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In the field of space geodetic techniques, such as global navigation satellite systems (GNSSs), tropospheric zenith hydrostatic delay (ZHD) is chosen as the a priori value of tropospheric total delay. Therefore, the inaccuracy of ZHD will definitely affect parameters like the wet delay and the horizontal gradient of tropospheric delay, accompanied by an indirect influence on the accuracy of geodetic parameters, if not dealt with well at low elevation angles. In fact, however, the most widely used ZHD model currently seems to contain millimeter-level biases from the precise integral method. We explored the bias of traditional ZHD models and analyzed the characteristics in different aspects on a global annual scale. It was found that biases differ significantly with season and geographical location, and the difference between the maximum and minimum values exceeds 30 mm, which should be fully considered in the field of high-precision measurement. Then, we constructed a global grid correction model, which is named ZHD_crct, based on the meteorological data of the year 2020 from the ECMWF (European Centre for Medium-Range Weather Forecasts), and it turned out that the bias of traditional models in the current year could be reduced by ∼ 50 % when the ZHD_crct was added. When we verified the effect of ZHD_crct on the biases in the next year, it worked almost the same as the former year. The mean absolute biases (MABs) of ZHD will be narrowed within ∼ 0.5 mm for most regions, and the SDs (standard deviations) will be within ∼ 0.7 mm. This improvement will be helpful for research on meteorological phenomena as well.

As a corporate communication and office tool created by Tencent's WeChat team, WeCom has the same communication experience as WeChat, rich OA applications, and the ability to connect with the WeChat ecosystem, which can help enterprises connect with internal, ecological partners, and consumers. This article mainly analyzes that under the background of the normalization of the prevention and control of the new crown pneumonia epidemic, online office, and online classes have gradually become the norm, as an excellent communication and office tool, how WeCom can give full play to its unique advantages to help colleges and universities complete digital transformation. This paper uses network effect analysis, SWOT analysis and other methods to analyze its competitiveness, competing products, charging strategies, etc., and finally puts forward four suggestions for the digital transformation of colleges and universities through WeChat: using sticky social characteristics to spread widely, focusing on "private" "Domain management" to achieve precise marketing, with SCRM system to help the efficient operation and expand the field of use.

Comparison of invasive and intraductal regions of tumors derived from IGO transplants of Slow-progressor organoids

Supplementary Table S1 Survival times of IGO and OGO mice Supplementary Table S2 Characteristics of patient-derived organoids, including KRAS, TP53, SMAD4, CDKN2A mutation status and patient stage Supplementary Table S3 Summary of Survival Data, including engraftment rate, mean survival, metastatic frequency Supplementary Table S4 Primers for quantitative PCR

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common malignancy, with little improvement in patient outcomes over the past decades. Recently, subtypes of pancreatic cancer with different prognoses have been elaborated; however, the inability to model these subtypes has precluded mechanistic investigation of their origins. Here, we present a xenotransplantation model of PDAC in which neoplasms originate from patient-derived organoids injected directly into murine pancreatic ducts. Our model enables distinction of the two main PDAC subtypes: intraepithelial neoplasms from this model progress in an indolent or invasive manner representing the classical or basal-like subtypes of PDAC, respectively. Parameters that influence PDAC subtype specification in this intraductal model include cell plasticity and hyperactivation of the RAS pathway. Finally, through intratumoral dissection and the direct manipulation of RAS gene dosage, we identify a suite of RAS-regulated secreted and membrane-bound proteins that may represent potential candidates for therapeutic intervention in patients with PDAC.Significance:Accurate modeling of the molecular subtypes of pancreatic cancer is crucial to facilitate the generation of effective therapies. We report the development of an intraductal organoid transplantation model of pancreatic cancer that models the progressive switching of subtypes, and identify stochastic and RAS-driven mechanisms that determine subtype specification.See related commentary by Pickering and Morton, p. 1448.This article is highlighted in the In This Issue feature, p. 1426

Confocal z-stack imaging of immunofluorescent (IF) images of mStrawberry-hT3 grafts 4 weeks after IGO transplantation

Method Used to Define the Thresholds for Fast- and Slow-Progressing IGO-Derived Tumors

Accurate localization is key to realizing an autonomous mobile robot. The fusion of depth data measured by a time-of-flight (TOF) camera with visual-inertial simultaneous localization and mapping (SLAM) can greatly improve depth estimation and mapping. To achieve a robust sensor fusion system, precise calibration of one sensor to another is essential. In this paper, we propose a joint extrinsic calibration method for a TOF- IMU RGB-camera system. Further, we design a pattern that consists of white circles with high reflectivity, and a black background with high absorptivity. Using our calibration method, circular features can be accurately extracted from amplitude images as well as from RGB images. We correct the TOF depth measurement errors, which depend on the pixel location and distance of the pixel away from the object, by establishing an error distribution model with a B-spline function. All sensors are fixed on a platform, and the position of each sensor relative to the other sensors is unchanged, forming loop closure constraints. Based on this prerequisite, we utilize the loop closure constraints between multiple sensors to obtain more accurate extrinsic parameters. By taking the loop closure constraints into account, the stability and robustness of the calibration is increased. The experimental results validate the proposed method and prove its accuracy. Thus, we achieve high precision in multi-sensor extrinsic calibration, which is the necessary foundation of SLAM research.

To analyze the relationship between vitamin D(VitD)-related single nucleotide polymorphism(SNP) and 25-hydroxyvitamin D(25(OH) D) levels and VitD nutritional status.A total of 1507 women of childbearing age aged 18-45 were selected from the sample bank of "2015 Chinese adult chronic disease and nutrition monitoring". Basic information(including region, season, age, height, weight, etc. ) of the subjects was collected. The SNPs related to VitD metabolism were screened, and the improved multiple ligase detection reaction was used for SNP testing. Liquid chromatography tandem mass spectrometry was used to determine the serum 25(OH)D concentration. The effects of genotypes on 25(OH)D level and VitD deficiency were analyzed by generalized linear model and binary logistic regression model, respectively.After adjusting for latitude, region, region type, season and age, CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 were associated with serum 25(OH)D levels in women of childbearing age. The risk of VitD deficiency in individuals carrying GG genotype at rs2282679 was significantly higher than that in individuals carrying TT genotype(OR=2.466, 95%CI 1.690-3.598, Plt;0.001), and the risk of VitD deficiency in individuals carrying A allele at rs2228570 was lower than that in individuals carrying G allele(OR_(AA)=0.625, 95%CI 0.446-0.876, P_(AA)=0.006;OR_(GA)=0.661, 95%CI 0.502-0.869, P_(GA)=0.003).The genotype distribution of CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 may be related to serum 25(OH)D level or VitD nutritional status of Chinese women of childbearing age.

Extensive efforts to enhance the oxygen evolution reaction (OER) catalytic performance of transition metal oxides mainly concentrate on the extrinsic morphology tailoring, lattice doping, and electrode interface optimizing. Nevertheless, little room is left for performance improvement using these methods and an obvious gap still exists compared to the precious metal catalysts. In this work, a novel "mixed-valent cobalt modulation" strategy is presented to enhance the electrocatalytic OER of perovskite LaCoO3 (LCO) oxide. The valence transition of cobalt is realized by ethylenediamine post reduction procedure at room temperature, which further induces the variation of magnetic properties for LCO catalyst. The optimized LCO catalyst with Co2+/Co3+ of 1.98% exhibits the best OER activity, and the overpotential at 10 mA cm-2 current density is decreased by 170 mV compared pristine LCO. Impressively, the ferromagnetic LCO catalyst can perform magnetic OER enhancement. By application of an external magnetic field, the overpotential of LCO at 10 mA cm-2 can be further decreased by 20 mV compared to that of under zero magnetic field, which arises from the enhanced energy states of electrons and accelerated electron transfer process driven by magnetic field. Our findings may provide a promising strategy to break the bottleneck for further enhancement of OER performance.

In the field of space geodetic techniques, such as global navigation satellite systems (GNSSs), tropospheric zenith hydrostatic delay (ZHD) is chosen as the a priori value of tropospheric total delay. Therefore, the inaccuracy of ZHD will definitely affect parameters like the wet delay and the horizontal gradient of tropospheric delay, accompanied by an indirect influence on the accuracy of geodetic parameters, if not dealt with well at low elevation angles. In fact, however, the most widely used ZHD model currently seems to contain millimeter-level biases from the precise integral method. We explored the bias of traditional ZHD models and analyzed the characteristics in different aspects on a global annual scale. It was found that biases differ significantly with season and geographical location, and the difference between the maximum and minimum values exceeds 30 mm, which should be fully considered in the field of high-precision measurement. Then, we constructed a global grid correction model, which is named ZHD_crct, based on the meteorological data of the year 2020 from the ECMWF (European Centre for Medium-Range Weather Forecasts), and it turned out that the bias of traditional models in the current year could be reduced by ∼ 50 % when the ZHD_crct was added. When we verified the effect of ZHD_crct on the biases in the next year, it worked almost the same as the former year. The mean absolute biases (MABs) of ZHD will be narrowed within ∼ 0.5 mm for most regions, and the SDs (standard deviations) will be within ∼ 0.7 mm. This improvement will be helpful for research on meteorological phenomena as well.

Let Ω ⊂ R 3 be a Lipschitz domain. Consider a harmonic map v : Ω → S 2 with boundary data v | ∂ Ω = φ which minimises the Dirichlet energy. For p ≥ 2 , we show that any energy minimiser u whose boundary map ψ has a small W 1 , p -distance to φ is close to v in Holder norm modulo bi-Lipschitz homeomorphisms, provided that v is the unique minimiser attaining the boundary data. The index p = 2 is sharp: the above stability result fails for p 2 due to the constructions by Almgren–Lieb [2] and Mazowiecka–Strzelecki [15] .

Short-read sequencers provide highly accurate reads at very low cost. Unfortunately, short reads are often inadequate for important applications such as assembly in complex regions or phasing across distant heterozygous sites. In this study, we describe novel bench protocols and algorithms to obtain haplotype-phased sequence assemblies with ultra-low error for regions 10 kb and longer using short reads only. We accomplish this by imprinting each template strand from a target region with a dense and unique mutation pattern. The mutation process randomly and independently converts ∼50% of cytosines to uracils. Sequencing libraries are made from both mutated and unmutated templates. Using de Bruijn graphs and paired-end read information, we assemble each mutated template and use the unmutated library to correct the mutated bases. Templates are partitioned into two or more haplotypes, and the final haplotypes are assembled and corrected for residual template mutations and PCR errors. With sufficient template coverage, the final assemblies have per-base error rates below 10–9. We demonstrate this method on a four-member nuclear family, correctly assembling and phasing three genomic intervals, including the highly polymorphic HLA-B gene.

Objective: To analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China. Methods: Subjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Anthropometry was measured by trained interviewers, and fasting blood was collected to test 25-hydroxyvitamin D [25(OH)D], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and other related parameters. Generalized linear mode and multivariate logistic analysis were performed to analyze the associations between serum 25(OH)D and MetS and its components, adjusting for the possible confounders. Results: Body mass index (BMI), serum alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), 25(OH)D, phosphorus (P), and parathyroid hormone (PTH) levels were associated with the number of MetS’s components. G allele carriers of GC rs2282679 had higher diastolic blood pressure (DBP) and FBG levels compared with the TT genotypes, while higher genetic risk score (GRS) seemed to be associated with reduced HDL-C level. The odds ratio (OR) for MetS in lowest group of 25(OH)D was 1.533 (0.980–2.399) after adjusting for season, district, area type, latitude, age, BMI, PTH, P, ALT, CRE, interleukin-6 (IL-6), and hs-CRP, compared with the median group, but the association was not significant. An insufficient 25(OH)D concentration (

Cerebellar ataxia is the predominant motor feature of multiple system atrophy cerebellar subtype (MSA-C). Although repetitive transcranial magnetic stimulation (TMS) of the cerebellum is growingly applied in MSA, the mechanism is unknown. We examined dynamic connectivity changes of 20 patients with MSA and 25 healthy controls using TMS combined with electroencephalography. Observations that significantly decreased dynamic cerebello-frontal connectivity in patients have inspired attempts to modulate cerebellar connectivity in order to benefit MSA. We further explore the therapeutic potential of a 10-day treatment of cerebellar intermittent theta burst stimulation (iTBS) in MSA by a randomized, double-blind, sham-controlled trial. The functional reorganization of cerebellar networks was investigated after the end of treatment in active and sham groups. The severity of the symptoms was evaluated using the Scale for Assessment and Rating of Ataxia scores. Patients treated with active stimulation showed an improvement of cerebello-frontal connectivity and balance functions, as revealed by a significant decrease in the ataxia scores (P < 0.01). Importantly, the neural activity of frontal connectivity from 80 to 100 ms after a single TMS was significantly related to the severity of the disease. Our study provides new proof that cerebellar iTBS improves motor imbalance in MSA by acting on cerebello-cortical plasticity.

We show that the spatial Lq-norm (q > 5/3) of the vorticity of an incompressible viscous fluid in ℝ3 remains bounded uniformly in time, provided that the direction of vorticity is Holder continuous in space, and that the space-time Lq-norm of vorticity is finite. The Holder index depends only on q. This serves as a variant of the classical result by Constantin-Fefferman (Direction of vorticity and the problem of global regularity for the Navier-Stokes equations, Indiana Univ. J. Math. 42 (1993), 775–789), and the related work by Grujic-Ruzmaikina (Interpolation between algebraic and geometric conditions for smoothness of the vorticity in the 3D NSE, Indiana Univ. J. Math. 53 (2004), 1073–1080).