The Role of Matrix Metalloproteinases in the Immunopathology of Cerebral Tuberculosis

Introduction: Central nervous system tuberculosis (CNS TB) has a high mortality. Microglial derived matrix metalloproteinases (MMPs) are implicated in the intense inflammatory response to Mycobacterium tuberculosis (M.tb) as the blood brain barrier is rich in MMP substrates. Methods: In a cellular model of CNS TB human microglial cells were stimulated with M.tb and conditioned media from M.tb infected human monocytes (CoMTb). Gene expression of all 23 MMPs and the 4 tissue inhibitors of MMP (TIMPs) was analysed by real time RT-PCR and secretion by Luminex and Western blotting. MMP gene transcription regulation was studied by luciferase promoter reporter assays and NFkB/AP-1 ELISAs. MAP kinases were studied by Western blotting. Immunohistochemistry of CNS TB biopsies and ELISA analysis of cerebrospinal fluid (CSF) was performed. Results: CoMTb up-regulated expression of MMP-1, -3 and -9, which was suppressed by dexamethasone. In contrast CoMTb did not alter TIMP-1 and reduced TIMP-2, -3 and -4 expression. M.tb up-regulated MMP-1 and -3 secretion. However, CoMTb drove MMP-1 and -3 secretion more potently than M.tb but suppressed MMP-2 secretion. Nuclear NFkB p50-p65 heterodimers and AP-1 cJun/FosB increased in CoMTb stimulated cells, with concomitant degradation of IkBα. Mutation of NFkB and AP-1 sites in the MMP-1 promoter abrogated CoMTb promoter activity. CoMTb drove early p38 and ERK MAP kinase phosphorylation. Chemical inhibition of both NFkB and p38 returned MMP-1 and 3 secretion to control levels but enhanced MMP-2 secretion that was also caspase 8 dependent. MMP/TIMP concentrations in CSF samples from TBM patients were predictive of coma severity and outcome and demonstrated that dexamethasone preferentially suppressed MMP-9. Conclusions: In CNS TB unopposed MMP-1 and -3 expression and secretion are driven by M.tb-infected monocyte networks and regulated by p38, NFkB and AP-1. CSF MMP/TIMP concentrations predict disease severity and offer a mechanism for the beneficial effect of dexamethasone therapy

Flight Mechanics Modeling and Post-Flight Analysis of ADEPT SR-1

Sounding Rocket One (SR-1), the first flight test of the Adaptable Deployable Entry and Placement Technology (ADEPT), was performed on Sept. 12, 2018. ADEPT is a deployable aeroshell that can be stowed during launch and then opened after launch to increase the drag area of the spacecraft when entering into a planetary atmosphere. The main objectives of the SR-1 flight test were to demonstrate that the ADEPT vehicle can be opened exo-atmospherically and to characterize the stability of the vehicle during atmospheric flight. The SR-1 test vehicle was a 0.7 m diameter 70 degree half-angle, faceted, sphere-cone, which was the primary payload on an UP Aerospace Spaceloft (SL) launch vehicle from the White Sands Missile Range (WSMR). ADEPT successfully separated from the spent booster in its stowed configuration, opened above 100 km altitude, and then landed in the deployed configuration within WSMR. The flight mechanics of the vehicle was modeled pre-flight for performance and range safety predictions. This paper describes the pre-flight ADEPT trajectory simulation and how the flight data compared with the predictions from the simulations

Subsonic Dynamic Testing of a Subscale ADEPT Entry Vehicle

The Adaptive Deployable Entry and Placement Technology (ADEPT) is a mechanically-deployed entry system. A sounding rocket test flight of an ADEPT vehicle, known as ADEPT SR-1, was conducted in September 2018. Prior to this sounding rocket test, an investigation was performed using the NASA Langley Research Center 20-ft Vertical Spin Tunnel (VST) to assess the free-flight dynamic characteristics of ADEPT SR-1 at subsonic speeds. The model of ADEPT SR-1 for this VST test was fabricated at 50-percent geometric scale, with dynamically scaled mass properties (Froude scaled) to represent full-scale flight at an altitude of 1.2 km above sea level. The subsonic dynamic characteristics of ADEPT SR-1 were of interest prior to the sounding rocket test because of payload recovery considerations. At low roll rates the model was found to have acceptable dynamic characteristics. It was statically stable in pitch and yaw, exhibiting limit cycle pitch/yaw oscillations of no greater than 20 degrees (the angle between the models longitudinal axis and nadir). The model was able to recover from large upsets in pitch and yaw, although if sufficiently provoked it tumbled. Damping in roll was low. At high roll rates the pitch and yaw oscillations grew in magnitude and rate. This behavior was also observed during the sounding rocket flight test

Parallelization of a Six Degree of Freedom Entry Vehicle Trajectory Simulation Using OpenMP and OpenACC

The art and science of writing parallelized software, using methods such as Open Multi-Processing (OpenMP) and Open Accelerators (OpenACC), is dominated by computer scientists. Engineers and non-computer scientists looking to apply these techniques to their project applications face a steep learning curve, especially when looking to adapt their original single threaded software to run multi-threaded on graphics processing units (GPUs). There are significant changes in mindset that must occur; such as how to manage memory, the organization of instructions, and the use of if statements (also known as branching). The purpose of this work is twofold: 1) to demonstrate the applicability of parallelized coding methodologies, OpenMP and OpenACC, to tasks outside of the typical large scale matrix mathematics; and 2) to discuss, from an engineers perspective, the lessons learned from parallelizing software using these computer science techniques. This work applies OpenMP, on both multi-core central processing units (CPUs) and Intel Xeon Phi 7210, and OpenACC on GPUs. These parallelization techniques are used to tackle the simulation of thousands of entry vehicle trajectories through the integration of six degree of freedom (DoF) equations of motion (EoM). The forces and moments acting on the entry vehicle, and used by the EoM, are estimated using multiple models of varying levels of complexity. Several benchmark comparisons are made on the execution of six DoF trajectory simulation: single thread Intel Xeon E5-2670 CPU, multi-thread CPU using OpenMP, multi-thread Xeon Phi 7210 using OpenMP, and multi-thread NVIDIA Tesla K40 GPU using OpenACC. These benchmarks are run on the Pleiades Supercomputer Cluster at the National Aeronautics and Space Administration (NASA) Ames Research Center (ARC), and a Xeon Phi 7210 node at NASA Langley Research Center (LaRC)

The Stars, The Stripes and You

https://digitalcommons.library.umaine.edu/mmb-vp/6187/thumbnail.jp

Cutaneous Ulcerations as the Presenting Sign of Acute Aortic Occlusion

This is a report of a case of acute aortic occlusion (AAO) in a 46-year-old woman who presented with confluent and coalescing punched-out ulcerations on the bilateral medial buttocks and abdominal ulcerations. This case highlights how AAO, although rare, should be considered in patients with cardiovascular risk factors presenting with acute lower extremity pain and new-onset cutaneous ulcerations of the perineum and/or abdomen

Gender & Physical Activity and Their Relationship to Binge Drinking & Overall Frequencey of Alcohol Consumption Among Adolescents

The purpose of this study is to explore how gender and physical activity (PA)are related to alcohol use (AU) among adolescents. A better understanding offactors that influence AU among adolescents will facilitate the developmentof preventive interventions in this population.The sample was pulled from the 2011 Youth Risk Behavior SurveillanceSystem (YRBSS), which used a systematic equal probability sampling of9-12 graders. It was hypothesized that males would have higher rates of AUthan would females. PA was also hypothesized to show stronger associationswith AU among males than among females.Consistent with our hypothesis, males were found to consume morealcohol versus females. Though a select-few research studies have found anassociation between higher levels of PA and high levels of alcohol use, thelarge association we found was unexpected. Additionally, we predictedappropriately that PA would have a greater influence on AU among males.While prior research has determined the importance of PA in advancinghealth-related outcomes, relatively few studies have examined therelationship between PA and specific problem health behaviors amongadolescents. Therefore, identifying the factors that influence the relationshipbetween PA and AU is important

Adaptive Control Allocation for Powered Descent Vehicles

The following work details a study into real-time failure adaptive control allocation method for powered descent vehicle systems. The motivation for this work is to enable future human and robotic missions utilizing a powered descent system to tolerate engine failures in flight without the loss of crew or assets. This study is conducted using a six degree-of-freedom trajectory simulation of a PDV (Powered Descent Vehicle) experiencing either a loss of thrust or an engine stuck full on failure scenario. Sequential least squares in the frequency domain is used on-board to process inertial measurement unit (IMU) data and generate an estimate of the PDV plant model, which is then fed to the guidance and control system. Data used by the sequential least squares method is generated from an in-flight maneuver. The work herein focuses on determining a maneuver that is least impactful to the PDV trajectory and enables a suitable plant model estimate. A 1.5-second-long maneuver with an amplitude of 5 percent throttle is determined to provide suitable data for the sequential least squares method to estimate a plant model. A PDV implementing this method can adapt to a single engine failure and continue to reach its touchdown conditions