Optimizing Energy Usage in a Solar-Powered Vehicle

The University of Missouri - Rolla (UMR) will be entering SUNRAYCE \u2793 and the World Solar Challenge and expects to excel in these solar-powered car races. Some of the factors involved in winning a race include efficiency, reliability, and high power. All of these are important considerations, but will be ineffective unless appropriately harnessed by a power management scheme appropriate to a race strategy. The power management scheme will be used to efficiently and effectively distribute available power to the car\u27s systems throughout a race day. My goal was to produce a software framework into which the specifications and performance models of the UMR car, Sol Survivor, can be inserted as they evolve. Data is taken from a telemetry system and processed to produce fuel gauges for the driver. As of yet, a final vehicle is not available, so the specifications are estimates based upon worst- case scenarios. Detail is added to the software model as work proceeds

The monstrous body of the law: Wollstonecraft vs. Shelley

Includes bibliographical references.Cover title.published_or_final_versio

John Austin or Jane Austen?: the province of jurisprudence determined in pride and prejudice

Cover title.Includes bibliographical references and index.January 1998.published_or_final_versio

Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011.

BackgroundSince the introduction of the Haemophilus influenzae serotype b vaccine, H influenzae epidemiology has shifted. In the United States, the largest burden of disease is now in adults aged ≥65 years. However, few data exist on risk factors for disease severity and outcome in this age group.MethodsA retrospective case-series review of invasive H influenzae infections in patients aged ≥65 years was conducted for hospitalized cases reported to Active Bacterial Core surveillance in 2011.ResultsThere were 299 hospitalized cases included in the analysis. The majority of cases were caused by nontypeable H influenzae, and the overall case fatality ratio (CFR) was 19.5%. Three or more underlying conditions were present in 63% of cases; 94% of cases had at least 1. Patients with chronic heart conditions (congestive heart failure, coronary artery disease, and/or atrial fibrillation) (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.65-6.46), patients from private residences (OR, 8.75; 95% CI, 2.13-35.95), and patients who were not resuscitate status (OR, 2.72; 95% CI, 1.31-5.66) were more likely to be admitted to the intensive care unit (ICU). Intensive care unit admission (OR, 3.75; 95% CI, 1.71-8.22) and do not resuscitate status (OR, 12.94; 95% CI, 4.84-34.55) were significantly associated with death.ConclusionsWithin this age group, burden of disease and CFR both increased significantly as age increased. Using ICU admission as a proxy for disease severity, our findings suggest several conditions increased risk of disease severity and patients with severe disease were more likely to die. Further research is needed to determine the most effective approach to prevent H influenzae disease and mortality in older adults

Penicillin Use in Meningococcal Disease Management: Active Bacterial Core Surveillance Sites, 2009.

In 2009, in the Active Bacterial Core surveillance sites, penicillin was not commonly used to treat meningococcal disease. This is likely because of inconsistent availability of antimicrobial susceptibility testing and ease of use of third-generation cephalosporins. Consideration of current practices may inform future meningococcal disease management guidelines

Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population

TAM family receptors in conjunction with MAPK signalling are involved in acquired resistance to PI3Kα inhibition in head and neck squamous cell carcinoma.

BACKGROUND: Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Despite pre-clinical and clinical studies, outcomes from targeting the PI3K pathway have been underwhelming and the development of drug resistance poses a significant barrier to patient treatment. In the present study, we examined mechanisms of acquired resistance to the PI3Kα inhibitor alpelisib (formerly BYL719) in HNSCC cell lines and patient-derived xenografts (PDXs). METHODS: Five unique PDX mouse models and three HNSCC cell lines were used. All cell lines and xenografts underwent genomic characterization prior to study. Serial drug treatment was conducted in vitro and in vivo to develop multiple, clinically-significant models of resistance to alpelisib. We then used reverse phase protein arrays (RPPAs) to profile the expression of proteins in parental and drug-resistant models. Top hits were validated by immunoblotting and immunohistochemistry. Flow cytometric analysis and RNA interference studies were then used to interrogate the molecular mechanisms underlying acquired drug resistance. RESULTS: Prolonged treatment with alpelisib led to upregulation of TAM family receptor tyrosine kinases TYRO3 and AXL. Importantly, a significant shift in expression of both TYRO3 and AXL to the cell surface was detected in drug-resistant cells. Targeted knockdown of TYRO3 and AXL effectively re-sensitized resistant cells to PI3Kα inhibition. In vivo, resistance to alpelisib emerged following 20-35 days of treatment in all five PDX models. Elevated TYRO3 expression was detected in drug-resistant PDX tissues. Downstream of TYRO3 and AXL, we identified activation of intracellular MAPK signalling. Inhibition of MAPK signalling also re-sensitized drug-resistant cells to alpelisib. CONCLUSIONS: We have identified TYRO3 and AXL receptors to be key mediators of resistance to alpelisib, both in vitro and in vivo. Our findings suggest that pan-TAM inhibition is a promising avenue for combinatorial or second-line therapy alongside PI3Kα inhibition. These findings advance our understanding of the role TAM receptors play in modulating the response of HNSCC to PI3Kα inhibition and suggest a means to prevent, or at least delay, resistance to PI3Kα inhibition in order to improve outcomes for HNSCC patients

Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (\u3e20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients