Showing papers by "Université libre de Bruxelles published in 2000"
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TL;DR: Computational results on the Traveling Salesman Problem and the Quadratic Assignment Problem show that MM AS is currently among the best performing algorithms for these problems.
2,739 citations
TL;DR: In this article, a generalized dynamic factor model with infinite dynamics and nonorthogonal idiosyncratic components is proposed, which generalizes the static approximate factor model of Chamberlain and Rothschild (1983), as well as the exact factor model a la Sargent and Sims (1977).
Abstract: This paper proposes a factor model with infinite dynamics and nonorthogonal idiosyncratic components. The model, which we call the generalized dynamic-factor model, is novel to the literature and generalizes the static approximate factor model of Chamberlain and Rothschild (1983), as well as the exact factor model a la Sargent and Sims (1977). We provide identification conditions, propose an estimator of the common components, prove convergence as both time and cross-sectional size go to infinity at appropriate rates, and present simulation results. We use our model to construct a coincident index for the European Union. Such index is defined as the common component of real GDP within a model including several macroeconomic variables for each European country.
1,832 citations
TL;DR: Understanding the control exerted by cytokines on T helper cell subsets 1 and 2 (TH1-TH2) development has progressed to a fairly satisfying knowledge of intracellular signals and transcription factors.
Abstract: Understanding the control exerted by cytokines on T helper cell subsets 1 and 2 (TH1-TH2) development has progressed to a fairly satisfying knowledge of intracellular signals and transcription factors. Less is understood about the molecular basis of TH1-TH2 development exerted by other parameters, such as how the antigen presenting cell can influence this process. Recent work suggests that dendritic cell subsets contribute significant polarizing influences on T helper differentiation, but how this comes about is less clear. In some cases known pathways may be used, as in the dendritic cell subset 1 exerting TH1 polarization by interleukin 12 (IL-12) production and STAT4 activation. In others, the effects are still in need of explanation.
1,177 citations
TL;DR: Research in social insect behaviour has provided computer scientists with powerful methods for designing distributed control and optimization algorithms that tend to exhibit a high degree of flexibility and robustness in a dynamic environment.
Abstract: Research in social insect behaviour has provided computer scientists with powerful methods for designing distributed control and optimization algorithms. These techniques are being applied successfully to a variety of scientific and engineering problems. In addition to achieving good performance on a wide spectrum of 'static' problems, such techniques tend to exhibit a high degree of flexibility and robustness in a dynamic environment.
923 citations
TL;DR: In this paper, the authors proposed regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis.
Abstract: Background Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. Methods The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated...
859 citations
TL;DR: This paper overviews some models derived from the observation of real ants, emphasizing the role played by stigmergy as distributed communication paradigm, and shows how these models have inspired a number of novel algorithms for the solution of distributed optimization and distributed control problems.
821 citations
TL;DR: Using positron emission tomography and regional cerebral blood flow measurements, it is shown that waking experience influences regional brain activity during subsequent sleep and supports the hypothesis that memory traces are processed during REM sleep in humans.
Abstract: The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.
706 citations
TL;DR: In this article, the cohomology groups of the differential introduced by Becchi, Rouet, Stora and Tyutin are computed in a self-contained manner, with the sources of the BRST variations of the fields included in the problem.
611 citations
TL;DR: Two cDNAs encoding NADPH oxidases and constituting the thyroid H2O2 generating system have been cloned and the dog mRNA expression is thyroid-specific and up-regulated by agents activating the cAMP pathway as is the synthesis of the polypeptides they are coding for.
609 citations
TL;DR: This paper presents a series of experiments where a group of mobile robots gather 81 randomly distributed objects and cluster them into one pile through stigmergy, a principle which allows indirect communication between agents through sensing and modification of the local environment which determines the agents’ behaviour.
Abstract: This paper presents a series of experiments where a group of mobile robots gather 81 randomly distributed objects and cluster them into one pile. Coordination of the agents’ movements is achieved through stigmergy. This principle, originally developed for the description of termite building behaviour, allows indirect communication between agents through sensing and modification of the local environment which determines the agents’ behaviour. The efficiency of the work was measured for groups of one to five robots working together. Group size is a critical factor. The mean time to accomplish the task decreases for one, two, and three robots respectively, then increases again for groups of four and five agents, due to an exponential increase in the number of interactions between robots which are time consuming and may eventually result in the destruction of existing clusters. We compare our results with those reported by Deneubourg et al. (1990) where similar clusters are observed in ant colonies, generated by the probabilistic behaviour of workers.
554 citations
TL;DR: The vocal quality of a patient is modeled by means of a Dysphonia Severity Index (DSI), which is designed to establish an objective and quantitative correlate of the perceived vocal quality.
Abstract: The vocal quality of a patient is modeled by means of a Dysphonia Severity Index (DSI), which is designed to establish an objective and quantitative correlate of the perceived vocal quality The DSI is based on the weighted combination of the following selected set of voice measurements: highest Frequency (F-0-High in Hz), lowest intensity (I-Low in dB), maximum phonation time (Mm in s), and jitter (%). The DSI is derived from a multivariate analysis of 387 subjects with the goal of describing, purely based on objective measures, the perceived voice quality It is constructed as DSI = 0.13 x MPT + 0.0053 x F-0-High - 0.26 x I-Low - 1.18 x Jitter (%)+ 12.4. The DSI For perceptually normal voices equals +5 and for severely dysphonic voices -5. The more negative the patient's index, the worse is his or her vocal quality As such, the DSI is especially useful to evaluate therapeutic evolution of dysphonic patients. Additionally, there is a high correlation between the DSI and the Voice Handicap Index score.
TL;DR: It is concluded that activation of presynaptic CB1 receptors decreases Ca2+‐dependent GABA release, and thereby reduces the power of hippocampal network oscillations.
Abstract: Using a new antibody developed against the C-terminus of the cannabinoid receptor (CB1), the immunostaining in the hippocampus revealed additional axon terminals relative to the pattern reported previously with an N-terminus antibody. Due to a greater sensitivity of this antibody, a large proportion of boutons in the dendritic layers displaying symmetrical (GABAergic) synapses were also strongly immunoreactive for CB1 receptors, as were axon terminals of perisomatic inhibitory cells containing cholecystokinin. Asymmetrical (glutamatergic) synapses, however, were always negative for CB1. To investigate the effect of presynaptic CB1 receptor activation on hippocampal inhibition, we recorded inhibitory postsynaptic currents (IPSCs) from principal cells. Bath application of CB1 receptor agonists (WIN55,212-2 and CP55,940) suppressed IPSCs evoked by local electrical stimulation, which could be prevented or reversed by the CB1 receptor antagonist SR141716A. Action potential-driven IPSCs, evoked by pharmacological stimulation of a subset of interneurons, were also decreased by CB1 receptor activation. We also examined the effects of CB1 receptor agonists on Ca2+-independent miniature IPSCs (mIPSC). Both agonists were without significant effect on the frequency or amplitude of mIPSCs. Synchronous gamma oscillations induced by kainic acid in the CA3 region of hippocampal slices were reversibly reduced in amplitude by the CB1 receptor agonist CP 55,940, which is consistent with an action on IPSCs. We used CB1-/- knock-out mice to confirm the specificity of the antibody and of the agonist (WIN55,212-2) action. We conclude that activation of presynaptic CB1 receptors decreases Ca2+-dependent GABA release, and thereby reduces the power of hippocampal network oscillations.
TL;DR: Mice lacking TIA‐1 are hypersensitive to the toxic effects of LPS, indicating that this translational control pathway may regulate the organismal response to microbial stress.
Abstract: TIA-1 and TIAR are related proteins that bind to an AU-rich element (ARE) in the 3' untranslated region of tumor necrosis factor alpha (TNF-alpha) transcripts. To determine the functional significance of this interaction, we used homologous recombination to produce mutant mice lacking TIA-1. Although lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type and TIA-1(-/-) mice express similar amounts of TNF-alpha transcripts, macrophages lacking TIA-1 produce significantly more TNF-alpha protein than wild-type controls. The half-life of TNF-alpha transcripts is similar in wild-type and TIA-1(-/-) macrophages, indicating that TIA-1 does not regulate transcript stability. Rather, the absence of TIA-1 significantly increases the proportion of TNF-alpha transcripts that associate with polysomes, suggesting that TIA-1 normally functions as a translational silencer. TIA-1 does not appear to regulate the production of interleukin 1 beta, granulocyte-macrophage colony-stimulating factor or interferon gamma, indicating that its effects are, at least partially, transcript specific. Mice lacking TIA-1 are hypersensitive to the toxic effects of LPS, indicating that this translational control pathway may regulate the organismal response to microbial stress.
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01 Jan 2000TL;DR: In this paper, the aggregate net effect of government funding on business RD Direct funding as well as tax incentives are quantified and shown to be more effective when they are stable over time.
Abstract: This paper attempts to quantify the aggregate net effect of government funding on business RD Direct funding as well as tax incentives are more effective when they are stable over time: firms do not invest in additional RD Direct government funding and RD The stimulating effect of government funding varies with respect to its generosity: it...
TL;DR: A new local optimizer called SOP-3-exchange is presented for the sequential ordering problem that extends a local search for the traveling salesman problem to handle multiple constraints directly without increasing computational complexity.
Abstract: We present a new local optimizer called SOP-3-exchange for the sequential ordering problem that extends a local search for the traveling salesman problem to handle multiple constraints directly without increasing computational complexity. An algorithm that combines the SOP-3-exchange with an Ant Colony Optimization algorithm is described, and we present experimental evidence that the resulting algorithm is more effective than existing methods for the problem. The best-known results for many of a standard test set of 22 problems are improved using the SOP-3-exchange with our Ant Colony Optimization algorithm or in combination with the MPO/AI algorithm (Chen and Smith 1996).
TL;DR: In this article, the authors analyse the decision of an agent with time-inconsistent preferences to consume a good that exerts an externality on future welfare, and show that when the agent cannot commit to future consumption and learning decisions, incomplete learning may occur on a Markov perfect equilibrium path of the resulting intrapersonal game.
Abstract: We analyse the decision of an agent with time-inconsistent preferences to consume a good that exerts an externality on future welfare. The extent of the externality is initially unknown, but may be learned via a costless sampling procedure. We show that when the agent cannot commit to future consumption and learning decisions, incomplete learning may occur on a Markov perfect equilibrium path of the resulting intra-personal game. In such a case, each agent's incarnation stops learning for some values of the posterior distribution of beliefs and acts under self-restricted information. This conduct is interpreted as strategic ignorance. All equilibria featuring this property strictly Pareto dominate the complete learning equilibrium for any posterior distribution of beliefs.
TL;DR: It is shown here that RhAG and also RhGK, a new human homologue expressed in kidney cells only, function as ammonium transport proteins when expressed in yeast, and specifically complement the growth defect of a yeast mutant deficient in ammonium uptake.
Abstract: The Rhesus blood-group antigens are defined by a complex association of membrane polypeptides that includes the non-glycosylated Rh proteins (RhD and RhCE) and the RHag glycoprotein, which is strictly required for cell surface expression of these antigens. RhAG and the Rh polypeptides are erythroid-specific transmembrane proteins belonging to the same family (36% identity). Despite their importance in transfusion medicine, the function of RhAG and Rh proteins remains unknown, except that their absence in Rh(null) individuals leads to morphological and functional abnormalities of erythrocytes, known as the Rh-deficiency syndrome. We recently found significant sequence similarity between the Rh family proteins, especially RhAG, and Mep/Amt ammonium transporters. We show here that RhAG and also RhGK, a new human homologue expressed in kidney cells only, function as ammonium transport proteins when expressed in yeast. Both specifically complement the growth defect of a yeast mutant deficient in ammonium uptake. Moreover, ammonium efflux assays and growth tests in the presence of toxic concentrations of the analogue methylammonium indicate that RhAG and RhGK also promote ammonium export. Our results provide the first experimental evidence for a direct role of RhAG and RhGK in ammonium transport. These findings are of high interest, because no specific ammonium transport system has been characterized so far in human.
TL;DR: The dyad and single-word analyses are efficient for the detection of regulatory patterns in gene clusters from DNA chip experiments and should provide a fast and efficient way to discover new regulatory sites for as yet unknown transcription factors.
Abstract: The application of microarray and related technologies is currently generating a systematic catalog of the transcriptional response of any single gene to a multiplicity of experimental conditions. Clustering genes according to the similarity of their transcriptional response provides a direct hint to the regulons of the different transcription factors, many of which have still not been characterized. We have developed a new method for deciphering the mechanism underlying the common transcriptional response of a set of genes, i.e. discovering cis-acting regulatory elements from a set of unaligned upstream sequences. This method, called dyad analysis, is based on the observation that many regulatory sites consist of a pair of highly conserved trinucleotides, spaced by a non-conserved region of fixed width. The approach is to count the number of occurrences of each possible spaced pair of trinucleotides, and to assess its statistical significance. The method is highly efficient in the detection of sites bound by C6 Zn2 binuclear cluster proteins, as well as other transcription factors. In addition, we show that the dyad and single-word analyses are efficient for the detection of regulatory patterns in gene clusters from DNA chip experiments. In combination, these programs should provide a fast and efficient way to discover new regulatory sites for as yet unknown transcription factors.
Posted Content•
TL;DR: In this paper, a search model that treats credit and labor market imperfections in a symmetrical way was proposed to explain why European and US unemployment differ so much when labor markets have become more similar at the margin in Europe and the US.
Abstract: Labor market frictions are not the only possible factor responsible for high unemployment. Credit market imperfections, driven by microeconomic frictions and impacted upon by macroeconomic factors such as monetary policy, could also be to blame. This paper shows that labor and credit market imperfections interact in a complementary way - which may explain why European and US unemployment differ so much when labor markets have become more similar at the margin in Europe and the US. To develop this idea, we build a search model that treats credit and labor market imperfections in a symmetrical way. We introduce specificity in credit relationships, and assume that credit to potential entrepreneurs is rationed due to endogenous search frictions, in the spirit of Diamond (1990). These imperfections mirror the job search frictions that we introduce, a la Mortensen- Pissarides (1994), in the labor market.
TL;DR: In this paper, the value of patents is influenced by patent strategy, technological diversity, domestic and international R&D collaborations and/or co-applications, and the mix of designated states for protection.
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TL;DR: For a given dimension d, the Lagrangians under consideration are labeled by an integer k=1,2,...,[(d-1)/2] as mentioned in this paper.
Abstract: Gravitation theories selected by requiring that they have a unique anti-de Sitter vacuum with a fixed cosmological constant are studied. For a given dimension d, the Lagrangians under consideration are labeled by an integer k=1,2, . . . ,[(d-1)/2]. Black holes for each d and k are found and are used to rank these theories. A minimum possible size for a localized electrically charged source is predicted in the whole set of theories, except general relativity. It is found that the thermodynamic behavior falls into two classes: If d-2k=1, these solutions resemble the three dimensional black hole; otherwise, their behavior is similar to the Schwarzschild-AdS4 geometry. ©2000 The American Physical Society.
TL;DR: Further exploration and precision of the role of NO and development of techniques to assess the NO balance in individual patients is necessary before further progress can be made in this field.
Abstract: Nitric oxide (NO) is believed to play a key role in the pathogenesis of septic shock, although many aspects of NO's involvement remain poorly defined. Recent years have seen advances in our understanding of the production and effects of NO, but much of the work has been done in animal models and may not be directly relevant to the clinical situation. Differences between species and models can account for many of the apparently conflicting results obtained. Nevertheless, NO-directed strategies have been developed and tested clinically. However, NO can have both beneficial and detrimental effects on many organ systems in sepsis and attempts to nonselectively block all its actions may therefore not yield positive results on outcome. Further exploration and precision of the role of NO and development of techniques to assess the NO balance in individual patients is necessary before further progress can be made in this field.
TL;DR: The results suggest that the stimulant effect of low doses of caffeine is mediated by A2A receptor blockade while the depressant effect seen at higher doses under some conditions is explained by A1 receptor blockade.
Abstract: 1. The locomotor stimulatory effects induced by caffeine (1,3, 7-trimethylxanthine) in rodents have been attributed to antagonism of adenosine A(1) and A(2A) receptors. Little is known about its locomotor depressant effects seen when acutely administered at high doses. The roles of adenosine A(1) and A(2A) receptors in these activities were investigated using a Digiscan actimeter in experiments carried out in mice. Besides caffeine, the A(2A) antagonist SCH 58261 (5-amino-7-(beta-phenylethyl)-2-(8-furyl)pyrazolo[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine), the A(1) antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), the A(1) agonist CPA (N(6)-cyclopentyladenosine) and A(2A) receptor knockout mice were used. 2. Caffeine had a biphasic effect on locomotion of wild-type mice not habituated to the open field, stimulating locomotion at 6.25 - 25 mg kg(-1) i.p. doses, while depressing it at 100 mg kg(-1). In sharp contrast, caffeine dose-dependently decreased locomotion in A(2A) receptor knockout mice over the whole range of tested doses. 3. The depressant effects induced by high doses of caffeine were lost in control CD1 mice habituated to the open field. 4. The A(1) agonist CPA depressed locomotion at 0.3 - 1 mg kg(-1) i.p. doses. 5. The A(1) antagonist DPCPX decreased locomotion of A(2A) receptor knockouts and CD1 mice at 5 mg kg(-1) i.p. and 25 mg kg(-1) i.p. respectively. 6. DPCPX (0.2 - 1 mg kg(-1) i.p.) left unaltered or even reduced the stimulant effect of SCH 58261 (1 - 3 mg kg(-1) i.p.) on CD1 mice. 7. These results suggest therefore that the stimulant effect of low doses of caffeine is mediated by A(2A) receptor blockade while the depressant effect seen at higher doses under some conditions is explained by A(1) receptor blockade.
TL;DR: In rectovaginal endometriotic nodules, there was a close histological relationship between nerves and endometRIotic foci, and between nerve and the fibrotic component of the nodule, and it is postulate that such topographical relationships could at least partially explain the strong association between this lesion and pain.
Abstract: The histological relationships between fibrotic tissue, endometriotic foci and nerves in the rectovaginal septum endometriotic or adenomyotic nodule were studied. This is considered to be one of the most severe forms of deep endometriosis. Masson's trichrome staining for fibrosis detection and immunohistochemistry with the S100 monoclonal antibody for nerve detection were performed in 28 rectovaginal endometriotic nodules from patients presenting with severe dysmenorrhoea and deep dyspareunia (23 patients with no other endometriotic location or potential cause of pain at laparoscopy and ultrasonography; five patients with multiple pelvic endometriotic localizations and other potential causes of pain at laparoscopy). Patients were allocated to two groups on the basis of their preoperative pain scores for pelvic pain, dysmenorrhoea and deep dyspareunia (group 1, score >7; group 2, score < or =7). For each symptom, the mean number of nerves and endometriotic lesions per high-power field and the mean largest diameter of the lesions were not statistically different in groups 1 and 2. The mean percentages of nerves located within the fibrosis of the nodule and within endometriotic lesions were significantly higher in group 1 than in group 2. Among nerves located within endometriotic lesions, there was a significantly higher proportion showing intraneurial and perineurial invasion by endometriosis in group 1 than in group 2. In rectovaginal endometriotic nodules, there was a close histological relationship between nerves and endometriotic foci, and between nerves and the fibrotic component of the nodule. We postulate that such topographical relationships could at least partially explain the strong association between this lesion and pain.
TL;DR: In this paper, the authors studied the relationship between the scalar potential and the non-minimal coupling of scalar fields to the Ricci curvature in inflation and quintessence models.
Abstract: The nonminimal coupling (NMC) of the scalar field to the Ricci curvature is unavoidable in many cosmological scenarios. Inflation and quintessence models based on nonminimally coupled scalar fields are studied, with particular attention to the balance between the scalar potential and the NMC term $\ensuremath{\xi}R{\ensuremath{\varphi}}^{2}/2$ in the action. NMC makes acceleration of the universe harder to achieve for the usual potentials, but it is beneficial in obtaining cosmic acceleration with unusual potentials. The slow-roll approximation with NMC, conformal transformation techniques, and other aspects of the physics of NMC are clarified.
01 Jan 2000
TL;DR: Termite societies display a wide array of polymorphism patterns, rivalled only by the most complex ant societies as mentioned in this paper, where immatures of either sex deviate from the straight hemimetabolous pathway leading from the egg to the winged imago.
Abstract: Termite societies display a wide array of polymorphism patterns, rivalled only by the most complex ant societies. Caste differentiation in termites occurs when immatures of either sex deviate from the straight hemimetabolous pathway leading from the egg to the winged imago. Two kinds of irreversible deviations are found in primitive termites: one leads to the sterile soldier caste, the other to neotenic reproductives. Social tasks are primitively done by immatures which may postpone their maturation but retain a full range of developmental options. A major event in the evolution of termite caste patterns is the polyphyletic onset of a worker caste which is irreversibly excluded from the imaginal pathway. Termites with workers went through a remarkable behavioural and ecological diversification. After defining terms, I review here the diversity of caste patterns in termites in an evolutionary perspective. I provide examples of relationships between caste patterns and behavioural ecology, and examine the decision and regulatory mechanisms affecting caste determination. Trends in the evolution of termite caste patterns are then outlined, of which the most salient and enigmatic ones are the repeated occurrence of sexual dimorphism among workers and the frequent specialization of one sex in the formation of sterile castes.
TL;DR: It is found that bisphosphonates inhibit breast cancer cell growth by inducing cell death in vitro, suggesting that the apoptotic process observed in the MCF‐7 cell line is mediated, at least partly, by the caspase system.
Abstract: Breast cancer frequently spreads to bone and is almost always associated with osteolysis. This tumor-induced osteolysis is caused by increased osteoclastic bone resorption. Bisphosphonates are used successfully to inhibit bone resorption in tumor bone disease and may prevent development of new osteolytic lesions. The classical view is that bisphosphonates only act on bone cells. We investigated their effects on breast cancer cells using three human cell lines, namely, MCF-7, T47D, and MDA.MB.231, and we tested four structurally different bisphosphonates: clodronate, pamidronate, ibandronate, and zoledronate. We performed time course studies for each bisphosphonate at various concentrations and found that all four compounds induced a nonreversible growth inhibition in both MCF-7 and T47D cell lines in a time- and dose-dependent manner. The MDA.MB.231 cell line was less responsive. Bisphosphonates induced apoptosis in MCF-7 and cell necrosis in T47D cells. The inhibition of MCF-7 cell proliferation could be reverted almost completely by the benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone (z-VAD-fmk) inhibitor of caspases, suggesting that the apoptotic process observed in the MCF-7 cell line is mediated, at least partly, by the caspase system. Caspase activity was little changed by bisphosphonates in T47D cells and the inhibitor of caspase did not modify bisphosphonates effects. In summary, we found that bisphosphonates inhibit breast cancer cell growth by inducing cell death in vitro. Such effects could contribute to the beneficial role of bisphosphonates in the treatment and the prevention of tumor-induced osteolysis.
TL;DR: The data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.
Abstract: Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (muMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and muMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-gamma, interleukin (IL)-2, and IL-4, whereas those from muMT mice produced IFN-gamma and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-gamma, and IL-2, whereas administration of DCs from muMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from muMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.
TL;DR: A reliable prenatal diagnosis of congenital CMV infection based on PCR on amniocentesis samples can be made after 21 weeks' pregnancy, after a 7-week interval between diagnosis of maternal infection and antenatal procedure.
TL;DR: In a family with multiple gastrointestinal stromal tumors and diffuse hyperplasia of myenteric plexus layer, another mutation of KIT is identified, a single base mutation, resulting in the substitution of Glu for Lys(642) in the kinase I domain, and studied its biological effect in a cellular system.
Abstract: The proto-oncogene KIT encodes the receptor tyrosine kinase KIT. Gain-of-function mutations in the juxtamembrane domain of KIT have been reported in human gastrointestinal stromal tumors. In a family with multiple gastrointestinal stromal tumors and diffuse hyperplasia of myenteric plexus layer, we have identified another mutation of KIT, a single base mutation, resulting in the substitution of Glu for Lys642 in the kinase I domain, and studied its biological effect in a cellular system. The mouse homologue of the human KIT mutant was generated by site-directed mutagenesis and stably transfected into the interleukin-3-dependent Ba/F3 murine cell line. The oncogenic potential of the mutated KIT was assessed in vitro by a proliferation assay and in vivo by transplantation into nude mice. Transfected Ba/F3 cells grew autonomously in absence of growth factors and formed tumors in nude mice. Substitution of Glu for Lys642 is an oncogenic mutation in the tyrosine kinase domain of KIT. As germline heterozygous mutation, it causes a diffuse hyperplasia of myenteric interstitial cells of Cajal during embryonic development and occurrence of multiple gastrointestinal stromal tumors at adulthood.