Boundedness and higher integrability of minimizers to a class of two-phase free boundary problems under non-standard growth conditions

In this paper, we are concerned with the existence, boundedness, and integrability of minimizers of heterogeneous, two-phase free boundary problems $\mathcal {J}_{\gamma}(u) = \int_{\Omega}\left(f(x, \nabla u)+\lambda_{+}(u^{+})^{\gamma}+\lambda_{-}(u^{-})^{\gamma}+gu\right)\text{d}x \rightarrow \text{min}$ under non-standard growth conditions. Included in such problems are heterogeneous jets and cavities of Prandtl-Batchelor type with $\gamma = 0$, chemical reaction problems with 0 < \gamma < 1 , and obstacle type problems with $\gamma = 1$, respectively

AN EMPIRICAL INVESTIGATION INTO THE EFFECT OF TECHNOSTRESS OF PHYSICIANS ON ADOPTION OF ELECTRONIC HEALTHCARE SYSTEMS

Information technology systems in healthcare have existed for several years and gained relatively widespread usage. Therefore, factors of IT adoption have largely been discussed in literatures in order to improve the efficiency and effectiveness of using systems. However, existing frameworks are failing to include an important aspect, the technostress undertaken by physicians. Our research idea is that IT adoption in a clinical environment depends on five different dimensions of technostress (e.g. work overload, techno-invasion and etc. al) of physicians through PU and PEOU based on TAM model. This paper first made comprehensive literature review to the content about technostress and different theories related to adoption, then put forward five hypotheses based on the TAM Model, which has been widely perceived by scholars. As for the model construction and data collection, the research intends to use a 5-point Likert scale and select physicians at different levels from 7 representative hospitals’ basic units located in Shaanxi province. Based on all above, we expect the research could offer a subtle theoretical understanding about the nature of technostress and their impact on adoption by physicians. On the practical front, the research has implications for managers intending to design managerial procedures or rules for the purpose of improving the adoption

Determination of dezocine in rabbit plasma by liquid chromatography-mass spectrometry and its application

A sensitive and selective liquid chromatography-mass spectrometry (LC–MS) method for determination of dezocine in rabbit plasma was developed and validated. After addition of diazepam as internal standard (IS), liquid–liquid extraction (LLE) was used for sample preparation, and chromatography involved Agilent SB-C18 column (2.1 mmx50 mm, 3.5 um) using 0.1 % formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragment ions m/z 245.8 for dezocine and m/z 284.8 for diazepam (internal standard, IS). The assay was linear over the range of 5–500 ng/mL for dezocine, with a lower limit of quantitation (LLOQ) of 5 ng/mL for dezocine. Intra- and inter-day precisions were less than 13 % and the accuracies were in the range of 93.1-105.2 % for dezocine. This developed method was successfully applied for the determination of dezocine in rabbit plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

FTO Knockout Causes Chromosome Instability and G2/M Arrest in Mouse GC-1 Cells

N6-methyladenosine (m6A) is the most abundant modification on eukaryotic mRNA. m6A plays important roles in the regulation of post-transcriptional RNA splicing, translation, and degradation. Increasing studies have uncovered the significance of m6A in various biological processes such as stem cell fate determination, carcinogenesis, adipogenesis, stress response, etc, which put forwards a novel conception called epitranscriptome. However, functions of the fat mass and obesity-associated protein (FTO), the first characterized m6A demethylase, in spermatogenesis remains obscure. Here we reported that depletion of FTO by CRISPR/Cas9 induces chromosome instability and G2/M arrest in mouse spermatogonia, which was partially rescued by expression of wild type FTO but not demethylase inactivated FTO. FTO depletion significantly decreased the expression of mitotic checkpoint complex and G2/M regulators. We further demonstrated that the m6A modification on Mad1, Mad2, Bub1b, Cdk1, and Ccnb2 were directly targeted by FTO. Therefore, FTO regulates cell cycle and mitosis checkpoint in spermatogonia because of its m6A demethylase activity. The findings give novel insights into the role of RNA methylation in spermatogenesis

Study of the spatial and temporal distributions of tidal flat surface sediment based on multitemporal remote sensing

IntroductionThe ecological environment of tidal flats often changes due to tidal erosion and sedimentation. The distribution of tidal flat surface sediment is a natural reflection of the changes in the external dynamic environment, the spatial and temporal distribution pattern is of great significance.MethodsIn this study, the output structure of traditional convolutional neural network is combined with BP neural network. Meanwhile, four phases of Sentinel-2 multispectral images were collected and combined with field data from the Doulonggang tidal flat in Jiangsu Province, China, to construct the sediment composition inversion model.ResultsThe inversion accuracy was higher than 80% compared with the measured results. According to the inversion result, from 2017 to 2022, the surface sediment particle size of the tidal flat in Jiangsu varied seasonally and was coarse in summer and fine in winter. Additionally, the sediment composition tended to coarsen, showing an interannual change trend of increasing sand content and decreasing clay and silt contents.DiscussionThe above change of the sedimentary environment of the tidal flat may be caused by the decrease of fine grained sediment deposition, the introduction of exotic vegetation, the global sea level rise and the influence of human activities

Risk-Stratified Screening for Colorectal Cancer Using Genetic and Environmental Risk Factors:A Cost-Effectiveness Analysis Based on Real-World Data

Background &amp; Aims: Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death. Methods: Risk predictions for CRC and competing causes of death from a large community-based cohort were used to stratify individuals into risk groups. A microsimulation model was used to optimize colonoscopy screening for each risk group by varying the start age (40–60 years), end age (70–85 years), and screening interval (5–15 years). The outcomes included personalized screening ages and intervals and cost-effectiveness compared with uniform colonoscopy screening (ages 45–75, every 10 years). Key assumptions were varied in sensitivity analyses. Results: Risk-stratified screening resulted in substantially different screening recommendations, ranging from a one-time colonoscopy at age 60 for low-risk individuals to a colonoscopy every 5 years from ages 40 to 85 for high-risk individuals. Nevertheless, on a population level, risk-stratified screening would increase net quality-adjusted life years gained (QALYG) by only 0.7% at equal costs to uniform screening or reduce average costs by 1.2% for equal QALYG. The benefit of risk-stratified screening improved when it was assumed to increase participation or costs less per genetic test. Conclusions: Personalized screening for CRC, accounting for competing causes of death risk, could result in highly tailored individual screening programs. However, average improvements across the population in QALYG and cost-effectiveness compared with uniform screening are small.</p

Forced Notch Signaling Inhibits Commissural Axon Outgrowth in the Developing Chick Central Nerve System

BACKGROUND: A collection of in vitro evidence has demonstrated that Notch signaling plays a key role in the growth of neurites in differentiated neurons. However, the effects of Notch signaling on axon outgrowth in an in vivo condition remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the neural tubes of HH10-11 chick embryos were in ovo electroporated with various Notch transgenes of activating or inhibiting Notch signaling, and then their effects on commissural axon outgrowth across the floor plate midline in the chick developing central nerve system were investigated. Our results showed that forced expression of Notch intracellular domain, constitutively active form of RBPJ, or full-length Hes1 in the rostral hindbrain, diencephalon and spinal cord at stage HH10-11 significantly inhibited commissural axon outgrowth. On the other hand, inhibition of Notch signaling by ectopically expressing a dominant-negative form of RBPJ promoted commissural axonal growth along the circumferential axis. Further results revealed that these Notch signaling-mediated axon outgrowth defects may be not due to the alteration of axon guidance since commissural axon marker TAG1 was present in the axons in floor plate midline, and also not result from the changes in cell fate determination of commissural neurons since the expression of postmitotic neuron marker Tuj1 and specific commissural markers TAG1 and Pax7 was unchanged. CONCLUSIONS/SIGNIFICANCE: We first used an in vivo system to provide evidence that forced Notch signaling negatively regulates commissural axon outgrowth

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → μ+μ−)/B(Bs → μ+μ−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier