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Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer immunotherapy. It is primarily expressed on activated T and natural killer (NK) cells, and once engaged with its ligand, PVRL2, it induces inhibitory signaling in T cells, thereby promoting the functional exhaustion of tumor-infiltrating lymphocytes (TILs). Here, we characterized IBI352g4a, a novel humanized anti-PVRIG antibody with Fc-competent function, explored the mechanism of its antitumor activity in preclinical models, and systemically evaluated the contribution of FcrR engagement to PVRIG blockade-induced antitumor activity. IBI352g4a binds to the extracellular domain of human PVRIG with high affinity (Kd = 0.53 nM) and specificity, and fully blocks the interaction between PVRIG and its ligand PVRL2. Unlike other immune checkpoints, IBI352g4a significantly induced NK cell activation and degranulation, but had a minimal effect on T-cell activation in in vitro functional assays. IBI352g4a induced strong antitumor effect in several preclinic models, through in vivo mechanism analysis we found that both NK and T cells contribute to the antitumor effect, but NK cells play predominant roles. Specifically, a single dose of IBI352g4a induced significant NK cell activation in TILs, but T-cell activation was observed only after the second dose. Moreover, the Fc effector function is critical for both NK cell activation and treatment efficacy in vitro and in vivo. Our study, for the first time, demonstrates that both NK activation and FcrR engagement are required for antitumor efficacy induced by PVRIG blockade. [ABSTRACT FROM AUTHOR]

In this paper, we consider some finite-time dividend and ruin problems in a class of risk models under the constant dividend barrier strategy. This class of risk models includes Brownian motion risk model and the compound Poisson model with and without diffusion. By using Laguerre series expansion, we derive infinite series expansion formulas for the time T-deferred Laplace transform of the ruin time and time T-deferred expected present valued of dividend payments until ruin. [ABSTRACT FROM AUTHOR]

An hp-version interior penalty discontinuous Galerkin method under nonconforming meshes is proposed to solve the quad-curl eigenvalue problem. We prove well-posedness of the numerical scheme for the quad-curl equation and then derive an error estimate in a mesh-dependent norm, which is optimal with respect to h but has different p-version error bounds under conforming and nonconforming tetrahedron meshes. The hp-version discrete compactness of the DG space is established for the convergence proof. The performance of the method is demonstrated by numerical experiments using conforming/nonconforming meshes and h-version/p-version refinement. The optimal h-version convergence rate and the exponential p-version convergence rate are observed. [ABSTRACT FROM AUTHOR]

Stimulating ion channels targeting in neuromodulation by external signals with the help of functionalized nanoparticles, which integrates the pioneering achievements in the fields of neurosciences and nanomaterials, has involved into a novel interdisciplinary field. The emerging technique developed in this field enable simple, remote, non-invasive, and spatiotemporally precise nerve regulations and disease therapeutics, beyond traditional treatment methods. In this paper, we define this emerging field as nano-neuromodulation and summarize the most recent developments of non-genetic nano-neuromodulation (non-genetic NNM) over the past decade based on the innovative design concepts of neuromodulation nanoparticle systems. These nanosystems, which feature diverse compositions, structures and synthesis approaches, could absorb certain exogenous stimuli like light, sound, electric or magnetic signals, and subsequently mediate mutual transformations between above signals, or chemical reactions, to regulate stimuli-sensitive ion channels and ion migrations which play vital roles in the nervous system. We will also discuss the obstacles and challenges in the future development of non-genetic NNM, and propose its future developments, to add the further progress of this promising field. [ABSTRACT FROM AUTHOR]

Background: Previous studies have identified that chromosome structure plays a very important role in gene control. The transcription factor Yin Yang 1 (YY1), a multifunctional DNA binding protein, could form a dimer to mediate chromatin loops and active enhancer-promoter interactions. The deletion of YY1 or point mutations at the YY1 binding sites significantly inhibit the enhancer-promoter interactions and affect gene expression. To date, only a few computational methods are available for identifying YY1-mediated chromatin loops. Results: We proposed a novel model named CapsNetYY1, which was based on capsule network architecture to identify whether a pair of YY1 motifs can form a chromatin loop. Firstly, we encode the DNA sequence using one-hot encoding method. Secondly, multi-scale convolution layer is used to extract local features of the sequence, and bidirectional gated recurrent unit is used to learn the features across time steps. Finally, capsule networks (convolution capsule layer and digital capsule layer) used to extract higher level features and recognize YY1-mediated chromatin loops. Compared with DeepYY1, the only prediction for YY1-mediated chromatin loops, our model CapsNetYY1 achieved the better performance on the independent datasets (AUC > 0.99 ). Conclusion: The results indicate that CapsNetYY1 is an excellent method for identifying YY1-mediated chromatin loops. We believe that the CapsNetYY1 method will be used for predictive classification of other DNA sequences. [ABSTRACT FROM AUTHOR]

Introduction: The lymph node metastasis stage of lung cancer is an important decisive factor in the need for postoperative adjuvant treatment and the difference between stage IIIa and stage IIIB that is the necessary information to distinguish whether surgery can be performed or not. The specificity of the clinical diagnosis of lung cancer with lymph node metastasis cannot meet the requirements of preoperative evaluation of surgical indications and prediction of surgical removal range in lung cancer. Methods: This was an early experimental laboratory trial. The model identification data included the RNA sequence data of 10 patients from our clinical data and 188 patients with lung cancer from The Cancer Genome Atlas dataset. The model development and validation data consisted of RNA sequence data for 537 cases from the Gene Expression Omnibus dataset. We explore the predictive value of the model on two independent clinical data. Results: A higher specificity of diagnostic model for patients with lung cancer with lymph node metastases consisted of DDX49, EGFR, and tumor stage (T‐stage), which were the independent predictive factors. The area under the curve value, specificity, and sensitivity for predicting lymph node metastases were 0.835, 70.4%, and 78.9% at RNA expression level in the training group, and 0.681, 73.2%, and 75.7% at RNA expression level in the validation group as shown as in result part. To verify the predictive performance of the combined model for lymph node metastases, we downloaded the GSE30219 data set (n = 291) and the GSE31210 data set (n = 246) from the Gene Expression Omnibus (GEO) database as the training group and validation group, respectively. In addition, the model had a higher specificity for predicting lymph node metastases in independent tissue samples. Conclusions: Determination of DDX49, EGFR, and T‐stage could form a novel prediction model to improve the diagnostic efficacy of lymph node metastasis in clinical application. [ABSTRACT FROM AUTHOR]

Variable annuities with complex surrender features are nowadays increasingly popular for managing longevity risks. The study of their accurate pricing and sensitivity analysis is one of the main actuarial research topics. This paper studies the valuation problem of variable annuity contracts with guaranteed minimum maturity benefits on a set of predetermined discrete tenor dates under regime-switching Lévy models. Extending from existing vanilla payoffs, we consider the guaranteed minimum maturity benefits with lookback and geometric average features. We customise the dynamic programming principle to solve the corresponding optimal stopping problem, relying on some semi-analytical valuation formulae resulting from an acute Fourier cosine series expansion. Finally, numerical illustrations are provided to show the accuracy and efficiency of the proposed method. We also demonstrate the use of our proposed method in a range of sensitivity analysis exercises, which shed light on the pricing and risk management of complex variable annuity products. [ABSTRACT FROM AUTHOR]

Annual mass balance is an important reflection of glacier status that is also very sensitive to climate fluctuations. However, there is no effective and universal albedo-based method for the reconstruction of annual mass balance due to the scarcity of field observations. Here, we present an improved albedo–mass balance (IAMB) method to estimate annual glacier surface mass balance series using remote sensing techniques. The averaged glacier-wide albedo derived with the MODImLab algorithm during the summer season provides an effective proxy of the annual mass change. Defined as the variation in the albedo as a function of elevation change, the altitude–albedo gradient ( ∂ z / ∂ α ) can be obtained from a glacier digital elevation model (DEM) and optical images. The Chhota Shigri glacier situated in the western Himalayas was selected to test and assess the accuracy of this method over the period from 2003 to 2014. Reconstructed annual mass budgets correlated well with those from the observed records, with an average difference and root mean square error (RMSE) of −0.75 mm w.e. a−1 and 274.91 mm w.e. a−1, respectively, indicating that the IAMB method holds promise for glacier mass change monitoring. This study provides a new technique for annual mass balance estimation that can be applied to glaciers with no or few mass balance observations. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening disease usually treated with therapeutic plasma exchange (TPE), but some patients are refractory to TPE. The study aimed to compare lymphoplasmapheresis (LPE), an innovative treatment for TTP based on plasma exchange, with TPE in TTP treatment. This retrospective study included patients with TTP treated at Xiang-Ya Hospital in China during 2009-2018. All patients with microangiopathic hemolysis and thrombocytopenia who received either LPE or TPE were included. The treatment outcomes were the number of sessions, volume of plasma, time in hospital, hospital costs, and rates of remission and relapse. All patients attended the hospital for follow-up. Forty-five patients were included in the study; 18 received TPE and 27 LPE. There were no significant differences in sex, etiology of TTP, initial platelet count, schistocyte, LDH, and bilirubin between the two groups. At the time of discharge, patients treated with TPE required more treatment sessions (4.5 vs. 2, P=0.04) and higher plasma volume (7300 vs. 3100 ml, P=0.01) than patients treated with LPE. The proportions of remission (P=0.197) and relapse (P=0.257) were not significantly different between the two groups. The time to remission from admission (P=0.75) and the time to remission from first therapy (P=0.53) were also not significantly different between the two groups. Compared with TPE, LPE reduced the number of treatment sessions and plasma volume needed to treat TTP. Therefore, we propose that LPE might be a suitable treatment for TTP. [ABSTRACT FROM AUTHOR]

It has been reported that lncRNA GAS5 can inhibit LPS-induced inflammation, indicating its involvement in sepsis. We observed the downregulation of GAS5 in plasma of sepsis patients. In addition, expression levels of GAS5 were positively correlated with the expression levels of miR-214. In cardiomyocytes, overexpression of GAS5 upregulated the expression of miR-214, while its knockdown resulted in decreased expression levels of miR-124. Methylation-specific PCR (MSP) revealed that GAS5 negatively regulated the methylation of miR-124. Cell apoptosis showed that overexpression of GAS5 and miR-214 suppressed the apoptosis of cardiomyocytes induced by LPS. In addition, overexpression of miR-214 also reduced the enhancing effects of silencing of GAS5 on cell apoptosis. Therefore, GAS5 may upregulate miR-214 through methylation pathway to inhibit the apoptosis of cardiomyocytes in sepsis. [ABSTRACT FROM AUTHOR]

A new spectral Galerkin method based on Log orthogonal functions (LOFs) is proposed for singularly perturbed problems (SSPs). The method uses only (orthogonal) basis functions to approximate the boundary layer function exp (- x / ε) without help from any specially designed mesh. An error estimate for the boundary layer function is derived and shows the exponential convergence of the new method. Ample numerical examples in 1d and 2d validate the high-efficiency and robustness of the Log spectral/spectral-element method for SSPs. [ABSTRACT FROM AUTHOR]

An increase in hydrostatic stress improves the plasticity of metallic materials. However, for some special components, such as large thin-walled components with high ribs, excessive hydrostatic stress can cause several problems that make it impossible to prepare such components using plastic forming methods. In this study, the effect of hydrostatic stress on the deformation behavior of large thin-walled components with high ribs was investigated using a combination of numerical simulations and theoretical derivations. The results indicated that excessive hydrostatic stress leads to die failure, causing metal flow difficulties, uneven deformation, inconsistent mechanical properties, and reduced forming accuracy. Therefore, a low-hydrostatic-stress extrusion method was proposed by adjusting the contact friction, metal flow direction and displacement, and force boundary conditions to reduce the hydrostatic compressive stress. These principles are mainly reflected in the following three aspects: First, the size of the difficult deformation zone was reduced by changing the friction conditions from dry friction to fluid friction or boundary friction to reduce the frictional resistance. Second, the high-stress zone was eliminated by changing the metal flow direction, adjusting the strain state from unidirectional to multi-directional flow, shortening the metal flow path, and reducing the metal flow resistance. Third, the strong compressive stress state in the three directions was weakened by regulating the force boundary conditions and changing the loading method from one-way extrusion to multi-directional loading. Based on these principles, a series of new forming technologies have been developed, such as actively counteracting frictional resistance, slotting, and ditching on dies for long-lasting lubrication, multi-directional short-range metal flow, drawing-assisted extrusion, and multi-directional active loading. The adoption of these technologies realizes the labor-efficient formation of large thin-walled components with high ribs and provides the formed members with high precision and uniform mechanical properties. [Display omitted] • The influences of hydrostatic stress on metal flow, forming forces and strains were revealed. • The principle of low hydrostatic stress extrusion was developed, which can be employed to reduce the working stress. • The forming force was reduced, and the deformation uniformity and forming accuracy of thin-walled components were improved. [ABSTRACT FROM AUTHOR]

Objective. To explore the effect of circular RNA circ-ABCB10 on the proliferation and apoptosis of laryngeal carcinoma via inhibiting KLF6. Methods. RT-qPCR assay was adopted to detect the expression of circ-ABCB10 and KFL6 in laryngeal carcinoma tissues and cell lines. Cell counting kit-8 (CCK-8) and clone formation assay were employed to detect laryngeal cancer cell viability and proliferation when circ-ABCB10 was silenced or upregulated. In this study, the apoptosis rate was detected by flow cytometry and the protein expression was detected by Western blotting. Wound healing and cross-hole invasion were used to study the migration and invasion of laryngeal cancer cells when circ-ABCB10 was silenced or upregulated. Results. The results of RT-qPCR detection indicated that the expression of circ-ABCB10 in all three laryngeal carcinoma cells was downregulated by 3.2 times compared with that of HaCat cells. There is low expression of circ-ABCB10 in most laryngeal carcinoma tissues, the diagnostic cutoff value of circ-ABCB10 is 0.0008, the area under the curve is 0.718, the sensitivity is 0.981, and the specificity is 0.556. The expression level of KLF6 in laryngeal carcinoma is on the rise, which is significantly higher compared to healthy tissues (P < 0.05); 48 hours after transfection, RT-qPCR analysis confirmed the transfection efficiency, and upregulation of circ-ABCB10 could significantly promote cell proliferation. Compared with the control group, silencing circ-MTCL1 could inhibit cell proliferation, overexpression of circ-ABCB10 promoted cell migration, and downregulation of circ-ABCB10 significantly inhibited cell movement (P < 0.001). Upregulation of circ-ABCB10 significantly enhanced the invasiveness and motility of laryngeal cancer cells, while downregulation of circ-ABCB10 was the opposite. Compared with the KLF6 NC group, KLF6 level increased significantly in the KLF6 group, while cell viability, colony formation, scratch healing rate, invasive cell number, and Bcl-2 expression level decreased significantly in the KLF6 group, while apoptosis rate and Bax expression level increased significantly (P < 0.05). KLF6 level in the si-circ-ABCB10+anti-KLF6 group was significantly lower than that in the si-circ-ABCB10+anti-KLF6-NC group (P < 0.05). Meanwhile, the cell activity, colony formation number, cell scratch healing rate, number of invaded cells, and Bcl-2 all indicated an upward trend, while the cell apoptosis rate and Bax expression indicated a downward trend (P < 0.05). Conclusion. The expression of circ-ABCB10 in laryngeal carcinoma was significantly higher compared to that in paracancerous tissues. Silencing circ-ABCB10 could significantly inhibit the growth and proliferation of laryngeal adenocarcinoma cells, while overexpression of circ-ABCB10 could significantly promote the growth of laryngeal adenocarcinoma cells, probably by inhibiting KLF6 to enhance the proliferation of laryngeal carcinoma and inhibit apoptosis. [ABSTRACT FROM AUTHOR]

Photoinhibition lithography (PIL) is a nanoscale fabrication technique that uses multicolor visible light to enable the printing of arbitrary 3D structures beyond the diffraction limit. Photoinhibition allows the control and confinement of the exposed region for photoinitiation during the photolithographic process, thus improving the resolution of existing lithographic techniques, such as direct laser writing. Because PIL enables super‐resolution 3D printing, it has a multitude of applications. In this review, practical applications of PIL in the areas of photonics, data storage, and biotechnology are highlighted; in addition, its unique features are revealed. The theory and recent advances in PIL for sub‐diffraction printing and high‐throughput fabrication are also discussed. Besides, challenges and tentative solutions are discussed with the hope of providing a preliminary roadmap for technological breakthroughs in PIL to enable developments of resolution and throughput. [ABSTRACT FROM AUTHOR]

Adversarial attack on neural networks has become an important problem restricting its security applications, and among adversarial attacks oriented towards the sample set, the universal perturbation design causing most sample output errors is critical to the study. This paper takes the neural network for image classification as the research object, summarizes the existing universal perturbation generation algorithm, proposes a universal perturbation generation algorithm combining batch stochastic gradient rise and spherical projection search, achieves loss function reduction through the iterative training of stochastic gradient rise in batch samples, and limits the universal perturbation search to a high-dimensional sphere with radius ε to reduce the search space of universal perturbation. Moreover, the regularized technology is introduced to improve the generation quality of universal perturbations. The experimental results show that compared with the baseline algorithm, the attack success rate increases by more than 10%, the solution efficiency of universal perturbation is improved by one order of magnitude, and the quality controllability of universal perturbation is better. [ABSTRACT FROM AUTHOR]

When engaging in activities such as using video display terminals, driving, or sports, effective fatigue monitoring is crucial. Nevertheless, obtaining biological information through contact devices may interfere with normal activities. Deterministic expressions in mainstream machine learning have limitations in reflecting the continuous, dynamic, and fuzzy process of fatigue status. Additionally, fatigue is a cumulative process where the previous state impacts the assessment of the current one. To address these needs and challenges, this paper proposes a novel model based on facial videos called the temporal adaptive fuzzy neural network (TAFNN) for fatigue assessment. TAFNN utilizes an adaptive fuzzy neural network as its foundation and employs causal and dilated convolutions for the time information processing method to achieve time series extraction and fatigue assessment. It leverages facial physiological and motion features to minimize interference during assessment. Furthermore, TAFNN introduces a new calculation method for rule antecedents to enhance stability. Experimental results demonstrate that TAFNN effectively captures the cumulation and fuzziness of state changes, outperforming other widely adopted methods in both assessment ability and runtime performance. The improved rule antecedent calculation method successfully mitigates the issue of multiple memberships rapidly approaching zero after combination. Through 1000 repeated experiments, the enhanced method reduces TAFNN's instability by 81.58%. • A novel temporal adaptive fuzzy neural network (TAFNN) for assessment is introduced. • TAFNN can simultaneously express fatigue state changes' cumulation and fuzziness. • The improved rule antecedent calculation method can enhance the stability of TAFNN. • TAFNN has advantages in both fatigue assessment capability and runtime performance. [ABSTRACT FROM AUTHOR]

We present a streamlined valuation method for the guaranteed minimum accumulation benefits incorporated within variable annuity contracts. At each contract renewal date, the insurer updates the policyholder's account value to the higher of the guaranteed value and the equity-linked investment value. In addition, we introduce lapse risks into the variable annuity contract, modeling the lapse decision under the assumption of stochastic intensity. Utilizing a combination of continuous-time Markov chain approximation and the Fourier cosine series expansion method, we derive closed-form valuation formulas under regime switching jump diffusion models. Numerical simulations showcase the precision and effectiveness of the proposed approach. • This paper proposes an efficient computational method for pricing variable annuities. • Our results significantly improve computational efficiency compared to Monte Carlo. • We introduce lapse risk and regime-switching into the paper. • Our method can be used to calculate option pricing. [ABSTRACT FROM AUTHOR]

Classification methods relying on multidimensional features have been widely applied in commerce, healthcare, and transportation. Nevertheless, haphazardly selecting inappropriate features may not only hinder the improvement of classification performance but also disrupt the convergence of classifier parameters, leading to prolonged classifier runtime and an increased storage burden. Therefore, this paper proposed a novel framework (dubbed as DFS-WR) to perform dual selection and weighted representation of multidimensional features. Firstly, DFS-WR employs Laplacian scores to conduct a de-redundant operation as the first feature selection. Subsequently, DFS-WR utilizes a correlation coefficient matrix and redundant sorting to eliminate duplicate deployment of similar features in classification through the second selection. Finally, for hierarchical expression, DFS-WR assigns weights by virtue of information gain (IG), thereby emphasizing the significance of dominant features. The performance of DFS-WR was further evaluated across four aspects: classification ability, runtime performance, storage occupancy, and portability and universality, using five public datasets and eleven widely adopted classifiers. Additionally, this paper considered the proper configuration of crucial parameters within DFS-WR and compared it with other related works. The results indicated that the dual selection strategy for eliminating redundancy and similarities among features could improve the performance of classifiers, and the weighted process based on IG outperformed unweighted and ReliefF-based weighted methods. By employing DFS-WR to multidimensional features, the classifier's runtime and data storage capacity were effectively reduced. In addition, it was proved that the deployment of DFS-WR generally had no limitations on datasets and classifiers, underscoring its good portability and universality in practical applications. • A dual selection and weighting framework (DFS-WR) for classification is introduced. • A method for selecting similar features combined with redundant sorting is proposed. • Using DFS-WR can improve classifier performance, reduce runtime, and decrease storage. • DFS-WR has portability and universality for datasets and classifiers in applications. [ABSTRACT FROM AUTHOR]

The aim of this work is to develop a conservative, positivity-preserving (PP), nonlinear finite volume (FV) scheme for the multi-term nonlocal Nagumo-type equations on distorted meshes. These equations involve anisotropic diffusion tensor coefficients, and the solution exhibits a weak singularity at t = 0. To achieve this, we combine the L1 scheme on a graded mesh with a PP-FV scheme on randomly distorted meshes, resulting in a conservative, positivity-preserving nonlinear L1-PP-FV scheme. By employing a nonlinear-splitting technique, we derive a series of simple nonlinear discrete equations that can be solved implicitly. We also provide proof that both the proposed FV scheme and the nonlinear iteration (NI) scheme are capable of maintaining positivity. Finally, we present numerical results to validate our theoretical analysis. [ABSTRACT FROM AUTHOR]

The unstable mechanical behavior of soil particles during suffusion, including migration and clogging of fine particles in porous media, is prone to induce seepage catastrophes. Mechanical behavior of migratory fines and porous soils during suffusion is significantly influenced by the particle shape, which remains unclear. In this study, a coupled computational fluid dynamics and the irregular discrete element method (CFD-iDEM) framework is developed to investigate the migration and clogging mechanisms. A series of numerical simulations that consider spheres and irregular particles with different levels of aspect ratio are carried out to elucidate the microscopic origins of shape effects on clogging. Migratory fine particles are discharged from the grain inlet and enter the coarse particle skeleton by imposing a downward seepage flow. The subsequent migration and clogging phenomena and microscopic mechanisms are investigated. The results reveal that irregular particles present varying degrees of ability to develop clogging clusters, and spheres are more prone to traverse deeper into soil skeleton. The proposed CFD-iDEM method is able to reproduce macroscopic phenomena of saturated porous medium as well as to analyze microscopic origins of fluid–particle interactions, which contributes to practical guidance for engineering applications. [ABSTRACT FROM AUTHOR]

Digital beamforming (DBF) with scan-on-receive (SCORE) technique in elevation is a powerful technique that enables a spaceborne synthetic aperture radar (SAR) to achieve high-resolution wide swath (HRWS) imaging. In the spaceborne DBF-SAR system, sampling signals from each channel are weighted by weights generated by a digital signal processing system in real-time. However, the contradiction between the shortage of spaceborne hardware resources and resource demand of the multichannel real-time signal processing increases the difficulty of system design. In order to solve this problem, a novel weight generator and an improved intermediate frequency (IF) DBF real-time processing architecture are proposed in this article. By taking advantage of the special properties of the SCORE algorithm, the proposed weight generator calculates weights using a linear polynomial algorithm. The simulation result shows that a low-order approximation can achieve high performance. The proposed generator can correct multichannel amplitude and phase error at a low cost on hardware resources. The effectiveness of the proposed method is verified by experiments with a raw data processing instance of an X-band 16 channels DBF-SAR. [ABSTRACT FROM AUTHOR]

The displaced phase center antennas in azimuth and digital beamforming (DBF) in elevation are two state-of-the-art techniques for achieving high-resolution wide swath (HRWS) imaging in the multichannel synthetic aperture radar (SAR) systems. However, due to the atmospheric turbulence, airborne HRWS-SARs inevitably suffer trajectory disturbances, which will consequently defocus the SAR image. Although various motion compensation (MoCo) methods have been proposed, they are mostly designed for the traditional single-channel SAR and, therefore, ignore the channel-dependent posture error. The posture motion error will introduce residual motion and time-variant channel errors, which not only defocuses the image but also causes azimuth ambiguity and degrades the SNR improvement of the final images of the azimuth multichannel and DBF-SAR, respectively. To solve these problems, a novel MoCo scheme for 2-D multichannel SAR systems is proposed. The posture error is described and calculated in matrix form through the use of quaternions. Then, the posture error is transformed into the translational motion error for each receiving channel and is subsequently compensated precisely. To address the residual aperture-variant motion error, a modified aperture-dependent MoCo is integrated into the proposed scheme. Simulations and airborne experiments, including processing the data of a C-band SAR system with four azimuth channels and an X-band DBF-SAR system with 16 elevation channels, have been implemented to validate the effectiveness of the proposed MoCo scheme. [ABSTRACT FROM AUTHOR]

Although the ruin probability in a renewal insurance risk model with credit interest may be viewed as a classical research problem, exact solutions are only available in the literature in very special cases when both the claim amounts and the interclaim times follow distributions such as the exponential. This is a long standing problem especially from a computational point of view, and the difficulty lies in the fact that the ruin probability usually satisfies a higher order integro-differential equation and/or an ordinary differential equation with non-constant coefficients. In this paper, for a large class of interclaim time distributions (including a combination of exponentials), we shall develop an approximation for the ruin probability using Laguerre series expansion as a function of the initial surplus level. It is shown that the (approximated) Laguerre coefficients can be solved from a system of linear equations, a procedure that is very easy to implement. A main advantage of our approach is that no specific distributional assumption on the claim amounts is required, apart from some mild differentiability and integrability conditions that can be verified. Numerical examples are provided to illustrate the very good performance of our approximation including both light-tailed and heavy-tailed claims. [ABSTRACT FROM AUTHOR]

Here, we investigate the two-parameter high-frequency localization for the eigenfunctions of a Schrödinger operator with a singular inverse square potential in high-dimensional balls and spherical shells as the azimuthal quantum number l and the principal quantum number k tend to infinity simultaneously, while keeping their ratio as a constant, generalizing the classical one-parameter localization for Laplacian eigenfunctions [B.-T. Nguyen and D. S. Grebenkov, SIAM J. Appl. Math. 73, 780–803 (2013)]. We prove that the eigenfunctions in balls are localized around an intermediate sphere whose radius is increasing with respect to the l–k ratio. The eigenfunctions decay exponentially inside the localized sphere and decay polynomially outside. Furthermore, we discover a novel phase transition for the eigenfunctions in spherical shells as the l–k ratio crosses a critical value. In the supercritical case, the eigenfunctions are localized around a sphere between the inner and outer boundaries of the spherical shell. In the critical case, the eigenfunctions are localized around the inner boundary. In the subcritical case, no localization could be observed, giving rise to localization breaking. [ABSTRACT FROM AUTHOR]

Recently most of the state-of-the-art semantic segmentation methods have focused on context modeling for more accurate prediction. As real-world images often contain multiple objects and stuff, image features may have complex and multi-modal distributions. However, existing methods do not fully consider sch complex distributions, having limited capability for context modeling. Towards addressing this problem, this paper proposes a second-order encoding network (SoENet) trainable end-to-end for harvesting complex contextual knowledge. At the core of SoENet is an encoding module which can capture second-order statistics in individual feature subspaces. Specifically, we divide the entire feature space into a set of subspaces (clusters) represented by codewords, in each of which a covariance matrix is computed for second-order statistical modeling. The covariance matrices of all subspaces are concatenated to form a 3D tensor, which is then subject to convolutions and nonlinear activations and finally used for scaling of input features. In this way, we can encode the context which involves the complex distribution into learning process in an end-to-end manner. The proposed SoENet is evaluated on four commonly used challenging benchmarks, i.e., PASCAL Context, PASCAL VOC 2012, ADE20K and Cityscapes. The experiments show that our network significantly outperforms its counterparts and is competitive compared to state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Arrhythmia is a kind of cardiovascular disease that seriously threats human health. Intelligent analysis of electrocardiogram (ECG) is an effective method for the early prevention and precise treatment to arrhythmia. In clinical ECG waveforms, it is common to see the multi-label phenomenon that one patient would be labeled with multiple types of arrhythmia. However, the current research is mainly to use the multiclass methods to solve the multi-label problem, ignoring the correlations between diseases and causing information loss. Therefore, this article aims: 1) to propose a multi-label feature selection method based on ECG (MS-ECG) and design an evaluation criterion of ECG features based on kernelized fuzzy rough sets so as to choose the optimal feature subset and optimize ECG feature space and 2) to propose the multi-label classification algorithm of arrhythmia based on ECG (MC-ECG) by establishing a multiobjective optimization model. This algorithm based on sparsity constraint explores the correlations between arrhythmia diseases and analyzes the mapping relationship between ECG features and arrhythmia diseases, so that one ECG signal would be automatically and accurately given multiple labels. Through sufficient experiments to prove the feasibility of our methods, we obtain the selected feature subset composed of 23 ECG features by MS-ECG. For the six evaluation criterions of MC-ECG, average precision is 0.8462, hamming loss is 0.1041, ranking loss is 0.1313, one-error is 0.2023, coverage is 0.4015, and micro-F1 is 0.6088. The outcome presents optimal to the current algorithms. [ABSTRACT FROM AUTHOR]

The variable two-step backward differentiation formula (BDF2) is revisited via a new theoretical framework using the positive semi-definiteness of BDF2 convolution kernels and a class of orthogonal convolution kernels. We prove that, if the adjacent time-step ratios rk := τk/τk-1 ≤ (3 + √17)/2 ≈ 3.561, the adaptive BDF2 time-stepping scheme for linear reaction-diffusion equations is unconditionally stable and (maybe, first-order) convergent in the L2norm. The second-order temporal convergence can be recovered if almost all of time-step ratios rk ≤ 1 + √2 or some high-order starting scheme is used. Specially, for linear dissipative diffusion problems, the stable BDF2 method preserves both the energy dissipation law (in the H1 seminorm) and the L2 norm monotonicity at the discrete levels. An example is included to support our analysis. [ABSTRACT FROM AUTHOR]

Consider a credit portfolio with the investments in various sectors and exposed to an external stochastic environment. The portfolio loss due to defaults is of critical importance for social and economic security particularly in times of financial distress. We argue that the dependences among obligors within sectors (intradependence) and across sectors (interdependence) may coexist and influence the portfolio loss. To quantify the portfolio loss, we develop a multi-sector structural model in which a multivariate regular variation structure is employed to model the intradependence within sectors, and the interdependence across sectors is implied in the arbitrarily dependent macroeconomic factors, although, given them, obligors in different sectors are conditionally independent. We establish some sharp asymptotic formulas for the tail probability and the (tail) distortion risk measures of the portfolio loss. Our results show that the portfolio loss is mainly driven by the latent variables and the recovery rate function, and is also potentially affected by the macroeconomic factors and the intradependence within sectors. Moreover, we implement intensive numerical studies to examine the accuracy of the obtained approximations and conduct some sensitivity analysis. [ABSTRACT FROM AUTHOR]

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration. [ABSTRACT FROM AUTHOR]

For the fabrication of curved microstructures, the fabrication fidelity is greatly affected by the nonlinear relationship between the gray levels of the digital micromirror device (DMD) and the exposure dose in DMD gray-scale lithography. In this study, a method is proposed for the high fidelity fabrication of curved microstructures using DMD based dynamical ultraviolet lithography. A target curved microstructure is mapped into multiple discretized exposure profiles to control DMD mirrors. By extracting the same rows in all the discretized exposure profiles and arranging all the extracted rows in sequence, binary frame images to be exposed are constructed and then combined into a dynamical digital mask. With the proposed method, the nonlinear modulation of the DMD in gray-scale lithography is replaced with a linear binary modulation; thus, the dynamical modulation range of the DMD has been improved. We demonstrate the effectiveness of the method by theoretically simulating and experimentally fabricating a curved microlens array, compared with DMD gray-scale lithography. The experimental results show that the fabrication deviation in the edge region of the fabricated curved microlens array has been effectively decreased. This method may have great potential for the precision and low-cost industrial production of curved microstructures. [ABSTRACT FROM AUTHOR]

• Proposing an extended process based on CEC - ECC. • Investigating the effect of backpressure on strain in the ECC process. • Effect of strain on recrystallization and tensile mechanical properties. The capability of a novel severe plastic deformation method for extrusion compression composite processing was investigated. Deform-3D software was used to study the effect of back pressure on the strain distribution of a workpiece by simulating the forming process with and without back pressure. The Mg-12.5Gd-4Y-2Zn-0.5Zr alloy was used to analyze the effect of strain on microstructure and mechanical properties. Results showed that back pressure led to the uniform strain distribution of the deformed workpiece and the decrease in the effective strain standard deviation from 0.73 to 0.68. With increasing strain, the grain size tended to decrease and then increase, contrary to the recrystallization rate trend. The tensile strength gradually increased with increasing strain, but the elongation change trend was changed due to the influence of the bimodal structure. [ABSTRACT FROM AUTHOR]

Suffusion refers to the process of fine particles carried away from a coarser soil matrix by seepage flow. Numerical simulations of coupled fluid–solid methods are wildly used in analyzing micro and macro behaviors of gap-graded soils during suffusion. However, the solid particles are usually simplified to spheres, resulting in inaccurate detachment, transmission and clogging mechanisms. In this study, the complex particle shape factor is taken into account in CFD–DEM. A series of numerical tests were conducted to explore the effects of aspect ratio both for fine and coarse particles. Macroscopic and microscopic information of suffusion process is obtained. Numerical results indicate that particle shape plays a significant role in suffusion. [ABSTRACT FROM AUTHOR]

In this work, a clamped-clamped boundary condition is considered for a family of bistable hybrid symmetric laminates in which the direction of curvature does not change during the snap-through process between the two stable configurations. The laminates were modeled using finite element analysis to predict the characteristics of stable configurations, including the distributions of curvatures and out-of-plane displacement in two directions, and then the results were validated by experiments. The snap-through behaviors of the bistable laminates under the clamped-clamped boundary condition were investigated numerically and experimentally and then compared with the preloaded laminates with the same boundary condition. The results showed that the bistable laminates require a lower snap-through load than the preloaded laminates when they have a similar maximum out-of-plane displacement. The loading position, lay-up design, and length of the clamped region were employed as variables to discover the features of snap-through behavior. It was found that the unsymmetric deformation mode was present regardless of the load position during the snap-through behavior of these bistable laminates. At last, a variable cross-section tube consisting of two bistable laminates was proposed, and the area of the cross-section could be increased by 80% after the snap-through of the two bistable laminates [ABSTRACT FROM AUTHOR]

The graphite floating ring is a key sealing element of the turbopump of aeroengines. Its wear induced by frequent flotation during its operation can result in stress concentration and microscopic cracks in its seal end face, more leakage from its sealing surface, a lower engine efficiency, and even serious safety concerns. However, there are currently no published studies regarding the modeling of the end face wear of the floating ring seal. This work presents a new fractal model for predicting the wear rate and wear evolution of the end face of the floating ring seal. Firstly, a new normal fractal contact model was implemented by microscopically considering the deformation mechanism, interaction forces, and flash points of the asperities on the end face of the floating ring. On this basis, a fractal model was built to predict the wear of the end face of the floating ring according to its wear mechanism and the corrected Archard theory. The wear rates predicted according to this model are in good agreement with the test results. The simulation results show that (i) the depth wear rate of the end face of the floating ring first decreases and then increases as the fractal dimension D increases (the minimum is reached when the fractal dimension ranges from 1.60 to 1.725); (ii) the depth wear rate of the end face of the floating ring increases as the characteristic scale G , friction factor f , floatation speed of the floating ring v , and end face pressure P increase; (iii) the impact of the end face pressure on the depth wear rate is minimum when the fractal dimension ranges from 1.60 to 1.65; (iv) the flotation displacement of the floating ring cannot exceed 12 μm when the engine speed is higher than 30,000 r/min. • Proposing a novel wear fractal prediction model for the graphite floating ring in aeroengines. • The wear tests verify the correctness of the wear fractal prediction model. • The physical properties of the asperities on the floating ring affect the prediction results of the wear model. • The effects of operating conditions and surface morphology on the floating ring's wear rate are predictable. [ABSTRACT FROM AUTHOR]

The assessment and prediction of regional water quality are fundamental inputs to environmental planning and watershed ecological management. This paper explored spatiotemporal changes in the correlation of water quality parameters (WQPs) and land-use types (LUTs) in a reticular river network area. Water samples of 44 sampling sites were collected every quarter from 2016 to 2018 and evaluated for dissolved oxygen (DO), total phosphorus (TP), ammonia nitrogen (NH3-N), and permanganate index (CODMn). A redundancy analysis (RDA) and stepwise multiple linear regression (SMLR) were applied to analyze the land-use type impacts on seasonal WQPs at five buffer scales (100, 200, 500, 800, and 1000 m). The Kruskal–Wallis test results revealed significant seasonal differences in NH3-N, TP, CODMn, and DO. The area percentages of farmland, water area and built-up land in the study area were 38.96%, 22.75% and16.20%, respectively, for a combined total area percentage of nearly 80%. Our study showed that orchard land had an especially favorable influence on WQPs. Land-use type impacts on WQPs were more significant during the dry season than the wet season. The total variation explained by LUTs regarding WQPs at the 1 km buffer scale was slightly stronger than at smaller buffer scales. Built-up land had a negative effect on WQPs, but orchard and forest-grassland had a positive effect on WQPs. The effects of water area and farmland on WQPs were complex on different buffer scales. These findings are helpful for improving regional water resource management and environmental planning. [ABSTRACT FROM AUTHOR]

In this paper we present a seven-velocity three-dimensional (D3N7) vectorial lattice Boltzmann method (LBM) including various types of approximations to the pressure and propose a family of two-parameterized second-order boundary schemes with accuracy independent of the boundary location. In order to show the numerical stability of the D3N7 model, we construct a symmetrizer to handle the nonlinear approximations to the pressure. In the meantime, we relate the stability based on the vectorial model to that based on the conventional scalar model through an orthogonal similarity transformation. Finally, two 3-D examples with straight and curved boundaries numerically validate the D3N7 model, including linear and nonlinear approximations to the pressure, together with the proposed boundary schemes. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA repair enzyme in the base excision repair pathway, has been pursued as an attractive cancer therapeutic target. Intervention with PARP-1 has been proved to be more sensitive to cancer cells carrying BRCA1/2 mutations. Several PARP-1 inhibitors have been available on market for the treatment of breast, ovarian and prostatic cancer. Promisingly, the newly developed proteolysis targeting chimaeras (PROTACs) may provide a more potential strategy based on the degradation of PARP-1. Here we report the design, synthesis, and evaluation of a proteolysis targeting chimaera (PROTAC) based on the combination of PARP-1 inhibitor olaparib and the CRBN (cereblon) ligand lenalidomide. In SW620 cells, our probe-quality degrader compound 2 effectively induced PARP-1 degradation which results in anti-proliferation, cells apoptosis, cell cycle arresting, and cancer cells migratory inhibition. Thus, our findings qualify a new chemical probe for PARP-1 knockdown. [ABSTRACT FROM AUTHOR]

Endometriosis (EM) is a common disease in women; however, the signaling pathways and related genes underlying the mechanisms of EM remain unclear. The present study aimed to investigate the role of angiotensin II receptor type 1 (AGTR1) in the pathogenesis of EM. Human EM tissues were collected, and the expression levels of AGTR1 and NF-κB in the tissues were analyzed using immunochemistry and western blotting, while the estrogen levels in the EM tissues were determined by ELISA. In vitro human endometrial stromal cells were used to investigate the expression levels of AGTR1 following exposure to estrogen; the interaction between AGTR1 and NF-κB was determined using reverse transcription-quantitative PCR and western blotting; and the effects of AGTR1 on cell proliferation, as well as the apoptotic and migratory abilities of the cells were evaluated using WST-1 assays, wound healing assays and flow cytometry, respectively. It was observed that both the expression levels of AGTR1 and the activity of NF-κB were increased in human EM tissues and stromal cells, and this activation of AGTR1 subsequently increased the activity of NF-κB. Moreover, estrogen was found to regulate the expression levels of AGTR1 in stromal cells. The activation of AGTR1 was demonstrated to promote cell proliferation and migration, in addition to preventing cells from undergoing apoptosis. In conclusion, the present study suggested that the increased activity of the AGTR1-NF-κB axis following the decreased exposure to estrogen may be important for the pathogenesis of EM. In addition, AGTR1 may be a potential therapeutic target for the treatment of EM. [ABSTRACT FROM AUTHOR]

Prunella vulgaris polysaccharides (PVPs) have a variety of biological activities, but the mechanism and extent of their anti-hyperlipidaemic effect remain unclear. In vitro, PVPs had a significant inhibitory effect on angiotensin (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. A metabolomics approach based on gas chromatography–mass spectrometry (GC–MS) and chemometrics was established in this study to evaluate the anti-hyperlipidaemic activity of PVPs in a high-fat Sprague-Dawley rat model. In vivo, PVPs could significantly reduce the weight gain and the increases in serum total cholesterol (TC), low-density lipoprotein (LDL)-C and non-high-density lipoprotein (HDL)-C levels observed in rats fed a high-fat diet; they could also significantly increase serum GSH-Px activity, reduce the content of MDA and TNF-α and decrease abdominal fat volume in rats. Furthermore, PVPs exerted a repairing effect on morphological and structural damage in liver tissue cells in hyperlipidaemic rats fed a high-fat diet. PVPs improved lipid metabolism disorder in rats. Alanine, threonine, succinic acid, proline, inositol and arachidonic acid levels in the serum were considered potential biomarkers involved in amino acid, glucose, energy and lipid metabolism. Therefore, PVPs may interfere with hyperlipidaemia through anti-lipid peroxidation effects, attenuation of inflammation and regulation of glucose, amino acid, energy and lipid metabolism. [ABSTRACT FROM AUTHOR]

Local superconvergence properties of the post-processed finite volume element method (FVEM) are studied. Some interpolation/extrapolation post-processing techniques are applied to a class of k th-order (k ≥ 2) FVE solutions for elliptic equations. A local analysis tool for the finite volume method is developed to analyze the proposed method, and some superconvergence results are established. The theoretical findings are supported by several numerical experiments. [ABSTRACT FROM AUTHOR]

Two novel Pb(II) coordination polymers: Pb(L)·H2O]n (I) and [Pb(L)·(4,4'-bipy)0.5]n (II) (H2L = N-3-pyridine sulfonyl amino succinic acid), were synthesized and characterized by FT-IR, elemental analysis, and single-crystal X-ray diffraction analysis. The results show that I crystallizes in orthorhombic system, Pbca space group, with a = 7.3492(7) Å, b = 15.4994(15) Å, c = 22.652(2) Å, α=β = γ = 90°, V = 2580.3(4) Å3; The II crystallizes in monoclinic system, P21/n space group, with a = 5.1885(7) Å, b = 19.7136(15) Å, c = 15.4593(11) Å, α = γ = 90°, β = 92.8330(10)°, V = 1579.3(3) Å3. Thermogravimetric analysis (TGA) indicated that I and II can maintain their structure at temperatures between 35∼234 °C and 35∼145 °C, respectively. The solid-state fluorescence of I and II showed that they had stronger fluorescence response than L. It can be seen that the introduction of ligands having aromatic rings can increase the fluorescence intensity of the polymer. [ABSTRACT FROM AUTHOR]

Background: Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT.Methods: This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5 years. The paired serum was collected before and after treatment and biomarkers were discovered by LNA-TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. Using the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively.Results: Using fold change≥2.0 or ≤ 0.5 and p ≤ 0.05 as cutoff levels, we identified 1 up-regulated and 6 down-regulated miRNAs, 1 up-regulated and 9 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After these down-regulated miRNAs were dealed with bioinformatics analysis and normalization, only 5 different miRNAs were significantly reduced, which there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT in the serum samples of 48 NPC patients. Based on this, we calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR = 3.149, 95%CI:1.018-9.115, p = 0.034), whereas combining the former two is independent for OS (HR = 5.146, 95%CI:1.674-15.817, p = 0.04).Conclusions: For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs, such as miRNA-29a, miRNA-125b and miRNA-26b etc., play an important role in predicting prognosis factors of PFS and OS, which will contribute to the strategic direction for future research. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance has become a hold back and major clinical challenge in osteosarcoma cancer. The alteration and subcellular distribution of apurinic/apyrimidinic endonuclease 1 (APE1) has been reported to be involved in chemotherapy resistance in many cancers. Here, we report that the cytoplasmic distribution of APE1 plays a key role in the sensitivity of combination platinum chemotherapy in osteosarcoma. Interestingly, the prevalence of cisplatin‐induced DNA damage and apoptosis in low cytoplasmic APE1 osteosarcoma cell lines was higher than in high expression of cytoplasmic APE1 cell lines. Overexpression of cytoplasmic APE1 protected the osteosarcoma cells from CDDP‐induced apoptosis. In addition, clinical data also show that the level of cytoplasmic APE1 was negatively associated with sensitivity to combination chemotherapy of cisplatin in osteosarcoma patients. Our findings suggest that cytoplasmic APE1 plays a significant role in chemotherapy resistance. This role is a supplement to the extranuclear function of APE1, and cytoplasmic APE1 expression level could be a promising predictor of platinum treatment prognosis for osteosarcoma patients. [ABSTRACT FROM AUTHOR]

The bromodomain and extra-terminal (BET) bromodomains, particularly BRD4, have been identified as promising therapeutic targets in the treatment of many human disorders such as cancer, inflammation, obesity, and cardiovascular disease. Recently, the discovery of novel BRD4 inhibitors has garnered substantial interest. Starting from scaffold hopping of the reported compound dihydroquinazolinone (PFI-1), a series of coumarin derivatives were designed and synthesised as a new chemotype of BRD4 inhibitors. Interestingly, the representative compounds 13 exhibited potent BRD4 binding affinity and cell proliferation inhibitory activity, and especially displayed a favourable PK profile with high oral bioavailability (F = 49.38%) and metabolic stability (T1/2 = 4.2 h), meaningfully making it as a promising lead compound for further drug development. [ABSTRACT FROM AUTHOR]

Image scanning microscopy based on pixel reassignment can improve the confocal resolution limit without losing the image signal-to-noise ratio (SNR) greatly [C. J. R. Sheppard, "Super-resolution in confocal imaging," Optik80(2) 53–54 (1988). C. B. Müller, E. Jörg, "Image scanning microscopy, "Phys. Rev. Lett.104(19) 198101 (2010). C. J. R. Sheppard, S. B. Mehta, R. Heintzmann, "Superresolution by image scanning microscopy using pixel reassignment," Opt. Lett.38(15) 2889–2892 (2013)]. Here, we use a tailor-made optical fiber and 19 avalanche photodiodes (APDs) as parallel detectors to upgrade our existing confocal microscopy, termed as parallel-detection super-resolution (PDSR) microscopy. In order to obtain the correct shift value, we use the normalized 2D cross correlation to calculate the shifting value of each image. We characterized our system performance by imaging fluorescence beads and applied this system to observing the 3D structure of biological specimen. [ABSTRACT FROM AUTHOR]

Abstract Recently, more and more actuarial researchers have paid attention to valuing life insurance products. In this paper, we study the valuation of equity-linked annuity contracts with guaranteed minimum death benefits (GMDB). The discounted density function approach is used to value this class of life insurance products. We develop the density function of the time-until-death variable on the Laguerre basis and value the GMDB contracts with various equity-linked death benefit functions, including basic options and lookback options. Compared to the Laplace inversion transform method in the literature, our method exhibits remarkable accuracy and efficiency. We also implement life table data to fit the density function of the time-until-death variable by Laguerre functions and provide numerical results for some death benefit functions. [ABSTRACT FROM AUTHOR]

• We synthesized up-conversion nanomaterial β-NaYF4:Yb/Er@SiO2@RB. • UCNPs can generate reactive oxygen species(ROS) with noninvasive light irradiation. • UCNPs can convert the secondary-structure of peptide and degrade amyloid fibrils. Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive and memory function impairment. Studies have shown that the overproduction and further misfolding of amyloid polypeptide (Aβ) are the main causes of AD. Therefore, how to reduce Aβ species, especially to disassemble the preformed amyloid aggregates, has become the focus of related research. Photodynamic therapy (PDT) using normal photosensitizers eg. porphyrins, is a traditional way of inhibiting amyloid aggregation or degrading the amyloid aggregates, but UV light irradiation presents a side effect for the damage of normal tissue, which limits its medical application. Upconversion nanoparticles (UCNPs) is a luminous material which can be modified by photodynamic agent to form the complex generating reactive oxygen species (ROS) with noninvasive light irradiation. It presents a good advantage in the disassembly of amyloid aggregates via ROS in noninvasive light irradiation. Herein, we prepared β-NaYF 4 :Yb/Er@SiO 2 @RB by combing UCNPs with photosensitizer to disassemble preformed Aβ aggregates under near-infrared light. The results displayed upconversion nanomaterials could degrade Aβ1–42 fibrils effectively by photo-generating ROS, which demonstrated that the functional UCNPs may have potential applications in the treatment of amyloid diseases in future. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) have been widely used in photocatalytic hydrogen peroxide (H2O2) production due to their favorable band structure and excellent light absorption. Due to the rapid recombination rate of charge carriers, however, their applications are mainly restricted. This study presents the design and development of two highly conjugated triazine-based COFs (TBP-COF and TTP-COF) and evaluates their photocatalytic H2O2 production performance. The nitrogen-rich structures and high degrees of conjugation of TBP-COF and TTP-COF facilitate improved light absorption, promote O2 adsorption, enhance their redox power, and enable the efficient separation and transfer of photogenerated charge carriers. There is thus an increase in the photocatalytic activity for the production of H2O2. When exposed to 10 W LED visible light irradiation at a wavelength of 420 nm, the pyridine-based TTP-COF produced 4244 μmol h−1 g−1 of H2O2 from pure water in the absence of a sacrificial agent. Compared to TBP-COF (1882 μmol h−1 g−1), which has a similar structure but lacks pyridine sites, TTP-COF demonstrated nearly 2.5 times greater efficiency. Furthermore, it exhibited superior performance compared to most previously published nonmetal COF-based photocatalysts. [ABSTRACT FROM AUTHOR]

This paper focuses on the valuation of variable annuities with a guaranteed minimum maturity benefit under a regime-switching Lévy model. The model allows policyholders to surrender their annuities and receive a surrender benefit at predetermined tenor times before maturity. Additionally, we consider a state-dependent periodic fee structure where fees are deducted from the policyholder's account if it exceeds a certain level at discrete time points. Incorporating this fee structure, the Fourier cosine series expansion method based on characteristic functions is employed to determine the values and optimal surrender strategies for variable annuity contracts. Finally, we provide a comprehensive set of numerical examples to demonstrate and assess the effectiveness of our approach thoroughly. [ABSTRACT FROM AUTHOR]