Determining the source(s) of hydrogen, carbon, and nitrogen accreted by Earth is important for understanding the origins of water and life and for constraining dynamical processes that operated ...during planet formation. Chondritic meteorites are asteroidal fragments that retain records of the first few million years of solar system history. The deuterium/hydrogen (D/H) values of water in carbonaceous chondrites are distinct from those in comets and Saturn's moon Enceladus, implying that they formed in a different region of the solar system, contrary to predictions of recent dynamical models. The D/H values of water in carbonaceous chondrites also argue against an influx of water ice from the outer solar system, which has been invoked to explain the nonsolar oxygen isotopic composition of the inner solar system. The bulk hydrogen and nitrogen isotopic compositions of CI chondrites suggest that they were the principal source of Earth's volatiles.
•Realised ES are a product of the potential service and specified beneficiaries.•Natural capital (NC) and human-derived capital (HDC) are both essential for ES.•HDC plays a role even at the stage of ...potential ecosystem services.•It is possible but not always easy to separate the contribution of NC and HDC to ES.•Sustainable management should identify critical NC and HDC for each service.
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There is growing interest in the role that natural capital plays in underpinning ecosystem services. Yet, there remain differences and inconsistencies in the conceptualisation of capital and ecosystem services and the role that humans play in their delivery. Using worked examples in a stocks and flows systems approach, we show that both natural capital (NC) and human-derived (produced, human, social, cultural, financial) capital (HDC) are necessary to create ecosystem services at many levels. HDC plays a role at three stages of ecosystem service delivery. Firstly, as essential elements of a combined social-ecological system to create a potential ecosystem service. Secondly, through the beneficiaries in shaping the demand for that service. Thirdly, in the form of additional capital required to realise the ecosystem service flow. We show that it is possible, although not always easy, to separately identify how these forms of capital contribute to ecosystem service flow. We discuss how applying a systems approach can help identify critical natural capital and critical human-derived capital to guide sustainable management of the stocks and flows of all forms of capital which underpin provision of multiple ecosystem services. The amount of realised ecosystem service can be managed in several ways: via the NC & HDC which govern the potential service, and via factors which govern both the demand from the beneficiaries, and the efficiency of use of the potential service by those beneficiaries.
The results from a novel, micro-tensile testing technique, employing a micro-electro-mechanical system, operated in a push-to-pull configuration, to study the effects of radiation damage on Inconel ...X-750, are presented. Non-irradiated material, along with material irradiated to 67 dpa and 81 dpa at two irradiation temperatures, 120–280 °C and 300–330 °C, is investigated. This testing approach implements a safe, lift-out, extraction method that enables the evaluation of material tensile behavior in specific locations of radioactive components with complex geometries outside of costly hot cell protective environments. Regional cold working and grinding manufacturing processes that go undetected in bulk component testing can be evaluated in parallel with radiation damage effects. Non-irradiated specimens on the order of 1 µm × 1 µm × 2.5 µm taken from center regions of the material unaffected by processing produced yield strengths of 938 MPa and 1043 MPa, in good agreement with the bulk yield strength of Inconel X-750: 972–1070 MPa. Mechanical strengths of material irradiated to 67 dpa decreased by ~75 MPa for material irradiated at 300–330 °C and ~176 MPa for material irradiated at 120–280 °C, compared to the non-irradiated material. However, material irradiated to 81 dpa has practically identical mechanical strengths at the two irradiation temperatures, and these strengths are ~100 MPa greater than those of non-irradiated material. Average ductility of the material decreases more quickly when irradiated at 300–330 °C, from an initial value of ~15% to ~5% after 67 dpa, whereas the ductility of the material irradiated at 120–280 °C remains close to the initial value at 67 dpa and decreases to ~2% after 81 dpa.
During infection, the fungal pathogen Aspergillus fumigatus forms biofilms that enhance its resistance to antimicrobials and host defenses. An integral component of the biofilm matrix is ...galactosaminogalactan (GAG), a cationic polymer of α-1,4-linked galactose and partially deacetylated N-acetylgalactosamine (GalNAc). Recent studies have shown that recombinant hydrolase domains from Sph3, an A. fumigatus glycoside hydrolase involved in GAG synthesis, and PelA, a multifunctional protein from Pseudomonas aeruginosa involved in Pel polysaccharide biosynthesis, can degrade GAG, disrupt A. fumigatus biofilms, and attenuate fungal virulence in a mouse model of invasive aspergillosis. The molecular mechanisms by which these enzymes disrupt biofilms have not been defined. We hypothesized that the hydrolase domains of Sph3 and PelA (Sph3h and PelAh, respectively) share structural and functional similarities given their ability to degrade GAG and disrupt A. fumigatus biofilms. MALDI-TOF enzymatic fingerprinting and NMR experiments revealed that both proteins are retaining endo-α-1,4-N-acetylgalactosaminidases with a minimal substrate size of seven residues. The crystal structure of PelAh was solved to 1.54 Å and structure alignment to Sph3h revealed that the enzymes share similar catalytic site residues. However, differences in the substrate-binding clefts result in distinct enzyme-substrate interactions. PelAh hydrolyzed partially deacetylated substrates better than Sph3h, a finding that agrees well with PelAh's highly electronegative binding cleft versus the neutral surface present in Sph3h. Our insight into PelAh's structure and function necessitate the creation of a new glycoside hydrolase family, GH166, whose structural and mechanistic features, along with those of GH135 (Sph3), are reported here.
Autism spectrum conditions (ASC) affect more males than females. This suggests that the neurobiology of autism: 1) may overlap with mechanisms underlying typical sex-differentiation or 2) alternately ...reflect sex-specificity in how autism is expressed in males and females. Here we used functional magnetic resonance imaging (fMRI) to test these alternate hypotheses. Fifteen men and fourteen women with Asperger syndrome (AS), and sixteen typically developing men and sixteen typically developing women underwent fMRI during performance of mental rotation and verbal fluency tasks. All groups performed the tasks equally well. On the verbal fluency task, despite equivalent task-performance, both males and females with AS showed enhanced activation of left occipitoparietal and inferior prefrontal activity compared to controls. During mental rotation, there was a significant diagnosis-by-sex interaction across occipital, temporal, parietal, middle frontal regions, with greater activation in AS males and typical females compared to AS females and typical males. These findings suggest a complex relationship between autism and sex that is differentially expressed in verbal and visuospatial domains.
Summary Background MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ...ligand-receptor complex. It also induces tumour cell apoptosis, and has no agonist activity. Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease. Methods This phase 1–2 study was undertaken in five US centres in 140 patients. Patients with progressive, metastatic, castration-resistant prostate cancer were enrolled in dose-escalation cohorts of three to six patients and given an oral daily starting dose of MDV3100 30 mg. The final daily doses studied were 30 mg (n=3), 60 mg (27), 150 mg (28), 240 mg (29), 360 mg (28), 480 mg (22), and 600 mg (3). The primary objective was to identify the safety and tolerability profile of MDV3100 and to establish the maximum tolerated dose. The trial is registered with ClinicalTrials.gov , number NCT00510718. Findings We noted antitumour effects at all doses, including decreases in serum prostate-specific antigen of 50% or more in 78 (56%) patients, responses in soft tissue in 13 (22%) of 59 patients, stabilised bone disease in 61 (56%) of 109 patients, and conversion from unfavourable to favourable circulating tumour cell counts in 25 (49%) of the 51 patients. PET imaging of 22 patients to assess androgen-receptor blockade showed decreased18 F-fluoro-5α-dihydrotestosterone binding at doses from 60 mg to 480 mg per day (range 20–100%). The median time to progression was 47 weeks (95% CI 34–not reached) for radiological progression. The maximum tolerated dose for sustained treatment (>28 days) was 240 mg. The most common grade 3–4 adverse event was dose-dependent fatigue (16 11% patients), which generally resolved after dose reduction. Interpretation We recorded encouraging antitumour activity with MDV3100 in patients with castration-resistant prostate cancer. The results of this phase 1–2 trial validate in man preclinical studies implicating sustained androgen-receptor signalling as a driver in this disease. Funding Medivation, the Prostate Cancer Foundation, National Cancer Institute, the Howard Hughes Medical Institute, Doris Duke Charitable Foundation, and Department of Defense Prostate Cancer Clinical Trials Consortium.
Interactions between electrons and lattice vibrations are responsible for a wide range of material properties and applications. Recently, there has been considerable interest in the development of ...resonant inelastic x-ray scattering (RIXS) as a tool for measuring electron-phonon (e-ph) interactions. Here, we demonstrate the ability of RIXS to probe the interaction between phonons and specific electronic states both near to, and away from, the Fermi level. We performed carbon $K$-edge RIXS measurements on graphite, tuning the incident x-ray energy to separately probe the interactions of the $\pi^*$ and $\sigma^*$ electronic states. Our high-resolution data reveals detailed structure in the multi-phonon RIXS features that directly encodes the momentum dependence of the e-ph interaction strength. We develop a Green's-function method to model this structure, which naturally accounts for the phonon and interaction-strength dispersions, as well as the mixing of phonon momenta in the intermediate state. This model shows that the differences between the spectra can be fully explained by contrasting trends of the e-ph interaction through the Brillouin zone, being concentrated at the $\Gamma$ and $K$ points for the $\pi^*$ states, while being significant at all momenta for the $\sigma^*$ states. Our results advance the interpretation of phonon excitations in RIXS, and extend its applicability as a probe of e-ph interactions to a new range of out-of-equilibrium situations.
•We model the fluvial degradation of impact craters on Titan.•This process can modify craters such that they would be unrecognizable from orbit.•It also removes central uplifts, explaining their ...infrequent occurrence on Titan.•Latitudinal differences in erosion rate may explain Titan’s crater distribution.
There are few identifiable impact craters on Titan, especially in the polar regions. One explanation for this observation is that the craters are being destroyed through fluvial processes, such as weathering, mass wasting, fluvial incision and deposition. In this work, we use a landscape evolution model to determine whether or not this is a viable mechanism for crater destruction on Titan. We find that fluvial degradation can modify craters to the point where they would be unrecognizable by an orbiting spacecraft such as Cassini, given enough time and a large enough erosion rate. A difference in the erosion rate between the equator and the poles of a factor of a few could explain the latitudinal variation in Titan’s crater population. Fluvial erosion also removes central peaks and fills in central pits, possibly explaining their infrequent occurrence in Titan craters. Although many craters on Titan appear to be modified by aeolian infilling, fluvial modification is necessary to explain the observed impact crater morphologies. Thus, it is an important secondary modification process even in Titan’s drier equatorial regions.
•We have generated the first, complete geomorphologic map of Titan's polar regions.•Most of Titan's lake depressions can be found with a single plains unit, suggesting that the unit is conducive to ...the formation of such features.•Uplands materials are not uniform in composition, where mountains and dissected uplands have different radar backscattering behaviors.•The observed landscape appears as an underlying bedrock material that was mantled by vast sedimentary deposits. Superposed on these sedimentary deposits are steep-sided depressions, canyons and seas.•We offer a conceptual model that is able to explain the distribution and superposition relationships among our map units, where in Titan's distant past the poles were submerged under larger liquid bodies.
We present a geomorphologic map of Titan's polar terrains. The map was generated from a combination of Cassini Synthetic Aperture Radar (SAR) and Imaging Science Subsystem imaging products, as well as altimetry, SARTopo and radargrammetry topographic datasets. In combining imagery with topographic data, our geomorphologic map reveals a stratigraphic sequence from which we infer process interactions between units. In mapping both polar regions with the same geomorphologic units, we conclude that processes that formed the terrains of the north polar region also acted to form the landscape we observe at the south. Uniform, SAR-dark plains are interpreted as sedimentary deposits, and are bounded by moderately dissected uplands. These plains contain the highest density of filled and empty lake depressions, and canyons. These units unconformably overlay a basement rock that outcrops as mountains and SAR-bright dissected terrains at various elevations across both poles. All these units are then superposed by surficial units that slope towards the seas, suggestive of subsequent overland transport of sediment. From estimates of the depths of the embedded empty depressions and canyons that drain into the seas, the SAR-dark plains must be >600m thick in places, though the thickness may vary across the poles. At the lowest elevations of each polar region, there are large seas, which are currently liquid methane/ethane filled at the north and empty at the south. The large plains deposits and the surrounding hillslopes may represent remnant landforms that are a result of previously vast polar oceans, where larger liquid bodies may have allowed for a sustained accumulation of soluble and insoluble sediments, potentially forming layered sedimentary deposits. Coupled with vertical crustal movements, the resulting layers would be of varying solubilities and erosional resistances, allowing formation of the complex landscape that we observe today.
While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains ...unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use.
The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided.
After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio HR = 0.65, 95% confidence interval CI = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22).
In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.
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