Acoustical and flow characteristics of a cough as an index of pulmonary function in the guinea pig

Human studies indicate that cough sound and flow analysis may be useful for diagnosing pulmonary abnormalities. The purpose of this study was to evaluate an animal model for cough sound and flow analysis. A system was designed to expose guinea pigs to aerosols of citric acid (0.39M) and record resulting coughs at different stages of chemically induced specific airway resistance (sRAW). Coughs were divided into three categories (low sRAW, n = 113; moderate sRAW, n = 143; high sR AW, n = 93). 124 cough sound parameters were derived from the analysis of the sound pressure waves recorded during the cough. A principal component analysis was performed on the acquired data, and the resulting parameters were used to train a single neuron feed-forward back propagation neural network. The classification system was able to correctly discriminate between members of the high and low airway constriction groups with an accuracy of 0.946 and a sensitivity and specificity of 0.893

Single-cell analysis of cell competition using quantitative microscopy and machine learning

Cell competition is a widely conserved, fundamental biological quality control mechanism. The cell competition assay of MDCK wild-type versus mutant MDCK Scribble-knockdown (ScribKD) relies on a mechanical mechanism of competition, which posits that the emergence of compressing stresses within the tissue at high confluency drive the competitive outcome. According to this mechanism, proliferating wild-type cells out-compete mutant ScribKD cells, resulting in their apoptosis and apical extrusion. Previous studies show that there is an increased division rate of wild-type cells in neighbourhoods with high numbers of ScribKD cells, but what still remains a mystery is whether this is a cause or consequence of increased apoptosis in the “loser” cell population. This project also interrogated the competitive assay of wild-type versus RasV12 , which is hypothesized to operate on a biochemical mechanism and results in the apical extrusion (but not apoptosis) of the loser RasV12 population. For both these mechanisms of competition it is still unknown which population of cells are driving the winner/loser outcome. Is the winner cell proliferation prompting the loser cell demise? Or is an autonomous loser elimination prompting a subsequent winner cell proliferation? In my research, I have employed multi-modal, time-lapse microscopy to image competition assays continuously for several days. These data were then segmented into wild-type or mutant instances using a Convolutional Neural Network (CNN) that can differentiate between the cell types, after which they were tracked across cellular generations using a Bayesian multi-object tracker. A conjugate analysis of fluorescent cell-cycle indicator probes was then utilised to automatically identify key time points of cellular fate commitment using deep-learning image classification. A spatio-temporal analysis was then conducted in order to quantify any correlation between wild-type proliferation and mutant cell demise. For the case of wild-type versus ScribKD , there was no clear evidence for the wild-type cells mitoses directly impacting upon the ScribKD cell apoptotic elimination. Instead, a subsequent analysis found that a more subtle mechanism of pre-emptive, local density increases around the apoptosis site appeared to be determining the eventual ScribKD fate. On the other hand, there was clear evidence of a direct impact of wild-type mitoses on the subsequent apical extrusion and competitive elimination of RasV12 cells. Both of these conclusions agree with the prevailing classification of cell competition types: mechanical interactions are more diffuse and occur over a larger spatio-temporal domain, whereas biochemical interactions are constrained to nearest neighbour cells. The hypothesized density-dependency of ScribKD elimination was further quantified on a single-cell scale by these analyses, as well as a potential new understanding of RasV12 extrusion. Most interestingly, it appears that there is a clear biophysical mechanism to the elimination in the biochemical RasV12 cell competition. This suggests that perhaps a new semantic approach is needed in the field of cell competition in order to accurately classify different mechanisms of elimination

Reconstruction of Twist Torque in Main Parachute Risers

The reconstruction of twist torque in the Main Parachute Risers of the Capsule Parachute Assembly System (CPAS) has been successfully used to validate CPAS Model Memo conservative twist torque equations. Reconstruction of basic, one degree of freedom drop tests was used to create a functional process for the evaluation of more complex, rigid body simulation. The roll, pitch, and yaw of the body, the fly-out angles of the parachutes, and the relative location of the parachutes to the body are inputs to the torque simulation. The data collected by the Inertial Measurement Unit (IMU) was used to calculate the true torque. The simulation then used photogrammetric and IMU data as inputs into the Model Memo equations. The results were then compared to the true torque results to validate the Model Memo equations. The Model Memo parameters were based off of steel risers and the parameters will need to be re-evaluated for different materials. Photogrammetric data was found to be more accurate than the inertial data in accounting for the relative rotation between payload and cluster. The Model Memo equations were generally a good match and when not matching were generally conservative

Rare variants contribute disproportionately to quantitative trait variation in yeast.

How variants with different frequencies contribute to trait variation is a central question in genetics. We use a unique model system to disentangle the contributions of common and rare variants to quantitative traits. We generated ~14,000 progeny from crosses among 16 diverse yeast strains and identified thousands of quantitative trait loci (QTLs) for 38 traits. We combined our results with sequencing data for 1011 yeast isolates to show that rare variants make a disproportionate contribution to trait variation. Evolutionary analyses revealed that this contribution is driven by rare variants that arose recently, and that negative selection has shaped the relationship between variant frequency and effect size. We leveraged the structure of the crosses to resolve hundreds of QTLs to single genes. These results refine our understanding of trait variation at the population level and suggest that studies of rare variants are a fertile ground for discovery of genetic effects

Investigating the role of Hedgehog/GLI1 signaling in glioblastoma cell response to temozolomide.

Resistance to chemotherapy substantially hinders successful glioblastoma (GBM) treatment, contributing to an almost 100% mortality rate. Resistance to the frontline chemotherapy, temozolomide (TMZ), arises from numerous signaling pathways that are deregulated in GBM, including Hedgehog (Hh) signaling. Here, we investigate suppression of Hh signaling as an adjuvant to TMZ using U87-MG and T98G cell lines as in vitro models of GBM. We found that silencing GLI1 with siRNA reduces cell metabolic activity by up to 30% in combination with TMZ and reduces multidrug efflux activity by 2.5-fold. Additionally, pharmacological GLI inhibition modulates nuclear p53 levels and decreases MGMT expression in combination with TMZ. While we surprisingly found that silencing GLI1 does not induce apoptosis in the absence of TMZ co-treatment, we discovered silencing GLI1 without TMZ co-treatment induces senescence as evidenced by a significant 2.3-fold increase in senescence associated β-galactosidase staining, and this occurs in a loss of PTEN-dependent manner. Finally, we show that GLI inhibition increases apoptosis in glioma stem-like cells by up to 6.8-fold in combination with TMZ, and this reduces the size and number of neurospheres grown from glioma stem-like cells. In aggregate, our data warrant the continued investigation of Hh pathway inhibitors as adjuvants to TMZ chemotherapy and highlight the importance of identifying signaling pathways that determine whether co-treatment will be successful

Slavery to Liberation: The African American Experience (Second Edition)

Slavery to Liberation: The African American Experience (Second Edition) gives instructors, students, and general readers a comprehensive and up-to-date account of African Americans’ cultural and political history, economic development, artistic expressiveness, and religious and philosophical worldviews in a critical framework. It offers sound interdisciplinary analysis of selected historical and contemporary issues surrounding the origins and manifestations of White supremacy in the United States. By placing race at the center of the work, the book offers significant lessons for understanding the institutional marginalization of Blacks in contemporary America and their historical resistance and perseverance.https://encompass.eku.edu/ekuopen/1002/thumbnail.jp

What makes a mitochondrion?

Experimental analyses of the proteins found in the mitochondria of yeast, humans and Arabidopsis have confirmed some expectations but given some surprises and some insights into the evolutionary origins of mitochondrial proteins

Bioactive Materials

Bioactive substantially silica-free glass material with a hydroxyapatite layer thereon is described, as well as methods for producing hydroxyapatite on a borate glass