Long-term non-invasive drug treatments in adult zebrafish that lead to melanoma drug resistance

Zebrafish embryos are widely used for drug discovery, however, administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we developed a drug formulation and administration method for adult zebrafish by producing food-based drug pellets that are consumed voluntarily. We applied this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Zebrafish with melanomas responded to short-term, precise and daily dosing with drug pellets made with the BRAF(V600E) inhibitor, vemurafenib. On-target drug efficacy was determined by phospho-Erk staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This method presents a controlled, non-invasive approach that permits long-term drug studies and can be widely applied to adult zebrafish models

Evaluating the Comprehensive Benefit of Public Transport Service – The Perspective of Three Stakeholders

Most studies investigate the benefit of public trans-port service from either the perspective of the operators or the public individually, failing to bind them together. Furthermore, they have not considered the significance of the government in quantifying the benefit. This pa-per explores the comprehensive benefit of public trans-port service from the perspectives of three stakeholders; namely, the operators, the public, and government. We develop a comprehensive benefit evaluation tool that is able to quantify production efficiency, service effect, and environmental effect, and test the effectiveness of the tool through a case study in 36 central cities of China. A network data envelopment analysis (NDEA) is used to evaluate the efficiency of the production and service sub-process, and comprehensive benefits. The results re-veal the following: (1) during the period 2010–2017, the production efficiency in 36 central cities showed a down-ward trend; (2) the service effectiveness did not change considerably from 2010 to 2013 but declined gradual-ly during the period 2014–2017; (3) the comprehensive benefits rarely changed during the period 2010–2013, but gradually got worse in response to reductions in the production efficiency and service effectiveness during the period 2014–2017. This study offers a robust tool to mea-sure the benefits of public transport in China for better decision-making, in terms of transit operation and man-agement

Improved IEEE 802.11 point coordination function considering fiber-delay difference in distributed antenna systems

In this paper, we present an improved IEEE 802.11 wireless local-area network (WLAN) medium access control (MAC) mechanism for simulcast radio-over-fiber-based distributed antenna systems where multiple remote antenna units (RAUs) are connected to one access point (AP). In the improved mechanism, the fiber delay between RAUs and central unit is taken into account in a modification to the conventional point coordination function (PCF) that achieves coordination by a centralized algorithm. Simulation results show that the improved PCF outperforms the distributed coordination function (DCF) in both the basic-access and request/clear-to-send modes in terms of the total throughput and the fairness among RAU

Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment

Neutrophils, the most abundant leukocytes in human blood, are essential fighter immune cells against microbial infection. Based on the finding that neutrophils can either restrict or promote cancer progression, tumor-associated neutrophils (TAN) are classified into anti-tumor N1 and pro-tumor N2 subsets. One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells, in particular, cytotoxic T lymphocytes. Currently, no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells (G/PMN-MDSC). In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy, as established from data obtained with diverse cancer models, therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy. Here, we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories: (1) depletion of existing PMN-MDSCs, (2) blockade of the development of PMN-MDSCs, (3) blockade of PMN-MDSC recruitment, (4) inhibition of immunosuppressive function. Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier, neutrophils are outstanding candidate carriers in nanoparticle-based therapies. Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery. In the second part of the review, we have highlighted recent advances in the field of neutrophil-based cancer drug delivery. Overall, we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits

Alterations of dendritic cell subsets in the peripheral circulation of patients with cervical carcinoma

Patients with cervical carcinoma (CC) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells. Using multicolor flow cytometry, the percentages of CD11c+ (DC1) and CD123+ (DC2) subsets, were determined in the peripheral blood of 37 patients with cervical carcinoma (CC), 54 patients with CIN, and 62 healthy individuals. A substantial reduction of circulating dendritic cells and accordingly immunodepression may be associated with increased IL-6 and TGF-β in serum. These findings could give expression to the immunosuppression of circulating dendritic cells in patients with CC and CIN, thus, may indicate novel aspects of cervical carcinoma immune evasion

PHYSICAL OR DIGITAL? FACTORS DRIVE CONSUMERS TO PURCHASE DIGITAL MUSIC

The development of digital products is booming in recent years because of the mature of entire environment. Among them, digital music should be the spotlight with unexpectedly expending speed. However, most studies of electronic commerce still focus on the field of physical products, but missing the value of digital wave. The purpose here is to explore and complements digital parts. In this study, we constructed the research model based on TRA and extended it with the advantage and disadvantage of intangibility (convenience, perceived risk), some characteristics of digital product (price, variety, trialability), and the factor related to entertainment (perceived playfulness) to predict what are consumer really concerned when they buy digital music.8 hypotheses were supported. Finally, we proved TRA is still a useful theory in the field of digital product

rPPG-MAE: Self-supervised Pre-training with Masked Autoencoders for Remote Physiological Measurement

Remote photoplethysmography (rPPG) is an important technique for perceiving human vital signs, which has received extensive attention. For a long time, researchers have focused on supervised methods that rely on large amounts of labeled data. These methods are limited by the requirement for large amounts of data and the difficulty of acquiring ground truth physiological signals. To address these issues, several self-supervised methods based on contrastive learning have been proposed. However, they focus on the contrastive learning between samples, which neglect the inherent self-similar prior in physiological signals and seem to have a limited ability to cope with noisy. In this paper, a linear self-supervised reconstruction task was designed for extracting the inherent self-similar prior in physiological signals. Besides, a specific noise-insensitive strategy was explored for reducing the interference of motion and illumination. The proposed framework in this paper, namely rPPG-MAE, demonstrates excellent performance even on the challenging VIPL-HR dataset. We also evaluate the proposed method on two public datasets, namely PURE and UBFC-rPPG. The results show that our method not only outperforms existing self-supervised methods but also exceeds the state-of-the-art (SOTA) supervised methods. One important observation is that the quality of the dataset seems more important than the size in self-supervised pre-training of rPPG. The source code is released at https://github.com/linuxsino/rPPG-MAE

Elite Opposition-Based Water Wave Optimization Algorithm for Global Optimization

Water wave optimization (WWO) is a novel metaheuristic method that is based on shallow water wave theory, which has simple structure, easy realization, and good performance even with a small population. To improve the convergence speed and calculation precision even further, this paper on elite opposition-based strategy water wave optimization (EOBWWO) is proposed, and it has been applied for function optimization and structure engineering design problems. There are three major optimization strategies in the improvement: elite opposition-based (EOB) learning strategy enhances the diversity of population, local neighborhood search strategy is introduced to enhance local search in breaking operation, and improved propagation operator provides the improved algorithm with a better balance between exploration and exploitation. EOBWWO algorithm is verified by using 20 benchmark functions and two structure engineering design problems and the performance of EOBWWO is compared against those of the state-of-the-art algorithms. Experimental results show that the proposed algorithm has faster convergence speed, higher calculation precision, with the exact solution being even obtained on some benchmark functions, and a higher degree of stability than other comparative algorithms