SAE Small Vehicle Lifts

The SAE (Society for Automotive Engineers) vehicle teams at Cal Poly need an easy way to access the undersides of their vehicles to facilitate maintenance and servicing. The purpose of this project was to provide a solution that could lift the vehicles effectively and safely from above so that the underside of the vehicles can be accessed, as well as elevating the vehicles to an ergonomic working height. Design specifications were determined based off each vehicle’s requirements in addition to what the team intends to do with their suspended vehicle. After several concept iterations, the team decided to purchase an engine hoist and replace the hydraulic cylinder with a fixed tube and construct a custom transmission thereby turning the engine hoist into a crane mechanism that can be operated easily without concerns of reliability. The team constructed a total of three lifts, each with different specifications, for the Baja, Formula, and F2000 cars. Material testing was done to verify that the unknown material of the purchased lifts was strong enough to support the loading, as well as final load testing by lifting a vehicle to its designed height

Predicted mechanisms of resistance to mTOR inhibitors

The serine/threonine kinase, mTOR (mammalian Target of Rapamycin) has become a focus for cancer drug development. Rapamycins are highly specific inhibitors of mTOR and potently suppress tumour cell growth by retarding cells in G1 phase or potentially inducing apoptosis. Currently, both rapamycin and several analogues are being evaluated as anticancer agents in clinical trials. Results indicate that many human cancers have intrinsic resistance and tumours initially sensitive to rapamycins become refractory, demonstrating acquired resistance. Here, we consider mechanisms of resistance to inhibitors of mTOR

Reduced fire severity offers near-term buffer to climate-driven declines in conifer resilience across the western United States

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots. Our findings highlight declining regeneration capacity across the West over the past four decades for the eight dominant conifer species studied. Postfire regeneration is sensitive to high-severity fire, which limits seed availability, and postfire climate, which influences seedling establishment. In the near-term, projected differences in recruitment probability between low- and high-severity fire scenarios were larger than projected climate change impacts for most species, suggesting that reductions in fire severity, and resultant impacts on seed availability, could partially offset expected climate-driven declines in postfire regeneration. Across 40 to 42% of the study area, we project postfire conifer regeneration to be likely following low-severity but not high-severity fire under future climate scenarios (2031 to 2050). However, increasingly warm, dry climate conditions are projected to eventually outweigh the influence of fire severity and seed availability. The percent of the study area considered unlikely to experience conifer regeneration, regardless of fire severity, increased from 5% in 1981 to 2000 to 26 to 31% by mid-century, highlighting a limited time window over which management actions that reduce fire severity may effectively support postfire conifer regeneration. © 2023 the Author(s)

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Interactions between the discriminative and aversive properties of punishment

Punishment acquires a discriminative property when it is selectively paired with either reinforcement or extinction. At the milder punishment intensities, the discriminative control exerted by punishment is similar to the discriminative control exerted by a response-produced neutral (nonaversive) stimulus. However, the effect of the aversive property is apparent as the intensity of the punishment is increased. The aversive property of the punishment acts to enhance the discriminative control when the punishment is selectively applied during extinction periods, and to attenuate the discriminative control when the punishment is selectively applied during reinforcement periods. One major difference was found between the control exerted by the punishment and the response-produced neutral simulus: Responding greatly increased after the S(Δ) punishment but not after the S(Δ) neutral stimulus; this increase in responding was independent of the punishment intensities studied

Stimulus control of avoidance behavior

The introduction of a warning signal preceding shocks greatly increased the effectiveness of avoidance responding. Periods of “warm-up” at the beginning of the session were eliminated, and the number of shocks received by the subjects was greatly reduced. With response-shock interval constant, response rate increased as the interval between the response and the onset of the warning signal was shortened. The response tended to occur shortly after the onset of the warning signal regardless of the duration of these “safe” periods. A greatly elevated response rate was maintained even when the duration of the safe period was reduced to 0.3 sec. Thus, the pre-shock signal obtained nearly exclusive control of the responding and overrode the usual “temporal discrimination” of the response-shock interval

Safety and Efficacy of Combined Resveratrol and Sirolimus in Lymphangioleiomyomatosis

BACKGROUND: A critical need exists to develop remission-inducing therapies for lymphangioleiomyomatosis. RESEARCH QUESTION: Is the addition of resveratrol safe and more efficacious than sirolimus alone in patients with lymphangioleiomyomatosis? STUDY DESIGN AND METHODS: We conducted a phase 2, dose-escalating, open-label trial of resveratrol in patients with lymphangioleiomyomatosis receiving a stable regimen of sirolimus. Resveratrol was started at 250 mg/d and escalated every 8 weeks to maximum dose of 1,000 mg/d over 24 weeks. The primary outcome was ≥ 42% decline in serum vascular endothelial growth factor D (VEGF-D) levels on combined therapy compared with baseline VEGF-D levels on sirolimus. Secondary objectives included an assessment of the safety profile and the effect on lung function and health-related quality of life (HRQOL). Longitudinal change in outcome measures was assessed using linear mixed models. Adverse effects were tabulated using the National Cancer Institute\u27s Common Terminology Criteria for Adverse Events version 4. RESULTS: Twenty-five patients with lymphangioleiomyomatosis with a median age of 51 years were enrolled. Pulmonary function parameters at study inclusion were: FEV: median absolute, 1.72 L; 64% predicted; FVC: median absolute, 2.99 L; 96% predicted; and diffusing capacity of the lungs for carbon monoxide: median absolute, 14.68 mL/mm Hg/min; 37% predicted. The median serum VEGF-D value at baseline was 617 pg/mL. Patients entered the study with a median sirolimus dose of 2 mg/d with median trough level of 6.3 ng/mL. Despite some GI side effects, the addition of resveratrol was well tolerated. Although the primary outcome was not met, a statistically significant reduction in serum VEGF-D levels and improvement in HRQOL during the study was found. INTERPRETATION: The addition of resveratrol was safe and well tolerated in patients with lymphangioleiomyomatosis taking sirolimus and was associated with modest improvement in HRQOL. Larger controlled trials of this combination might be warranted to assess definitively the usefulness of resveratrol as an additive therapy in lymphangioleiomyomatosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03253913; URL: www. CLINICALTRIALS: gov