Showing papers by "University of Nice Sophia Antipolis published in 1998"

Stretched exponential distributions in nature and economy: ``fat tails'' with characteristic scales

Abstract: To account quantitatively for many reported “natural” fat tail distributions in Nature and Economy, we propose the stretched exponential family as a complement to the often used power law distributions. It has many advantages, among which to be economical with only two adjustable parameters with clear physical interpretation. Furthermore, it derives from a simple and generic mechanism in terms of multiplicative processes. We show that stretched exponentials describe very well the distributions of radio and light emissions from galaxies, of US GOM OCS oilfield reserve sizes, of World, US and French agglomeration sizes, of country population sizes, of daily Forex US-Mark and Franc-Mark price variations, of Vostok (near the south pole) temperature variations over the last 400 000 years, of the Raup-Sepkoski's kill curve and of citations of the most cited physicists in the world. We also discuss its potential for the distribution of earthquake sizes and fault displacements. We suggest physical interpretations of the parameters and provide a short toolkit of the statistical properties of the stretched exponentials. We also provide a comparison with other distributions, such as the shifted linear fractal, the log-normal and the recently introduced parabolic fractal distributions.

Nuclear Accumulation of p21Cip1 at the Onset of Mitosis: a Role at the G2/M-Phase Transition

Abstract: Progression through the phases of the cell cycle is driven by the periodic activation of several cyclin-dependent kinases (Cdks). The activity of Cdk complexes is tightly regulated by a variety of mechanisms, such as periodic cyclin accumulation and degradation, nuclear localization, phosphorylation of Cdks, and association with a number of different Cdk inhibitors (CKIs) (31). These inhibitors were originally recovered from inactive cyclin-Cdk complexes isolated from quiescent cells and cells arrested in G1 by γ irradiation or incubation with transforming growth factor β or cyclic AMP, as well as from senescent fibroblasts (reviewed in reference 36). Their primary targets appeared to be Cdks associated with G1 cyclins (D-type cyclins and cyclin E), rate-limiting regulators of the G1/S-phase transition (23, 24, 30, 32). A model has therefore gained acceptance whereby activity of cyclin D1- and cyclin E-associated kinases and hence S-phase entry are inhibited when the cells are exposed to conditions that result in accumulation of CKIs (36). Cell cycle arrest in G1 caused by DNA damage or cellular senescence is, at least in part, mediated by p53-dependent accumulation of p21Cip1/Waf1/Sdi1 (p21) (reviewed in reference 36). Ectopic expression of p21 induces G1 arrest (17, 22), whereas the presence of p21 antisense RNA in quiescent cells promotes S phase (21). Consistent with its role as a G1 regulator, p21 was shown to accumulate in the nucleus during G1 phase, whereas both p21 mRNA and protein levels decline before S phase (11, 21). However, several observations raise the possibility that p21 has roles at other stages of the cell cycle. First, p21 mRNA in human fibroblasts shows bimodal periodicity, with peaks in G1 and G2/M (19). Second, p21 protein was detected in a variety of different cyclin-Cdk complexes in nontransformed fibroblasts, including those not associated with the G1/S-phase transition (17, 40, 42). Whereas its association with cyclin D1 did not seem to vary during the cell cycle, p21 was shown to be present in cyclin A and cyclin B complexes only during the latter phases of the cell cycle, suggesting a functional interaction with cyclin A- and cyclin B-associated kinases (19). To gain additional insight into the cell cycle roles of p21, we analyzed its cell cycle-dependent subcellular localization by immunofluorescence microscopy in nontransformed cells. This approach allowed the analysis of individual and unperturbed cells and, by simultaneous staining of proteins in pairs, was able to provide accurate information on relative subcellular localization and periodicity of each. In conjunction with biochemical analysis of cyclin complexes in extracts from synchronized cells, our immunolocalization experiments suggest that p21 plays a role during the G2/M-phase transition.

Crashes as Critical Points

Abstract: We study a rational expectation model of bubbles and crashes. The model has two components : (1) our key assumption is that a crash may be caused by local self-reinforcing imitation between noise traders. If the tendency for noise traders to imitate their nearest neighbors increases up to a certain point called the ``critical'' point, all noise traders may place the same order (sell) at the same time, thus causing a crash. The interplay between the progressive strengthening of imitation and the ubiquity of noise is characterized by the hazard rate, i.e. the probability per unit time that the crash will happen in the next instant if it has not happened yet. (2) Since the crash is not a certain deterministic outcome of the bubble, it remains rational for traders to remain invested provided they are compensated by a higher rate of growth of the bubble for taking the risk of a crash. Our model distinguishes between the end of the bubble and the time of the crash,: the rational expectation constraint has the specific implication that the date of the crash must be random. The theoretical death of the bubble is not the time of the crash because the crash could happen at any time before, even though this is not very likely. The death of the bubble is the most probable time for the crash. There also exists a finite probability of attaining the end of the bubble without crash. Our model has specific predictions about the presence of certain critical log-periodic patterns in pre-crash prices, associated with the deterministic components of the bubble mechanism. We provide empirical evidence showing that these patterns were indeed present before the crashes of 1929, 1962 and 1987 on Wall Street and the 1997 crash on the Hong Kong Stock Exchange. These results are compared with statistical tests on synthetic data.

Automatic test data generation using constraint solving techniques

Abstract: Automatic test data generation leads to identify input values on which a selected point in a procedure is executed. This paper introduces a new method for this problem based on constraint solving techniques. First, we statically transform a procedure into a constraint system by using well-known "Static Single Assignment" form and control-dependencies. Second, we solve this system to check whether at least one feasible control flow path going through the selected point exists and to generate test data that correspond to one of these paths.The key point of our approach is to take advantage of current advances in constraint techniques when solving the generated constraint system. Global constraints are used in a preliminary step to detect some of the non feasible paths. Partial consistency techniques are employed to reduce the domains of possible values of the test data. A prototype implementation has been developped on a restricted subset of the C language. Advantages of our approach are illustrated on a non-trivial example.

Variational approach for edge-preserving regularization using coupled PDEs

Abstract: This paper deals with edge-preserving regularization for inverse problems in image processing. We first present a synthesis of the main results we have obtained in edge-preserving regularization by using a variational approach. We recall the model involving regularizing functions /spl phi/ and we analyze the geometry-driven diffusion process of this model in the three-dimensional (3-D) case. Then a half-quadratic theorem is used to give a very simple reconstruction algorithm. After a critical analysis of this model, we propose another functional to minimize for edge-preserving reconstruction purposes. It results in solving two coupled partial differential equations (PDEs): one processes the intensity, the other the edges. We study the relationship with similar PDE systems in particular with the functional proposed by Ambrosio-Tortorelli (1990, 1992) in order to approach the Mumford-Shah (1989) functional developed in the segmentation application. Experimental results on synthetic and real images are presented.

Engineering chromosomes in mice through targeted meiotic recombination (TAMERE).

Abstract: Functional studies of large transcription units, clustered genes and chromosomal loci require the design of novel experimental tools to engineer genomic macro-rearrangements. Here, we present a strategy to produce deficiencies or duplications by crossing mice carrying loxP sites in homologous loci. This trans-allelic targeted meiotic recombination (TAMERE) protocol allows for the combination of various alleles within a particular locus as well as for generation of interchromosomal unequal exchanges. Novel genetic configurations can thus be produced without multiple targeting and selection steps in embryonic stem (ES) cells. A concomitant deletion/duplication event of the Hoxdl2 locus shows the potential of this approach. The high frequency of such targeted exchanges in vivo makes TAMERE a powerful genetic tool applicable to research areas in which complex genomic modifications are required.

Developing a Scientific Knowledge of Simulation/Gaming:

Abstract: This article first speculates on why such little progress has been made regarding the effective application of educational simulation/games. It suggests that the field's eclectic foundation has bee...

Precursors, aftershocks, criticality and self-organized criticality

Abstract: We present a simple model of earthquakes on a pre-existing hierarchical fault structure. The system self-organizes at large times in a stationary state with a power law Gutenberg-Richter distribution of earthquake sizes. The largest fault carries irregular great earthquakes preceded by precursors developing over long time scales and followed by aftershocks obeying an Omori's law. The cumulative energy released by precursors follows a time-to-failure power law with log-periodic structures, qualifying a large event as an effective dynamical (depinning) critical point. Down the hierarchy, smaller earthquakes exhibit the same phenomenology, albeit with increasing irregularities.

Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia.

Abstract: Cell-matrix interactions contribute to regulating the adhesion, growth, migration, and differentiation of epithelial intestinal cells. Alterations in matrix components and their cellular receptors have been found in tumours but their specific roles remain unclear. The tissue patterns of laminin-5 and alpha 3, beta 3 and gamma 2 subunits, as well as those of the alpha 3, alpha 6, beta 1, and beta 4 integrin chains, were determined by immunofluorescence on frozen sections of 12 colorectal mucosal samples from four patients, 15 adenomas, 29 adenocarcinomas, and eight metastases. Distinct patterns of laminin-5 and integrin expression were found along the mucosa-adenoma, and adenoma-carcinoma transitions. Expression of basement membrane laminin-5 and subunits was continuous and gradient-like in normal mucosa, enhanced at the periphery of adenomas, and discontinuous in places in carcinomas and metastases. Decrease of the alpha 3 integrin chain was found in adenomas, together with that of alpha 6 and beta 4 chains in carcinomas. A subpopulation of carcinoma cells dissociating (budding) from neoplastic tubules was found to accumulate the laminin-5 beta 3 gamma 2 heterodimer in the cytoplasm, with progressive loss of surface integrin expression. These results suggest that in colorectal cancer, an abnormal expression of laminin-5 subunits and integrin chains may identify a subset of carcinoma cells prone to invade focally and to contribute to disease aggressiveness.

Stage-specific expression of the Kit receptor and its ligand (KL) during male gametogenesis in the mouse: a Kit-KL interaction critical for meiosis

Abstract: The Kit receptor and its ligand KL, which together constitute an essential effector at various stages of embryonic development, are both present during adult gametogenesis. In the testis, KL is expressed in Sertoli cells, and Kit in germ cells, starting at the premeiotic stages. A series of observations indicated previously a role in spermatogonia survival, without excluding a possible function at later stages. We identified a complex pattern of expression of the two components in the adult murine testis, suggestive of a role in the meiotic progression of spermatocytes. At stages VII-VIII of the cycle of the seminiferous epithelium, the time when spermatocytes enter meiosis, the membrane-associated form of KL extends on the Sertoli cell from the peripheral to the adluminal compartment of the tubule. We also found that the receptor is present on the surface of germ cells up to the pachytene stage. The availability of differentiated Sertoli cell lines, which express the KL protein and support part of the maturation of germ cells in coculture, allowed us to ask whether, in the in vitro reconstructed system, transit of spermatocytes through meiosis requires the Kit-KL interaction. Addition of a blocking monoclonal antibody against the Kit receptor (ACK2) inhibited extensively the appearance of haploid cells and the expression of a haploid-phase-specific gene (Prm1). Recognition of the supporting Sertoli cell by germ cells was not affected, indicating a requirement for the activity of the receptor for either entering or completing meiosis. Involvement of the membrane-associated form of the ligand was suggested by the observation that addition of the soluble form of KL was equally inhibitory.

Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults.

Abstract: To investigate the effects of an oral creatine supplementation in older adults, 32 elderly subjects (67-80 years; 16 females, 16 males) were randomly assigned to four equivalent subgroups (control-creatine; control-placebo; trained-creatine; trained-placebo) based on whether or not they took part in an 8-week strength training programme and an 8-week oral creatine monohydrate creatine supplementation programme. The strength training programme consisted of three sets of eight repetitions at 80% of one-repetition maximum, for leg press, leg extension and chest press, 3 days a week. The 52-day supplementation programme consisted of 20 g of creatine monohydrate (or glucose) and 8 g of glucose per day for the initial 5 days followed by 3 g of creatine monohydrate (or glucose), and 2 g of glucose per day. Prior to and after the training and supplementation periods, body mass, body fat, lower limb muscular volume, 1-, 12-repetitions maxima and isometric intermittent endurance tests for leg press, leg extension and chest press were determined. In all groups, no significant changes in anthropometric parameters were observed. For all movements, the increases in 1- and 12-repetitions maxima were greater (P < 0.02) in trained than control subjects. No significant interactions (supplementation/training/time) were observed for the 1-, 12-repetitions maxima, and the isometric intermittent endurance, whatever the movement considered. We conclude that oral creatine supplementation does not provide additional benefits for body composition, maximal dynamical strength, and dynamical and isometric endurances of healthy elderly subjects, whether or not it is associated with an effective strength training.

Clustering and switching strategies in verbal fluency tasks: comparison between schizophrenics and healthy adults.

Abstract: Verbal fluency tasks are frequently used in clinical neuropsychology. Clustering (the production of words within semantic subcategories) and switching (the ability to shift between clusters) have been described as 2 components underlying fluency performance. We compared the use of clustering and switching in schizophrenic patients and healthy subjects. Seventy-eight schizophrenic subjects (DSM-IV criteria) and 64 control participants matched for age and educational level were recruited. Negative, disorganized, and productive clinical dimensions were evaluated using the SANS and SAPS scales. The number of words generated per semantic-phonemic cluster and the number of switches were evaluated during 2 verbal fluency tasks (phonemic and semantic). In the healthy controls switching and clustering were closely related to the total number of words generated in the verbal fluency tests. The role of the 2 components was partly dependent on the specific task. Switching was prevalent in formal fluency, while both switching and clustering contributed to semantic fluency. In comparison to the healthy controls, the overall group of schizophrenic patients showed a significant impairment of switching in the formal fluency task and of both switching and clustering in the semantic fluency task, and both the negative and disorganized dimensions correlated with verbal fluency performance, the number of swtiches during the phonemic fluency task, and the clustering during semantic fluency task.

Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface

Abstract: Purpose. Long term use of topical drugs has clearly been shown to induce toxic immunopathological changes in the ocular surface. However, little is known concerning the respective roles of active compounds and preservatives. Benzalkonium chloride (BAC) is the most used preservative and its cytotoxicity is well known, but other preservatives have not yet been clearly evaluated. We thus performed a comparative study to investigate toxic side effects induced in the rat ocular surface by applications of various preservatives, with special attention to inflammatory infiltrates.Methods. A total of 35 brown Norway rats were divided into seven groups of five each. They received, for one month, in both eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chloride, 0.01% benzododecinium bromide, 0.004% thiomersal, 0.05% methyl parahydroxybenzoate or phosphate-buffered saline (PBS), the last group remaining untreated. Then, animals were sacrificed and eyes were processed for histological and immunological pro...

A hierarchical model of financial crashes

Abstract: We follow up our previous conjecture that large stock market crashes are analogous to critical points in statistical physics. The term “critical” refers to regimes of cooperative behavior, such as magnetism at the Curie temperature and liquid–gas transitions, and is characterized by the singular mathematical behavior of relevant observables. To illustrate the concept of criticality, we present a simple hierarchical model of traders exhibiting “crowd” behavior and show that it has a well-defined critical point, whose mathematical signature is a power law dependence of the price, modulated by log-periodic structures, as recently found in market data by several independent groups.

Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa.

Abstract: Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3 polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin-5 and to assemble hemidesmosomes, maintained the impairment of their adhesive properties, and displayed a decrease of their colony-forming ability. A retroviral construct expressing a human beta3 cDNA was used to transduce primary beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced with an efficiency of 100%. Beta3-transduced keratinocytes were able to synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully restored the keratinocyte adhesion machinery, including the capacity of proper hemidesmosomal assembly, and prevented the loss of the colony-forming ability, suggesting a direct link between adhesion to laminin-5 and keratinocyte proliferative capacity. Clonal analysis demonstrated that holoclones expressed the transgene permanently, suggesting stable correction of epidermal stem cells. Because cultured keratinocytes are used routinely to make autologous grafts for patients suffering from large skin or mucosal defects, the full phenotypic reversion of primary human epidermal stem cells defective for a structural protein opens new perspectives in the long-term treatment of genodermatoses.

Focusing on a Turbulent Layer: Principle of the "Generalized SCIDAR"

Abstract: During the last two decades, much effort has been put into the remote sensing of atmospheric turbulent layers, using optical devices. The main scientific interest concerns optical path fluctuations relevant to communication and astronomy and the widening of our understanding of atmospheric physics. Here we describe an original technique that involves moving a virtual plane of analysis in the atmosphere. Using this technique, a simple optical combination allows us to explore the atmosphere, wiping out a particular layer while distant layers located beneath or above are reinforced. When combined with the SCIDAR technique, this phenomenon leads to the "generalized SCIDAR" concept, allowing turbulence profiles to be remotely assessed throughout the whole atmosphere, including the boundary layer. The potential of this new concept is shown in a laboratory experiment using a vein to simulate an atmospheric turbulent layer.

Financial markets as adaptive systems

Abstract: We show, by studying in detail the market prices of options on liquid markets, that the market has empirically corrected the simple, but inadequate Black-Scholes formula to account for two important statistical features of asset fluctuations: "fat tails" and correlations in the scale of fluctuations. These aspects, although not included in the pricing models, are very precisely reflected in the price fixed by the market as a whole. Financial markets thus behave as rather efficient adaptive systems.

Evolutionary model for Alpine Corsica: mechanism for ophiolite emplacement and exhumation of high‐pressure rocks

Abstract: A tectonic model of Alpine Corsica is proposed based on geological studies. Its evolution starts after the Jurassic with intraoceanic subduction, followed by mid-Cretaceous subduction of the European continental margin under the oceanic segment of the Adriatic plate. After subduction of the continental crust to a depth of ≈ 150 km, slices of crustal material are buoyantly uplifted together with high-pressure oceanic rocks (ophiolites and ‘schistes lustres’). High pressure–low temperature continental gneiss units overthrust the outer segments of the European crust, while producing a normal sense motion along the upper surface of the rising crustal body. During the Eocene, the closure of the remnant Ligurian oceanic basin separating the proto Corsican belt and Adria, resulted in a second orogenic phase with the emplacement of unmetamorphosed ophiolitic nappes which overthrust the previously exhumed and eroded HP belt. This Corsican model suggests an original evolutionary path for orogenic belts when continental collision is preceded by intraoceanic subduction.

A new design tapered slot antenna for ultra-wideband applications

Abstract: This paper describes the design and the high performance of a new balanced antipodal Vivaldi antenna for ultra-wideband applications. The return loss, radiation pattern, antenna gain, and level of cross polarization of this antenna are presented for both simulated and experimental results. The antenna is demonstrated to have greater than decade bandwidth (impedance within 10 dB over 1.3–20 GHz) and low cross polarization (<−17 dB in the broadside direction) over the band. © 1998 John Wiley & Sons, Inc. Microwave Opt Technol Lett 19: 286–289, 1998.

Onychomatricoma: Clinical and histopathologic findings in 12 cases

Abstract: Background: Onychomatricoma is a nail matrix tumor that has been well characterized clinically but not histologically. Objective: The purpose of this study was to establish histologic criteria for the diagnosis of onychomatricoma to differentiate it from other fibroepithelial tumors of the nail matrix. Methods: We observed 12 cases and were able to examine 4 of these excised specimens, including the attached nail plate. In 8 patients, avulsion of the nail was performed before excision of the tumor so that the nail plate was examined separately from the tumor. Results: Onychomatricoma is a fibroepithelial tumor consisting of 2 anatomic zones. The proximal zone is located beneath the proximal nail fold with a proximal border starting at the root of the nail and distal border corresponding to the cuticle. It is characterized by deep epithelial invaginations filled with a thick V-shaped keratogenous zone, a thickened nail plate without cavitation but with an undulating inferior border ending in ungual spurs, and a fibrillary stroma clearly demarcated from the undersurface. The distal zone corresponds to the lunula and is characterized by multiple "glove finger" digitations lined with matrix epithelium and oriented around antero-oblique connective tissue axes; perforation of the nail plate by multiple cavities that, generally at the distal edge of the lunula, lose their epithelial digitations and become filled with serous fluid; the connective-tissue stoma of the digitations extends deeply into the dermis and is not demarcated form healthy tissue. Conclusion: On the basis of the mentioned characteristics, we have been able to define onychomatricoma histologically. In addition, we have identified an unusual clinical form of onychomatricoma that has the appearance of a cutaneous horn and is situated at the junction of the undersurface of the proximal nailfold and the lateral nailfold. (J Am Acad Dermatol 1998;39:560-4.)

ATP-evoked increases in [Ca2+]i and peptide release from rat isolated neurohypophysial terminals via a P2X2 purinoceptor.

Abstract: 1. The effect of externally applied ATP on cytosolic free Ca2+ concentration ([Ca2+]i) was tested in single isolated rat neurohypophysial nerve terminals by fura-2 imaging. The release of vasopressin (AVP) and oxytocin (OT) upon ATP stimulation was also studied from a population of terminals using specific radioimmunoassays. 2. ATP evoked a sustained [Ca2+]i increase, which was dose dependent in the 1-100 microM range (EC50 = 4.8 microM). This effect was observed in only approximately 40 % of the terminals. 3. Interestingly, ATP, in the same range (EC50 = 8.6 microM), evoked AVP, but no significant OT, release from these terminals. 4. Both the [Ca2+]i increase and AVP release induced by ATP were highly and reversibly inhibited by suramin, suggesting the involvement of a P2 purinergic receptor in the ATP-induced responses. Pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), another P2 purinergic receptor antagonist, strongly reduced the ATP-induced [Ca2+]i response. 5. To further characterize the receptor, different agonists were tested, with the following efficacy: ATP = 2-methylthio-ATP > ATP-gamma-S > alpha, beta-methylene-ATP > ADP. The compounds adenosine, AMP, beta, gamma-methylene-ATP and UTP were ineffective. 6. The ATP-dependent [Ca2+]i increase was dependent on extracellular Ca2+ concentration ([Ca2+]o). Fluorescence-quenching experiments with Mn2+ showed that externally applied ATP triggered a Mn2+ influx. The ATP-induced [Ca2+]i increase and AVP release were independent of and additive to a K+-induced response, in addition to being insensitive to Cd2+. The ATP-induced [Ca2+]i increase was strongly reduced in the presence of Gd3+. These results suggest that the observed [Ca2+]i increases were elicited by Ca2+ entry through a P2X channel receptor rather than via a voltage-dependent Ca2+ channel. 7. We propose that ATP, co-released with neuropeptides, could act as a paracrine-autocrine messenger, stimulating, via Ca2+ entry through a P2X2 receptor, the secretion of AVP, in particular, from neurohypophysial nerve terminals.