of FCCU, the change in operating conditions and the substantial economic benefits are the motivation behind this research. To solve the time optimal control problem based on the realistic model, the four-lump FCC model proposed by Ali and Rohani (1997) is used with small modifications. The modifications are justified by providing better agreement with the industrial data of the steady state and dynamic simulations. During the operation of a FCCU, the kinetic parameters may change and for adequate control, those parameters should be up-dated, especially when the feed is changed. In this work, Luus-Jaakola (LJ) optimization procedure is first applied to the estimation of kinetic parameters in the four-lump kinetic model for the riser reactor, and is then applied to the entire model of FCC unit. The results show better agreement with experimental data of Wang (Lee et al., 1989a) and the industrial data (Ali and Rohani, 1997). In addition, the significance of incorporating line search into LJ optimization procedure is illustrated by faster convergence and more accurate results for all the optimization problems in parameter estimation. The computations are reasonably fast, so in the future with faster computers the parameters can be up-dated on-line. Based on the developed dynamic model with the estimated kinetic parameters, a steady state optimization problem is solved to provide the desired optimal operation point for time optimal control. Compared with the industrial operating conditions, the optimal steady state obtained by using LJ optimization procedure increases the economic benefit by 17.33%. In solving the time optimal control problem of FCC unit, iterative dynamic programming (IDP) provides an efficient way to obtain the optimal control policy and to handle the constraints in a highly nonlinear dynamic system. The time to reach the vicinity of the desired state is significantly reduced with the use of time optimal control policy.
Assimilation of Mn-Al metal powder compacts in liquid Mg

The assimilation fundamentals of Mn-Al metal powder compacts in liquid pure Mg have been studied by immersing cylindrical Mn-Al powder compacts into pure Mg baths. Various factors, such as the Mg bath temperature, the Mn-Al compact size, and Mn composition in the Mn-Al compact, on the exothermic behaviour during the Mn-Al powder compact assimilation and Mn recovery, were evaluated. It was found that a series of strongly exothermic Mn-Al intermetallic reactions occurred in the compact during the immersion test. The reaction products include a full series of Mn-Al phases which exist in the binary Mn-Al phase diagram, i.e., αMn, βMn, Al8Mn5, Al11Mn 4, Al4Mn, Al6Mn and Al. The compositions of these phases are in a non-stoichiometric range compared to the equilibrium counterparts. The assimilation mechanism of the Mn-Al compact into liquid Mg is the melting of reaction products with lower melting points by the reaction heat. An assimilation mode of Mn-Al powder compacts in liquid Mg has been proposed. It is divided into three stages: incubation stage, intermetallic reaction stage, and homogenization stage. Under the experimental conditions in use, the Mn-Al powder compact in 750°C Mg bath, with 19.05 mm diameter and 50wt%Mn50wt%Al composition, exhibits the best Mn recovery. In the computational part of this thesis, the impact of specimen on the Mg bath was investigated using the FLOW-3D simulator. In addition, the effective thermal conductivities of Mn-Al compacts with various compositions have been estimated by an inverse heat transfer procedure, which was developed by utilizing and tailoring a SIMPLER code. The estimated effective thermal conductivities are in the range of 5.5 to 10.5 W m-1°C-1. The dependence of the effective thermal conductivity on temperature is minimal in the examined temperature range from about 250 to 600°C. The effective thermal conductivity decreases with an increase in the compact's Mn composition and porosity. Moreover, the heat generations in various Mn-Al compacts during the 750°C Mg bath immersion test have been estimated. The estimated heat generations are comparable to those from the thermodynamic calculations.

Keywords: Materials science
Low frequency modulations in fundamental frequency and speech envelope in patients with Parkinson's disease

Phonatory instabilities such as low frequency modulations of fundamental frequency, F0 (frequency modulation, FM) and speech waveform envelope (amplitude modulation, AM) are associated with Parkinson's disease (PD). This study aims to characterize differences in FM and AM features between 10 PD speakers and two groups of healthy speakers using a Fine Structure Spectrogram-based method to extract the fundamental frequency (F0). Low frequency AM and FM vocal features were analysed with a two-way ANOVA with group and gender as between-subject factors. A Discriminant Analysis was used to identify variables that would distinguish individuals from the PD group from those of the combined control groups. The results showed that with three predictor variables, over 90% group identification accuracy was achieved. The findings are discussed with respect to the suitability of the proposed method to identify vocal features in PD and how they compare to data published in the literature.
Nonlinear control of a planar magnetic levitation system

This thesis initiates a research aimed at developing tools that may have practical significance in contactless position control applications such as, e.g., photolithography. We describe a simple three-magnet planar positioning device, its mathematical model, and design a nonlinear controller that stabilizes it about an equilibrium. Specifically, we derive a feedback transformation mapping the nonlinear system with three positive inputs into a linear system in Brunovsky normal form with two inputs. Robust, adaptive and robust adaptive controllers are then designed in the transformed input domain and their effectiveness in handling uncertainties is compared through simulations. An experimental testbed of the planar magnetic levitation device has been constructed but due to hardware limitations it cannot yet be used as a benchmark to test the controllers developed here. However, two simpler experiments give insight into applied nonlinear control design.