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In this study, the biological electromagnetic dose variations and uncertainty caused by body weight differences in experimental animals were evaluated. An electromagnetic dose simulation environment of experimental rats under plane wave excitation was established using bio-electromagnetic simulation software and a three-dimensional digital model. The study frequency band was 0.1－6 GHz. The results showed that there was a linear relationship between the body weight of experimental rats and the whole-body average specific absorption rate under conditions of body weight disturbance. Below the resonant frequency point, the linear relationship was positive, whereas above the resonant frequency point, the linear relationship was negative. In the 1－6 GHz region, the degree of the linear fit was close to 1. The dose uncertainty for the experimental rats was investigated and a fitting calculation method was proposed. Combined with the experimental design case, the calculation process, calculation amount, and evaluation accuracy of the fitting calculation evaluation method were compared. The evaluation method had high accuracy and a low modeling calculation amount. The results of this study have certain guiding significance for the experimental design and dose evaluation of bioelectromagnetics.

The CO-dark molecular gas (DMG), which refers to the molecular gas not traced by CO emission, is crucial for the evolution of the interstellar medium (ISM). While the gas properties of DMG have been widely explored in the Solar neighborhood, whether or not they are similar in the outer disk regions of the Milky Way is still not well understood. In this Letter, we confirm the existence of DMG toward a cold H I arc structure at 13 kpc away from the Galactic center with both OH emission and H I narrow self-absorption (HINSA). This is the first detection of HINSA in the outer disk region, in which the HINSA fraction (NHINSA/NH2 = 0.022 ± 0.011) is an order of magnitude higher than the average value observed in nearby evolved dark clouds, but is consistent with that of the early evolutionary stage of dark clouds. The inferred H2 column density from both extinction and OH emission (NH2 ≈ 1020 cm−2) is an order of magnitude higher than previously estimated. Although the ISM environmental parameters are expected to be different between the outer Galactic disk regions and the Solar neighborhood, we find that the visual extinction (AV = 0.19 ± 0.03 mag), H2-gas density (nH2 = 91 ± 46 cm−3), and molecular fraction (58% ± 28%) of the DMG are rather similar to those of nearby diffuse molecular clouds. The existence of DMG associated with the expanding H I supershell supports a scenario where the expansion of supershells may trigger the formation of molecular clouds within a crossing timescale of the shock wave (∼106 yr). [ABSTRACT FROM AUTHOR]

Ovarian cancer is characterized by aberrant activation of the mitogen-activated protein kinase (MAPK), highlighting the importance of targeting the MAPK pathway as an attractive therapeutic strategy. However, the clinical efficacy of MEK inhibitors is limited by intrinsic or acquired drug resistance. Here, we established patient-derived ovarian cancer models resistant to MEK inhibitors and demonstrated that resistance to the clinically approved MEK inhibitor trametinib was associated with enhancer reprogramming. We also showed that enhancer decommissioning induced the downregulation of negative regulators of the MAPK pathway, leading to constitutive ERK activation and acquired resistance to trametinib. Epigenetic compound screening uncovered that HDAC inhibitors could alter the enhancer reprogramming and upregulate the expression of MAPK negative regulators, resulting in sustained MAPK inhibition and reversal of trametinib resistance. Consequently, a combination of HDAC inhibitor and trametinib demonstrated a synergistic antitumor effect in vitro and in vivo, including patient-derived xenograft mouse models. These findings demonstrated that enhancer reprogramming of the MAPK regulatory pathway might serve as a potential mechanism underlying MAPK inhibitor resistance and concurrent targeting of epigenetic pathways and MAPK signaling might provide an effective treatment strategy for advanced ovarian cancer., Introduction Epithelial ovarian cancer (OV) is the leading cause of mortality from gynecological malignancies (1); the overall survival rate has remained poor at 30% to 50% for decades, mainly owing [...]

The variations of elemental abundance and their ratios along the Galactocentric radius result from the chemical evolution of the Milky Way discs. The |$\rm ^{12}C/^{13}C$| ratio in particular is often used as a proxy to determine other isotopic ratios, such as |$\rm ^{16}O/^{18}O$| and |$\rm ^{14}N/^{15}N$|⁠. Measurements of |$\rm ^{12}CN$| and |$\rm ^{13}CN$| (or |$\rm C^{15}N$|⁠) – with their optical depths corrected via their hyper-fine structure lines – have traditionally been exploited to constrain the Galactocentric gradients of the CNO isotopic ratios. Such methods typically make several simplifying assumptions (e.g. a filling factor of unity, the Rayleigh–Jeans approximation, and the neglect of the cosmic microwave background) while adopting a single average gas phase. However, these simplifications introduce significant biases to the measured |$\rm ^{12}C/^{13}C$| and |$\rm ^{14}N/^{15}N$|⁠. We demonstrate that exploiting the optically thin satellite lines of 12CN constitutes a more reliable new method to derive |$\rm ^{12}C/^{13}C$| and |$\rm ^{14}N/^{15}N$| from CN isotopologues. We apply this satellite-line method to new IRAM 30-m observations of 12CN, 13CN, and C15N N  = 1 → 0 towards 15 metal-poor molecular clouds in the Galactic outer disc (R gc > 12 kpc), supplemented by data from the literature. After updating their Galactocentric distances, we find that |$\rm ^{12}C/^{13}C$| and |$\rm ^{14}N/^{15}N$| gradients are in good agreement with those derived using independent optically thin molecular tracers, even in regions with the lowest metallicities. We therefore recommend using optically thin tracers for Galactic and extragalactic CNO isotopic measurements, which avoids the biases associated with the traditional method. [ABSTRACT FROM AUTHOR]

Astrochemistry has been widely developed as a power tool to probe the physical properties of the interstellar medium (ISM) in various conditions of the Milky Way (MW) Galaxy, and in near and distant galaxies. Most current studies conventionally apply linear scaling to all elemental abundances based on the gas-phase metallicity. However, these elements, including carbon and oxygen, are enriched differentially by stellar nucleosynthesis and the overall galactic chemical evolution, evident from α-enhancement in multiple galactic observations such as starbursts, high-redshift star-forming galaxies, and low-metallicity dwarfs. We perform astrochemical modelling to simulate the impact of an α-enhanced ISM gas cloud on the abundances of the three phases of carbon (C+, C, CO) dubbed as 'the carbon cycle'. The ISM environmental parameters considered include two cosmic-ray ionization rates (ζCR = 10−17 and |$10^{-15}\, {\rm s}^{-1}$|⁠), two isotropic FUV radiation field strengths (χ/χ0 = 1 and 102), and (sub-)linear dust-to-gas relations against metallicity, mimicking the ISM conditions of different galaxy types. In galaxies with [C/O] < 0, CO, C, and C+, all decrease in both abundances and emission, though with differential biases. The low- J CO emission is found to be the most stable tracer for the molecular gas, while C and C+ trace H2 gas only under limited conditions, in line with recent discoveries of [C  i ]-dark galaxies. We call for caution when using [C  ii ] |$158\, \mu$| m and [C  i ](1–0) as alternative H2-gas tracers for both diffuse and dense gas with non-zero [C/O] ratios. [ABSTRACT FROM AUTHOR]

Background: Leucine‐rich repeat kinase 2 (LRRK2) common gene variants (tagged by rs76904798) are associated with Parkinson's disease (PD) risk. In a previous study, we found that rs76904798 was associated with CSF GRN levels, but a comprehensive unbiased analysis of associated proteins remains incomplete due to prior focus on cis‐protein quantitative trait loci (pQTL). Using the largest aptamer‐based CSF proteomics study to date (7,006 aptamers (6,138 unique proteins) in 3,107 individuals), we performed a trans‐pQTL study to identify proteins associated with the LRRK2 variants and used additional mediation and pathway analyses to better understand downstream effects (Figure 1). Method: SNP selection using Conditional and Joint Association Analysis (GTCA‐COJO) and PLINK LD r2 scores identified 11 other independently associated SNPs. Fine mapping was performed between each significant aptamer and PD GWAS via proteome‐wide association studies (PWAS) and Mendelian randomization (MR). These aptamers were further analyzed based on PD risk association, brain cell‐type specificity, and gene pathway annotations. Result: Overall, 26 proteins passed FDR correction and eleven were implicated in PD prior like GRN and GPNMB. PWAS analyses using TWAS/FUSION also indicate 12 proteins were significant and positively associated with PD risk, such as novel proteins C1QTNF1 and SDCBP2, and half were validated by the PPMI data. MR analyses indicate that GRN, GPNMB, HLA‐DQA2, CD68, and LCT are also causal for PD risk (Table 1). Cell‐type enrichment analyses indicate microglia‐specific protein enrichment (Fold change: 7.35, P = 4.91×10−5). Enrichment analyses indicate enrichment for leukocyte activation (GO:0045321, P = 0.002) and microglial cell activation (GO:0001774, P = 0.003) pathways. Conclusion: Trans‐pQTL can identify novel protein interactions in an unbiased manner. This study linked LRRK2 variants with both PD implicated (GRN, GPNMB) and novel (ITGB2, C1QTNF1) proteins that have support in our PWAS, MR, and PPMI differential protein level analyses. Microglia and lysosome enrichment support the previous observations regarding the importance of microglia and immune system function in the underlying pathobiology of PD (Figure 2). Our results suggest that the CSF concentrations of these proteins (such as GRN, GPNMB, C1QTNF1, and ITGB2) have potential as biomarkers for target engagement and disease progression modification in clinical trials that target LRRK2. [ABSTRACT FROM AUTHOR]

We herein report a synthetic strategy for alternating copolymers of styrene and substituted styrenes by utilizing α‐styryl boronate pinacol ester (StBpin) as the co‐monomer through radical alternating copolymerization followed by protodeboronation. The excellent alternating polymerization behavior of the StBpin co‐monomer in such a radical polymerization system is considered to be attributed to the steric hindrance and radical stabilization exerted by the Bpin group. This strategy is effective with a wide range of substituted styrene co‐monomers regardless of the electronic nature of the substituents, and the protodeboronation of the alternating Bpin‐containing polymers is highly efficient without polymer backbone alternation. RAFT living polymerization was also compatible with this approach. Thus, this strategy provides a way to build‐up alternating copolymers consisting of similar styrene‐type co‐monomers, which has been inaccessible by conventional synthetic methods. [ABSTRACT FROM AUTHOR]

With the development of sharing economy, a joint distribution mode has been increasingly adopted as the preferred cooperation mode of third-party logistics enterprises to achieve the efficient, resource-saving, and profit-optimal business goals of enterprises. In the joint distribution mode, the distribution price is one of key factors that influences the operation of the joint distribution. Thus, to acquire the optimal pricing for the logistics enterprises, we establish a pricing model based on dynamic game theory for a joint distribution system including one joint distribution company and two express enterprises. In the proposed model, two dimensions of games exist simultaneously, including the game between express competitors and the game between express and distribution enterprises. The multidimensional game leads to more complex system characteristics. Through the stability analysis, we find the Nash equilibrium point and its stability conditions. Numerical simulations are conducted to investigate the complex dynamical behaviors of the game model, such as the system stability region, the bifurcation diagram, the largest Lyapunov exponent, strange attractors, etc. The simulation results indicate that different price adjustment speeds and ranges have a significant impact on the system stability and the profits of all participants in the game. The parameter adjustment control can well dominate the chaotic behaviors of the system. Enterprises should make pricing decisions based on their market positions to promote the continuous and stable development of the operation mode of the multi-agent joint sharing distribution center. [ABSTRACT FROM AUTHOR]

The Baeyer–Villiger oxidation represents a valuable reaction that enables the conversion of ketones into esters or lactones. Here, we present a novel and efficient approach utilizing I2 as a catalyst for the oxidative rearrangement of cyclobutenones, resulting in the synthesis of furan-2(5H)-one. Notably, this method employs dimethyl sulfoxide (DMSO) as a greener oxidant and source of oxygen. The reaction proceeds smoothly with catalytic amounts of iodine, yielding lactones in good yields. Compared to conventional Baeyer–Villiger oxidation reactions that rely on peroxyl acids or hydrogen peroxide, the use of DMSO offers a safer and more versatile alternative. [ABSTRACT FROM AUTHOR]

Natural killer/T‐cell lymphoma (NKTL) is an uncommon malignancy with poor prognosis and limited therapeutic options. Activating mutations of signal transducer and activator of transcription 3 (STAT3) are frequently found in patients with NKTL, suggesting that targeted inhibition of STAT3 is a potential therapeutic option for this disease. Here, we have developed a small molecule drug WB737 as a novel and potent STAT3 inhibitor that directly binds to the STAT3‐Src homology 2 domain with high affinity. In addition, the binding affinity of WB737 to STAT3 is 250‐fold higher than STAT1 and STAT2. Interestingly, WB737 is more selective for NKTL with STAT3‐activating mutations in terms of growth inhibition and apoptotic induction when compared with Stattic. Mechanistically, WB737 inhibits both canonical and noncanonical STAT3 signaling via suppression of STAT3 phosphorylation at Tyr705 and Ser727, respectively, thereby inhibiting the expression of c‐Myc and mitochondria‐related genes. Moreover, WB737 inhibited STAT3 more potently than Stattic, resulting in a significant antitumor effect with undetectable toxicity, followed by almost complete tumor regression in an NKTL xenograft model harboring a STAT3‐activating mutation. Taken together, these findings provide preclinical proof‐of‐concept for WB737 as a novel therapeutic strategy for the treatment of NKTL patients with STAT3‐activating mutations. [ABSTRACT FROM AUTHOR]

The traffic operational efficiency of the urban expressway system will affect one of the entire cities. Moreover, the idea that traffic control can improve the traffic operational efficiency of the urban expressway system has been fully confirmed. At present, the main control methods include on-ramp metering and speed guidance control. However, there is a gap in using these two control methods together, such as unclear application conditions and unsystematic methods. In this paper, on-ramp metering and speed guidance control are combined effectively. Based on the research of METANET macroscopic traffic flow model and model predictive control (MPC), a novel joint control method based on MPC and connected vehicles (CVs) for on-ramp metering and speed guidance control of the urban expressway is proposed. Finally, the simulation results show that the proposed control method can effectively improve the traffic efficiency and traffic safety., 1. Introduction The urban expressway system is a corridor for urban mass transit and rapid traffic, and its smoothness directly affects the traffic efficiency of the entire city. At present, [...]

Heteroepitaxial growth and alloys with novel physicochemical properties are attracting great attention in the photoelectric field, and inorganic heteroepitaxial growth and inorganic alloys have been well controlled via changing experimental conditions. Meanwhile, organic heterostructures (OHSs) and organic alloys (OAs) are less studied due to strict requirements for lattice parameters. Moreover, the occurrence of organic homogeneous nucleation is another main problem to solve in OHSs and OAs. Herein, by taking advantage of the similarity between N＝N and C＝C, we present a cocrystal strategy to maintain the molecular arrangement and lattice parameters, and perfect lattice matching is realized in the case of mutual substitution of N＝N and C＝C in molecules. Furthermore, we successfully achieved perfect organic heteroepitaxy and organic alloys with the same materials. We expect the realization of more versatile OHSs and OAs by introducing N＝N and C＝C into the photoelectric field. [ABSTRACT FROM AUTHOR]

To further improve the computational performance of the diffractive deep neural network (D2NN) model, we use the ReLU function to limit the phase parameters, which effectively solves the problem of vanishing gradient that occurs in the mitigation model. We add various commonly used nonlinear activation functions to the hidden layer of the model and establish the ReLU phase-limit nonlinear diffractive deep neural network (ReLU phase-limit N-D2NN) model. We evaluate the model by comparing the performance of various nonlinear activation functions, where confusion matrix and accuracy are used as evaluation methods. The numerical simulation results show that the model achieves better classification performance on the MNIST and Fashion-MNIST datasets, respectively. In particular, the highest classification performance is obtained by the ReLU phase-limit N-D2NN model, in which the hidden layer uses PReLU, with 98.38% and 90.14%, respectively. This paper provides a theoretical basis for applying the nonlinear D2NN systems in natural scenes. [ABSTRACT FROM AUTHOR]

Multiple internal conflicts and external emergencies can occur when an enterprise implements a project portfolio (PP), making the PP inevitably deviate from the enterprise's strategic objectives. As a means of project portfolio change (PPC) that aims to align the PP with strategic objectives, adding new projects can compensate for this deviation. Furthermore, the synergistic relationships in the PP can significantly impact the achievement of the enterprise's strategic objectives. Therefore, this study presents a procedure for the selection of new projects that considers the synergistic relationships in the PP. First, the deviation between the PP and the enterprise's strategic objectives is identified. Second, the synergistic relationships between candidate new projects and the projects in the PP are analyzed, based on which a model of new project selection is built. Third, by comparing the model simulation results of the attainment of the strategic objectives of several PPs, the new projects that can best achieve these strategic objectives are added to the PP. This procedure is illustrated using a numerical example showing its applicability and efficacy. For academia, this study provides a theoretical framework for the selection of new projects. Moreover, the straightforward procedure can help manage PPs in business practice. [ABSTRACT FROM AUTHOR]