Quantitative X-ray microradiography for high-throughput phenotyping of osteoarthritis in mice

Objective To investigate and validate digital X-ray microradiography as a novel, high-throughput and cost-effective screening approach to identify abnormal joint phenotypes in mice. Method Digital X-ray microradiography was used to quantify the subchondral bone mineral content (BMC) in the medial tibial plateau. Accuracy and reproducibility of the method were determined in 22 samples from C57BL/6(B6Brd;B6Dnk;B6N-Tyrc-Brd) wild-type mice. The method was then validated in wild-type mice that had undergone surgical destabilisation of medial meniscus (DMM) and in a genetically modified mouse strain with an established increase in trabecular bone mass. Results The measurement of subchondral BMC by digital X-ray microradiography had a coefficient of variation of 3.6%. Digital X-ray microradiography was able to demonstrate significantly increased subchondral BMC in the medial tibial plateau of male mice 4 and 8 weeks after DMM surgery and in female mice 8 weeks after surgery. Furthermore, digital X-ray microradiography also detected the increase in subchondral BMC in a genetically modified mouse strain with high trabecular bone mass. Conclusion Quantitation of subchondral BMC by digital X-ray microradiography is a rapid, sensitive and cost-effective method to identify abnormal joint phenotypes in mice of both genders at several ages

Nd:YAG development for spaceborne laser ranging system

The results of the development of a unique modelocked laser device to be utilized in future NASA space-based, ultraprecision laser ranger systems are summarized. The engineering breadboard constructed proved the feasibility of the pump-pulsed, actively modelocked, PTM Q-switched Nd:YAG laser concept for the generation of subnanosecond pulses suitable for ultra-precision ranging. The laser breadboard also included a double-pass Nd:YAG amplifier and provision for a Type II KD*P frequency doubler. The specific technical accomplishment was the generation of single 150 psec, 20-mJ pulses at 10 pps at a wavelength of 1.064 micrometers with 25 dB suppression of pre-and post-pulses

PROVE Endurance Car Front Suspension

This document details the collaborative Mechanical Engineering Senior Project with Cal Poly PROVE Lab on PROVE Lab’s Project 2; an electric vehicle designed to travel 1000 miles on a single charge. Logan Simon, Justine Kwan, and Lauren Williams are given the challenge of designing an innovative proof of concept front suspension suspension for this vehicle. After detailed research of new suspension systems, it was determined that the innovative nature could be in the form of unique manufacturing methods, materials use, or mechanical design. At this point in time, this vehicle is a purely conceptual design with no concrete requirements. Therefore engineering specifications were generated based on vehicles of similar size and function, such as PROVE Lab Project 1, Tesla’s Roadster, and the BMW z4. These specification included vehicle weight, speed, vertical travel, system weight, travel speed, and track width. Since this car is aimed to travel 1000 miles on one charge, efficiency is a big concern for the design. From ideation, the three suspension configurations of interest were MacPherson, double wishbone, and multi-link. A decision matrix was created to evaluate these designs based on design requirements, resulting in the selection of the multi-link configuration. However, after further investigation it was decided that a double wishbone configuration would provide nearly equal performance and be much more manageable of a task on the senior project time frame, compared to multi-link. The focus of the project then shifted to innovative manufacturing methods. Carbon fiber was chosen as the material to be used due to its lightweight nature, its accessibility through PROVE lab, and its lack of usage in a suspension system thus far. The upright would provide the most weight savings, so it was designed as a carbon fiber sandwich panel. Computer analysis of the system included SolidWorks FEA, Tsai Wu Failure Analysis, and ANSYS composite analysis to verify Tsai Wu. Four destructive tests were performed to validate the analysis and to determine the number of plies to be used for the final part. With all four tests passing the minimum load requirements with a factor of safety above 1, 16 plies per laminate was chosen and with an additional 8 plies around the edges. The final system proves that a carbon fiber suspension that is structurally sound for maximum loading cases and that cuts weight down to 4.3 pounds is possible. The full non-destructive test will be performed by the PROVE Project 2 team in the future, unassociated with this senior project

Unsupervised Multimodal Surface Registration with Geometric Deep Learning

This paper introduces GeoMorph, a novel geometric deep-learning framework designed for image registration of cortical surfaces. The registration process consists of two main steps. First, independent feature extraction is performed on each input surface using graph convolutions, generating low-dimensional feature representations that capture important cortical surface characteristics. Subsequently, features are registered in a deep-discrete manner to optimize the overlap of common structures across surfaces by learning displacements of a set of control points. To ensure smooth and biologically plausible deformations, we implement regularization through a deep conditional random field implemented with a recurrent neural network. Experimental results demonstrate that GeoMorph surpasses existing deep-learning methods by achieving improved alignment with smoother deformations. Furthermore, GeoMorph exhibits competitive performance compared to classical frameworks. Such versatility and robustness suggest strong potential for various neuroscience applications

System Safety Engineering for Social and Ethical ML Risks: A Case Study

Governments, industry, and academia have undertaken efforts to identify and mitigate harms in ML-driven systems, with a particular focus on social and ethical risks of ML components in complex sociotechnical systems. However, existing approaches are largely disjointed, ad-hoc and of unknown effectiveness. Systems safety engineering is a well established discipline with a track record of identifying and managing risks in many complex sociotechnical domains. We adopt the natural hypothesis that tools from this domain could serve to enhance risk analyses of ML in its context of use. To test this hypothesis, we apply a "best of breed" systems safety analysis, Systems Theoretic Process Analysis (STPA), to a specific high-consequence system with an important ML-driven component, namely the Prescription Drug Monitoring Programs (PDMPs) operated by many US States, several of which rely on an ML-derived risk score. We focus in particular on how this analysis can extend to identifying social and ethical risks and developing concrete design-level controls to mitigate them.Comment: 14 pages, 5 figures, 3 tables. Accepted to 36th Conference on Neural Information Processing Systems, Workshop on ML Safety (NeurIPS 2022

Winter locations of red-throated divers from geolocation and feather isotope signatures.

Migratory species have geographically separate distributions during their annual cycle, and these areas can vary between populations and individuals. This can lead to differential stress levels being experienced across a species range. Gathering informa-tion on the areas used during the annual cycle of red- throated divers (RTDs; Gavia stel-lata) has become an increasingly pressing issue, as they are a species of concern when considering the effects of disturbance from offshore wind farms and the associated ship traffic. Here, we use light- based geolocator tags, deployed during the summer breeding season, to determine the non- breeding winter location of RTDs from breed-ing locations in Scotland, Finland, and Iceland. We also use δ15N and δ13C isotope signatures, from feather samples, to link population- level differences in areas used in the molt period to population- level differences in isotope signatures. We found from geolocator data that RTDs from the three different breeding locations did not overlap in their winter distributions. Differences in isotope signatures suggested this spatial separation was also evident in the molting period, when geolocation data were unavailable. We also found that of the three populations, RTDs breeding in Iceland moved the shortest distance from their breeding grounds to their wintering grounds.In contrast, RTDs breeding in Finland moved the furthest, with a westward migration from the Baltic into the southern North Sea. Overall, these results suggest that RTDs breeding in Finland are likely to encounter anthropogenic activity during the win-ter period, where they currently overlap with areas of future planned developments. Icelandic and Scottish birds are less likely to be affected, due to less ship activity and few or no offshore wind farms in their wintering distributions. We also demonstrate that separating the three populations isotopically is possible and suggest further work to allocate breeding individuals to wintering areas based solely on feather samples.Migratory species have geographically separate distributions during their annual cycle, and these areas can vary between populations and individuals. This can lead to differential stress levels being experienced across a species range. Gathering information on the areas used during the annual cycle of red-throated divers (RTDs; Gavia stellata) has become an increasingly pressing issue, as they are a species of concern when considering the effects of disturbance from offshore wind farms and the associated ship traffic. Here, we use light-based geolocator tags, deployed during the summer breeding season, to determine the non-breeding winter location of RTDs from breeding locations in Scotland, Finland, and Iceland. We also use delta N-15 and delta C-13 isotope signatures, from feather samples, to link population-level differences in areas used in the molt period to population-level differences in isotope signatures. We found from geolocator data that RTDs from the three different breeding locations did not overlap in their winter distributions. Differences in isotope signatures suggested this spatial separation was also evident in the molting period, when geolocation data were unavailable. We also found that of the three populations, RTDs breeding in Iceland moved the shortest distance from their breeding grounds to their wintering grounds. In contrast, RTDs breeding in Finland moved the furthest, with a westward migration from the Baltic into the southern North Sea. Overall, these results suggest that RTDs breeding in Finland are likely to encounter anthropogenic activity during the winter period, where they currently overlap with areas of future planned developments. Icelandic and Scottish birds are less likely to be affected, due to less ship activity and few or no offshore wind farms in their wintering distributions. We also demonstrate that separating the three populations isotopically is possible and suggest further work to allocate breeding individuals to wintering areas based solely on feather samples.Peer reviewe

Spatial and temporal variation in foraging of breeding red‐throated divers

Differing environmental conditions can have profound effects on many behaviours in animals, especially where species have large geographic ranges. Seasonal changes or progression through life history stages impose differential constraints, leading to changes in behaviours. Furthermore, species which show flexibility in behaviours, may have a higher capacity to adapt to anthropogenic-induced changes to their environment. The red-throated diver (RTD) is an aquatic bird, that is able to forage in both freshwater and marine environments, though little else is known about its behaviours and its capacity to adapt to different environmental conditions. Here, we use time-depth recorders and saltwater immersion loggers to examine the foraging behaviour of RTDs from three regions across northwest Europe. We found that in the breeding season, birds from two regions (Iceland and Scotland) foraged in the marine environment, while birds from Finland, foraged predominantly in freshwater. Most of the differences in diving characteristics were at least partly explained by differences in foraging habitat. Additionally, while time spent foraging did not change through the breeding season, dives generally became more pelagic and less benthic over the season, suggesting RTDs either switched prey or followed vertical prey movements, rather than increasing foraging effort. There was a preference for foraging in daylight over crepuscular hours, with a stronger effect at two of the three sites. Overall, we provide the first investigation of RTD foraging and diving behaviour from multiple geographic regions and demonstrate variation in foraging strategies in this generalist aquatic predator, most likely due to differences in their local environment.Peer reviewe

Deletion of the Stress Response Gene \u3ci\u3eDDR48\u3c/i\u3e From \u3ci\u3eHistoplasma capsulatum\u3c/i\u3e Increases Sensitivity to Oxidative Stress, Increases Susceptibility to Antifungals, and Decreases Fitness In Macrophages

The stress response gene DDR48 has been characterized in Saccharomyces cerevisiae and Candida albicans to be involved in combating various cellular stressors, from oxidative agents to antifungal compounds. Surprisingly, the biological function of DDR48 has yet to be identified, though it is likely an important part of the stress response. To gain insight into its function, we characterized DDR48 in the dimorphic fungal pathogen Histoplasma capsulatum. Transcriptional analyses showed preferential expression of DDR48 in the mycelial phase. Induction of DDR48 in Histoplasma yeasts developed after treatment with various cellular stress compounds. We generated a ddr48∆ deletion mutant to further characterize DDR48 function. Loss of DDR48 alters the transcriptional profile of the oxidative stress response and membrane synthesis pathways. Treatment with ROS or antifungal compounds reduced survival of ddr48∆ yeasts compared to controls, consistent with an aberrant cellular stress response. In addition, we infected RAW 264.7 macrophages with DDR48-expressing and ddr48∆ yeasts and observed a 50% decrease in recovery of ddr48∆ yeasts compared to wild-type yeasts. Loss of DDR48 function results in numerous negative effects in Histoplasma yeasts, highlighting its role as a key player in the global sensing and response to cellular stress by fungi