The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a ...predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease.
In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes.
Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.
We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.).
Major imaging biomarkers of Alzheimer’s disease include amyloid deposition imaged with ¹¹CPittsburgh compound B (PiB) PET, altered glucose metabolism (imaged with ¹⁸Ffluro-deoxyglucose PET), and ...structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer’s disease. We now extend this work to include a larger cohort, whole-brain analyses integrating all three imaging modalities, and longitudinal data to examine regional differences in imaging biomarker dynamics. The anatomical distribution of imaging biomarkers is described in relation to estimated years from symptom onset. Autosomal dominant Alzheimer’s disease mutation carrier individuals have elevated PiB levels in nearly every cortical region 15 y before the estimated age of onset. Reduced cortical glucose metabolism and cortical thinning in the medial and lateral parietal lobe appeared 10 and 5 y, respectively, before estimated age of onset. Importantly, however, a divergent pattern was observed subcortically. All subcortical gray-matter regions exhibited elevated PiB uptake, but despite this, only the hippocampus showed reduced glucose metabolism. Similarly, atrophy was not observed in the caudate and pallidum despite marked amyloid accumulation. Finally, before hypometabolism, a hypermetabolic phase was identified for some cortical regions, including the precuneus and posterior cingulate. Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease.
In the internet of vehicles (IoVs), vehicle users should provide location information continuously when they want to acquire continuous location-based services (LBS), which may disclose the vehicle ...trajectory privacy. To solve the vehicle trajectory privacy leakage problem in the continuous LBS, we propose a vehicle trajectory privacy preservation method based on caching and dummy locations, abbreviated as TPPCD, in IoVs. In the proposed method, when a vehicle user wants to acquire a continuous LBS, the dummy locations-based location privacy preservation method under road constraint is used. Moreover, the cache is deployed at the roadside unit (RSU) to reduce the information interaction between vehicle users covered by the RSU and the LBS server. Two cache update mechanisms, the active cache update mechanism based on data popularity and the passive cache update mechanism based on dummy locations, are designed to protect location privacy and improve the cache hit rate. The performance analysis and simulation results show that the proposed vehicle trajectory privacy preservation method can resist the long-term statistical attack (LSA) and location correlation attack (LCA) from inferring the vehicle trajectory at the LBS server and protect vehicle trajectory privacy effectively. In addition, the proposed cache update mechanisms achieve a high cache hit rate.
The fusion of hyperspectral (HS) and panchromatic (PAN) images aims to generate a fused HS image that combines spectral information of the HS image with spatial information of the PAN image. In this ...article, we propose a multiresolution spatial-spectral feature learning (MSSL) framework for fusing HS and PAN images. The proposed MSSL transforms the existing deep and complex network into several simple and shallow subnetworks to simplify the feature learning process. MSSL upsamples the HS image while downsamples the PAN image and designs multiresolution 3-D convolutional autoencoder (CAEs) networks with a spectral constraint to learn complete spatial-spectral features of the HS image. MSSL designs multiresolution 2-D CAEs with spatial constraint to extract spatial features of the PAN image, with a low computational cost. In order to effectively generate the pansharpened HS image with high spatial and spectral fidelity, a multiresolution residual network is presented to reconstruct the HS image from the extracted spatial-spectral features. Extensive experiments are conducted on three widely used remote sensing data sets in comparison with state-of-the-art HS image fusion methods, demonstrating the superiority of the proposed MSSL method. Code is available at https://github.com/Jiahuiqu/MSSL .
Catalytic oxidation of toluene over noble metal catalysts is a representative reaction for elimination of volatile organic compounds (VOCs). However, to fully understand the activation of molecular ...oxygen and the role of active oxygen species generated in this reaction is still a challenging target. Herein, MgO nanosheets and single-atom Pt loaded MgO (Pt SA/MgO) nanosheets were synthesized and used as catalysts in toluene oxidation. The activation process of molecular oxygen and oxidation performance on the two catalysts were contrastively investigated. The Pt SA/MgO exhibited significantly enhanced catalytic activity compared to MgO. The oxygen vacancies can be easily generated on the Pt SA/MgO surface, which facilitate the activation of molecular oxygen and the formation of active oxygen species. Based on the experimental data and theoretical calculations, an active oxygen species promoted oxidation mechanism for toluene was proposed. In the presence of H
2
O, the molecular oxygen is more favorable to be dissociated to generate •OH on the oxygen vacancies of the Pt SA/MgO surface, which is the dominant active oxygen species. We anticipate that this work may shed light on further investigation of the oxidation mechanism of toluene and other VOCs over noble metal catalysts.
Objective
To evaluate the role of POGLUT2 in pan-cancer through bioinformatics analysis and experimental verification.
Methods
Expression, gene mutation and amplification, methylation, and copy ...number alteration (CNA) of POGLUT2 were evaluated using The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) databases. Moreover, POGLUT2 on survival and disease progression in pan-cancer was performed using TCGA data. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuneScore, ImmuCellAI, and TIMER databases. POGLUT2 correlated drug resistance analysis was performed using the GDSC2 database. Furthermore, POGLUT2 knockdown of breast cancer cells was established, followed by
in vitro
biological function assays and
in vivo
tumor growth study. The mechanisms of POGLUT2 in breast cancer were briefly evaluated
via
its connection with Notch signaling.
Results
Increased levels of POGLUT2 were found in multiple types of cancer tissues and cell lines. Moreover, increased gene mutation and amplification, methylation, and CNA of POGLUT2 were found in several types of cancers. POGLUT2 was mainly expressed in stromal cells as verified by StromalScore, ESTIMATEScore, ImmuneScore, and Tumor purity, and POGLUT2 was positively correlated with cancer-associated fibroblasts, macrophages, monocytes, and neutrophils in the tumor microenvironment.
In vitro
and
in vivo
results showed that POGLUT2 knockdown could delay tumor growth and progression. Notch signaling components were related to the function of POGLUT2.
Conclusions
Increased levels of POGLUT2 could result in the dysregulated immune cell infiltration and tumor microenvironment and showed a significant regulatory effect on the progression of breast cancer through Notch-related signaling.
Dopamine modified aramid fiber (AF) surface was grafted with amino functionalized graphene oxide to improve the interfacial adhesive performance. The self-polymerized polydopamine (PDA) coating and ...subsequent amino GO grafting on the AF surface attributed to the increase in its surface roughness and surface-active groups. The functional groups, chemical composition and surface topography of unmodified and modified AF was investigated by Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and Scanning electron microscopy (SEM). The interfacial properties were analyzed by measuring interfacial shear strength (IFSS) of unmodified and modified AF embedded epoxy matrix. Further, the properties were tuned by optimizing the reaction temperature and concentration of ethylenediamine. The IFSS of AF/epoxy composites was increased by 34% after grafting amino graphene oxide.
•The self-polymerized polydopamine) (PDA) layer was deposited on aramid fibers.•An efficient route to functionalize aramid fibers based on dopamine chemistry was developed.•With PDA coating and further amino GO grafting, the rougher fiber surface significantly improved the IFSS.
During the procedure, a location-based service (LBS) query, the real location provided by the vehicle user may results in the disclosure of vehicle location privacy. Moreover, the point of interest ...retrieval service requires high accuracy of location information. However, some privacy preservation methods based on anonymity or obfuscation will affect the service quality. Hence, we study the location privacy-preserving method based on dummy locations in this paper. We propose a vehicle location privacy-preservation method based on dummy locations under road restriction in Internet of vehicles (IoV). In order to improve the validity of selected dummy locations under road restriction, entropy is used to represent the degree of anonymity, and the effective distance is introduced to represent the characteristics of location distribution. We present a dummy location selection algorithm to maximize the anonymous entropy and the effective distance of candidate location set consisting of vehicle user’s location and dummy locations, which ensures the uncertainty and dispersion of selected dummy locations. The proposed location privacy-preservation method does not need a trustable third-party server, and it protects the location privacy of vehicles as well as guaranteeing the LBS quality. The performance analysis and simulation results show that the proposed location privacy-preservation method can improve the validity of dummy locations and enhance the preservation of location privacy compared with other methods based on dummy locations.
Estimating the gamma dose rate at one meter above ground level and determining the distribution of radioactive pollution from aerial radiation monitoring data are the core technical issues of ...unmanned aerial vehicle nuclear radiation monitoring. In this paper, a reconstruction algorithm of the ground radioactivity distribution based on spectral deconvolution was proposed for the problem of regional surface source radioactivity distribution reconstruction and dose rate estimation. The algorithm estimates unknown radioactive nuclide types and their distributions using spectrum deconvolution and introduces energy windows to improve the accuracy of the deconvolution results, achieving accurate reconstruction of multiple continuous distribution radioactive nuclides and their distributions, as well as dose rate estimation of one meter above ground level. The feasibility and effectiveness of the method were verified through cases of single-nuclide (
Cs) and multi-nuclide (
Cs and
Co) surface sources by modeling and solving them. The results showed that the cosine similarities between the estimated ground radioactivity distribution and dose rate distribution with the true value were 0.9950 and 0.9965, respectively, which could prove that the proposed reconstruction algorithm would effectively distinguish multiple radioactive nuclides and accurately restore their radioactivity distribution. Finally, the influences of statistical fluctuation levels and the number of energy windows on the deconvolution results were analyzed, showing that the lower the statistical fluctuation level and the more energy window divisions, the better the deconvolution results.
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