Potential Impact of Global Navigation Satellite Services on Total Power HI Intensity Mapping Surveys

Future total-power single-dish HI intensity mapping (HI IM) surveys have the potential to provide unprecedented insight into late time ($z < 1$) cosmology that are competitive with Stage IV dark energy surveys. However, redshifts between $0 < z < 0.2$ lie within the transmission bands of global navigation satellite services (GNSS), and even at higher redshifts out-of-band leakage from GNSS satellites may be problematic. We estimate the impact of GNSS satellites on future single-dish HI IM surveys using realistic estimates of both the total power and spectral structure of GNSS signals convolved with a model SKA beam. Using a simulated SKA HI IM survey covering 30000 sq. deg. of sky and 200 dishes, we compare the integrated GNSS emission on the sky with the expected HI signal. It is found that for frequencies $> 950$ MHz the emission from GNSS satellites will exceed the expected HI signal for all angular scales to which the SKA is sensitive when operating in single-dish mode.Comment: 13 pages, 11 figures, "matches published version

Modelling the spinning dust emission from LDN 1780

We study the anomalous microwave emission (AME) in the Lynds Dark Nebula (LDN) 1780 on two angular scales. Using available ancillary data at an angular resolution of 1 degree, we construct an SED between 0.408 GHz to 2997 GHz. We show that there is a significant amount of AME at these angular scales and the excess is compatible with a physical spinning dust model. We find that LDN 1780 is one of the clearest examples of AME on 1 degree scales. We detected AME with a significance > 20$\sigma$. We also find at these angular scales that the location of the peak of the emission at frequencies between 23-70 GHz differs from the one on the 90-3000 GHz map. In order to investigate the origin of the AME in this cloud, we use data obtained with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) that provides 2 arcmin resolution at 30 GHz. We study the connection between the radio and IR emissions using morphological correlations. The best correlation is found to be with MIPS 70$\mu$m, which traces warm dust (T$\sim$50K). Finally, we study the difference in radio emissivity between two locations within the cloud. We measured a factor $\approx 6$ of difference in 30 GHz emissivity. We show that this variation can be explained, using the spinning dust model, by a variation on the dust grain size distribution across the cloud, particularly changing the carbon fraction and hence the amount of PAHs.Comment: 14 pages, 11 figures, submitted to MNRA

Constraining the Anomalous Microwave Emission Mechanism in the S140 Star Forming Region with Spectroscopic Observations Between 4 and 8 GHz at the Green Bank Telescope

Anomalous microwave emission (AME) is a category of Galactic signals that cannot be explained by synchrotron radiation, thermal dust emission, or optically thin free-free radiation. Spinning dust is one variety of AME that could be partially polarized and therefore relevant for ongoing and future cosmic microwave background polarization studies. The Planck satellite mission identified candidate AME regions in approximately $1^\circ$ patches that were found to have spectra generally consistent with spinning dust grain models. The spectra for one of these regions, G107.2+5.2, was also consistent with optically thick free-free emission because of a lack of measurements between 2 and 20 GHz. Follow-up observations were needed. Therefore, we used the C-band receiver (4 to 8 GHz) and the VEGAS spectrometer at the Green Bank Telescope to constrain the AME mechanism. For the study described in this paper, we produced three band averaged maps at 4.575, 5.625, and 6.125 GHz and used aperture photometry to measure the spectral flux density in the region relative to the background. We found if the spinning dust description is correct, then the spinning dust signal peaks at $30.9 \pm 1.4$ GHz, and it explains the excess emission. The morphology and spectrum together suggest the spinning dust grains are concentrated near S140, which is a star forming region inside our chosen photometry aperture. If the AME is sourced by optically thick free-free radiation, then the region would have to contain HII with an emission measure of $5.27^{+2.5}_{-1.5}\times 10^8$ $\rm{cm^{-6}\,pc}$ and a physical extent of $1.01^{+0.21}_{-0.20} \times 10^{-2}\,\rm{pc}$. This result suggests the HII would have to be ultra or hyper compact to remain an AME candidate.Comment: 21 pages, 14 figures. Submitted to Ap

Impact of Simulated 1/f Noise for HI Intensity Mapping Experiments

Cosmology has entered an era where the experimental limitations are not due to instrumental sensitivity but instead due to inherent systematic uncertainties in the instrumentation and data analysis methods. The field of HI intensity mapping (IM) is still maturing, however early attempts are already systematics limited. One such systematic limitation is 1/f noise, which largely originates within the instrumentation and manifests as multiplicative gain fluctuations. To date there has been little discussion about the possible impact of 1/f noise on upcoming single-dish HI IM experiments such as BINGO, FAST or SKA. Presented in this work are Monte-Carlo end-to-end simulations of a 30 day HI IM survey using the SKA-MID array covering a bandwidth of 950 and 1410 MHz. These simulations extend 1/f noise models to include not just temporal fluctuations but also correlated gain fluctuations across the receiver bandpass. The power spectral density of the spectral gain fluctuations are modelled as a power-law, and characterised by a parameter $\beta$. It is found that the degree of 1/f noise frequency correlation will be critical to the success of HI IM experiments. Small values of $\beta$ ($\beta$ < 0.25) or high correlation is preferred as this is more easily removed using current component separation techniques. The spectral index of temporal fluctuations ($\alpha$) is also found to have a large impact on signal-to-noise. Telescope slew speed has a smaller impact, and a scan speed of 1 deg s$^{-1}$ should be sufficient for a HI IM survey with the SKA.Comment: 22 pages, 15 figures, 2 table

HI intensity mapping with FAST

We discuss the detectability of large-scale HI intensity fluctuations using the FAST telescope. We present forecasts for the accuracy of measuring the Baryonic Acoustic Oscillations and constraining the properties of dark energy. The FAST $19$-beam L-band receivers ($1.05$--$1.45$ GHz) can provide constraints on the matter power spectrum and dark energy equation of state parameters ($w_{0},w_{a}$) that are comparable to the BINGO and CHIME experiments. For one year of integration time we find that the optimal survey area is $6000\,{\rm deg}^2$. However, observing with larger frequency coverage at higher redshift ($0.95$--$1.35$ GHz) improves the projected errorbars on the HI power spectrum by more than $2~\sigma$ confidence level. The combined constraints from FAST, CHIME, BINGO and Planck CMB observations can provide reliable, stringent constraints on the dark energy equation of state.Comment: 7 pages, 3 figures, submitted to "Frontiers in Radio Astronomy and FAST Early Sciences Symposium 2015" conference proceedin

Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation.

Thioredoxin (Trx) is an oxidoreductase with important physiological function. Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated with a number of pathologies, particularly cancer, and a number of clinical trials for thioredoxin and thioredoxin reductase inhibitors have been carried out or are underway. Due to the emerging role and importance of oxidoreductases for haemostasis and the current interest in developing inhibitors for clinical use, we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin reductase/thioredoxin system affects platelet function and thrombosis. We used small molecule inhibitors of Trx (PMX 464 and PX-12) to determine whether Trx activity influences platelet function, as well as an unbiased proteomics approach to identify potential Trx substrates on the surface of platelets that might contribute to platelet reactivity and function. Using LC-MS/MS we found that PMX 464 and PX-12 affected the oxidation state of thiols in a number of cell surface proteins. Key surface receptors for platelet adhesion and activation were affected, including the collagen receptor GPVI and the von Willebrand factor receptor, GPIb. To experimentally validate these findings we assessed platelet function in the presence of PMX 464, PX-12, and rutin (a selective inhibitor of the related protein disulphide isomerase). In agreement with the proteomics data, small molecule inhibitors of thioredoxin selectively inhibited GPVI-mediated platelet activation, and attenuated ristocetin-induced GPIb-vWF-mediated platelet agglutination, thus validating the findings of the proteomics study. These data reveal a novel role for thioredoxin in regulating platelet reactivity via proteins required for early platelet responses at sites of vessel injury (GPVI and GPIb). This work also highlights a potential opportunity for repurposing of PMX 464 and PX-12 as antiplatelet agents.CM is funded by Medical Research Council Grant No G9826026. AR was funded by a British Heart Foundation Centre of Research Excellence-funded Vacation Studentship. CHC is funded by British Heart Foundation Fellowship FS/11/49/28751.This is the final version of the article. It first appeared from PLOS via https://doi.org/10.1371/journal.pone.016300

Induction of HO-1 in tissue macrophages and monocytes in fatal falciparum malaria and sepsis

BACKGROUND: As well as being inducible by haem, haemoxygenase -1 (HO-1) is also induced by interleukin-10 and an anti-inflammatory prostaglandin, 15d PGJ(2), the carbon monoxide thus produced mediating the anti-inflammatory effects of these molecules. The cellular distribution of HO-1, by immunohistochemistry, in brain, lung and liver in fatal falciparum malaria, and in sepsis, is reported. METHODS: Wax sections were stained, at a 1:1000 dilution of primary antibody, for HO-1 in tissues collected during paediatric autopsies in Blantyre, Malawi. These comprised 37 acutely ill comatose patients, 32 of whom were diagnosed clinically as cerebral malaria and the other 5 as bacterial diseases with coma. Another 3 died unexpectedly from an alert state. Other control tissues were from Australian adults. RESULTS: Apart from its presence in splenic red pulp macrophages and microhaemorrhages, staining for HO-1 was confined to intravascular monocytes and certain tissue macrophages. Of the 32 clinically diagnosed cerebral malaria cases, 11 (category A) cases had negligible histological change in the brain and absence of or scanty intravascular sequestration of parasitized erythrocytes. Of these 11 cases, eight proved at autopsy to have other pathological changes as well, and none of these eight showed HO-1 staining within the brain apart from isolated moderate staining in one case. Two of the three without another pathological diagnosis showed moderate staining of scattered monocytes in brain vessels. Six of these 11 (category A) cases exhibited strong lung staining, and the Kupffer cells of nine of them were intensely stained. Of the seven (category B) cases with no histological changes in the brain, but appreciable sequestered parasitised erythrocytes present, one was without staining, and the other six showed strongly staining, rare or scattered monocytes in cerebral vessels. All six lung sections not obscured by neutrophils showed strong staining of monocytes and alveolar macrophages, and all six available liver sections showed moderate or strong staining of Kupffer cells. Of the 14 (category C) cases, in which brains showed micro-haemorrhages and intravascular mononuclear cell accumulations, plus sequestered parasitised erythrocytes, all exhibited strong monocyte HO-1 staining in cells forming accumulations and scattered singly within cerebral blood vessels. Eleven of the available and readable 13 lung sections showed strongly staining monocytes and alveolar macrophages, and one stained moderately. All of the 14 livers had strongly stained Kupffer cells. Of five cases of comatose culture-defined bacterial infection, three showed a scattering of stained monocytes in vessels within the brain parenchyma, three had stained cells in lung sections, and all five demonstrated moderately or strongly staining Kupffer cells. Brain sections from all three African controls, lung sections from two of them, and liver from one, showed no staining for HO-1, and other control lung and liver sections showed few, palely stained cells only. Australian-origin adult brains exhibited no staining, whether the patients had died from coronary artery disease or from non-infectious, non-cerebral conditions CONCLUSIONS: Clinically diagnosed 'cerebral malaria' in children includes some cases in whom malaria is not the only diagnosis with the hindsight afforded by autopsy. In these patients there is widespread systemic inflammation, judged by HO-1 induction, at the time of death, but minimal intracerebral inflammation. In other cases with no pathological diagnosis except malaria, there is evidence of widespread inflammatory responses both in the brain and in other major organs. The relative contributions of intracerebral and systemic host inflammatory responses in the pathogenesis of coma and death in malaria deserve further investigation

Minocycline 200 mg or 400 mg versus placebo for mild Alzheimer's disease: the MADE Phase II, three-arm RCT

Background: Minocycline is an anti-inflammatory drug and protects against the toxic effects of β-amyloid in vitro and in animal models of Alzheimer’s disease. To the best of our knowledge, no randomised placebo-controlled clinical trials in patients with Alzheimer’s disease looking at the efficacy and tolerability of minocycline have been carried out. Objectives: The trial investigated whether or not minocycline was superior to placebo in slowing down the rate of decline in cognitive and functional ability over 2 years. The safety and tolerability of minocycline were also assessed. Design: A Phase II, three-arm, randomised, double-blind, multicentre trial with a semifactorial design. Participants continued on trial treatment for up to 24 months. Setting: Patients were identified from memory services, both within the 32 participating NHS trusts and within the network of memory services supported by the Dementias and Neurodegenerative Diseases Research Network (also known as DeNDRoN). Participants: Patients with standardised Mini Mental State Examination scores of > 23 points and with Alzheimer’s disease assessed by the National Institute on Aging–Alzheimer’s Association’s criteria were identified from memory services. Intervention: Patients with mild Alzheimer’s disease were randomly allocated 1 : 1 : 1 to receive one of three treatments: arm 1 – 400 mg per day of minocycline; arm 2 – 200 mg per day of minocycline; or arm 3 – placebo. Patients continued treatment for 24 months. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures: Primary outcome measures were decline in standardised Mini Mental State Examination and Bristol Activities of Daily Living Scale scores of combined minocycline treatment arms versus placebo, as analysed by intention-to-treat repeated measures regression. Results: Between 23 May 2014 and 14 April 2016, 554 participants were randomised. Of the 544 eligible participants, the mean age was 74.3 years and the average standardised Mini Mental State Examination score was 26.4 points. A total of 252 serious adverse events were reported, with the most common categories being neuropsychiatric and cardiocirculatory. Significantly fewer participants completed treatment with 400 mg of minocycline [29% (53/184)] than 200 mg [62% (112/181)] or placebo [64% (114/179)] (p < 0.0001), mainly because of gastrointestinal symptoms (p = 0.0008), dermatological side effects (p = 0.02) and dizziness (p = 0.01). Assessment rates were also lower in the 400-mg treatment arm: 68% (119 of 174 expected) for standardised Mini Mental State Examination scores at 24 months, compared with 82% (144/176) for the 200-mg treatment arm and 84% (140/167) for the placebo arm. Decline in standardised Mini Mental State Examination scores over the 24-month study period in the combined minocycline arms was similar to that in the placebo arm (4.1- vs. 4.3-point reduction; p = 0.9), as was the decline in the 400- and 200-mg treatment arms (3.3 vs. 4.7 points; p = 0.08). Likewise, worsening of Bristol Activities of Daily Living Scale scores over 24 months was similar in all trial arms (5.7, 6.6 and 6.2 points in the 400-mg treatment arm, 200-mg treatment arm and placebo arm, respectively; a p-value of 0.57 for minocycline vs. placebo and a p-value of 0.77 for 400 vs. 200 mg of minocycline). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Limitations: Potential limitations of the study include that biomarkers were not used to confirm the diagnosis of Alzheimer’s disease, as these and apolipoprotein E (APOE) genotyping are not routinely available within the NHS. Compliance was also worse than expected and differential follow-up rates were observed, with fewer assessments obtained for the 400-mg treatment arm than for the 200-mg treatment and placebo arms. Conclusions: Minocycline does not delay the progress of cognitive or functional impairment in people with mild Alzheimer’s disease over a 2-year period. Minocycline at a dose of 400 mg is poorly tolerated in this population. Future work: The Minocycline in mild Alzheimer’s DiseasE (MADE) study provides a framework for a streamlined trial design that can be usefully applied to test other disease-modifying therapies