Shouting from far away: three poems about living with speechlessness.

We present three poems written from personal experience of living with primary progressive non-fluent aphasia (primary progressive apraxia of speech). The poems provide a window on this illness 'from the inside', and vividly illustrate how intellect and inner life may survive strikingly intact, even after speech is lost.

Pharmacological characterisation of GSK3335103, an oral αvβ6 integrin small molecule RGD-mimetic inhibitor for the treatment of fibrotic disease.

Fibrosis is the formation of scar tissue due to injury or long-term inflammation and is a leading cause of morbidity and mortality. Activation of the pro-fibrotic cytokine transforming growth factor-β (TGFβ) via the alpha-V beta-6 (αvβ6) integrin has been identified as playing a key role in the development of fibrosis. Therefore, a drug discovery programme to identify an orally bioavailable small molecule αvβ6 arginyl-glycinyl-aspartic acid (RGD)-mimetic was initiated.

Magma Ocean Evolution of the TRAPPIST-1 Planets.

Recent observations of the potentially habitable planets TRAPPIST-1 e, f, and g suggest that they possess large water mass fractions of possibly several tens of weight percent of water, even though the host star's activity should drive rapid atmospheric escape. These processes can photolyze water, generating free oxygen and possibly desiccating the planet. After the planets formed, their mantles were likely completely molten with volatiles dissolving and exsolving from the melt.

Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis.

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points.

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar.

Artemisinin-based combination therapies (ACTs) are first-line treatments for uncomplicated Plasmodium falciparum malaria. ACT resistance is spreading in Asia but not yet in Africa. Reduced effects of ACT partner drugs have been reported but with little information regarding widely used artesunate/amodiaquine (ASAQ).

Parasite clearance, cure rate, post-treatment prophylaxis and safety of standard 3-day versus an extended 6-day treatment of artemether-lumefantrine and a single low-dose primaquine for uncomplicated Plasmodium falciparum malaria in Bagamoyo district, Tanzania: a randomized controlled trial.

Background: Artemisinin-based combination therapy (ACT) resistant Plasmodium falciparum represents an increasing threat to Africa. Extended ACT regimens from standard 3 to 6 days may represent a means to prevent its development and potential spread in Africa.

Methods: Standard 3-day treatment with artemether-lumefantrine (control) was compared to extended 6-day treatment and single low-dose primaquine (intervention); in a randomized controlled, parallel group, superiority clinical trial of patients aged 1-65 years with microscopy confirmed uncomplicated P.

The Habitability of Proxima Centauri b: Environmental States and Observational Discriminants.

Proxima Centauri b provides an unprecedented opportunity to understand the evolution and nature of terrestrial planets orbiting M dwarfs. Although Proxima Cen b orbits within its star's habitable zone, multiple plausible evolutionary paths could have generated different environments that may or may not be habitable. Here, we use 1-D coupled climate-photochemical models to generate self-consistent atmospheres for several evolutionary scenarios, including high-O, high-CO, and more Earth-like atmospheres, with both oxic and anoxic compositions.

IDENTIFYING PLANETARY BIOSIGNATURE IMPOSTORS: SPECTRAL FEATURES OF CO AND O RESULTING FROM ABIOTIC O/O PRODUCTION.

O and O have been long considered the most robust individual biosignature gases in a planetary atmosphere, yet multiple mechanisms that may produce them in the absence of life have been described. However, these abiotic planetary mechanisms modify the environment in potentially identifiable ways. Here we briefly discuss two of the most detectable spectral discriminants for abiotic O/O: CO and O.

Formation, habitability, and detection of extrasolar moons.

The diversity and quantity of moons in the Solar System suggest a manifold population of natural satellites exist around extrasolar planets. Of peculiar interest from an astrobiological perspective, the number of sizable moons in the stellar habitable zones may outnumber planets in these circumstellar regions. With technological and theoretical methods now allowing for the detection of sub-Earth-sized extrasolar planets, the first detection of an extrasolar moon appears feasible.

Astrobiological stoichiometry.

Chemical composition affects virtually all aspects of astrobiology, from stellar astrophysics to molecular biology. We present a synopsis of the research results presented at the "Stellar Stoichiometry" Workshop Without Walls hosted at Arizona State University April 11-12, 2013, under the auspices of the NASA Astrobiology Institute. The results focus on the measurement of chemical abundances and the effects of composition on processes from stellar to planetary scales.

Habitable planets around white and brown dwarfs: the perils of a cooling primary.

White and brown dwarfs are astrophysical objects that are bright enough to support an insolation habitable zone (IHZ). Unlike hydrogen-burning stars, they cool and become less luminous with time; hence their IHZ moves in with time. The inner edge of the IHZ is defined as the orbital radius at which a planet may enter a moist or runaway greenhouse, phenomena that can remove a planet's surface water forever.

Tidal Venuses: triggering a climate catastrophe via tidal heating.

Traditionally, stellar radiation has been the only heat source considered capable of determining global climate on long timescales. Here, we show that terrestrial exoplanets orbiting low-mass stars may be tidally heated at high-enough levels to induce a runaway greenhouse for a long-enough duration for all the hydrogen to escape. Without hydrogen, the planet no longer has water and cannot support life.

Exomoon habitability constrained by illumination and tidal heating.

The detection of moons orbiting extrasolar planets ("exomoons") has now become feasible. Once they are discovered in the circumstellar habitable zone, questions about their habitability will emerge. Exomoons are likely to be tidally locked to their planet and hence experience days much shorter than their orbital period around the star and have seasons, all of which works in favor of habitability.

Habitability of extrasolar planets and tidal spin evolution.

Stellar radiation has conservatively been used as the key constraint to planetary habitability. We review here the effects of tides, exerted by the host star on the planet, on the evolution of the planetary spin. Tides initially drive the rotation period and the orientation of the rotation axis into an equilibrium state but do not necessarily lead to synchronous rotation.

Tides and the evolution of planetary habitability.

Tides raised on a planet by the gravity of its host star can reduce the planet's orbital semi-major axis and eccentricity. This effect is only relevant for planets orbiting very close to their host stars. The habitable zones of low-mass stars are also close in, and tides can alter the orbits of planets in these locations.