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Parkinson’s disease (PD) diagnosis mostly relies on (late) clinical (parkinsonism) symptoms, whereas we need early diagnostic markers in order to initiate and monitor the effects of forthcoming disease-modifying drugs in the earliest phase of this disease. Therefore, reliable diagnostic and prognostic biomarkers are urgently needed. Evidence suggests the potential (differential) diagnostic and prognostic value of clinical, genetic, neuroimaging, and biochemical markers (e.g., in saliva, urine, blood and cerebrospinal fluid). Such biomarkers may include α-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain, closely reflecting the pathophysiology of PD. Here, we provide an overview of these markers with practical guidelines for facilitating early PD diagnosis.
Pebrine disease, caused by Nosema bombycis (Nb) infection in silkworms, is a severe and long-standing disease that threatens sericulture. As parasitic pathogens, a complex relationship exists between microsporidia and their hosts at the mitochondrial level. Previous studies have found that the translocator protein (TSPO) is involved in various biological functions, such as membrane potential regulation, mitochondrial autophagy, immune responses, calcium ion channel regulation, and cell apoptosis. In the present study, we found that TSPO expression in silkworms (BmTSPO) was upregulated following Nb infection, leading to an increase in cytoplasmic calcium, adenosine triphosphate, and reactive oxygen species levels. Knockdown and overexpression of BmTSPO resulted in the promotion and inhibition of Nb proliferation, respectively. We also demonstrated that the overexpression of BmTSPO promotes host cell apoptosis and significantly increases the expression of genes involved in the immune deficiency and Janus kinase-signal transducer and the activator of the transcription pathways. These findings suggest that BmTSPO activates the innate immune signalling pathway in silkworms to regulate Nb proliferation. Targeting TSPO represents a promising approach for the development of new treatments for microsporidian infections.
Multilayer dielectric gratings (MLDGs) are crucial for pulse compression in picosecond–petawatt laser systems. Bulged nodular defects, embedded in coating stacks during multilayer deposition, influence the lithographic process and performance of the final MLDG products. In this study, the integration of nanosecond laser conditioning (NLC) into different manufacturing stages of MLDGs was proposed for the first time on multilayer dielectric films (MLDFs) and final grating products to improve laser-induced damage performance. The results suggest that the remaining nodular ejection pits introduced by the two protocols exhibit a high nanosecond laser damage resistance, which remains stable when the irradiated laser fluence is more than twice the nanosecond-laser-induced damage threshold (nanosecond-LIDT) of the unconditioned MLDGs. Furthermore, the picosecond-LIDT of the nodular ejection pit conditioned on the MLDFs was approximately 40% higher than that of the nodular defects, and the loss of the grating structure surrounding the nodular defects was avoided. Therefore, NLC is an effective strategy for improving the laser damage resistance of MLDGs.
To estimate the association of catastrophic health expenditure (CHE) with the risk of depression in middle-aged and old people in China.
Methods
We used data of 2011, 2013, 2015 and 2018 from the China Health and Retirement Longitudinal Study, which covered 150 counties of 28 provinces in China. CHE was calculated as out-of-pocket health expenditure exceeding 40% of a household’s capacity to pay. Depression was measured by a 10-item Centre for Epidemiological Studies Depression Scale. We evaluated CHE prevalence and applied Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) for the risk of depression among participants with CHE after controlling potential confounders, compared with those without CHE.
Results
Among 5765 households included in this study, CHE prevalence at baseline was 19.24%. The depression incidence of participants with CHE (8.00 per 1000 person-month) was higher than that of those without CHE (6.81 per 1000 person-month). After controlling confounders, participants with CHE had a 13% higher risk (aHR = 1.13, 95% CI: 1.02–1.26) of depression than those without CHE. In subgroup analysis, the association of CHE with depression was significant in males and in people with chronic diseases, of younger age, living in rural areas and of lowest family economic level (all P < 0.05).
Conclusions
Nearly one of five middle-aged and old people in China incurred CHE, and CHE was associated with the risk of depression. Concerted efforts should be made to monitor CHE and related depression episode. Moreover, timely interventions about CHE and depression need to be implemented and strengthened among middle-aged and old people.
High-performance 86 μJ, 11.2 fs pulses with a spectrum range of 800–1050 nm are generated based on 1030 nm, 190 fs Yb femtosecond pulses by using multi-plate-based spectral broadening and filtering. Taking advantage of single beam configuration, the obtained pulses have excellent power and spectral stabilities. Since the output spectrum is obtained by spectrally filtering the broadened components, the temporal contrast of the output pulses is enhanced by at least four orders of magnitude. Together with the robust and simple setup, the proposed method is expected to be a competitive option for the generation of seed pulses for 10s–100s petawatt lasers.
Multilayer dielectric gratings typically remove multiple-grating pillars after picosecond laser irradiation; however, the dynamic formation process of the removal is still unclear. In this study, the damage morphologies of multilayer dielectric gratings induced by an 8.6-ps laser pulse were closely examined. The damage included the removal of a single grating pillar and consecutive adjacent grating pillars and did not involve the destruction of the internal high-reflection mirror structure. Comparative analysis of the two damage morphological characteristics indicated the removal of adjacent pillars was related to an impact process caused by the eruption of localized materials from the left-hand pillar, exerting impact pressure on its adjacent pillars and eventually resulting in multiple pillar removal. A finite-element strain model was used to calculate the stress distribution of the grating after impact. According to the electric field distribution, the eruptive pressure of the dielectric materials after ionization was also simulated. The results suggest that the eruptive pressure resulted in a stress concentration at the root of the adjacent pillar that was sufficient to cause damage, corresponding to the experimental removal of the adjacent pillar from the root. This study provides further understanding of the laser-induced damage behavior of grating pillars and some insights into reducing the undesirable damage process for practical applications.
Western Kunlun Mountain (WKM) glaciers show balanced or even slightly positive mass budgets in the early 21st century, and this is anomalous in a global context of glacier reduction. However, it is unknown whether the stability prevails at longer time scales because mass budgets have been unavailable before 2000. Here topographical maps, Shuttle Radar Topography Mission and Landsat data are used to examine the area and surface elevation changes of glaciers on the WKM since the 1970s. Heterogeneous glacier behaviors are observed not only in the changes of length and area, but also in the spatial distribution of surface elevation changes. However, on average, glacier area and elevation changes are not significant. Glaciers reduce in the area by 0.07 ± 0.1% a−1 from the 1970s to 2016. Averaged glacier mass loss is −0.06 ± 0.13 m w.e. a−1 from the 1970s to 1999. These findings show that the WKM glacier anomaly extends back at least to the 1970s.
Radioisotopes (239Pu, 240Pu, 236U) formed during atmospheric nuclear weapons testing (NWT) can be used for dating and therefore be applied as markers of the beginning of the Anthropocene Epoch. Moreover, 240Pu/239Pu ratios enable source identification (general fallout, local emission sources). Ice core segments from a 57.6 m ice core to bedrock from eastern Tien Shan, China were selected for 239,240Pu and 236U analyses by using compact low-energy accelerator mass spectrometry. The observed 240Pu/239Pu atom ratios were 0.18 ± 0.02, with one exception, indicating global fallout. No evidence for emissions from the nearby local sources Lop Nor was observed. The total deposition rates during NWT for 239Pu and 240Pu amount to 1.55 × 109 atoms·cm−2 and 3.1 × 108 atoms·cm−2, respectively. With the higher undisturbed fallout of 239Pu compared with values reported for glaciers from European Alps at Col du Dome and Colle Gnifetti as well as from the polar region, the eastern Tien Shan glacier would be an ideal site for defining the start of the Anthropocene. 236U is a rather new environmental tracer, while little is known about its global fallout from NWT. The observed deposition flux of 236U during NWT amounts to 3.5 × 108 atoms·cm−2 at the drill site. The average 236U/239Pu ratio of 0.27 ± 0.09 is in good agreement with literature values from global fallout.
Glacier changes in the Karlik Shan, eastern Tien Shan, from 1971/72 to 2001/02 were monitored in this study. Topographic maps of 1 : 50 000 scale based on aerial photographs from 1971/72 and satellite images (Landsat TM, Landsat ETM+ and ASTER) from 1992, 2001 and 2002 were used to map glacier extent through a process of manual digitizing. The total glacier area decreased by 5.3% from 1971/72 to 2001/02. The rate of glacier area shrinkage was 0.13% a–1 between 1972 and 1992, but it was 0.27% a–1 from 1992 to 2001/02, suggesting accelerated glacier retreat in recent decades. Glacier changes in the region are a response to summer temperature increase. Annual precipitation also showed an upward trend, but this could not compensate for the mass loss due to ablation.
In 2005, two ice cores with lengths of 58.7 and 57.6 m respectively to bedrock were recovered from the Miaoergou flat-topped glacier (43°03′19″ N, 94°19′21″ E; 4512 m a.s.l.), eastern Tien Shan. 210Pb dating of one of the ice cores (57.6 m) was performed, and an age of AD 1851 ± 6 at a depth of 35.2 mw.e. was determined. For the period AD 1851-2005, a mean annual net accumulation of 229 ± 7 mm w.e. a–1 was calculated. At the nearby oasis city of Hami (~80 km from the Miaoergou flat-topped glacier) the annual precipitation rate is 38 mm w.e. a–1, hence glacial meltwater is a major water supply for local residents. The surface activity concentration of 210Pbex was found to be ~400 mBq kg–1, which is higher than observed at other continental sites such as Belukha, Russia, and Tsambagarav, Mongolia, which have surface activity concentrations of 280 mBq kg–1. The 210Pb dating agrees well with the chronological sequence deduced from the annual-layer counting resulting from the seasonalities of d18O and trace metals for the period AD 1953-2005, and ^-activity horizons resulting from atmospheric nuclear testing during the period AD 1962-63. We conclude that 210Pb analysis is a suitable method for obtaining a continuous dating of the Miaoergou ice core for ~160 years, which can also be applied to other ice cores recovered from the mountains of western China.
Two ice cores drilled to the bottom were recovered from Miaoergou flat-topped glacier (43°03'19“N, 94°19'21“E; 4512 ma.s.l.), eastern Tien Shan, central Asia, in 2005. A high–resolution record of cadmium was established by applying inductively coupled plasma mass spectrometry to one of the ice cores (57.6 m), covering a 228 year period from AD 1776 to 2004. The results showed long-term variations of atmospheric transport and deposition of cadmium at high altitudes. Trend analysis based on the sequential Mann-Kendall test and the analysis of crustal enrichment factors of the cadmium shows that natural contribution, mainly from rock and mineral dust, dominated the atmospheric cycles of cadmium during the period AD 1776–1957, which was confirmed by the significant correlation between the winter North Atlantic Oscillation (NAO) index and annual cadmium concentration. The concentration of cadmium increased sharply from AD 1957 to 2004, suggesting increasing influence from human activities, such as metals production. The ice–core record indicated increasing atmospheric cadmium pollution in response to rapid economic growth after AD 1957 in the region.
The effect of erosion speed on the interaction between erosion and corrosion of the Fe–3.5 wt% B alloy in a flowing zinc bath has been investigated using a rotating-disk technique. The total erosion–corrosion rate increases rapidly, whereas the pure erosion rate tends to increase linearly with an increase in erosion speed and with low damage. The increase in total erosion–corrosion rate is strongly dependent on erosion–corrosion interaction. During the erosion–corrosion process, the severe corrosion reaction roughens the surface by forming a loose corrosion layer and cracks in the anticaustic Fe2B skeleton, which eventually facilitates erosion. The micromechanical scouring effect of liquid zinc worsens corrosion by accelerating the removal of corrosion products and causing spallation of anticaustic Fe2B. An increase in erosion speed intensifies the micromechanical scouring effect of flowing zinc significantly. A strong erosion–corrosion interaction occurs at high erosion speed, which leads to a greater material loss rate.
The erosion–corrosion properties and interface microstructure of a Fe–B alloy that contains 3.5 wt% B in flowing liquid zinc have been investigated by electron backscattered diffraction, x-ray diffraction, and scanning electron microscopy to clarify the flowing effect of liquid zinc on erosion performance using a rotating-disk technique. The Fe–B alloy erodes at a low and steady rate in flowing liquid zinc. Flowing liquid zinc can accelerate the iron and zinc mass transfer to form Fe–Zn compounds and promote the removal of loose FeZn13. Much residual corrosion-resistant Fe2B and some erosion products coexist at the erosion interface because of the chemical and micromechanical effects that are created by flowing liquid zinc. The failure of the Fe2B corrosion-resistant skeleton in flowing liquid zinc occurs because of the loss of supporting matrix and also the formation and spread of microcracks during erosion.
We predict a possible phase transition of ZnO from wurtzite to zinc blende structure using first-principles molecular-dynamics simulations. By calculating the Gibbs free energies of the two phases as a function of temperature and hydrostatic pressure, we show that their energy difference decreases continuously with increasing temperature and pressure, and the vibrational entropy plays an important role on the location of the phase transition point. At 300 K, the phase transition is expected to occur at a pressure lower than 30 GPa with an activation energy barrier of 0.386 eV/atom. The transition path was also simulated, along which the system goes through a transient face-centered orthorhombic structure to overcome the energy barrier. Our theory results may be valuable for stabilizating the zinc blende ZnO in experiment.
For a given nonlinear partial differential equation defined on a bounded domain with irregular boundary, the available analytical tools are very limited in relation to the study of positive solutions. In this paper wer first use weak convergence methods to show that for an elliptic equation of a certain type, classical positive solutions on nearby smooth domains approach a generalised positive solution on the given domain. The idea is then applied to sublinear elliptic problems to obtain existence and uniqueness results.
Photonic integrated circuits in silicon require waveguiding through a material compatible with silicon VLSI technology. Polysilicon (polySi), with a high index of refraction compared to SiO2 and air, is an ideal candidate for use in silicon optical interconnect technology. Inspite of its advantages, the biggest hurdle to this technology is that losses of 350dB/cm have been measured in as-deposited polySi waveguide structures, as against ldB/cm losses measured in waveguides fabricated in crystalline silicon. We report methods for reducing scattering and absorption, which are the main sources of losses in this system. To reduce surface scattering losses we fabricate waveguides in smooth recrystallized amorphous silicon and Chemo-Mechanically Polished (CMP) polySi, both of which reduce losses by about 40dB/cm to 15dB/cm. Atomic Force Microscopy (AFM) and spectrophotometry studies are used to monitor surface roughness which has been reduced from an RMS roughness value of 19–20nm down to about 4–6nm. Bulk absorption/scattering losses can depend on size, structure, and quality of grains and grain boundaries which we investigate by means of Transmission Electron Microscopy (TEM). Although the lowest temperature deposition has twice as large a grain size as the highest temperature deposition, the losses appear to not be greatly dependent on grain size in the 0.1pm to 0.4pm range. Additionally, absorption/scattering at dangling bonds is investigated before and after a low temperature Electron-Cyclotron Resonance (ECR) hydrogenation step. After hydrogenation, we obtain the lowest reported polySi loss values at λ = 1.54μm of about 15dB/cm.
The atomic structure of [001] tilt grain boundaries of Σ25 (210), Σ5 (310), Σ213 (320) and Σ217 (410) in TiO2 (rutile) were studied using high resolution electron microscopy and computer simulation. Regularly separated small steps (1/2 [120] high) and big steps (3/2 [120] high) which contain secondary dislocations were found in the (210) boundary as a result of deviation from the exact Σ5 misorientation and (210) symmetric plane. Similar steps were also found in (310) and (320) boundaries. Flat segments between the steps were found to have very accurate misorientation of their, Σ's and a nearly symmetric boundary plane. Their rigid body translation, volume expansion and relaxed structures were determined by comparing HRTEM images with computer calculated structures and simulated images. An irregular core structure was found in the (410) boundary when its misorientation deviated 2° from the exact Σ17 misorientation.
A class of semilinear elliptic systems of two equations is considered. Sufficient conditions are given for the existence of different types of sign-definite solutions. These conditions relate the larger eigenvalues of certain 2 × 2 real matrices associated with the system to the first eigenvalue of − ∆ under the homogeneous Dirichlet boundary condition. A special case provides a complementary result to some of the recent works.
The stress-induced phase transformation between C36 and C15 structures in Fe2Zr is studied by electron microscopy. The nucleus of the transformation is believed to be some pre-existing C15 layers in C36 particles. Microstructural evidence for three mechanisms of growth of a new phase were found: Fault accumulation and rearrangement, moving of individual partial dislocations between two phases, and the migration of microscopic ledges composed of a series of Shockley partials between C36 and C15. Plastic deformation by slip on non-basal planes of C36 caused by indentation is studied.
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