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Showing papers by "Université catholique de Louvain published in 1999"


Journal ArticleDOI
06 Aug 1999-Science
TL;DR: A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome), finding that 17 percent were essential for viability in rich medium.
Abstract: The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches are required to systematically determine their function. A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome). Of the deleted ORFs, 17 percent were essential for viability in rich medium. The phenotypes of more than 500 deletion strains were assayed in parallel. Of the deletion strains, 40 percent showed quantitative growth defects in either rich or minimal medium.

4,051 citations


Journal ArticleDOI
TL;DR: In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days, but after six months there was a significant survival benefit, and earlyRevascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenesis.
Abstract: Background The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. Methods Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. Results The mean (+/-SD) age of the patients was 66+/-10 years, 32 percent were women, and 55 percent had been transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P = 0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). Conclusions In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock. (N Engl J Med 1999;341:625-34.) (C) 1999, Massachusetts Medical Society.

2,481 citations


Journal ArticleDOI
11 Aug 1999-JAMA
TL;DR: In untreated older patients with isolated Systolic Hypertension in Europe, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.
Abstract: ContextThe clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies.ObjectiveTo compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension.DesignSubstudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique.SettingFamily practices and outpatient clinics at primary and secondary referral hospitals.ParticipantsA total of 808 older (aged ≥60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic.InterventionsFor the overall study, patients were randomized to nitrendipine (n=415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n=393).Main Outcome MeasuresTotal and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points.ResultsAfter adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval {CI}, 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement.ConclusionsIn untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.

1,571 citations


Journal ArticleDOI
TL;DR: In this article, the authors define a statistical model allowing determination of the statistical properties of the nonparametric estimators in the multi-output and multi-input case, and provide the asymptotic sampling distribution of the FDH estimator in a multivariate setting and of the DEA estimator for the bivariate case.
Abstract: Efficiency scores of firms are measured by their distance to an estimated production frontier. The economic literature proposes several nonparametric frontier estimators based on the idea of enveloping the data (FDH and DEA-type estimators). Many have claimed that FDH and DEA techniques are non-statistical, as opposed to econometric approaches where particular parametric expressions are posited to model the frontier. We can now define a statistical model allowing determination of the statistical properties of the nonparametric estimators in the multi-output and multi-input case. New results provide the asymptotic sampling distribution of the FDH estimator in a multivariate setting and of the DEA estimator in the bivariate case. Sampling distributions may also be approximated by bootstrap distributions in very general situations. Consequently, statistical inference based on DEA/FDH-type estimators is now possible. These techniques allow correction for the bias of the efficiency estimators and estimation of confidence intervals for the efficiency measures. This paper summarizes the results which are now available, and provides a brief guide to the existing literature. Emphasizing the role of hypotheses and inference, we show how the results can be used or adapted for practical purposes.

1,099 citations


Journal ArticleDOI
TL;DR: Aminoglycosides are highly potent, broad-spectrum antibiotics with many desirable properties for the treatment of life-threatening infections and have a history marked by the successive introduction of a series of milestone compounds.
Abstract: Aminoglycosides are highly potent, broad-spectrum antibiotics with many desirable properties for the treatment of life-threatening infections ([28][1]). Their history begins in 1944 with streptomycin and was thereafter marked by the successive introduction of a series of milestone compounds (

1,018 citations


Journal ArticleDOI
TL;DR: The results suggest that injection of the MAGE‐3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced.
Abstract: Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed. Of the 25 patients who received the complete treatment, 7 displayed significant tumor regressions. All but one of these regressions involved cutaneous metastases. Three regressions were complete and 2 of these led to a disease-free state, which persisted for more than 2 years after the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL) response was found in the blood of the 4 patients who were analyzed, including 2 who displayed complete tumor regression. Our results suggest that injection of the MAGE-3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced.

837 citations


Journal ArticleDOI
TL;DR: In this paper, the relative location of different income groups depends on the spatial pattern of amenities in a city, and when the center has a strong amenity advantage over the suburbs, the rich are likely to live at central locations.

813 citations


Journal ArticleDOI
TL;DR: Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation and decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources.
Abstract: Background Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease. Methods A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation. Results Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment limiting. The rates of other adverse events were similar among the groups. Conclusions Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation. (N Engl J Med 1999; 340:1462-70.) (C) 1999, Massachusetts Medical Society.

654 citations


Journal ArticleDOI
TL;DR: In this paper, a model of endogenous growth and endogenous industry location where the two interact is presented. But with global spillovers in RD O30, R12, and RD O16, the model is not robust enough.

544 citations


Journal ArticleDOI
TL;DR: A consistent bootstrap estimation procedure for obtaining confidence intervals for Malmquist indices of productivity and their decompositions and in terms of input-oriented indices is developed.

531 citations


Journal ArticleDOI
TL;DR: In this paper, a discussion is organized around two divisions of student motivation: intrinsic-extrinsic motivation and future-present orientation, and an extensive review of both the history of this concept and several studies that provide insight into the relation of future time perspective to human motivation is provided.
Abstract: Students' multiple goals and motivations for engaging in school learning are discussed. Our discussion is organized around two divisions of student motivation: intrinsic-extrinsic motivation and future-present orientation. In the case of future-present orientation, an extensive review of both the history of this concept and several studies that provide insight into the relation of Future Time Perspective (FTP) to human motivation is provided. A brief review of literature on intrinsic motivation and goal theory is also provided. We consider the possibility that intrinsic motivation and FTP can be integrated in a meaningful way. We believe that providing a theoretical base for understanding this interaction will contribute toward developing a multidimensional picture of student motivation.

Journal ArticleDOI
TL;DR: Uremia may be described as a state of carbonyl overload or "carbonyl stress" resulting from either increased oxidation of carbohydrates and lipids (oxidative stress) or inadequate detoxification or inactivation of reactive carbonyL compounds derived from both carbohydrates andlipids by oxidative and nonoxidatives.

Journal ArticleDOI
TL;DR: It is suggested that proline accumulation is a symptom of salt-stress injury in rice and that its accumulation in salt-sensitive plants results from an increase in OAT activity and a increase in the endogenous pool of its precursor glutamate.
Abstract: Salt-stress effects on osmotic adjustment, ion and proline concentrations as well as proline metabolizing enzyme activities were studied in two rice (Oryza sativa L.) cultivars differing in salinity resistance: I Kong Pao (IKP; salt-sensitive) and Nona Bokra (salt-resistant), The salt-sensitive cultivar exposed to 50 and 100 mM NaCl in nutritive solution for 3 and 10 days accumulated higher levels of sodium land proline than the salt-resistant cultivar and displayed lower levels of osmotic adjustment. Proline accumulation was not related to proteolysis and could not be explained by stress-induced modifications in Delta(1)-pyrroline-5-carboxylate reductase (P5CR; EC 1.5.1.2) or proline dehydrogenase (PDN; EC 1.5.1.2) activities recorded in vitro. The extracted ornithine delta-aminotransferase (OAT;: EC 2.6.1.13) activity was increased by salt stress in the salt-sensitive cultivar only. In both genotypes, salt stress induced an increase in the aminating activity of root glutamate dehydrogenase (GDH; EC 1.4.1.2) while deaminating activity was reduced in the leaves of the salt-sensitive cultivar, The total extracted glutamine synthetase activity (CS; EC 6.3.1.2) was reduced in response to salinity but NaCl had contrasting effects on GS1 and GS2 isoforms in salt-sensitive IKP, Salinity increased the activity of ferredoxin-dependent glutamate synthase (Fd-GOGAT; EC 1.4.7.1) extracted from leaves of both genotypes and increased the activity of NADH-dependent glutamate synthase (NADH-GOGAT; EC 1.4.1.14) in the salt-sensitive cultivar, It is suggested that proline accumulation is a symptom of salt-stress injury in rice and that its accumulation in salt-sensitive plants results from an increase in OAT activity and an increase in the endogenous pool of its precursor glutamate. The physiological significance of the recorded changes are analyzed in relation to the functions of these enzymes in plant metabolism.

Journal ArticleDOI
TL;DR: The results complement and specify, at a neural level, previous behavioral and divided visual field studies which have suggested that the loss of configural face information by inversion may slow down and increase the difficulty of face processing, particularly in the RH.

Journal ArticleDOI
Klaus F. X. Mayer1, C. Schüller1, R. Wambutt, George Murphy2  +230 moreInstitutions (21)
16 Dec 1999-Nature
TL;DR: Analysis of 17.38 megabases of unique sequence, representing about 17% of the Arabidopsis genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements.
Abstract: The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

Journal ArticleDOI
TL;DR: Even at a low degree of environmental exposure, cadmium may promote skeletal demineralisation, which may lead to increased bone fragility and raised risk of fractures.

Journal ArticleDOI
TL;DR: 2 well-known clinical concepts of myocardial glucose metabolism require critical reevaluation: the diagnostic concept of metabolic imaging with PET and the glucose tracer analogue 18F-2-deoxy- 2-fluoro-d-glucose (FDG) and the therapeutic concept of metabolism support for the postischemic heart with glucose, insulin, and K+ (GIK).
Abstract: The homeostasis of plasma glucose levels is essential for survival of the mammalian organism. Since blood glucose concentration is maintained within a narrow range, glucose is a most reliable substrate for energy production in the heart. The importance of glucose metabolism via glycolysis is well appreciated in ischemic and hypertrophied heart muscle,1 2 3 4 but aerobic glucose metabolism for support of normal contractile function has received less attention, mainly because of the well-known fact that fatty acids are normally the predominant fuel for cardiac energy production.2 5 6 We have drawn attention to the heart as a true “omnivore,” ie, an organ that functions best when it oxidizes different substrates simultaneously.7 In light of this concept, we wish to reexamine myocardial glucose metabolism and its relevance to the human heart. In recent years, the tools of molecular and cellular biology have provided new insight into the mechanisms of glucose transport and phosphorylation. Glycogen metabolism has come into greater focus. The regulation of glycolysis is more accurately defined, and the effects of second messengers on myocardial glucose utilization are better known. In view of this background, 2 well-known clinical concepts of myocardial glucose metabolism require critical reevaluation: (1) the diagnostic concept of metabolic imaging with PET and the glucose tracer analogue 18F-2-deoxy-2-fluoro-d-glucose (FDG) and (2) the therapeutic concept of metabolic support for the postischemic heart with glucose, insulin, and K+ (GIK). The simple sugar d-glucose is the most abundant organic molecule in nature. Glucose for the heart is derived either from the bloodstream or from intracellular stores of glycogen (Figure 1⇓). The transport of glucose into the cardiomyocyte occurs along a steep concentration gradient and is regulated by specific transporters. Intracellular glucose is rapidly phosphorylated and becomes a substrate for the …

Journal ArticleDOI
01 May 1999-Chest
TL;DR: At presentation, the symptoms seen with AFBs do not differ according to the age of the patient; however, the delay to diagnosis, the location of the AFBs, and the radiographic images differ between child and adult populations.

Journal ArticleDOI
TL;DR: Among the ORFs with a high degree of similarity to known sequences are a collection of putative transposases, resolvases, and integrases, suggesting an evolution involving lateral movement of DNA among species.
Abstract: The Bacillus anthracis Sterne plasmid pXO1 was sequenced by random, "shotgun" cloning. A circular sequence of 181,654 bp was generated. One hundred forty-three open reading frames (ORFs) were predicted using GeneMark and GeneMark.hmm, comprising only 61% (110,817 bp) of the pXO1 DNA sequence. The overall guanine-plus-cytosine content of the plasmid is 32.5%. The most recognizable feature of the plasmid is a "pathogenicity island," defined by a 44.8-kb region that is bordered by inverted IS1627 elements at each end. This region contains the three toxin genes (cya, lef, and pagA), regulatory elements controlling the toxin genes, three germination response genes, and 19 additional ORFs. Nearly 70% of the ORFs on pXO1 do not have significant similarity to sequences available in open databases. Absent from the pXO1 sequence are homologs to genes that are typically required to drive theta replication and to maintain stability of large plasmids in Bacillus spp. Among the ORFs with a high degree of similarity to known sequences are a collection of putative transposases, resolvases, and integrases, suggesting an evolution involving lateral movement of DNA among species. Among the remaining ORFs, there are three sequences that may encode enzymes responsible for the synthesis of a polysaccharide capsule usually associated with serotype-specific virulent streptococci.

Journal ArticleDOI
TL;DR: A new mechanism for the cholesterol-induced impairment of NO production through the modulation of caveolin abundance in endothelial cells is established, a mechanism that may participate in the pathogenesis of endothelial dysfunction and the proatherogenic effects of hypercholesterolemia.
Abstract: Hypercholesterolemia is a central pathogenic factor of endothelial dysfunction caused in part by an impairment of endothelial nitric oxide (NO) production through mechanisms that remain poorly characterized. The activity of the endothelial isoform of NO synthase (eNOS) was recently shown to be modulated by its reciprocal interactions with the stimulatory Ca2+-calmodulin complex and the inhibitory protein caveolin. We examined whether hypercholesterolemia may reduce NO production through alteration of this regulatory equilibrium. Bovine aortic endothelial cells were cultured in the presence of serum obtained from normocholesterolemic (NC) or hypercholesterolemic (HC) human volunteers. Exposure of endothelial cells to the HC serum upregulated caveolin abundance without any measurable effect on eNOS protein levels. This effect of HC serum was associated with an impairment of basal NO release paralleled by an increase in inhibitory caveolin-eNOS complex formation. Similar treatment with HC serum significantly attenuated the NO production stimulated by the calcium ionophore A23187. Accordingly, higher calmodulin levels were required to disrupt the enhanced caveolin-eNOS heterocomplex from HC serum-treated cells. Finally, cell exposure to the low-density lipoprotein (LDL) fraction alone dose-dependently reproduced the inhibition of basal and stimulated NO release, as well as the upregulation of caveolin expression and its heterocomplex formation with eNOS, which were unaffected by cotreatment with antioxidants. Together, our data establish a new mechanism for the cholesterol-induced impairment of NO production through the modulation of caveolin abundance in endothelial cells, a mechanism that may participate in the pathogenesis of endothelial dysfunction and the proatherogenic effects of hypercholesterolemia.

Journal ArticleDOI
01 Jun 1999-Test
TL;DR: A method for exploring the structure of populations of complex objects, such as images, is considered, and endemic outliers motivate the development of a bounded influence approach to PCA.
Abstract: A method for exploring the structure of populations of complex objects, such as images, is considered. The objects are summarized by feature vectors. The statistical backbone is Principal Component Analysis in the space of feature vectors. Visual insights come from representing the results in the original data space. In an ophthalmological example, endemic outliers motivate the development of a bounded influence approach to PCA.

Journal ArticleDOI
TL;DR: Investigation of the impact of LP on islet cell ontogeny in the late fetal and neonatal rat and any associated changes in the presence of IGFs and their binding proteins suggests that the beta cell cycle may have a prolonged G1 phase in LP-fed animals in vivo.
Abstract: A programmed turnover of pancreatic beta cells occurs in the neonatal rat involving a loss of beta cells by apoptosis, and their replacement by islet cell replication and neogenesis. The timing of apoptosis is associated with a loss of expression of a survival factor, insulin-like growth factor-II (IGF-II), in the pancreatic islets. Offspring from rats chronically fed a low protein isocalorific diet (LP) exhibit a reduced pancreatic beta cell mass at birth and a reduced insulin secretion in later life. This study therefore investigated the impact of LP on islet cell ontogeny in the late fetal and neonatal rat, and any associated changes in the presence of IGFs and their binding proteins (IGFBPs). Pregnant Wistar rats were fed either LP (8% protein) or normal (C) (20% protein) chow from shortly after conception until the offspring were 21 days postnatal (PN). Bromo-deoxyuridine (BrdU) was administered 1 h before rats were killed and pancreata removed from animals between 19.5 days fetal life and postnatal day 21. Offspring of rats given LP diet had reduced birthweight, pancreatic beta cell mass, and pancreas insulin content, with smaller islets compared with control fed animals, which persisted to weaning. Histological analysis showed that islets from pups given LP diet had a lower nuclear labeling index with BrdU in the beta cells, although, paradoxically, more beta cells showed immunoreactivity for proliferating cell nuclear antigen (PCNA). Because PCNA is present in G1 as well as S phase of the cell cycle, we quantified the number of beta cells immunopositive for cyclin D1, a marker of G1, and NEK2, an indicator of cells in G2 and mitosis, More beta cells in islets from LP-fed animals contained cyclin D1, but less contained NEK2 than did those in controls. This suggests that the beta cell cycle may have a prolonged G1 phase in LP-fed animals in vivo. Offspring of rats given C diet had a low rate of islet cell apoptosis detected by the TUNEL method in fetal and neonatal life (1-2%), with a transient increase to 8% at PN day 14. Offspring of rats receiving LP diet demonstrated a significantly greater level of islet cell apoptosis at every age, rising to 15% at PN 14. IGF-II mRNA was quantified in whole pancreas and was significantly reduced in LP-fed animals at ages up to PN day 10. IGF-II immunoreactivity within the islets of LP-fed rats was also less apparent, but no changes were seen in immunoreactive IGF-I or IGFBPs-2 to -5. These findings show that LP diet changes the balance of beta cell replication and apoptosis in fetal and neonatal neonatal life, which may involve an altered length of beta cell cycle, and contribute to the smaller islet size and impaired insulin release seen in later life. A reduced pancreatic expression of IGF-II may contribute to the lower beta cell proliferation rate and increased apoptosis seen in the fetus and neonate after feeding LP diet.

Journal ArticleDOI
TL;DR: In this paper, the authors proposed a methodology of indicators that allow for the assessment of business participation into sustainable development, based on both the concepts of cost-benefit analysis and the principles of productive efficiency.

Journal ArticleDOI
TL;DR: A control mechanism is proposed that incorporates a spatial displacement integrator in the cerebellum; under such conditions, it is shown that a partial directional control arises automatically.
Abstract: Experimental evidence indicates that the superior colliculus (SC) is important but neither necessary nor sufficient to produce accurate saccadic eye movements. Furthermore both clinical and experimental evidence points to the cerebellum as an indispensable component of the saccadic system. Accordingly, we have devised a new model of the saccadic system in which the characteristics of saccades are determined by the cooperation of two pathways, one through the SC and the other through the cerebellum. Both pathways are influenced by feedback information: the feedback determines the decay of activity for collicular neurons and the timing of the activation for cerebellar neurons. We have modeled three types of cells (burst, buildup, and fixation neurons) found in the intermediate layers of the superior colliculus. We propose that, from the point of view of motor execution, the burst neurons and the buildup neurons are not functionally distinct with both providing a directional drive to the brain stem circuitry. The fixation neurons determine the onset of the saccade by disfacilitating the omnipause neurons in the brain stem. Excluding noise-related variations, the ratio of the horizontal to the vertical components of the collicular drive is fixed throughout the saccade (i.e., its direction is fixed); the duration of the drive is such that it always would produce hypermetric movements. The cerebellum plays three roles: first, it provides an additional directional drive, which improves the acceleration of the eyes; second, it keeps track of the progress of the saccade toward the target; and third, it ends the saccade by choking off the collicular drive. The drive provided by the cerebellum can be adjusted in direction to exert a directional control over the saccadic trajectory. We propose here a control mechanism that incorporates a spatial displacement integrator in the cerebellum; under such conditions, we show that a partial directional control arises automatically. Our scheme preserves the advantages of several previous models of the saccadic system (e.g., the lack of a spatial-to-temporal transformation between the SC and the brain stem; the use of efference copy feedback to control the saccade), without incurring many of their drawbacks, and it accounts for a large amount of experimental data.

Journal ArticleDOI
TL;DR: Diverse physiological functions may be assigned to the cell wall, which contribute to the technological and health-related attributes of lactic acid bacteria, for instance, phage receptor activity relates to the presence of specific substituents on teichoic acids and polysaccharides.
Abstract: The cell wall of lactic acid bacteria has the typical gram-positive structure made of a thick, multilayered peptidoglycan sacculus decorated with proteins, teichoic acids and polysaccharides, and surrounded in some species by an outer shell of proteins packed in a paracrystalline layer (S-layer). Specific biochemical or genetic data on the biosynthesis pathways of the cell wall constituents are scarce in lactic acid bacteria, but together with genomics information they indicate close similarities with those described in Escherichia coli and Bacillus subtilis, with one notable exception regarding the peptidoglycan precursor. In several species or strains of enterococci and lactobacilli, the terminal D-alanine residue of the muramyl pentapeptide is replaced by D-lactate or D-serine, which entails resistance to the glycopeptide antibiotic vancomycin. Diverse physiological functions may be assigned to the cell wall, which contribute to the technological and health-related attributes of lactic acid bacteria. For instance, phage receptor activity relates to the presence of specific substituents on teichoic acids and polysaccharides; resistance to stress (UV radiation, acidic pH) depends on genes involved in peptidoglycan and teichoic acid biosynthesis; autolysis is controlled by the degree of esterification of teichoic acids with D-alanine; mucosal immunostimulation may result from interactions between epithelial cells and peptidoglycan or teichoic acids.

Journal ArticleDOI
TL;DR: Results show that the intake of Chinese herbs containing AA has a dramatic carcinogenic effect and is associated with the overexpression of p53, which suggests a role for a p53 gene mutation.

Journal ArticleDOI
TL;DR: The current version of the GEISA-97 database is described in this paper, which contains 1,346,266 entries and includes a catalog of absorption cross-sections of molecules such as chlorofluorocarbons which exhibit unresolvable spectra.
Abstract: The current version GEISA-97 of the computer-accessible database system GEISA (Gestion et Etude des Informations Spectroscopiques Atmospheriques: Management and Study of Atmospheric Spectroscopic Information) is described. This catalogue contains 1,346,266 entries. These are spectroscopic parameters required to describe adequately the individual spectral lines belonging to 42 molecules (96 isotopic species) and located between 0 and 22,656 cm-1. The featured molecules are of interest in studies of the terrestrial as well as the other planetary atmospheres, especially those of the Giant Planets. GEISA-97 contains also a catalog of absorption cross-sections of molecules such as chlorofluorocarbons which exhibit unresolvable spectra. The modifications and improvements made to the earlier edition (GEISA-92) and the data management software are described. GEISA-97 and the associated management software are accessible from the ARA/LMD (Laboratoire de Meteorologie Dynamique du CNRS, France) web site: http://ara01.polytechnique.fr/registration.

Journal ArticleDOI
TL;DR: Among neonates with hyperinsulinism, about half may have focal islet-cell hyperplasia that can be treated with partial pancreatectomy, and these neonates can be identified through pancreatic catheterization and intraoperative histologic studies.
Abstract: BACKGROUND: Neonatal hyperinsulinemic hypoglycemia is often resistant to medical therapy and is often treated with near-total pancreatectomy. However, the pancreatic lesions may be focal and treatable by partial pancreatic resection. METHODS: We studied 52 neonates with hyperinsulinism who were treated surgically. The type and location of the pancreatic lesions were determined by preoperative pancreatic catheterization and intraoperative histologic studies. Partial pancreatectomy was performed in infants with focal lesions, and near-total pancreatectomy was performed in those with diffuse lesions. The postoperative outcome was determined by measurements of plasma glucose and glycosylated hemoglobin and by oral glucose-tolerance tests. RESULTS: Thirty neonates had diffuse beta-cell hyperfunction, and 22 had focal adenomatous islet-cell hyperplasia. Among the latter, the lesions were in the head of the pancreas in nine, the isthmus in three, the body in eight, and the tail in two. The clinical manifestations were similar in both groups. The infants with focal lesions had no symptoms of hypoglycemia and had normal preprandial and postprandial plasma glucose and glycosylated hemoglobin values and normal results on oral glucose-tolerance tests after partial pancreatectomy (performed in 19 of 22 neonates). By contrast, after near-total pancreatectomy, 13 of the patients with diffuse lesions had persistent hypoglycemia, type 1 diabetes mellitus developed in 8, and hyperglycemia developed in another 7; overall, only 2 patients with diffuse lesions had normal plasma glucose concentrations in the first year after surgery. CONCLUSIONS: Among neonates with hyperinsulinism, about half may have focal islet-cell hyperplasia that can be treated with partial pancreatectomy. These neonates can be identified through pancreatic catheterization and intraoperative histologic studies.

Journal ArticleDOI
TL;DR: This paper demonstrates that there is a strategic reason why software firms have followed consumers' desire to drop software protection, and shows that when network effects are strong, unprotecting is an equilibrium for a noncooperative industry.
Abstract: This paper demonstrates that there is a strategic reason why software firms have followed consumers' desire to drop software protection. We analyze software protection policies in a price-setting duopoly software industry selling differentiated software packages, where consumers' preference for particular software is affected by the number of other consumers who (legally or illegally) use the same software. Increasing network effects make software more attractive to consumers, thereby enabling firms to raise prices. However, it also generates a competitive effect resulting from feircer competition for market shares. We show that when network effects are strong, unprotecting is an equilibrium for a noncooperative industry.

Journal ArticleDOI
TL;DR: The results suggest that the monomorphous pilomyxoid tumors have some resemblance to classical PA, and the former is a more aggressive variant or a separate entity that needs to be recognized for prognostic purposes.
Abstract: Among tumors classified as pilocytic astrocytoma (PA) in the Johns Hopkins Hospital Department of Pathology files, we identified 18 cases with a distinctive monomorphous pilomyxoid histological pattern and a higher recurrence rate than that of PA with classical histological features (classical PA). The majority of the tumors occurred in infants and young children and involved the hypothalamic/chiasmatic region. The tumors were histologically similar to PA, but they were more monomorphous and more myxoid. Rosenthal fibers were not seen and only 1 of 18 tumors had eosinophilic granular bodies. At the end of the follow-up period, 6 patients were dead and 12 were alive with evidence of disease. Progression free survival (PFS) at 1 year was 38.7%. In comparison, we identified a control group of 13 classical PAs in the same age range and location as the study group. In this group, PFS at 1 year was 69.2%, which was significantly better than that for pilomyxoid tumors (p = 0.04). There was no CSF dissemination or death due to tumor progression among patients with classical PA. Eight of these patients are alive with recurrent disease, and 4 have no evidence of disease. While the monomorphous pilomyxoid tumors have some resemblance to classical PA, our results suggest that the former is a more aggressive variant or a separate entity that needs to be recognized for prognostic purposes.