Alien Registration- Perron, Marie A. (Auburn, Androscoggin County)

https://digitalmaine.com/alien_docs/31014/thumbnail.jp

Time-trends and treatment gaps in the antithrombotic management of patients with atrial fibrillation after percutaneous coronary intervention: Insights from the CHUM AF-STENT Registry.

BACKGROUND: The management of atrial fibrillation and flutter (AF) patients undergoing percutaneous coronary intervention (PCI) has undergone a rapid recent evolution. In 2016, the Canadian Cardiovascular Society (CCS) published expert recommendations to help guide clinicians in balancing bleeding and thrombotic risks in these patients. HYPOTHESIS: Antithrombotic regimen prescriptions for AF patients undergoing PCI evolved after the publication of the 2016 CCS AF guidelines. METHODS: A prospective cohort of AF patients undergoing PCI with placement of a coronary stent from a single tertiary academic center was analyzed for the recommended antithrombotic regimen at discharge. Prescribing behavior was compared between three time periods (Cohort A [2010-2011]; Cohort B [2014-2015]; Cohort C [2017]) using the χ2 test. In addition, antithrombotic management in Cohorts B and C were compared to guideline-recommended therapy. RESULTS: A total of 459 patients with AF undergoing PCI were identified. Clinical and procedural characteristics were similar between cohorts, with the exception of an increase in drug-eluting stent (DES) use over time (P < .01). Overall, the rate of oral anticoagulation (OAC) increased over time (P < .01), associated with an increase in nonvitamin K OAC prescription (P < .01) and a concomitant decrease in vitamin K antagonist prescription (P < .01). Despite this, the overall rate of anticoagulation remains below what would be predicted with perfect guideline compliance (75% vs 94%, P < .01). CONCLUSION: There has been a dramatic shift in clinical practice for AF patients requiring PCI, with increases in prescription of OAC even in the context of an increase in the use of DES. However, room for further practice optimization still exists

Fill in Fabrics: Body-Aware Self-Supervised Inpainting for Image-Based Virtual Try-On

Previous virtual try-on methods usually focus on aligning a clothing item with a person, limiting their ability to exploit the complex pose, shape and skin color of the person, as well as the overall structure of the clothing, which is vital to photo-realistic virtual try-on. To address this potential weakness, we propose a fill in fabrics (FIFA) model, a self-supervised conditional generative adversarial network based framework comprised of a Fabricator and a unified virtual try-on pipeline with a Segmenter, Warper and Fuser. The Fabricator aims to reconstruct the clothing image when provided with a masked clothing as input, and learns the overall structure of the clothing by filling in fabrics. A virtual try-on pipeline is then trained by transferring the learned representations from the Fabricator to Warper in an effort to warp and refine the target clothing. We also propose to use a multi-scale structural constraint to enforce global context at multiple scales while warping the target clothing to better fit the pose and shape of the person. Extensive experiments demonstrate that our FIFA model achieves state-of-the-art results on the standard VITON dataset for virtual try-on of clothing items, and is shown to be effective at handling complex poses and retaining the texture and embroidery of the clothing

Modeling the carbon isotope signatures of methane and dissolved inorganic carbon to unravel mineralization pathways in boreal lake sediments

Vertical profiles of the concentration and isotopic composition (δ13C) of methane (CH4) and dissolved inorganic carbon (DIC), as well as of ancillary parameters, were obtained in the top 25 cm sediment column of a seasonally anoxic basin from an oligotrophic boreal lake. Modeling the profiles of CH4 and DIC concentrations and those of their δ13C signatures with reaction-transport equations allowed us to determine the organic matter (OM) degradation rates according to various reactions and to constrain the in situ isotopic fractionation factors and diffusivity coefficients of CH4 and DIC. This exercise reveals inter alia that (i) CH4 production occurs below 5 cm depth, with the highest production rate between 5 and 7.5 cm depth, (ii) all CH4 is produced through hydrogenotrophy, and (iii) methanogenesis yields a production rate of CH4 about three times greater than that of DIC. This latter observation indicates either that fermentation of OM is not the exclusive source of H2 sustaining hydrogenotrophy, or that the commonly assumed model molecule CH2O does not adequately represent the fermenting OM, since its fermentation yields identical rates of CH4 and DIC production. The porewater profiles of Fe and View the MathML source suggest that some H2 may be produced during the reoxidation of reduced sulfur by Fe(III), but the rate of H2 production via this process, if active, would be insignificant in comparison to that required to sustain the estimated rate of hydrogenotrophy. We deduce that the imbalance between CH4 and DIC production rates is rather due to the fermentation of organic substrates that are more reduced than CH2O, i.e., having a negative average carbon oxidation state (COS). From the constraints on reaction rates and on fermentation pathways imposed by the δ13C data, we infer that the organic substrate fermenting between 5 and 7.5 cm depth should have a COS of −1.87. We thus submit that CH4 is produced in the sediments of the seasonally anoxic basin of our boreal lake through hydrogenotrophy coupled to the fermentation of reduced organic substrates that can be represented by a mixture of fatty acids (e.g. C16H32O2; COS of −1.75) and fatty alcohols (e.g., C16H34O; COS of −2.00). This study emphasizes the importance of characterizing the sedimentary OM undergoing mineralization in order to improve diagenetic model predictions of CH4 cycling in boreal lakes and of its significance in climate change

Distribution and sources of organic matter in surface marine sediments across the North American Arctic margin

As part of the International Polar Year research program, we conducted a survey of surface marine sediments from box cores along a section extending from the Bering Sea to Davis Strait via the Canadian Archipelago. We used bulk elemental and isotopic compositions, together with biomarkers and principal components analysis, to elucidate the distribution of marine and terrestrial organic matter in different regions of the North American Arctic margin. Marked regional contrasts were observed in organic carbon loadings, with the highest values (1 mg C m(-2) sediment) found in sites along Barrow Canyon and the Chukchi and Bering shelves, all of which were characterized by sediments with low oxygen exposure, as inferred from thin layers (\u3c2 \u3ecm) of Mn oxihydroxides. We found strong regional differences in inorganic carbon concentrations, with sites from the Canadian Archipelago and Lancaster Sound displaying elevated values (2-7 wt %) and highly depleted C-14 compositions consistent with inputs from bedrock carbonates. Organic carbon:nitrogen ratios, stable carbon isotopes, and terrigenous organic biomarkers (lignin phenols and cutin acids) all indicate marked regional differences in the proportions of marine and terrigenous organic matter present in surface sediments. Regions such as Barrow Canyon and the Mackenzie River shelf were characterized by the highest contributions of land-derived organic matter, with compositional characteristics that suggested distinct sources and provenance. In contrast, sediments from the Canadian Archipelago and Davis Strait had the smallest contributions of terrigenous organic matter and the lowest organic carbon loadings indicative of a high degree of post-depositional oxidation

A Synthetic Interaction Screen Identifies Factors Selectively Required for Proliferation and TERT Transcription in p53-Deficient Human Cancer Cells

Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi)-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53-) human cancer cells. We find that compared to p53-competent (p53+) human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53- but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells

The Human Gonadotropin Releasing Hormone Type I Receptor Is a Functional Intracellular GPCR Expressed on the Nuclear Membrane

The mammalian type I gonadotropin releasing hormone receptor (GnRH-R) is a structurally unique G protein-coupled receptor (GPCR) that lacks cytoplasmic tail sequences and displays inefficient plasma membrane expression (PME). Compared to its murine counterparts, the primate type I receptor is inefficiently folded and retained in the endoplasmic reticulum (ER) leading to a further reduction in PME. The decrease in PME and concomitant increase in intracellular localization of the mammalian GnRH-RI led us to characterize the spatial distribution of the human and mouse GnRH receptors in two human cell lines, HEK 293 and HTR-8/SVneo. In both human cell lines we found the receptors were expressed in the cytoplasm and were associated with the ER and nuclear membrane. A molecular analysis of the receptor protein sequence led us to identify a putative monopartite nuclear localization sequence (NLS) in the first intracellular loop of GnRH-RI. Surprisingly, however, neither the deletion of the NLS nor the addition of the Xenopus GnRH-R cytoplasmic tail sequences to the human receptor altered its spatial distribution. Finally, we demonstrate that GnRH treatment of nuclei isolated from HEK 293 cells expressing exogenous GnRH-RI triggers a significant increase in the acetylation and phosphorylation of histone H3, thereby revealing that the nuclear-localized receptor is functional. Based on our findings, we conclude that the mammalian GnRH-RI is an intracellular GPCR that is expressed on the nuclear membrane. This major and novel discovery causes us to reassess the signaling potential of this physiologically and clinically important receptor

Distribution and sources of organic matter in surface marine sediments across the North American Arctic margin

As part of the International Polar Year research program, we conducted a survey of surface marine sediments from box cores along a section extending from the Bering Sea to Davis Strait via the Canadian Archipelago. We used bulk elemental and isotopic compositions, together with biomarkers and principal components analysis, to elucidate the distribution of marine and terrestrial organic matter in different regions of the North American Arctic margin. Marked regional contrasts were observed in organic carbon loadings, with the highest values (1 mg C m(-2) sediment) found in sites along Barrow Canyon and the Chukchi and Bering shelves, all of which were characterized by sediments with low oxygen exposure, as inferred from thin layers (<2 cm) of Mn oxihydroxides. We found strong regional differences in inorganic carbon concentrations, with sites from the Canadian Archipelago and Lancaster Sound displaying elevated values (2-7 wt %) and highly depleted C-14 compositions consistent with inputs from bedrock carbonates. Organic carbon:nitrogen ratios, stable carbon isotopes, and terrigenous organic biomarkers (lignin phenols and cutin acids) all indicate marked regional differences in the proportions of marine and terrigenous organic matter present in surface sediments. Regions such as Barrow Canyon and the Mackenzie River shelf were characterized by the highest contributions of land-derived organic matter, with compositional characteristics that suggested distinct sources and provenance. In contrast, sediments from the Canadian Archipelago and Davis Strait had the smallest contributions of terrigenous organic matter and the lowest organic carbon loadings indicative of a high degree of post-depositional oxidation.Keywords: Arctic margins, sedimentary organic matter, radiocarbon, organic biomarker

Induction of Selective Blood-Tumor Barrier Permeability and Macromolecular Transport by a Biostable Kinin B1 Receptor Agonist in a Glioma Rat Model

Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg9BK (LDBK) and SarLys[dPhe8]desArg9BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T1-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites