Progranulin, a Glycoprotein Deficient in Frontotemporal Dementia, Is a Novel Substrate of Several Protein Disulfide Isomerase Family Proteins

The reduced production or activity of the cysteine-rich glycoprotein progranulin is responsible for about 20% of cases of familial frontotemporal dementia. However, little is known about the molecular mechanisms that govern the level and secretion of progranulin. Here we show that progranulin is expressed in mouse cortical neurons and more prominently in mouse microglia in culture and is abundant in the endoplasmic reticulum (ER) and Golgi. Using chemical crosslinking, immunoprecipitation, and mass spectrometry, we found that progranulin is bound to a network of ER Ca2+-binding chaperones including BiP, calreticulin, GRP94, and four members of the protein disulfide isomerase (PDI) family. Loss of ERp57 inhibits progranulin secretion. Thus, progranulin is a novel substrate of several PDI family proteins and modulation of the ER chaperone network may be a therapeutic target for controlling progranulin secretion

Bivariate grid-connection speed control of hydraulic wind turbines

The requirement for An electrical grid-connected wind turbine is that the synchronous generator speed is stable within a required speed range for the electrical grid. In this paper, a hydraulic wind turbine (HWT) system is considered, and the working principle and working conditions of the HWT are introduced. A novel speed control method is proposed in this paper, using both a proportional flow control valve and a variable displacement motor, which are adjusted in combination to control the speed of the HWT. By establishing a state space model of the HWT and solving the nonlinear system with a feedback linearization method, a bivariate tracking controller is constructed to realize accurate speed control under fluctuating wind speed and the load disturbance conditions. The effectiveness of the control method is verified by simulation, but experimental results highlight problems with the method. The theoretical controller is simplified to reduce sensitivity to measurement noise and modeling error. The control effect has been improved to some extent, but it is limited. Based on these results, combined with the sliding mode variable structure control method and the feedback linearization method to solve the problem of measurement noise and modeling error, and the effectiveness of the control law is finally verified experimentally. It lays a theoretical foundation for the practical application of HWT

Characterization of two β-galactosidases LacZ and WspA1 from Nostoc flagelliforme with focus on the latter’s central active region

The identification and characterization of new β-galactosidases will provide diverse candidate enzymes for use in food processing industry. In this study, two β-galactosidases, Nf-LacZ and WspA1, from the terrestrial cyanobacterium Nostoc flagelliforme were heterologously expressed in Escherichia coli, followed by purification and biochemical characterization. Nf-LacZ was characterized to have an optimum activity at 40\ua0\ub0C and pH 6.5, different from that (45\ua0\ub0C and pH 8.0) of WspA1. Two enzymes had a similar Michaelis constant (Km = 0.5\ua0mmol/liter) against the substrate o-nitrophenyl-β-D-galactopyranoside. Their activities could be inhibited by galactostatin bisulfite, with IC50 values of 0.59\ua0\ub5M for Nf-LacZ and 1.18\ua0\ub5M for WspA1, respectively. Gel filtration analysis suggested that the active form of WspA1 was a dimer, while Nf-LacZ was functional as a larger multimer. WspA1 was further characterized by the truncation test, and its minimum central region was found to be from residues 188 to 301, having both the glycosyl hydrolytic and transgalactosylation activities. Finally, transgenic analysis with the GFP reporter protein found that the N-terminus of WspA1 (35 aa) might play a special role in the export of WspA1 from cells. In summary, this study characterized two cyanobacterial β-galactosidases for potential applications in food industry

VIVO: Visual Vocabulary Pre-Training for Novel Object Captioning

It is highly desirable yet challenging to generate image captions that can describe novel objects which are unseen in caption-labeled training data, a capability that is evaluated in the novel object captioning challenge (nocaps). In this challenge, no additional image-caption training data, other thanCOCO Captions, is allowed for model training. Thus, conventional Vision-Language Pre-training (VLP) methods cannot be applied. This paper presents VIsual VOcabulary pretraining (VIVO) that performs pre-training in the absence of caption annotations. By breaking the dependency of paired image-caption training data in VLP, VIVO can leverage large amounts of paired image-tag data to learn a visual vocabulary. This is done by pre-training a multi-layer Transformer model that learns to align image-level tags with their corresponding image region features. To address the unordered nature of image tags, VIVO uses a Hungarian matching loss with masked tag prediction to conduct pre-training. We validate the effectiveness of VIVO by fine-tuning the pre-trained model for image captioning. In addition, we perform an analysis of the visual-text alignment inferred by our model. The results show that our model can not only generate fluent image captions that describe novel objects, but also identify the locations of these objects. Our single model has achieved new state-of-the-art results on nocaps and surpassed the human CIDEr score.Comment: AAAI 202

Effects of the Largest Lake of the Tibetan Plateau on the Regional Climate

Qinghai Lake is the largest lake in China. However, its influence on the local climate remains poorly understood. By using an atmosphere-lake coupled model, we investigated the impact of the lake on the local climate. After the adjustment of four key parameters, the model reasonably reproduced the lake-air interaction. Superimposed by the orographic effects on lake-land breeze circulation, the presence of the lake enhanced precipitation over the southern part of the lake and its adjacent land, while slightly reduced precipitation along the northern shore of the lake. The lake effect on local precipitation revealed a distinct seasonal and diurnal variability, reducing precipitation in May (-6.6%) and June (-4.5%) and increasing it from July (5.7%) to November (125.6%). During the open water season, the lake's daytime cooling effect weakened and the nighttime warming effect strengthened, affecting spatial distribution and intensity of lake-induced precipitation. In early summer, precipitation slightly decreased over the north part of the lake due to the lake's daytime cooling. In turn, lake-induced nighttime warming increased precipitation over the southern section of the lake and its adjacent land. With the start of the autumn cooling in September, heat and moisture fluxes from the lake resulted in precipitation increase in both daytime and nighttime over the entire lake. In October, the background atmospheric circulation coupled with the strong lake effects lead to a small amount but high proportion of lake-induced precipitation spreading evenly over the lake.Peer reviewe

The trajectories and correlation between physical limitation and depression in elderly residents of Beijing, 1992-2009

Background Physical limitation and psychological distress have been reported to be related, but studies describing the change of instrumental activities of daily living (IADLs) and depression syndrome over time or exploring the link pattern for their development are limited. The study was to assess distinctive patterns for the development of physical limitation and depression and to explore their correlation to form a proper prevention strategy. Methods Dual trajectory analysis was conducted using data from the Beijing Longitudinal Study of Aging (BLSA) 1992–2009 hosted by Xuanwu hospital for subjects with full information on depression and physical limitation for all available visits. Physical limitation was measured by the Instrumental Activities of Daily Living (IADL) scale and depression by the Center for Epidemiological Studies Depression scale (CES-D). The covariates were gender, age at baseline and number of chronic conditions. Results Three heterogeneous trajectories for physical limitation and two distinct groups for an increase in depression were detected. Among them, 10.13% of subjects experienced an increase in physical limitation, while 13.22% demonstrated a high, stable level of depressive mood. In all, 80.4% of the subjects enjoyed a relatively low, stable level of IADL and CES-D scores. People in the late increase group for IADL score were more likely to have depressive mood when adjusted for gender, age and number of chronic conditions (OR = 3.900, 95%CI = 1.347–11.290). Conclusions The development of physical limitation among the elderly may significantly increase the risk for depressive symptom

Changing Patterns of Spatial Clustering of Schistosomiasis in Southwest China between 1999–2001 and 2007–2008: Assessing Progress toward Eradication after the World Bank Loan Project

We compared changes in the spatial clustering of schistosomiasis in Southwest China at the conclusion of and six years following the end of the World Bank Loan Project (WBLP), the control strategy of which was focused on the large-scale use of chemotherapy. Parasitological data were obtained through standardized surveys conducted in 1999–2001 and again in 2007–2008. Two alternate spatial cluster methods were used to identify spatial clusters of cases: Anselin’s Local Moran’s I test and Kulldorff’s spatial scan statistic. Substantial reductions in the burden of schistosomiasis were found after the end of the WBLP, but the spatial extent of schistosomiasis was not reduced across the study area. Spatial clusters continued to occur in three regions: Chengdu Plain, Yangtze River Valley, and Lancang River Valley during the two periods, and regularly involved five counties. These findings suggest that despite impressive reductions in burden, the hilly and mountainous regions of Southwest China remain at risk of schistosome re-emergence. Our results help to highlight specific locations where integrated control programs can focus to speed the elimination of schistosomiasis in China