Glen Torridon Mineralogy and the Sedimentary History of the Clay Mineral Bearing Unit

Clay minerals are common in ancient terrains on Mars and their presence at the surface alludes to aqueous processes in the Noachian to Early Hesperian (>3.5 Ga). Gale crater was selected as Curiositys landing site largely because of the identification of clay mineral rich strata from orbit. On Earth, the types of clay minerals (i.e., smectites) identified in Gale crater are typically juvenile weathering products that ultimately record the interaction between primary igneous minerals with the hydrosphere, atmosphere, and biosphere. Trioctahedral and dioctahedral smectite were identified by Curiosity in units stratigraphically below the Clay Mineral-Bearing Unit (CBU) identified from orbit. Compositional and sedimentological data suggest the smectite formed via authigenesis in a lake environment and may have been altered during early diagenesis. The CBU is stratigraphically equivalent to a hematite-rich unit to the north and stratigraphically underlies sulfate-rich units to the south, suggesting a dynamic environment and evolving history of water in the ancient Gale crater lake. Targeting these clay mineral rich areas on Mars with rover missions provides an opportunity to explore the aqueous and sedimentary history of the planet

Mineralogy of Vera Rubin Ridge in Gale Crater from the Mars Science Laboratory CheMin instrument

Gale crater was selected as the landing site for the Mars Science Laboratory Curiosity rover because of orbital evidence for a variety of secondary minerals in the lower slopes of Aeolis Mons (aka Mount Sharp) that indicate changes in aqueous conditions over time. Distinct units demonstrate orbital spectral signatures of hematite, phyllosilicate (smectite), and sulfate minerals, which suggest that ancient aqueous environments in Gale crater varied in oxidation potential, pH, and water activity. Vera Rubin ridge (VRR) is the first of these units identified from orbit to have been studied by Curiosity. Orbital near-infrared data from VRR show a strong band at 860 nm indicative of hematite. Before Curiosity arrived at VRR, the hypotheses to explain the formation of hematite included (1) precipitation at a redox interface where aqueous Fe2+ was oxidized to Fe3+, and (2) acidic alteration of olivine in oxic fluids. Studying the composition and sedimentology of the rocks on VRR allow us to test and refine these hypotheses and flesh out the depositional and diagenetic history of the ridge. Here, we focus on the mineralogical results of four rock powders drilled from and immediately below VRR as determined by CheMin

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Building operational research capacity in the Pacific

Operational research (OR) in public health aims to investigate strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of health systems. Attention has recently been drawn to the lack of OR capacity in public health programmes throughout the Pacific Islands, despite considerable investment in implementation. This lack of ongoing and critical reflection may prevent health programme staff from understanding why programme objectives are not being fully achieved, and hinder long-term gains in public health. The International Union Against Tuberculosis and Lung Disease (The Union) has been collaborating with Pacific agencies to conduct OR courses based on the training model developed by The Union and Médecins Sans Frontières Brussels-Luxembourg in 2009. The first of these commenced in 2011 in collaboration with the Fiji National University, the Fiji Ministry of Health, the World Health Organization and other partners. The Union and the Secretariat of the Pacific Community organised a second course for participants from other Pacific Island countries and territories in 2012, and an additional course for Fijian participants commenced in 2013. Twelve participants enrolled in each of the three courses. Of the two courses completed by end 2013, 18 of 24 participants completed their OR and submitted papers by the course deadline, and 17 papers have been published to date. This article describes the context, process and outputs of the Pacific courses, as well as innovations, adaptations and challenges

LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA.

The DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs). Laboratory of genetics and physiology 2 (LGP2) is thought to influence IFN production by regulating the activity of RIG-I and mda-5, although its mechanism of action is not known and its function is controversial. Here we show that expression of LGP2 potentiates IFN induction by polyinosinic-polycytidylic acid [poly(I:C)], commonly used as a synthetic mimic of viral dsRNA, and that this is particularly significant at limited levels of the inducer. The observed enhancement is mediated through co-operation with mda-5, which depends upon LGP2 for maximal activation in response to poly(I:C). This co-operation is dependent upon dsRNA binding by LGP2, and the presence of helicase domain IV, both of which are required for LGP2 to interact with mda-5. In contrast, although RIG-I can also be activated by poly(I:C), LGP2 does not have the ability to enhance IFN induction by RIG-I, and instead acts as an inhibitor of RIG-I-dependent poly(I:C) signaling. Thus the level of LGP2 expression is a critical factor in determining the cellular sensitivity to induction by dsRNA, and this may be important for rapid activation of the IFN response at early times post-infection when the levels of inducer are low

Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure

Characteristics and Programme-Defined Treatment Outcomes among Childhood Tuberculosis (TB) Patients under the National TB Programme in Delhi

Childhood tuberculosis (TB) patients under India's Revised National TB Control Programme (RNTCP) are managed using diagnostic algorithms and directly observed treatment with intermittent thrice-weekly short-course treatment regimens for 6–8 months. The assignment into pre-treatment weight bands leads to drug doses (milligram per kilogram) that are lower than current World Health Organization (WHO) guidelines for some patients.The main aim of our study was to describe the baseline characteristics and treatment outcomes reported under RNTCP for registered childhood (age <15 years) TB patients in Delhi. Additionally, we compared the reported programmatic treatment completion rates between children treated as per WHO recommended anti-TB drug doses with those children treated with anti-TB drug doses below that recommended in WHO guidelines.For this cross-sectional retrospective study, we reviewed programme records of all 1089 TB patients aged <15 years registered for TB treatment from January to June, 2008 in 6 randomly selected districts of Delhi. WHO disease classification and treatment outcome definitions are used by RNTCP, and these were extracted as reported in programme records.Among 1074 patients with records available, 651 (61%) were females, 122 (11%) were <5 years of age, 1000 (93%) were new cases, and 680 (63%) had extra-pulmonary TB (EP-TB)—most commonly peripheral lymph node disease [310 (46%)]. Among 394 pulmonary TB (PTB) cases, 165 (42%) were sputum smear-positive. The overall reported treatment completion rate was 95%. Similar reported treatment completion rates were found in all subgroups assessed, including those patients whose drug dosages were lower than that currently recommended by WHO. Further studies are needed to assess the reasons for the low proportion of under-5 years of age TB case notifications, address challenges in reaching all childhood TB patients by RNTCP, the accuracy of diagnosis, and the clinical validity of reported programme defined treatment completion

Surface and Temporal Biosignatures

Recent discoveries of potentially habitable exoplanets have ignited the prospect of spectroscopic investigations of exoplanet surfaces and atmospheres for signs of life. This chapter provides an overview of potential surface and temporal exoplanet biosignatures, reviewing Earth analogues and proposed applications based on observations and models. The vegetation red-edge (VRE) remains the most well-studied surface biosignature. Extensions of the VRE, spectral "edges" produced in part by photosynthetic or nonphotosynthetic pigments, may likewise present potential evidence of life. Polarization signatures have the capacity to discriminate between biotic and abiotic "edge" features in the face of false positives from band-gap generating material. Temporal biosignatures -- modulations in measurable quantities such as gas abundances (e.g., CO2), surface features, or emission of light (e.g., fluorescence, bioluminescence) that can be directly linked to the actions of a biosphere -- are in general less well studied than surface or gaseous biosignatures. However, remote observations of Earth's biosphere nonetheless provide proofs of concept for these techniques and are reviewed here. Surface and temporal biosignatures provide complementary information to gaseous biosignatures, and while likely more challenging to observe, would contribute information inaccessible from study of the time-averaged atmospheric composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets. Fixed figure conversion error

High-Temperature, Perhaps Silicic, Volcanism on Mars Evidenced by Tridymite Detection in High-SiO2 Sedimentary Rock at Gale Crater, Mars

The Mars Science Laboratory (MSL) rover, Curiosity, has been exploring sedimentary rocks within Gale crater since landing in August, 2012. On the lower slopes of Aeolis Mons (a.k.a. Mount Sharp), drill powder was collected from a high-silica (74 wt% SiO2) outcrop named Buckskin (BK). It was a surprise to find that the Buckskin sample contained significant amounts of the relatively rare silica polymorph tridymite. We describe the setting of the Buckskin sample, the detection of tridymite by the MSL Chemistry and Mineralogy (CheMin) X-ray diffraction instrument, and detection implications. Geologic setting: The Buckskin outcrop is part of the Murray formation exposed in the Marias Pass area. The formation was previously studied by CheMin in the Pahrump Hills member [1] where three samples of drill fines were analyzed (Confidence Hills (CH), Mojave2 (MJ) and Telegraph Peak (TP) [2]). Assuming approximately horizontal bedding, the Buckskin outcrop is approx.15 m stratigraphically above the bottom of the Pahrump Hills member. Mudstone, generally characterized by fine lamination, is the dominant depositional facies [1]. Buckskin Mineralogical and Chemical Composition: The CheMin instrument and XRD pattern analysis procedures have been previously discussed [3-6]. The diffraction pattern used for quantitative XRD analysis (Fig. 1) is the sum of the first 4 of 45 diffraction images. The remaining images are all characterized by both on-ring and off-ring diffraction spots that we attributed to poor grain motion and particle clumping. Coincident with particle clumping was a significant decrease in the intensity of the tridymite diffraction peaks (Fig. 2a). The derived mineralogical composition of the crystalline component (derived from the first 4 diffraction images) is given in Table 1. The tridymite is well-crystalline and its pattern is refined as monoclinic tridymite (Fig 1). Mineral chemical compositions were derived from XRD unit cell parameters or obtained from stoichiometry. The XRD-calculated amorphous component was 50 +/- 15 wt%. We constrained the value to 60 wt% because it is the minimum value necessary to give a positive Al2O3 concentration for the amorphous component using APXS data for the post-sieve dump pile (Table 2). The amorphous component has high SiO2 (approx.77 wt%) and high anion (SO3+P2O5+Cl ~10 wt%) concentrations. Calculation shows that a cation-anion balance is achieved if the cations in the amorphous component except SiO2 and TiO2, which do not readily form salts, are assumed to be present as amorphous mixed-cation sulfates, phosphates, and chlorides (or perchlorates/ chlorates)