acase@tulane.edu

During the development of the nervous system, a complex system of chemical and mechanical cues guide nerve cell projections toward appropriate targets by eliciting attractive or repulsive responses from navigating structures called growth cones. Current in vitro models of neural guidance lack the capacity to provide multiple cues within the same substrate. This dissertation presents in vitro models with tunable presentation of multiple chemical and mechanical guidance cues in a single substrate for elucidating a more complete understanding of growth cone responses to the extracellular environment. In the first study, our model utilized a light-sensitive agarose gel as the growth substrate and a polyethylene glycol gel that contained three dimensional neural growth in specific geometries. This model incorporated molecular cues as immobilized proteins and gradients of soluble factors in a quantifiable manner. The agarose gel presented issues with gelation and supporting neural growth, so we sought to improve upon our initial design by changing the growth substrate. The second study employed a novel light-sensitive dextran gel in place of the agarose of the first study. The chemoattractant neurotrophin-3 and chemorepellant semaphorin3A were immobilized within this dextran gel in a spatially defined manner, and the response from growth cones quantified. The growth cones did not respond to the control protein NeutrAvidin, exhibited a moderate response to neurotrophin-3, and showed a strong repulsive response to semaphorin 3A. The third study investigated neural responses to changes in substrate stiffness. Dextran gels with light-degradable crosslinks exhibited different elastic moduli based upon irradiation time. Specified regions of dextran gels were irradiated with light to present growth cones with a choice between two different elastic moduli. Growth cones exhibited preference for a narrow range of elastic moduli spanning less than 200 Pa, an observation unattainable with other in vitro models. The results establish our models as possible platforms for observing and manipulating specific growth cone responses to both chemical and mechanical cues. Understanding how the growth cone interacts with its environment may lead to improved wound healing therapies, and expanding our model into a high-throughput assay could contribute to the development of these new treatments. / acase@tulane.edu

acase@tulane.edu

acase@tulane.edu

Clinico-genomic modeling refers to the statistical analysis that incorporates both clinical data such as medical test results, demographic information and genomic data such as gene expression profiles. It is an emerging research area in biomedical science and has been shown to be able to extend our understanding of complex diseases. We describe a general statistical modeling strategy for the integrated analysis of clinical and genomic data in which the clinical data are longitudinal observations. Our modeling strategy is aimed at the identification of disease-associated genes and it consists of two stages. In the first stage, we propose a hierarchical B spline model to estimate the disease severity trajectory based on the clinical variables. This disease severity trajectory is a functional summary of the disease progression. We can extract any characteristics of interest from the trajectory. In the second stage, combinations of the extracted characteristics are included in the gene-wise linear model to detect the genes that are responsible for variations in the disease progression. We illustrate our modeling approach in the context of two biomedical studies of complex diseases: tuberculosis (Tb) and colitis-associated carcinoma. The animal experimental subjects were measured longitudinally for clinical information and biological samples were extracted at the final points of the subjects to determine the gene expression profiles. Our results demonstrate that the incorporation of the longitudinal clinical data increases the value of information extracted from the expression profiles and contributes to the identification of predictive biomarkers. / acase@tulane.edu

he focus of this research has been devoted to study the interaction between two or more self-propelled toroidal swimmers in Stokes flow by applying the method of regularized Stokeslets and also study the effect of a nearby wall to the movement of a helical ring by using the method of regurlarized Stokeslets with images. In the study of the interaction between two or more toroidal swimmers, we interpret these as three-dimensional, zero Reynolds number analogues of finite vortex dipoles in an ideal fluid. Then, we examine the stability of relative equilibria that can form for these swimmers when they are initially placed in tandem or abreast. In addition, we examine the dynamics of the torus when a spherical cell body is placed at its center. This gives us an insight into the mechanical role of the transverse flagellum of dinoflagellates. Moreover, we show that the torus with a sphere moves more efficiently than one without. Lastly, we model the transverse flagellum of a dinoflagellate as a helical ring and study the effect of a nearby wall on its movement. The numerical results show that the wall baffles the movement of the helical ring, which is consistent with the phenomenon of sperm accumulation near surfaces. / acase@tulane.edu

Degradation processes change the chemical composition of oil and can be affected by the mixing of oil into the environment. Here, a ramped pyrolysis (RP) isotope technique is implemented to investigate thermochemical and isotopic changes in coastal environments impacted by the 2010 BP Deepwater Horizon oil spill (DwH). Marsh sediment determined to contain oil by PAH analysis display relatively low thermochemical stability and depleted stable carbon (13C) and radiocarbon (14C) isotopic signatures. The ability of RP to separate oil from background organic material (OM) is established by high oil composition for pyrolysates evolved at low temperatures, as determined by radiocarbon measurement. Applying the RP isotopic technique to beach sediment, tar, and marsh samples collected over a span of 881 days reveals a predominance of oil in the organic material for up to 881 days and varying rates of degradation. Pyrolysis profiles show that the oil degraded faster where rates of mixing were higher. Observing how oil changes thermochemically over time provides a new perspective on oil degradation and its relationship with mixing. / acase@tulane.edu

"Hydrophobic hydration of non polar molecules is the principal driving force that dictates several interfacial phenomena in nature such as self assembly of surfactant molecules, fate of environmental pollutants, wetting of surfaces, solution behavior of polymers and folding of biological molecules such as proteins. However, the physics associated with hydrophobic interactions on a molecular length scale, which is central to self assembly and protein folding, is different from the macroscopic phenomena of de-mixing of oil and water or wetting of surfaces. This dissertation seeks to understand the implication of hydrophobic interactions to energy and environmental applications using different approaches. The first approach is to examine the behavior of water molecules with hydrophobic moieties at a molecular level using molecular dynamics simulations and evaluate macroscopic thermodynamic properties. The first problem addressed in this dissertation is the enclathration of gas molecules by water molecules in the presence of quaternary ammonium ions. Small polar organic molecules such as quaternary ammonium salts form crystalline inclusion compounds called semi-clathrate hydrates, where these polar molecules occupy a lattice position of the hydrogen bond network of water molecules. These crystalline structures of water are formed at ambient temperature and pressure conditions and can store as much 3%(w/w) of methane, making them potential materials for gas storage. The stability and structure of semi-clathrate hydrates of tetrabutylammonium bromide (TBAB) and methane were investigated using molecular dynamics (MD) simulations. MD simulations were done at varying conditions of temperature and pressure for methane-TBAB ratios of 0, 0.5, 1, 1.5 and 2. Thermo-mechanical properties evaluated using MD simulations were in agreement with experimental data available. Our investigation of this system shows that enclathration of methane in these semi-clathrate hydrates is thermodynamically favorable even at higher temperatures and shows signatures of hydrophobic hydration. Our estimation of free energies associated with successive inclusion of methane molecules in these cavities suggests a Langmuir-type adsorption of methane in these cages. Another problem investigated in this dissertation is the effect of chemical heterogeneity of crystalline cellulose (110) and (100) surfaces on their respective wetting behavior. Understanding the interaction of water with cellulose is important in the view of its role in consumer textiles made from cotton cellulose and potential applications of cellulose as biomaterials and as an energy source. The difference in the wetting behavior of (110) and (100) crystal surfaces is due to the asymmetry in the exposure of the hydroxyl groups by these surfaces. MD simulations were used to evaluate the contact angles of hemi-cylindrical water nanodroplets on crystalline (110) and (100) surfaces of the cellulose Iβ allomorph. While the native crystalline surfaces were completely wetted by water nanodroplets, substituting the primary hydroxyl groups with methyl and methoxy groups results in dewetting. The contact angle of a hemicylidrical water nanodroplet on the hydrophobically-modified (110) surface is greater than on the (100) surface suggesting that the (110) surface has a greater exposure of the primary hydroxyl groups. The solubility of cellulose in aliphatic N-oxides has been of particular interest because of its application in industrial processes such as Lyocell process. However, the mechanisms that dictate the dissolution of cellulose in these selective solvents are not clearly understood. Attempt is made to understand the solvation of cellulose in N-Methylmorpholine oxide (NMMO) and water from a molecular perspective. MD simulations of a model cellohexaose crystallite solvated respectively in pure water, NMMO and in an equimolar mixture suggest that while NMMO molecules preferentially cluster around the primary hydroxyl groups in cellohexaose chains, the role of water is critical in its ability to access the glycosidic oxygen. The second approach is to study the implication of introducing hydrophobicity at molecular level and experimental determination of its implication to addressing interfacial aspects of environmental remediation. Sub-micron size carbon particles derived from hydrothermal decomposition of sucrose are effective in stabilizing water-in-trichloroethylene (TCE) emulsions. Irreversible adsorption of carbon particles at the TCE-water interface resulting in the formation of a monolayer around the water droplet in the emulsion phase is identified as the key reason for emulsion stability. Cryogenic Scanning Electron Microscopy was used to clearly image the assembly of carbon particles at the TCE-water interface and the formation of bilayers at regions of droplet-droplet contact. The results from this study have broad implications to the subsurface injection of carbon submicron particles containing zerovalent iron nanoparticles to treat pools of chlorinated hydrocarbons that are sequestered in fractured bedrock. Interfacial aspects of hydrophobically modified biopolymer and its ability to enhance the stability of crude-oil droplets formed were investigated. Turbidimetric analyses show that emulsions of crude oil in saline water prepared using a combination of the biopolymer and the well-studied chemical dispersant (Corexit 9500A) remain stable for extended periods in comparison to emulsions stabilized by the dispersant alone. The hydrophobic residues attached to the polymer preferentially anchor at the oil-water interface and form a protective layer of the polymer around the droplets. The enhanced stability of the droplets is due to the polymer layer providing an increase in electrostatic and steric repulsions and thereby a large barrier to droplet coalescence. The implication of this study to current remediation methods is significant since the addition of hydrophobically modified chitosan following the application of chemical dispersant to an oil spill can potentially reduce the use of chemical dispersants. Increasing the molecular weight of the biopolymer changes the rheological properties of the oil-in-water emulsion. Emulsions stabilized by using a combination of Corexit 9500A and high molecular weight hydrophobically modified chitosan show characteristics of a weak gel. The ability of the biopolymer to tether the oil droplets in a gel-like matrix has potential applications in the immobilization of surface oil spills for enhanced removal. Carbon microspheres containing magnetite nanoparticles, synthesized using inexpensive precursors such as sucrose and iron chloride, are ferromagnetic and have affinity to the oil phase. We demonstrate that a thin layer of crude oil can be corralled and thickened by the application of nonionic surfactant. Following the application of magnetite-carbon particles, hydrophobically modified chitosan was applied to form a gel-like phase. This gel-like phase of crude oil containing magnetic carbon spheres can be removed as an aggregate using a magnet resulting in enhanced recovery of crude oil. The results from the current study point to developing potential applications for confinement, magnetic tracking and removal of surface oil. " / acase@tulane.edu

acase@tulane.edu

Acute respiratory distress syndrome (ARDS) is a pulmonary disease caused by surfactant dysfunction as a result of various types of trauma including sepsis and smoke inhalation. ARDS has a mortality rate of ~40% and affects ~150,000 people in the United States annually. Mechanical ventilation is a necessary life sustaining therapy to reopen collapsed airways. However, without a sufficient amount of active surfactant, the pressure required to reopen the airway increases significantly. Unfortunately, conventional ventilation, while necessary, can cause ventilator-induced lung injury. Atelectrauma is a type of lung injury that occurs at low volumes, and involves a repeated recruitment and de-recruitment (RecDer) of lung airways that induces mechanical stress on the epithelial lining. Our goal is to elucidate the fluid mechanics of RecDer in compliant airway models designed to mimic pulmonary airways. Here we design and build an apparatus that allows us to evaluate airway model compliance. Secondly, we characterize “tube laws” of these compliant airway models using this apparatus and identify suitable lab-manufactured airway models for experimentation. Finally, we investigate the RecDer phenomena in these models by measuring the frequency of de-recruitment as a result of the change in tube angle orientation and find a maximum frequency associated with angle orientation and reopening velocity. This research may provide a starting point for investigating further implications of RecDer, both mechanically and biologically, as well as developing novel ventilation waveforms to improve outcomes in ARDS patients. / acase@tulane.edu