190 research outputs found

    Inflammatory Mediators in Atherosclerotic Vascular Remodeling.

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    Atherosclerotic vascular disease remains the most common cause of ischemia, myocardial infarction, and stroke. Vascular function is determined by structural and functional properties of the arterial vessel wall, which consists of three layers, namely the adventitia, media, and intima. Key cells in shaping the vascular wall architecture and warranting proper vessel function are vascular smooth muscle cells in the arterial media and endothelial cells lining the intima. Pathological alterations of this vessel wall architecture called vascular remodeling can lead to insufficient vascular function and subsequent ischemia and organ damage. One major pathomechanism driving this detrimental vascular remodeling is atherosclerosis, which is initiated by endothelial dysfunction allowing the accumulation of intimal lipids and leukocytes. Inflammatory mediators such as cytokines, chemokines, and modified lipids further drive vascular remodeling ultimately leading to thrombus formation and/or vessel occlusion which can cause major cardiovascular events. Although it is clear that vascular wall remodeling is an elementary mechanism of atherosclerotic vascular disease, the diverse underlying pathomechanisms and its consequences are still insufficiently understood

    Double radio peak and non-thermal collimated ejecta in RS Ophiuchi following the 2006 outburst

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    We report Multi-Element Radio-Linked Interferometer Network, Very Large Array, One-Centimetre Radio Array, Very Long Baseline Array (VLBA), Effelsberg and Giant Metrewave Radio Telescope observations beginning 4.5 days after the discovery of RS Ophiuchi undergoing its 2006 recurrent nova outburst. Observations over the first 9 weeks are included, enabling us to follow spectral development throughout the three phases of the remnant development. We see dramatic brightening on days 4 to 7 at 6 GHz and an accompanying increase in other bands, particularly 1.46 GHz, consistent with transition from the initial ‘free expansion’ phase to the adiabatic expansion phase. This is complete by day 13 when the flux density at 5 GHz is apparently declining from an unexpectedly early maximum (compared with expectations from observations of the 1985 outburst). The flux density recovered to a second peak by approximately day 40, consistent with behaviour observed in 1985. At all times the spectral index is consistent with mixed non-thermal and thermal emission. The spectral indices are consistent with a non-thermal component at lower frequencies on all dates, and the spectral index changes show that the two components are clearly variable. The estimated extent of the emission at 22 GHz on day 59 is consistent with the extended east and west features seen at 1.7 GHz with the VLBA on day 63 being entirely non-thermal. We suggest a two-component model, consisting of a decelerating shell seen in mixed thermal and non-thermal emission plus faster bipolar ejecta generating the non-thermal emission, as seen in contemporaneous VLBA observations. Our estimated ejecta mass of 4 ± 2 × 10−7 M⊙ is consistent with a white dwarf (WD) mass of 1.4 M⊙. It may be that this ejecta mass estimate is a lower limit, in which case a lower WD mass would be consistent with the data

    The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

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    Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

    Hanford Site ground-water monitoring for July through December 1987

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    The Pacific Northwest Laboratory monitors ground-water quality at the Hanford Site for the US Department of Energy to assess the impact of Site operations on the environment. Work undertaken between July and December 1987 included monitoring ground-water elevations across the Site, monitoring hazardous chemicals and radionuclides in ground water, geochemical evaluations of unconfined ground-water data, and calibration of ground-water flow and transport models. Water levels continued to rise in areas receiving increased recharge (e.g., beneath B Pond) and decline in areas where the release of water to disposal facilities has been terminated (e.g., U Pond). The major areas of ground-water contamination defined by monitoring activities are (1) carbon tetrachloride in the 200-West Area; (2) cyanide in and north of the 200-East and 200-West Areas; (3) hexavalent chromium contamination in the 100-B, 100-D, 100-F, 100-H, 100-K, and 200-West Areas; (4) chlorinated hydrocarbons in the vicinity of the Central Landfill and 300 Area; (5) uranium in the 100-F, 100-H, 200-West, and 300 Areas; and (6) tritium and nitrate across the Site. The MINTEQ geochemical code was used to identify chemical reactions that may be affecting the concentrations of dissolved hazardous chemicals in the unconfined ground water. Results indicate that many cations are present mainly as dissolved carbonate complexes and that a majority of the ground-water samples are in near equilibrium with carbonate minerals (e.g., calcite, dolomite, otavite)

    Assessing the Effects of Personal Characteristics and Context on U.S. House Speakers’ Leadership Styles, 1789-2006

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    Research on congressional leadership has been dominated in recent decades by contextual interpretations that see leaders’ behavior as best explained by the environment in which they seek to exercise leadership—particularly, the preference homogeneity and size of their party caucus. The role of agency is thus discounted, and leaders’ personal characteristics and leadership styles are underplayed. Focusing specifically on the speakers of the U.S. House of Representatives from the first to the 110th Congress, we construct measures of each speaker’s commitment to comity and leadership assertiveness. We find the scores reliable and then test the extent to which a speaker’s style is the product of both political context and personal characteristics. Regression estimates on speakers’ personal assertiveness scores provide robust support for a context-plus-personal characteristics explanation, whereas estimates of their comity scores show that speakers’ personal backgrounds trump context

    Postoperative outcomes in oesophagectomy with trainee involvement

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    BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery
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