Stellar x-ray polarimetry from the Ariel-V satellite.

X-ray polarisation observations from the Ariel-V satellite are described. Notably, an upper limit to the X-ray polarisation of Sco X-1 was produced, more sensitive than previous results had managed to achieve, and for which constraints could be placed upon models for the X-ray emission mechanism. Analysis of the data provided strong empirical confirmation of the desirability for future polarimeters to incorporate some previously proposed design features. These include utilisation of focusing methods to allow a smaller detector, and hence a reduced background level; increased area of collection, so that much weaker X-ray sources may be usefully observed; and also sufficiently accurate pointing, narrow f.o.v. and a capability for simultaneous measurement of more than one component of linear polarisation, all to suppress possible spurious modulations. It would be expected that the advantages obtained by following the advocated design features would result in a polarimeter sufficiently sensitive to be able to measure X-ray polarization from weak X-ray sources, and to achieve accuracies that have not yet been remotely approached. Characteristics of a Bragg crystal instrument capable of a sufficient degree of broad band X-ray polarimetry to test for the existence of a fast rotating black hole in the Cyg X-1 system, are also described. Finally, the need for X-ray polarisation measurements throughout the field of current X-ray astronomy is illuminated

A selective inhibitor of the osteoclastic V-H(+)-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats

A potent and selective inhibitor of the osteoclastic V-H(+)-ATPase, (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl) -2,4-pentadienamide (SB 242784), was evaluated in two animal models of bone resorption. SB 242784 completely prevented retinoid-induced hypercalcemia in thyroparathyroidectomized (TPTX) rats when administered orally at 10 mg/kg. SB 242784 was highly efficacious in the prevention of ovariectomy-induced bone loss in the rat when administered orally for 6 months at 10 mg/kg/d and was partially effective at 5 mg/kg/d. Its activity was demonstrated by measurement of bone mineral density (BMD), biochemical markers of bone resorption, and histomorphometry. SB 242784 was at least as effective in preventing bone loss as an optimal dose of estrogen. There were no adverse effects of compound administration and no effects on kidney function or urinary acidity. Selectivity of the inhibitor was further studied using an in situ cytochemical assay for bafilomycin-sensitive V-H(+)-ATPase using sections of osteoclastoma and numerous other tissues. SB 242784 inhibited the osteoclast enzyme at 1,000-fold lower concentrations than enzymes in any of the other tissues evaluated. SB 242784 demonstrates the utility of selective inhibition of the osteoclast V-H(+)-ATPase as a novel approach to the prevention of bone loss in humans

Application of penetrators within the solar system

About the book: This invaluable volume set of Advances in Geosciences continues the excellent tradition of the Asia-Oceania scientific community in providing the most up-to-date research results on a wide range of geosciences and environmental science. The information is vital to the understanding of the effects of climate change, extreme weathers on the most populated regions and fastest moving economies in the world. Besides, these volumes also highlight original papers from many prestigious research institutions which are doing cutting edge study in atmospheric physics, hydrological science and water resource, ocean science and coastal study, planetary exploration and solar system science, seismology, tsunamis, upper atmospheric physics and space science

New ⁴⁰Ar/³⁹Ar age progression for the Louisville hot spot trail and implications for inter–hot spot motion

In this study we present 42 new ⁴⁰Ar/³⁹Ar incremental heating age determinations updated age progression for the Louisville seamount trail. Louisville is the South Hawaiian‐Emperor seamount trail, both trails representing intraplate volcanism (~80 Ma to present) and being examples of primary hot spot lineaments. Our age‐progressive trend from 71 to 21 Ma. Assuming fixed hot spots, this makes to the Hawaiian‐Emperor age progression and the most recent absolute plate (WK08G) of Wessel and Kroenke (2008). We observe that for the Louisville ages are systematically older relative to both the WK08G model predictions and with offsets ranging up to 6 Myr. Taking into account the uncertainty about the magmatic succession at individual Louisville volcanoes, these age offsets should estimates, as our sampling probably tended to recover the youngest lava flows. to either a contribution of inter–hot spot motion between the Louisville and easterly location of the Louisville hot spot than the one inferred in the WK08G investigated in this paper, whereby the more eastern hot spot location (52.0°S, 137.2°W) reduces the average age offset, but still results in a relatively large 3.7 Myr. When comparing the new ages to the APM models (S04P, S04G) by attempt to compensate for the motion of hot spots in the Pacific (Hawaii) or Reunion and Walvis), the measured and predicted ages are more in agreement, offset of 2.3 Myr with respect to the S04G model. At face value these more consider both plate and hot spot motions, therefore provide a better fit to the is particularly good for seamounts younger than 50 Ma, a period for which there for the Louisville hot spot and little inter–hot spot motion with Hawaii. However, discrepancies in the Louisville age‐distance record prior to 50 Ma indicate there between Louisville and the other Pacific hot spots that was not corrected for in Finally, based on six new ⁴⁰Ar/³⁹Ar age dates, the 169°W bend in the Louisville formed at least 3 Myr before the formation of the Hawaiian‐Emperor bend. The of both bends thus appears to be asynchronous, which would require other than a global plate motion change between 50 and 47 Ma to explain these two observations.Keywords: Pacific plate, ⁴⁰Ar/³⁹ Ar geochronology, seamounts, Submarine alteration, Guyots, Hot spot

TLR3 deletion limits mortality and disease severity due to Phlebovirus infection.

TLR3 was the first member of the TLR family of pattern recognition receptors found to detect a conserved viral molecular pattern, dsRNA, yet supporting evidence for a major role in host defense against viral pathogens is limited. Punta Toro virus (PTV) has been shown to produce severe infection in mice, modeling disease caused by the related highly pathogenic Rift Valley fever phlebovirus in humans and domesticated ungulates. Using TLR3-deficient mice, we investigated the involvement of TLR3 in host defense against PTV infection. Compared with wild-type, TLR3(-/-) mice demonstrate increased resistance to lethal infection and have reduced liver disease associated with hepatotropic PTV infection. Infectious challenge produced comparable peak liver and serum viral loads; however, TLR3(-/-) mice were able to clear systemic virus at a slightly faster rate. Cytokine profiling suggests that TLR3 plays an important role in PTV pathogenesis through the overproduction of inflammatory mediators, which may be central to the observed differences in survival and disease severity. Compared with TLR3-deficient mice, IL-6, MCP-1, IFN-gamma, and RANTES were all present at higher levels in wild-type animals. Most dramatic was the exaggerated levels of IL-6 found systemically and in liver tissue of infected wild-type mice; however, IL-6-deficient animals were found to be more susceptible to lethal PTV infection. Taken together, we conclude that the TLR3-mediated response to PTV infection is detrimental to disease outcome and propose that IL-6, although critical to establishing antiviral defense, contributes to pathogenesis when released in excess, necessitating its controlled production as is seen with TLR3(-/-) mice

Comprehensive genomic profiling aids in distinguishing metastatic recurrence from second primary cancers

BACKGROUND. Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer‐specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios. MATERIALS AND METHODS. We identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next‐generation sequencing‐based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities. RESULTS. A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination. CONCLUSIONS. Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. IMPLICATIONS FOR PRACTICE. Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management

An update on MoonLITE

MoonLITE is a proposed, UK-led lunar science mission comprising 4 scientific penetrators that will make in-situ measurements at widely separated locations on the Moon. They will form a global seismic network capable of investigating the interior of the Moon including the existence of a core, its size and nature such as whether it is liquid or not. Particular landing sites at 1 each pole will also allow determination of the existence of water and other volatiles, and astrobiological organics possibly deposited by impacting comets. The other two landing sites will include the far side which has also not yet seen a landing, and a landing near an Apollo site to allow correlation with previous results. Additionally, detection of lunar water resources and possible sites to avoid large seismic events potentially dangerous to lunar bases offer information very valuable to future human missions. We will present a brief overview of this mission and its current status, including results from the forthcoming full scale impact tests currently on-schedule for late May this year, and from the pre-trial survival modelling. The current status of the planned Phase-A analysis and NASA involvement, and associated parallel hardware development programme will also be presented, together with their potential impact on the future development programme. We will additionally discuss the current status of possible coordination with the recently NASA proposed lunar geophysical network, and with other proposed lunar missions

Multifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses

Abstract The zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined. Surprisingly, the Gn domain-A antibody does not directly block RVFV Gn interaction with the host receptor low density lipoprotein receptor-related protein 1 (LRP1) as determined by a competitive assay. This study identifies a rationally designed combination of human mAbs deserving of future investigation for use in humans against RVFV infection. Using a two-pronged mechanistic approach, we demonstrate the potent efficacy of a rationally designed combination mAb therapeutic