MK-0448, a Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics and Pharmacodynamic Electrophysiology in Experimental Animal Models and in Humans.

BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0.1 mg/kg. These data led to a two-part first-in-human study: Part I evaluated safety and pharmacokinetics, and Part II was an invasive electrophysiologic (EP) study in healthy subjects. MK-0448 was well-tolerated with mild adverse experiences, most commonly irritation at the injection site. During the EP study, ascending doses of MK-0448 were administered, but no increases in atrial or ventricular refractoriness were detected despite achieving plasma concentrations in excess of 2 μM. Follow-up studies in normal anesthetized dogs designed to assess the influence of autonomic tone demonstrated that prolongation of atrial refractoriness with MK-0448 was markedly attenuated in the presence of vagal nerve simulation, suggesting that the effects of I(Kur) blockade on atrial repolarization may be negated by enhanced parasympathetic neural tone. CONCLUSIONS: -The contribution of I(Kur) to human atrial electrophysiology is less prominent than in preclinical models and therefore is likely to be of limited therapeutic value for the prevention of atrial fibrillation

Mulit-Photon Events with Large Missing energy in e+e- collisions at sqrt(s)=192-209 GeV

Events with a final state consisting of two or more photons and large missing transverse energy have been observed in e+e- collisions at centre-of-mass energies in the range 192 - 209 GeV using the OPAL detector at LEP. Cross-section measurements are performed within the kinematic acceptance of the selection and compared with the expectation from the Standard Model process e+e- -> nu nu gamma gamma(gamma). No evidence for new physics contributions to this final state is observed. Upper limits on sigma (e+e- -> XX) BR^2(X -> Ygamma) are derived for the case of stable and invisible Y. In the case of massive Y the combined limits obtained from all the data range from 10 fb to 60 fb, while for the special case of massless Y the range is 20 fb to 40 fb. The limits apply to pair production of excited neutrions (X=nu^*,Y=nu), to neutralino production (X=~chi^0_2, Y=~chi^0_1) and to supersymmetric models in which X=~chi^0_1 and Y=~G is a light gravitino.Comment: 18 pages, 4 figures, Submitted to Phys. Letts

Roadmap for Enhanced Languages and Methods to Aid Verification

This roadmap describes ways that researchers in four areas — specification languages, program generation, correctness by construction, and programming languages — might help further the goal of verified software. It also describes what advances the “verified software” grand challenge might anticipate or demand from work in these areas. That is, the roadmap is intended to help foster collaboration between the grand challenge and these research areas. A common goal for research in these areas is to establish language designs and tool architectures that would allow multiple annotations and tools to be used on a single program. In the long term, researchers could try to unify these annotations and integrate such tools

Visual steering commands for trade space exploration: userguided sampling with example

Recent advancements in computing powe

Interline Transfer CCD Camera

An interline CCD sensing device for use in a camera system, includes an imaging area sensitive to impinging light, for generating charges corresponding to the intensity of the impinging light. Sixteen independent registers R1 - R16 sequentially receive the interline data from the imaging area, corresponding to the generated charges. Sixteen output amplifiers S1 - S16 and sixteen ports P1 - P16 for sequentially transferring the interline data, one pixel at a time, in order to supply a desired image transfer speed. The imaging area is segmented into sixteen independent imaging segments A1 - A16, each of which corresponds to one register, on output amplifier, and one output port. Each one of the imaging segments A1 - A16 includes an array of rows and columns of pixels. Each pixel includes a photogate area, an interline CCD channel area, and an anti-blooming area. The anti-blooming area is, in turn, divided into an anti-blooming barrier and an anti-blooming drain

Trade Space Exploration of Satellite Datasets Using a Design by Shopping Paradigm

Abstract—One of the goals of early stage conceptual design is to execute broad trade studies of possible design concepts, evaluating them for their capability to meet minimum requirements, and choosing the one that best satisfies the goals of the project. To support trade space exploration, we have developed the Advanced Trade Space Visualizer (ATSV) that facilitates a design by shopping paradigm, which allows a decision-maker to form a preference a posteriori and use this preference to select a preferred satellite. Design automation has allowed us to implement this paradigm, since a large number of designs can be synthesized in a short period of time. The ATSV uses multidimensional visualization techniques, preference shading

Member ASME,

The use of visualization to support engineering design and decision-making is gaining considerable attention as the requisite computer tools and technologies become more readily available. Companies such as Chrysler �1�, Raytheon �2�, and Boeing �3,4