Crosstalk between Chemokine Receptor CXCR4 and Cannabinoid Receptor CB2 in Modulating Breast Cancer Growth and Invasion

Cannabinoids bind to cannabinoid receptors CB(1) and CB(2) and have been reported to possess anti-tumorigenic activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid receptor CB(2) may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4 and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer progression and metastasis.We observed high expression of both CB(2) and CXCR4 receptors in breast cancer patient tissues by immunohistochemical analysis. We further found that CB(2)-specific agonist JWH-015 inhibits the CXCL12-induced chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4), highly metastatic clone of MDA-MB-231 (SCP2) and NT 2.5 cells (derived from MMTV-neu) by using chemotactic and wound healing assays. Elucidation of the molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a critical role in breast cancer invasion and metastasis. In addition, we have shown that JWH-015 significantly inhibits orthotopic tumor growth in syngenic mice in vivo using NT 2.5 cells. Furthermore, our studies have revealed that JWH-015 significantly inhibits phosphorylation of CXCR4 and its downstream signaling in vivo in orthotopic and spontaneous breast cancer MMTV-PyMT mouse model systems.This study provides novel insights into the crosstalk between CB(2) and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB(2) receptors could be used for developing innovative therapeutic strategies against breast cancer

An Improved Semisoft Threshold Algorithm and Its Evaluation for Denoising Random Walk in GNSS Time Series

The differences in the satellite orbit and signal quality of global navigation satellite positioning system, resulting in the complexity of random walk noise in GNSS time series, has become a bottleneck problem in applying GNSS technology to the high precision deformation monitoring industry. For the complex characteristics of random walk noise, small magnitude, low frequency and low sensitivity, an improved semisoft threshold algorithm is presented. Then it forms a unified system of semisoft threshold function, so as to improve the adaptability of conventional semisoft threshold for random walk noise. In order to verify and evaluate the effect of improved semisoft threshold algorithm, MATLAB platform is used to generate a linear trend, periodic and random walk noise of the GNSS time series, a total of 1700 epochs. The results show that the improved semisoft threshold method is better than the classical method, and has better performance in the SNR and root mean square error. The evaluation results show that the morphological character has been performanced high consistency between the noise reduced by improved method with random walk noise. Further from the view of quantitative point, the evaluation results of spectral index analysis verify the applicability of the improved method for random walk noise

Automatic Registration of Vehicle-borne Mobile Mapping Laser Point Cloud and Sequent Panoramas

An automatic registration method of mobile mapping system laser point cloud and sequence panoramic image is proposed in this paper.Firstly,hierarchical object extraction method is applied on LiDAR data to extract the building façade and outline polygons are generated to construct the skyline vectors.A virtual imaging method is proposed to solve the distortion on panoramas and corners on skylines are further detected on the virtual images combining segmentation and corner detection results.Secondly,the detected skyline vectors are taken as the registration primitives.Registration graphs are built according to the extracted skyline vector and further matched under graph edit distance minimization criteria.The matched conjugate primitives are utilized to solve the 2D-3D rough registration model to obtain the initial transformation between the sequence panoramic image coordinate system and the LiDAR point cloud coordinate system.Finally,to reduce the impact of registration primitives extraction and matching error on the registration results,the optimal transformation between the multi view stereo matching dens point cloud generated from the virtual imaging of the sequent panoramas and the LiDAR point cloud are solved by a 3D-3D ICP registration algorithm variant,thus,refine the exterior orientation parameters of panoramas indirectly.Experiments are undertaken to validate the proposed method and the results show that 1.5 pixel level registration results are achieved on the experiment dataset.The registration results can be applied to point cloud and panoramas fusion applications such as true color point cloud generation

WHU-helmet: a helmet-based multisensor SLAM dataset for the evaluation of real-time 3-D mapping in large-scale GNSS-denied environments

Real-time 3-D mapping of large-scale global navigation satellite system (GNSS)-denied environments plays an important role in forest inventory management, disaster emergency response, and underground facility maintenance. Compact helmet laser scanning (HLS) systems keep the same direction as the user's line of sight and have the advantage of 'what you see is what you get,' providing a promising and efficient solution for 3-D geospatial information acquisition. However, the violent motion of the helmet, the limited field of view (FoV) of the laser scanner, and the repeated symmetrical geometric structures in the GNSS-denied environments pose enormous challenges for the existing simultaneous localization and mapping (SLAM) algorithms. To promote the development of HLS and explore its application in large-scale GNSS-denied environments, the first large-scale HLS dataset covering multiple difficult GNSS-denied areas (e.g., forests, mountains, underground spaces) was built in this study. Besides using an additional very high accuracy fiber-optic inertial measurement unit (IMU), a novel postprocessing multisource fusion method - progressive trajectory correction (PTC) - is proposed to generate a reliable ground-truth trajectory for the benchmark, which overcomes the problems of scan matching degradation and nonrigid distortion. The accuracies of the ground truth are controlled and checked by manually surveyed feature points along the trajectory. Finally, the existing state-of-the-art SLAM methods were evaluated on the WHU-Helmet dataset, summarizing the future HLS SLAM research trends. The full dataset is available for download at: https://github.com/kafeiyin00/WHU-HelmetDataset.This work was supported in part by the National Natural Science Foundation Project under Grant 42130105 and Grant 42201477, in part by the National Science Fund for Distinguished Young Scholars under Grant 41725005, in part by the China Postdoctoral Science Foundation under Grant 2022M712441 and Grant 2022TQ0234, and in part by the Laboratory Independent Research Project of the State Key Laboratory of Information Engineering in Surveying, Mapping and Remote Sensing (LIESMARS)

Oral microbial community assembly under the influence of periodontitis.

Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell's neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.'s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li & Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher's exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or 'phenotype' of community assembly), it does not seem to cause the 'mutation' of the 'genotype" (mechanism) of community assembly. We argue that the 'phenotypic' changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation

Cdk4 disruption renders primary mouse cells resistant to oncogenic transformation, leading to Arf/p53-independent senescence

A large number of human cancers display alterations in the Ink4a/cyclin D/Cdk4 genetic pathway, suggesting that activation of Cdk4 plays an important role in oncogenesis. Here we report that Cdk4-null mouse embryonic fibroblasts are resistant to transformation in response to Ras activation with dominant-negative (DN) p53 expression or in the Ink4a/Arf-null background, judged by foci formation, anchorage-independent growth, and tumorigenesis in athymic mice. Cdk4-null fibroblasts proliferate at normal rates during early passages. Whereas Cdk4(+/+)Ink4a/Arf(−/−) cells are immortal in culture, Cdk4(−/−)Ink4a/Arf(−/−) cells undergo senescence during continuous culture, as do wild-type cells. Activated Ras also induces premature senescence in Cdk4(−/−)Ink4a/Arf(−/−) cells and Cdk4(−/−) cells with DNp53 expression. Thus, Cdk4 deficiency causes senescence in a unique Arf/p53-independent manner, which accounts for the loss of transformation potential. Cdk4-null cells express high levels of p21(Cip1/Waf1) with increased protein stability. Suppression of p21(Cip1/Waf1) by small interfering RNA (siRNA), as well as expression of HPV-E7 oncoprotein, restores immortalization and Ras-mediated transformation in Cdk4(−/−)Ink4a/Arf(−/−) cells and Cdk4(−/−) cells with DNp53 expression. Therefore, Cdk4 is essential for immortalization, and suppression of Cdk4 could be a prospective strategy to recruit cells with inactive Arf/p53 pathway to senescence

Inter-sector backup behaviors in parallel approach ATC: The effect of job satisfaction

Inter-sector cooperation between air traffic controllers (ATCos) can provide an effective way to manage controllers&rsquo; workload by redistributing individual task-load at a group level, yet this area has not been fully explored. Based on our previous studies which have identified the effects of certain task-level features, this present research aimed to identify the influence of individual difference variables on controllers&rsquo; backup decisions. Forty licensed controllers performed thirty-two simulated final approach scenarios in which they had to decide whether to accept a hand-over request made by a controller working in the neighboring sector. We manipulated three key task-level features across scenarios: (1) participants&rsquo; task-load, (2) the requestors&rsquo; task-load and (3) the close-landing demands of the to-be-hand-over aircraft. We also measured controllers&rsquo; work experience and job satisfaction. HLM analysis showed that: after controlling for the effects of task-level variables, job satisfaction had a unique contribution and also interacted with task-level variables in predicting backing up behaviors. &copy; Springer International Publishing AG, part of Springer Nature 2018.</p