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New Insights in the Amyloid-Beta Interaction with Mitochondria
Carlos Spuch,Saida Ortolano,Carmen Navarro
Journal of Aging Research , 2012, DOI: 10.1155/2012/324968
Abstract: Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer’s disease (AD). Particularly, mitochondrial dysfunction is a hallmark of amyloid-beta-induced neuronal toxicity in Alzheimer’s disease. The recent emphasis on the intracellular biology of amyloid-beta and its precursor protein (APP) has led researchers to consider the possibility that mitochondria-associated and mitochondrial amyloid-beta may directly cause neurotoxicity. Both proteins are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron transport chain, increase reactive oxygen species production, cause mitochondrial damage, and prevent neurons from functioning normally. In this paper, we will outline current knowledge of the intracellular localization of amyloid-beta. Moreover, we summarize evidence from AD postmortem brain as well as animal AD models showing that amyloid-beta triggers mitochondrial dysfunction through a number of pathways such as impairment of oxidative phosphorylation, elevation of reactive oxygen species production, alteration of mitochondrial dynamics, and interaction with mitochondrial proteins. Thus, this paper supports the Alzheimer cascade mitochondrial hypothesis such as the most important early events in this disease, and probably one of the future strategies on the therapy of this neurodegenerative disease. 1. Introduction Each year, over 10 million people globally suffer from neurodegenerative diseases. This figure is expected to grow by 20% over the next decade as the aging population increases and lives longer. This disease group is the fourth biggest killer in the developed world after heart diseases, cancer, and stroke [1]. The most common neurodegenerative diseases are AD, Parkinson disease, Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis [2]. The most widely recognized is AD, which is among the principal debilitating conditions of the current century. Approximately 24 million people worldwide suffer from dementia, 60% of cases being due to AD, which occurs in 1% of individuals aged 50 to 70 years old and dramatically increases to 50% of those over 70 years old [3]. Dramatically, these numbers are estimated to increase to 15 million in the next 40 years [4]. From the neuropathological point of view, AD is characterized by selective neuronal loss, marked synaptic alteration, morphological mitochondrial abnormalities, and Tau pathology. The
Boundary Value Problems for Burgers Equations, through Nonstandard Analysis  [PDF]
Saida Bendaas
Applied Mathematics (AM) , 2015, DOI: 10.4236/am.2015.66099
Abstract: In this paper we study inviscid and viscid Burgers equations with initial conditions in the half plane \"\". First we consider the Burgers equations with initial conditions admitting two and three shocks and use the HOPF-COLE transformation to linearize the problems and explicitly solve them. Next we study the Burgers equation and solve the initial value problem for it. We study the asymptotic behavior of solutions and we show that the exact solution of boundary value problem for viscid Burgers equation as viscosity parameter is sufficiently small approach the shock type solution of boundary value problem for inviscid Burgers equation. We discuss both confluence and interacting shocks. In this article a new approach has been developed to find the exact solutions. The results are formulated in classical mathematics and proved with infinitesimal technique of non standard analysis.
The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss
Sarah L. Spiden equal contributor,Mario Bortolozzi equal contributor,Francesca Di Leva equal contributor,Martin Hrabé de Angelis,Helmut Fuchs,Dmitry Lim,Saida Ortolano,Neil J. Ingham,Marisa Brini,Ernesto Carafoli,Fabio Mammano,Karen P. Steel
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000238
Abstract: Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone.
Bridge connection of quantum Hall elementary devices
Luca Callegaro,Massimo Ortolano
Physics , 2013,
Abstract: Multiple-series and multiple-parallel connections of quantum Hall elementary devices allow the realization of multiple or fractional values of the quantized Hall resistance, rejecting the effect of contact and wiring resistances. We introduce here the multiple-bridge connection, which maintains the properties of multiple-series and parallel connections and allows more freedom in the choice of the topology of networks composed of quantum Hall elements, and the design of more efficient quantum Hall array resistance standards (and other devices). As an example, a 5-element network is analyzed in detail.
Matrix method analysis of quantum Hall effect device connections
Massimo Ortolano,Luca Callegaro
Physics , 2011, DOI: 10.1088/0026-1394/49/1/001
Abstract: The modelling of electrical connections of single, or several, multiterminal quantum Hall effect (QHE) devices is relevant for electrical metrology: it is known, in fact, that certain particular connections allow i) the realization of multiples or fractions of the quantised resistance, or ii) the rejection of stray impedances, so that the configuration maintains the status of quantum standard. Ricketts-Kemeny and Delahaye equivalent circuits are known to be accurate models of the QHE: however, the numerical or analytical solution of electrical networks including these equivalent circuits can be difficult. In this paper, we introduce a method of analysis based on the representation of a QHE device by means of the \emph{indefinite admittance matrix}: external connections are then represented with another matrix, easily written by inspection. Some examples, including the solution of double- and triple-series connections, are shown.
Circuit models and SPICE macro-models for quantum Hall effect devices
Massimo Ortolano,Luca Callegaro
Physics , 2015,
Abstract: Quantum Hall effect (QHE) devices are a pillar of modern quantum electrical metrology. Electrical networks including one or more QHE elements can be used as quantum resistance and impedance standards. The analysis of these networks allows metrologists to evaluate the effect of the inevitable parasitic parameters on their performance as standards. This paper presents a systematic analysis of the various circuit models for QHE elements proposed in the literature, and the development of a new model. This last model is particularly suited to be employed with the analogue electronic circuit simulator SPICE. The SPICE macro-model and examples of SPICE simulations, validated by comparison with the corresponding analytical solution and/or experimental data, are provided.
Universal Property of Quantum Gravity implied by Uniqueness Theorem of Bekenstein-Hawking Entropy
Hiromi Saida
Entropy , 2011, DOI: 10.3390/e13091611
Abstract: This paper consists of three parts. In the first part, we prove that the Bekenstein-Hawking entropy is the unique expression of black hole entropy. Our proof is constructed in the framework of thermodynamics without any statistical discussion. In the second part, intrinsic properties of quantum mechanics are shown, which justify the Boltzmann formula to yield a unique entropy in statistical mechanics. These properties clarify three conditions, one of which is necessary and others are sufficient for the validity of Boltzmann formula. In the third part, by combining the above results, we find a reasonable suggestion from the sufficient conditions that the potential of gravitational interaction among microstates of underlying quantum gravity may not diverge to negative infinity (such as Newtonian gravity) but is bounded below at a finite length scale. In addition to that, from the necessary condition, the interaction has to be repulsive within the finite length scale. The length scale should be Planck size. Thus, quantum gravity may become repulsive at Planck length. Also, a relation of these suggestions with action integral of gravity at semi-classical level is given. These suggestions about quantum gravity are universal in the sense that they are independent of any existing model of quantum gravity.
Les candidates du PJD: Quel encadrement politique de la femme marocaine dans la perspective de l’action parlementaire 2007?
Saida Latmani
Historia Actual Online , 2007,
Abstract: La constitución de 1962 ha insistido literalmente en la paridad entre hombres y mujeres en el ejercicio de los derechos políticos. Este espíritu se ha visto confirmado por las constituciones siguientes (1970, 1972, 1992 y 1996). En un país donde las elecciones revisten una gran importancia, en el cuadro de la lucha por el poder político, este derecho adquiere una extrema importancia en la medida que el género femenino tiene un gran peso, no sólo en términos numéricos. Sin embargo, el derecho de la mujer a la candidatura política permanece incierto. Esgrimir la consigna de la participación política no es suficiente y no altera el marco del discurso, tanto al no haber una conciencia de la participación de la mujer en el juego político como que ésta no es considerada un elemento activo y esencial en toda lucha emprendida por la elite marroquí. Con el concurso de los partidos, será posible familiarizar a la mujer con la práctica política y proporcionarle una experiencia decisiva en este campo.
Microstructure And Market Maker Price Strategies: Study Of A Tunisian Market Maker Activity
Review of Economic and Business Studies (REBS) , 2010,
Abstract: This paper provides evidence on market making behaviour of FX dealer in the Tunisian FX. It uses a complete data set that includes intra-day trades for the euro and US dollar. The sample period is 1 January 2007 to 31 December 2007. The results are consistent with the findings of the literature that used trades and inventories data. I find evidence that customer order flow has information effect on USD/TND. However, I do not find evidence that customer order flow has information effect on EUR/TND. Moreover, inter-dealer order flow has a positive effect on the market maker price strategy. I also find that the central bank intervention has positive and significant effect on dealer’s behaviour and price formation process. My study also suggests that dealer is risk aversion and his quotes flows the references quotes tendency.
de Sitter thermodynamics in the canonical ensemble
Hiromi Saida
Physics , 2009, DOI: 10.1143/PTP.122.1239
Abstract: The existing thermodynamics of the cosmological horizon in de-Sitter spacetime is established in the micro-canonical ensemble, while thermodynamics of black hole horizons are established in the canonical ensemble. Generally in the ordinary thermodynamics and statistical mechanics, both of the micro-canonical and canonical ensembles yield the same equation of state for any thermodynamic system. This implies the existence of a formulation of de-Sitter thermodynamics based on the canonical ensemble. This paper reproduces the de-Sitter thermodynamics in the canonical ensemble. The procedure is as follows: We put a spherical wall at the center of de-Sitter spacetime, whose mass is negligible and perfectly reflects the Hawking radiation coming from the cosmological horizon. Then the region enclosed by the wall and horizon settles down to a thermal equilibrium state, for which the Euclidean action is evaluated and the partition function is obtained. The integration constant (subtraction term) of Euclidean action is determined to reproduce the equation of state (e.g. entropy-area law) verified already in the micro-canonical ensemble. Our de-Sitter canonical ensemble is well-defined to preserve the "thermodynamic consistency", which means that the state variables satisfy not only the four laws of thermodynamics but also the appropriate differential relations with thermodynamic functions; e.g. partial derivatives of the free energy give the entropy, pressure, and so on. The special role of cosmological constant in de-Sitter thermodynamics is also revealed.
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