Performance study of ground-based infrared Bracewell interferometers - Application to the detection of exozodiacal dust disks with GENIE

Nulling interferometry, a powerful technique for high-resolution imaging of the close neighbourhood of bright astrophysical objets, is currently considered for future space missions such as Darwin or the Terrestrial Planet Finder Interferometer (TPF-I), both aiming at Earth-like planet detection and characterization. Ground-based nulling interferometers are being studied for both technology demonstration and scientific preparation of the Darwin/TPF-I missions through a systematic survey of circumstellar dust disks around nearby stars. In this paper, we investigate the influence of atmospheric turbulence on the performance of ground-based nulling instruments, and deduce the major design guidelines for such instruments. End-to-end numerical simulations allow us to estimate the performance of the main subsystems and thereby the actual sensitivity of the nuller to faint exozodiacal disks. Particular attention is also given to the important question of stellar leakage calibration. This study is illustrated in the context of GENIE, the Ground-based European Nulling Interferometer Experiment, to be installed at the VLTI and working in the L' band. We estimate that this instrument will detect exozodiacal clouds as faint as about 50 times the Solar zodiacal cloud, thereby placing strong constraints on the acceptable targets for Darwin/TPF-I.Comment: A&A, accepte

Ontology Domain Modeling Support for Multilingual Servicies in e-commerce: MKBEEM

One of the main objectives of a truly user-friendly Information Society is to focus on advanced human language technologies enabling cost-effective interchange across language and culture and more natural interfaces to digital services. The recently launched IST-1999-10589 project MKBEEM (Multilingual Knowledge Based European Electronic Marketplace, 1st Feb. 2000 - 1st Aug. 2002) is rightly in that direction and the work will address basically, written language technologies and its use in the key sector of global business and electronic commerce. In particular MKBEEM will focus on adding multilinguality to all stages of the information cycle, including multilingual content generation and maintenance, automated translation and interpretation and enhancing the natural interactivity and usability of the service with unconstrained language input. On the Knowledge engineering side, the MKBEEM Ontologies will provide a consensual representation of the electronic commerce field in three typical Domains (Tourism, Mail order, Retailers) allowing the exchanges independently of the language of the end user, the service, or the content provider. Ontologies will be used for classifying and indexing catalogues, for filtering user’s query, for facilitating multilingual man-machine dialogues between user and software agent, and for inferring information that is relevant to the user’s request. This paper concentrates on ontology issues, while the used human language processing approaches will be presented closely in our later papers

Increasing the imaging capabilities of the VLTI using integrated optics

Several scientific topics linked to the observation of extended structures around astrophysical sources (dust torus around AGN, disks around young stars, envelopes around AGBs) require imaging capability with milli-arcsecond spatial resolution. The current VLTI instruments, AMBER and MIDI, will provide in the coming months the required high angular resolution, yet without actual imaging. As a rule of thumb, the image quality accessible with an optical interferometer is directly related to the number of telescopes used simultaneously: the more the apertures, the better and the faster the reconstruction of the image. We propose an instrument concept to achieve interferometric combination of N telescopes (4 ≤ N ≤ 8) thanks to planar optics technology: 4 x 8-m telescopes in the short term and/or 8 x 1.8-m telescopes in the long term. The foreseen image reconstruction quality in the visible and/or in the near infrared will be equivalent to the one achieved with millimeter radio interferometers. Achievable spatial resolution will be better than the one foreseen with ALMA. This instrument would be able to acquire routinely 1 mas resolution images. A 13 to 20 magnitude sensitivity in spectral ranges from 0.6 to 2.5 μm is expected depending on the choice of the phase referencing guide source. High dynamic range, even on faint objects, is achievable thanks to the high accuracy provided by integrated optics for visibility amplitude and phase measurements. Based on recent validations of integrated optics presented here an imaging instrument concept can be proposed. The results obtained using the VLTI facilities give a demonstration of the potential of the proposed technique

Apoptosis screening of human chromosome 21 proteins reveals novel cell death regulators

The functional analysis of chromosome 21 (Chr21) proteins is of great medical relevance. This refers, in particular, to the trisomy of human Chr21, which results in Down’s syndrome, a complex developmental and neurodegenerative disease. In a previous study we analyzed 89 human Chr21 genes for the subcellular localization of their encoded proteins using a transfected-cell array technique. In the present study, the results of the follow-up investigation are presented in which 52 human Chr21 genes were over-expressed in HEK cells using the transfected-cell array platform, and the effect of this protein over-expression on the induction of apoptosis has been analyzed. We found that the over-expression of two Chr21 proteins (claudin-14 and -8) induced cell death independent of the classic caspase-mediated apoptosis. Our results strongly suggest the functional involvement of claudins in the control of the cell cycle and regulation of the cell death induction mechanism

Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

BACKGROUND: The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA). As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d.) and 100 mg twice daily (b.i.d.) with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. METHODS: In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years) with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1) to lumiracoxib 100 mg o.d. (n = 755), lumiracoxib 100 mg b.i.d. (n = 1,519) or celecoxib 200 mg o.d. (n = 758). The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS) total score, rescue medication use, and safety and tolerability. RESULTS: Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively). It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. CONCLUSION: Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well tolerated as celecoxib 200 mg o.d. in patients with OA. TRIAL REGISTRATION: clinicaltrials.gov NCT00145301

A roadmap for the Human Developmental Cell Atlas

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development

Carbohydrate Metabolism Is Essential for the Colonization of Streptococcus thermophilus in the Digestive Tract of Gnotobiotic Rats

Streptococcus thermophilus is the archetype of lactose-adapted bacterium and so far, its sugar metabolism has been mainly investigated in vitro. The objective of this work was to study the impact of lactose and lactose permease on S. thermophilus physiology in the gastrointestinal tract (GIT) of gnotobiotic rats. We used rats mono-associated with LMD-9 strain and receiving 4.5% lactose. This model allowed the analysis of colonization curves of LMD-9, its metabolic profile, its production of lactate and its interaction with the colon epithelium. Lactose induced a rapid and high level of S. thermophilus in the GIT, where its activity led to 49 mM of intra-luminal L-lactate that was related to the induction of mono-carboxylic transporter mRNAs (SLC16A1 and SLC5A8) and p27Kip1 cell cycle arrest protein in epithelial cells. In the presence of a continuous lactose supply, S. thermophilus recruited proteins involved in glycolysis and induced the metabolism of alternative sugars as sucrose, galactose, and glycogen. Moreover, inactivation of the lactose transporter, LacS, delayed S. thermophilus colonization. Our results show i/that lactose constitutes a limiting factor for colonization of S. thermophilus, ii/that activation of enzymes involved in carbohydrate metabolism constitutes the metabolic signature of S. thermophilus in the GIT, iii/that the production of lactate settles the dialogue with colon epithelium. We propose a metabolic model of management of carbohydrate resources by S. thermophilus in the GIT. Our results are in accord with the rationale that nutritional allegation via consumption of yogurt alleviates the symptoms of lactose intolerance