Coronary arterial findings after accidental death immediately after successful percutaneous transluminal coronary angioplasty

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Maintenance of increased coronary blood flow in excess of demand by nisoldipine administered as an intravenous infusion

Systemic and hemodynamic effects of nisoldipine, administered as a 4.5-micrograms/kg intravenous bolus over 3 minutes followed immediately by an infusion of 0.2 microgram/kg/min over 30 minutes, were studied in 13 patients undergoing diagnostic catheterization for suspected coronary artery disease or follow-up catheterization after coronary angioplasty. Responses to the drug tended to be exaggerated in the first 8 minutes of the infusion, but thereafter produced a steady state, with heart rate increased by 14 +/- 3% at 16 minutes and by 15 +/- 3% at 24 minutes (p less than 0.05), mean aortic pressure decreased 12 +/- 2% and 13 +/- 3% at the same times (p less than 0.05) and coronary venous blood flow increased by 31 +/- 5% and 34 +/- 6% (p less than 0.05). Myocardial oxygen consumption and the heart rate-systolic aortic pressure product were unchanged and cardiac output and stroke volume were significantly increased. Study during matched coronary sinus pacing produced similar trends. Nisoldipine is a potent coronary and peripheral vasodilator that maintains an increase in myocardial oxygen supply in excess of demand when given as an intravenous infusion

Coronary and systemic hemodynamic effects of intravenous nisoldipine

Systemic and coronary hemodynamic effects of the new dihydropyridine calcium antagonist nisoldipine were studied over a 30-minute period in 12 patients with angina pectoris. Previously instituted beta-blocker therapy was continued. Nisoldipine was administered in an intravenous bolus of 6 micrograms/kg over 3 minutes. Heart rate increased as mean aortic pressure and systemic vascular resistance decreased in all patients. Cardiac output increased significantly, from 5.8 +/- 0.3 to 7.9 +/- 0.5 liters/min, 10 minutes after nisoldipine infusion. These trends were maintained over the 30-minute observation period. Coronary sinus blood flow increased from 103 +/- 11 to 139 +/- 13 ml/min immediately after nisoldipine, but had returned to the control level by 30 minutes, as had the reduction in coronary vascular resistance. Myocardial oxygen consumption and heart rate-systolic blood pressure product did not change significantly. Nisoldipine is a potent peripheral and coronary vasodilator free of major myocardial depressant effects after acute intravenous administration. The systemic vasodilatory effects appear to outlast the coronary effects over 30 minutes

Amyloid-β oligomerization monitored by single-molecule stepwise photobleaching

A major hallmark of Alzheimer’s disease is the misfolding and aggregation of the amyloid- β peptide (Aβ). While early research pointed towards large fibrillar- and plaque-like aggregates as being the most toxic species, recent evidence now implicates small soluble Aβ oligomers as being orders of magnitude more harmful. Techniques capable of characterizing oligomer stoichiometry and assembly are thus critical for a deeper understanding of the earliest stages of neurodegeneration and for rationally testing next-generation oligomer inhibitors. While the fluorescence response of extrinsic fluorescent probes such as Thioflavin-T have become workhorse tools for characterizing large Aβ aggregates in solution, it is widely accepted that these methods suffer from many important drawbacks, including an insensitivity to oligomeric species. Here, we integrate several biophysics techniques to gain new insight into oligomer formation at the single-molecule level. We showcase single-molecule stepwise photobleaching of fluorescent dye molecules as a powerful method to bypass many of the traditional limitations, and provide a step-by-step guide to implementing the technique in vitro. By collecting fluorescence emission from single Aβ(1–42) peptides labelled at the N-terminal position with HiLyte Fluor 555 via wide-field total internal reflection fluorescence (TIRF) imaging, we demonstrate how to characterize the number of peptides per single immobile oligomer and reveal heterogeneity within sample populations. Importantly, fluorescence emerging from Aβ oligomers cannot be easily investigated using diffraction-limited optical microscopy tools. To assay oligomer activity, we also demonstrate the implementation of another biophysical method involving the ratiometric imaging of Fura-2-AM loaded cells which quantifies the rate of oligomer-induced dysregulation of intracellular Ca2+ homeostasis. We anticipate that the integrated single-molecule biophysics approaches highlighted here will develop further and in principle may be extended to the investigation of other protein aggregation systems under controlled experimental conditions

Advantages of a Modular Mars Surface Habitat Approach

Early crewed Mars mission concepts developed by the National Aeronautics and Space Administration (NASA) assumed a single, large habitat would house six crew members for a 500-day Mars surface stay. At the end of the first mission, all surface equipment, including the habitat, -would be abandoned and the process would be repeated at a different Martian landing site. This work was documented in a series of NASA publications culminating with the Mars Design Reference Mission 5.0 (NASA-SP-2009-566). The Evolvable Mars Campaign (EMC) explored whether re-using surface equipment at a single landing site could be more affordable than the Apollo-style explore-abandon-repeat mission cadence. Initial EMC assumptions preserved the single, monolithic habitat, the only difference being a new requirement to reuse the surface habitat for multiple expedition crews. A trade study comparing a single large habitat versus smaller, modular habitats leaned towards the monolithic approach as more mass-efficient. More recent work has focused on the operational aspects of building up Mars surface infrastructure over multiple missions, and has identified compelling advantages of the modular approach that should be considered before making a final decision. This paper explores Mars surface mission operational concepts and integrated system analysis, and presents an argument for the modular habitat approach

Three dimensional intravascular ultrasonic assessment of the local mechanism of restenosis after balloon angioplasty

OBJECTIVE: To assess the mechanism of restenosis after balloon angioplasty. DESIGN: Prospective study. PATIENTS: 13 patients treated with balloon angioplasty. INTERVENTIONS: 111 coronary subsegments (2 mm each) were analysed after balloon angioplasty and at a six month follow up using three dimensional intravascular ultrasound (IVUS). MAIN OUTCOME MEASURES: Qualitative and quantitative IVUS analysis. Total vessel (external elastic membrane), plaque, and lumen volume were measured in each 2 mm subsegment. Delta values were calculated (follow up - postprocedure). Remodelling was defined as any (positive or negative) change in total vessel volume. RESULTS: Positive remodelling was observed in 52 subsegments while negative remodelling occurred in 44. Remodelling, plaque type, and dissection were heterogeneously distributed along the coronary segments. Plaque composition was not associated with changes in IVUS indices, whereas dissected subsegments had a greater increase in total vessel volume than those without dissection (1.7 mm(3) v -0.33 mm(3), p = 0.04). Change in total vessel volume was correlated with changes in lumen (p < 0.05, r = 0.56) and plaque volumes (p < 0.05, r = 0.64). The site with maximum lumen loss was not the same site as the minimum lumen area at follow up in the majority (n = 10) of the vessels. In the multivariate model, residual plaque burden had an influence on negative remodelling (p = 0.001, 95% confidence interval (CI) -0.391 to -0.108), whereas dissection had an effect on total vessel increase (p = 0.002, 95% CI 1.168 to 4.969). CONCLUSIONS: The mechanism of lumen renarrowing after balloon angioplasty appears to be determined by unfavourable remodelling. However, different patterns of remodelling may occur in individual injured coronary segments, which highlights the complexity and influence of local factors in the restenotic process

Current-carrying cosmic string loops 3D simulation: towards a reduction of the vorton excess problem

The dynamical evolution of superconducting cosmic string loops with specific equations of state describing timelike and spacelike currents is studied numerically. This analysis extends previous work in two directions: first it shows results coming from a fully three dimensional simulation (as opposed to the two dimensional case already studied), and it now includes fermionic as well as bosonic currents. We confirm that in the case of bosonic currents, shocks are formed in the magnetic regime and kinks in the electric regime. For a loop endowed with a fermionic current with zero-mode carriers, we show that only kinks form along the string worldsheet, therefore making these loops slightly more stable against charge carrier radiation, the likely outcome of either shocks or kinks. All these combined effects tend to reduce the number density of stable loops and contribute to ease the vorton excess problem. As a bonus, these effects also may provide new ways of producing high energy cosmic rays.Comment: 11 pages, RevTeX 4 format, 8 figures, submitted to PR

Topology and Computational Performance of Attractor Neural Networks

To explore the relation between network structure and function, we studied the computational performance of Hopfield-type attractor neural nets with regular lattice, random, small-world and scale-free topologies. The random net is the most efficient for storage and retrieval of patterns by the entire network. However, in the scale-free case retrieval errors are not distributed uniformly: the portion of a pattern encoded by the subset of highly connected nodes is more robust and efficiently recognized than the rest of the pattern. The scale-free network thus achieves a very strong partial recognition. Implications for brain function and social dynamics are suggestive.Comment: 2 figures included. Submitted to Phys. Rev. Letter