46 research outputs found

    Environmental Restoration - Flood Plains vs Potholes

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    Formal ratification of subseries for the Pleistocene Series of the Quaternary System

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    The Pleistocene Series/Epoch of the Quaternary System/Period has been divided unofficially into three subseries/subepochs since at least the 1870s. On 30 January, 2020, the Executive Committee of the International Union of Geological Sciences ratified two proposals approved by the International Commission on Stratigraphy formalizing: 1) the Lower Pleistocene Subseries, comprising the Gelasian Stage and the superjacent Calabrian Stage, with a base defined by the GSSP for the Gelasian Stage, the Pleistocene Series, and the Quaternary System, and currently dated at 2.58 Ma; and 2) the term Upper Pleistocene, at the rank of subseries, with a base currently undefined but provisionally dated at ~129 ka. Defining the Upper Pleistocene Subseries and its corresponding stage with a GSSP is in progress. The Middle Pleistocene Subseries is defined by the recently ratified GSSP for the Chibanian Stage currently dated at 0.774 Ma. These ratifications complete the official division of the Pleistocene into three subseries/subepochs, in uniformity with the similarly subdivided Holocene Series/Epoch

    Mid-Infrared Laser Ablation of Stratum Corneum Enhances In Vitro Percutaneous Transport of Drugs

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    The precise removal of stratum corneum from cadaveric swine skin by a mid-infrared erbium: yttrium scandium gallium garnet laser (λ = 2.79 μm; 250 μsec pulse width) was assessed by electrical resistance measurements and documented by histology. The effects of stratum corneum removal by laser ablation and by adhesive tape-stripping on the in vitro penetration of 3H-hydrocortisone and 125I-γ-interferon were determined. Excised swine skin was irradiated with laser (1 J/cm2 31 mJ/pulse; 1 Hz; 2mm spot diameter). For skin penetration studies, laser pulses were delivered to discrete 2-mm areas to ablate up to 12.6% of the total 3-cm2 stratum corneum diffusional area. Franz in vitro skin penetration chambers were used to measure the cumulative 48-h penetration of 3H-hydrocortisone and 125I-γ-interferon in laser-treated and tape-stripped skin. Electrical resistance measurements and histologic studies demonstrated that 10-14 laser pulses at the above energy density were required to abolish skin resistance and selectively ablate stratum corneum without damage to adjacent dermal structures. Laser ablation of 12.6% of the surface area of stratum corneum produced a 2.8 and 2.1-times increase in permeability constant (kp) for 3H-hydrocortisone and 125I-λ-interferon, respectively. These studies demonstrate that a pulsed mid-infrared laser can reliably and precisely remove the stratum corneum, facilitating penetration of large molecules such as 125I-λ-interferon that cannot penetrate intact skin. This new technique may be useful for basic and clinical investigation of skin barrier properties

    Persistent suborbital climate variability in marine isotope stage 5 and termination II

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    New surface water records from two high sedimentation rate sites, located in the western subtropical North Atlantic near the axis of the Gulf Stream, provide clear evidence of suborbital climate variations through marine isotope stage (MIS) 5 persisting even into the warm peak of the interglaciation (substage 5e). We found that the amplitude of suborbital climate oscillations did not vary significantly for the whole of MIS 5, implying that ice volume has little or no influence on the amplitude of suborbital climate variability in this region. Although some records suggest that longer suborbital variations (4–10 kyr) during MIS 5 are linked to deepwater changes, none of the existing records is of sufficient resolution to assess if a linkage occurred for oscillations shorter than 4 kyr. However, when examined in conjunction with published data from the Norwegian Sea, new evidence from the subpolar North Atlantic suggests that coupled surface-deepwater oscillations occurred during the penultimate deglaciation. This supports the hypothesis that during glacial and deglacial times, ocean-ice interactions and deepwater variability amplify suborbital climate change at higher latitudes. We suggest that during the penultimate deglaciation the North Atlantic deepwater source varied between Nordic Sea and open North Atlantic locations, in parallel with surface temperature oscillations

    Recent Engagements with Adam Smith and the Scottish Enlightenment

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    Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

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    Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

    Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

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    Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p
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