Characterization of Low-Temperature, Co-Fired Ceramic-Manufactured Electrostatic Thruster-Closeout Report

The goal of the project was to evaluate prototypes of an experimental thruster developed by the University of Arkansas (UA), Fayetteville, AR. The design under evaluation is a radio frequency (RF) electrostatic thruster that was fabricated using the low-temperature, co-fired ceramic (LTCC) materials and fabrication process. This materials system is analogous to printed circuit board (PCB) technology with the most significant difference being that the laminate is replaced by a ceramic material and the copper layer is replaced by printed sinterable silver paste. LTCC designs are baked after fabrication and assembled to realize an entirely monolithic structure with internal conductors, vias, and cavities. In this process, the LTCC electrostatic thruster (LTCC-ET) that is the subject of the present work becomes a monolithic ceramic thruster capable of withstanding temperatures in excess of 500 C. The UA and NASA Marshall Space Flight Center (MSFC) jointly performed prototype testing on the LTCC-ET under a NASA Cooperative Agreement Notice (CAN) award. The LTCC-ET was tested at MSFC in May 2018 over a 1-week period. There were two goals for the test program: (1) Testing to determine the operating parameters required to create plasma ignition in the test articles. This was explored by setting a propellant flowrate and increasing RF power until plasma ignition was observed. Testing was conducted with both argon and krypton. (2) Investigate the thrust and specific impulse (Isp) performance of the thruster as a function of propellant flowrate and grid voltage. This goal was not met during the project as technical challenges in maintaining stable plasma ignition arose due to stress and heating of the RF power feed. In summary, a prototype thruster design (consisting of three packaged units) was fabricated by UA and tested for the first time under vacuum conditions at MSFC to experimentally determine basic performance metrics and functionality. It was found that the design was not sufficiently optimized or robust enough in its initial iteration to support a significant test campaign or characterization program. It was concluded that the propellant outlet channels must be reduced in size with the flowpaths adjusted to increase propellant residence time in the thruster, and that the RF connector must be replaced with a version capable of handling higher power throughput and heating. However, even in its unoptimized form, a plasma could be produced in the LTCCET, demonstrating the efficacy of the design approach. The design is especially compelling due to its low cost to manufacture and, more importantly, its scalability of size and power throughput. Low cost and scalability are also important in that additional functionalities, such as thrust vectoring and plume charge neutralization, can be integrated into future designs with minimal additional cost. This project has matured the LTCC-ET development Technology Readiness Level (TRL) from 1 to 2. The low-cost RF plasma source portion of the LTCC device was matured from TRL 2 to 4 through the demonstration of RF plasma ignition under vacuum conditions

Targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and causes osteoarthritis-like disease

Objective The matricellular protein NOV/CCN3, is implicated in osteoarthritis (OA) and targeted mutation of NOV in mice (Novdel3) leads to joint abnormalities. This investigation tested whether NOV is required for joint homeostasis and if its disruption causes joint degeneration. Method NOV expression in the adult mouse joint was characterized by immunohistochemistry. A detailed comparison of the joints of Novdel3−/− and Novdel3+/+ (wild-type) males and females at 2, 6 and 12 months of age was determined by X-ray, histology and immunohistochemistry. Results NOV protein was found in specific cells in articular cartilage, meniscus, synovium and ligament attachment sites in adult knees. Novdel3−/− males exhibited severe OA-like pathology at 12 months (OARSI score 5.0 ± 0.5, P < 0.001), affecting all tissues of the joint: erosion of the articular cartilage, meniscal enlargement, osteophytic outgrowths, ligament degeneration and expansion of fibrocartilage. Subchondral sclerosis and changes in extracellular matrix composition consistent with OA, were also seen. The density of articular cartilage cells in Novdel3+/+ knee joints is maintained at a constant level from 2 to 12 months of age whereas this is not the case in Novdel3−/− mice. Compared with age and sex-matched Novdel3+/+ mice, a significant increase in articular cartilage density was seen in Novdel3−/− males at 2 months, whereas a significant decrease was seen at 6 and 12 months in both Novdel3−/− males and females. Conclusion NOV is required for the maintenance of articular cartilage and for joint homeostasis, with disruption of NOV in ageing Novdel3−/− male mice causing OA-like disease

Deep Impact Mission to Tempel 1 Favours New Explosive Cosmogony of Comets

The assumption that short-period (SP) comets are fragments of massive icy envelopes of Ganymede-like bodies saturated by products of ice electrolysis that underwent global explosions provides a plausible explanation of all known manifestations of comets, including the jet character of outflows, the presence of ions in the vicinity of the nucleus, the bursts and splitting of cometary nuclei, etc., with solar radiation initiating burning of the products of electrolysis in the nucleus. As shown persuasively by numerical simulation carried out in hydrodynamic approximation, the shock wave initiated by the Deep Impact (DI) impactor in the cometary ice saturated originally by the electrolysis products 2H2 + O2 is capable of activating under certain conditions exothermal reactions (of the type O2 + H2 + organics = H2O + CO + HCN + other products of incomplete burning of organics including its light and heavy pyrolyzed compounds, soot, etc.), which will slow down shock wave damping (forced detonation) and increase many times the energy release. As a result, the measured energetics of ejections and outflows from the crater have to exceed the DI energetics. Analysis of different clusters of the DI experiment data confirms these conclusions and expectations and thus it favours the planetary origin of comets.Comment: 21 pages incluging 3 figure

A survey to investigate the association of pain, foot disability and quality of life with corns

Background Corns are a common foot problem affecting a large proportion of the population. This study describes the characteristics of corns experienced by 201 participants taking part in a randomised controlled trial to investigate associations between demographic and corn parameters on pain, foot related disability and quality of life (QoL). Methods Pain from the main (index) corn was measured using a visual analogue scale (VAS); foot related disability was assessed with the Foot Disability Questionnaire (now known as the Manchester Foot Pain and Disability Index) and quality of life was recorded with the EQ-5D questionnaire. The effect of demographic and corn parameters on the pain and quality of life outcomes was assessed with analysis of variance (ANOVA) methods. The effect of the same factors on a linear combination of the foot-related disability outcome measures was assessed using multivariate ANOVA methods. Pain was also tested for its mediating properties on the causal pathway between the independent variables and quality of life. Results The mean pain score was 5.29 points on a 10 cm VAS, with females reporting substantively higher pain levels than males. Age affected foot-related disability, with lower levels on all domains of the MFPDI reported in older participants; each year of advancing age was associated with falls of: 0.009 points on the Concern about Appearance (CA) domain; 0.047 points on the Functional Limitation (FL) domain and 0.048 points on the Pain Intensity (PI) domain. Sex and corn type also affected disability, with higher scores reported by females and participants with plantar corns. Conclusions The effect of pain was shown to mediate the relationship between sex and foot-related disability. The presence of plantar corns has a more detrimental effect on QoL than dorsal/inter-digital corns

An evaluation of seasonal variations in footwear worn by adults with inflammatory arthritis: a cross-sectional observational study using a web-based survey

Background: Foot problems are common in adults with inflammatory arthritis and therapeutic footwear can be effective in managing arthritic foot problems. Accessing appropriate footwear has been identified as a major barrier, resulting in poor adherence to treatment plans involving footwear. Indeed, previous New Zealand based studies found that many people with rheumatoid arthritis and gout wore inappropriate footwear. However, these studies were conducted in a single teaching hospital during the New Zealand summer therefore the findings may not be representative of footwear styles worn elsewhere in New Zealand, or reflect the potential influence of seasonal climate changes. The aim of the study was to evaluate seasonal variations in footwear habits of people with inflammatory arthritic conditions in New Zealand. Methods: A cross-sectional study design using a web-based survey. The survey questions were designed to elicit demographic and clinical information, features of importance when choosing footwear and seasonal footwear habits, including questions related to the provision of therapeutic footwear/orthoses and footwear experiences. Results: One-hundred and ninety-seven participants responded who were predominantly women of European descent, aged between 46–65 years old, from the North Island of New Zealand. The majority of participants identified with having either rheumatoid arthritis (35%) and/or osteoarthritis (57%) and 68% reported established disease (>5 years duration). 18% of participants had been issued with therapeutic footwear. Walking and athletic shoes were the most frequently reported footwear type worn regardless of the time of year. In the summer, 42% reported wearing sandals most often. Comfort, fit and support were reported most frequently as the footwear features of greatest importance. Many participants reported difficulties with footwear (63%), getting hot feet in the summer (63%) and the need for a sandal which could accommodate a supportive insole (73%). Conclusions: Athletic and walking shoes were the most popular style of footwear reported regardless of seasonal variation. During the summer season people with inflammatory arthritis may wear sandals more frequently in order to accommodate disease-related foot deformity. Healthcare professionals and researchers should consider seasonal variation when recommending appropriate footwear, or conducting footwear studies in people with inflammatory arthritis, to reduce non-adherence to prescribed footwear

Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect

Ion-neutral Coupling During Deep Solar Minimum

The equatorial ionosphere under conditions of deep solar minimum exhibits structuring due to tidal forces. Data from instruments carried by the Communication Navigation Outage Forecasting System (CNOFS) which was launched in April 2008 have been analyzed for the first 2 years following launch. The Planar Langmuir Probe (PLP), Ion Velocity Meter (IVM) and Vector Electric Field Investigation (VEFI) all detect periodic structures during the 20082010 period which appear to be tides. However when the tidal features detected by these instruments are compared, there are distinctive and significant differences between the observations. Tides in neutral densities measured by the Gravity Recovery and Climate Experiment (GRACE) satellite were also observed during June 2008. In addition, Broad Plasma Decreases (BPDs) appear as a deep absolute minimum in the plasma and neutral density tidal pattern. These are co-located with regions of large downward-directed ion meridional velocities and minima in the zonal drifts, all on the nightside. The region in which BPDs occur coincides with a peak in occurrence rate of dawn depletions in plasma density observed on the Defense Meterological Satellite Program (DMSP) spacecraft, as well as a minimum in radiance detected by UV imagers on the Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) and IMAGE satellite

Acute Myocardial Infarction in Autoimmune Rheumatologic Disease : A Nationwide Analysis of Clinical outcomes and Predictors of Management Strategy

Funding M.O.M is funded by an unrestricted educational PhD studentship from Medtronic Ltd. Medtronic Ltd was not involved in the conceptualization or design of the present study. C.M. is funded by the National Institute for Health Research (NIHR) Applied Research (West Midlands), the NIHR School for Primary Care Research and an NIHR Research Professorship in General Practice (NIHR-RP-2014-04-026). The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, our funding bodies or the Department of Health and Social Care.Peer reviewedPostprin

Tunable control of CAR T cell activity through tetracycline mediated disruption of protein-protein interaction

Chimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an "off-switch" by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule