The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species.

Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg

When will it end? Long-lived intracontinental reactivation in central Australia

The post-Mesoproterozoic tectonometamorphic history of the Musgrave Province, central Australia, has previously been solely attributed to intracontinental compressional deformation during the 580–520 Ma Petermann Orogeny. However, our new structurally controlled multi-mineral geochronology results, from two north-trending transects, indicate protracted reactivation of the Australian continental interior over ca. 715 million years. The earliest events are identified in the hinterland of the orogen along the western transect. The first tectonothermal event, at ca. 715 Ma, is indicated by 40Ar/39Ar muscovite and U–Pb titanite ages. Another previously unrecognised tectonometamorphic event is dated at ca. 630 Ma by U–Pb analyses of metamorphic zircon rims. This event was followed by continuous cooling and exhumation of the hinterland and core of the orogen along numerous faults, including the Woodroffe Thrust, from ca. 625 Ma to 565 Ma as indicated by muscovite, biotite, and hornblende 40Ar/39Ar cooling ages. We therefore propose that the Petermann Orogeny commenced as early as ca. 630 Ma. Along the eastern transect, 40Ar/39Ar muscovite and zircon (U–Th)/He data indicate exhumation of the foreland fold and thrust system to shallow crustal levels between ca. 550 Ma and 520 Ma, while the core of the orogen was undergoing exhumation to mid-crustal levels and cooling below 600–660 °C. Subsequent cooling to 150–220 °C of the core of the orogen occurred between ca. 480 Ma and 400 Ma (zircon [U–Th]/He data) during reactivation of the Woodroffe Thrust, coincident with the 450–300 Ma Alice Springs Orogeny. Exhumation of the footwall of the Woodroffe Thrust to shallow depths occurred at ca. 200 Ma. More recent tectonic activity is also evident as on the 21 May, 2016 (Sydney date), a magnitude 6.1 earthquake occurred, and the resolved focal mechanism indicates that compressive stress and exhumation along the Woodroffe Thrust is continuing to the present day. Overall, these results demonstrate repeated amagmatic reactivation of the continental interior of Australia for ca. 715 million years, including at least 600 million years of reactivation along the Woodroffe Thrust alone. Estimated cooling rates agree with previously reported rates and suggest slow cooling of 0.9–7.0 °C/Ma in the core of the Petermann Orogen between ca. 570 Ma and 400 Ma. The long-lived, amagmatic, intracontinental reactivation of central Australia is a remarkable example of stress transmission, strain localization and cratonization-hindering processes that highlights the complexity of Continental Tectonics with regards to the rigid-plate paradigm of Plate Tectonics

Introduction: approaching space in intellectual history

This article serves as an introduction to the special issue on Conceptions of Space in Intellectual History. It opens with a brief inquiry into the place of ‘space’, both as a topic and as an analytical lens, in the field of intellectual history. The remainder of the introduction suggests a pathway through the special issue. Under three broad headings – ‘territory,’ ‘oceans and empire’, and ‘geopolitics’ – the volume’s articles are presented, brought into dialogue, and situated within a wider trajectory of recent research on conceptions of ‘space’ in intellectual history.Arts and Humanities Research Council; Cambridge Commonwealth, European & International Trust; Levy-Plumb Fund for the Humanities at Christ's College, Cambridge

Magnetic and structural depth profiles of Heusler alloy Co2FeAl0.5Si0.5 epitaxial films on Si(1 1 1)

The depth-resolved chemical structure and magnetic moment of Co2FeAl0.5Si0.5, thin films grown on Si(1 1 1) have been determined using x-ray and polarized neutron reflectometry. Bulk-like magnetization is retained across the majority of the film, but reduced moments are observed within 45˚A of the surface and in a 25˚A substrate-interface region. The reduced moment is related to compositional changes due to oxidation and diffusion, which are further quantified by elemental profiling using electron microscopy with electron energy loss spectroscopy. The accuracy of structural and magnetic depth-profiles obtained from simultaneous modeling is discussed using different approaches with different degree of constraints on the parameters. Our approach illustrates the challenges in fitting reflectometry data from these multi-component quaternary Heusler alloy thin films

The role of chemical structure on the magnetic and electronic properties of Co2FeAl0.5Si0.5/Si(111) interface

We show that Co2FeAl0.5Si0.5 film deposited on Si(111) has a single crystal structure and twin related epitaxial relationship with the substrate. Sub-nanometer electron energy loss spectroscopy shows that in a narrow interface region there is a mutual inter-diffusion dominated by Si and Co. Atomic resolution aberration-corrected scanning transmission electron microscopy reveals that the film has B2 ordering. The film lattice structure is unaltered even at the interface due to the substitu- tional nature of the intermixing. First-principles calculations performed using structural models based on the aberration corrected electron microscopy show that the increased Si incorporation in the film leads to a gradual decrease of the magnetic moment as well as significant spin-polarization reduction. These effects can have significant detrimental role on the spin injection from the Co2FeAl0.5Si0.5 film into the Si substrate, besides the structural integrity of this junction

Shell structure of superheavy nuclei in self-consistent mean-field models

We study the extrapolation of nuclear shell structure to the region of superheavy nuclei in self-consistent mean-field models -- the Skyrme-Hartree-Fock approach and the relativistic mean-field model -- using a large number of parameterizations. Results obtained with the Folded-Yukawa potential are shown for comparison. We focus on differences in the isospin dependence of the spin-orbit interaction and the effective mass between the models and their influence on single-particle spectra. While all relativistic models give a reasonable description of spin-orbit splittings, all non-relativistic models show a wrong trend with mass number. The spin-orbit splitting of heavy nuclei might be overestimated by 40%-80%. Spherical doubly-magic superheavy nuclei are found at (Z=114,N=184), (Z=120,N=172) or (Z=126,N=184) depending on the parameterization. The Z=114 proton shell closure, which is related to a large spin-orbit splitting of proton 2f states, is predicted only by forces which by far overestimate the proton spin-orbit splitting in Pb208. The Z=120 and N=172 shell closures predicted by the relativistic models and some Skyrme interactions are found to be related to a central depression of the nuclear density distribution. This effect cannot appear in macroscopic-microscopic models which have a limited freedom for the density distribution only. In summary, our findings give a strong argument for (Z=120,N=172) to be the next spherical doubly-magic superheavy nucleus.Comment: 22 pages REVTeX, 16 eps figures, accepted for publication in Phys. Rev.

Enhancing cooperative responses by regional fisheries management organisations to climate-driven redistribution of tropical Pacific tuna stocks

Climate change is predicted to alter the distributions of tropical tuna stocks in the Pacific Ocean. Recent modelling projects significant future shifts in tuna biomass from west to east, and from national jurisdictions to high seas areas. As the distributions of these stocks change, the relevant regional fisheries management organisations (RFMOs)—the Western and Central Pacific Fisheries Commission (WCPFC) and the Inter-American Tropical Tuna Commission (IATTC)—will need to develop an expanded framework for cooperation and collaboration to fulfil their conservation and management responsibilities under international law. The key elements of a possible expanded framework for cooperation can be developed, and fundamental areas for collaboration identified, by applying and adapting principles established in the United Nations Convention on the Law of the Sea, the United Nations Fish Stocks Agreement, and the constituent instruments of the RFMOs themselves. Our analysis reveals a wide range of important issues requiring cooperation, and three clear priorities. First, a formal mechanism for cooperation is needed to enable effective and efficient decision-making and action by the two RFMOs on key issues. Second, further cooperation is required in scientific research and modelling to better understand the biology and distributions of Pacific tuna stocks and how they will respond to climate change, and to inform stock assessments and harvest strategies. Third, the RFMOs must cooperate to define appropriate limits on fishing for each stock in a way that ensures they are compatible across the two organisations, taking into account their different members and management regimes

Operationalizing marketable blue carbon

The global carbon sequestration and avoided emissions potentially achieved via blue carbon is high (∼3% of annual global greenhouse gas emissions); however, it is limited by multidisciplinary and interacting uncertainties spanning the social, governance, financial, and technological dimensions. We compiled a transdisciplinary team of experts to elucidate these challenges and identify a way forward. Key actions to enhance blue carbon as a natural climate solution include improving policy and legal arrangements to ensure equitable sharing of benefits; improving stewardship by incorporating indigenous knowledge and values; clarifying property rights; improving financial approaches and accounting tools to incorporate co-benefits; developing technological solutions for measuring blue carbon sequestration at low cost; and resolving knowledge gaps regarding blue carbon cycles. Implementing these actions and operationalizing blue carbon will achieve measurable changes to atmospheric greenhouse gas concentrations, provide multiple co-benefits, and address national obligations associated with international agreements