19,790 research outputs found
NEW ROLES FOR FC RECEPTORS IN NEURODEGENERATION-THE IMPACT ON IMMUNOTHERAPY FOR ALZHEIMER’S DISEASE
No full textThere are an estimated 18 million Alzheimer’s disease (AD) sufferers worldwide and with no disease modifying treatment currently available, development of new therapies represents an enormous unmet clinical need. AD is characterised by episodic memory loss followed by severe cognitive decline and is associated with many neuropathological changes. AD is characterised by deposits of amyloid beta (Aβ), neurofibrillary tangles, and neuroinflammation. Active immunisation or passive immunisation against Aβ leads to the clearance of deposits in transgenic mice expressing human Aβ. This clearance is associated with reversal of associated cognitive deficits, but these results have failed to translate to humans, with both active and passive immunotherapy failing to improve memory loss. One explanation for these observations is that certain anti-Aβ antibodies mediate damage to the cerebral vasculature limiting the top dose and potentially reducing efficacy. Fc gamma receptors (Fcγ) are a family of immunoglobulin like receptors which bind to the Fc portion of IgG, and mediate the response of effector cells to immune complexes. Data from both mouse and human studies suggest that cross-linking Fc receptors by therapeutic antibodies and the subsequent pro-inflammatory response mediates the vascular side effects seen following immunotherapy. Increasing evidence is emerging that Fc receptor expression on CNS resident cells, including microglia and neurons, is increased during aging and functionally involved in the pathogenesis of age-related neurodegenerative diseases. We propose that increased expression and ligation of Fc receptors in the CNS, either by endogenous IgG or therapeutic antibodies, has the potential to induce vascular damage and exacerbate neurodegeneration. To produce safe and effective immunotherapies for AD and other neurodegenerative diseases it will be vital to understand the role of Fc receptors in the healthy and diseased brain
Metabolism of territrem A by liver microsomes of Wistar rats: Cytochrome P450 isoforms catalyzing TRA metabolism.
No full textMetabolism of territrem A by liver microsomes of Wistar rats: identification of the metabolites and their metabolic pathway.
No full textMetabolism of territrem A by liver microsomes of Wistar rats: Sex differences and regulation with gonadal hormones and phenobarbital.
No full textControl and Filtering for Discrete Linear Repetitive Processes with H infty and ell 2--ell infty Performance
No full textRepetitive processes are characterized by a series of sweeps, termed passes, through a set of dynamics defined over a finite duration known as the pass length. On each pass an output, termed the pass profile, is produced which acts as a forcing function on, and hence contributes to, the dynamics of the next pass profile. This can lead to oscillations which increase in amplitude in the pass to pass direction and cannot be controlled by standard control laws. Here we give new results on the design of physically based control laws for the sub-class of so-called discrete linear repetitive processes which arise in applications areas such as iterative learning control. The main contribution is to show how control law design can be undertaken within the framework of a general robust filtering problem with guaranteed levels of performance. In particular, we develop algorithms for the design of an H? and dynamic output feedback controller and filter which guarantees that the resulting controlled (filtering error) process, respectively, is stable along the pass and has prescribed disturbance attenuation performance as measured by and – norms
Synthesis and Properties of New Dialkoxyphenylene Quinoxaline-Based Donor-Acceptor Conjugated Polymers and Their Applications on Thin Film Transistors and Solar Cells
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Cytochrome P4503A1 catalyzes the formation of MA1 from territrem A in liver microsomes of 7-week-old female Wistar rats.
No full textMethamphetamine and diazepam suppress antigen-specific cytokine expression and antibody production in ovalbumin-sensitized BALB/c mice
No full textAcoustic radiation due to scattering of T-S wave by the mean-flow distortion induced by steady local suction
No full textSubstantial sound waves can be generated by boundary-layer instability modes when the latter are scattered by a rapid mean-flow distortion. This is a rather generic mechanism and operates when an oncoming T-S wave is scattered by a steady local suction slot. This paper focuses on this problem by extending a recently developed Local Scattering Theory (Wu & Dong, J. Fluid Mech. submitted), where a so-called transmission coefficient, defined as the ratio of the T-S wave amplitude downstream of the scatter to that upstream, is introduced to characterize the effect of a local scatter on boundary-layer instability and transition. As in the earlier work, the mathematical formulation is based on triple-deck formulism, but in order to accommodate the acoustic far field, which was not considered in the paper mentioned, the unsteady terms in the upper deck, which play a leading-order role in radiation, are retained, and the influence of the radiated sound on the near-wall perturbation is included. The upper deck equation for the pressure is the Helmholtz equation rather than the Laplace equation. This leads to a modified pressure-displacement relation, which is coupled with the linearized boundary-layer equations in the lower deck. Discretization of the whole system formulates a generalized eigenvalue problem, which is solved numerically. It is found that suction suppresses oncoming T-S waves, and this effect increases with the suction velocity and the slot width. The directivity is ndependent of the flow parameters only when the Mach number is low. The intensity of the radiated sound in general increases with the frequency, the suction velocity and the width of the suction slot. Interestingly, for O(1) suction velocities, the radiated sound is very weak, indicating that the gain of stabilizing effect does not cause aeroacoustic penalty
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