Recently a hybrid-type terahertz (THz) pulse source was proposed for high energy terahertz pulse generation. It is the combination of the conventional tilted-pulse-front setup and a nonlinear crystal ...with a transmission stair-step echelon of period in the hundred-micrometer range etched into the front face. The tilt angle introduced by the conventional tilted-pulse-front setup (pre-tilt) was chosen to be equal to the tilt-angle needed inside the nonlinear crystal (62° for lithium niobate (LN)) in order to fulfill velocity-matching. In this case, plane-parallel nonlinear optical crystals can be used. The possibility of using a plane-parallel nonlinear optical crystal for producing good-quality, symmetric THz beams was considered the most important advantage of this setup. In the present paper, a thorough numerical investigation of a modified version of that setup is presented. In the new version, the tilted pulse-front is created by a transmission grating without any imaging optics, and a wedged nonlinear optical crystal with a small wedge angle is supposed. According to a 1D numerical code, significantly higher THz generation efficiency can be achieved with a transmission stair-step echelon-faced nonlinear crystal having a 5 - 15-degree wedge angle than with a plane-parallel one or with the conventional tilted-pulse-front setup. Because of the spatially-dependent group-delay dispersion introduced by the transmission grating, a small wedge in the nonlinear crystal improves the spatial homogeneity of the THz-generation process, resulting in higher efficiencies and better beam profiles. At 100 K temperature, and by using 800 nm pump pulses with 20 mJ pulse energy, 100 fs pulse length and 8 mm beam spot radius, approximately 4.5% conversion efficiency and close to 1 mJ terahertz pulse energy can be reached with the newly-proposed setup.
Hadron therapy motivates research dealing with the production of particle beams with ∼100MeV/nucleon energy and relative energy fluctuation on the order of 1%. Laser-driven accelerators produce ion ...beams with only tens of MeV/nucleon energy and an extremely broad spectra. Here, a novel method is proposed for postacceleration and monochromatization of particles, leaving the laser-driven accelerator, by using intense THz pulses. It is based on further developing the idea of using the evanescent field of electromagnetic waves between a pair of dielectric crystals. Simple model calculations show that the energy of a proton bunch can be increased from 40 to 56 MeV in five stages and its initially broad energy distribution can be significantly narrowed down.
A robust method for producing half-cycle-few-cycle attosecond pulses in the extreme ultraviolet spectral range is proposed. It is based on coherent undulator radiation of relativistic ultrathin ...electron layers (nanobunches), which are produced by nanobunching of ultrashort electron bunches by a 10-TW power laser in a modulator undulator. Our numerical calculations predict the generation of nanobunches shorter than 10 nm. By using these electron nanobunches the production of carrier-envelope-phase stable attosecond pulses with up to a few tens of nJ energy and down to 10 nm wavelength and 35 as duration is predicted.
This work aims to determine the roles of reactive oxygen species HO∙ and HO2- in the bleaching of melanins by alkaline hydrogen peroxide. Experiments using melanosomes isolated from human hair ...indicated that the HO∙ radical generated in the outside solution does not contribute significantly to bleaching. However, studies using soluble Sepia melanin demonstrated that both HO2- and HO∙ will individually bleach melanin. Additionally, when both oxidants are present, bleaching is increased dramatically in both rate and extent. Careful experimental design enabled the separation of the roles and effects of these key reactive species, HO∙ and HO2-. Rationalisation of the results presented, and review of previous literature, allowed the postulation of a simplified general scheme whereby the strong oxidant HO∙ is able to pre-oxidise melanin units to o-quinones enabling more facile ring opening by the more nucleophilic HO2-. In this manner the efficiency of the roles of both species is maximised.
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•The roles of oxidants in the mechanism of hair melanin bleaching are proposed.•Both hydroxyl radical and perhydroxyl anion contribute to melanin bleaching.•Hydroxyl radicals pre-oxidise melanin facilitating reaction with perhydroxyl anion.•Ammonia plays no role in bleaching beyond melanin solubilisation and pH control.
Near- and far-field beam profiles were measured for THz pulses generated in LiNbO3 by optical rectification of 200 fs pulses with a tilted pulse front. The variation of the THz beam size and a ...dramatically increasing divergence angle with increasing pump fluence were observed in the (horizontal) plane of the pulse front tilt. No significant variation was observed in the vertical direction. The reason for the observed nonlinear beam distortion is the shortening of the effective interaction length for THz generation caused by the combined effect of pump spectral broadening and angular dispersion in the tilted pulse front geometry. Our results indicate that nonlinear THz beam distortion effects have to be taken into account when designing intense THz sources and related experiments.
Hypertension in the elderly substantially increases both the risk of vascular cognitive impairment (VCI) and Alzheimer’s disease (AD); however, the underlying mechanisms are not completely ...understood. This review discusses the effects of hypertension on structural and functional integrity of cerebral microcirculation, including hypertension-induced alterations in neurovascular coupling responses, cellular and molecular mechanisms involved in microvascular damage (capillary rarefaction, blood-brain barrier disruption), and the genesis of cerebral microhemorrhages and their potential role in exacerbation of cognitive decline associated with AD. Understanding and targeting the hypertension-induced cerebromicrovascular alterations that are involved in the onset and progression of AD and contribute to cognitive impairment are expected to have a major role in preserving brain health in high-risk older individuals.
Whole brain irradiation (WBI) is a mainstream therapy for patients with both identifiable brain metastases and prophylaxis for microscopic malignancies. However, it also promotes accelerated ...senescence in healthy tissues and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long term after treatment, due to γ-irradiation-induced cerebromicrovascular injury. Moment-to-moment adjustment of cerebral blood flow (CBF) via neuronal activity-dependent cerebromicrovascular dilation (functional hyperemia) has a critical role in maintenance of healthy cognitive function. To determine whether cognitive decline induced by WBI associates with impaired cerebromicrovascular function, C56BL/6 mice (3 months) subjected to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks) and control mice were compared. Mice were tested for spatial memory performance (radial arm water maze), sensorimotor coordination (computerized gait analysis, CatWalk), and cerebromicrovascular function (whisker-stimulation-induced increases in CBF, measured by laser Doppler flowmetry) at 3 to 6 months post-irradiation. We found that mice with WBI exhibited impaired cerebromicrovascular function at 3 months post-irradiation, which was associated with impaired performance in the radial arm water maze. At 6 months, post-irradiation progressive impairment in gait coordination (including changes in the regularity index and phase dispersion) was also evident. Collectively, our findings provide evidence for early and persisting neurovascular impairment after a clinically relevant protocol of fractionated WBI, which predict early manifestations of cognitive impairment.
Connective tissue growth factor (CTGF, also known as CCN2) is a matricellular protein expressed in the vascular wall, which regulates diverse cellular functions including cell adhesion, matrix ...production, structural remodeling, angiogenesis, and cell proliferation and differentiation. CTGF is principally regulated at the level of transcription and is induced by mechanical stresses and a number of cytokines and growth factors, including TGFβ. In this mini-review, the role of age-related dysregulation of CTGF signaling and its role in a range of macro- and microvascular pathologies, including pathogenesis of aorta aneurysms, atherogenesis, and diabetic retinopathy, are discussed. A potential role of CTGF and TGFβ in regulation and non-cell autonomous propagation of cellular senescence is also discussed.
Abstract
Age-related gait dysfunction and balance disorders are a major cause of falls and injury in the elderly population. Epidemiological studies have shown that disturbances in gait coordination ...which manifest with age are associated with increased morbidity and mortality, impaired cognitive capacity, as well as reduced level of function and loss of independence. In geroscience, mice are the most frequently used model system to test efficiency of antiaging interventions. Despite the clinical importance of age-related gait abnormalities in older adults, the impact of aging on mouse gait coordination is not well documented in the literature. To characterize the effect of aging on mouse gait, we assessed gait function in young (3-month-old) and aged (24-month-old) freely moving C57BL/6 mice using the semiautomated, highly sensitive CatWalk XT system for quantitative assessment of footfall and motor performance. We found that aged mice exhibited significantly decreased cadence and increased stride time variability. Aging also tended to alter footfall patterns. In aged mice, speed, swing speed, stride length, duty cycle, base of support, terminal dual stance, the regularity index, and the gait symmetry index were unaltered. Thus, aging is associated with characteristic alterations in gait function in C57BL/6 mice, which could potentially be assessed as clinically relevant endpoints in geroscience studies testing the effects of antiaging interventions.
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