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Showing papers by "Université libre de Bruxelles published in 2002"


Journal ArticleDOI
25 Jul 2002-Nature
TL;DR: It is shown that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment, and less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal Growth in four of the tested conditions.
Abstract: Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.

4,328 citations


Journal ArticleDOI
TL;DR: Spag e d i as discussed by the authors is a software primarily designed to characterize the spatial genetic structure of mapped individuals or populations using genotype data of codominant markers, which is useful for detecting isolation by distance within or among populations and estimating gene dispersal parameters; assessing genetic relatedness between individuals and its actual variance, a parameter of interest for marker-based inferences of quantitative inheritance.
Abstract: spag e d i version 1.0 is a software primarily designed to characterize the spatial genetic structure of mapped individuals or populations using genotype data of codominant markers. It computes various statistics describing genetic relatedness or differentiation between individuals or populations by pairwise comparisons and tests their significance by appropriate numerical resampling. spag e d i is useful for: (i) detecting isolation by distance within or among populations and estimating gene dispersal parameters; (ii) assessing genetic relatedness between individuals and its actual variance, a parameter of interest for marker based inferences of quantitative inheritance; (iii) assessing genetic differentiation among populations, including the case of haploids or autopolyploids.

3,509 citations


Journal ArticleDOI
25 Sep 2002-JAMA
TL;DR: This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients and provides evidence of an association between transfusions and diminished organ function as well as between transfusion and mortality.
Abstract: Context Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the. critically ill is poorly defined. Objectives To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. Design Prospective observational study conducted November 1999, with 2. components: a blood sampling study and an, anemia and blood transfusion study. Setting and Patients The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. Main Outcome Measures Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. Results The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r=0.34; P<.001) and total volume drawn (r=0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; chi(2)=50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; chi(2) =88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P=.02); the Kaplan-Meier log-rank test confirmed this difference. Conclusions This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.

1,523 citations


Journal ArticleDOI
TL;DR: The information gained by a potential eavesdropper applying a cloning-based individual attack is derived, along with an upper bound on the error rate that ensures unconditional security against coherent attacks.
Abstract: We consider two quantum cryptographic schemes relying on encoding the key into qudits, i.e., quantum states in a d-dimensional Hilbert space. The first cryptosystem uses two mutually unbiased bases (thereby extending the BB84 scheme), while the second exploits all d+1 available such bases (extending the six-state protocol for qubits). We derive the information gained by a potential eavesdropper applying a cloning-based individual attack, along with an upper bound on the error rate that ensures unconditional security against coherent attacks.

1,188 citations


Journal ArticleDOI
TL;DR: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.
Abstract: OBJECTIVE: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment. METHODS: In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed. RESULTS: Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant. CONCLUSION: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.

912 citations


Journal ArticleDOI
TL;DR: Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic Acid might be an effective treatment for postmenopausal osteoporosis.
Abstract: Background Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored. Methods We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point. Results There were similar increases in bone ...

867 citations


01 Jan 2002
TL;DR: Members Ahti Anttila, Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Liisankatu 21 B, 00170 Helsinki, Finland Ramesh V. Bhat, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania PO, Hyderabad-500 007 AP, India.
Abstract: Members Ahti Anttila, Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Liisankatu 21 B, 00170 Helsinki, Finland Ramesh V. Bhat, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania PO, Hyderabad-500 007 AP, India James A. Bond, Chemico-Biological Interactions, Toxcon, 5505 Frenchmans Creek, Durham, NC 27713, USA Susan J. Borghoff, CIIT Centers for Health Research, 6 Davis Drive, Box 12137, Research Triangle Park, NC 27709-2127, USA F. Xavier Bosch, Epidemiology Unit and Cancer Registry, Catalan Institute of Oncology, Av. Gran via s/n, Km. 2.7, 08907 L’Hospitalet del Llobregat, Spain Gary P. Carlson, School of Health Sciences, 1338 Civil Engineering Building, Purdue University, West Lafayette, IN 47907-1338, USA Marcel Castegnaro, Les Collanges, 07240 Saint-Jean-Chambre, France George Cruzan, ToxWorks, 1153 Roadstown Road, Bridgeton, NJ 08302-6640, USA Wentzel C.A. Gelderblom, Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council (MRC), PO Box 19070, Tygerberg, South Africa 7505 Ulla Hass, Institute of Food Safety and Toxicology, Morkhoj Bygade 19, 2860 Soborg, Denmark Sara H. Henry, 5100 Paint Branch Parkway, College Park, MD 20740-3835, USA Ronald A. Herbert, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, PO Box 12233, Mail Drop B3-08, Research Triangle Park, NC 27709-2233, USA Marc Jackson, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle Park, NC 27709, USA IARC WORKING GROUP ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS: SOME TRADITIONAL HERBAL MEDICINES, SOME MYCOTOXINS, NAPHTHALENE AND STYRENE

836 citations


Journal ArticleDOI
TL;DR: This work gives an analytic description of previous numerical results and generalizes them to arbitrarily high dimensionality and constructs a family of Bell inequalities for bipartite quantum systems of arbitrarily high Dimensionality which are strongly resistant to noise.
Abstract: We develop a novel approach to Bell inequalities based on a constraint that the correlations exhibited by local variable theories must satisfy. This is used to construct a family of Bell inequalities for bipartite quantum systems of arbitrarily high dimensionality which are strongly resistant to noise. In particular, our work gives an analytic description of previous numerical results and generalizes them to arbitrarily high dimensionality.

832 citations


Journal ArticleDOI
TL;DR: Results from population samples of the two plant species show that there is a negative relationship between AFLP fragment size and fragment population frequency, and Monte Carlo simulations reveal that size homoplasy, arising from pulling together nonhomologous fragments of the same size, generates patterns similar to those observed in P. lunatus and L. perenne.
Abstract: We investigate the distribution of sizes of fragments obtained from the amplified fragment length polymorphism (AFLP) marker technique. We find that empirical distributions obtained in two plant species, Phaseolus lunatus and Lolium perenne, are consistent with the expected distributions obtained from analytical theory and from numerical simulations. Our results indicate that the size distribution is strongly asymmetrical, with a much higher proportion of small than large fragments, that it is not influenced by the number of selective nucleotides nor by genome size but that it may vary with genome-wide GC-content, with a higher proportion of small fragments in cases of lower GC-content when considering the standard AFLP protocol with the enzyme MseI. Results from population samples of the two plant species show that there is a negative relationship between AFLP fragment size and fragment population frequency. Monte Carlo simulations reveal that size homoplasy, arising from pulling together nonhomologous fragments of the same size, generates patterns similar to those observed in P. lunatus and L. perenne because of the asymmetry of the size distribution. We discuss the implications of these results in the context of estimating genetic diversity with AFLP markers.

813 citations


Journal ArticleDOI
TL;DR: In this paper, it was shown that there is a bijective correspondence between equivalence classes of asymptotic reducibility parameters and (n−2)-forms in the context of Lagrangian gauge theories.

744 citations


Journal ArticleDOI
TL;DR: This review shows that even though many innovative bacterial detection methods have been developed, few have the potential for becoming a standardized method for the detection of coliforms in drinking water samples.


Journal ArticleDOI
14 Nov 2002-Nature
TL;DR: Examples ranging from calcium oscillations to pulsatile intercellular communication and circadian rhythms illustrate how computational biology contributes to clarify the molecular and dynamical bases of cellular rhythms.
Abstract: Oscillations arise in genetic and metabolic networks as a result of various modes of cellular regulation. In view of the large number of variables involved and of the complexity of feedback processes that generate oscillations, mathematical models and numerical simulations are needed to fully grasp the molecular mechanisms and functions of biological rhythms. Models are also necessary to comprehend the transition from simple to complex oscillatory behaviour and to delineate the conditions under which they arise. Examples ranging from calcium oscillations to pulsatile intercellular communication and circadian rhythms illustrate how computational biology contributes to clarify the molecular and dynamical bases of cellular rhythms.

Journal ArticleDOI
TL;DR: In this article, the authors apply the time-dependent Hamiltonian approach to Grover's problem and find that by adjusting the evolution rate of the Hamiltonian so as to keep the evolution adiabatic on each infinitesimal time interval, the total running time is of order N, where N is the number of items in the database.
Abstract: The adiabatic theorem has been recently used to design quantum algorithms of a new kind, where the quantum computer evolves slowly enough so that it remains near its instantaneous ground state, which tends to the solution. We apply this time-dependent Hamiltonian approach to Grover's problem, i.e., searching a marked item in an unstructured database. We find that by adjusting the evolution rate of the Hamiltonian so as to keep the evolution adiabatic on each infinitesimal time interval, the total running time is of order $\sqrt{N},$ where N is the number of items in the database. We thus recover the advantage of Grover's standard algorithm as compared to a classical search, scaling as N. This is in contrast with the constant-rate adiabatic approach of Farhi et al. (e-print quant-ph/0001106), where the requirement of adiabaticity is expressed only globally, resulting in a time of order N.

Proceedings Article
09 Jul 2002
TL;DR: A procedure that empirically evaluates a set of candidate configurations by discarding bad ones as soon as statistically sufficient evidence is gathered against them and allows to focus on the most promising ones is proposed.
Abstract: This paper describes a racing procedure for finding, in a limited amount of time, a configuration of a metaheuristic that performs as good as possible on a given instance class of a combinatorial optimization problem. Taking inspiration from methods proposed in the machine learning literature for model selection through cross-validation, we propose a procedure that empirically evaluates a set of candidate configurations by discarding bad ones as soon as statistically sufficient evidence is gathered against them. We empirically evaluate our procedure using as an example the configuration of an ant colony optimization algorithm applied to the traveling salesman problem. The experimental results show that our procedure is able to quickly reduce the number of candidates, and allows to focus on the most promising ones.

Journal ArticleDOI
TL;DR: Treatment of mice with SRP299, a killed Mycobacterium vaccae-suspension gives rise to allergen-specific CD4+CD45RBLo regulatory T cells, which confer protection against airway inflammation and may have an essential role in restoring the balance of the immune system to prevent and treat allergic diseases.
Abstract: Allergic asthma is a chronic inflammatory disease and despite the introduction of potent and effective drugs, the prevalence has increased substantially over the past few decades(1). The explanation that has attracted the most attention is the 'hygiene hypothesis', which suggests that the increase in allergic diseases is caused by a cleaner environment and fewer childhood infections(2-4). Indeed, certain mycobacterial strains can cause a shift from T-helper cell 2 (Th2) to Th1 immune responses, which may subsequently prevent the development of allergy in mice(5-7). Although the reconstitution of the balance between Th1 and Th2 is an attractive theory, it is unlikely to explain the whole story, as autoimmune diseases characterized by Th1 responses can also benefit from treatment with mycobacteria and their prevalence has also increased in parallel to allergies(8). Here we show that treatment of mice with SRP299, a killed Mycobacterium vaccae-suspension, gives rise to allergen-specific CD4(+)CD45RB(Lo) regulatory T cells, which confer protection against airway inflammation. This specific inhibition was mediated through interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), as antibodies against IL-10 and TGF-beta completely reversed the inhibitory effect of CD4(+)CD45RB(Lo) T cells. Thus, regulatory T cells generated by mycobacteria treatment may have an essential role in restoring the balance of the immune system to prevent and treat allergic diseases.

Journal ArticleDOI
TL;DR: It is demonstrated that the murine homologue of the previously identified human "pre‐B‐cell colony‐enhancing factor" (PBEF) gene coding for a putative cytokine has been identified by screening a subtractive library enriched in genes expressed in activated T lymphocytes, and NAD biosynthesis may play an important role in lymphocyte activation.
Abstract: The murine homologue of the previously identified human "pre-B-cell colony-enhancing factor" (PBEF) gene coding for a putative cytokine has been identified by screening a subtractive library enriched in genes expressed in activated T lymphocytes. Unlike most cytokine genes known to date, the PBEF gene is ubiquitously expressed in lymphoid and non-lymphoid tissues and displays significant homology with genes from primitive metazoans (marine sponges) and prokaryotic organisms. Recently, a bacterial protein encoded by nadV, a gene from the prokaryote Haemophilus ducreyi displaying significant homology with PBEF, has been identified as a nicotinamide phosphoribosyltranferase (NAmPRTase), an enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis. Using a panel of antibodies to murine PBEF, we demonstrate in this work that, similarly to its microbial counterpart, the murine protein is a NAmPRTase, catalyzing the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. The role of PBEF as a NAmPRTase was further confirmed by showing that the mouse gene was able to confer the ability to grow in the absence of NAD to a NAmPRTase-defective bacterial strain. The present findings are in keeping with the ubiquitous nature of this protein, and indicate that NAD biosynthesis may play an important role in lymphocyte activation.

Journal ArticleDOI
TL;DR: The coherence of the supercontinuum is shown to depend strongly on the input pulse's duration and wavelength, and optimal conditions for the generation of coherent supercontinua are discussed.
Abstract: Numerical simulations have been used in studies of the temporal and spectral features of supercontinuum generation in photonic crystal and tapered optical fibers. In particular, an ensemble average over multiple simulations performed with random quantum noise on the input pulse allows the coherence of the supercontinuum to be quantified in terms of the dependence of the degree of first-order coherence on the wavelength. The coherence is shown to depend strongly on the input pulse’s duration and wavelength, and optimal conditions for the generation of coherent supercontinua are discussed.

Journal ArticleDOI
TL;DR: Findings demonstrate that endogenous cannabinoids through the activation of CB1 receptors are implicated in the control of emotional behaviour and participate in the physiological processes of learning and memory.
Abstract: RATIONALE: Endogenous and exogenous cannabinoids acting through the CB1 cannabinoid receptors are implicated in the control of a variety of behavioural and neuroendocrine functions, including emotional responses, and learning and memory processes. Recently, knockout mice deficient in the CB1 cannabinoid receptor have been generated, and these animals result in an excellent tool to evaluate the neurophysiology of the endogenous cannabinoid system. OBJECTIVES: To establish the role of the CB1 cannabinoid receptor in several emotional-related behavioural responses, including aggressiveness, anxiety, depression and learning models, using CB1 knockout mice. METHODS: We evaluated the spontaneous responses of CB1 knockout mice and wild-type controls under different behavioural paradigms, including the light/dark box, the chronic unpredictable mild stress, the resident-intruder test and the active avoidance paradigm. RESULTS: Our findings showed that CB1 knockout mice presented an increase in the aggressive response measured in the resident-intruder test and an anxiogenic-like response in the light/dark box. Furthermore, a higher sensitivity to exhibit depressive-like responses in the chronic unpredictable mild stress procedure was observed in CB1 knockout mice, suggesting an increased susceptibility to develop an anhedonic state in these animals. Finally, CB1 knockout mice showed a significant increase in the conditioned responses produced in the active avoidance model, suggesting an improvement of learning and memory processes. CONCLUSIONS: Taken together these findings demonstrate that endogenous cannabinoids through the activation of CB1 receptors are implicated in the control of emotional behaviour and participate in the physiological processes of learning and memory.

Journal ArticleDOI
TL;DR: A formal "small tension" expansion of D=11 supergravity near a spacelike singularity is shown to be equivalent, at least up to 30th order in height, to a null geodesic motion in the infinite-dimensional coset space E(10)/K(E 10), where K(E10) is the maximal compact subgroup of the hyperbolic Kac-Moody group E10(R).
Abstract: A formal ``small tension'' expansion of $D=11$ supergravity near a spacelike singularity is shown to be equivalent, at least up to 30th order in height, to a null geodesic motion in the infinite-dimensional coset space ${E}_{10}/K({E}_{10})$, where $K({E}_{10})$ is the maximal compact subgroup of the hyperbolic Kac-Moody group ${E}_{10}(\mathbb{R})$. For the proof we make use of a novel decomposition of ${E}_{10}$ into irreducible representations of its $\mathrm{S}\mathrm{L}(10,\mathbb{R})$ subgroup. We explicitly show how to identify the first four rungs of the ${E}_{10}$ coset fields with the values of geometric quantities constructed from $D=11$ supergravity fields and their spatial gradients taken at some comoving spatial point.

Journal ArticleDOI
TL;DR: It is shown that robust circadian oscillations can occur already with a limited number of mRNA and protein molecules, in the range of tens and hundreds, respectively.
Abstract: We use a core molecular model capable of generating circadian rhythms to assess the robustness of circadian oscillations with respect to molecular noise. The model is based on the negative feedback exerted by a regulatory protein on the expression of its gene. Such a negative regulatory mechanism underlies circadian oscillations of the PER protein in Drosophila and of the FRQ protein in Neurospora. The model incorporates gene transcription into mRNA, translation of mRNA into protein, reversible phosphorylation leading to degradation of the regulatory protein, transport of the latter into the nucleus, and repression of gene expression by the nuclear form of the protein. To assess the effect of molecular noise, we perform stochastic simulations after decomposing the deterministic model into elementary reaction steps. The oscillations predicted by the stochastic simulations agree with those obtained with the deterministic version of the model. We show that robust circadian oscillations can occur already with a limited number of mRNA and protein molecules, in the range of tens and hundreds, respectively. Entrainment by light/dark cycles and cooperativity in repression enhance the robustness of circadian oscillations with respect to molecular noise.

Journal ArticleDOI
TL;DR: It is proved that for a sufficiently large number of algorithm iterations t, the probability of finding an optimal solution at least once is P*(t) /spl ges/ 1 - /spl epsiv/ and that this probability tends to 1 for t/spl rarr//spl infin/.
Abstract: We prove some convergence properties for a class of ant colony optimization algorithms. In particular, we prove that for any small constant /spl epsiv/ > 0 and for a sufficiently large number of algorithm iterations t, the probability of finding an optimal solution at least once is P*(t) /spl ges/ 1 - /spl epsiv/ and that this probability tends to 1 for t/spl rarr//spl infin/. We also prove that, after an optimal solution has been found, it takes a finite number of iterations for the pheromone trails associated to the found optimal solution to grow higher than any other pheromone trail and that, for t/spl rarr//spl infin/, any fixed ant will produce the optimal solution during the tth iteration with probability P /spl ges/ 1 /spl epsiv//spl circ/(/spl tau//sub min/, /spl tau//sub max/), where /spl tau//sub min/ and /spl tau//sub max/ are the minimum and maximum values that can be taken by pheromone trails.

Journal ArticleDOI
TL;DR: In this paper, the authors studied the generation of supercontinua in air-silica microstructured fibers by both nanosecond and femtosecond pulse excitation.
Abstract: We study the generation of supercontinua in air–silica microstructured fibers by both nanosecond and femtosecond pulse excitation. In the nanosecond experiments, a 300-nm broadband visible continuum was generated in a 1.8-m length of fiber pumped at 532 nm by 0.8-ns pulses from a frequency-doubled passively Q-switched Nd:YAG microchip laser. At this wavelength, the dominant mode excited under the conditions of continuum generation is the LP11 mode, and, with nanosecond pumping, self-phase modulation is negligible and the continuum generation is dominated by the interplay of Raman and parametric effects. The spectral extent of the continuum is well explained by calculations of the parametric gain curves for four-wave mixing about the zero-dispersion wavelength of the LP11 mode. In the femtosecond experiments, an 800-nm broadband visible and near-infrared continuum has been generated in a 1-m length of fiber pumped at 780 nm by 100-fs pulses from a Kerr-lens model-locked Ti:sapphire laser. At this wavelength, excitation and continuum generation occur in the LP01 mode, and the spectral width of the observed continuum is shown to be consistent with the phase-matching bandwidth for parametric processes calculated for this fiber mode. In addition, numerical simulations based on an extended nonlinear Schrodinger equation were used to model supercontinuum generation in the femtosecond regime, with the simulation results reproducing the major features of the experimentally observed spectrum.

Journal ArticleDOI
TL;DR: The recent way in which the expression of galectins and galectin-binding sites may affect the behavior of a variety of human neoplastic tissues is discussed.

Journal ArticleDOI
TL;DR: The original method, based on the EM algorithm, is shown to be superior to the standard one for a priori probability estimation and always performs better than the original one in terms of classification accuracy, when the a Priori probability conditions differ from the training set to the real-world data.
Abstract: It sometimes happens (for instance in case control studies) that a classifier is trained on a data set that does not reflect the true a priori probabilities of the target classes on real-world data. This may have a negative effect on the classification accuracy obtained on the real-world data set, especially when the classifier's decisions are based on the a posteriori probabilities of class membership. Indeed, in this case, the trained classifier provides estimates of the a posteriori probabilities that are not valid for this real-world data set (they rely on the a priori probabilities of the training set). Applying the classifier as is (without correcting its outputs with respect to these new conditions) on this new data set may thus be suboptimal. In this note, we present a simple iterative procedure for adjusting the outputs of the trained classifier with respect to these new a priori probabilities without having to refit the model, even when these probabilities are not known in advance. As a by-product, estimates of the new a priori probabilities are also obtained. This iterative algorithm is a straightforward instance of the expectation-maximization (EM) algorithm and is shown to maximize the likelihood of the new data. Thereafter, we discuss a statistical test that can be applied to decide if the a priori class probabilities have changed from the training set to the real-world data. The procedure is illustrated on different classification problems involving a multilayer neural network, and comparisons with a standard procedure for a priori probability estimation are provided. Our original method, based on the EM algorithm, is shown to be superior to the standard one for a priori probability estimation. Experimental results also indicate that the classifier with adjusted outputs always performs better than the original one in terms of classification accuracy, when the a priori probability conditions differ from the training set to the real-world data. The gain in classification accuracy can be significant.

Journal ArticleDOI
TL;DR: Findings suggest that the discrepancy between the effects of the genetic and pharmacological blockade of the CB1 receptor suggests that the novel receptor plays a role in anxiety, as the cannabinoid receptor antagonist affected anxiety in both wild type and CB1‐knockout mice.
Abstract: The aim of this study was to compare the effects of the genetic and pharmacological disruption of CB1 cannabinoid receptors on the elevated plus-maze test of anxiety. In the first experiment, the behaviour of CB1-knockout mice and wild-type mice was compared. In the second experiment, the cannabinoid antagonist SR141716A (0, 1, and 3 mg/kg) was administered to both CB1-knockout and wild type mice. Untreated CB1-knockout mice showed a reduced exploration of the open arms of the plus-maze apparatus, thus appearing more anxious than the wild-type animals, however no changes in locomotion were noticed. The vehicle-injected CB1-knockout mice from the second experiment also showed increased anxiety as compared with wild types. Surprisingly, the cannabinoid antagonist SR141716A reduced anxiety in both wild type and CB1 knockout mice. Locomotor behaviour was only marginally affected. Recent evidence suggests the existence of a novel cannabinoid receptor in the brain. It has also been shown that SR141716A binds to both the CB1 and the putative novel receptor. The data presented here supports these findings, as the cannabinoid receptor antagonist affected anxiety in both wild type and CB1-knockout mice. Tentatively, it may be suggested that the discrepancy between the effects of the genetic and pharmacological blockade of the CB1 receptor suggests that the novel receptor plays a role in anxiety.

Journal ArticleDOI
TL;DR: A new role of the muscarinic cholinergic system in mammalian brain is revealed andReplication of the effects of CCh by blocking acetylcholinesterase with eserine suggests that mAChR-mediated endocannabinoid release is physiologically relevant.
Abstract: Endogenous cannabinoids (endocannabinoids) are endogenous compounds that resemble the active ingredient of marijuana and activate the cannabinoid receptor in the brain. They mediate retrograde signaling from principal cells to both inhibitory ["depolarization-induced suppression of inhibition" (DSI)] and excitatory ("depolarization-induced suppression of excitation") afferent fibers. Transient endocannabinoid release is triggered by voltage-dependent Ca(2+) influx and is upregulated by group I metabotropic glutamate receptor activation. Here we show that muscarinic acetylcholine receptor (mAChR) activation also enhances transient endocannabinoid release (DSI) and induces persistent release. Inhibitory synapses in the rat hippocampal CA1 region of acute slices were studied using whole-cell patch-clamp techniques. We found that low concentrations (0.2-0.5 microm) of carbachol (CCh) enhanced DSI without affecting basal evoked IPSCs (eIPSCs) by activating mAChRs on postsynaptic cells. Higher concentrations of CCh (> or =1 microm) enhanced DSI and also persistently depressed basal eIPSCs, mainly by releasing endocannabinoids. Persistent CCh-induced endocannabinoid release did not require an increase in [Ca2+]i but was dependent on G-proteins. Although they were independent at the receptor level, muscarinic and glutamatergic mechanisms of endocannabinoid release shared intracellular machinery. Replication of the effects of CCh by blocking acetylcholinesterase with eserine suggests that mAChR-mediated endocannabinoid release is physiologically relevant. This study reveals a new role of the muscarinic cholinergic system in mammalian brain.

Journal ArticleDOI
TL;DR: It is found that in all fetal fluids the concentrations of T(4) available to developing tissues, namely FT(4), reach values that are at least one third of those biologically active in their euthyroid mothers.
Abstract: Maternal hypothyroxinemia in early pregnancy is often associated with irreversible effects on neuropsychomotor development. To evaluate fetal tissue exposure to maternal thyroid hormones up to midgestation, we measured total T(4) and free T(4) (FT(4)), T(3), rT(3), TSH, and possible binding proteins in first trimester coelomic and amniotic fluids and in amniotic fluid and fetal serum up to 17 wk. Samples were obtained before interruption of maternal-fetal connections. The concentrations in fetal compartments of T(4) and T(3) are more than 100-fold lower than those in maternal serum, and their biological relevance for fetal development might be questioned. We found, however, that in all fetal fluids the concentrations of T(4) available to developing tissues, namely FT(4), reach values that are at least one third of those biologically active in their euthyroid mothers. FT(4) levels in fetal fluids are determined by both their T(4)-binding protein composition and the T(4) or FT(4) in maternal serum. The binding capacity is determined ontogenically, is independent of maternal thyroid status, and is far in excess of the T(4) in fetal fluids. Thus, the availability of FT(4) for embryonic and fetal tissues would decrease in hypothyroxinemic women, even if they were euthyroid. A decrease in the availability of FT(4), a major precursor of intracellular nuclear receptor-bound T(3), may result in adverse effects on the timely sequence of developmental events in the human fetus. These findings ought to influence our present approach to maternal hypothyroxinemia in early pregnancy regardless of whether TSH is increased or whether overt or subclinical hypothyroidism is detected.

Journal ArticleDOI
TL;DR: Teriparatide, a bone formation agent, increased BMD at most sites and decreased nonvertebral fractures more than alendronate in 146 postmenopausal women with osteoporosis.
Abstract: Teriparatide (rDNA origin) injection [recombinant human PTH (1-34)] stimulates bone formation, increases bone mineral density (BMD), and restores bone architecture and integrity. In contrast, bisphosphonates reduce bone resorption and increase BMD. We compared the effects of teriparatide and alendronate sodium on BMD, nonvertebral fracture incidence, and bone turnover in 146 postmenopausal women with osteoporosis. Women were randomized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo (n = 73) or oral alendronate 10 mg plus placebo injection (n = 73). Median duration of treatment was 14 months. At 3 months, teriparatide increased lumbar spine BMD significantly more than did alendronate (P < 0.001). Lumbar spine-BMD increased by 12.2% in the teriparatide group and 5.6% in the alendronate group (P < 0.001 teriparatide vs. alendronate). Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate, but BMD at the one third distal radius decreased, compared with alendronate (P < or = 0.05). Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group (P < 0.05). Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment. In conclusion, teriparatide, a bone formation agent, increased BMD at most sites and decreased nonvertebral fractures more than alendronate.

Book ChapterDOI
TL;DR: The results demonstrate that the MAX-MIN Ant System is able to construct significantly better timetables than an algorithm that iterates the local search procedure from random starting solutions.
Abstract: We consider a simplification of a typical university course timetabling problem involving three types of hard and three types of soft constraints. A MAX-MIN Ant System, which makes use of a separate local search routine, is proposed for tackling this problem. We devise an appropriate construction graph and pheromone matrix representation after considering alternatives. The resulting algorithm is tested over a set of eleven instances from three classes of the problem. The results demonstrate that the ant system is able to construct significantly better timetables than an algorithm that iterates the local search procedure from random starting solutions.