Multiservice optical network: main concepts and first achievementsof the ROM program

With the tremendous introduction of internet protocol (IP) applications, the quality-of-service (QoS) becomes more and more an emergent issue. Concrete solutions can be adopted (IP/ATM/SONET/WDM) opening the way to new types of applications (interactive applications through the exploitation of voice and video) in a short-term approach. However, all the telecommunication community tries to provide new solutions offering capacity and flexibility in a simpler manner. In this paper, we present the concepts of a multiservice optical network studied in the framework of a French Research Program. The QoS could be offered through the combined exploitation of electronic memories in the edges and optical resources in the core of the optical network and through the coexistence of different types of connections. In particular, the traffic shaping in the edges is highlighted through simulation and demonstrates the real impact of this function to maintain the logical performance at its highest level. To propose concrete solutions for its implementation, two network scenarios are proposed. The first one, for the backbone, exhibits a novel optical packet switching architecture taking benefit of the massive presence of wavelengths to solve the contention. The second one, for the metro, shows a second optical packet switching architecture really adapted to the cost constraints (upgradability, compactness, granularity)     

Rotavirus infection reduces sucrase-isomaltase expression in human intestinal epithelial cells by perturbing protein targeting and organization of microvillar cytoskeleton

Rotavirus infection is the most common cause of severe infantile gastroenteritis worldwide. These viruses infect mature enterocytes of the small intestine and cause structural and functional damage, including a reduction in disaccharidase activity. It was previously hypothesized that reduced disaccharidase activity resulted from the destruction of rotavirus-infected enterocytes at the villus tips. However, this pathophysiological model cannot explain situations in which low disaccharidase activity is observed when rotavirus-infected intestine exhibits few, if any, histopathologic changes. In a previous study, we demonstrated that the simian rotavirus strain RRV replicated in and was released from human enterocyte-like Caco-2 cells without cell destruction (N. Jourdan, M. Maurice, D. Delautier, A. M. Quero, A. L. Servin, and G. Trugnan, J. Virol. 71:8268-8278, 1997). In the present study, to reinvestigate disaccharidase expression during rotavirus infection, we studied sucrase-isomaltase (SI) in RRV-infected Caco-2 cells. We showed that SI activity and apical expression were specifically and selectively decreased by RRV infection without apparent cell destruction. Using pulse-chase experiments and cell surface biotinylation, we demonstrated that RRV infection did not affect SI biosynthesis, maturation, or stability but induced the blockade of SI transport to the brush border. Using confocal laser scanning microscopy, we showed that RRV infection induces important alterations of the cytoskeleton that correlate with decreased SI apical surface expression. These results lead us to propose an alternate model to explain the pathophysiology associated with rotavirus infection.     

An Exploration of Instruction Fetch Requirement in Out-of-Order Superscalar Processors

The performance of superscalar processors depends on many parameters with correlated effects. This paper explores the relations between some of these parameters, and more particularly, the requirement in instruction fetch bandwidth. We introduce new enhancements to increase the bandwidth of conventional instruction fetch engines. However, experiments show that the performance does not increase proportionally to the fetch. Once the measured IPC is half the instruction fetch bandwidth, increasing the fetch bandwidth brings very little improvement. In order to better understand this behavior, we develop a model from the empirical observation that the available instruction parallelism grows as the square root of the instruction window size. From the model, we derive that the fetch bandwidth requirement grows as the square root of the distance between mispredicted branches. We also verify experimentally that, to double the IPC, one should both double the fetch bandwidth and decrease the number of mispredicted branches fourfold.     

Mesoscale cloud pattern classification over ocean with a neural network using a new index of cloud variability

The purpose of this study is to determine the feasibility of a mesoscale (<300 km) cloud classification using infrared radiance data of satellite‐borne instruments. A new method is presented involving an index called the diversity index (DI), derived from a parameter commonly used to describe ecosystem variability. In this respect, we consider several classes of value ranges of standard deviation of the brightness temperature at 11 µm (σ_BT). In order to calculate DI for 128×128 km² grids, subframes of 8 km×8 km are superimposed to the satellite image, and then σ_BT is calculated for all 256 subframes and assigned to one of the classes. Each observed cloud pattern is associated with an index characterized by the frequency of σ_BT classes within the scene, representative of a cloud type. Classification of different clouds is obtained from Advanced Very High Resolution Radiometer (AVHRR)‐NOAA 16 data at 1 km resolution. Stratus, stratocumulus and cumulus are specifically recognized by this window analysis using a DI threshold. Then, a six‐class scheme is presented, with the standard deviation of the infrared brightness temperature of the entire cloud scene (σ_c) and DI as inputs of a neural network algorithm. This neural network classifier achieves an overall accuracy of 77.5% for a six‐class scheme, and 79.4% for a three‐class scheme, as verified against the analyses of nephanalists as verified against a cloud classification from Météo France. As an application of the proposed methodology, regional cloud variability over Pacific is examined using cloud patterns derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) carried aboard Earth Observing System (EOS) Terra polar orbiter platform, for February 2003 and 2004. The comparison shows regional change in monthly mean cloud types, associated with 2003 El Niño and 2004 neutral events. A significant increase in the occurrence of convective clouds (+15%) and a decrease in stratiform clouds (?10%) are observed between the two months.     

Speeding up circularity tests for attribute grammars

Summary We present three improvements to be applied to algorithms testing the circularity of attribute grammars. The first one, originally introduced in [10], discards from the set of graphs attached to a nonterminal symbol those graphs that are included in (covered by) others of the same set. The second one, first presented by Chebotar [1], establishes an optimal order for selection of productions and eliminates at each step those graphs that are unnecessary for subsequent stages of the algorithm, thus requiring less time and space. The last one skips recomputations on terminal trees, thus saving time. These three methods can be used alone or together to speed up circularity tests. We also discuss the practical complexity of circularity tests.     

Synthesis,Anti‐tubulin and Antiproliferative SAR of Steroidomimetic Dihydroisoquinolinones

A SAR translation strategy adopted for the discovery of tetrahydroisoquinolinone (THIQ)‐based steroidomimetic microtubule disruptors has been extended to dihydroisoquinolinone (DHIQ)‐based compounds. A steroid A,B‐ring‐mimicking DHIQ core was connected to methoxyaryl D‐ring mimics through methylene, carbonyl, and sulfonyl linkers, and the resulting compounds were evaluated against two cancer cell lines. The carbonyl‐linked DHIQs in particular exhibit significant in vitro antiproliferative activities (e.g., 6‐hydroxy‐7‐methoxy‐2‐(3,4,5‐trimethoxybenzoyl)‐3,4‐dihydroisoquinolin‐1(2H)‐one ( 16 g ): GI₅₀ 51 nM in DU‐145 cells). The broad anticancer activity of DHIQ 16 g was confirmed in the NCI 60‐cell line assay giving a mean activity of 33 nM . Furthermore, 6‐hydroxy‐2‐(3,5‐dimethoxybenzoyl)‐7‐methoxy‐3,4‐dihydroisoquinolin‐1(2H)‐one ( 16 f ) and 16 g and their sulfamate derivatives 17 f and 17 g (2‐(3,5‐dimethoxybenzoyl)‐7‐methoxy‐6‐sulfamoyloxy‐3,4‐dihydroisoquinolin‐1(2H)‐one and 7‐methoxy‐2‐(3,4,5‐trimethoxybenzoyl)‐6‐sulfamoyloxy‐3,4‐dihydroisoquinolin‐1(2H)‐one, respectively) show excellent activity against the polymerization of tubulin, close to that of the clinical combretastatin A‐4, and bind competitively at the colchicine binding site of tubulin. Compounds 16 f and 17 f were also shown to demonstrate in vitro anti‐angiogenic activity. Additionally, X‐ray and computational analyses of 17 f reveal that electrostatic repulsion between the two adjacent carbonyl groups, through conformational biasing, dictates the adoption of a “steroid‐like” conformation that may partially explain the excellent in vitro activities.     

Chemical Synthesis,Pharmacokinetic Properties and Biological Effects of JM-00266, a Putative Non-Brain Penetrant Cannabinoid Receptor 1 Inverse Agonist

Targeting cannabinoid 1 receptors (CB1R) with peripherally restricted antagonists (or inverse agonists) shows promise to improve metabolic disorders associated with obesity. In this context, we designed and synthetized JM-00266, a new CB1R blocker with limited blood–brain barrier (BBB) permeability. Pharmacokinetics were tested with SwissADME and in vivo in rodents after oral and intraperitoneal administration of JM-00266 in comparison with Rimonabant. In silico predictions indicated JM-00266 is a non-brain penetrant compound and this was confirmed by brain/plasma ratios and brain uptake index values. JM-00266 had no impact on food intake, anxiety-related behavior and body temperature suggesting an absence of central activity. cAMP assays performed in CB1R-transfected HEK293T/17 cells showed that the drug exhibited inverse agonist activity on CB1R. In addition, JM-00266 counteracted anandamide-induced gastroparesis indicating substantial peripheral activity. Acute administration of JM-00266 also improved glucose tolerance and insulin sensitivity in wild-type mice, but not in CB1R^−/− mice. Furthermore, the accumulation of JM-00266 in adipose tissue was associated with an increase in lipolysis. In conclusion, JM-00266 or derivatives can be predicted as a new candidate for modulating peripheral endocannabinoid activity and improving obesity-related metabolic disorders.     

Synthesis,Antitubulin, and Antiproliferative SAR of C3/C1‐Substituted Tetrahydroisoquinolines

The syntheses and antiproliferative activities of novel substituted tetrahydroisoquinoline derivatives and their sulfamates are discussed. Biasing of conformational populations through substitution on the tetrahydroisoquinoline core at C1 and C3 has a profound effect on the antiproliferative activity against various cancer cell lines. The C3 methyl‐substituted sulfamate (±)‐7‐methoxy‐2‐(3‐methoxybenzyl)‐3‐methyl‐6‐sulfamoyloxy‐1,2,3,4‐tetrahydroisoquinoline ( 6 b ), for example, was found to be ～10‐fold more potent than the corresponding non‐methylated compound 7‐methoxy‐2‐(3‐methoxybenzyl)‐6‐sulfamoyloxy‐1,2,3,4‐tetrahydroisoquinoline ( 4 b ) against DU‐145 prostate cancer cells (GI₅₀ values: 220 nM and 2.1 μM , respectively). Such compounds were also found to be active against a drug‐resistant MCF breast cancer cell line. The position and nature of substitution of the N‐benzyl group in the C3‐substituted series was found to have a significant effect on activity. Whereas C1 methylation has little effect on activity, introduction of C1 phenyl and C3‐gem‐dimethyl substituents greatly decreases antiproliferative activity. The ability of these compounds to inhibit microtubule polymerisation and to bind tubulin in a competitive manner versus colchicine confirms the mechanism of action. The therapeutic potential of a representative compound was confirmed in an in vivo multiple myeloma xenograft study.