How do navy escorts influence piracy risk in East Africa? A Bayesian network approach.

Navy escorts are considered crucial in countering illegal piracy attacks. In this paper, a novel approach is developed to investigate the effect of navy escorts on piracy incidents by models based on two enhanced Tree-Augmented Naïve (TAN) Bayesian networks. This approach offers a systematic investigation into the various factors that influence pirate activities, and helps to identify changes in piracy attack behaviors when confronted by navy escorts and assess the effectiveness of anti-piracy measures. An empirical study is conducted utilizing a unique data set compiled from multiple sources from 2000 to 2019. The empirical evidence shows that there was a gradual reduction in the incidence of piracy attacks in East Africa following the implementation of navy escorts in 2009, but with a surge in 2010 and 2011. The data set is, thus, divided into two time periods at the point of 2009 to facilitate a robust and comprehensive analysis, resulting in the development of two TAN models. Meanwhile, the geographical distribution of pirate attacks has shifted from international waters to port areas and territorial waters. We argue that the surge and geographical shift could be attributed to the calculating behavior of pirates when they encounter external pressures. Finally, a Shapely approach is introduced to evaluate the potential effectiveness of the implemented risk management strategies from a Game Theory perspective. This study offers new insights into the promotion of navy escorts and contributes to the development of a framework for assessing piracy risks in uncertain and dynamic anti-piracy environments.

Measurement and Modeling of Transport Across the Blood-Brain Barrier.

The blood-brain barrier (BBB) is a dynamic regulatory barrier at the interface of blood circulation and the brain parenchyma, which plays a critical role in protecting homeostasis in the central nervous system. However, it also significantly impedes drug delivery to the brain. Understanding the transport across BBB and brain distribution will facilitate the prediction of drug delivery efficiency and the development of new therapies. To date, various methods and models have been developed to study drug transport at the BBB interface, including in vivo brain uptake measurement methods, in vitro BBB models, and mathematic brain vascular models. Since the in vitro BBB models have been extensively reviewed elsewhere, we provide a comprehensive summary of the brain transport mechanisms and the currently available in vivo methods and mathematic models in studying the molecule delivery process at the BBB interface. In particular, we reviewed the emerging in vivo imaging techniques in observing drug transport across the BBB. We discussed the advantages and disadvantages associated with each model to serve as a guide for model selection in studying drug transport across the BBB. In summary, we envision future directions to improve the accuracy of mathematical models, establish noninvasive in vivo measurement techniques, and bridge the preclinical studies with clinical translation by taking the altered BBB physiological conditions into consideration. We believe these are critical in guiding new drug development and precise drug administration in brain disease treatment.

Optical Modulation of the Blood-Brain Barrier for Glioblastoma Treatment.

The blood-brain barrier (BBB) is a major obstacle to the diagnostics and treatment of many central nervous system (CNS) diseases. A prime example of this challenge is seen in glioblastoma (GBM), the most aggressive and malignant primary brain tumor. The BBB in brain tumors, or the blood-brain-tumor barrier (BBTB), prevents the efficient delivery of most therapeutics to brain tumors. Current strategies to overcome the BBB for therapeutic delivery, such as using hyperosmotic agents (mannitol), have impeded progress in clinical translation limited by the lack of spatial resolution, high incidences of complications, and potential for toxicity. Focused ultrasound combined with intravenously administered microbubbles enables the transient disruption of the BBB and has progressed to early-phase clinical trials. However, the poor survival with currently approved treatments for GBM highlights the compelling need to develop and validate treatment strategies as well as the screening for more potent anticancer drugs. In this protocol, we introduce an optical method to open the BBTB (OptoBBTB) for therapeutic delivery via ultrashort pulse laser stimulation of vascular targeting plasmonic gold nanoparticles (AuNPs). Specifically, the protocol includes the synthesis and characterization of vascular-targeting AuNPs and a detailed procedure of optoBBTB. We also report the downstream characterization of the drug delivery and tumor treatment efficacy after BBB modulation. Compared with other barrier modulation methods, our optical approach has advantages in high spatial resolution and minimally invasive access to tissues. Overall, optoBBTB allows for the delivery of a variety of therapeutics into the brain and will accelerate drug delivery and screening for CNS disease treatment. Key features • Pulsed laser excitation of vascular-targeting gold nanoparticles non-invasively and reversibly modulates the blood-brain barrier permeability. • OptoBBTB enhances drug delivery in clinically relevant glioblastoma models. • OptoBBTB has the potential for drug screening and evaluation for superficial brain tumor treatment.

Mechanobiological modulation of blood-brain barrier permeability by laser stimulation of endothelial-targeted nanoparticles.

The blood-brain barrier (BBB) maintains an optimal environment for brain homeostasis but excludes most therapeutics from entering the brain. Strategies that reversibly increase BBB permeability are essential for treating brain diseases and are the focus of significant preclinical and translational interest. Picosecond laser excitation of tight junction-targeted gold nanoparticles (AuNPs) generates a nanoscale mechanical perturbation and induces a graded and reversible increase in BBB permeability (OptoBBB). Here we advanced this technique by showing that targeting endothelial glycoproteins leads to >10-fold higher targeting efficiency than targeting tight junctions both in vitro and in vivo. With both tight-junction and glycoprotein targeting, we demonstrate that OptoBBB is associated with a transient elevation and propagation of Ca2+, actin polymerization, and phosphorylation of ERK1/2 (extracellular signal-regulated protein kinase). These collectively activate the cytoskeleton resulting in increased paracellular permeability. The Ca2+ response involves internal Ca2+ depletion and Ca2+ influx with contributions from mechanosensitive ion channels (TRPV4, Piezo1). We provide insight into how the excitation of tight junction protein (JAM-A)-targeted and endothelial (glycocalyx)-targeted AuNPs leads to similar mechanobiological modulation of BBB permeability while targeting the glycocalyx significantly improves the nanoparticle accumulation in the brain. The results will be critical for guiding the future development of this technology for brain disease treatment.

Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment.

The treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human glioblastoma. Here we analyze the intratumoral blood-brain-tumor barrier heterogeneity in human glioblastoma and characterize two genetically engineered models in female mice that recapitulate two important glioma phenotypes, including the diffusely infiltrative tumor margin and angiogenic core. We show that pulsed laser excitation of vascular-targeted gold nanoparticles non-invasively and reversibly modulates the blood-brain-tumor barrier permeability (optoBBTB) and enhances the delivery of paclitaxel in these two models. The treatment reduces the tumor volume by 6 and 2.4-fold and prolongs the survival by 50% and 33%, respectively. Since paclitaxel does not penetrate the blood-brain-tumor barrier and is abandoned for glioblastoma treatment following its failure in early-phase clinical trials, our results raise the possibility of reevaluating a number of potent anticancer drugs by combining them with strategies to increase blood-brain-tumor barrier permeability. Our study reveals that optoBBTB significantly improves therapeutic delivery and has the potential to facilitate future drug evaluation for cancers in the central nervous system.

Improved Multi-Stream Convolutional Block Attention Module for sEMG-Based Gesture Recognition.

As a key technology for the non-invasive human-machine interface that has received much attention in the industry and academia, surface EMG (sEMG) signals display great potential and advantages in the field of human-machine collaboration. Currently, gesture recognition based on sEMG signals suffers from inadequate feature extraction, difficulty in distinguishing similar gestures, and low accuracy of multi-gesture recognition. To solve these problems a new sEMG gesture recognition network called Multi-stream Convolutional Block Attention Module-Gate Recurrent Unit (MCBAM-GRU) is proposed, which is based on sEMG signals. The network is a multi-stream attention network formed by embedding a GRU module based on CBAM. Fusing sEMG and ACC signals further improves the accuracy of gesture action recognition. The experimental results show that the proposed method obtains excellent performance on dataset collected in this paper with the recognition accuracies of 94.1%, achieving advanced performance with accuracy of 89.7% on the Ninapro DB1 dataset. The system has high accuracy in classifying 52 kinds of different gestures, and the delay is less than 300 ms, showing excellent performance in terms of real-time human-computer interaction and flexibility of manipulator control.