Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae.

Combination therapy that includes artemisinin derivatives cures most falciparum malaria infections. Lowering transmission by reducing gametocyte infectivity would be an additional benefit. To examine the effect of such therapy on transmission, Gambian children with Plasmodium falciparum malaria were treated with standard regimens of chloroquine or pyrimethamine-sulfadoxine alone or in combination with 1 or 3 doses of artesunate. The infectivity to mosquitoes of gametocytes in peripheral blood was determined 4 or 7 days after treatment. Infection of mosquitoes was observed in all treatment groups and was positively associated with gametocyte density. The probability of transmission was lowest in those who received pyrimethamine-sulfadoxine and 3 doses of artesunate, and it was 8-fold higher in the group that received pyrimethamine-sulfadoxine alone. Artesunate reduced posttreatment infectivity dramatically but did not abolish it completely. The study raises questions about any policy to use pyrimethamine-sulfadoxine alone as the first-line treatment for malaria

Galaxies at z = 6 - 9 from the WFC3/IR imaging of the HUDF

We present the results of a systematic search for galaxies in the redshift range z = 6 - 9, within the new, deep, near-infrared imaging of the Hubble Ultra Deep Field provided by the Wide Field Camera 3 (WFC3) on HST. We have performed full SED fitting to the optical+infrared photometry of all high-redshift galaxy candidates detected at greater than 5-sigma in at least one of the WFC3/IR broad-band filters. After rejection of contaminants, the result is a sample of 49 galaxies with primary redshift solutions z > 5.9. Our sample, selected without recourse to specific colour cuts, re-selects all but the faintest one of the 16 z-drops selected by Oesch et al. (2009), recovers all 5 of the Y-drops reported by Bouwens et al. (2009), and adds a further 29 galaxy candidates, of which 12 lie beyond z = 6.3, and 4 lie beyond z = 7. We also present confidence intervals on our photometric redshift estimates, and caution that acceptable low-redshift (z < 2) solutions exist for 28 out of the 37 galaxies at z > 6.3, and for all 8 galaxy candidates at z > 7.5. Nevertheless, the very highest redshift candidates appear to be strongly clustered in the field. We derive new estimates of the ultraviolet galaxy luminosity function at z = 7 and z = 8. Where our results are most robust, at a characteristic luminosity M(1500) ~ -19.5 (AB), we find that the comoving number density of galaxies declines by a factor of ~ 2.5 between z = 6 and z = 7, and by a further factor of ~ 2 by z = 8. These results suggest that it is difficult for the observed population of high-redshift star-forming galaxies to achieve reionisation by z ~ 6 without a significant contribution from galaxies well below the detection limits, plus alterations in the escape fraction of ionising photons and/or continued vigorous star formation at z > 15.Comment: 25 Pages, Accepted for publication in MNRA

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV

The Hawk-I UDS and GOODS Survey (HUGS): Survey design and deep K-band number counts

We present the results of a new, ultra-deep, near-infrared imaging survey executed with the Hawk-I imager at the ESO VLT, of which we make all the data public. This survey, named HUGS (Hawk-I UDS and GOODS Survey), provides deep, high-quality imaging in the K and Y bands over the CANDELS UDS and GOODS-South fields. We describe here the survey strategy, the data reduction process, and the data quality. HUGS delivers the deepest and highest quality K-band images ever collected over areas of cosmological interest, and ideally complements the CANDELS data set in terms of image quality and depth. The seeing is exceptional and homogeneous, confined to the range 0.38"-0.43". In the deepest region of the GOODS-S field, (which includes most of the HUDF) the K-band exposure time exceeds 80 hours of integration, yielding a 1-sigma magnitude limit of ~28.0 mag/sqarcsec. In the UDS field the survey matches the shallower depth of the CANDELS images reaching a 1-sigma limit per sq.arcsec of ~27.3mag in the K band and ~28.3mag in the Y-band, We show that the HUGS observations are well matched to the depth of the CANDELS WFC3/IR data, since the majority of even the faintest galaxies detected in the CANDELS H-band images are also detected in HUGS. We present the K-band galaxy number counts produced by combining the HUGS data from the two fields. We show that the slope of the number counts depends sensitively on the assumed distribution of galaxy sizes, with potential impact on the estimated extra-galactic background light (abridged).Comment: Accepted for publication on Astronomy and Astrophysic

The UV continua and inferred stellar populations of galaxies at z ≃ 7–9 revealed by the Hubble Ultra-Deep Field 2012 campaign

We use the new ultra-deep, near-infrared imaging of the Hubble Ultra-Deep Field (HUDF) provided by our UDF12 Hubble Space Telescope (HST) Wide Field Camera 3/IR campaign to explore the rest-frame ultraviolet (UV) properties of galaxies at redshifts z > 6.5. We present the first unbiased measurement of the average UV power-law index, 〈β〉, (fλ ∝ λ^β) for faint galaxies at z ≃ 7, the first meaningful measurements of 〈β〉 at z ≃ 8, and tentative estimates for a new sample of galaxies at z ≃ 9. Utilizing galaxy selection in the new F140W (J_140) imaging to minimize colour bias, and applying both colour and power-law estimators of β, we find 〈β〉 = −2.1 ± 0.2 at z ≃ 7 for galaxies with M_UV ≃ −18. This means that the faintest galaxies uncovered at this epoch have, on average, UV colours no more extreme than those displayed by the bluest star-forming galaxies at low redshift. At z ≃ 8 we find a similar value, 〈β〉 = −1.9 ± 0.3. At z ≃ 9, we find 〈β〉 = −1.8 ± 0.6, essentially unchanged from z ≃ 6 to 7 (albeit highly uncertain). Finally, we show that there is as yet no evidence for a significant intrinsic scatter in β within our new, robust z ≃ 7 galaxy sample. Our results are most easily explained by a population of steadily star-forming galaxies with either ≃ solar metallicity and zero dust, or moderately sub-solar (≃10–20 per cent) metallicity with modest dust obscuration (AV ≃ 0.1–0.2). This latter interpretation is consistent with the predictions of a state-of-the-art galaxy-formation simulation, which also suggests that a significant population of very-low metallicity, dust-free galaxies with β ≃ −2.5 may not emerge until M_UV > −16, a regime likely to remain inaccessible until the James Webb Space Telescope

Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza

Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon a single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel is an alternative clinically proven antiviral target, yet a near-ubiquitous S31N polymorphism in M2 evokes resistance to licensed adamantane drugs. Hence, inhibitors capable of targeting N31 containing M2 (M2-N31) are highly desirable. Rational in silico design and in vitro screens delineated compounds favouring either lumenal or peripheral M2 binding, yielding effective M2-N31 inhibitors in both cases. Hits included adamantanes as well as novel compounds, with some showing low micromolar potency versus pandemic “swine” H1N1 influenza (Eng195) in culture. Interestingly, a published adamantane-based M2-N31 inhibitor rapidly selected a resistant V27A polymorphism (M2-A27/N31), whereas this was not the case for non-adamantane compounds. Nevertheless, combinations of adamantanes and novel compounds achieved synergistic antiviral effects, and the latter synergised with the neuraminidase inhibitor (NAi), Zanamivir. Thus, site-directed drug combinations show potential to rejuvenate M2 as an antiviral target whilst reducing the risk of drug resistance

The properties of (sub)millimetre-selected galaxies as revealed by CANDELS HST WFC3/IR imaging in GOODS-South

We have exploited the HST CANDELS WFC3/IR imaging to study the properties of (sub-)mm galaxies in GOODS-South. After using the deep radio and Spitzer imaging to identify galaxy counterparts for the (sub-)mm sources, we have used the new CANDELS data in two ways. First, we have derived improved photometric redshifts and stellar masses, confirming that the (sub-)mm galaxies are massive (=2.2x10^11 M_solar) galaxies at z=1-3. Second, we have exploited the depth and resolution of the WFC3/IR imaging to determine the sizes and morphologies of the galaxies at rest-frame optical wavelengths, fitting two-dimensional axi-symmetric Sersic models. Crucially, the WFC3/IR H-band imaging enables modelling of the mass-dominant galaxy, rather than the blue high-surface brightness features which often dominate optical (rest-frame UV) images of (sub-)mm galaxies, and can confuse visual morphological classification. As a result of this analysis we find that >95% of the rest-frame optical light in almost all of the (sub-)mm galaxies is well-described by either a single exponential disk, or a multiple-component system in which the dominant constituent is disk-like. We demonstrate that this conclusion is consistent with the results of high-quality ground-based K-band imaging, and explain why. The massive disk galaxies which host luminous (sub-)mm emission are reasonably extended (r_e=4 kpc), consistent with the sizes of other massive star-forming disks at z~2. In many cases we find evidence of blue clumps within the sources, with the mass-dominant disk becoming more significant at longer wavelengths. Finally, only a minority of the sources show evidence for a major galaxy-galaxy interaction. Taken together, these results support the view that most (sub-)mm galaxies at z~2 are simply the most extreme examples of normal star-forming galaxies at that era.Comment: 30 pages, 9 figure

LoCuSS: First Results from Strong-lensing Analysis of 20 Massive Galaxy Clusters at z~0.2

We present a statistical analysis of a sample of 20 strong lensing clusters drawn from the Local Cluster Substructure Survey (LoCuSS), based on high resolution Hubble Space Telescope imaging of the cluster cores and follow-up spectroscopic observations using the Keck-I telescope. We use detailed parameterized models of the mass distribution in the cluster cores, to measure the total cluster mass and fraction of that mass associated with substructures within R<250kpc.These measurements are compared with the distribution of baryons in the cores, as traced by the old stellar populations and the X-ray emitting intracluster medium. Our main results include: (i) the distribution of Einstein radii is log-normal, with a peak and 1sigma width of =1.16+/-0.28; (ii) we detect an X-ray/lensing mass discrepancy of =1.3 at 3 sigma significance -- clusters with larger substructure fractions displaying greater mass discrepancies, and thus greater departures from hydrostatic equilibrium; (iii) cluster substructure fraction is also correlated with the slope of the gas density profile on small scales, implying a connection between cluster-cluster mergers and gas cooling. Overall our results are consistent with the view that cluster-cluster mergers play a prominent role in shaping the properties of cluster cores, in particular causing departures from hydrostatic equilibrium, and possibly disturbing cool cores. Our results do not support recent claims that large Einstein radius clusters present a challenge to the CDM paradigm.Comment: 28 pages, 14 figures, accepted for publication in MNRAS, replaced with accepted versio

Physical properties of z>4 submillimeter galaxies in the COSMOS field

We study the physical properties of a sample of 6 SMGs in the COSMOS field, spectroscopically confirmed to lie at z>4. We use new GMRT 325 MHz and 3 GHz JVLA data to probe the rest-frame 1.4 GHz emission at z=4, and to estimate the sizes of the star-forming (SF) regions of these sources, resp. Combining our size estimates with those available in the literature for AzTEC1 and AzTEC3 we infer a median radio-emitting size for our z>4 SMGs of (0.63"+/-0.12")x(0.35"+/-0.05") or 4.1x2.3 kpc^2 (major times minor axis; assuming z=4.5) or lower if we take the two marginally resolved SMGs as unresolved. This is consistent with the sizes of SF regions in lower-redshift SMGs, and local normal galaxies, yet higher than the sizes of SF regions of local ULIRGs. Our SMG sample consists of a fair mix of compact and more clumpy systems with multiple, perhaps merging, components. With an average formation time of ~280 Myr, derived through modeling of the UV-IR SEDs, the studied SMGs are young systems. The average stellar mass, dust temperature, and IR luminosity we derive are M*~1.4x10^11 M_sun, T_dust~43 K, and L_IR~1.3x10^13L_sun, resp. The average L_IR is up to an order of magnitude higher than for SMGs at lower redshifts. Our SMGs follow the correlation between dust temperature and IR luminosity as derived for Herschel-selected 0.1=1.95+/-0.26 for our sample, compared to q~2.6 for IR luminous galaxies at z4 SMGs put them at the high end of the L_IR-T_dust distribution of SMGs, and that our SMGs form a morphologically heterogeneous sample. Thus, further in-depth analyses of large, statistical samples of high-redshift SMGs are needed to fully understand their role in galaxy formation and evolution