Search

This article presents a multi-robot trajectory planning method which not only guarantees optimization feasibility and but also resolves deadlocks in obstacle-dense environments. The method is proposed via formulating a recursive optimization problem, where a novel safe corridor is generated online to ensure obstacle avoidance in trajectory planning. A dynamic-priority mechanism is combined with the right-hand rule to handle potential deadlocks that are much harder to resolve due to static obstacles. Comparisons with other state-of-the-art results are conducted to validate the improved safety and success rate. Additional hardware experiments are carried out with up to eight nano-quadrotors in various cluttered scenarios.

Recently, the application of deep convolutional neural networks (DCNN) in underwater acoustic communication has become a growing research hotspot. However, it is hindered by the large amounts of training data required to achieve a complex communication system. In this paper, we propose a novel approach of combining variational mode decomposition (VMD) and DCNN networks to address this issue. Considering filter-bank multicarrier (FBMC) technologies offer promising performance in terms of spectral efficiency and robustness to interference, and the Bellhop model is also capable of providing effective and accurate communication data, this study adopts FBMC technologies for signal modulation and Bellhop models for communication data. The results show that the VMD-DCNN equalizer has a lower BER compared with the other seven contrast methods, thus further promoting the application and development of VMD-DCNN technologies in underwater acoustic communications.

Chongqing is a mountain city in western China, with complex geological environment, which brings many difficulties to the construction of large section underground projects. The construction experience of a large number of underground projects shows that ordinary engineering geological survey is difficult to meet the requirement of engineering design and construction. Therefore, on the basis of the initial survey, intensive drilling and coring work were carried out for the engineering area of the Guobo underground station with large cross-section to be built, and the basic mechanical, softening properties of the surrounding rock and in-situ stress field of the project area are obtained by laboratory tests. Based on the present experimental results and engineering experiences, it is proposed that the potential risks of Guobo station excavation include: ①bias pressure;②High in-situ stress;③Surrounding rock deterioration. The present study has practical significance for the design and construction of Guobo underground station, and it has certain reference value for the construction of underground projects in similar geological areas.

Genetic code expansion technology allows for the use of noncanonical amino acids (ncAAs) to create semisynthetic organisms for both biochemical and biomedical applications. However, exogenous feeding of chemically synthesized ncAAs at high concentrations is required to compensate for the inefficient cellular uptake and incorporation of these components into proteins, especially in the case of eukaryotic cells and multicellular organisms. To generate organisms capable of autonomously biosynthesizing an ncAA and incorporating it into proteins, we have engineered a metabolic pathway for the synthesis of O-methyltyrosine (OMeY). Specifically, we endowed organisms with a marformycins biosynthetic pathway-derived methyltransferase that efficiently converts tyrosine to OMeY in the presence of the co-factor S-adenosylmethionine. The resulting cells can produce and site-specifically incorporate OMeY into proteins at much higher levels than cells exogenously fed OMeY. To understand the structural basis for the substrate selectivity of the transferase, we solved the X-ray crystal structures of the ligand-free and tyrosine-bound enzymes. Most importantly, we have extended this OMeY biosynthetic system to both mammalian cells and the zebrafish model to enhance the utility of genetic code expansion. The creation of autonomous eukaryotes using a 21st amino acid will make genetic code expansion technology more applicable to multicellular organisms, providing valuable vertebrate models for biological and biomedical research.

Electromagnetic vibroseis is an important seismic wave excitation device. At present, the research of electromagnetic vibroseis mainly focuses on application and prototype design, lacking research on electromagnetic-mechanical coupling. Analyzing the electromagnetic-mechanical coupling and optimizing the air gap magnetic field is of great significance to improve the excitation quality of low-frequency seismic waves. In this paper, the electromagnetic-mechanical coupling is analyzed by studying the parameter force factor, and two novel optimal designs of the air gap magnetic field are proposed. Firstly, the finite element model of the air gap magnetic field is established, and the influence of the force factor distribution curve on the vibration signal is analyzed by using the Gaussian function and parameter spline difference method. Further, an asymmetrical axial dual-magnet design is proposed to enhance the radial magnetic induction intensity B r in the air gap. The design of adding a radial magnet to the outer yoke is proposed to compensate for the nonlinearity of the B r in the air gap. The simulation results show that the asymmetric axial dual-magnet structure increases the B r by 22.2% compared with the axial single-magnet structure. Adding a radial magnet to the outer yoke reduces the amplitude ratio of the third harmonic to the fundamental wave from 23.24% to 4.66%. It is necessary to consider the influence of the height of the driving coils on the maximum displacement, force factor distribution curve, and harmonic distortion.

Incorporation of noncanonical amino acids (ncAAs) into proteins holds great promise for modulating the structure and function of those proteins and for influencing evolutionary dynamics in organisms. Despite significant progress in improving the efficiency of translational machinery needed for incorporating ncAAs, exogenous feeding of high concentrations of chemically-synthesized ncAAs, especially in the case of polar ncAAs, is required to ensure adequate intracellular ncAA levels. Here, we report the creation of autonomous cells, both prokaryotic and eukaryotic, with the ability to biosynthesize and genetically encode sulfotyrosine (sTyr), an important protein post-translational modification with low membrane permeability. We discovered the first enzyme catalyzing tyrosine sulfation, sulfotransferase 1C1 from Nipponia nippon (NnSULT1C1), using a sequence similarity network (SSN). The unique specificity of NnSULT1C1 for tyrosine has been systematically explored using both bioinformatics and computational methods. This NnSULT1C1 was introduced into both bacterial and mammalian cells so as to yield organisms capable of biosynthesizing high levels of intracellular sTyr. These engineered cells produced site-specifically sulfated proteins at a higher yield than cells fed exogenously even with the highest level of sTyr reported in literature. We have used these autonomous cells to prepare highly potent thrombin inhibitors with site-specific sulfation. By enhancing ncAA incorporation efficiency, this added ability of cells to biosynthesize ncAAs and genetically incorporate them into proteins greatly extends the utility of genetic code expansion methods.TOC

Photoactivatable fluorophores are emerging optical probes for biological applications. Most photoactivatable fluorophores are relatively large in size and need to be activated by ultraviolet light; this dramatically limits their applications. To introduce photoactivatable fluorophores into proteins, recent investigations have explored several protein-labeling technologies, including fluorescein arsenical hairpin (FlAsH) Tag, HaloTag labeling, SNAPTag labeling, and other bioorthogonal chemistry-based methods. However, these technologies require a multistep labeling process. Here, by using genetic code expansion and a single sulfur-for-oxygen atom replacement within an existing fluorescent amino acid, we have site-specifically incorporated the photoactivatable fluorescent amino acid thioacridonylalanine (SAcd) into proteins in a single step. Moreover, upon exposure to visible light, SAcd can be efficiently desulfurized to its oxo derivatives, thus restoring the strong fluorescence of labeled proteins.

While most organisms utilize 20 canonical amino acid building blocks for protein synthesis, adding additional candidates to the amino acid repertoire can greatly facilitate the investigation and manipulation of protein structures and functions. In this study, we report the generation of completely autonomous organisms with a 21st ncAA, 5-hydroxytryptophan (5HTP). Like 20 canonical amino acids, 5-hydroxytryptophan can be biosynthesized in vivo from simple carbon sources and is subsequently incorporated into proteins in response to the amber stop codon. Using this unnatural organism, we have prepared a single-chain immunoglobulin variable fragment conjugated with a fluorophore and demonstrated the utility of these autonomous cells to monitor oxidative stress. Creation of this and other cells containing the 21st amino acid will provide an opportunity to generate proteins and organisms with novel activities, as well as to determine the evolutionary consequences of using additional amino acid buildings.

Therapeutic antibodies have gone a long way toward realizing their clinical potential and have become very useful for treating a variety of pathologies. Despite the rapid evolution of therapeutic antibodies, their clinical efficacy in treatment of bone tumors has been hampered by the inadequate pharmacokinetics and poor bone tissue accessibility of these large macromolecules. Here, we show that engineering therapeutic antibodies to include bone-homing peptide sequences dramatically enhances their concentration in the bone metastatic niche, resulting in significantly reduced survival and progression of breast cancer bone metastases. To enhance the bone tumor-targeting ability of engineered antibodies, we introduced varying numbers of a bone-homing peptide into permissive internal sites of the anti-HER2 antibody trastuzumab. Compared to the unmodified antibody, the engineered bone-targeting antibodies have similar pharmacokinetics andin vitrocytotoxic activity against HER2-positive cancer cells, but exhibit improved bone tumor distributionin vivo. Accordingly, in xenograft models of breast cancer metastasis to bone sites, engineered antibodies with enhanced bone specificity exhibit increased inhibition of both initial bone metastases and secondary multi-organ metastases from bone lesions. Furthermore, this engineering strategy is also applied to prepare bone-targeting antibody-drug conjugates with enhanced therapeutic efficacy. These results demonstrate that adding bone-specific targeting to antibody therapy results in robust delivery of therapeutic antibodies to the bone tumor niche. This provides a powerful strategy for overcoming inadequate treatment of bone cancer and the development of potentially acquired resistance to therapy.

Nosocomial infections transmitted through airborne, droplet, aerosol, and particulate-transported modes pose substantial infection risks to patients and healthcare employees. In this study, we demonstrate a self-cleaning filter comprised of laser-induced graphene (LIG), a porous conductive graphene foam formed through photothermal conversion of a polyimide film by a commercial CO2 laser cutter. LIG was shown to capture particulates and bacteria. The bacteria cannot proliferate even when submerged in culture medium. Through a periodic Joule-heating mechanism, the filter readily reaches >300 °C. This destroys any microorganisms including bacteria, along with molecules that can cause adverse biological reactions and diseases. These molecules include pyrogens, allergens, exotoxins, endotoxins, mycotoxins, nucleic acids, and prions. Capitalizing on the high surface area and thermal stability of LIG, the utility of graphene for reduction of nosocomial infection in hospital settings is suggested.

This paper introduces a general state estimation framework fusing multiple sensor information for hybrid wheeled-legged robots performing mobile manipulation tasks. At the core of the state estimator is a novel unified odometry for hybrid locomotion which can seamlessly maintain tracking and has no need to switch between stepping and rolling modes. To the best of our knowledge, the proposed odometry is the first work in this area. It is calculated based on the robot kinematics and instantaneous contact points of wheels with sensor inputs from IMU, joint encoders, joint torque sensors estimating wheel contact status, as well as RGB-D camera detecting geometric features of the terrain (e.g. elevation and surface normal vector). Subsequently, the odometry output is utilized as the motion model of a 3D Lidar map-based Monte Carlo Localization module for drift-free state estimation. As part of the framework, visual localization is integrated to provide high precision guidance for the robot movement relative to an object of interest. The proposed approach was verified thoroughly by two experiments conducted on the Pholus robot with OptiTrack measurements as ground truth.

We used whole-organ mapping to study loco-geographic molecular changes in evolution of human bladder cancer from mucosal field effects. The integrative multi-platform analyses based on genome-wide RNA sequencing, methylation, copy number variations, and whole exome sequencing identified over 100 dysregulated canonical pathways involving immunity, tissue differentiation and transformation as initiators of bladder carcinogenesis. Widespread dysregulation of interleukin signaling was the dominant change signifying the important role of inflammation and immunity in the incipient phases of urothelial carcinogenesis. The analyses of mutational patterns identified three types of mutations based on their geographic distribution and variant allele frequencies. The most common were low frequency subclonal mutations restricted to individual mucosal samples which were the progeny of their respective uroprogenitor cells. The two additional types of mutations were associated with clonal expansion and involved large areas of bladder mucosa. The first group referred to as α mutations, showed a low mutational frequency across the mucosa. The second group referred to as β mutations increased in their frequencies with disease progression and a large proportion of them represented mutated transcriptional regulators controlling proliferation. Time modeling revealed that bladder carcinogenesis is spanning 10-15 years and can be divided into dormant and progressive phases. The progressive phase lasted 1-2 years and was primarily driven by β mutations with high proliferative advantage. This is the first detailed molecular characterization of mucosal field effects initiating bladder carcinogenesis on the whole-organ scale. It provides novel insights into incipient phases of bladder carcinogenesis and biomarkers for early detection of bladder cancer as well as targets for preventive therapies.

While 20 canonical amino acids are used by most organisms for protein synthesis, the creation of cells that can use noncanonical amino acids (ncAAs) as additional protein building blocks holds great promise for preparing novel medicines and for studying complex questions in biological systems. However, only a small number of biosynthetic pathways for ncAAs have been reported to date, greatly restricting our ability to generate cells with ncAA building blocks. In this study, we report the creation of a completely autonomous bacterium that utilizes 3,4-dihydroxy-L-phenylalanine (DOPA) as its 21st amino acid building block. Like canonical amino acids, DOPA can be biosynthesized without exogenous addition and can be genetically incorporated into proteins in a site-specific manner. Equally important, the protein production yields of DOPA-containing proteins from these autonomous cells are greater than those from cells exogenously fed with 9 mM DOPA. The unique catechol moiety of DOPA can be used as a versatile handle for site-specific protein functionalizations via either oxidative coupling or strain-promoted oxidation-controlled cyclooctyne-1,2-quinone (SPOCQ) cycloaddition reactions. We further demonstrate the use of these autonomous cells in preparing fluorophore-labeled anti-human epidermal growth factor 2 (HER2) antibodies for the detection of HER2 expression on cancer cells.

While most organisms utilize 20 canonical amino acid building blocks for protein synthesis, adding additional candidates to the amino acid repertoire can greatly facilitate the investigation and manipulation of protein structures and functions. In this study, we report the generation of completely autonomous organisms with a 21(st) ncAA, 5-hydroxytryptophan (5HTP). Like 20 canonical amino acids, 5-hydroxytryptophan can be biosynthesized in vivo from simple carbon sources and is subsequently incorporated into proteins in response to the amber stop codon. Using this unnatural organism, we have prepared a single-chain immunoglobulin variable fragment conjugated with a fluorophore and demonstrated the utility of these autonomous cells to monitor oxidative stress. Creation of this and other cells containing the 21(st) amino acid will provide an opportunity to generate proteins and organisms with novel activities, as well as to determine the evolutionary consequences of using additional amino acid buildings.

Precision modification of antibodies with bone-targeting moieties unleashes their potential for the treatment of bone metastases., Antibody-based therapies have proved to be of great value in cancer treatment. Despite the clinical success of these biopharmaceuticals, reaching targets in the bone microenvironment has proved to be difficult due to the relatively low vascularization of bone tissue and the presence of physical barriers. Here, we have used an innovative bone-targeting (BonTarg) technology to generate a first-in-class bone-targeting antibody. Our strategy involves the use of pClick antibody conjugation technology to chemically couple the bone-targeting moiety bisphosphonate to therapeutic antibodies. Bisphosphonate modification of these antibodies results in the delivery of higher conjugate concentrations to the bone metastatic niche, relative to other tissues. In xenograft mice models, this strategy provides enhanced inhibition of bone metastases and multiorgan secondary metastases that arise from bone lesions. Specific delivery of therapeutic antibodies to the bone, therefore, represents a promising strategy for the treatment of bone metastatic cancers and other bone diseases.

In order to cope with the operational instability and scheduling complexity brought by wind power access to the grid, this paper aims at multi-domain optimal dispatching of wind power systems based on voltage stability constraints. The wind power system is divided into different grid operation domains, and the system is divided into normal domains, abnormal domains, and emergency domains according to the regulation capacity of conventional units and their changing trends. The optimal scheduling model considering voltage stability constraints in different operation regions is established. Through the simulation calculation of a typical example of IEEE-30 node, it is verified that the optimized scheduling method can improve the economy, security and wind power capacity of the system operation.

For wheels and rails during actual service process, due to the combined impact of heat generated by friction and plastic deformation, martensite white etching layers (M-WELs) tend to form on the wear surface of wheel/rail materials. However, M-WELs are regarded as a double-edged sword: their relatively high hardness enhances wear resistance, but during wear process, cracks initiate easily due to great amounts of substructures inside M-WELs. Therefore, local laser quenching is adopted to simulate the wheel surface on which M-WELs form. Investigating the effects of M-WELs on wheels’ tribological properties is conducive to the improvement of high-speed trains’ wheel service longevity. The quenched spot with depth of 250 µm and diameter in 4 mm can be formed after local laser quenching on the specimen surface of D1 wheel steel and the hardness is about 930–997 HV0.1. The effect of the quenched layer on tribological properties of specimens was studied by rolling wear test. The results show that the main fatigue damage of non-quenched specimens is shallow spalling, and cracks propagated along the fibrous structure can be observed. There are striking differences for local quenched specimens. It's obvious that cracks initiate easily at the edge of the quenched layer as well as the quenched layer surface, and then propagate along the heat-affected zone at the early worn stage. This leads to spalling of the edge of the quenched layer. Cracks initiated on the surface can extend towards the bottom of the quenched layer with the increase of rotation cycles and the convergence of cracks would result shallow spalling of the quenched layer. After the edge of the quenched layer falls off completely, cracks initiate in the heat-affected zone and propagate along the heat-affected zone or along the fibrous structure of the matrix, leading to shallow spalling. In the subsequent process of rolling wear, cracks extend to the heat-affected zone and continue to propagate along this zone to the area where the maximum shear stress exists; under the impact of the maximum shear stress, the cracks further expand to the matrix. However, if these cracks converge other ones before arriving at the heat-affected zone, large pieces of the quenched layer fall off. The quenched layer can not only accelerate the surface spalling damage of the specimen and wear unevenly, but also can promote the formation of polygonization and reduce wear resistance of the specimen under axial vibration condition.

Site-specific antibody conjugates with a well-defined structure and superb therapeutic index are of great interest for basic research, disease diagnostics, and therapy. Here, we develop a novel proximity-induced antibody conjugation strategy enabling site-specific covalent bond formation between functional moieties and native antibodies without antibody engineering or additional UV/chemical treatment. A high conjugation efficiency and specificity was achieved with IgGs from different species and subclasses. The utility of this approach was demonstrated by site-specific conjugation of the small-molecule fluorophore to a native antibody and in vitro characterization of its activities.

Genetically site-specific introduction of noncanonical amino acids (ncAAs) for protein conjugation generally requires incorporation through exogenous feeding of chemically synthesized ncAAs. We developed a p-amino-phenylalanine (pAF)-based relay system that enables site-specific functionalization of proteins without chemical synthesis of the building blocks. pAF was biosynthesized under optimized conditions, followed by site-specific incorporation into a specific protein residue. The resulting protein was ready for functionalization using an oxidative conjugation reaction. We demonstrated the use of this relay system by preparing a fluorophore-labeled anti-HER2 single-chain variable fragment antibody for fluorescent imaging.

Site-specific introduction of bioorthogonal handles into biomolecules provides powerful tools for studying and manipulating the structures and functions of proteins. Recent advances in bioorthogonal chemistry demonstrate that tetrazine-based bioorthogonal cycloaddition is a particularly useful methodology due to its high reactivity, biological selectivity, and turn-on property for fluorescence imaging. Despite its broad applications in protein labeling and imaging, utilization of tetrazine-based bioorthogonal cycloaddition has been limited to date by the requirement of a hydrophobic strained alkene reactive moiety. Circumventing this structural requirement, we report the site-specific incorporation of noncanonical amino acids (ncAAs) with a small isocyanide (or isonitrile) group into proteins in both bacterial and mammalian cells. We showed that under physiological conditions and in the absence of a catalyst these isocyanide-containing ncAAs could react selectively with tetrazine molecules via [4 + 1]-cycloaddition, thus providing a versatile bioorthogonal handle for site-specific protein labeling and protein decaging. Significantly, these bioorthogonal reactions between isocyanides and tetrazines also provide a unique mechanism for the activation of tetrazine-quenched fluorophores. The addition of these isocyanide-containing ncAAs to the list of 20 commonly used, naturally occurring amino acids expands our repertoire of reagents for bioorthogonal chemistry, therefore enabling new biological applications ranging from protein labeling and imaging studies to the chemical activation of proteins.