Properties of solid-liquid interfaces determine ionic and molecular transport through nanopores, affecting separation systems and the functioning of energy storage devices, such as supercapacitors and batteries. The distribution of electric potentials and ionic concentrations next to charged surfaces, for example, can often be described using the Debye-Huckel theory. To date, solid-liquid interfaces in aqueous media have been studied thoroughly, but in organic media, are less understood. Herein, we use the resistive-pulse technique and single nanopores to observe the electroosmotic transport of individual polystyrene and silica particles in organic solvents including propylene carbonate and acetone. Each individual particle within the nanopore causes a transient decrease of the transmembrane current. Duration of the current decrease is a measure of the particles’ velocity and can be related to the effective surface charge of the pore walls since the particles used, are not expected to be charged. The direction of the particles’ passage informs us about the effective surface charge polarity of the pore walls. The polymer nanopores that we chose for our experiments are negatively charged in aqueous media. In propylene carbonate and acetone however, the effective surface charge polarity of the nanopore was shown to go from negative to positive. The origin of the positive surface charge of the pore walls can be explained possibly by the reorganization of the solvent molecules at the pore walls, cation adsorption, or a surface potential caused by the solvent dipole moment.
School of Medicine
Introduction: The most frequent hospital-acquired infection is Clostridium difficile infection (CDI). The estimated financial burden of CDI on the United States annual expenditures is $4.8 billion. Recent literature suggests that use of prophylactic probiotics holds potential for prevention of CDI among high risk patients. Currently, clinical tool exists for deciding who should receive probiotics to prevent CDI.
Objective: The aim is to develop a calculator for the risk of acquiring CDI, to identify patients who are at high risk of acquiring CDI and would benefit from prophylactic probiotics administration.
Methods: We searched the Cochrane Library and PubMed for (1) papers reporting use of probiotics to prevent CDI and (2) studies suggesting use of a CDI risk scoring system. We analyzed a total of more than 10 risk scoring systems in order to create a calculator with the most predictive risk factors for which a patient would be considered high risk (≥5%) of developing CDI.
Results: The Cochrane findings regarding use of probiotics to prevent CDI were incorporated with these calculators to create recommended risk score cutoffs for whether to administer probiotics. We developed an online calculator that offers recommendations distinguishing between patients at high risk of CDI (should receive probiotics) and those who are at low risk (should not receive probiotics). Our calculator: https://shonitnairsharma.wixsite.com/probiotics.
Conclusions: The combination of peer-reviewed CDI risk score models, along with the current guidelines on probiotic administration, allowed us to create an online clinical tool for determining which patients should receive probiotics to prevent CDI. Implementing this calculator on hospital floors would support more appropriate and earlier decision points for administration of probiotics during admission. The estimated US total annual savings of using our calculator for probiotic prophylaxis is $2.4 billion. Further study is currently underway concerning the clinical efficacy and financial implications of our calculator.
Neurobiology and Behavior
Nicotinic acetylcholine receptors (nAChRs) have been implicated in various cognitive processes, including learning, memory and sensory processing. However, little is known about the endogenous mechanisms that modulate the function of nAChRs and their impact on behavior. Here, we examined the role of an endogenous protein modulator of nAChRs, lynx1, in a knockout mouse model. We hypothesized that the absence of lynx1 would increase operant learning and sensory gating, since its presence has been proposed to dampen nAChR signaling. To test the effects of lynx1 on sensory processing, male lynx1 knockout mice and their wildtype littermates were examined in the prepulse inhibition test. To examine the effects on operant learning and cognitive flexibility, lynx1 knockout and wildtype mice were trained to press a lever to receive food reward under a fixed ratio schedule of reinforcement. After acquisition and establishing baseline levels of responding, mice were then assessed in a lever reversal task. Together, these findings further define the function of lynx1 proteins in behaviors mediated by cholinergic signaling mechanisms.
Mechanical and Aerospace Engineering
Applications of sealant and adhesive technologies in aerospace industries require appropriate and reliable sealing materials and tools to provide suitable sealing. Due to a growing use of integral fuel tanks, which utilize the aircraft structure for fuel containment, this study focuses on nozzle geometry optimization of aircraft fuel tank sealant in order to develop and facilitate sealant approval process and to ensure the implementation of suitable fuel tank sealing.
Computational Fluid Dynamics (CFD) analyses were performed to numerically study the sealant flow characterization and behavior using Star-CCM+ software. In this study, high viscous shear thinning sealant material was modeled properly by generalized Newtonian Carreau-Yasuda model for the first time, when it was used to be modeled by generalized Newtonian power law model. Response Surface Methodology (RSM) was implemented by the aid of Design of Experiments (DOE) techniques, to develop the optimized mathematical model based on the collected data from numerical results. Afterward, a 3D model of the optimized nozzle geometry model was built to conduct the experiment with the sealant material and to verify the results of the numerical investigations. Scanning Electron Microscopy (SEM) was utilized to investigate the fracture/deformation of hollow glass microballoons and entrapped air bubbles within the cured sealant.
The results of this research concluded that the bent angle in nozzle geometry increases the sealant pressure drop throughout the nozzle. There is an optimized value for travel distance and cross sectional dimension and geometrical shape within the nozzle geometry that minimizes overall dynamic viscosity of the sealant. The geometry optimization pattern that was conducted in this study is a valuable pattern for geometry optimization and design of the fluid systems that deal with non-Newtonian fluids. In addition, the identified nozzle geometry model can be considered an applicable sealant nozzle template for the aerospace industries equipment manufacturers.
Neurobiology & Behavior
The innate immune system, particularly microglia, have been strongly implicated in Alzheimer‚Äôs disease (AD) pathogenesis, however the role of the adaptive immune system remains poorly understood. To investigate the impact of adaptive immunity on AD pathology, our lab previously generated a transgenic mouse model of immune deficient AD mice (RAG2…£c-/-5xfAD). Interestingly, deletion of adaptive immune cells in these mice leads to a dramatic increase in amyloid beta plaque load and an activated microglial neuroinflammatory state with decreased ability to phagocytose amyloid beta. To recapitulate the adaptive immune system, bone marrow transplants (BMT) from GFP+ immune-intact 5xfAD mice into RAG2…£c-/-5xfAD and RAG2…£c-/- wild-type controls were performed. Reconstituted Rag2…£c-/-5xfAD mice exhibited a decrease in amyloid beta plaques, indicating a fundamental role for the adaptive immune system in AD pathology. To further investigate the role of T cells in AD, we next performed BMT and T cell adoptive transfers into aged RAG2…£c-/-5xfAD and RAG2…£c-/- mice. Immunohistochemistry (IHC) and flow cytometry revealed an increase in GFP+ CD4+ T cells and an even greater increase in GFP+ CD8+ T cells in the RAG2…£c-/-5xfAD brain parenchyma. Interestingly, T cells were frequently observed adjacent to microglia in the RAG2…£c-/-5xfAD brain. Therefore, we hypothesize that infiltrating CD8+ T cells may directly interact with microglia to modulate their activity and decrease amyloid beta in the AD brain. These data suggest that further exploration of the crosstalk between adaptive immune cells and innate immune cells is needed to determine the mechanisms by which adaptive immunity influence AD pathogenesis.
Proteins are fundamental building blocks of life: understanding protein structure, function, aggregation, and degradation is, therefore, one of the central questions in biology. My work investigates protein aggregation and degradation through computational modeling, protein structure network analysis, and experimental verification. One theme of my work is the discovery of new enzymes from the carnivorous plant, Drosera capensis. Swiftly moving from raw data to chemical results is imperative to keep up with the ever-expanding genome sequencing data. Our target selection pipeline aids rapid in silico protein structure prediction from raw genomic data to direct the subsequent experimental characterization of promising candidates. In our in silico maturation process, initial structural models undergo post-translational modifications, followed by equilibration using explicit-solved molecular dynamics simulations. Subsequent network analysis predicts interesting protein properties such as aggregation propensity and potential enzyme activity, aiding the selection of functionally useful proteins for characterization. So far, this work has resulted in three publications- proteases, chitinases, and esterase/lipases. The protease resistance of amyloid fibrils and their central role in more than 40 human diseases, including Alzheimer’s, makes them an attractive target to test the activity of new proteases from D.capensis. To advance and streamline scientific discovery related to amyloid fibrils, it was crucial to have a standardized nomenclature. We introduced a systematic approach to the nomenclature of fibril topology using graph theoretic concepts to abstract the structure. Our scheme encompasses all amyloid fibrils currently in the PDB, and can be easily extended to accommodate newer discoveries. We also showed that the vast majority of known fibril structures fall into just three topological categories, something that was previously unnoticed. My work has improved the discussion of fibril structures by condensing the descriptions of complicated structural features using a set of universal structural motifs.
Before a pesticide is ever sprayed on a plant, its effects on the environment and non-target species, like bees and humans are thoroughly evaluated. But once applied to soil or a leaf, it is exposed to sunlight and air where it can potentially transform into a variety of new chemicals. These atmospheric reaction products will have their own toxicity and environmental fates and have the potential to impact bees pollinating the crop, humans near the application site, or anyone who goes on to eat the produce. My chemistry research is a hunt for the environmental fate of the most widely used pesticide class on the market: neonicotinoids. Discovering their degradation products‚Äô prevalence, toxicity, and fate at the molecular level is imperative to our health and safety. Results will be discussed of recent studies comparing the degradation in the presence of sunlight on surfaces compared to in water. Degradation products identified and their implications will be discussed, as well as differences observed between pure neonicotinoids and their commercial formulations.
Materials Science and Engineering
State-of-the-art X-ray imaging techniques, such as transmission X-ray microscopy and its three-dimension version X-ray computed tomography (CT) combined with the operando and in-suit environments, offer unprecedented insight into the processes at micro-scale. With 1.3 um spatial resolution and potential for sub-second scan temporal resolution the changes of the materials under a realistic operating condition can be captured. Here, we present the in-situ study of pyrolysis process of catalyst for fuel cell application. A custom built pyrolysis chamber was used for this in-situ study. The sample was pyrolized in-suit at the beamline with two ramp-up stages, one hold stage and one cold-down stage, whereas at the same time three-dimensional images were collected. The catalyst sample is made from iron precursor and the mixture of three nitrogen-rich organic precursors, which then were put into the furnace and. With the images of the sample in the furnace, the evaporation of precursors resulted in crack formation. We analyze the resulting porosity and tutorsity changes during the pyrolysis process.