UH Faculty, Staff, and Student Works
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Browsing UH Faculty, Staff, and Student Works by Department "Chemical and Biomolecular Engineering, Department of"
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Item A More Robust Assessment of Antibiotic Combinations by Dynamic Susceptibility Model(2019) Altman, RachelBackground: Evolving bacterial resistance presents a rising challenge to public health. One mechanism of resistance, the production of drug degrading enzymes, is traditionally treated with a combination of active first line antibiotic and enhancing inhibitor. The conventional testing method currently used to guide treatment with these combinations has deficiencies. Objective: To develop a robust computational tool that will help identify the most effective treatment options. Methods: A clinical strain of Klebsiella pneumoniae expressing CTX-M15 was studied. Piperacillin (an antibiotic) susceptibility testing was performed at varying concentrations of avibactam (an enzyme inhibitor). The susceptibility results were modeled against the changing inhibitor concentrations to produce a dynamic model of susceptibility. Accounting for fluctuating antibiotic concentrations in the body, an integrated metric (% T > MICi) was used to assess the potential effectiveness of various drug combination dosing regimens. Results: Piperacillin susceptibility was well characterized as a function of avibactam (r2 = 98). A range of % T > MICi (from 67.5% to 83.1%) was simulated by the computational model using escalating doses of piperacillin every 8 hours. These simulations will be experimentally validated in a preclinical infection model in the future. Conclusions: Integrating changing drug concentration levels in the body with a dynamic measure of susceptibility will likely provide a more comprehensive picture of how a bacterial infection might respond to a given drug combination. If validated, this computational model in combination with a revised testing method would help doctors to choose the best available treatment for the patient.Item Analysis of CRP-Mediated Persister Cell Metabolism in Bacteria(2020-09-29) Rossodivita, Laura; Mohiuddin, Sayed GolamAntibiotic resistance is regarded as a global public health crisis and is much worse in many developing countries. Bacterial persistence contributes to this problem because persisters are thought to facilitate the recurrence of chronic and biofilm related infections (e.g., tuberculosis, cystic fibrosis lung infection, chronic wound infections, and urinary tract infections) and serve as a reservoir for the emergence of drug resistant mutants. Persisters enter a non-growing state before antibiotic treatments, survive lethal concentrations of antibiotics, and become resuscitated after the conclusion of the antibiotic treatments. Upon the removal of antibiotic treatment, persisters can regain the ability to initiate cell growth and produce daughter cells that are sensitive to the same antibiotic treatment. The Orman lab found that persisters survive antibiotic treatment by getting their energy from self-digestion. This causes self-inflicted damage that gives persister cells its non-growing characteristic. They also found that reducing stationary phase metabolic activity decreases persister levels since they cannot undergo self-digestion and get their energy to survive the antibiotic treatment. Since most metabolism related genes are regulated by CRP/cAMP, targeting any key component related to CRP will reduce bacterial persistence. During my SURF project, I identified persistence related genes mediated by CRP/cAMP and analyzed measured metabolites in wild-type and knockout E. coli strains to identify differences in the metabolic profile. By understanding the genes and metabolites involved in persister formation, certain drugs can be identified to target specific metabolic pathways that eliminate persisters and substantially improve drug efficacy.Item Analyzing Nanoparticle Dynamics in Complex Fluids Using Microscopy Techniques(2017-10-12) Perez, Ben; Smith, Maxwell; Poling-Skutvik, RyanImproving our understanding of nanoparticle dynamics in complex fluids allows for advancements in Point-of-Care diagnostics such as targeted drug delivery. Our group currently studies how a nanoparticle’s shape affects its dynamics in complex fluids. A previous study on spherical nanoparticles in complex fluids indicated that diffusivity collapses with increasing length scale (ratio of particle size to space between polymer chains) the diffusivities exceeded expected values made by bulk rheology. These two findings motivated this project.Item Antibody-Functionalized Nanophosphor Particles for Use as Reporters in Lateral Flow Assays(2017-10-12) Hasan, Aisha; Goux, Heather; Trabuco, JoãoThe main goal of this project was to identify important buffer components that improve the performance of nanophosphor reporters in a lateral flow assay. A model system based on the capture of the human chorionic gonadotropin (hCG) by two antibodies: monoclonal mouse anti-β hCG antibodies (Arista Biologicals, item # ABBCG-0402) and goat polyclonal anti-α hCG antibodies (Arista Biologicals, item # ABACG-0500). The principles of partial factorial design of experiments were used to screen common buffer additives. Comparing the relative effect of such components is key to develop better buffer formulations that enhance the performance of nanophosphor-based LFAs. Furthermore, relating the effects of certain buffer components to its mechanism of action could also shed a light on the interactions involved in the assay such as specific and nonspecific interactions or liquid diffusion through a porous membrane.Item Atomistic Simulations of Hydrogen Production Kinetics at Novel Fuel Cell Electrodes(2018-10-18) Hiew, Shu NingElectrocatalysts such as platinum (Pt), are used to minimize the overpotential for the hydrogen evolution reaction (HER) during electrochemical water splitting or fuel cell operation. Iron phosphide materials (FexP) were recently identified as one of the more promising transition metal phosphide electrocatalysts for HER that can substitute Pt at a much lower cost. To further understand their activity’s origin, the thermodynamics and kinetics of hydrogen recombination was investigated on six FexP (x=1,2,3) surface facets using density functional theory (DFT). As the differential Gibbs free binding energy of hydrogen (∆G_H) reaches zero, the adsorption of protons on FexP surfaces and the desorption of H2 are both expected to be facile. We analyzed the recombination kinetics of H2 on FexP surfaces for the number of hydrogen coverage that satisfy the necessary criterion ∆GH≈0 kJ/mol. The activation and recombination energies for 2 H* to form H2 were calculated using the Vienna Ab initio Simulation Package (VASP). The energy change of different hydrogen combination from 2 H* to H2 was used to identify the easiest detachable H2 from each surface. The most favourable H2 combination pair for each FexP surface was selected to calculate its activation barrier using the Nudged Elastic Band (NEB) algorithm. Our results show that a stable intermediate, i.e. a surface hydrogen molecule (H2*) is formed on the surface before desorption of H2. Our results also suggest that Fe2P and FeP have better HER kinetics, which we tentatively attribute to their lower metal concentration allowing for higher H mobility.Item Design of Better Performed Diesel Oxidation Catalysts at Reduced Temperature(2017) Song, Yuying; Grabow, Lars C.Item Designing Chemical Treatments for Mineral Scale Using Microfluidics(2018-10-18) Nguyen, AmyMineral scale is a major production challenge for upstream oil and gas processes. Over time, the formation of inorganic precipitates hinders flow capacity by obstructing equipment. Treating and preventing these deposits is extremely expensive and time consuming. Barite, the most insoluble component of scale, needs more efficient treatments. Several organic molecules are used commercially as scale inhibitors. Barite inhibitors may bind to barium ions in solution to prevent further incorporation into active sites, while others may adsorb onto specific crystal surfaces and hinder or arrest crystal growth. The ultimate goal is to design more efficient chemical treatments exhibiting enhanced inhibition and dissolution of barite in a dynamic setting. These experiments reveal additive and synergistic effects on inhibition and dissolution of barite using a combination of modifiers. I conducted bulk crystallization assays with several commercial and environmentally friendly scale inhibitors in individual and binary studies to observe the effect on binding specificity through changes in aspect ratio. Inhibition and dissolution kinetics were investigated using a microfluidic platform designed for rapid parametric screening of potential modifiers. Real time images were captured using an optical microscope to quantify growth kinetics and analyzed. Binary inhibitor combinations with synergistic cooperativity showed enhanced inhibition and dissolution properties. However, their combined effect on the environment is unknown. An ecosystem’s exposure to these chemicals can disturb the stability and organisms.Item Development of a lateral flow assay for the detection of β-actin in whole cell extracts(2019) Ahmed, Sehrrish; Brosamer, KristenThe primary objective of this summer project was to gain hands-on experience in Lateral Flow Assay (LFA) development for cancer diagnostics and more specifically the development of an LFA for the detection of β-actin in whole cell extracts. Initially, a model LFA for the detection of human Chorionic Gonadotropin (hCG) was used. Then, an LFA for the detection of β-actin in CA46 human B-cell lymphoma cells was developed. The Lateral Flow Assay is a rapid, point-of-care immunodiagnostic test commonly seen as the home pregnancy test. This method of diagnosis is convenient due its user-friendly format and ease of use without specialized personnel. In typical LFAs, gold nanoparticles are conjugated to antibodies that capture the target analyte from the sample. As the sample flows through the LFA membrane, the gold nanoparticle-antibody-target complex is captured onto the antibodies immobilized (test line) on the membrane of the strip. Detection of β-actin in whole cell extracts allows researchers to confirm reproducibility of sample preparation and normalization of the number of cells in specimens. Thus, a β-actin LFA can serve as a control in a rapid Acute Promyelocytic Leukemia (APL) LFA test for blood, which is under development in Professor Willson’s lab at the University of Houston.Item Development of a Monte Carlo Algorithm for the Prediction of Acid Site Distribution in Zeolites(2020-05) Hiew, Shu NingZeolites are porous aluminosilicates that afford exceptional benefits as catalysts in the petrochemical industry, or for vehicle emission control, to name a few. The presence of aluminum (Al) in the silicate (SiO4) framework creates a charge defect, which leads to Brønsted acid sites when compensated with a proton. If the defect is compensated by a metal cation, a Lewis acid site is formed. For metal-exchanged zeolites, in particular, the Al distribution and probability of forming paired Al sites in the framework determines the metal speciation and, in turn, the selectivity and activity of the catalyst. This thesis project aims to create an algorithm that can estimate the Al distribution and probability of forming paired Al sites in zeolites based on user-defined parameters: a) Silicon-to-aluminum ratio (SAR), b) simulation temperature, c) number of trials generated for statistical analysis, and d) Al-Al interaction energy. Two different implementations of a Monte Carlo algorithm were tested and evaluated for zeolites with CHA, MFI and MWW framework structures. The traditional (MC1) and modified (MC2) Metropolis Monte Carlo Methods have different means in generating the initial guess for the Al distribution. In MC1, the initial population is random while conforming to Löwenstein’s rule, while in MC2, Löwenstein’s rule is used to generate an initial guess with maximized density of Al site pairs. Even though MC2 has a higher computational cost than MC1, MC2 is better than MC1 because it is less prone to error and has a higher overall efficiency. The final algorithm generates population statistics that are in full agreement with expected results for the provided Al substitution energies and the probability of forming paired Al sites.Item Development of ultrasensitive lateral flow assays based on horseradish peroxidase enzyme reporters(2018-10-18) Teremah, ZahraLateral flow assays (LFAs), the basis of the home pregnancy test, have been widely used in medical diagnosis, environmental monitoring and forensics. LFAs are attractive point-of care diagnostics due to many reasons, including short test-to-result time, user-friendly format, low cost, storage stability and the ability of non-specialized personnel to run the test. In a typical LFA, gold nanoparticles bearing antibodies to the target are used as the reporter. However, LFA sensitivity lags behind more complex laboratory methods currently used in the clinic. Professor Willson’s group in the Department of Chemical and Biomolecular Engineering (UH) has been developing ultrasensitive LFAs using horseradish peroxidase enzymes (HRP) as the reporter. The primary objective of my summer project was to gain a hands-on experience on how to develop a highly sensitive point-of-care LFA based on HRP enzymes and to evaluate three enzyme substrates using a model LFA.Item Dynamics of Pathological Crystallization: A Microfluidity Study(2017-10-12) Guala, Diego; Sosa, Ricardo; Geng, Xi; Alamani, Bryan GencianeoItem Experimental Study of Flow Patterns and Pressure Drop in Cocurrent Gas-liquid Down Flow in a Packed Column(2019-05) Stroh, ChristinePacked bed columns are widely used throughout many chemical processes to carry out reactions between gas and liquid reactants requiring a solid catalyst. Flow patterns and their associated pressure drops are two important parameters that can optimize the operation of these reactors. However, the analysis of these parameters is usually above the understanding of the operators who control the reactors. This thesis evaluates these parameters in a laboratory scale packed column, compares the results to literature values, and analyzes the data in a simpler way using parameters easily found with equipment in a chemical plant. The experimental data reasonably fit the well-known Tosun flow map and a modified Lockhart-Martinelli correlation. New analysis showed that when plotted as a pressure trace standard deviation normalized by its average versus its gas flow rate, the data had a visual change in slope whenever the flow pattern transitioned, giving operators a simpler way to identify transitioning flows.Item Exploring Novel Methods to Tailor the Crystal Morphology of ZSM-11 Catalysts(2017-10-12) Garcia, Rosendo; Shen, Yufeng; Le, ThuyResearch goal: Optimize synthesis parameters to investigate the role of these parameters in the morphology of ZSM-11 catalyst. Optimizing the parameters of ZSM-11 synthesis to yield a uniform zeolite structure. Increasing sodium content led to a decrease in surface defects. As SAR is increased a more uniform structure is developed. Using an alternative Si source led to crystals with spheroidal morphology.Item Exploring the Efficacy of Single-Atom Alloy Catalysts for the Haber-Bosch Process(2017-10-12) Mai, Cindy; Do, Quan K.; Wang, ShengguangThe Haber-Bosch process is used for the production of ammonia from gaseous nitrogen and hydrogen through the reaction N2 + 3H2 → 2NH3. Ammonia is used in fertilizer and its production uses approximately 2% of the world’s energy. Our Goals. To break or circumvent the established BEP trendlines and design a novel catalyst that supersedes existing ones through density functional theory (DFT). To design an inexpensive single atom alloy that optimizes N2 dissociation. To quantify the improvement of these single atom alloys over Ru(0001) using microkinetic modeling (MKM). Conclusions. Mo-promoted Co(0001) single atom alloy catalysts show markedly improved performance over conventional ruthenium catalysts and the industrially-used iron catalysts. Single atom alloys can be used to break the BEP trendlines in a variety of catalysis applications, including the Haber-Bosch process. Microkinetic modeling is a powerful tool that can predict results for a wide variety of systems of reactions.Item Finite Element Mesh Design With Quadrilateral Transition(2019) Pham, KristopherThe focus of the research was the design of finite element meshes with direct application to computational fluid mechanics. This design concentrated primarily on coarsening a dense mesh or refining a coarse mesh. Structured meshes have been produced using the fundamentals of analytical geometry. Source codes in MATLAB and in Fortran have been written that transform the meshes into figures and can be readily used in computer codes of finite elements. To the best of our knowledge, there is no relevant literature that documents this kind of effort that has been produced in this work, although there are figures that can be found on the internet with relevant content that lack documentation. There are numerous applications in fluid mechanics where this kind of work is useful, such as, flow around submerged objects (flow around a cylinder, submarine, automobile), surface mounted obstacles (flow around a cube, building), and in channel flows with emphasis on the outflow boundary conditions where a refined mesh at the exit of the domain is crucial for accurate results. Additionally, the meshes produced in the study can be directly applied to the area of computational structured mechanics.Item Gene Expression Data Analysis of Persister Cancer Cells(2020-09-29) Landestoy Acosta, Tahimy; Mier, Juan C.; Karki, PrashantMany cancer patients experience recurrence of the disease within months or years after the first treatment. Recent studies have shown that many of these relapses can arise due to the presence of drug-tolerant persister cells. Persisters are a subpopulation of transiently drug-tolerant cells that can enter a state of negligible growth, through reversible, non-mutational mechanisms. These cells have shown to have unique but conserved metabolic mechanisms that are essential for their survival. In this study we analyzed publicly release data from the Connectivity Map (CMap) at the Broad Institute, a genome-scale library of cellular signatures that catalogs transcriptional responses to chemical, genetic, and disease perturbation. The perturbational data is generated using the L1000 assay and was used to screen for metabolic pathways associated with persister formation and survival. By using one of the most high-level, interpreted and general-purpose dynamic programming languages, Python, we identified specific metabolic pathways active in persisters.Item IDENTIFICATION OF STABLE NEAR SURFACE ALLOY SYSTEMS USING DENSITY FUNCTIONAL THEORY AND DATA SCIENCE(2018-10-18) Pham, KhoaRecently, a new class of catalysts, called single-atom alloy (SAA), has been discovered, synthesized, and studied. These heterogeneous catalysts contain a single, highly active promoter metal that sits within the surface of a less reactive host metal. The promising potential of these SAAs was demonstrated by Sykes and co-workers for selective hydrogenation reactions using a single palladium atom in copper. Our research group has also found multiple varieties of SAAs that are promising candidates for many industrial processes. However, there are only a few studies on the stabilities of these SAAs. We used Density Functional Theory (DFT) and the Atomic Simulation Environment (ASE) to refine and expand the work by Ruban et al. and determined if a given promoter metal will cluster on the surface, diffuse to the subsurface, stay as an ad-atom, or form an SAA within any other host metal. Then, we used data science and statistical analyses to extract heuristic rules from our database of the stability of SAAs. By using the open source machine learning package TensorFlow, an artificial neural network has been trained to classify the alloys as stable/unstable systems, showing the relation between the alloy’s stability and its component’s properties. These guidelines provide fundamental insight into the formation of stable surface structures of binary alloys where one component is a minority species, helping scientists and researchers to focus their efforts on stable SAAs in their quest to develop new catalyst for industrial applications.Item Identifying Chemical Compounds Targeting Persister Cell's Related Mechanisms in Bacteria(2018-10-18) Nguyen, Thao VyBacterial persisters are rare, phenotypic variants that are temporarily tolerant to high concentrations of antibiotics. They are generally non-growing cells, and genetically identical to their antibiotic-susceptible kin. These cells are an important health concern because they underlie the proclivity of recurrent infections to relapse, and they serve as a reservoir from which drug resistance mutants can emerge. In fact, recurrent infections account for 65% of hospital-treated infections, and in the US alone it is estimated that they are attributed to half a million deaths, and cost the healthcare system approximately $94 billion per year. Conventional therapies for the recurrent and chronic infections function by targeting the mechanisms that enable the rapid growth of bacterial cell populations. Although this can provide a clinical benefit, this benefit is usually short-lived for these infections and a large body of evidence suggests that persister cells invariably survive this initial selection pressure. Therefore, it is desirable to discover novel compounds that can potentially serve as adjuvants to enhance the persister killing. We approach the problem of persister through inhibiting the SOS response of bacteria under stress. When antibiotics are introduced into the bacterial culture, the cell’s DNA is damaged. Persister cells respond to this DNA damage by inducing the SOS response genes, such as recA, a gene essential for the repair mechanisms of DNA. Inhibition of the SOS response or impairing the DNA repair mechanisms have been found to decrease persister levels. Identifying medicinally relevant chemical compounds that target DNA repair mechanisms so that the cells’ DNA will be permanently damaged can significantly reduce the level of persister cells.Item Identifying Chemical Compounds Targeting Persister Related Mechanisms in Bacteria(2019-05) Nguyen, Thao VyBacterial persisters are rare, phenotypic variants that are temporarily tolerant to high concentrations of antibiotics. They are generally non-growing cells and are genetically identical to their antibiotic-susceptible kin. These cells are an important health concern because they underlie the proclivity of the relapse of recurrent infections, and they can serve as a reservoir from which drug-resistance mutants can emerge. It is believed that persister cells survive quinolone antibiotic treatment by activating their DNA repair mechanisms, such as recA, which is an essential protein for the repair of the damaged DNA. It has been found that impairment of the DNA repair mechanisms could significantly decrease persistence. Therefore, it is desirable to discover medicinally relevant chemical compounds that target bacterial DNA repair mechanisms to serve as adjuvants to enhance antibiotic effect. In this project, we developed a rapid and efficient method to screen for potential chemical inhibitors. From the Phenotype MicroArrays chemical library from Biolog Inc. (Hayward, CA), we were able to identify a number of FDA-approved chemical compounds that can serve as inhibitors of the bacterial cells' DNA repair mechanisms, thus eliminate persistence without independently eradicating the cell cultures.Item MIL-100(Cr): A Novel Adsorbent for CO2 Capture(2020-09-29) Fleming, KevinExhaust gases from a wide variety of industrial processes continue to release considerable amounts of CO2 gas into the atmosphere, thereby exacerbating anthropogenic climate change. A new class of porous inorganic-organic hybrid materials referred to as Metal-Organic Frameworks (MOFs) have recently gained attention due to their gas storage and separation capabilities – notably the capture of CO2 present in industrial exhaust gas. In this study, the CO2 adsorption of the MOF MIL-100(Cr) was studied. Five batches of MIL-100(Cr) were synthesized and characterized using three primary material characterization techniques: x-ray diffraction, thermogravimetric analysis, and N2 physisorption. The comparison between the results of these characterization experiments and literature data indicate that the five batches of synthesized material have the same structure as the MIL-100(Cr) material reported in the literature, enabling the samples to be mixed and subsequently used for CO2 adsorption experiments. The CO2 adsorption isotherms revealed that the CO2 adsorption of the MOF increased with pretreatment temperature. A similar trend has been reported in the literature for ethylene adsorption on MIL-100(Cr), which corresponded to the thermally-induced formation of Cr2+ metal sites on the MOF material. IR spectroscopy and quantum chemistry computational simulations can be utilized during future investigations to obtain a molecular-level perspective on why increasing pretreatment temperature enhances CO2 uptake in MIL-100(Cr).