76 research outputs found
Numerical methods of integration applied in the nonlinear dynamic analysis of shells of revolution
Evaluating methods of numerically integrating equations of motion for nonlinear dynamic analyses of shells of revolution by matrix displacement metho
Stiffness and mass matrices for shells of revolution (SAMMSOR II)
Utilizing element properties, structural stiffness and mass matrices are generated for as many as twenty harmonics and stored on magnetic tape. Matrices generated constitute input data to be used by other stiffness of revolution programs. Variety of boundary and loading conditions can be employed without having to create new mass and stiffness matrices for each case
Dynamic nonlinear analysis of shells of revolution (DYNASOR II)
Equations of motion of shell are solved using Houbolt's numerical procedure with nonlinear terms being moved to right-hand side of equilibrium equations and treated as generalized loads. Program was written in FORTRAN IV for IBM 360 or CDC 6000 series computers
DYNASOR 2 - A finite element program for the dynamic nonlinear analysis of shells of revolution
DYNASOR-2 finite element program for dynamic nonlinear analysis of shells of revolutio
SAMMSOR 2 - A finite element program to determine Stiffness And Mass Matrices of Shells Of Revolution
Finite element program for determining stiffness and mass matrices of shells of revolution - users manua
Nonlinear dynamic analysis of shells of revolution by matrix displacement method
Nonlinear dynamic analysis of shells of revolution by matrix displacement metho
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Dynamic compaction of salt: Initial demonstration and performance testing
Reconsolidated crushed salt is proposed as the sole long-term shaft seal between the Waste Isolation Pilot Plant (WIPP) and the biosphere. The concept for a long-term shaft seal for the WIPP repository is to place crushed salt in the four shafts and to develop an effective seal as the surrounding salt creeps into the shafts, reconsolidating the salt. Permeability of the salt components is calculated to achieve performance objectives at some acceptable time in the future, an expectation which is a key to performance assessment calculations for the WIPP. Such a seal has never been constructed, and until now no performance measurements have been made on an appropriately large scale. A full understanding of construction methods, achievable initial density and permeability and time-wise performance of reconsolidating salt is required. This paper discusses nearly full-scale dynamic compaction of mine-run WIPP salt, preliminary measurements of density and permeability, and their variability within a relatively large volume of compacted materia
Idebenone and Resveratrol Extend Lifespan and Improve Motor Function of HtrA2 Knockout Mice
Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington's disease (HD) and Parkinson's disease (PD). Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD
Design and baseline characteristics of the ParkFit study, a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients
<p>Abstract</p> <p>Background</p> <p>Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity.</p> <p>Methods</p> <p>We developed the ParkFit Program: a PD-specific and multifaceted behavioral program to promote physical activity. The emphasis is on creating a behavioral change, using a combination of accepted behavioral motivation techniques. In addition, we designed a multicentre randomized clinical trial to investigate whether this ParkFit Program increases physical activity levels over two years in sedentary PD patients. We intended to include 700 sedentary patients. Primary endpoint is the time spent on physical activities per week, which will be measured every six months using an interview-based 7-day recall.</p> <p>Results</p> <p>In total 3453 PD patients were invited to participate. Ultimately, 586 patients - with a mean (SD) age of 64.1 (7.6) years and disease duration of 5.3 (4.5) years - entered the study. Study participants were younger, had a shorter disease duration and were less sedentary compared with eligible PD patients not willing to participate.</p> <p>Discussion</p> <p>The ParkFit trial is expected to yield important new evidence about behavioral interventions to promote physical activity in sedentary patients with PD. The results of the trial are expected in 2012.</p> <p>Trial registration</p> <p><url>http://clinicaltrials.gov</url> (nr NCT00748488).</p
Nitrated α–Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons
The neuropathology of Parkinson's disease (PD) includes loss of dopaminergic neurons in the substantia nigra, nitrated alpha-synuclein (N-alpha-Syn) enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration.Nitrotyrosine (NT)-modified alpha-Syn was detected readily in cervical lymph nodes (CLN) from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Antigen-presenting cells within the CLN showed increased surface expression of major histocompatibility complex class II, initiating the molecular machinery necessary for efficient antigen presentation. MPTP-treated mice produced antibodies to native and nitrated alpha-Syn. Mice immunized with the NT-modified C-terminal tail fragment of alpha-Syn, but not native protein, generated robust T cell proliferative and pro-inflammatory secretory responses specific only for the modified antigen. T cells generated against the nitrated epitope do not respond to the unmodified protein. Mice deficient in T and B lymphocytes were resistant to MPTP-induced neurodegeneration. Transfer of T cells from mice immunized with N-alpha-Syn led to a robust neuroinflammatory response with accelerated dopaminergic cell loss.These data show that NT modifications within alpha-Syn, can bypass or break immunological tolerance and activate peripheral leukocytes in draining lymphoid tissue. A novel mechanism for disease is made in that NT modifications in alpha-Syn induce adaptive immune responses that exacerbate PD pathobiology. These results have implications for both the pathogenesis and treatment of this disabling neurodegenerative disease
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