Fragile X‐associated tremor/ataxia syndrome (FXTAS) is an adult‐onset neurodegenerative disorder associated with premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Approximately ...40% of older male premutation carriers, and a smaller proportion of females, are affected by FXTAS; due to the lower penetrance the characterization of the disorder in females is much less detailed. Core clinical features of FXTAS include intention tremor, cerebellar gait ataxia and frequently parkinsonism, autonomic dysfunction and cognitive deficits progressing to dementia in up to 50% of males.
In this study, we report the clinical, molecular and neuropathological findings of eight female premutation carriers. Significantly, four of these women had dementia; of the four, three had FXTAS plus dementia. Post‐mortem examination showed the presence of intranuclear inclusions in all eight cases, which included one asymptomatic premutation carrier who died from cancer. Among the four subjects with dementia, three had sufficient number of cortical amyloid plaques and neurofibrillary tangles to make Alzheimer's disease a highly likely cause of dementia and a fourth case had dementia with cortical Lewy bodies. Dementia appears to be more common than originally reported in females with FXTAS. Although further studies are required, our observation suggests that in a portion of FXTAS cases there is Alzheimer pathology and perhaps a synergistic effect on the progression of the disease may occur.
•The oblique fin maintains boundary layer to be re-developed periodically.•The injection of secondary flow accelerates the heat propagation into fluid core.•The temperatures on the oblique fin are ...lower than those on the straight channel.•The T uniformity on oblique fin is much uniform than that on straight channel.•The oblique LCP achieves higher heat transfer coefficient.
The development of electric vehicles (EVs) demands for complementary technologies in battery thermal management. To achieve fast charging/discharging capacity, liquid cooling is an effective means of maintaining temperature of a battery in operation within a narrow optimal range. In conventional straight channels, convective heat transfer deteriorates along the axial direction with the development of the hydrodynamic boundary layer, resulting in elevated maximum temperature and significant temperature gradient in the fully developed region. This is a serious problem as temperature uniformity is of utmost importance to the performance and lifespan of a Li–ion battery. In this research, a simple configuration of oblique cuts across the straight fins of a conventional straight channel design was developed, to enhance the performance of the conventional channel with minimal pressure penalty. These oblique cuts across the straight fins form an oblique fin array. The designed liquid cold plate (LCP) contains these simple oblique fins with optimized angle and width. This segmentation of the continuous fin into oblique sections leads to the re-initialization of boundary layers, providing a solution to the elevated temperatures caused by a thick boundary layer in the fully developed region. Experimental results show that heat transfer coefficients of oblique minichannel are higher than those of conventional straight minichannel. The oblique LCP is able to maintain the battery surface average temperature below 50°C for a heat load of 1240W at a flow rate lower than 0.9l/min. This implies that a proper designed minichannel cold plate could be a promising solution for EV battery thermal management.
Abstract
In order to detect the pulse of LSI with high accuracy and efficiency, a new detection method of low frequency pulse signal of LSI based on deep self coding algorithm is proposed in this ...paper. Firstly, Radon transform is used to reduce the dimension of the time-frequency diagram of the pulse signal of the integrated circuit, and the short-time Fourier transform of the pulse signal is completed according to the Hamming window. Secondly, the principle of the depth self encoder is analyzed, and the pulse signal after the short time Fourier transform processing is input into the depth self encoder. Finally, according to the distance function, the gradient descent algorithm is used to update the parameters. Through iterative calculation, the detection of low frequency pulse signal of LSI is completed. The experimental results show that, compared with the traditional low-frequency pulse signal detection method, the detection accuracy of this method is greatly improved, up to 99.79%, and can shorten the overall detection time.
Objective To assess systemically with meta-analysis the trend of survival and its determinants, which are hindering further improvement of survival of patients with systemic lupus erythematosus (SLE) ...over the past 5 decades. Methods Retrospective, cross-sectional, and prospective observational studies addressing survival and damage in SLE patients published between 1 January 1950 and 31 July 2010 were identified in electronic databases. Using the random-effects model, effect size was calculated based on the logit of the overall 5- and 10-year survival rates. The pooled logit and its robust 95% confidence interval were transformed back into the 5- and 10-year survival rates, after adjusting for potential dependence on the data. Potential factors predicting the pooled survival rates were explored by meta-regression. Results Seventy-seven studies involving 18,998 SLE patients were analyzed. Between the 1950s and the 2000s, their overall survival significantly increased, from 74.8% to 94.8% and 63.2% to 91.4% for the overall 5-year and 10-year survival, respectively ( P < 0.001). The survival improvement, however, appeared to slow down between 1980 and 1990. Meta-regression revealed that neuropsychiatric and renal damage negatively affected the overall 5-year survival, whereas neuropsychiatric damage remained so for the 10-year survival for the past 50 years. Furthermore, the prevalence of neuropsychiatric damage has been significantly increasing over the past 5 decades. Conclusions For the past 50 years, damage involving the renal and neuropsychiatric systems has been negatively affecting survival of SLE patients. Early detection and aggressive management of renal and neuropsychiatric involvement may potentially improve further the survival of lupus patients.
Two large-scale pharmacogenomic studies were published recently in this journal. Genomic data are well correlated between studies; however, the measured drug response data are highly discordant. ...Although the source of inconsistencies remains uncertain, it has potential implications for using these outcome measures to assess gene-drug associations or select potential anticancer drugs on the basis of their reported results.
We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection.
...TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%.
These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.
Creating an optimal microenvironment that mimics the extracellular matrix (ECM) of natural pulp and securing an adequate blood supply for the survival of cell transplants are major hurdles that need ...to be overcome in dental pulp regeneration. However, many currently available scaffolds fail to mimic essential functions of natural ECM. The present study investigated a novel approach involving the use of scaffold-free microtissue spheroids of dental pulp stem cells (DPSCs) prevascularized by human umbilical vein endothelial cells (HUVECs) in pulp regeneration. In vitro-fabricated microtissue spheroids were inserted into the canal space of tooth-root slices and were implanted subcutaneously into immunodeficient mice. Histological examination revealed that, after four-week implantation, tooth-root slices containing microtissue spheroids resulted in well-vascularized and cellular pulp-like tissues, compared with empty tooth-root slices, which were filled with only subcutaneous fat tissue. Immunohistochemical staining indicated that the tissue found in the tooth-root slices was of human origin, as characterized by the expression of human mitochondria, and contained odontoblast-like cells organized along the dentin, as assessed by immunostaining for nestin and dentin sialoprotein (DSP). Vascular structures formed by HUVECs in vitro were successfully anastomosed with the host vasculature upon transplantation in vivo, as shown by immunostaining for human CD31. Collectively, these findings demonstrate that prevascularized, scaffold-free, microtissue spheroids can successfully regenerate vascular dental pulp-like tissue and also highlight the significance of the microtissue microenvironment as an optimal environment for successful pulp-regeneration strategies.
Open burning of crop residue is an important source of carbonaceous pollutants, and has a large impact on the regional environment and global climate change. Laboratory burn tests were conducted ...using a custom-made combustion chamber to determine pollutants (i.e. CO2, CO, PM2.5, organic carbon (OC) and elemental carbon (EC)) emission factors (EFs) of wheat straw, rice straw and corn stalk; the three major agricultural crop residues in China. The average EFs were estimated to be 1351 ± 147 g kg−1 for CO2, 52.0 ± 18.9 g kg−1 for CO, 10.6 ± 5.6 g kg−1 for PM2.5, 4.8 ± 3.1 g kg−1 for OC and 0.24 ± 0.12 g kg−1 for EC. In addition, the effect of fuel moisture was investigated through the controlled burning of wheat straw. Increasing the moisture content decreased the CO2 EF, and increased the EFs of CO, PM2.5 and OC. Based on measurements from this study and nationwide statistics in crop type and area, pollutants emission inventories for crop residue combustion with 1° × 1° resolution were compiled for 2008. Total emissions were 120 Tg CO2, 4.6 Tg CO, 0.88 Tg PM2.5, 0.39 Tg OC and 0.02 Tg EC.
•Custom-made combustion chamber was used to determine emission factors (EFs).•EFs of crop residue open burning specific to China and elsewhere were compared.•Increased moisture content decreased CO2 and enhanced CO, PM2.5 & OC emissions.•Emission inventories for crop residue combustion in China were compiled for 2008.
Reinforced concretes were corroded to varying degrees by exposing to cyclic NaCl spray and 40
°C drying. The amount of corrosion products and induced damage were measured using image analysis. We ...found that corrosion products can accumulate at steel–concrete interface as well as penetrate cement paste and deposit within hydration products, relicts of reacted slag, and air voids. As corrosion increases, the products tend to accumulate at the steel–concrete interface, while the amount penetrating cement paste remains relatively constant. Only a small amount of corrosion is needed to induce visible cover cracking. Implications on modelling time to cover cracking are discussed.
High-energy cosmic-ray electrons and positrons (CREs), which lose energy quickly during their propagation, provide a probe of Galactic high-energy processes and may enable the observation of ...phenomena such as dark-matter particle annihilation or decay. The CRE spectrum has been measured directly up to approximately 2 teraelectronvolts in previous balloon- or space-borne experiments, and indirectly up to approximately 5 teraelectronvolts using ground-based Cherenkov γ-ray telescope arrays. Evidence for a spectral break in the teraelectronvolt energy range has been provided by indirect measurements, although the results were qualified by sizeable systematic uncertainties. Here we report a direct measurement of CREs in the energy range 25 gigaelectronvolts to 4.6 teraelectronvolts by the Dark Matter Particle Explorer (DAMPE) with unprecedentedly high energy resolution and low background. The largest part of the spectrum can be well fitted by a 'smoothly broken power-law' model rather than a single power-law model. The direct detection of a spectral break at about 0.9 teraelectronvolts confirms the evidence found by previous indirect measurements, clarifies the behaviour of the CRE spectrum at energies above 1 teraelectronvolt and sheds light on the physical origin of the sub-teraelectronvolt CREs.
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