The weaver mutation causes a loss of inward rectifier current regulation in premigratory granule cells of the mouse cerebellum

Considerable interest has recently focused on the weaver mutation, which causes inward rectifier channel alterations leading to profound impairment of neuronal differentiation and to severe motor dysfunction in mice (Hess, 1996). The principal targets of mutation are cerebellar granule cells, most of which fail to differentiate and degenerate in a premigratory position (Rakic and Sidman, 1973a,b). Two hypotheses have been put forward to explain the pathogenetic role of mutant inward rectifier channels: namely that inward rectifier channel activity is either lacking (Surmeier et al., 1996) or altered (Kofuji et al., 1996; Silverman et al., 1996; Slesinger et al., 1996). We have examined this question by recording inward rectifier currents from cerebellar granule cells in situ at different developmental stages in wild-type and weaver mutant mice. In wild-type mice, the inward rectifier current changed from a G-protein-dependent activation to a constitutive activation as granule cells developed from premigratory to postmigratory stages. In weaver mutant mice, G-protein-dependent inward rectifier currents were absent in premigratory granule cells. A population of putative granule cells in the postmigratory position expressed a constitutive inward rectifier current with properties compatible with mutated GIRK2 channels expressed in heterologous systems. Because granule cells degenerate at the premigratory stage (Smeyne and Goldowitz, 1989), the loss of inward rectifier current and its regulation of membrane potential are likely to play a key role in the pathogenesis of weaver neuronal degeneration.     

A multiagent system for retrieving bioinformatics publications from web sources

Due to the enormous amount of information available on the Internet, extracting and classifying it has become one of the most important tasks. This principle is valid also while searching for scientific publications. This paper describes a system able to retrieve scientific publications from the Web throughout a text categorization process. To this end, a generic multiagent architecture has been customized according to the requirements imposed by the specific task. Experiments have been performed on publications extracted from BMC Bioinformatics and PubMed digital archives.     

On the accessibility of Moodle 2 by visually impaired users,with a focus on mathematical content

In this paper we study the accessibility by visually impaired people of the learning management system (LMS) Moodle 2. The study is conducted by testing four different visually impaired subjects, with different degrees of disability and performing different tasks connected to different roles in the LMS. A peculiar focus is given to the accessibility of content involving mathematics. At the end of the paper, some recommendations to improve the accessibility of Moodle 2 are given.     

A communication micro-kernel for implementing object-oriented programming on closely coupled distributed architectures

Within the framework of distributed object-oriented programming, this paper illustrates the main features of a communication micro-kernel able to perform, in a transparent way, both local and remote communications among objects located on a network of closely coupled microcomputers. The communication micro-kernel allows one to address an object by specifying its virtual location, which usually corresponds to a set of microcomputers considered as a whole. By default, an object is allowed to migrate within the bounds of a given virtual location; hence, any migration activity may occur without overloading the network with broadcast messages. As a high-level environment, a non-standard CLOS-like interpreter, enhanced with message-passing capabilities, has been defined and used to test the communication micro-kernel. Due to the virtualization capabilities provided by such an environment, both an application and the network where the application is intended to be run can be decomposed into several layers and then merged together, thus making it possible to meet hardware and software requirements at a suitable level of abstraction. We believe that the described communication micro-kernel will turn out to be very useful in building adaptive systems and in improving their load-balancing by dynamically performing object/method migration. © 1999 John Wiley & Sons, Ltd.     

Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy fiber-granule cell transmission in rat cerebellum

Long-term potentiation (LTP) is a form of synaptic plasticity that can be revealed at numerous hippocampal and neocortical synapses following high-frequency activation of N-methyl--aspartate (NMDA) receptors. However, it was not known whether LTP could be induced at the mossy fiber-granule cell relay of cerebellum. This is a particularly interesting issue because theories of the cerebellum do not consider or even explicitly negate the existence of mossy fiber-granule cell synaptic plasticity. Here we show that high-frequency mossy fiber stimulation paired with granule cell membrane depolarization (-40 mV) leads to LTP of granule cell excitatory postsynaptic currents (EPSCs). Pairing with a relatively hyperpolarized potential (-60 mV) or in the presence of NMDA receptor blockers [5-amino--phosphonovaleric acid (APV) and 7-chloro-kynurenic acid (7-Cl-Kyn)] prevented LTP, suggesting that the induction process involves a voltage-dependent NMDA receptor activation. Metabotropic glutamate receptors were also involved because blocking them with (+)-alpha-methyl-4-carboxyphenyl-glycine (MCPG) prevented potentiation. At the cytoplasmic level, EPSC potentiation required a Ca2+ increase and protein kinase C (PKC) activation. Potentiation was expressed through an increase in both the NMDA and non-NMDA receptor-mediated current and by an NMDA current slowdown, suggesting that complex mechanisms control synaptic efficacy during LTP. LTP at the mossy fiber-granule cell synapse provides the cerebellar network with a large reservoir for memory storage, which may be needed to optimize pattern recognition and, ultimately, cerebellar learning and computation.     

Multiple alignment through protein secondary-structure information

It is well known that protein secondary-structure information can help the process of performing multiple alignment, in particular when the amount of similarity among the involved sequences moves toward the "twilight zone" (less than 30% of pairwise similarity). In this paper, a multiple alignment algorithm is presented, explicitly designed for exploiting any available secondary-structure information. A layered architecture with two interacting levels has been defined for dealing with both primary- and secondary-structure information of target sequences. Secondary structure (either available or predicted by resorting to a technique based on multiple experts) is used to calculate an initial alignment at the secondary level, to be arranged by locally scoped operators devised to refine the alignment at the primary level. Aimed at evaluating the impact of secondary information on the quality of alignments, in particular alignments with a low degree of similarity, the technique has been implemented and assessed on relevant test cases.     

Multiagent systems and information retrieval our experience with X.MAS

Autonomous agents and multiagent systems have been successfully applied to a number of problems and have been largely used in different application fields. In particular, in this paper we are interested in information retrieval. In fact, in this field multiagent solutions are very useful and effective since they decouple the problem in a network of software agents that interact to solve problems that are beyond the individual capabilities or knowledge. In so doing, multiagent systems allow to overwhelm typical problems of single agent and centralized approaches. To discuss the lesson learnt in using the multiagent technology in the field of information retrieval, in this paper, we present our experience in using X.MAS, a generic multiagent architecture aimed at retrieving, filtering and reorganizing information according to user interests. To this end, after presenting X.MAS, we illustrate six applications built upon it. Our conclusion is that multiagent technology is quite effective to design and realize concrete information retrieval applications.     

CUDA‐quicksort: an improved GPU‐based implementation of quicksort

Sorting is a very important task in computer science and becomes a critical operation for programs making heavy use of sorting algorithms. General‐purpose computing has been successfully used on Graphics Processing Units (GPUs) to parallelize some sorting algorithms. Two GPU‐based implementations of the quicksort were presented in literature: the GPU‐quicksort, a compute‐unified device architecture (CUDA) iterative implementation, and the CUDA dynamic parallel (CDP) quicksort, a recursive implementation provided by NVIDIA Corporation. We propose CUDA‐quicksort an iterative GPU‐based implementation of the sorting algorithm. CUDA‐quicksort has been designed starting from GPU‐quicksort. Unlike GPU‐quicksort, it uses atomic primitives to perform inter‐block communications while ensuring an optimized access to the GPU memory. Experiments performed on six sorting benchmark distributions show that CUDA‐quicksort is up to four times faster than GPU‐quicksort and up to three times faster than CDP‐quicksort. An in‐depth analysis of the performance between CUDA‐quicksort and GPU‐quicksort shows that the main improvement is related to the optimized GPU memory access rather than to the use of atomic primitives. Moreover, in order to assess the advantages of using the CUDA dynamic parallelism, we implemented a recursive version of the CUDA‐quicksort. Experimental results show that CUDA‐quicksort is faster than the CDP‐quicksort provided by NVIDIA, with better performance achieved using the iterative implementation. Copyright © 2015 John Wiley & Sons, Ltd.