Showing papers by "University of Geneva published in 1995"

Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population.

Abstract: Molecular techniques allow the survey of a large number of linked polymorphic loci in random samples from diploid populations. However, the gametic phase of haplotypes is usually unknown when diploid individuals are heterozygous at more than one locus. To overcome this difficulty, we implement an expectation-maximization (EM) algorithm leading to maximum-likelihood estimates of molecular haplotype frequencies under the assumption of Hardy-Weinberg proportions. The performance of the algorithm is evaluated for simulated data representing both DNA sequences and highly polymorphic loci with different levels of recombination. As expected, the EM algorithm is found to perform best for large samples, regardless of recombination rates among loci. To ensure finding the global maximum likelihood estimate, the EM algorithm should be started from several initial conditions. The present approach appears to be useful for the analysis of nuclear DNA sequences or highly variable loci. Although the algorithm, in principle, can accommodate an arbitrary number of loci, there are practical limitations because the computing time grows exponentially with the number of polymorphic loci. Although the algorithm, in principle, can accommodate an arbitrary number of loci, there are practical limitations because the computing time grows exponentially with the number of polymorphic loci.

Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar.

Abstract: Granulation tissue formation and contraction is an important step of second intention wound healing. Granulation tissue develops from the connective tissue surrounding the damaged or missing area and its cellular components are mainly small vessel and inflammatory cells as well as fibroblasts and myofibroblasts. As the wound closes and evolves into a scar, there is an important decrease in cellularity; in particular myofibroblasts disappear. The question arises as to which process is responsible for this cellular loss. During a previous investigation on the expression of alpha-smooth muscle actin in myofibroblasts (Darby I, Skalli O, Gabbiani G, Lab Invest, 1990, 63:21-29), we have observed that in late phases of wound healing, many myofibroblasts show changes compatible with apoptosis and suggested that this type of cell death could be responsible for the disappearance of myofibroblasts. We have now tested this hypothesis by means of morphometry at the electron microscopic level and by in situ end labeling of fragmented DNA. Our results indicate that the number of myofibroblastic and vascular cells undergoing apoptosis increases as the wound closes and support the assumption that this is the mechanism of granulation tissue evolution into a scar. The regulation of apoptotic phenomena during wound healing may be important in scar establishment and development of pathological scarring.

POLYPHASIC CHLOROPHYLL a FLUORESCENCE TRANSIENT IN PLANTS AND CYANOBACTERIA

Abstract: The variable chlorophyll (Chl) a fluorescence yield is known to be related to the photochemical activity of photosystem I1 (PSII) of oxygen-evolving organisms. The kinetics of the fluorescence rise from the minimum yield, F,, to the maximum yield, F,, is a monitor of the accumulation of net reduced primary bound plastoquinone (QA) with time in all the PSII centers. Using a shutter-less system (Plant Efficiency Analyzer, Hansatech, UK), which allows data accumulation over several orders of magnitude of time (40 11s to 120 s), we have measured on a logarithmic time scale, for the first time, the complete polyphasic fluorescence rise for a variety of oxygenic plants and cyanobacteria at different light intensities. With increasing light intensity, the fluorescence rise is changed from a typical 0-I-P characteristic to curves with two intermediate levels J and I, both of which show saturation at high light intensity but different intensity dependence. Under physiological conditions, Chl a fluorescence transients of all the organisms examined follow the sequence of 0-J-I-P. The characteristics of the kinetics with respect to light intensity and temperature suggest that the 0-J phase is the photochemical phase, leading to the reduction of QA to QA-. The intermediate level I is suggested to be related to a heterogeneity in the filling up of the plastoquinone pool. The P is reached when all the plastoquinone (PQ) molecules are reduced to PQH2. The addition of 3-(3-4-dichIorophenyl)- 1,l -dimethylurea leads to a transformation of the 0-J-I-P rise into an 0-J rise. The kinetics of 0-J-I-P observed here was found to be similar to that of 0-1,-12-P, reported by Neubauer and Schreiber (2. Naturforsch. 42c, 1246-1254, 1987). The biochemical significance of the fluorescence steps 0-J-I-P with respect to the filling up of the plasto- quinone pool by PSII reactions is discussed.

Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11

Abstract: We report the results of two studies examining the genetic overlap between schizophrenia and velocardiofacial syndrome. In study A, we characterize two interstitial deletions identified on chromosome 22q11 in a sample of schizophrenic patients. The size of the deletions was estimated to be between 1.5 and 2 megabases. In study B, we examine whether variations in deletion size are associated with the schizophrenic phenotype in velocardiofacial syndrome patients. Our results show that a region of the genome that has been previously implicated by genetic linkage analysis can harbor genetic lesions that increase the susceptibility to schizophrenia. Our findings should facilitate identification and cloning of the schizophrenia susceptibility gene(s) in this region and identification of more homogeneous subgroups of patients.

Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A

Abstract: Haemophilia A is a classic X-linked disease which affects 1 in 5-10,000 males in all populations and is caused by defects in coagulation factor VIII. Roughly 60% of patients have severe disease with factor VIII activity < 1% of normal; they have frequent spontaneous bleeding into joints, soft tissues, muscles and internal organs. These patients usually require regular injections of plasma-derived or recombinant human factor VIII. Because this is expensive and can potentially lead to life-threatening complications, other forms of therapy, including gene therapy, have been proposed. Natural canine models of factor VIII and factor IX deficiency have been available for many years, and gene therapy attempts on these dogs have met with partial success. However, a small animal model of the disease is desirable for studies of factor VIII function and gene therapy. Using gene targeting, we have made a mouse with severe factor VIII deficiency.

Quantum cryptography with coherent states

Abstract: The safety of a quantum key distribution system relies on the fact that any eavesdropping attempt on the quantum channel creates errors in the transmission. For a given error rate, the amount of information that may have leaked to the eavesdropper depends on both the particular system and the eavesdropping strategy. In this work, we discuss quantum cryptographic protocols based on the transmission of weak coherent states and present a system, based on a symbiosis of two existing systems, for which the information available to the eavesdropper is significantly reduced. This system is therefore safer than the two previous ones. We also suggest a possible experimental implementation.

The Syntax of Negation

Abstract: Preface 1. Introduction 2. The WH-criterion and the NEG-criterion 3. NEG-movement and the NEG-criterion 4. The application of the NEG-criterion 5. A-positions and A'-positions and the syntax of negation 6. The syntax of negative operators Notes References Index.

Lactate released by Muller glial cells is metabolized by photoreceptors from mammalian retina

Abstract: The nature of fuel molecules trafficking between mammalian glial cells and neurons was explored using acute retinal cell preparations of solitary Muller glial cells, Muller cells still attached to photoreceptors (the “cell complex”), and solitary photoreceptors. 14C- Molecules in the cell complex, Muller cells, and respective baths were quantitated following 30 min incubation in bicarbonate-buffered Ringer's solution carrying 5 mM 14C(U)-glucose, and substrate preference by solitary photoreceptors was assessed by measuring 14CO2 production. Muller cells alone metabolized 14C-glucose predominantly to carbohydrate intermediates, while the presence of photoreceptors raised proportionately the amount of radiolabeling in amino acids. 14C-Lactate was the major carbohydrate found in the bath. However, in the presence of photoreceptors, its amount was 70% less than that for Muller cells alone. This decrease matched the expected production of 14CO2 by photoreceptor oxidative metabolism and was antagonized by the addition of unlabeled lactate. Moreover, while solitary photoreceptors consumed both exogenous 14C-lactate and 14C-glucose, lactate was a better substrate for their oxidative metabolism. In the cell complex, the metabolism of amino acids increased and illumination affected primarily glutamate and glutamine production: the specific activity of glutamate changed in parallel with that of lactate, and that of glutamine increased by eightfold in darkness. These results demonstrate transfer of lactate from Muller cells to photoreceptors and underscore a photoreceptor-dependent modulation of lactate and amino acid metabolism. We propose that net production and release of lactate by Muller cells serves to maintain their glycolysis elevated and to fuel mitochondrial oxidative metabolism and glutamate resynthesis in photoreceptors.

Versatile and efficient techniques for simulating cloth and other deformable objects

Abstract: We are presenting techniques for simulating the motion and the deformation of cloth, fabrics or, more generally, deformable surfaces. Our main goal is to be able to simulate any kind of surface without imposing restrictions on shape or geometrical environment. In particular, we are considering difficult situations with respect to deformations and collisions, like wrinkled fabric falling on the ground. Thus, we have enhanced existing algorithms in order to cope with any possible situation. A mechanical model has been implemented to deal with any irregular triangular meshes, handle high deformations despite rough discretisation, and cope with complex interacting collisions. Thus, it should deal efficiently with situations where nonlinearities and discontinuities are really non marginal. Collision detection has also been improved to efficiently detect self-collisions, and also to correctly consider collision orientations despite the lack of surface orientation information from preset geometrical contexts, using consistency checking and correction. We illustrate these features through simulation examples.

Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis. A mouse model of progressive pulmonary fibrosis

Abstract: The murine TNF-alpha gene was expressed under the control of the human surfactant protein SP-C promoter in transgenic mice. A number of the SP-C TNF-alpha mice died at birth or after a few weeks with very severe lung lesions. Surviving mice transmitted a pulmonary disease to their offspring, the severity and evolution of which was related to the level of TNF-alpha mRNA in the lung; TNF-alpha RNA was detected in alveolar epithelium, presumably in type II epithelial cells. In a longitudinal study of two independent mouse lines, pulmonary pathology, at 1-2 mo of age, consisted of a leukocytic alveolitis with a predominance of T lymphocytes. Leukocyte infiltration was associated with endothelial changes and increased levels of mRNA for the endothelial adhesion molecule VCAM-1. In the following months, alveolar spaces enlarged in association with thickening of the alveolar walls due to an accumulation of desmin-containing fibroblasts, collagen fibers, and lymphocytes. Alveolar surfaces were lined by regenerating type II epithelial cells, and alveolar spaces contained desquamating epithelial cells in places. Platelet trapping in the damaged alveolar capillaries was observed. Pulmonary pathology in the SP-C TNF-alpha mice bears a striking resemblance to human idiopathic pulmonary fibrosis, in which increased expression of TNF-alpha in type II epithelial cells has also been noted. These mice provide a valuable animal model for understanding the pathogenesis of pulmonary fibrosis and exploring possible therapeutic approaches.

Direct vortex lattice imaging and tunneling spectroscopy of flux lines on YBa2Cu3O7- delta.

Abstract: We report the observation of the flux line lattice in ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{7\ensuremath{-}\ensuremath{\delta}}$ by scanning tunneling microscopy. The measurements were carried out at 4.2 K and in a magnetic field of 6 T applied along the $c$ axis. The vortices appear arranged in an oblique lattice in which the primitive vectors are nearly equal and form an angle of approximately 77\ifmmode^\circ\else\textdegree\fi{}. We also report local tunneling spectroscopy into a vortex core which reveals two peaks separated by about 11 meV. The zero-field spectra are reproducible over large areas of the sample and show a multiple peak structure.

Minimum-jerk, two-thirds power law, and isochrony: converging approaches to movement planning.

Abstract: Two approaches to the study of movement planning were contrasted. Data on the drawing of complex two-dimensional trajectories were used to test whether the covariations of the kinematic and geometrical parameters of the movement formalized by the two-thirds power law and by the isochrony principle (P. Viviani & R. Schneider, 1991) can be derived from the minimum-jerk model hypothesis (T. Flash & N. Hogan, 1985). The convergence of the 2 approaches was satisfactory insofar as the relation between tangential velocity and curvature is concerned (two-thirds power law). Global isochrony could not be deduced from the optimal control hypothesis. Scaling of velocity within movement subunits can instead be derived from the minimum-jerk hypothesis. The implications vis-a-vis the issue of movement planning are discussed with an emphasis on the representation used by the motor control system for coding the intended trajectories.

A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome).

Abstract: Regulation of MHC class II gene expression is an essential aspect of the control of the immune response. Primary MHC class II deficiency is a genetically heterogeneous disease of gene regulation that offers the unique opportunity of a genetic approach for the identification of the functionally relevant regulatory genes and factors. Most patients exhibit a characteristic defect in the binding of a nuclear complex, RFX, to the X box motif of MHC class II promoters. Genetic complementation of a B-lymphocyte cell line from such a patient with a cDNA expression library has allowed us to isolate RFX5, the regulatory gene responsible for the MHC class II deficiency. This gene encodes a novel DNA-binding protein that is indeed a subunit of the RFX complex. Mutations in the RFX5 gene have been characterized in two patients. Transfection of the patient's cells with the RFX5 cDNA repairs the binding defect and fully restores expression of all the endogenous MHC class II genes in vivo.

Site-specific recombination of a transgene in fertilized eggs by transient expression of Cre recombinase.

Abstract: An efficient method of transgene modulation in fertilized eggs has been developed that uses the Cre/loxP recombination system. Twelve transgenic mouse lines carrying a chicken beta-actin promoter-loxP-chloramphenicol acetyltransferase (CAT) gene-loxP-beta-galactosidase gene construct were produced. After selection of the line showing the highest expression of the CAT gene in a variety of tissues, eggs of this line were injected in the male or female pronucleus with a Cre expression vector placed under the control of the chicken beta-actin promoter and kept in a circular form to avoid genomic integration. This resulted in a transient expression of Cre in the eggs, leading to recombination of the transgene as detected by galactosidase expression and DNA analysis. Recombination was completed before the morula stage with both types of pronuclear injections and occurred with a very high frequency; no mosaicism, no incomplete recombination, and no integration of the Cre sequence were observed in 18 mice born with this modified transgene. The beta-galactosidase gene was expressed in various tissues at levels comparable to those found for the CAT gene in the founder line. This Cre transient expression system should be useful for breeding transgenic lines in which transgene expression leads to sterility or lethality--in particular, for selecting transgenic lines with high expression of a potentially lethal transgene whose full activity is difficult to explore in a conventional transgenic system because of the risk of selecting for transgenic lines carrying only poorly expressed transgenes.

Recurrence Plots of Dynamical Systems

Abstract: A new graphical tool for measuring the time constancy of dynamical systems is presented and illustrated with typical examples.

Tensile Bond Strength and SEM Evaluation of Caries-affected Dentin Using Dentin Adhesives

Abstract: Tensile bond strength measurements are commonly used for the evaluation of dentin adhesive systems. Most tests are performed using extracted non-carious human or bovine dentin. However, the adhesion of resins to caries-affected dentin is still unclear. The objectives of this study were to test the hypothesis that bonding to caries-affected dentin is inferior to bonding to normal dentin, and that the quality of the hybrid layer plays a major role in creating good adhesion. We used a micro-tensile bond strength test to compare test bond strengths made to either caries-affected dentin or normal dentin, using three commercial adhesive systems (All Bond 2, Scotchbond Multi-Purpose, and Clearfil Liner Bond II). For scanning electron microscopy, the polished interfaces between the adhesive bond and dentin were subjected to brief exposure to 10% phosphoric acid solution and 5% sodium hypochlorite, so that the quality of the hybrid layers could be observed. Bonding to normal dentin with either All Bond 2 (26.9 ± 8...

A Controlled Trial of Zidovudine in Primary Human Immunodeficiency Virus Infection

Abstract: Background It is possible that antiretroviral treatment given early during primary infection with the human immunodeficiency virus (HIV) may reduce acute symptoms, help preserve immune function, and improve the long-term prognosis. Methods To assess the effect of early antiviral treatment, we conducted a multicenter, double-blind, placebo-controlled trial in which 77 patients with primary HIV infection were randomly assigned to receive either zidovudine (250 mg twice daily; n = 39) or placebo (n = 38) for six months. Results The mean time from the onset of symptoms until enrollment in the study was 25.1 days. Among the 43 patients who were still symptomatic at the time of enrollment, there was no appreciable difference in the mean (±SE) duration of the retroviral syndrome between the zidovudine group (15.0±4.1 days) and the placebo group (15.8±3.6 days). During a mean follow-up period of 15 months, minor opportunistic infections developed in eight patients: oral candidiasis in four, herpes zoster in two, ...

Hox gene expression in teleost fins and the origin of vertebrate digits.

Abstract: Hox genes are essential for growth and patterning of the tetrapod limb skeleton. Mice mutant for the Hoxd-13 gene have an important delay in morphogenesis owing to reduced proliferation. Based on the appearance of atavisms in such mice, we suggested that modifications of Hox gene regulation may have been a source of morphological variation during the evolution of tetrapod limbs. Pectoral and pelvic fins are homologous to fore- and hindlimbs, respectively. To compare the relative importance of Hox genes during fin versus limb morphogenesis, we cloned zebrafish (Danio rerio) HoxD and HoxA complex genes and analysed their expression during fin development. The results suggest a scheme for the fin-limb transition in which the distal autopods (digits) are neomorphic structures produced by unequal proliferation of the posterior part of an ancestral appendix.

Stress fatigue: basic principles and prosthodontic implications.

Abstract: Clinical evidence indicates that the majority of fractures that occur in prosthodontic structures do so after a period of many years. Such failures generally are not related to an episode of acute overload but result from fatigue failure. This paper reviews the current knowledge of fatigue failure and test methods. An overview of published studies is given, and the authors suggest guidelines for future prosthodontic studies of this nature.

Apoptosis participates in cellularity regulation during rat aortic intimal thickening.

Abstract: Intimal thickening induced after endothelial denudation of rat aorta is though to be due to migration and proliferation of smooth muscle cells (SMC). When the reendothelialization is achieved, intimal thickening shows an important decrease in cellularity. Using in situ end labeling of fragmented DNA and electron microscopy, we show that this remodeling is accompanied by apoptosis of SMC. The number of apoptotic SMC becomes important 15 days after endothelial injury and reaches a maximum at 20 days; at 45 days the intimal thickening is reendothelialized and no more apoptotic SMC are detected. Apoptotic SMC show nuclear and cytoplasmic condensation as well as cytoplasmic vacuolization. Our results indicate that apoptosis is an important mechanism in the regulation of intimal thickening evolution.