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Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.Fat1cadherin was conditionally deleted in murine hematopoietic stem cells, and while FAT1 is frequently overexpressed in acute leukemias, no major perturbation of normal hematopoiesis was observed.

Styrene-butadiene rubber (SBR) is an indispensable material in modern society, and the necessity for enhanced mechanical properties in SBR persists, particularly to withstand the rigors of challenging environmental conditions. To surmount the limitations of conventional cross-linking modes, mechanical bonds stabilized by host-guest recognition are incorporated as the cross-linking points of SBR to form mechanically interlocked networks (MINs). Compared with covalently cross-linked network, the representative MIN exhibits superior mechanical performance in terms of elongation (1392%) and breaking strength (4.6 MPa), whose toughness has surged by 17 times. Dissociation of host-guest recognition and subsequent sliding motion provide an effective energy dissipation mechanism, and the release of hidden length is also beneficial to enhance toughness. Furthermore, the introduction of the rotaxane cross-links made the network more pliable and possess damping and elastic properties, which can return to initial state with one minute rest interval. We aspire that this direct introduction method can serve as a blueprint, offering valuable insights for the enhancement of mechanical properties in conventional commercial polymer materials.

As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins (GPs), have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of EBOV-like vesicles (eVLVs) incorporating both EBOV GP and VP40. The eVLVs exhibited similar antigenicity as EBOV. In murine models, eVLVs were highly attenuated and elicited robust GP-specific antibodies with neutralizing activities. Importantly, a single dose of eVLVs conferred complete protection in a surrogate EBOV lethal mouse model. Furthermore, our VLVs strategy was also successfully applied to Marburg virus (MARV), the representative member of the genus Marburgvirus. Taken together, our findings indicate the feasibility of an alphavirus-derived VLVs strategy in combating infection of filoviruses represented by EBOV and MARV, which provides further evidence of the potential of this platform for universal live-attenuated vaccine development.

The transient electromagnetic interference in practical existing engineering have measuring testability limitation. This limitation makes it difficult to assess electromagnetic effect. A multidimensional physical information based assessment method via physics-informed neural network (PINN) and Gaussian process regression (GPR) is proposed in this article. First, the physical topology of the disturbed equipment under electromagnetic interference is analyzed, and the partial differential equation of the space electric field is derived from the measurable electric quantity. Then, the electric field near the disturbed equipment is predicted by PINN which can characterize the physical information. Finally, combining calculated electric field data and measured magnetic field data, a two-dimensional GPR regression is used to assess the electromagnetic effect with multiple inputs and outputs, and the probabilities under each state are then calculated based on the assessed state. Expanded verification is conducted by combining different electromagnetic complexity calculation methods, proving the applicability and effectiveness of the proposed assessment model.

Classifying patterns of known classes and rejecting ambiguous and novel (also called as out-of-distribution (OOD)) inputs are involved in open world pattern recognition. Deep neural network models usually excel in closed-set classification while perform poorly in rejecting OOD inputs. To tackle this problem, numerous methods have been designed to perform open set recognition (OSR) or OOD rejection/detection tasks. Previous methods mostly take post-training score transformation or hybrid models to ensure low scores on OOD inputs while separating known classes. In this paper, we attempt to build a unified framework for building open set classifiers for both classification and OOD rejection. We formulate the open set recognition of K-known-class as a (K+1)-class classification problem with model trained on known-class samples only. By decomposing the K-class problem into Kone-versus-all (OVA) binary classification tasks and binding some parameters, we show that combining the scores of OVA classifiers can give (K+1)-class posterior probabilities, which enables classification and OOD rejection in a unified framework. To maintain the closed-set classification accuracy of the OVA trained classifier, we propose a hybrid training strategy combining OVA loss and multi-class cross-entropy loss. We implement the OVA framework and hybrid training strategy on the recently proposed convolutional prototype network and prototype classifier on vision transformer (ViT) backbone. Experiments on popular OSR and OOD detection datasets demonstrate that the proposed framework, using a single multi-class classifier, yields competitive performance in closed-set classification, OOD detection, and misclassification detection. The code is available at https://github.com/zhen-cheng121/CPN_OVA_unified.

Medium-chain chlorinated paraffins (MCCPs, C14–C17) are frequently detected in diverse environmental media. It has been proposed to be listed in Annex A of the Convention on Persistent Organic Pollutants in 2023. Although MCCPs are a crucial health concern, their toxicity remains unclear. This study investigated the toxic effects of MCCPs (0.1–50 mg/kg body weight/day) on the thyroid gland of female Sprague–Dawley rats and characterized the potential toxic pathways via transcriptomics and metabolomics approaches. MCCPs exposure caused histopathological changes to the endoplasmic reticula and mitochondria in thyroid follicular cells at a dose of 50 mg/kg bw/d and increased serum thyrotropin-releasing hormone, thyroid-stimulating hormones, and thyroxine when exposed to a higher dose of MCCPs. Transcriptomic analysis indicated the excessive expression of key genes related to thyroid hormone synthesis induced by MCCPs. Integrating the dual-omics analysis revealed mitochondrial dysfunction of the thyroid by mediating fatty acid oxidation, Kreb’s cycle, and oxidative phosphorylation. Significant metabolic toxicity on the thyroid might be linked to the characteristics of the chlorine content of MCCPs. This study revealed the toxicity of MCCPs to the thyroid gland via triggering thyroid hormone synthesis and interfering with mitochondrial function, which can provide new insights into the modes of action and mechanism-based risk assessment of MCCPs.

The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test.

Accurate 3-D force sensing technology plays a crucial role in monitoring the electromechanical signals of the manipulator. Despite the design of various flexible capacitive 3-D force sensors, their sensitivity often fails to meet the requirements for monitoring manipulators effectively. To address this issue, this work has designed an ionic flexible capacitive 3-D force sensor with pyramidal microstructure. This sensor relies on the mechanical deformation of the pyramidal microstructure and the coupling of the capacitive effect of the electric double layer to output sensing information. The sensitivity of this sensor can reach 38.3 kPa $^{-{1}}$ , and it has a fast response time (62 ms), excellent hysteresis, and repeatability. With the application of backpropagation neural network (BPNN), the accuracy of decoupling can be optimized, resulting in the error being reduced to $10^{-{3}}$ . The sensors have the ability to monitor electromechanical signals that can help the manipulator identify the topographic features of a target object, as well as monitor the gripping force of the manipulator and whether the target object is sliding. This unique 3-D force sensor provides novel ideas for the design of new multidimensional force sensors, paving the way for the development of human-computer interaction and wearable devices.

A 100-MHz high-efficiency cross-coupled stacked rectifier in an isolated power transfer system is presented. The proposed rectifier utilizes stacked MOSFETs and employs cross-coupled structures to reduce conduction loss. To enhance power conversion efficiency, DC voltage biasing is applied to all NMOS and PMOS gate voltages. Moreover, the cross-coupled stacked rectifier enables a swift shutdown when the transmitter side stop oscillating, thereby improving overall system efficiency. The proposed cross-coupled stacked rectifier is fabricated in a 180-nm BCD process using 5-V devices and 1.8-V devices. Measurement results demonstrate that peak PCE reaches to 63.3% at 0.8 W output power in the isolated power transfer system.

The formation of holes in epithelial tissue is essential for development, but it can also be associated with epithelial barrier dysfunction and cancer progression. Here we show that active cell contraction in epithelioid monolayer tissues derived from human embryonic stem cells can spontaneously launch a morphological transition cascade consisting of hole nucleation, coalescence and network formation. Accumulated tissue-level tensile stresses drive hole expansion from isotropic round expansion to local fracture of intercellular junctions. This is followed by fast crack propagation, which is later suppressed by the self-organized supracellular actomyosin ring and accompanied by crack blunting and a fracture-to-rounding transition. During hole coalescence, we find a fracture–slip mechanism that enables layer-by-layer breaking of the multicellular bridge but without inducing excessive cell deformation. Our multiscale theory captures these experimental observations and predicts that substrate rigidity sensing and adhesion of cells compete with cellular contraction to mediate the morphological dynamics. These findings suggest that living tissues may coordinate the mechanics across molecular, cellular and tissue scales to drive topological changes while reducing the risk of mechanical damage to cells.

In recent years, analog circuits have received extensive attention and are widely used in many emerging applications. The high demand for analog circuits necessitates shorter circuit design cycles. To achieve the desired performance and specifications, various geometrical symmetry constraints must be carefully considered during the analog layout process. However, the manual labeling of these constraints by experienced analog engineers is a laborious and time-consuming process. To handle the costly runtime issue, we propose a graph-based learning framework to automatically extract symmetric constraints in analog circuit layout. The proposed framework leverages the connection characteristics of circuits and the devices’ information to learn the general rules of symmetric constraints, which effectively facilitates the extraction of device-level constraints on circuit netlists. The experimental results demonstrate that compared to state-of-the-art symmetric constraint detection approaches, our framework achieves higher accuracy and F1-score.

This brief presents a low-power multi-channel analog front-end (AFE) for bio-potential recording. Time-division-multiplexing (TDM) technique is used to save chip area by sharing one ADC among multiple recording channels. To reduce the power consumption brought by additional ADC drivers, buffers are only turned on while connected to the ADC. The chip is implemented in a 65 nm CMOS process. The AFE consumes 29 $\mu \text{W}$ under 1 V supply. Measurement results show that the AFE achieved an input referred noise of 1.34 $\mu $ Vrms in a 350 Hz bandwidth and a NEF of 3.58 for the analog recording chain. The analog signals of all channels are converted to digital code at 20 kS/s by a 12-bit SAR ADC with 66.1 dB SNDR. The AFE chip is experimented by measuring human ECG.

Bottle-brush polymers possessing densely grafted side chains have special properties that are distinct from linear macromolecules. Herein, an efficient method for preparing bottle-brush polymers based on a selective photoactivation strategy in the photoinduced electron/energy transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization was developed. A methacrylate monomer 2-(2-(dodecylthiocarbonothioylthio)propionate)ethyl methacrylate (DTPEMA) containing a 2-(dodecylthiocarbonothioylthio)propionate (DTP) unit with a secondary R group was designed. Utilizing the unique selectivity of metal naphthalocyanine photocatalyst zinc 2,11,20,29-tetra-tert-butyl-2,3-naphthalocyanine (ZnTtBNc) toward trithiocarbonate with tertiary R group, the PET-RAFT polymerization of DTPEMA catalyzed by ZnTtBNc was performed under near infrared (NIR) light (λmax= 760 nm) irradiation at room temperature, using 4-cyano-4-[(dodecylsulfanylthiocarbonyl)-sulfanyl] pentanoic acid (CDTPA) with a tertiary R group as a chain transfer agent (CTA). Proton nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC) results demonstrated that the DTP units in the side chains were inert during the polymerization. By grafting poly(methyl acrylate) (PMA) from PDTPEMA viathermal-initiated RAFT polymerization, well-defined P(DTPEMA-g-PMA) bottle-brush polymers could be afforded. Furthermore, the film prepared from the bottle-brush polymer exhibited excellent scratch self-healing property due to the interlocking of side chains.

This paper constructs a coupled aero-hydro-elastic-servo simulation framework for a monopile offshore wind turbine (OWT). In this framework, a detailed multi-body dynamics model of the monopile OWT including the gearbox, blades, tower and other components (nacelle, hub, bedplate, etc.) has been explicitly established. The effects of pile–soil interaction, controller and operational conditions on the turbine dynamic responses are studied systematically in time domain and frequency domain. The results show that (1) a comprehensive drivetrain model has the capability to provide a more precise representation of the complex dynamic characteristics exhibited by drivetrain components, which can be used as the basis for further study on the dynamic characteristics of the drivetrain. (2) The pile–soil interaction can influence the wind turbine dynamic responses, particularly under the parked condition. (3) The effect of the pile–soil interaction on tower responses is more significant than that on blade responses. (4) The use of the controller can substantially affect the rotor characteristics, which in turn influences the turbine dynamic responses. (5) The tower and blade displacements under the operational condition are much larger than those under the parked condition. The model and methodology presented in this study demonstrate potential for examining complex dynamic behaviors of the monopile OWTs. To ensure accuracy and precision, it is imperative to construct a detailed model of the wind turbine system, while also taking into account simulation efficiency.

The FRC algorithm is a commonly employed technique in LCD displays, aimed at enhancing the data bit depth through pixel dithering. However, it can also give rise to certain display issues such as noise, scrolling stripes, and flickering [1]. To address these problems comprehensively, this paper conducts an analysis from both temporal and spatial dimensions. It reveals that screen noise is closely associated with the uniformity of pixel data distribution throughout the entire FRC cycle time, while rolling stripes are linked to the spatial distribution of pixel data in both row and column directions. Furthermore, flickering arises due to variations in the number of FRC pattern pixels actually displayed per frame. The validity of these theories has been verified on an FPGA platform.

The effects of deoxidation methods on the inclusion characteristics and corrosion behaviour of high-strength low-alloy steels were examined in marine environments using various microcharacterisation techniques and first-principles calculations. After Ca treatment, MnS–MgO–Al2O3inclusions were modified to CaS–MgO–Al2O3and microcrevices were existed at the interface between inclusions and Fe. After Zr–Ti-RE deoxidation, spherical CaS + TiN + ZrO2+MgAl2O4+(Ca, La) Al3O7inclusions appeared. (Ca, La)Al3O7in steel displayed similar mechanical properties to Fe, reducing the degree of lattice distortion and the formation of microcrevices around the inclusions. Micro-galvanic corrosion between Fe and MnS accelerated the localised corrosion rate and promoted the formation of large pits on the surface. However, the chemical activity of CaS resulted in dissolution of the inclusion, which relatively inhibited the localised corrosion propagation. The enrichment of Cr in the rust layer after Zr–Ti-RE deoxidation improved the compactness, contributed to a reduction in the localised corrosion rate and long-term corrosion rate. Finally, the underlying mechanism influencing corrosion behaviour was established.

ABSTRACTIn this paper, we propose a method of route optimization of vacant taxicab based on the abstract grid network. Firstly, an abstract grid network is built by the quadtree technology with the vacant trajectory data embedded. Secondly, the Markov decision process framework considering the sequential dependence is used to model the problem. Finally, we solve this problem by the policy iteration and compare the method by taking the GPS trajectory data in different hours of 797 taxicabs in a typical working day in Shenzhen, comparing that with the optimal strategy without considering sequential dependence, MNP, local hotspot and random walk algorithm by simulation, respectively. The results show that: The use of quadtree can reduce the sparseness of matching probability from 80.46% to 30.18%. The average revenue per unit distance has increased by 6.10%, 8.75%, 33.24% and 60.06%. The vacant driving rate has decreased by 5.33%, 6.15%, 18.86%, and 23.18%.

The FRC algorithm is a commonly employed technique in LCD displays, aimed at enhancing the data bit depth through pixel dithering. However, it can also give rise to certain display issues such as noise, scrolling stripes, and flickering [1]. To address these problems comprehensively, this paper conducts an analysis from both temporal and spatial dimensions. It reveals that screen noise is closely associated with the uniformity of pixel data distribution throughout the entire FRC cycle time, while rolling stripes are linked to the spatial distribution of pixel data in both row and column directions. Furthermore, flickering arises due to variations in the number of FRC pattern pixels actually displayed per frame. The validity of these theories has been verified on an FPGA platform.

A mild, facile, and metal-free approach via the N-heterocyclic carbene-catalyzed SNAr reaction between aryl aldehydes with perfluoroarenes to obtain the coveted functional perfluorinated diarylmethanones is disclosed. This method accommodates a diverse substrate range and exhibits notable tolerance toward various functional groups. Our success in modifying biologically relevant molecules, crafting a fully fluorinated bioisosteric analogue of drug candidate D1, and highlighting the potential of these ketones as valuable electrolyte additives for lithium-ion batteries (LIBs) underscores the versatility of our methodology.

A one-pot, sequential three-component reaction between salicylaldehyde, indole, and 2-bromoprop-2-ene-1-sulfonyl fluoride (BPESF) has been demonstrated for the synthesis of sulfonyl fluoride substituted 4H-chromene derivatives in moderate to excellent yields (45%–94%). This one-pot sequential method features easily available starting materials, wide substrate scope, mild conditions, and great efficiency.

Based on the five main activation mechanisms, this study explored the potential activating elements in Al-based sacrificial anodes (SAs) combining electrochemical experiments and theoretical calculation. Mn, Y, Zr, Nb, and Ta, aligning with several activation mechanisms, are expected to be the potential activating elements besides the acknowledged activating elements (In, Sn, Ga, Zn, Bi). In addition, the negative shift of potential effect of In to Al matrix is denied both experimentally and theoretically. This study will contribute to establish a comprehensive understanding for the development of Al SAs.

•Infection with drug-resistant bacteria decreased IMI and MEM PK/PD target attainment.•IMI concentration was associated with the ICU stay.•MEM concentration was not associated with ICU stay but associated with effectiveness.•Elevated doses of IMI and MEM should be given to patients with drug-resistant bacteria infection.

Encapsulating enzymes within metal–organic frameworks has enhanced their structural stability and interface tunability for catalysis. However, the small apertures of the frameworks restrict their effectiveness to small organic molecules. Herein, we present a green strategy directed by visible linker micelles for the aqueous synthesis of MAF-6 that enables enzymes for the catalytic asymmetric synthesis of chiral molecules. Due to the large pore aperture (7.6 Å), double the aperture size of benchmark ZIF-8 (3.4 Å), MAF-6 allows encapsulated enzyme BCL to access larger substrates and do so faster. Through the optimization of surfactants’ effect during synthesis, BCL@MAF-6-SDS (SDS = sodium dodecyl sulfate) displayed a catalytic efficiency (Kcat/Km) that was 420 times greater than that of BCL@ZIF-8. This biocomposite efficiently catalyzed the synthesis of drug precursor molecules with 94–99% enantioselectivity and nearly quantitative yields. These findings represent a deeper understanding of de novo synthetic encapsulation of enzyme in MOFs, thereby unfolding the great potential of enzyme@MAF catalysts for asymmetric synthesis of organics and pharmaceuticals.

ABSTRACTTravel times in real-world transportation networks are affected by many disruptions. When we conduct the network design optimization, the traffic condition and its resulting travel time variability should be taken into account. However, most of the previous network design optimizations adopted the lengths or expected travel times of links. Based on travel time means and standard deviations, we develop an arc-based model that is a nonlinear and concave integer program. By the Dantzig-Wolfe reformulation, we transform it into an equivalent column-based model that is an integer linear program with a large number of variables. Based on the column-based model, we develop a hybrid method based on column generation and Lagrangian relaxation. The restricted master problem can be settled by the linear programming solvers. The pricing subproblems incorporate independent reliable shortest path problems and a knapsack problem. In numerical experiments, the proposed method can generate feasible solutions with good integrality gaps.

This article focuses on the average-tracking control issue for heterogeneous linear multiagent systems via a fixed-time approach. The agents, with varied dynamics and state dimensions, are subject to external disturbances and each has a unique reference signal that cannot be accessed by the other agents. In this setting, each agent is provided a multiple reference signal state compensator in order to estimate the states of all reference signals. Furthermore, external disturbances are estimated using a fixed-time sliding mode disturbance observer. An anti-disturbance control protocol is proposed by combining the disturbance observer and the state compensator for agents to track the average value of reference signals within a fixed time, which is predetermined and independent of initial states. The efficiency of the suggested average-tracking control mechanism is shown by numerical experiments.

The terminal guidance problem considering nonlinearity, optimality, and impact angle constraints is investigated. First, the conditions for optimal guidance in the longitudinal plane are derived based on the Pontryagin's maximum principle, and then the to-be-solved two-point boundary value problem is equivalent to a backward integration problem. Then, analytical boundaries are given to initialize the states for backward integration. Based on the easily accessible dataset, a neural network is trained to approximate the optimal guidance commands. Lastly, an optimal terminal guidance scheme combined with the neural network and a biased proportional navigation guidance is proposed. Compared with the existing terminal guidance methods, the proposed guidance strategy balances the performances about flight optimality, on-board implementation capability, and impact angle satisfaction when high dynamical nonlinearity is considered. Simulations are given to validate the effectiveness of the proposed techniques, and demonstrate the advantages of the algorithm on optimality, real-time performance, and impact angle satisfaction in nonlinear cases.