Study of temporal pulse shape effects on W using simulations and laser heating

Transient heat pulses with triangular, square, and ELM-like temporal shapes are investigated in order to further understand how transient plasma instabilities will affect plasma facing components in tokamaks. A solution to the 1D heat equation for triangular pulses allows the peak surface temperature to be written analytically for arbitrary rise times. The solution as well as ANSYS simulations reveal that a positive ramp (maximum rise time) triangular pulse has a higher peak surface temperature by a factor of sqrt{2} compared to that from a negative ramp (rise time = 0) pulse shape with equal energy density, peak power, and pulse width. Translating the results to ITER, an ELM or disruption pulse with the shortest rise time is the most benign compared to other pulse shapes with the same peak heat flux and same energy density.</p

Multi-period Project Portfolio Selection under Risk considerations and Stochastic Income

This paper deals with multi-period project portfolio selection problem. In this problem, the available budget is invested on the best portfolio of projects in each period such that the net profit is maximized. We also consider more realistic assumptions to cover wider range of applications than those reported in previous studies. A novel mathematical model is presented to solve the problem, considering risks, stochastic incomes, and possibility of investing extra budget in each time period. Due to the complexity of the problem, an effective meta-heuristic method hybridized with a local search procedure is presented to solve the problem. The algorithm is based on genetic algorithm (GA), which is a prominent method to solve this type of problems. The GA is enhanced by a new solution representation and well selected operators. It also is hybridized with a local search mechanism to gain better solution in shorter time. The performance of the proposed algorithm is then compared with well-known algorithms, like basic genetic algorithm (GA), particle swarm optimization (PSO), and electromagnetism-like algorithm (EM-like) by means of some prominent indicators. The computation results show the superiority of the proposed algorithm in terms of accuracy, robustness and computation time. At last, the proposed algorithm is wisely combined with PSO to improve the computing time considerably

Achilles tendon mechanosensitivity is preserved in old age: In vivo evidence from a 1.5 years long resistance training intervention

Introduction Ageing deteriorates musculoskeletal system structure and function and limits its adaptability to mechanical loading. Medium-term (12-14 weeks) exercise interventions in older adults have been shown to increase tendon stiffness by increasing the tendon’s Young’s modulus [1], rather than the tendon’s cross-sectional area (CSA). However, little is known about the time-adaptive response relationship of the tendon in long-term (years) interventions involving alteration in mechanical loading. Therefore, we investigated whether the older human Achilles tendon (AT) demonstrates mechanosensitivity and alterations in material and/or size in response to long-term mechanical loading. Methods Thirty-four older female adults (age: 65±7 y) were recruited to a medium-term (14 weeks; n=21) strength training intervention with high AT strain cyclic loading (five sets of four repetitions of isometric plantarflexion contractions 3 times a week with 90% of MVC as in [2]) or a control group (n=13), with a sub-group of the intervention group (n=12) continuing exercise for 1.5 years. AT stiffness and Young’s modulus were quantified in vivo using ultrasonography and dynamometry. Tendon CSA was measured along the whole free AT by means of magnetic resonance imaging. Results Following 14 weeks of resistance training, the intervention group showed a significant (p<.05) increase in ankle plantarflexor muscle strength (141.5±36.2 vs 116.3±30.8 Nm at baseline), along with a 23% increase in AT stiffness (598.2±141.2 Nmm-1 vs 488.4±136.9 Nmm-1 at baseline), 20% increase in Young’s modulus (1.63±0.46 GPa vs 1.37±0.39 GPa at baseline) and a homogenous hypertrophy by about 6% along the entire free AT. However, continuing the exercise training for 1.5 years did not cause any further changes in muscle strength and tendon properties. The control group did not show any differences in muscle and tendon functional and structural properties between time points. Discussion The AT seems to have the capability to increase its stiffness in response to 14 weeks of mechanical loading exercise by altering both its material and size, and may thereby tolerate higher mechanical loading by reducing both the strain and stress it experiences during tensile loading. Continuing strength training appears to maintain, but not cause any further adaptive changes in tendons, which implies that the time-adaptive response relationship to mechanical loading is non-linear in ageing tendons. References 1. Reeves et al. (2003). J Physiol, 548, 971–981. 2. Arampatzis et al. (2007). J Exp Biol, 210, 2743–2753

Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID)

ObjectiveThe objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. MethodsThe GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud's and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, the investigators rated their patients as non-, partial or complete responders based on clinical grounds. ResultsData from 85 SLE patients were collected, 69 female and 16 male, with a mean disease duration of 9.8 years. The mean follow-up period was 9.67.4 months, resulting in 66.8 patient years of observation. A complete response was reported in 37 patients (46.8%), partial response in 27 (34.2%), no response in 15 (19.0%). On average, major clinical as well as laboratory efficacy parameters improved substantially, with the SLEDAI decreasing significantly from 12.2 to 3.3 points. Concerning safety, one infusion reaction leading to discontinuation of treatment occurred. Infections were reported with a rate of 19.5 (including six severe infections) per 100 patient years. ConclusionWith the restrictions of a retrospective data collection, the results of this study confirm data of other registries, which suggest a favourable benefit-risk ratio of rituximab in patients with treatment-refractory SLE

B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus

Background: Neuropsychiatric lupus (NPSLE) can be one of the earliest clinical manifestations in human lupus. However, its mechanisms are not fully understood. In lupus, a compromised blood-brain barrier may allow for the passage of circulating autoantibodies into the brain, where they can induce neuropsychiatric abnormalities including depression-like behavior and cognitive abnormalities. The purpose of this study was to determine the role of B cells and/or autoantibodies in the pathogenesis of murine NPSLE. Methods: We evaluated neuropsychiatric manifestations, brain pathology, and cytokine expression in constitutively (JhD/MRL/lpr) and conditionally (hCD20-DTA/MRL/lpr, inducible by tamoxifen) B cell-depleted mice as compared to MRL/lpr lupus mice. Results: We found that autoantibody levels were negligible (JhD/MRL/lpr) or significantly reduced (hCD20-DTA/MRL/lpr) in the serum and cerebrospinal fluid, respectively. Nevertheless, both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice showed profound depression-like behavior, which was no different from MRL/lpr mice. Cognitive deficits were also observed in both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice, similar to those exhibited by MRL/lpr mice. Furthermore, although some differences were dependent on the timing of depletion, central features of NPSLE in the MRL/lpr strain including increased blood-brain barrier permeability, brain cell apoptosis, and upregulated cytokine expression persisted in B cell-deficient and B cell-depleted mice. Conclusions: Our study surprisingly found that B cells and/or autoantibodies are not required for key features of neuropsychiatric disease in murine NPSLE