Showing papers by "Université libre de Bruxelles published in 1997"
TL;DR: An artificial ant colony capable of solving the travelling salesman problem (TSP) is described, an example of the successful use of a natural metaphor to design an optimization algorithm.
Abstract: We describe an artificial ant colony capable of solving the travelling salesman problem (TSP). Ants of the artificial colony are able to generate successively shorter feasible tours by using information accumulated in the form of a pheromone trail deposited on the edges of the TSP graph. Computer simulations demonstrate that the artificial ant colony is capable of generating good solutions to both symmetric and asymmetric instances of the TSP. The method is an example, like simulated annealing, neural networks and evolutionary computation, of the successful use of a natural metaphor to design an optimization algorithm.
1,908 citations
TL;DR: In this article, the authors developed a model of growth and income inequalities in the presence of imperfect capital markets, and analyzed the trickle-down effect of capital accumulation, showing that when the rate of accumulation is sufficiently high, the economy converges to a unique invariant wealth distribution.
Abstract: This paper develops a model of growth and income inequalities in the presence of imperfect capital markets, and it analyses the trickle-down effect of capital accumulation. Moral hazard with limited wealth constraints on the part of the borrowers is the source of both capital market imperfections and the emergence of persistent income inequalities. Three main conclusions are obtained from this model. First, when the rate of capital accumulation is sufficiently high, the economy converges to a unique invariant wealth distribution. Second, even though the trickle-down mechanism can lead to a unique steady-state distribution under laissez-faire, there is room for government intervention: in particular, redistribution of wealth from rich lenders to poor and middle-class borrowers improves the production efficiency of the economy both because it brings about greater equality of opportunity and also because it accelerates the trickle-down process. Third, the process of capital accumulation initially has the effect of widening inequalities but in later stages it reduces them: in other words, this model can generate a Kuznets curve.
1,559 citations
TL;DR: A global view of thyroidal economy in pregnancy and the hypothalamic-pituitary-thyroid axis and the role of hCG are presented.
Abstract: I. Introduction II. The Regulation of Thyroid Function in Normal Pregnancy A. The thyroid hormone transport proteins B. The thyroid hormones 1. Total thyroid hormones 2. Free thyroid hormones 3. Peripheral metabolism of thyroid hormones C. The serum levels of thyroglobulin (TG) D. The metabolism of iodine E. The hypothalamic-pituitary control of thyroid function and the role of hCG 1. Hypothalamic-pituitary-thyroid axis (HPTA) 2. Regulation of serum TSH 3. Thyrotropic action of hCG F. A global view of thyroidal economy in pregnancy III. Pathological Alterations of Thyroidal Regulation Associated with Pregnancy A. IDD 1. Consequences of iodine deficiency during pregnancy 2. Assessment of increased thyroidal stimulation 3. Gestational goitrogenesis and its prevention by iodine supplementation 4. Consequences of iodine deficiency for the offspring B. Hypothyroidism and pregnancy 1. Fertility and pregnancy outcome in hypothyroid women 2. Thyroid hormone replacement in the hypothyroid pregnant woman 3. Subclin...
1,189 citations
TL;DR: In this way, the two bodies discipline each other to the voters' advantage as discussed by the authors, which helps the voters elicit information and also helps to prevent the abuse of power, but only with appropriate checks and balances.
Abstract: Political constitutions are incomplete contracts and therefore leave room for abuse of power. In democracies, elections are the primary mechanism for disciplining public officials, but they are not sufficient. Separation of powers between executive and legislative bodies also helps to prevent the abuse of power, but only with appropriate checks and balances. Checks and balances work by creating a conflict of interest between the executive and the legislature, yet requiring both bodies to agree on public policy. In this way, the two bodies discipline each other to the voters' advantage. Under appropriate checks and balances, separation of powers also helps the voters elicit information.
1,113 citations
TL;DR: It was found that A2aR-knockout mice were viable and bred normally, and male mice were much more aggressive towards intruders, whereas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity.
Abstract: Adenosine is released from metabolically active cells by facilitated diffusion, and is generated extracellularly by degradation of released ATP. It is a potent biological mediator that modulates the activity of numerous cell types, including various neuronal populations, platelets, neutrophils and mast cells, and smooth muscle cells in bronchi and vasculature. Most of these effects help to protect cells and tissues during stress conditions such as ischaemia. Adenosine mediates its effects through four receptor subtypes: the A1, A2a, A2b and A3 receptors. The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used psychoactive drug. Here we investigate the role of the A2a receptor by disrupting the gene in mice. We found that A2aR-knockout (A2aR-/-) mice were viable and bred normally. Their exploratory activity was reduced, whereas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity. Knockout animals scored higher in anxiety tests, and male mice were much more aggressive towards intruders. The response of A2aR-/- mice to acute pain stimuli was slower. Blood pressure and heart rate were increased, as well as platelet aggregation. The specific A2a agonist CGS 21680 lost its biological activity in all systems tested.
914 citations
TL;DR: In this article, the authors developed a model of the breakup or unification of nations and analyzed some important economic and political determinants of the process of unification and separation of democratic nations, concluding that from an economic efficiency point of view, separation of nations is never desirable.
Abstract: This paper develops a model of the breakup or unification of nations. In each nation the decision to separate is taken by majority voting. A basic trade-off between the efficiency gains of unification and the costs in terms of loss of control on political decisions is highlighted. The model emphasizes political conflicts over redistribution policies. The main results of the paper are i) when income distributions vary across regions and the efficiency gains from unification are small, separation occurs in equilibrium; and ii) when all factors of production are perfectly mobile, all incentives for separation disappear. I. INTRODUCTION Following the demise of communism, the entire map of Europe, from the Atlantic coast to the Urals, is being redrawn and issues of separation, unification, and the redrawing of borders are yet again at the forefront of European concerns. Many of the issues raised by this process are primarily of a political, cultural, or linguistic nature. However, there are also economic considerations that bear on this problem. The objective of this paper is to analyze some important economic and political determinants of the process of unification and separation of democratic nations. The starting point of our analysis is to suppose that from an economic efficiency point of view, separation of nations is never desirable. A unified nation is always more efficient since free trade among regions is guaranteed, duplication costs in defense and law enforcement are avoided, and local public goods provision (such as transportation and communication networks, or common standards) can be coordinated. Furthermore, any benefits of decentralization that might be obtained in a world with several nations may also be achieved within a unified nation by replicating the administrative structure of the world with several
726 citations
TL;DR: It is concluded that even partial acute sleep loss delays the recovery of the HPA from early morning circadian stimulation and is thus likely to involve an alteration in negative glucocorticoid feedback regulation.
Abstract: Sleep curtailment constitutes an increasingly common condition in industrialized societies and is thought to affect mood and performance rather than physiological functions. There is no evidence for prolonged or delayed effects of sleep loss on the hypothalamo-pituitary-adrenal (HPA) axis. We evaluated the effects of acute partial or total sleep deprivation on the nighttime and daytime profile of cortisol levels. Plasma cortisol profiles were determined during a 32-hour period (from 1800 hours on day 1 until 0200 hours on day 3) in normal young men submitted to three different protocols: normal sleep schedule (2300-0700 hours), partial sleep deprivation (0400-0800 hours), and total sleep deprivation. Alterations in cortisol levels could only be demonstrated in the evening following the night of sleep deprivation. After normal sleep, plasma cortisol levels over the 1800-2300-hour period were similar on days 1 and 2. After partial and total sleep deprivation, plasma cortisol levels over the 1800-2300-hour period were higher on day 2 than on day 1 (37 and 45% increases, p = 0.03 and 0.003, respectively), and the onset of the quiescent period of cortisol secretion was delayed by at least 1 hour. We conclude that even partial acute sleep loss delays the recovery of the HPA from early morning circadian stimulation and is thus likely to involve an alteration in negative glucocorticoid feedback regulation. Sleep loss could thus affect the resiliency of the stress response and may accelerate the development of metabolic and cognitive consequences of glucocorticoid excess.
724 citations
TL;DR: This description does not rely on individual complexity to account for complex spatiotemporal features that emerge at the colony level, but rather assumes that intractions among simple individuals can produce highly structured collective behaviours.
Abstract: Self-organization was introduced originally in the context of physics and chemistry to describe how microscopic processes give rise to macroscopic stuctures in out-of-equilibrium systems, Recent research that extends this concept to ethology suggests that it provides a concise description of a wide range of collective phenomena in animals, especially in social insects. This description does not rely on individual complexity to account for complex spatiotemporal features that emerge at the colony level, but rather assumes that intractions among simple individuals can produce highly structured collective behaviours.
638 citations
TL;DR: The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode, and in the developing kidney, the expression pattern is indicative of a role for Eya 1 in the metanephric cells surrounding the ‘just-divided’ ureteric branches.
Abstract: A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.
616 citations
TL;DR: The data show that DC that have undergone maturation in vitro in the presence of IL‐10, have an impaired capacity to induce a Th1‐type response in vivo, leading to the development of Th2 lymphocytes, and suggest thatIL‐10 skews the Th1/Th2 balance to Th2 in vivo by selectively blocking IL‐12 synthesis by the antigen‐presenting cells that play a role of adjuvant of the primary immune response.
Abstract: The main function of dendritic cells (DC) is to induce the differentiation of naive T lymphocytes into helper cells producing a large array of lymphokines, including interleukin (IL)-2; interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-10. The potent immunostimulatory properties of DC develop during a process of maturation that occurs spontaneously in vitro. Since IL-10 has been shown to inhibit Th1 responses, we determined its effect on DC maturation and accessory function. Our data show that DC that have undergone maturation in vitro in the presence of IL-10, have an impaired capacity to induce a Th1-type response in vivo, leading to the development of Th2 lymphocytes. Their inability to promote the synthesis of IFN-gamma seems to correlate with a decreased production of IL-12, an heterodimeric cytokine necessary for optimal generation of Th1-type cells. These results suggest that IL-10 skews the Th1/Th2 balance to Th2 in vivo by selectively blocking IL-12 synthesis by the antigen-presenting cells that play a role of adjuvant of the primary immune response. The cytokines present in the environment at the presentation step may, therefore, determine the class of the immune response induced by DC in vivo, i.e. Th0, Th1 and/or Th2.
592 citations
TL;DR: The characterization of two additional NH4+ transporters, Mep2p and Mep3p, both of which are highly similar to Mep1p are described, and analysis of databases suggests that families of NH4-transporters exist in other organisms as well.
Abstract: Ammonium is a nitrogen source supporting growth of yeast cells at an optimal rate. We recently reported the first characterization of an NH4+ transport protein (Mep1p) in Saccharomyces cerevisiae. Here we describe the characterization of two additional NH4+ transporters, Mep2p and Mep3p, both of which are highly similar to Mep1p. The Mep2 protein displays the highest affinity for NH4+ (Km, 1 to 2 microM), followed closely by Mep1p (Km, 5 to 10 microM) and finally by Mep3p, whose affinity is much lower (Km, approximately 1.4 to 2.1 mM). A strain lacking all three MEP genes cannot grow on media containing less than 5 mM NH4+ as the sole nitrogen source, while the presence of individual NH4+ transporters enables growth on these media. Yet, the three Mep proteins are not essential for growth on NH4+ at high concentrations (>20 mM). Feeding experiments further indicate that the Mep transporters are also required to retain NH4+ inside cells during growth on at least some nitrogen sources other than NH4+. The MEP genes are subject to nitrogen control. In the presence of a good nitrogen source, all three MEP genes are repressed. On a poor nitrogen source, MEP2 expression is much higher than MEP1 and MEP3 expression. High-level MEP2 transcription requires at least one of the two GATA family factors Gln3p and Nil1p, which are involved in transcriptional activation of many other nitrogen-regulated genes. In contrast, expression of either MEP1 or MEP3 requires only Gln3p and is unexpectedly down-regulated in a Nil1p-dependent manner. Analysis of databases suggests that families of NH4+ transporters exist in other organisms as well.
TL;DR: Electron microscopic analysis confirms that cells treated with PT inducers alone undergo apoptosis, whereas cells kept in identical conditions in the presence of Z-VAD.fmk die from necrosis, compatible with the hypothesis that PT would be a rate limiting step in both the apoptotic and the necrotic modes of cell death.
Abstract: Mitochondrial alterations including permeability transition (PT) constitute critical events of the apoptotic cascade and are under the control of Bcl-2 related gene products. Here we show that induction of PT is sufficient to activate CPP32-like proteases with DEVDase activity and the associated cleavage of the nuclear DEVDase substrate poly(ADP-ribose) polymerase (PARP). Thus, direct intervention on mitochondria using a ligand of the mitochondrial benzodiazepin receptor or a protonophore causes DEVDase activation. In addition, the DEVDase activation triggered by conventional apoptosis inducers (glucocorticoids or topoisomerase inhibitors) is prevented by inhibitors of PT. The protease inhibitor N-benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk) completely prevents the activation of DEVDase and PARP cleavage, as well as the manifestation of nuclear apoptosis (chromatin condensation, DNA fragmentation, hypoploidy). In addition, Z-VAD.fmk delays the manifestation of apoptosis-associated changes in cellular redox potentials (hypergeneration of superoxide anion, oxidation of compounds of the inner mitochondrial membrane, depletion of non-oxidized glutathione), as well as the exposure of phosphatidylserine residues in the outer plasma membrane leaflet. Although Z-VAD.fmk retards cytolysis, it is incapable of preventing disruption of the plasma membrane during protracted cell culture (12-24 h), even in conditions in which it completely blocks nuclear apoptosis (chromatin condensation and DNA fragmentation). Electron microscopic analysis confirms that cells treated with PT inducers alone undergo apoptosis, whereas cells kept in identical conditions in the presence of Z-VAD.fmk die from necrosis. These observations are compatible with the hypothesis that PT would be a rate limiting step in both the apoptotic and the necrotic modes of cell death. In contrast, it would be the availability of apoptogenic proteases that would determine the choice between the two death modalities.
16 Dec 1997
TL;DR: This paper focuses on four issues: how to design robust behavior-producing modules; how to coordinate the activity of several such modules;How to use data from the sensors; and how to integrate high-level reasoning and low-level execution.
Abstract: The development of techniques for autonomous navigation in real-world environments constitutes one of the major trends in the current research on robotics. An important problem in autonomous navigation is the need to cope with the large amount of uncertainty that is inherent of natural environments. Fuzzy logic has features that make it an adequate tool to address this problem. In this paper, we review some of the possible uses of fuzzy logic in the field of autonomous navigation. We focus on four issues: how to design robust behavior-producing modules; how to coordinate the activity of several such modules; how to use data from the sensors; and how to integrate high-level reasoning and low-level execution. For each issue, we review some of the proposals in the literature, and discuss the pros and cons of fuzzy logic solutions.
TL;DR: The second extracellular loop of CCR5 is an ideal target site for the development of inhibitors of either chemokine or HIV-1 binding to CCR4, suggesting a complicated pattern of HIV- 1 gp120 binding to different regions of C CR5, but a relatively simple pattern for chemokin binding.
Abstract: CCR5 is a chemokine receptor expressed by T cells and macrophages, which also functions as the principal coreceptor for macrophage (M)-tropic strains of HIV-1. To understand the molecular basis of the binding of chemokines and HIV-1 to CCR5, we developed a number of mAbs that inhibit the various interactions of CCR5, and mapped the binding sites of these mAbs using a panel of CCR5/CCR2b chimeras. One mAb termed 2D7 completely blocked the binding and chemotaxis of the three natural chemokine ligands of CCR5, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1α, and MIP-1β, to CCR5 transfectants. This mAb was a genuine antagonist of CCR5, since it failed to stimulate an increase in intracellular calcium concentration in the CCR5 transfectants, but blocked calcium responses elicited by RANTES, MIP-1α, or MIP-1β. This mAb inhibited most of the RANTES and MIP-1α chemotactic responses of activated T cells, but not of monocytes, suggesting differential usage of chemokine receptors by these two cell types. The 2D7 binding site mapped to the second extracellular loop of CCR5, whereas a group of mAbs that failed to block chemokine binding all mapped to the NH2-terminal region of CCR5. Efficient inhibition of an M-tropic HIV-1–derived envelope glycoprotein gp120 binding to CCR5 could be achieved with mAbs recognizing either the second extracellular loop or the NH2-terminal region, although the former showed superior inhibition. Additionally, 2D7 efficiently blocked the infectivity of several M-tropic and dual-tropic HIV-1 strains in vitro. These results suggest a complicated pattern of HIV-1 gp120 binding to different regions of CCR5, but a relatively simple pattern for chemokine binding. We conclude that the second extracellular loop of CCR5 is an ideal target site for the development of inhibitors of either chemokine or HIV-1 binding to CCR5.
TL;DR: The multiple facets of r IL-10 in experimental immunopathology indicate that the success of clinical trials with rIL-10 will depend both on the appropriate selection of the patient populations to be treated and on the early detection of possible adverse effects.
Abstract: Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine secreted by several cell types. Most anti-inflammatory effects of IL-10 are caused by its ability to deactivate macrophages and monocytes, whereas its immunosuppressive properties are due to functional inhibition of both antigen-presenting cells and T cells. On the other hand, IL-10 also exerts immunostimulatory effects, especially on B cells, CD8+ cytotoxic T cells and natural killer cells. In vivo administration of recombinant IL-10 (rIL-10) efficiently prevents experimental septic shock induced by endotoxin, staphylococcal superantigen or cecal ligation and puncture, as well as experimental autoimmune diseases mediated by T helper type 1 (T(H)1) cells and other inflammatory disorders. rIL-10 exerts paradoxical effects in cancer models, where it promotes tumour rejection, probably due to its stimulatory properties on cytotoxic cells. On the other hand, rIL-10 increases the severity of experimental infections caused by fungi or bacteria, and enhances systemic autoimmune features in mice with spontaneous lupus syndrome. Although the therapeutic potential of rIL-10 in human diseases seems promising, the multiple facets of rIL-10 in experimental immunopathology indicate that the success of clinical trials with rIL-10 will depend both on the appropriate selection of the patient populations to be treated and on the early detection of possible adverse effects.
TL;DR: In both the paediatric and adult populations, L‐AMB treated patients had a 2–6‐fold decrease in the incidence of test‐drug‐related side‐effects, compared to c‐ AMB.
Abstract: One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 mg/kg/d(L-AMB1) or liposomal amphotericin B 3 mg/ kg/d (L-AMB3) Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 05 x 10(9)/l) The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38 degrees C) without the development of any new fungal infection Clinical and laboratory parameters were collected for safety analysis In both the paediatric and adult populations, L-AMB treated patients had a 2-6-fold decrease in the incidence (P < or = 001) of test-drug-related side-effects, compared to c-AMB Severe trial-drug-related side-effects were seen in 1% of L-AMB treated patients, in contrast to 12% of patients on c-AMB (P < 001) Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L-AMB1 arm whereas the incidence was 3% in patients on L-AMB3 and 23% in those on c-AMB (P < 001) Moreover, time to develop nephrotoxicity was longer in both L-AMB arms than c-AMB (P < 001) Severe hypokalaemia was observed less frequently in both L-AMB arms (P < 001) Analysis was by intention-to-treat and included all patients randomized Success was defined by a minimum of 3 consecutive days with fever (< 38 degrees C) continuing to study end indicated by recovery of neutrophils to 05 x 10(9)/l Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end Efficacy assessments indicated success in 49% of the total group treated with c-AMB, 58% of patients responded to L-AMB1 and 64% to L-AMB3 A statistically significant difference was found between c-AMB and L-AMB3 (P = 003) but a Kaplan-Meier analysis of time to differvescence of fever showed there was no significant difference between the arms It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults The main aim of this open-label study was to compare safety between the three trial arms However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin Subsequent trials should compare amphotericin preparations in defined fungal infections
TL;DR: The data are consistent with a dominant role of IL-10 in the natural suppression of arthritis expression, whereas combined treatment with IL-4 andIL-10 appears of potential therapeutic value, not only at the onset, but also in established arthritis.
Abstract: Objective. To examine the role of endogenous interleukin-4 (IL-4) and interleukin-10 (IL-10) and the therapeutic effect of the addition of IL-4 and IL-10 in early and established murine collagen-induced arthritis (CIA).
Methods. Murine recombinant IL-4, IL-10, or the combination was given intraperitoneally twice daily from the day of arthritis onset up to 7–10 days of CIA in DBA/1 mice. Anti-IL-4, anti–IL-10, or both antibodies were given intraperitoneally before or after the onset of CIA. The effect of cytokine or anticytokine treatment was monitored visually by macroscopic scoring. Histology and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at the end of the treatment period.
Results. IL-4 alone did not provoke any effect, IL-10 slightly suppressed the arthritis, but a more pronounced amelioration was found with the combination. This cooperative effect was noted after early treatment but also occurred when the start of treatment was delayed until 1 week after onset. Apart from suppression of macroscopic signs of inflammation, combined treatment with IL-4/IL-10 also reduced cellular infiltrates in the synovial tissue and caused pronounced protection against cartilage destruction. Moreover, levels of mRNA for tumor necrosis factor α (TNFα) and IL-1 were highly suppressed both in the synovial tissue and in the articular cartilage. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) mRNA remained elevated, which suggests that the mechanism of protection may be related to suppressed production of TNFα and IL-1, with concomitant up-regulation of the IL-1Ra/IL-1 balance. However, accelerated onset of CIA and increased severity could be achieved with neutralizing anti–IL-10 antibodies. This expression could be further optimized with a combination of anti–IL-4 and anti–IL-10 antibodies, although anti–IL-4 alone was without effect.
Conclusion. Our data are consistent with a dominant role of IL-10 in the natural suppression of arthritis expression, whereas combined treatment with IL-4 and IL-10 appears of potential therapeutic value, not only at the onset, but also in established arthritis.
Washington University in St. Louis1, Max Planck Society2, Université libre de Bruxelles3, German Cancer Research Center4, Goethe University Frankfurt5, Université catholique de Louvain6, University of Liège7, John Radcliffe Hospital8, MediGene9, Vrije Universiteit Brussel10, Katholieke Universiteit Leuven11
TL;DR: No correlation was found between G+C content and gene density along the chromosome, and their variations are random, so accurate verification procedures demonstrate that there are less than two errors per 10,000 base pairs in the published sequence.
Abstract: Here we report the sequence of 569,202 base pairs of Saccharomyces cerevisiae chromosome V. Analysis of the sequence revealed a centromere, two telomeres and 271 open reading frames (ORFs) plus 13 tRNAs and four small nuclear RNAs. There are two Ty1 transposable elements, each of which contains an ORF (included in the count of 271). Of the ORFs, 78 (29%) are new, 81 (30%) have potential homologues in the public databases, and 112 (41%) are previously characterized yeast genes.
TL;DR: The use of dynamic MR pancreatography with secretin stimulation may be useful for diagnosing pancreatic papillary stenosis or dysfunction and for detecting reduced pancreatic exocrine reserve.
Abstract: PURPOSE: To assess the utility of dynamic MR pancreatography in the evaluation of the behavior of the pancreatic duct after secretin stimulation and to estimate pancreatic exocrine reserve in patients suspected of having acute recurrent or chronic pancreatitis. MATERIALS AND METHODS: Ten healthy volunteers and 13 patients suspected of having pancreatic disease and no obvious markers of chronic pancreatitis were studied. Single-shot turbo spin-echo T2-weighted dynamic MR pancreatograms were obtained before and every 30 seconds during the 10 minutes after secretin administration. Morphologic features and diameter of the pancreatic duct were monitored before and during secretin stimulation. Duodenal filling volume was graded. Results were compared with those of endoscopic retrograde cholangiopancreatography and secretin stimulation testing with collection of pancreatic fluid. RESULTS: Secretin improved the delineation of ductal morphologic features in both groups. Persistent dilatation of the pancreatic duct...
TL;DR: The new receptor was stably expressed in 1321N1 astrocytoma and CHO-K1 cells, where it couples to the stimulation of both the phosphoinositide and adenylyl cyclase pathways, a unique feature among the P2Y family.
TL;DR: The identification of an antigen recognized by autologous cytolytic T lymphocytes on a human squamous cell carcinoma of the oral cavity is reported, encoded by a mutated form of the CASP-8 gene, suggesting that a significant fraction of the point mutations generating a tumor antigen also play a role in the tumoral transformation or progression.
Abstract: Of the antigens recognized on human tumors by autologous cytolytic T lymphocytes, all those defined thus far have been identified on melanoma or renal cell carcinoma. We report here the identification of an antigen recognized by autologous cytolytic T lymphocytes on a human squamous cell carcinoma of the oral cavity. The antigen is encoded by a mutated form of the CASP-8 gene. This gene, also named FLICE or MACH, codes for protease caspase-8, which is required for induction of apoptosis through the Fas receptor and tumor necrosis factor receptor-1. The mutation, which was found in the tumor cells but not in the normal cells of the patient, modifies the stop codon and adds an Alu repeat to the coding region, thereby lengthening the protein by 88 amino acids. The ability of the altered protein to trigger apoptosis appears to be reduced relative to the normal caspase-8. The antigenic peptide is a nonamer presented by HLA-B*3503. The five last amino acids are encoded by the extension of the reading frame caused by the mutation. This, together with previous observations of CDK4 and beta-catenin mutations, suggests that a significant fraction of the point mutations generating a tumor antigen also play a role in the tumoral transformation or progression.
TL;DR: In this paper, the authors propose a model which describes the dynamics of vast classes of terrestrial plant communities growing in arid or semi-arid regions throughout the world, and show that the vegetation stripes (tiger bush) formed by these communities result from an interplay between short-range cooperative interactions controlling plant reproduction and long-range self-inhibitory interactions originating from plant competition for environmental resources.
TL;DR: This is the first demonstration of the existence of IRES-dependent translation for a proto-oncogene, allowing activation of c-myc expression under the control of trans-acting factors and in response to specific cell stimuli.
TL;DR: It is concluded that updates of growth standards are required in all populations and more marked secular changes appear to occur in the lower height centiles, which may have direct implications on the future definition of ‘short stature’ in a population.
Abstract: Secular changes in growth and maturation in recent decades have been reviewed for various populations. The secular increase in attained height during the growth period is continuing in most countries, but has slowed down. The increase in adult stature over the past decades has varied between 0.3 and 3.0 cm/decade. The secular trend in the tempo of growth (earlier menarche and peak height velocity, and shortening of the growth cycle) has come to a halt in some populations, but is continuing or has been reversed in others. The secular trend in attained height and in the tempo of growth is usually more pronounced in children from low socioeconomic backgrounds, in those with poorly educated parents or in those from rural areas. It is concluded that updates of growth standards are required in all populations. More marked secular changes appear to occur in the lower height centiles, which may have direct implications on the future definition of 'short stature' in a population.
TL;DR: It is concluded that IL‐10 prevents the generation of DC induced by GM‐CSF+IL‐4 and favors the development of macrophages with a lower T cell stimulatory potential, but secreting higher levels of IL‐8 than DC.
Abstract: We evaluated the effects of interleukin (IL)-10 on the differentiation of dendritic cells (DC) obtained by culturing plastic-adherent peripheral blood mononuclear cells for 7 days in presence of granulocyte/macrophage-colony-stimulating factor (GM-CSF) + IL-4. The addition of IL-10 at the initiation of culture resulted in the generation of macrophage-like cells with expressing high levels of CD14 and decreased levels of CD1a and CD1c. Furthermore, cells generated in presence of IL-10 secreted lower levels of IL-12, but higher levels of IL-8 compared with DC generated in absence of IL-10, both spontaneously and after CD40 engagement. Finally, cells generated in presence of IL-10 were less efficient than DC in stimulating the production of IL-2, interferon-gamma, and IL-4 by allogeneic T cells. We conclude that IL-10 prevents the generation of DC induced by GM-CSF + IL-4 and favors the development of macrophages with a lower T cell stimulatory potential, but secreting higher levels of IL-8 than DC.
TL;DR: In this article, the relationship between technological activity and patent applications is analyzed and several econometric models for count panel data are estimated, dealing with the discrete nature of patents and firm specific unobservables arising from the panel data context.
Abstract: This paper analyses the relationship between the main determinants of technological activity and patent applications. To this end, an original panel of 181 international manufacturing firms investing substantial amounts in R&D during the late 1980s has been constructed. The number of patent applications by firms is explained by current and lagged levels of R&D expenditures and technological spillovers. Technological and geographical opportunities are also taken into account as additional determinants. In order to examine this relationship, several econometric models for count panel data are estimated. These models deal with the discrete nature of patents and firm specific unobservables arising from the panel data context. The main findings of the paper are first, a high sensitivity of results to the specification of patent distribution. Second, the estimates of the preferred GMM panel data method suggest decreasing returns to scale in technological activity and finally a positive impact of technological spillovers on firm's own innovation. © 1997 John Wiley & Sons, Ltd.
TL;DR: The identification of cDNAs for a new SH2-domain-containing protein showing homology to the inositol 5-phosphatase SHIP and therefore referred to as SHIP2 is reported, which encodes a 1258 amino acid protein with a predicted molecular mass of 142 kDa.
TL;DR: It is demonstrated that, in a cohort of patients from a moderately iodine deficient area, somatic mutations increasing the constitutive activity of the TSH receptor are the major cause of autonomous hot nodules.
Abstract: A total of 33 different autonomous hot nodules from 31 patients, originating mainly from Belgium, were investigated for the presence of somatic mutations in the TSH receptor and Gs alpha genes. This constitutes an extension of our previous study, including the first 11 nodules of the series. The complete coding sequence of the TSH receptor gene and the segments of Gs alpha known to harbor mutations impairing guanosinetriphosphotase activity were studied by direct sequencing of genomic DNA extracted from the nodules. DNA from the juxtanodular tissue or peripheral white blood cells was analyzed in all patients to confirm that the mutations identified were somatic. Twenty-seven mutations (82%) were found in the TSH receptor gene, affecting a total of 12 different residues or locations. All these mutations but 2 (see below) have been identified previously as activating mutations. Only 2 mutations were found in Gs alpha (6%). In 4 nodules, no mutation was detected. Five residues (Ser281, Ile486, Ile568, Phe631, and Asp633) were found mutated in 3 or 4 different nodules, making them hot spots for activating mutations. Phe631 and Asp633 belong to a cluster of 5 consecutive residues (629-633) in the N-terminal half of transmembrane segment VI; which harbor together 44% of the mutations identified in this cohort. Two novel mutations were identified: a point mutation causing substitution of Phe for Leu at position 629 (L629F); and a deletion of 12 bases removing residues 658-661 at the C-terminal portion of exoloop 3 (del658-661). When tested by transfection in COS-7 cells, both mutant receptors display increase in constitutive stimulation of basal cAMP accumulation. Although it is still capable of binding TSH, the del658-661 mutant has completely lost the ability to respond to the stimulation by the hormone. Our results demonstrate that, in a cohort of patients from a moderately iodine deficient area, somatic mutations increasing the constitutive activity of the TSH receptor are the major cause of autonomous hot nodules.
TL;DR: The results suggest that viral tropism may be influenced not only by the coreceptors used by a given virus strain but also by how a given coreceptor is used.
Abstract: Certain chemokine receptors serve as cofactors for HIV type 1 envelope (env)-mediated cell-cell fusion and virus infection of CD4-positive cells. Macrophage tropic (M-tropic) HIV-1 isolates use CCR5, and T cell tropic (T-tropic) strains use CXCR4. To investigate the cofactors used by simian immunodeficiency viruses (SIV), we tested four T-tropic and two M-tropic SIV env proteins for their ability to mediate cell-cell fusion with cells expressing CD4 and either human or nonhuman primate chemokine receptors. Unlike HIV-1, both M- and T-tropic SIV envs used CCR5 but not CXCR4 or the other chemokine receptors tested. However, by testing a panel of CCR5/CCR2b chimeras, we found that the structural requirements for CCR5 utilization by M-tropic and T-tropic SIV strains were different. T-tropic SIV strains required the second extracellular loop of CCR5 whereas a closely related M-tropic SIV strain could, like M-tropic HIV-1 strains, use the amino-terminal domain of CCR5. As few as two amino acid changes in the SIV env V3 domain affected the regions of CCR5 that were critical for fusogenic activity. Receptor signaling was not required for either fusion or infection. Our results suggest that viral tropism may be influenced not only by the coreceptors used by a given virus strain but also by how a given coreceptor is used.