Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia

BACKGROUND: Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1. METHODS: Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV) ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF) using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL) were detected by ELISA. RESULTS: Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls. CONCLUSION: This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin

PR3-ANCA:a promising biomarker in primary sclerosing cholangitis (PSC)

BACKGROUND AND AIMS:The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients. METHODS:A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF. RESULTS:When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes. CONCLUSION:PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD

Real-Time Science Operations to Support a Lunar Polar Volatiles Rover Mission

Future human exploration of the Moon will likely rely on in situ resource utilization (ISRU) to enable long duration lunar missions. Prior to utilizing ISRU on the Moon, the natural resources (in this case lunar volatiles) must be identified and characterized, and ISRU demonstrated on the lunar surface. To enable future uses of ISRU, NASA and the CSA are developing a lunar rover payload that can (1) locate near subsurface volatiles, (2) excavate and analyze samples of the volatile-bearing regolith, and (3) demonstrate the form, extractability and usefulness of the materials. Such investigations are important both for ISRU purposes and for understanding the scientific nature of these intriguing lunar volatile deposits. Temperature models and orbital data suggest near surface volatile concentrations may exist at briefly lit lunar polar locations outside persistently shadowed regions. A lunar rover could be remotely operated at some of these locations for the approx. 2-14 days of expected sunlight at relatively low cost. Due to the limited operational time available, both science and rover operations decisions must be made in real time, requiring immediate situational awareness, data analysis, and decision support tools. Given these constraints, such a mission requires a new concept of operations. In this paper we outline the results and lessons learned from an analog field campaign in July 2012 which tested operations for a lunar polar rover concept. A rover was operated in the analog environment of Hawaii by an off-site Flight Control Center, a rover navigation center in Canada, a Science Backroom at NASA Ames Research Center in California, and support teams at NASA Johnson Space Center in Texas and NASA Kennedy Space Center in Florida. We find that this type of mission requires highly efficient, real time, remotely operated rover operations to enable low cost, scientifically relevant exploration of the distribution and nature of lunar polar volatiles. The field demonstration illustrated the need for science operations personnel in constant communications with the flight mission operators and the Science Backroom to provide immediate and continual science support and validation throughout the mission. Specific data analysis tools are also required to enable immediate data monitoring, visualization, and decision making. The field campaign demonstrated that this novel methodology of real-time science operations is possible and applicable to providing important new insights regarding lunar polar volatiles for both science and exploration

Documenting Surface and Sub-surface Volatiles While Drilling in Frozen Lunar Simulant

NASA's Resource Prospector (RP) mission is intended to characterize the three-dimensional nature of volatiles in lunar polar regions and permanently shadowed regions. RP is slated to carry two instruments for prospecting purposes. These include the Neutron Spectrometer System (NSS) and Near-Infrared Volatile Spectrometer System (NIRVSS). A Honybee Robotics drill (HRD) is intended to sample to depths of 1 m, and deliver a sample to a crucible that is processed by the Oxygen Volatile Extraction Node (OVEN) where the soil is heated and evolved gas is delivered to the gas chromatograph / mass spectrometer of the Lunar Advanced Volatile Analysis system (LAVA). For several years, tests of various sub-systems have been undertaken in a large cryo-vacuum chamber facility (VF-13) located at Glenn Research Center. In these tests a large tube (1.2 m high x 25.4 cm diameter) is filled with lunar simulant, NU-LHT-3M, prepared with known abundances of water. There are thermo-couples embedded at different depths, and also across the surface of the soil tube. The soil tube is placed in the chamber and cooled with LN2 as the pressure is reduced to approx.5-6x10(exp -6) Torr. Here we discuss May 2016 tests where two soil tubes were prepared and placed in the chamber. Also located in the chamber were 5 crucibles, an Inficon mass spectrometer, and a trolly permitting x-y translation, where the HRD and NIRVSS, were mounted. The shroud surrounding the soil tube was held at different temperatures for each tube to simulate a warm and cold lunar environment

Near-Infrared Monitoring of Volatiles in Frozen Lunar Simulants While Drilling

In Situ Resource Utilization (ISRU) focuses on using local resources for mission consumables. The approach can reduce mission cost and risk. Lunar polar volatiles, e.g. water ice, have been detected via remote sensing measurements and represent a potential resource for both humans and propellant. The exact nature of the horizontal and depth distribution of the ice remains to be documented in situ. NASA's Resource Prospector mission (RP) is intended to investigate the polar volatiles using a rover, drill, and the RESOLVE science package. RP component level hardware is undergoing testing in relevant lunar conditions (cryovacuum). In March 2015 a series of drilling tests were undertaken using the Honeybee Robotics RP Drill, Near-Infrared Volatile Spectrometer System (NIRVSS), and sample capture mechanisms (SCM) inside a 'dirty' thermal vacuum chamber at the NASA Glenn Research Center. The goal of these tests was to investigate the ability of NIRVSS to monitor volatiles during drilling activities and assess delivery of soil sample transfer to the SCMs in order to elucidate the concept of operations associated with this regolith sampling method