997 resultados para disjunctive model (DM)
Resumo:
Background: There is growing evidence that microglia are key players in the pathological process of amyotrophic lateral sclerosis (ALS). It is suggested that microglia have a dual role in motoneurone degeneration through the release of both neuroprotective and neurotoxic factors. Results: To identify candidate genes that may be involved in ALS pathology we have analysed at early symptomatic age (P90), the molecular signature of microglia from the lumbar region of the spinal cord of hSOD1(G93A) mice, the most widely used animal model of ALS. We first identified unique hSOD1(G93A) microglia transcriptomic profile that, in addition to more classical processes such as chemotaxis and immune response, pointed toward the potential involvement of the tumour suppressor gene breast cancer susceptibility gene 1 (Brca1). Secondly, comparison with our previous data on hSOD1(G93A) motoneurone gene profile substantiated the putative contribution of Brca1 in ALS. Finally, we established that Brca1 protein is specifically expressed in human spinal microglia and is up-regulated in ALS patients. Conclusions: Overall, our data provide new insights into the pathogenic concept of a non-cell-autonomous disease and the involvement of microglia in ALS. Importantly, the identification of Brca1 as a novel microglial marker and as possible contributor in both human and animal model of ALS may represent a valid therapeutic target. Moreover, our data points toward novel research strategies such as investigating the role of oncogenic proteins in neurodegenerative diseases.
Resumo:
Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia ll/Iyotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.
Resumo:
In order to extend the Cam clay model an inner kinematically hardening bubble is added in order to match experimentally observed hysteretic response. The new model is found to be quite successful in reproducing patterns of response observed in slow cyclic oedometer and triaxial tests. -from Authors
Resumo:
Lateral insulated gate bipolar transistors (LIGBTs) in silicon-on-insulator (SOI) show a unique turn off characteristic when compared to junction-isolated RESURF LIGBTs or vertical IGBTs. The turn off characteristic shows an extended `terrace' where, after the initial fast transient characteristic of IGBTs due to the loss of the electron current, the current stays almost at the same value for an extended period of time, before suddenly dropping to zero. In this paper, we show that this terrace arises because there is a value of LIGBT current during switch off where the rate of expansion of the depletion region with respect to the anode current is infinite. Once this level of anode current is approached, the depletion region starts to expand very rapidly, and is only stopped when it reaches the n-type buffer layer surrounding the anode. Once this happens, the current rapidly drops to zero. A quasi-static analytic model is derived to explain this behaviour. The analytically modelled turn off characteristic agrees well with that found by numerical simulation.
Resumo:
This paper proposes a movement trajectory planning model, which is a maximum task achievement model in which signal-dependent noise is added to the movement command. In the proposed model, two optimization criteria are combined, maximum task achievement and minimum energy consumption. The proposed model has the feature that the end-point boundary conditions for position, velocity, and acceleration need not be prespecified. Consequently, the method can be applied not only to the simple point-to-point movement, but to any task. In the method in this paper, the hand trajectory is derived by a psychophysical experiment and a numerical experiment for the case in which the target is not stationary, but is a moving region. It is shown that the trajectory predicted from the minimum jerk model or the minimum torque change model differs considerably from the results of the psychophysical experiment. But the trajectory predicted from the maximum task achievement model shows good qualitative agreement with the hand trajectory obtained from the psychophysical experiment. © 2004 Wiley Periodicals, Inc.
Resumo:
An important first step in spray combustion simulation is an accurate determination of the fuel properties which affects the modelling of spray formation and reaction. In a practical combustion simulation, the implementation of a multicomponent model is important in capturing the relative volatility of different fuel components. A Discrete Multicomponent (DM) model is deemed to be an appropriate candidate to model a composite fuel like biodiesel which consists of four components of fatty acid methyl esters (FAME). In this paper, the DM model is compared with the traditional Continuous Thermodynamics (CTM) model for both diesel and biodiesel. The CTM model is formulated based on mixing rules that incorporate the physical and thermophysical properties of pure components into a single continuous surrogate for the composite fuel. The models are implemented within the open-source CFD code OpenFOAM, and a semi-quantitative comparison is made between the predicted spray-combustion characteristics and optical measurements of a swirl-stabilised flame of diesel and biodiesel. The DM model performs better than the CTM model in predicting a higher magnitude of heat release rate in the top flame brush region of the biodiesel flame compared to that of the diesel flame. Using both the DM and CTM models, the simulation successfully reproduces the droplet size, volume flux, and droplet density profiles of diesel and biodiesel. The DM model predicts a longer spray penetration length for biodiesel compared to that of diesel, as seen in the experimental data. Also, the DM model reproduces a segregated biodiesel fuel vapour field and spray in which the most abundant FAME component has the longest vapour penetration. In the biodiesel flame, the relative abundance of each fuel component is found to dominate over the relative volatility in terms of the vapour species distribution and vice versa in the liquid species distribution. © 2014 Elsevier Ltd. All rights reserved.
Resumo:
The SWAP operation in a two-qubit Heisenberg model in the presence of Dzyaloshinskii-Moriya (DM) anisotropic antisymmetric interaction is investigated. 1t is shown that the SWAP operation can be implemented for some kinds of DM coupling and the influence of DM couplings is divided into different cases. The conditions of the DM coupling under which the SWAP operation is feasible are established. (C) 2007 Elsevier B.V. All rights reserved.