Application of MEMS Microphone Array Technology to Airframe Noise Measurements

Current generation microphone directional array instrumentation is capable of extracting accurate noise source location and directivity data on a variety of aircraft components, resulting in significant gains in test productivity. However, with this gain in productivity has come the desire to install larger and more complex arrays in a variety of ground test facilities, creating new challenges for the designers of array systems. To overcome these challenges, a research study was initiated to identify and develop hardware and fabrication technologies which could be used to construct an array system exhibiting acceptable measurement performance but at much lower cost and with much simpler installation requirements. This paper describes an effort to fabricate a 128-sensor array using commercially available Micro-Electro-Mechanical System (MEMS) microphones. The MEMS array was used to acquire noise data for an isolated 26%-scale high-fidelity Boeing 777 landing gear in the Virginia Polytechnic Institute and State University Stability Tunnel across a range of Mach numbers. The overall performance of the array was excellent, and major noise sources were successfully identified from the measurements

Composites of Heavy Rain Producing Elevated Thunderstorms in the Central United States

Composite analyses of the atmosphere over the central United States during elevated thunderstorms producing heavy rainfall are presented. Composites were created for five National Weather Service County Warning Areas (CWAs) in the region. Events studied occurred during the warm season (April–September) during 1979–2012. These CWAs encompass the region determined previously to experience the greatest frequency of elevated thunderstorms in the United States. Composited events produced rainfall of \u3e50 mm 24 hr−1 within the selected CWA. Composites were generated for the 0–3 hr period prior to the heaviest rainfall, 6–9 hours prior to it, and 12–15 hours prior to it. This paper focuses on the Pleasant Hill, Missouri (EAX) composites, as all CWA results were similar; also these analyses focus on the period 0–3 hours prior to event occurrence. These findings corroborate the findings of previous authors. What is offered here that is unique is (1) a measure of the interquartile range within the composite mean fields, allowing for discrimination between variable fields that provided a strong reliable signal, from those that may appear strong but possess large variability, and (2) composite soundings of two subclasses of elevated thunderstorms. Also, a null case (one that fits the composite but failed to produce significant rainfall) is also examined for comparison

Adoptive immunotherapy against allogeneic kidney grafts in dogs with stable hematopoietic trichimerism.

Dogs given nonmyeloablative conditioning and marrow grafts from 2 dog leukocyte antigen (DLA)-identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. In this study, we used trichimeras to evaluate strategies for adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from 2 DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy of total body irradiation (TBI) and given a short course of postgraft immunosuppression. After stable hematopoietic engraftment was confirmed, a kidney was transplanted from 1 of the 2 marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes from each kidney donor were then used to sensitize the alternate marrow donor. The trichimeric recipients were given donor lymphocyte infusions (DLIs) from the sensitized dogs and monitored for chimerism, graft-versus-host disease (GVHD), and kidney rejection. After DLI, we observed both prompt rejection of the transplanted marrow and donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably due to shared minor histocompatibility antigens, host chimerism also disappeared, and GVHD in skin, gut, and liver developed. The native kidneys, although exhibiting lymphocytic infiltration, remained functionally normal. This study demonstrates that under certain experimental conditions, the kidney--an organ ordinarily not involved in graft-versus-host reactions--can be targeted by sensitized donor lymphocytes

Silent progression in disease activity-free relapsing multiple sclerosis.

ObjectiveRates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation.MethodsDisability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates.ResultsRelapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05).InterpretationLong-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation