Inflammatory Activity on Natalizumab Predicts Short-term but not Long-term Disability in Multiple Sclerosis

BACKGROUND: In people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict a poor prognosis. OBJECTIVE: To study this association in those receiving natalizumab. METHODS: Data were collected on relapses, new MRI activity, and Modified Rio Score after initiation of natalizumab in an observational cohort of 161 patients with high baseline disability. These were correlated with Expanded Disability Status Scale (EDSS) progression at years 1, 2, 3, and 3-7 after treatment initiation, versus pre-treatment baseline. RESULTS: 46/161 patients had a relapse in the first year and 44/161 had EDSS progression by year 2. Relapses and Modified Rio Score in the first year of treatment predicted EDSS progression at year 1 and 2 after treatment initiation. However, this effect disappeared with longer follow-up. Paradoxically, there was a trend towards inflammatory activity on treatment (first year Modified Rio Score, relapses, and MRI activity) predicting a lower risk of EDSS progression by years 3-7, although this did not reach statistical significance. Those with and without EDSS progression did not differ in baseline age, EDSS, or pre-treatment relapse rate. Relapses in year 0-1 predicted further relapses in years 1-3. CONCLUSIONS: Breakthrough inflammatory activity after natalizumab treatment is predictive of short-term outcome measures of relapses or EDSS progression, but does not predict longer term EDSS progression, in this cohort with high baseline disability

Spectral Absorption Coefficient of Additive Manufacturing Polymers

As NASA turns to additive manufacturing processes, there is a need to ensure that the parts they produce are reliable. This is especially true when creating parts in space, where resources are limited and failure could result in catastrophe. Active thermography has shown potential as a non-destructive quality assurance technique for additive manufacturing processes. Heat transfer models used in active thermography techniques require accurate material property measurements in order to extract useful information about the system, including defect location. The spectral absorption coefficient, which determines the depth at which radiative power is absorbed into a surface, is a material property necessary for performing active thermography on AM polymers. This paper presents measurements of spectral absorption coefficients of polymers commonly used in additive manufacturing. Spectral absorption coefficients for fully dense PLA, ABS, and Nylon 12 samples are reported. Future work is needed to measure the spectral absorption coefficients of different materials and colored filaments commonly used in additive manufacturing

Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from \u3cem\u3eShigella flexneri\u3c/em\u3e

Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents

Trace gas emissions from savanna fires in northern Australia

We present analyses of near‐infrared ground‐based Fourier transform infrared solar absorption spectra recorded from a site in Darwin, Northern Territory, Australia (12.4°S, 130.9°E) from August 2005 to June 2008. Total column amounts of carbon monoxide derived from these spectra show a very clear annual cycle, with evidence of transported pollution from Indonesian fires in 2006. Aerosol optical depth measurements from the same site show a similar annual cycle but without exceptional values in 2006, suggesting significant loss of aerosol loading in the transported and aged smoke. In addition, we report the first ever measurements by remote sensing solar Fourier transform infrared of emission ratios with respect to carbon monoxide for formaldehyde (0.022 ± 0.007), acetylene (0.0024 ± 0.0003), ethane (0.0020 ± 0.0003), and hydrogen cyanide (0.0018 ± 0.0003) from Australian savanna fires. These are derived from mid‐infrared spectra recorded through smoke plumes over Darwin on 20 separate days. The only previous measurements of emission ratios for formaldehyde and hydrogen cyanide from Australian savanna fires involved cryogenic trapping and storage of samples that were gathered in very fresh smoke. The results reported here are nearly an order of magnitude higher (but in agreement with laboratory studies), suggesting losses in the collection, storage, or transfer of the gases in the earlier measurements and/or chemical production of these reactive gases within the smoke plumes. Emission ratios for acetylene and ethane from this work are in broad agreement with other literature values

Evidence for Shared Genetic Aetiology Between Schizophrenia, Cardiometabolic, and Inflammation-Related Traits: Genetic Correlation and Colocalization Analyses.

Funder: MQ: Transforming Mental Health; Grant(s): MQDS17/40BACKGROUND: Schizophrenia commonly co-occurs with cardiometabolic and inflammation-related traits. It is unclear to what extent the comorbidity could be explained by shared genetic aetiology. METHODS: We used GWAS data to estimate shared genetic aetiology between schizophrenia, cardiometabolic, and inflammation-related traits: fasting insulin (FI), fasting glucose, glycated haemoglobin, glucose tolerance, type 2 diabetes (T2D), lipids, body mass index (BMI), coronary artery disease (CAD), and C-reactive protein (CRP). We examined genome-wide correlation using linkage disequilibrium score regression (LDSC); stratified by minor-allele frequency using genetic covariance analyzer (GNOVA); then refined to locus-level using heritability estimation from summary statistics (ρ-HESS). Regions with local correlation were used in hypothesis prioritization multi-trait colocalization to examine for colocalisation, implying common genetic aetiology. RESULTS: We found evidence for weak genome-wide negative correlation of schizophrenia with T2D (rg = -0.07; 95% C.I., -0.03,0.12; P = .002) and BMI (rg = -0.09; 95% C.I., -0.06, -0.12; P = 1.83 × 10-5). We found a trend of evidence for positive genetic correlation between schizophrenia and cardiometabolic traits confined to lower-frequency variants. This was underpinned by 85 regions of locus-level correlation with evidence of opposing mechanisms. Ten loci showed strong evidence of colocalization. Four of those (rs6265 (BDNF); rs8192675 (SLC2A2); rs3800229 (FOXO3); rs17514846 (FURIN)) are implicated in brain-derived neurotrophic factor (BDNF)-related pathways. CONCLUSIONS: LDSC may lead to downwardly-biased genetic correlation estimates between schizophrenia, cardiometabolic, and inflammation-related traits. Common genetic aetiology for these traits could be confined to lower-frequency common variants and involve opposing mechanisms. Genes related to BDNF and glucose transport amongst others may partly explain the comorbidity between schizophrenia and cardiometabolic disorders

Seasonal variations of CO and HCN in the troposphere measured by solar absorption spectroscopy over Poker Flat, Alaska

Tropospheric partial column abundances of CO and HCN have been retrieved from infrared solar spectra observed with a ground-based spectrometer at Poker Flat Alaska (65°N, 147°W) over the time period from 2000 to 2004. From these data we report the transpacific transport induced inter-annual variability of tropospheric CO over Poker Flat. This is the first report of solar infrared data from the Poker Flat station, where the geographical location of the site means that remote sensing measurements are sampling the transport of transpacific air parcels going to Northern America from Eastern Siberia and Asia. The five year time-span of the data also show significant differences in year to year CO and HCN tropospheric column enhancements driven by changes in Siberian/Asian pollution sources

GlobSim (v1.0): Deriving meteorological time series for point locations from multiple global reanalyses

Simulations of land-surface processes and phenomena often require driving time series of meteorological variables. Corresponding observations, however, are unavailable in most locations, even more so, when considering the duration, continuity and data quality required. Atmospheric reanalyses provide glo

Seasonal cycle in atmospheric HCl at 45 deg S

High resolution Fourier transform infrared interferometric atmospheric solar absorption measurements have been performed at the National Institute for Water and Atmospheric Research Laboratory at Lauder, New Zealand on a routine basis since October 1989. This laboratory has been selected as the Mid-latitude Charter Site of the Network for the Detection of Stratospheric Change and is at a latitude of 45 deg S. Particular attention has been paid to the absorption by atmospheric hydrogen chloride at 2925.9 cm(exp -1) and in this paper the results of the seasonal cycle in CHl above Lauder will be presented. Because of the very clean troposphere at this site, the CHl column measured from the ground is essentially a stratospheric column measurement

Long-term tropospheric formaldehyde concentrations deduced from ground-based fourier transform solar infrared measurements

We report a 13-year (1992–2005) dataset of total column measurements of formaldehyde (HCHO) over Lauder, New Zealand, inferred from solar infrared spectra measured using a high-resolution Fourier Transform Spectrometer (FTS). Ambient HCHO concentrations at this rural location are often close to levels typical of remote marine environments (\u3c250 ppt), which are close to the detection limit using standard techniques. Consequently we develop a new method that successfully produces HCHO columns with sufficient sensitivity throughout the whole season. HCHO columns over Lauder have a strong seasonal cycle (±50%), with a mean column of 4.9×1015 molecules cm−2, peaking during summer months. A simple box model of CH4 oxidation reproduces the observed broad-scale seasonal cycle, but significantly underestimates the seasonal peak HCHO ground concentrations during summer. This suggests the existence of an additional significant source of HCHO, possibly isoprene that cannot be explained by oxidation of CH4 alone. The ground-based FTS column data compare well with collocated HCHO column measurements from the Global Ozone Monitoring Experiment (GOME) satellite instrument during the operational period of GOME (1996–2001, r2=0.65, mean bias=10%, n=48)

Satellite and ground-based measurements of XCO2 in a remote semiarid region of Australia

In this study, we present ground-based measurements of column-averaged dry-air mole fractions (DMFs) of CO2 (or XCO2) taken in a semiarid region of Australia with an EM27/SUN portable spectrometer equipped with an automated clamshell cover. We compared these measurements to space-based XCO2 retrievals from the Greenhouse Gases Observing Satellite (GOSAT). Side-by-side measurements of EM27/SUN with the Total Carbon Column Observing Network (TCCON) instrument at the University of Wollongong were conducted in 2015-2016 to derive an XCO2 scaling factor of 0.9954 relative to TCCON. Although we found a slight drift of 0.13 % over 3 months in the calibration curve of the EM27/SUN vs. TCCON XCO2, the alignment of the EM27/SUN proved stable enough for a 2-week campaign, keeping the retrieved Xair values, another measure of stability, to within 0.5 % and the modulation efficiency to within 2 %. From the measurements in Alice Springs, we confirm a small bias of around 2 ppm in the GOSAT M-gain to H-gain XCO2 retrievals, as reported by the NIES GOSAT validation team. Based on the reported random errors from GOSAT, we estimate the required duration of a future campaign in order to better understand the estimated bias between the EM27/SUN and GOSAT. The dataset from the Alice Springs measurements is accessible at https://doi.org/10.4225/48/5b21f16ce69bc (Velazco et al., 2018)