Probabilistic fracture mechanics and optimum fracture control of the solid rocket motor case of the shuttle

Development of a procedure for the reliability analysis of the solid rocket motor case of the space shuttle is described. The analysis is based on probabilistic fracture mechanics and consideration of a probability distribution for the initial flaw sizes. The reliability analysis can be used to select design variables, such as the thickness of the SRM case, projected design life and proof factor, on the basis of minimum expected cost and specified reliability bounds. Effects of fracture control plans such as the non-destructive inspections and the material erosion between missions can also be considered in the developed methodology for selection of design variables. The reliability-based procedure can be easily modified to consider other similar structures and different fracture control plans

Probabilistic Fracture Mechanics and Optimum Fracture Control Analytical Procedures for a Reusable Solid Rocket Motor Case

A methodology for the reliability analysis of a reusable solid rocket motor case is discussed. The analysis is based on probabilistic fracture mechanics and probability distribution for initial flaw sizes. The developed reliability analysis is used to select the structural design variables of the solid rocket motor case on the basis of minimum expected cost and specified reliability bounds during the projected design life of the case. Effects of failure prevention plans such as nondestructive inspection and the material erosion between missions are also considered in the developed procedure for selection of design variables. The reliability-based procedure can be modified to consider other similar structures of reusable space vehicle systems with different failure prevention plans

Achieve complete robust path delay fault testability

Recently, Pomeranz and Reddy [7], presented a test point insertion method to improve path delay fault testability in large combinational circuits. A test application scheme was developed that allows test points to be utilized as primary inputs and primary outputs during testing. The placement of test points was guided by the number of paths and was aimed at reducing this number. Indirectly, this approach achieved complete robust path delay fault testability in very low computation times. In this paper, we use their test application scheme, however, we use morre exact measures for guiding test point insertion like test generation and RD fault identification. Thus, we reduce the number of test point needed to achieve complete testability by ensuring that test points are inserted only on paths associated with path delay faults that are necessary to be tested and that are not robustly testable. Experimental results show that an average reduction of about 70% in the number of test points over the approach of [7] can be obtained.

Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis

Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60–80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis

Patient Perspectives on Medication Assisted Therapy in Vermont

Introduction. Medication-Assisted Therapy (MAT) for opioid addiction has dramatically increased in Vermont, supported by a novel statewide system that integrates specialty treatment centers ( Hubs ) with primary care office-based opioid therapy ( Spokes ). In 2010, Vermont had the highest per capita buprenorphine use in the US. Previous studies of patient perspectives of MAT have identified social barriers, rigid program rules, and concerns about withdrawal and relapse as common causes of treatment failure. Our goal was to elicit patient perspectives on barriers and enablers of successful MAT to further inform system refinement. Methods. An interview guide was developed based on previous literature as well as discussions with program leadership, staff and clinicians, and community stakeholders. Responses were organized using thematic content analysis with consensus across seven interviewers and two analysts. The interviews were conducted with 44 patients enrolled in MAT at two Hub sites in Burlington, VT in October 2016. Results. The median age of subjects was 34 years, 34% were employed at least part-time, and 72% were female. Half reported a mental health condition and 20% reported chronic pain. Barriers included transportation (25%), lack of stable housing, and stigma (41%). Enablers included feeling supported (82% felt well-supported; 52% felt supported by healthcare professionals). Subjects expressed high confidence in the treatment system and high self-efficacy for sobriety. Conclusions. Patients in MAT have complex medical, mental health, social, personal, and work lives. A comprehensive system that addresses this wide range of domains is critical to achieving optimal outcomes.https://scholarworks.uvm.edu/comphp_gallery/1245/thumbnail.jp

mTOR and MEK1/2 inhibition differentially modulate tumor growth and the immune microenvironment in syngeneic models of oral cavity cancer

We investigated the effects of mTOR and MEK1/2 inhibition on tumor growth and the tumor microenvironment in immunogenic and poorly immunogenic models of murine oral cancer. In vitro, rapamycin and PD901 inhibited signaling through expected downstream targets, but only PD901 reduced viability and altered function of MOC cells. Following transplantation of MOC cells into immune-competent mice, effects on both cancer and infiltrating immune cells were characterized following rapamycin and/or PD901 treatment for 21 days. In vivo, both rapamycin and PD901 inhibition reduced primary growth of established MOC tumors on treatment. Following withdrawal of PD901, rapid rebound of tumor growth limited survival, whereas durable tumor control was observed following rapamycin treatment in immunogenic MOC1 tumors despite more robust inhibition of oncogenic signaling by PD901. Characterization of the immune microenvironment revealed diminished infiltration and activation of antigen-specific CD8+ T-cells and other immune cells following PD901 but not rapamycin in immunogenic tumors. Subsequent in vitro T-cell assays validated robust inhibition of T-cell expansion and activation following MEK inhibition compared to mTOR inhibition. CD8 cell depletion abrogated rapamycin-induced primary tumor growth inhibition in MOC1 mice. These data have critical implications in the design of combination targeted and immune therapies in oral cancer

A Patient\u27s Perspective on Lower Urinary Tract Symptoms

Lower urinary tract symptoms (LUTS) have been increasing in incidence and prevalence in the United States. With a large annual health care cost, an association with a significantly reduced quality of life, and an aging population, LUTS is increasingly becoming more of a burden on the health care system. The American Urological Association created a symptom index in 1992 that assesses for the severity of seven LUTS associated with benign prostatic hyperplasia. This project seeks to address the question of which symptoms from the index score are more common; whether certain symptoms are more concerning from a patient’s perspective.https://scholarworks.uvm.edu/fmclerk/1370/thumbnail.jp