Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Large reference displacement analysis of composite plates. Part II: Computer implementation

This investigation concerns itself with the computer implementation of the dynamic formulation of thin laminated composite plates consisting of layers of orthotropic laminae that undergo large arbitrary rigid body displacements and small elastic deformations. A finite element preprocessor computer program is developed to automatically generate the invariants of the laminae, which may have arbitrary orientations. The laminae invariants are then used to obtain the invariants of the elements and the composite laminated plate. The consistent and lumped mass formulations of the invariants of motion of composite plates are compared and it is concluded that the two methods are comparable, if a fine enough finite element mesh is used. The structure of the dynamic equations of motion, based on the formulation presented in Part I of this paper, is examined. Non-linear centrifugal and Coriolis forces arising as the result of the finite rotations of the laminae are defined, and the solution schemes of the resulting non-linear differential equations of motion are discussed. Numerical examples illustrating the differences between homogeneous isotropic and laminated composite plates are presented. An RSSR (Revolute-Spherical-Spherical-Revolute) mechanism is used in the numerical examples, with the coupler modelled as a laminated plate flexible body. It is found that the inertia of the plate contributed greatly to the transverse deformation. The effects of laminae orientation is also investigated.     

Exploring the Interaction between Java's Implicitly Thrown Exceptions and Instruction Scheduling

The frequent occurrence of implicitly thrown exceptions poses one of the challenges present in a Java compiler. Not only do these implicitly thrown exceptions directly affect the performance by requiring explicit checks, they also indirectly impact the performance by restricting code movement in order to satisfy the precise exception model in Java. In particular, instruction scheduling is one transformation that is restricted by implicitly thrown exceptions due to the heavy reliance on reordering instructions to exploit maximum hardware performance. The goal of this study is two-fold: first, investigate the degree to which implicitly thrown exceptions in Java hinder instruction scheduling, and second, find new techniques for allowing more efficient execution of Java programs containing implicitly thrown exceptions. Experimental results show that with aggressive scheduling techniques, such as superblock scheduling, the negative performance impact can be greatly reduced.     

Formal Analysis of Multiparty Contract Signing

We analyze the multiparty contract-signing protocols of Garay and MacKenzie (GM) and of Baum and Waidner (BW). We use a finite-state tool, Mocha, which allows specification of protocol properties in a branching-time temporal logic with game semantics. While our analysis does not reveal any errors in the BW protocol, in the GM protocol we discover serious problems with fairness for four signers and an oversight regarding abuse-freeness for three signers. We propose a complete revision of the GM subprotocols in order to restore fairness.     

Thermophysical Properties of Binary Mixtures of R125 + R143a in Comparison with a Simple Prediction Method

The thermal diffusivity and sound speed of binary refrigerant mixtures of R143a (1,1,1-trifluoroethane) and R125 (pentafluoroethane) have been determined for both the saturated liquid and vapor phase using dynamic light scattering (DLS). Measurements were performed for four quite different mixture compositions over a wide temperature range from 293 to 345 K approaching the vapor-liquid critical point. The results obtained corroborate the usefulness of a simple prediction method for the determination of different thermophysical properties of multicomponent mixtures in the two-phase region up to the critical point. Besides the information on the properties for the pure components, the successful application of the prediction method is also based on an exact knowledge of the critical temperature. The composition dependence of the critical temperature has been determined by observation of the vanishing meniscus between liquid and vapor phases. The mixture results are discussed in detail and compared with available literature data.     

Landslide susceptibility mapping of the Sea to Sky transportation corridor, British Columbia, Canada: comparison of two methods

The Sea to Sky corridor stretches over a distance of 135?km into British Columbia’s Coast Mountains. The corridor has witnessed hundreds of historical and pre-historic landslides. In the last 154?years, 155 landslide events have been reported. The most common types of landslides are rockfalls and debris flows, which are small in volume, but can be quite damaging. These are more abundant in the southern part of the corridor where infrastructure is built close to steep slopes. Two different methods were adapted to create debris flow and rockfall/rock slide susceptibility maps. Both qualitative heuristic and fuzzy logic susceptibility maps showed a similar distribution of susceptibility zones, especially high susceptibility. Correlation of high susceptibility zones with occurrence of historical and mapped geological landslide events was very good. Success rate curves were calculated for extrapolated zones of initiation for debris flow and rockfall/rock slide deposits. Success rate curves were better for debris flow than rockfall/rockslide maps.     

Strategic decision making for multiple-generation product lines using dynamic state variable models: The cannibalization case

Multiple-generation product lines require carefully planned strategies. Under a multiple-generation product development strategy, companies introduce a line of products to the market instead of introducing a single product to better utilize technology assets and resources in an elongated time span. For such product development and launch scenarios, cannibalization can occur, however. That is, multiple product generations compete in the same market and partition the company's market shares. In the paper, we propose a new framework to predict the sales and introduction timing for every product generation in a multiple-generation product line while considering cannibalization. We demonstrate a case study implementing the proposed framework on Apple Inc.’s iPhone product line. The results show that the forecast performance of the model matches the realized data. Moreover, because the proposed framework is not computationally prohibitive, it can be used widely.