Biochemical and immunochemical analysis of the arrangement of connexin43 in rat heart gap junction membranes

A 43 × 10^3 M_r protein (designated connexin43 or Cx43) is a major constituent of heart gap junctions. The understanding of its arrangement in junctional membranes has been extended by means of site-directed antibodies raised against synthetic peptides of Cx43. These represent part of the first extracellular loop (EL-46), the cytoplasmic loop (CL-100), the second extracellular loop (EL-186) and carboxy-terminal sequences (CT-237 and CT-360). All of the antibodies raised reacted with their respective peptides and the Cx43 protein on Western blots. By immunoelectron microscopy two of the antibodies (CL-100 and CT-360) were shown to label the cytoplasmic surface of isolated gap junction membranes. Immunofluorescent labeling at locations of neonatal cardiac myocyte-myocyte apposition required an alkali/urea treatment when the EL-46 and EL-186 antibodies were used. Immunoblot analysis of endoproteinase Lys-C-digested gap junctions revealed that the Cx43 protein passed through the lipid bilayer four times. Alkaline phosphatase digestion of isolated junctions was used to show that the CT-360 antibody recognized many phosphorylated forms of Cx43. Our results unequivocally confirm models of the organization of Cx43 that were based on a more limited set of data and a priori considerations of the sequence

Current practice in project appraisal in Europe.

The work reported in this paper presents the results from the compilation of the national assessment practices in EU25 Member States and Switzerland. The work was completed as part of the current European Union 6th Framework project HEATCO (Developing Harmonised European Approaches for Transport Costing and Project Assessment), which has the objective of developing a set of harmonised guidelines for project assessment and transport costing at an EU level. This paper presents the starting point to this project. Based on the work described in this paper the HEATCO consortium will be developing common definitions and consistent valuation methods for the evaluation of TEN projects. Previous projects such as EUNET had conducted a similar review to the research presented in this paper. The key reason for repeating the research was the expansion of the EU to 25 countries in May 2004 and the fact that appraisal practices in many countries has evolved since the last survey. A proforma was designed and sent to country representatives to complete. This paper is based predominantly on the results that this data provided. The proforma focused specifically on the use of Cost Benefit Analysis in appraisal with the aim of identifying similarities and differences in country practice. Aside from the national appraisal framework the proforma also considered the individual impacts included in appraisal. The paper describes some of the similarities and differences in how construction costs, time savings, safety and environmental impacts are used across Europe. The paper then concludes with the key differences and similarities as identified by the analysis. This paper aims at providing an overview of the current appraisal practice and more country specific details are given in Odgaard et al (2005)

Network effects and total economic impact in transport appraisal

It is claimed that transport infrastructure projects have network effects which are not taken into account in the appraisal of these projects. This paper reviews the concept of network effects, relates this to transport appraisal practice, and links to the concept of ‘total economic impact’. The limitations of transport modelling and appraisal in estimating total economic impact are reviewed. Good quality appraisals should be capable of picking up relevant network effects in the transport market, but the state of the art remains limited on the linkages between transport and the wider economy

An Architectural Approach to Ensuring Consistency in Hierarchical Execution

Hierarchical task decomposition is a method used in many agent systems to organize agent knowledge. This work shows how the combination of a hierarchy and persistent assertions of knowledge can lead to difficulty in maintaining logical consistency in asserted knowledge. We explore the problematic consequences of persistent assumptions in the reasoning process and introduce novel potential solutions. Having implemented one of the possible solutions, Dynamic Hierarchical Justification, its effectiveness is demonstrated with an empirical analysis

Flexibly Instructable Agents

This paper presents an approach to learning from situated, interactive tutorial instruction within an ongoing agent. Tutorial instruction is a flexible (and thus powerful) paradigm for teaching tasks because it allows an instructor to communicate whatever types of knowledge an agent might need in whatever situations might arise. To support this flexibility, however, the agent must be able to learn multiple kinds of knowledge from a broad range of instructional interactions. Our approach, called situated explanation, achieves such learning through a combination of analytic and inductive techniques. It combines a form of explanation-based learning that is situated for each instruction with a full suite of contextually guided responses to incomplete explanations. The approach is implemented in an agent called Instructo-Soar that learns hierarchies of new tasks and other domain knowledge from interactive natural language instructions. Instructo-Soar meets three key requirements of flexible instructability that distinguish it from previous systems: (1) it can take known or unknown commands at any instruction point; (2) it can handle instructions that apply to either its current situation or to a hypothetical situation specified in language (as in, for instance, conditional instructions); and (3) it can learn, from instructions, each class of knowledge it uses to perform tasks.Comment: See http://www.jair.org/ for any accompanying file

Generating Generalized Distributions from Dynamical Simulation

We present a general molecular-dynamics simulation scheme, based on the Nose' thermostat, for sampling according to arbitrary phase space distributions. We formulate numerical methods based on both Nose'-Hoover and Nose'-Poincare' thermostats for two specific classes of distributions; namely, those that are functions of the system Hamiltonian and those for which position and momentum are statistically independent. As an example, we propose a generalized variable temperature distribution that designed to accelerate sampling in molecular systems.Comment: 10 pages, 3 figure

fgui: A Method for Automatically Creating Graphical User Interfaces for Command-Line R Packages

The fgui R package is designed for developers of R packages, to help rapidly, and sometimes fully automatically, create a graphical user interface for a command line R package. The interface is built upon the Tcl/Tk graphical interface included in R. The package further facilitates the developer by loading in the help files from the command line functions to provide context sensitive help to the user with no additional effort from the developer. Passing a function as the argument to the routines in the fgui package creates a graphical interface for the function, and further options are available to tweak this interface for those who want more flexibility.

A molecular-dynamics algorithm for mixed hard-core/continuous potentials

We present a new molecular-dynamics algorithm for integrating the equations of motion for a system of particles interacting with mixed continuous/impulsive forces. This method, which we call Impulsive Verlet, is constructed using operator splitting techniques similar to those that have been used successfully to generate a variety molecular-dynamics integrators. In numerical experiments, the Impulsive Verlet method is shown to be superior to previous methods with respect to stability and energy conservation in long simulations.Comment: 18 pages, 6 postscript figures, uses rotate.st

Fresh-Register Automata

What is a basic automata-theoretic model of computation with names and fresh-name generation? We introduce Fresh-Register Automata (FRA), a new class of automata which operate on an infinite alphabet of names and use a finite number of registers to store fresh names, and to compare incoming names with previously stored ones. These finite machines extend Kaminski and Francez’s Finite-Memory Automata by being able to recognise globally fresh inputs, that is, names fresh in the whole current run. We exam-ine the expressivity of FRA’s both from the aspect of accepted languages and of bisimulation equivalence. We establish primary properties and connections between automata of this kind, and an-swer key decidability questions. As a demonstrating example, we express the theory of the pi-calculus in FRA’s and characterise bisimulation equivalence by an appropriate, and decidable in the finitary case, notion in these automata