High Precision X-ray CT-scanning of Biological Samples

Visualizing the micro-scale details of an item without disturbing its natural structure is always desirable because critical information is often lost during dissection or destructive analysis. High precision X-ray CT scans are used in engineering analyses to non-destructively view samples with volume elements as small as 10micro-meters, but this technique is problematic for non-rigid biological samples. Other problems arise from low x-ray contrast of tissue and the long scan times required. We will present results of micro-CT scans performed on biological samples as small as a bovine embryo and as large at a coyote skull. We will also discuss techniques to enhance the details captured in the x-ray images using contrast enhancers such as iodine (stains). We are working on post scan techniques to improve image quality, reduce scan times and to isolate items appearing in CT scans so they can be accurately recreated using a 3-D printer. Results and progress will be reported

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Molecular modulation of Schottky barrier height in metal-molecule-silicon diodes: Capacitance and simulation results

There is considerable current interest in using molecular materials to influence the surface potential of semiconductor devices for nanoelectronic and sensing applications. We present experimental capacitance-voltage results showing that systematic Schottky barrier height modulation can be achieved using dipolar molecular layers in gold-molecule-silicon devices. A computational methodology that combines quantum chemistry and traditional electrostatic calculations is used to explore various physical effects that can influence barrier heights in such systems. Nonidealities such as silicon surface states can influence both the potential profile within the device and the validity of the extracted barrier height. Our devices exhibit low surface state densities, but the magnitude of surface potential modulation is modest due to molecular depolarization from the gold contact

High Precision X-ray CT-scanning of Biological Samples

Visualizing the micro-scale details of an item without disturbing its natural structure is always desirable because critical information is often lost during dissection or destructive analysis. High precision X-ray CT scans are used in engineering analyses to non-destructively view samples with volume elements as small as 10micro-meters, but this technique is problematic for non-rigid biological samples. Other problems arise from low x-ray contrast of tissue and the long scan times required. We will present results of micro-CT scans performed on biological samples as small as a bovine embryo and as large at a coyote skull. We will also discuss techniques to enhance the details captured in the x-ray images using contrast enhancers such as iodine (stains). We are working on post scan techniques to improve image quality, reduce scan times and to isolate items appearing in CT scans so they can be accurately recreated using a 3-D printer. Results and progress will be reported.</p

Solvation Station: Microsolvation for Modeling Vibrational Sum-Frequency Spectra of Acids at Aqueous Interfaces

Vibrational sum-frequency spectra of a pair of poly­(methacrylic acid) isomers at an oil/water interface and glutaric acid at an air/water interface were calculated in the carbonyl stretching region. Orientational, conformational, and solvation information was determined using classical molecular dynamics (MD), while second-order susceptibility vibrational response tensors were determined for a set of density functional theory (DFT) structures. The DFT structures were microsolvated with water molecules corresponding to the major solvation states present in the MD calculations. The inclusion of the microsolvating waters incorporates solvation effects important to the carboxylic acid stretching modes in the studied spectral region. The calculated spectra strongly agree with experimental spectra when a cutoff of 1.975 Å is used to define a hydrogen bond in the MD trajectories. With the chosen cutoff, the most common solvation state of the carboxylic acid moieties involves a single hydrogen bond to the carbonyl oxygen and a single hydrogen bond to the carboxylic acid hydrogen. The sensitivity of the spectra to the hydrogen bond cutoff definition and the included DFT structures was investigated. Moderate changes in the relative intensities of the contributing peaks were found in both cases. Shortening the hydrogen bond cutoff definition predictably leads to a decrease in the relative intensity of peaks corresponding to well-solvated structures, while altering the set of DFT solvation structures results in more complex behavior that is dependent on the specific structures included

Computational Vibrational Sum Frequency Spectra of Formaldehyde and Hydroxymethanesulfonate at Aqueous Interfaces

The identity and arrangement of aqueous species at the interface of atmospheric aerosol impacts aerosol properties including albedo and propensity to uptake additional gas phase species. Formaldehyde and sulfur dioxide are two common atmospheric species that alter (individually and in concert) aqueous atmospheric aerosol interfaces. Vibrational sum frequency (VSF) spectroscopy studies of planar aqueous formaldehyde solution surfaces have shown alteration during exposure to sulfur dioxide gas. Additional changes were observed once exposure was ceased. The results suggested the formation of a new organic species, hydroxymethanesulfonate (HMS), which acts as a thermodynamic sink for aqueous sulfur dioxide and lead to acidification of the aerosol particles. The coherent nature of the VSF response and its strong dependence on surface species present and their orientations, however, made definite vibrational assignments for exact species notoriously difficult. The focus of this paper is on elucidating the species and orientations that give rise to specific experimentally derived spectral features through VSF spectra calculated using a combination of classical molecular dynamics (MD) and density functional theory (DFT). The results demonstrate that the most prevalent surface species for a formaldehyde containing aqueous solution is hydrated formaldehyde in the form of methylene glycol. Calculated VSF spectral frequencies for the proposed product HMS are in agreement with experiment. Furthermore, changes in the experimental spectra both during and after the flow of sulfur dioxide are consistent with HMS in different interfacial orientations

Combined Quantum Mechanics (TDDFT) and Classical Electrodynamics (Mie Theory) Methods for Calculating Surface Enhanced Raman and Hyper-Raman Spectra

Multiscale models that combine quantum mechanics and classical electrodynamics are presented, which allow for the evaluation of surface-enhanced Raman (SERS) and hyper-Raman scattering spectra (SEHRS) for both chemical (CHEM) and electrodynamic (EM) enhancement mechanisms. In these models, time-dependent density functional theory (TDDFT) for a system consisting of the adsorbed molecule and a metal cluster fragment of the metal particle is coupled to Mie theory for the metal particle, with the surface of the cluster being overlaid with the surface of the metal particle. In model A, the electromagnetic enhancement from plasmon-excitation of the metal particle is combined with the chemical enhancement associated with a static treatment of the molecule–metal structure to determine overall spectra. In model B, the frequency dependence of the Raman spectrum of the isolated molecule is combined with the enhancements determined in model A to refine the enhancement estimate. An equivalent theory at the level of model A is developed for hyper-Raman spectra calculations. Application to pyridine interacting with a 20 nm diameter silver sphere is presented, including comparisons with an earlier model (denoted G), which combines plasmon enhanced fields with gas-phase Raman (or hyper-Raman) spectra. The EM enhancement factor for spherical particles at 357 nm is found to be 10⁴ and 10⁶ for SERS and SEHRS, respectively. Including both chemical and electromagnetic mechanisms at the level of model A leads to enhancements on the order of 10⁴ and 10⁹ for SERS and SEHRS