High-power lasers, such as the Laser MegaJoule (LMJ), have to be phase modulated to avoid stimulated Brillouin scattering (SBS) that may strongly damage optics at the end of the laser chain. Current spectral broadening on LMJ is performed with a sinusoidal phase modulation. This pure sinusoidal phase modulation leads to inhomogeneous spectral power densities (SPD). Thus, for a same SBS power threshold, the sinusoidal phase-modulated spectrum has to be larger than the equivalent ideal SPD with isoenergetic peaks. We present in this paper a technique to generate energy-balanced Dirac peaks spectra thanks to nonsinusoidal phase modulations. Thus, we can build a narrower spectrum with a nonsinusoidal phase modulation that has the same SBS threshold as a sinusoidal phase modulation, and we show that FM-to-AM conversion can be strongly reduced, which is of great interest for LMJ laser performance, with reductions up to 40%.
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http://dx.doi.org/10.1364/AO.49.001104 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFBackground: CT1812 is an experimental therapeutic sigma-2 receptor modulator in development for Alzheimer's disease (AD) and dementia with Lewy bodies. CT1812 reduces the affinity of Aβ oligomers to bind to neurons and exert synaptotoxic effects. This phase 2, multi-center, international, randomized, double-blind, placebo-controlled trial assessed safety, tolerability and effects of CT1812 on cognitive function in individuals with AD.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most common cause of age-related dementia, and the presence of amyloid-β (Aβ) plaques and tau-containing neurofibrillary tangles is associated with the neurodegeneration and cognitive impairment in this incurable disease. Growing evidence shows that epigenetic dysregulation through histone deacetylases (HDACs) plays a critical role in synaptic dysfunction and memory loss in AD, and HDACs have been highlighted as a novel class of anti-Alzheimer targets. Moreover, restoring Wnt/β-catenin signaling, which is greatly suppressed in AD brains, is a promising therapeutic strategy for AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Good T Cells, Seoul, Mapo-gu, Korea, Republic of (South); YONSEI University, Seoul, Seodaemun-gu, Korea, Republic of (South).
Background: Neurodegenerative diseases, including Alzheimer's disease (AD), have been long thought to be independent of the peripheral immune system, but their pathogenesis status is functionally influenced by various T cell subsets in the periphery. Especially Treg cells are emerging as an important dynamic population in the brain, but the detailed immunological molecular and cellular processes are poorly characterized METHOD: We reported that the cell surface protein Lrig1 is enriched in Treg cells and is an essential regulator of the functions of Treg cells in vitro and in vivo. To evaluate the functional importance of Treg cells in AD pathogenesis, the modulating mAb specific to Lrig1 (GTC 310-01) via intravenous injection route was administered into 5xFAD or 6xTg mice, the genetic mouse model of AD, and the various AD symptoms were investigated.
View Article and Find Full Text PDFBackground: Microglial activation is one of the neuropathological hallmarks of Alzheimer's disease (AD). Evidence suggest that chronic activation of microglia cause neuroinflammation and neuronal injuries, contributing to cognitive impairment. Therefore, modulation of microglial pathway like CSF-1R represents an attractive therapeutic strategy.
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