Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans

Thymidine monophosphate kinase (TMPK) from Mycobacterium tuberculosis (TMPKmt) is an attractive target for the design of specific inhibitors. This fact is the result of its key role in the thymidine pathway and of unique structural features in the active site observed by X-ray crystallography, especially in comparison to its human counterpart (TMPKh). Different 5-modified thymidine derivatives, as well as purine and pyrimidine analogues or C-nucleosides were tested on TMPKmt and TMPKh, and the results were rationalized by docking studies. 5-Halogenated 2'-deoxyuridines are the best inhibitors of TMPKmt found and present the highest selectivity indexes in favor of TMPKmt.     

Towards efficient data distribution on computational desktop grids with BitTorrent

Datacentric applications are still a challenging issue for large-scale distributed computing systems. The emergence of new protocols and software for collaborative content distribution over the Internet offers a new opportunity for efficient and fast delivery of a high volume of data. This paper presents an evaluation of the BitTorrent protocol for computational desktop grids. We first present a prototype of a generic subsystem dedicated to data management and designed to serve as a building block for any desktop grid system. Based on this prototype we conduct experiments to evaluate the potential of BitTorrent compared to a classical approach based on FTP data server. The preliminary results obtained with a 65-node cluster measure the basic characteristics of BitTorrent in terms of latency and bandwidth and evaluate the scalability of BitTorrent for the delivery of large input files. Moreover, we show that BitTorrent has a considerable latency overhead compared to FTP but clearly outperforms FTP when distributing large files or files to a high number of nodes. Tests on a synthetic application show that BitTorrent significantly increases the communication/computation ratio of the applications eligible to run on a desktop grid system.     

Extension of the Hansen-Bliek Method to Right-Quantified Linear Systems

The problem of finding the smallest box enclosing the united solution set of a linear interval system, also known as the “interval hull” problem, was proven to be NP-hard. However, Hansen, Bliek, and others subsequently, have provided a polynomial-time solution in the case of systems preconditioned by the midpoint inverse matrix. Based upon a similar approach, this paper deals with the interval hull problem in the context of AE-solution sets, where parameters may be given different quantifiers. A polynomial-time algorithm is proposed for computing the hull of AE-solution sets where parameters involved in the matrix are constrained to be existentially quantified. Such AE-solution sets are called right-quantified solution sets. They have recently been shown to be of practical interest.     

Well-structured languages

This paper introduces the notion of well-structured language. A well-structured language can be defined by a labelled well-structured transition system, equipped with an upward-closed set of accepting states. That peculiar class of transition systems has been extensively studied in the field of computer-aided verification, where it has direct an important applications. Petri nets, and their monotonic extensions (like Petri nets with non-blocking arcs or Petri nets with transfer arcs), for instance, are special subclasses of well-structured transition systems. We show that the class of well-structured languages enjoy several important closure properties. We propose several pumping lemmata that are applicable respectively to the whole class of well-structured languages and to the classes of languages recognized by Petri nets or Petri nets with non-blocking arcs. These pumping lemmata allow us to characterize the limits in the expressiveness of these classes of language. Furthermore, we exploit the pumping lemmata to strictly separate the expressive power of Petri nets, Petri nets with non-blocking arcs and Petri nets with transfer arcs.     

Quantum speed-up for unsupervised learning

We show how the quantum paradigm can be used to speed up unsupervised learning algorithms. More precisely, we explain how it is possible to accelerate learning algorithms by quantizing some of their subroutines. Quantization refers to the process that partially or totally converts a classical algorithm to its quantum counterpart in order to improve performance. In particular, we give quantized versions of clustering via minimum spanning tree, divisive clustering and k-medians that are faster than their classical analogues. We also describe a distributed version of k-medians that allows the participants to save on the global communication cost of the protocol compared to the classical version. Finally, we design quantum algorithms for the construction of a neighbourhood graph, outlier detection as well as smart initialization of the cluster centres.     

Multiprocessor schedulability of arbitrary-deadline sporadic tasks: complexity and antichain algorithm

Baker and Cirinei (Lecture Notes in Computer Science, vol. 4878, Springer, pp. 62–75, 2007) have introduced an exact but naive algorithm, that consists in solving a state reachability problem in a finite automaton, to check whether a set of sporadic hard real-time tasks is schedulable on an identical multiprocessor platform. However, this algorithm suffers from poor performance due to the exponential size of the automaton relative to the size of the task set. In this paper, we build on the work of Baker and Cirinei, and rely on their formalism to characterise the complexity of this problem. We prove that it is PSpace-complete. In order to obtain an algorithm that is applicable in practice to systems of realistic sizes, we successfully apply techniques developed by the formal verification community, specifically antichain techniques (Doyen and Raskin in Lecture Notes in Computer Science, vol. 6015, Springer, pp. 2–22, 2010) to this scheduling problem. For that purpose, we define and prove the correctness of a simulation relation on Baker and Cirinei’s automaton. We show that our improved algorithm yields dramatically improved performance for the schedulability test and opens for many further improvements. This work is an extended and revised version of a previous conference paper by the same authors (Lindström et al., Proceedings of the 19th International Conference on Real-Time and Network Systems (RTNS 2011), pp. 25–34, 2011).     

Left invertibility,flatness and identifiability of switched linear dynamical systems: a framework for cryptographic applications

The purpose of this article is to illustrate the potential interest of the control theory framework for cryptographic applications. It is shown that under the properties of left invertibility and flatness, dynamical systems are structurally equivalent to some specific cryptographic primitives called self-synchronising stream ciphers. After having motivated the interest of considering hybrid systems for such ciphers, the development is particularised for the special class of switched linear systems. We also show that identifiability is a necessary condition for security, and we describe an identification procedure as a possible attack and assess its complexity.     

The MISTIGRI thermal infrared project: scientific objectives and mission specifications

This article presents the MISTIGRI project of a microsatellite developed by the French space agency Centre National d'Etudes Spatiales (CNES) in cooperation with Spain (Image Processing Laboratory of the University of Valencia and Centro para el Desarrollo Tecnológico Industrial (CDTI)). MISTIGRI is a mission that has the originality of combining a high spatial resolution (～50 m) with a daily revisit in the thermal infrared (TIR). MISTIGRI is an experimental mission devoted to demonstrate the potential of such TIR data for future operational missions. The scientific goals and expected applications of the mission are described: they encompass the monitoring of (i) agricultural areas and related hydrological processes, (ii) urban areas, and (iii) coastal areas and continental waters. Then, the specifications on spatial resolution, revisit frequency, overpass time, and spectral configuration are justified. The strategy of the mission is based on the combination with a network of long-term experimental sites. It will also make possible observing some areas facing rapid climatic change. The choice of the orbit is presented. Finally, we give rapid overviews of both the instrumental concept and the proposed mission architecture.     

Non-linear dynamic system identification: A multi-model approach

We are concerned with models which are able to describe multiple-input multiple-output (MIMO) non-linear dynamic systems. These models are represented in the form of rules and are known as Tagaki-Sugeno models. An identification algorithm for these models based on input and output data is presented. Parameter estimation is based on the calculation of model sensitivity functions with respect to their parameters. Some aspects of structure identification are also tackled, i.e. determination of local model orders and number of rules.     

Design of a General‐Purpose European Compound Screening Library for EU‐OPENSCREEN

This work describes a collaborative effort to define and apply a protocol for the rational selection of a general‐purpose screening library, to be used by the screening platforms affiliated with the EU‐OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening‐compliant physicochemical properties, loose compliance to drug‐likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre‐filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in‐house methodology and expertise. An in‐depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics‐driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general‐purpose self‐organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU‐OPENSCREEN library could be directly compared with distributions of known bioactives of various classes. This mapping highlights the relevance of the selection and shows how the consensus reached by merging the five different 40K selections contributes to achieve this relevance. The approach also allows one to readily identify subsets of target‐ or target‐class‐oriented compounds from the EU‐OPENSCREEN library to suit the needs of the diverse range of potential users. The final EU‐OPENSCREEN library, assembled by merging five independent selections of 40K compounds from various expert groups, represents an excellent example of a Europe‐wide collaborative effort toward the common objective of building best‐in‐class European open screening platforms.