Electrophysiologic mechanisms of antiarrhythmic efficacy of a sotalol and class Ia drug combination: elimination of reverse use dependence

We have generated a C-terminally-truncated form of recombinant tissue inhibitor of metalloproteinases-2 (designated rTIMP-2 delta) in which the region of the inhibitor extending from residue 128 to 194 and including 3 of the 6 disulfide bonds is deleted. rTIMP-2 and rTIMP-2 delta had similar inhibitory activities toward interstitial collagenase and inhibited the activation of the precursor form of matrix metalloproteinase-2 (proMMP-2). rTIMP-2 also bound with high affinity (Kd 0.99 nM) to HT1080 human fibrosarcoma cells treated with 12-O-tetradecanoyl-phorbol-13-acetate. However deletion of the C-terminal domain of TIMP-2 significantly lowered the cell surface binding affinity, with competition experiments indicating a 2 order of magnitude difference between rTIMP-2 and rTIMP-2 delta in the concentrations needed to displace 125I-labeled rTIMP-2 binding. These data indicate that the C-terminal domain of TIMP-2 is not required for the antimetalloproteinase activity but plays a major role in the high affinity cell surface binding of the inhibitor.     

Improved Method for Creating Time-Domain Unsteady Aerodynamic Models

Multidisciplinary aeroservoelastic interactions are studied by the combination of knowledge acquired in two main disciplines: aeroelasticity and servocontrols. In aeroelasticity, the doublet lattice method is used to calculate the unsteady aerodynamic forces for a range of reduced frequencies and Mach numbers on a business aircraft in the subsonic flight regime by use of NASTRAN software. For aeroservoelasticity studies, there is the need to conceive methods for these unsteady aerodynamic forces conversions from frequency into Laplace domain. A new method different from classical methods is presented, in which Chebyshev polynomials theories and their orthogonality properties are applied. In this paper, a comparison between flutter results expressed in terms of flutter speeds and frequencies obtained with our method with flutter results obtained with classical Padé and least squares methods is presented for a business aircraft at one Mach number and a range of reduced frequencies. It has been found that results obtained with our method are better in terms of average error than results obtained with the two classical methods here presented.     

Childhood ADHD symptoms and risk for cigarette smoking during adolescence: School adjustment as a potential mediator.

Although a large body of research suggests that children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for cigarette smoking during adolescence compared with their non-ADHD peers, much less research has examined why. The current study addressed this gap in the literature by examining middle school adjustment, broadly defined, as a possible mediator of the relation between childhood ADHD symptoms and cigarette smoking during middle adolescence (10th grade). Longitudinal data were collected from a community sample of 754 youth using self-report and parent report along with school records, and a novel statistical technique was used in the process of testing for mediation. Consistent with hypotheses, school adjustment was found to mediate the relation between childhood ADHD symptoms and later cigarette smoking, even after controlling for early externalizing problems. Results have implications for etiological theories of adolescent deviant behavior and suggest that successful smoking prevention programs targeting youth with ADHD should include a school adjustment component. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Seismic design of outrigger systems using equivalent energy design procedure

An outrigger system is an effective structural scheme that is commonly used in high‐rise construction to increase the stiffness of concrete core walls and to reduce the moment demand within the walls. Despite the on‐going use of outrigger systems around the world, a formal seismic design procedure is yet available. This paper presents an equivalent energy design procedure (EEDP) to design outrigger systems for seismic applications. Three prototype outrigger‐wall buildings of various heights are designed for Vancouver, Canada. Detailed finite element models are developed to assess the seismic performance of the prototype buildings and to assess the safety using the FEMA P695 methodology. The result shows that EEDP is an efficient method to design outrigger systems which results in structures that can achieve sufficient margin of safety against collapse and satisfy multiple performance objectives at different seismic hazard levels.