X-Ray Diffraction of Ramp-Compressed Silicon to 390 GPa.

Silicon (Si) exhibits a rich collection of phase transitions under ambient-temperature isothermal and shock compression. This report describes in situ diffraction measurements of ramp-compressed Si between 40 and 389 GPa. Angle-dispersive x-ray scattering reveals that Si assumes an hexagonal close-packed (hcp) structure between 40 and 93 GPa and, at higher pressure, a face-centered cubic structure that persists to at least 389 GPa, the highest pressure for which the crystal structure of Si has been investigated. The range of hcp stability extends to higher pressures and temperatures than predicted by theory.

Sut-6/NIPP1 modulates tau toxicity.

Neurodegenerative diseases exhibiting the pathological accumulation of tau such as Alzheimer's disease and related disorders still have no disease-modifying treatments and the molecular mechanisms of neurodegeneration remain unclear. To discover additional suppressor of tauopathy (sut) genes that mediate or modulate the toxicity of pathological tau, we performed a classical genetic screen using a tau transgenic Caenorhabditis elegans model. From this screen, we identified the suppressing mutation W292X in sut-6, the C. elegans homolog of human NIPP1, which truncates the C-terminal RNA-binding domain. Using CRISPR-based genome editing approaches, we generated null and additional C-terminally truncated alleles in sut-6 and found that loss of sut-6 or sut-6(W292X) suppresses tau-induced behavioral locomotor deficits, tau protein accumulation and neuron loss. The sut-6(W292X) mutation showed stronger and semi-dominant suppression of tau toxicity while sut-6 deletion acted recessively. Neuronal overexpression of SUT-6 protein did not significantly alter tau toxicity, but neuronal overexpression of SUT-6 W292X mutant protein reduced tau-mediated deficits. Epistasis studies showed tauopathy suppression by sut-6 occurs independent of other known nuclear speckle-localized suppressors of tau such as sut-2, aly-1/aly-3 and spop-1. In summary, we have shown that sut-6/NIPP1 modulates tau toxicity and found a dominant mutation in the RNA-binding domain of sut-6 which strongly suppresses tau toxicity. This suggests that altering RNA-related functions of SUT-6/NIPP1 instead of complete loss of SUT-6/NIPP1 will provide the strongest suppression of tau.

Measurement of the Charge-Averaged Elastic Lepton-Proton Scattering Cross Section by the OLYMPUS Experiment.

We report the first measurement of the average of the electron-proton and positron-proton elastic scattering cross sections. This lepton charge-averaged cross section is insensitive to the leading effects of hard two-photon exchange, giving more robust access to the proton's electromagnetic form factors. The cross section was extracted from data taken by the OLYMPUS experiment at DESY, in which alternating stored electron and positron beams were scattered from a windowless gaseous hydrogen target. Elastic scattering events were identified from the coincident detection of the scattered lepton and recoil proton in a large-acceptance toroidal spectrometer. The luminosity was determined from the rates of Møller, Bhabha, and elastic scattering in forward electromagnetic calorimeters. The data provide some selectivity between existing form factor global fits and will provide valuable constraints to future fits.

Equation of State of CO_{2} Shock Compressed to 1 TPa.

Equation-of-state (pressure, density, temperature, internal energy) and reflectivity measurements on shock-compressed CO_{2} at and above the insulating-to-conducting transition reveal new insight into the chemistry of simple molecular systems in the warm-dense-matter regime. CO_{2} samples were precompressed in diamond-anvil cells to tune the initial densities from 1.35 g/cm^{3} (liquid) to 1.74 g/cm^{3} (solid) at room temperature and were then shock compressed up to 1 TPa and 93 000 K. Variation in initial density was leveraged to infer thermodynamic derivatives including specific heat and Gruneisen coefficient, exposing a complex bonded and moderately ionized state at the most extreme conditions studied.

Meteorological and Air Quality Modeling for Hawaii, Puerto Rico, and Virgin Islands.

A photochemical model platform for Hawaii, Puerto Rico, and Virgin Islands predicting O3, PM2.5, and regional haze would be useful to support assessments relevant for the National Ambient Air Quality Standards (NAAQS), Regional Haze Rule, and the Prevention of Significant Deterioration (PSD) program. These areas have not traditionally been modeled with photochemical transport models, but a reasonable representation of meteorology, emissions (natural and anthropogenic), chemistry, and deposition could support air quality management decisions in these areas. Here, a prognostic meteorological model (Weather Research and Forecasting) and photochemical transport (Community Multiscale Air Quality) model were applied for the entire year of 2016 at 27, 9, and 3 km grid resolution for areas covering the Hawaiian Islands and Puerto Rico/Virgin Islands. Model predictions were compared against surface and upper air meteorological and chemical measurements available in both areas. The vertical gradient of temperature, humidity, and winds in the troposphere was well represented. Surface layer meteorological model performance was spatially variable, but temperature tended to be underestimated in Hawaii. Chemically speciated daily average PM2.5 was generally well characterized by the modeling system at urban and rural monitors in Hawaii and Puerto Rico/Virgin Islands. Model performance was notably impacted by the wildfire emission methodology. Model performance was mixed for hourly SO2, NO2, PM2.5, and CO and was often related to how well local emissions sources were characterized. SO2 predictions were much lower than measurements at monitors near active volcanos on Hawaii, which was expected since volcanic emissions were not included in these model simulations. Further research is needed to assess emission inventory representation of these areas and how microscale meteorology influenced by the complex land-water and terrain interfaces impacts higher time resolution performance.

Differences in fine particle chemical composition on clear and cloudy days.

Clouds are prevalent and alter PM2.5 mass and chemical composition. Cloud-affected satellite retrievals are often removed from data products, hindering estimates of tropospheric chemical composition during cloudy times. We examine surface fine particulate matter (PM2.5) chemical constituent concentrations in the Interagency Monitoring of PROtected Visual Environments network during Cloudy and Clear Sky times defined using Moderate Resolution Imaging Spectroradiometer (MODIS) cloud flags from 2010-2014 with a focus on differences in particle hygroscopicity and aerosol liquid water (ALW). Cloudy and Clear Sky periods exhibit significant differences in PM2.5 and chemical composition that vary regionally and seasonally. In the eastern US, relative humidity alone cannot explain differences in ALW, suggesting emissions and in situ chemistry exert determining impacts. An implicit clear sky bias may hinder efforts to quantitatively to understand and improve model representation of aerosol-cloud interactions.

Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.

Preventable warfarin-induced birth defects: A missed opportunity?

BACKGROUND: Congenital abnormalities and pregnancy losses due to the teratogenic effects of warfarin are prevalent among the South African population. These are potentially preventable if the challenges and barriers faced by at-risk women are understood and addressed effectively. OBJECTIVES: To determine the practice, knowledge and attitudes regarding the teratogenic risks experienced by women administered warfarin. METHODS: A descriptive study was performed. Quantitative data were collected through a researcher-administered questionnaire. The target population comprised 101 women of reproductive age who received warfarin treatment and attended a single tertiary-level anticoagulation clinic. RESULTS: Patient-related challenges identified in this study are: language barriers, poor understanding of basic terminology and mathematics, poor contraceptive and family planning practices, lack of knowledge regarding the risks of warfarin in pregnancy and passive attitudes towards information attainment. CONCLUSIONS: Interventions are necessary to address the challenges in such settings. These include increased awareness of the teratogenic potential of specific chronic medications among healthcare providers, patients and the public. Standardised management protocols for women of reproductive age initiated on teratogenic medications should be implemented, including contraceptive and family planning discussions at follow-up visits. Improvement of the counselling skills of healthcare providers and the availability of translators or healthcare providers fluent in local languages could assist in risk reduction.

Atmospheric implications of large C2-C5 alkane emissions from the U.S. oil and gas industry.

Emissions of C2-C5 alkanes from the U.S. oil and gas sector have changed rapidly over the last decade. We use a nested GEOS-Chem simulation driven by updated 2011NEI emissions with aircraft, surface and column observations to 1) examine spatial patterns in the emissions and observed atmospheric abundances of C2-C5 alkanes over the U.S., and 2) estimate the contribution of emissions from the U.S. oil and gas industry to these patterns. The oil and gas sector in the updated 2011NEI contributes over 80% of the total U.S. emissions of ethane (C2H6) and propane (C3H8), and emissions of these species are largest in the central U.S. Observed mixing ratios of C2-C5 alkanes show enhancements over the central U.S. below 2 km. A nested GEOS-Chem simulation underpredicts observed C3H8 mixing ratios in the boundary layer over several U.S. regions and the relative underprediction is not consistent, suggesting C3H8 emissions should receive more attention moving forward. Our decision to consider only C4-C5 alkane emissions as a single lumped species produces a geographic distribution similar to observations. Due to the increasing importance of oil and gas emissions in the U.S., we recommend continued support of existing long-term measurements of C2-C5 alkanes. We suggest additional monitoring of C2-C5 alkanes downwind of northeastern Colorado, Wyoming and western North Dakota to capture changes in these regions. The atmospheric chemistry modeling community should also evaluate whether chemical mechanisms that lump larger alkanes are sufficient to understand air quality issues in regions with large emissions of these species.

Erratum: Measurement of Body-Centered-Cubic Aluminum at 475 GPa [Phys. Rev. Lett. 119, 175702 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.119.175702.

Invited review: A position on the Global Livestock Environmental Assessment Model (GLEAM).

The livestock sector is one of the fastest growing subsectors of the agricultural economy and, while it makes a major contribution to global food supply and economic development, it also consumes significant amounts of natural resources and alters the environment. In order to improve our understanding of the global environmental impact of livestock supply chains, the Food and Agriculture Organization of the United Nations has developed the Global Livestock Environmental Assessment Model (GLEAM). The purpose of this paper is to provide a review of GLEAM. Specifically, it explains the model architecture, methods and functionality, that is the types of analysis that the model can perform. The model focuses primarily on the quantification of greenhouse gases emissions arising from the production of the 11 main livestock commodities. The model inputs and outputs are managed and produced as raster data sets, with spatial resolution of 0.05 decimal degrees. The Global Livestock Environmental Assessment Model v1.0 consists of five distinct modules: (a) the Herd Module; (b) the Manure Module; (c) the Feed Module; (d) the System Module; (e) the Allocation Module. In terms of the modelling approach, GLEAM has several advantages. For example spatial information on livestock distributions and crops yields enables rations to be derived that reflect the local availability of feed resources in developing countries. The Global Livestock Environmental Assessment Model also contains a herd model that enables livestock statistics to be disaggregated and variation in livestock performance and management to be captured. Priorities for future development of GLEAM include: improving data quality and the methods used to perform emissions calculations; extending the scope of the model to include selected additional environmental impacts and to enable predictive modelling; and improving the utility of GLEAM output.

Measurement of Body-Centered-Cubic Aluminum at 475 GPa.

Nanosecond in situ x-ray diffraction and simultaneous velocimetry measurements were used to determine the crystal structure and pressure, respectively, of ramp-compressed aluminum at stress states between 111 and 475 GPa. The solid-solid Al phase transformations, fcc-hcp and hcp-bcc, are observed at 216±9 and 321±12 GPa, respectively, with the bcc phase persisting to 475 GPa. The high-pressure crystallographic texture of the hcp and bcc phases suggests close-packed or nearly close-packed lattice planes remain parallel through both transformations.

Hard Two-Photon Contribution to Elastic Lepton-Proton Scattering Determined by the OLYMPUS Experiment.

The OLYMPUS Collaboration reports on a precision measurement of the positron-proton to electron-proton elastic cross section ratio, R_{2γ}, a direct measure of the contribution of hard two-photon exchange to the elastic cross section. In the OLYMPUS measurement, 2.01 GeV electron and positron beams were directed through a hydrogen gas target internal to the DORIS storage ring at DESY. A toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight scintillators detected elastically scattered leptons in coincidence with recoiling protons over a scattering angle range of ≈20° to 80°. The relative luminosity between the two beam species was monitored using tracking telescopes of interleaved gas electron multiplier and multiwire proportional chamber detectors at 12°, as well as symmetric Møller or Bhabha calorimeters at 1.29°. A total integrated luminosity of 4.5 fb^{-1} was collected. In the extraction of R_{2γ}, radiative effects were taken into account using a Monte Carlo generator to simulate the convolutions of internal bremsstrahlung with experiment-specific conditions such as detector acceptance and reconstruction efficiency. The resulting values of R_{2γ}, presented here for a wide range of virtual photon polarization 0.456<ε<0.978, are smaller than some hadronic two-photon exchange calculations predict, but are in reasonable agreement with a subtracted dispersion model and a phenomenological fit to the form factor data.

Rickettsia parkeri and "Candidatus Rickettsia andeanae" in Questing Amblyomma maculatum (Acari: Ixodidae) From Mississippi.

Amblyomma maculatum Koch (Acari: Ixodidae), the primary vector for Rickettsia parkeri, may also be infected with a rickettsia of unknown pathogenicity, "Candidatus Rickettsia andeanae." Infection rates with these rickettsiae vary geographically, and coinfected ticks have been reported. In this study, infection rates of R. parkeri and "Ca. R. andeanae" were evaluated, and rickettsial DNA levels quantified, in 335 questing adult A. maculatum collected in 2013 (n = 95), 2014 (n = 139), and 2015 (n = 101) from Oktibbeha County, MS. Overall infection rates of R. parkeri and "Ca. R. andeanae" were 28.7% and 9.3%, respectively, with three additional A. maculatum (0.9%) coinfected. While R. parkeri-infected ticks were detected all three years (34.7% in 2013; 13.7% in 2014; 43.6% in 2015), "Ca. R. andeanae" was not detected in 2013, and was detected at rates of 10.8% in 2014, and 15.8% in 2015. Interestingly, rickettsial DNA levels in singly-infected ticks were significantly lower in "Ca. R. andeanae"-infected ticks compared to R. parkeri-infected ticks (P < 0.0001). Thus, both infection rates and rickettsial DNA levels were higher for R. parkeri than "Ca. R. andeanae." Infection rates of R. parkeri were also higher, and "Ca. R. andeanae" lower, here compared to A. maculatum reported previously in Kansas and Oklahoma. As we continue to monitor infection rates and levels, we anticipate that understanding temporal changes will improve our awareness of human risk for spotted fever rickettsioses. Further, these data may lead to additional studies to evaluate potential interactions among sympatric Rickettsia species in A. maculatum at the population level.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

Climate change and pastoralism: impacts, consequences and adaptation.

The authors discuss the main climate change impacts on pastoralist societies, including those on rangelands, livestock and other natural resources, and their extended repercussions on food security, incomes and vulnerability. The impacts of climate change on the rangelands of the globe and on the vulnerability of the people who inhabit them will be severe and diverse, and will require multiple, simultaneous responses. In higher latitudes, the removal of temperature constraints might increase pasture production and livestock productivity, but in tropical arid lands, the impacts are highly location specific, but mostly negative. The authors outline several adaptation options, ranging from implementing new technical practices and diversifying income sources to finding institutional support and introducing new market mechanisms, all of which are pivotal for enhancing the capacity of pastoralists to adapt to climate variability and change. Due to the dynamism of all the changes affecting pastoral societies, strategies that lock pastoral societies into specified development pathways could be maladaptive. Flexible and evolving combinations of practices and policies are the key to successful pastoral adaptation.

Les auteurs examinent les principaux effets du changement climatique sur les sociétés pastorales, en particulier ceux qui affectent les prairies, le bétail et d'autres ressources naturelles ainsi que les répercussions durables sur la sécurité alimentaire, sur les revenus et sur la vulnérabilité des populations. Le changement climatique va profondément et diversement affecter les prairies de la planète et le degré de vulnérabilité des personnes qui y vivent, ce qui imposera de déployer des réponses multiples et simultanées. Si dans les latitudes plus élevées, la suppression de certaines contraintes liées aux températures permet d'augmenter la production d'herbage et d'accroître la productivité du bétail, dans les terres arides tropicales les effets du climat, très spécifiques selon les endroits, sont majoritairement négatifs. Les diverses solutions adaptatives mises en avant par les auteurs, depuis la mise en oeuvre de nouvelles techniques et la diversification des sources de revenus jusqu'à la recherche de soutiens institutionnels et la création de nouveaux mécanismes de marché, sont toutes déterminantes pour améliorer la capacité des pasteurs à s'adapter à la variabilité et au changement climatiques. En raison du caractère dynamique des changements affectant les sociétés pastorales, les stratégies consistant à confiner ces sociétés dans des tracés spécifiques de développement risquent de s'avérer contreproductives en termes d'adaptation. Un assortiment souple et évolutif de pratiques et de politiques est la clé d'une adaptation pastorale réussie.

Los autores examinan los principales efectos del cambio climático sobre las sociedades pastorales, en particular los que afectan a las tierras de pasto, el ganado y otros recursos naturales, así como sus repercusiones más indirectas sobre la seguridad alimentaria, los ingresos y la vulnerabilidad. El cambio climático traerá consigo diversos efectos de gravedad que influirán en los pastizales del planeta y la vulnerabilidad de quienes viven de ellos, efectos que exigirán múltiples respuestas simultáneas. En altas latitudes, la desaparición de las limitaciones ligadas a la temperatura podría deparar una mayor producción de los pastizales y con ello una mayor productividad del ganado, pero en las tierras áridas tropicales los efectos dependerán en gran medida de las condiciones de cada localidad y serán mayormente negativos. Los autores destacan varias posibilidades de adaptación, desde la aplicación de nuevos procedimientos técnicos y la diversificación de las fuentes de ingresos hasta la obtención de apoyo institucional, pasando por la instauración de nuevos mecanismos de mercado, todas ellas soluciones cruciales para dotar a las sociedades de pastores de mayor capacidad de adaptación a la variabilidad y la evolución del clima. Teniendo en cuenta el dinamismo de cuantos cambios afectan a las sociedades pastorales, toda estrategia que las encorsete en una u otra vía específica de desarrollo podría resultar inadaptada. La clave para una adaptación fructífera de esas sociedades estriba en combinaciones de prácticas y políticas que sean flexibles y evolucionen en el tiempo.

Pamidronate treatment for osteogenesis imperfecta in black South Africans.

BACKGROUND: Osteogenesis imperfecta is a heritable disorder of bone connective tissue. Type III has a high incidence in the black pop-ulation of South Africa. Affected people experience numerous fractures, bone pain and progressive disability. Until the introduction of bisphosphonates to reduce fracture incidence, treatment revolved around orthopaedic and supportive care. Objective. To assess the subjective attitude of patients towards pamidronate treatment. METHODS: Thirty black patients with osteogenesis imperfecta type III treated at Universitas Hospital were approached and 26 were included in this study. Patients or their parents were interviewed using a standardised researcher-administered questionnaire, either in person or by telephone. RESULTS: Most patients reported a reduction in symptoms, a feeling of increased wellbeing, increased strength and rated the pamidronate treatment highly. The intravenous route of administration and the side-effects experienced were bearable. Overall all patients would recommend this treatment to other affected persons. CONCLUSION: This is first study to look at bisphosphonate treatment for osteogenesis imperfecta type III in black South Africans. The treatment is well tolerated and highly rated by the patients. Reported improvements and side-effects are similar to those reported in other populations. Using this form of treatment in this population is supported by these findings.