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In real-world applications, multiple robots need to be dynamically deployed to their appropriate locations as teams while the distance cost between robots and goals is minimized, which is known to be an NP-hard problem. In this paper, a new framework of team-based multi-robot task allocation and path planning is developed for robot exploration missions through a convex optimization-based distance optimal model. A new distance optimal model is proposed to minimize the traveled distance between robots and their goals. The proposed framework fuses task decomposition, allocation, local sub-task allocation, and path planning. To begin, multiple robots are firstly divided and clustered into a variety of teams considering interrelation and dependencies of robots, and task decomposition. Secondly, the teams with various arbitrary shape enclosing intercorrelative robots are approximated and relaxed into circles, which are mathematically formulated to convex optimization problems to minimize the distance between teams, as well as between a robot and their goals. Once the robot teams are deployed into their appropriate locations, the robot locations are further refined by a graph-based Delaunay triangulation method. Thirdly, in the team, a self-organizing map-based neural network (SOMNN) paradigm is developed to complete the dynamical sub-task allocation and path planning, in which the robots are dynamically assigned to their nearby goals locally. Simulation and comparison studies demonstrate the proposed hybrid multi-robot task allocation and path planning framework is effective and efficient.

The widespread adoption of autonomous vehicles has generated considerable interest in their autonomous operation, with path planning emerging as a critical aspect. However, existing road infrastructure confronts challenges due to prolonged use and insufficient maintenance. Previous research on autonomous vehicle navigation has focused on determining the trajectory with the shortest distance, while neglecting road construction information, leading to potential time and energy inefficiencies in real‐world scenarios involving infrastructure development. To address this issue, a digital twin‐embedded multi‐objective autonomous vehicle navigation is proposed under the condition of infrastructure construction. The authors propose an image processing algorithm that leverages captured images of the road construction environment to enable road extraction and modelling of the autonomous vehicle workspace. Additionally, a wavelet neural network is developed to predict real‐time traffic flow, considering its inherent characteristics. Moreover, a multi‐objective brainstorm optimisation (BSO)‐based method for path planning is introduced, which optimises total time‐cost and energy consumption objective functions. To ensure optimal trajectory planning during infrastructure construction, the algorithm incorporates a real‐time updated digital twin throughout autonomous vehicle operations. The effectiveness and robustness of the proposed model are validated through simulation and comparative studies conducted in diverse scenarios involving road construction. The results highlight the improved performance and reliability of the autonomous vehicle system when equipped with the authors’ approach, demonstrating its potential for enhancing efficiency and minimising disruptions caused by road infrastructure development.

The assembly of prereplicative complex (pre-RC) during G1 phase must be tightly controlled to sustain cell proliferation and maintain genomic stability. Mechanisms to prevent pre-RC formation in G2/M and S phases are well appreciated, whereas how cells ensure efficient pre-RC assembly during G1 is less clear. Here we report that cyclin K regulates pre-RC formation. We find that cyclin K expression positively correlates with cell proliferation, and knockdown of cyclin K or its cognate kinase CDK12 prevents the assembly of pre-RC in G1 phase. Mechanistically we uncover that cyclin K promotes pre-RC assembly by restricting cyclin E1 activity in G1. We identify a cyclin K-dependent, novel phosphorylation site in cyclin E1 that disrupts its interaction with CDK2. Importantly, this antagonistic relationship is largely recapitulated in cyclin E1-overexpressing tumors. We discuss the implications of our findings in light of recent reports linking cyclin K and CDK12 to human tumorigenesis. Prereplicative complex (pre-RC) formation during G1 is fundamental for cell replication. Here the authors report a role for cyclin K in regulating pre-RC formation in mammalian cells by affecting cyclin E1 activity.

Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG)-diamine to create a nanoconjugate (IRPDcov) with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential -0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05) plasma half-life, elimination half-life, and area under the curve (AUC) value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization, targeting, and customization. The conjugation of PEG-diamine with a near-infrared dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments.

Germ cell and embryonic stem cells are inextricably linked in many aspects. Remarkably both can generate all somatic cell types in organisms. Yet the molecular regulation accounting for these similarities is not fully understood. Cyclin K was previously thought to associate with CDK9 to regulate gene expression. However, we and others have recently shown that its cognate interacting partners are CDK12 and CDK13 in mammalian cells. We further demonstrated that cyclin K is essential for embryonic stem cell maintenance. In this study, we examined the expression of cyclin K in various murine and human tissues. We found that cyclin K is highly expressed in mammalian testes in a developmentally regulated manner. During neonatal spermatogenesis, cyclin K is highly expressed in gonocytes and spermatogonial stem cells. In adult testes, cyclin K can be detected in spermatogonial stem cells but is absent in differentiating spermatogonia, spermatids and spermatozoa. Interestingly, the strongest expression of cyclin K is detected in primary spermatocytes. In addition, we found that cyclin K is highly expressed in human testicular cancers. Knockdown of cyclin K in a testicular cancer cell line markedly reduces cell proliferation. Collectively, we suggest that cyclin K may be a novel molecular link between germ cell development, cancer development and embryonic stem cell maintenance.

The realm of autonomous robotics has seen impressive advancements in recent years, with robots taking on essential roles in various sectors, including disaster response, environmental monitoring, agriculture, and healthcare. As these highly intelligent machines continue to integrate into our daily lives, the pressing imperative is to elevate and refine their performance, enabling them to adeptly manage complex tasks with remarkable efficiency, adaptability, and keen decision-making abilities, all while prioritizing safety-aware navigation, mapping, and control systems. Ensuring the safety-awareness of these robotic systems is of paramount importance in their development and deployment. In this research, bio-inspired neural networks, nature-inspired intelligence, deep learning, heuristic algorithm and optimization techniques are developed for safety-aware autonomous robots navigation, mapping and control.A bio-inspired neural network (BNN) local navigator coupled with dynamic moving windows (DMW) is developed in this research to enhance obstacle avoidance and refines safe trajectories. A hybrid model is proposed to optimize trajectory of the global path of a mobile robot that maintains a safe distance from obstacles using a graph-based search algorithm associated with an improved seagull optimization algorithm (iSOA). A Bat-Pigeon algorithm (BPA) is proposed to undertake adjustable speed navigation of autonomous vehicles in light of object detection for safety-aware vehicle path planning, which can automatically adjust the speed in different road conditions. In order to perform effective collision avoidance in multi-robot task allocation, a spatial dislocation scheme is developed by introduction of an additional dimension for UAVs at different altitudes, whereas UAVs avoid collision at the same altitude using a proposed velocity profile paradigm. A multi-layer robot navigation system is developed to explore row-based environment. A directed coverage path planning (DCPP) fused with an informative planning protocol (IPP) method is proposed to efficiently and safely search the entire workspace. A human-autonomy teaming strategy is proposed to facilitate cooperation between autonomous robots and human expertise for safe navigation to desired areas. Simulation, comparison studies and on-going experimental results of optimization algorithms applied for autonomous robot systems demonstrate their effectiveness, efficiency and robustness of the proposed methodologies.

Purpose To test the effectiveness of a dual-agent-loaded PLGA nanoparticulate drug delivery system containing doxorubicin (DOX) and indocyanine green (ICG) in a DOX-sensitive cell line and two resistant cell lines that have different resistance mechanisms. Methods The DOX-sensitive MES-SA uterine sarcoma cell line was used as a negative control. The two resistant cell lines were uterine sarcoma MES-SA/Dx5, which overexpresses the multidrug resistance exporter P-glycoprotein, and ovarian carcinoma SKOV-3, which is less sensitive to doxorubicin due to a p53 gene mutation. The cellular uptake, subcellular localization and cytotoxicity of the two agents when delivered via nanoparticles (NPs) were compared to their free-form administration. Results The cellular uptake and cytotoxicity of DOX delivered by NPs were comparable to the free form in MES-SA and SKOV-3, but much higher in MES-SA/Dx5, indicating the capability of the NPs to overcome P-glycoprotein resistance mechanisms. NP-encapsulated ICG showed slightly different subcellular localization, but similar fluorescence intensity when compared to free ICG, and retained the ability to generate heat for hyperthermia delivery. Conclusion The dual-agent-loaded system allowed for the simultaneous delivery of hyperthermia and chemotherapy, and this combinational treatment greatly improved cytotoxicity in MES-SA/Dx5 cells and to a lesser extent in SKOV-3 cells.

Embryonic stem cells (ESCs) are self-renewing pluripotent cells, capable of differentiating into all somatic cell types. The molecular control of self-renewal is relatively well-characterized, whereas how ESCs exit pluripotent state to differentiate is poorly understood. Here we identify two genes are required for differentiation and dozens of intergenic regions that potentially regulate ESC differentiation. We used PiggyBac (PB) transposon-based approach to randomly mutate the genome of ESCs, and generated hundreds of clones that resisted differentiation signals. Each clone was sequenced to determine genomic regions mutated by PB insertion. Intriguingly, many mutations were localized among intergenic regions and we identified two genes are required for differentiation. This study should facilitate further exploration of novel molecular determinants of embryonic stem cell differentiation.

Anthracyclines cause severe irreversible cardiac toxicity. The study of changes in cardiac permeability with chemotherapy could enhance the understanding of mechanisms behind cardiac damage, and provide useful information to evaluate anthracycline cardiotoxicity. Thirty-six rats (12 Sprague–Dawley, 12 Wistar, 12 Fischer-344) were randomly assigned to control ( n  = 21) or doxorubicin ( n  = 15), and injected i.p. with a cumulative dose of 18 mg/kg doxorubicin in saline (vehicle) or vehicle alone over 12 days. Echocardiography was performed at baseline and on day 11. An isolated heart experiment was done on day 12 to obtain perfused heart pressure values, and to measure cardiac capillary permeability using a Texas Red/sodium fluorescein multiple indicator dilution method. Control animals had significantly lower average permeability-surface-area-products (0.035 ± 0.013 cm 3 /s) than doxorubicin animals (0.066 ± 0.023 cm 3 /s), PSP ± SD, p  < 0.001. These permeability changes correlated with significant functional changes. There was a significant decline in cardiac function with a deleterious effect of chemotherapy on fractional shortening ( p  < 0.001), left ventricular developed pressure ( p  < 0.001), contractility ( p  < 0.001), and relaxation ( p  = 0.02). Based on our results, cardiac capillary permeability changes can be detected after in vivo chemotherapy treatment using our fluorescent multiple indicator dilution technique, and may provide valuable information in evaluating cardiotoxicity of novel drugs.

A novel biocompatible and biodegradable polymer, termed poly(Glycerol malate co-dodecanedioate) (PGMD), was prepared by thermal condensation method and used for fabrication of nanoparticles (NPs). PGMD NPs were prepared using the single oil emulsion technique and loaded with an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The size of the void PGMD NPs, IR820-PGMD NPs and DOX-IR820-PGMD NPs were approximately 90 nm, 110 nm, and 125 nm respectively. An acidic environment (pH=5.0) induced higher DOX and IR820 release compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of DOX-IR820-PGMD NPs was comparable in MES-SA but was higher in Dx5 cells compared to free DOX plus IR820 (p<0.05). The combination of hyperthermia (HT) and chemotherapy improved cytotoxicity in both cell lines. We also explored the cellular response after rapid, short-term and low thermal dose (laser/Dye/NP) induced-heating, and compared it to slow, long-term and high thermal dose cell incubator heating by investigating the reactive oxygen species (ROS) level, hypoxia-inducible factor-1 (HIF-1 ) and vascular endothelial growth factor (VEGF) expression. The cytotoxicity of IR820-PGMD NPs after laser/Dye/NP HT resulted in higher cancer cell killing compared to incubator HT. ROS level, HIF-1 and VEGF expression were elevated under incubator HT, while maintained at the baseline level under the laser/Dye/NP HT. In vivo mouse studies showed that NP formulation significantly improved the plasma half-life of IR820 after tail vein injection. Significant lower IR820 content was observed in kidney in DOX-IR820-PGMD NP treatment as compared to free IR820 treatment in our biodistribution studies (p<0.05). In conclusion, both IR820-PGMD NPs and DOX-IR820-PGMD NPs were successfully developed and used for both imaging and therapeutic purposes. Rapid and short-term laser/Dye/NP HT, with a low thermal dose, did not up-regulate HIF-1 and VEGF expression, whereas slow and long-term incubator HT, with a high thermal dose, can enhance expression of both HIF-1 and VEGF.