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Metastatic tumor cells are thought to reach distant organs by traveling through the blood circulation or the lymphatic system. Two studies of mouse models now suggest a hybrid route for tumor cell dissemination. Pereira et al. and Brown et al. used distinct methodologies to monitor the fate of tumor cells in lymph nodes. They found that tumor cells could invade local blood vessels within a node, exit the node by entering the blood circulation, then go on to colonize the lung. Whether this dissemination route occurs in cancer patients is unknown; the answer could potentially change the way that affected lymph nodes are treated in cancer. Science , this issue p. 1403 , p. 1408 In mice, tumor cells can metastasize via lymph node blood vessels. During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.

Overlapping risks for cancer and cardiovascular diseases (CVD), the two leading causes of mortality worldwide, suggest a shared biology between these diseases. The role of senescence in the development of cancer and CVD has been established. However, its role as the intersection between these diseases remains unclear. Senescence was originally characterized by an irreversible cell cycle arrest after a high number of divisions, namely replicative senescence (RS). However, it is becoming clear that senescence can also be instigated by cellular stress, so-called stress-induced premature senescence (SIPS). Telomere shortening is a hallmark of RS. The contribution of telomere DNA damage and subsequent DNA damage response/repair to SIPS has also been suggested. Although cellular senescence can mediate cell cycle arrest, senescent cells can also remain metabolically active and secrete cytokines, chemokines, growth factors, and reactive oxygen species (ROS), so-called senescence-associated secretory phenotype (SASP). The involvement of SASP in both cancer and CVD has been established. In patients with cancer or CVD, SASP is induced by various stressors including cancer treatments, pro-inflammatory cytokines, and ROS. Therefore, SASP can be the intersection between cancer and CVD. Importantly, the conventional concept of senescence as the mediator of cell cycle arrest has been challenged, as it was recently reported that chemotherapy-induced senescence can reprogram senescent cancer cells to acquire “stemness” (SAS: senescence-associated stemness). SAS allows senescent cancer cells to escape cell cycle arrest with strongly enhanced clonogenic growth capacity. SAS supports senescent cells to promote both cancer and CVD, particularly in highly stressful conditions such as cancer treatments, myocardial infarction, and heart failure. As therapeutic advances have increased overlapping risk factors for cancer and CVD, to further understand their interaction may provide better prevention, earlier detection, and safer treatment. Thus, it is critical to study the mechanisms by which these senescence pathways (SAS/SASP) are induced and regulated in both cancer and CVD.

The interaction between a shock wave and an object causes an impulsive force on the object that lasts for a very short time on the order of milliseconds. This study proposes impulsive force measurements using anodized aluminum pressure-sensitive paint (AA-PSP), which is an optical pressure measurement technique. The response time of AA-PSP is on the order of microseconds, indicating the potential for fast pressure drag measurements by integrating the pressure distribution on the surface. In this study, at first, the response time of the fabricated AA-PSP is measured and determined to be 3.3 μ s . A cylindrical model coated with the AA-PSP is installed at the outlet of a shock tube, and the surface pressure is measured in order to calculate the pressure drag with a time resolution of 10 μ s . The experimental results are compared with an Euler CFD simulation computed using an in-house code. The maximum pressure drag in the numerical result exceeds that in the experimental result; however, the maximum pressure drag timings are in good quantitative agreement. In addition to measuring the impulsive force, the AA-PSP results allow for the visualization of complex flow phenomena, such as diffraction and decay in the shock wave strength. This simultaneous measurement of the flow field and impulsive forces can deepen the understanding of the relationship between them.

Four degrees of freedom (4DoF) registration is a class of point cloud registration problems for finding a rigid transformation to align two point clouds under the constraint that the rigid transformation is composed of a three-dimensional (3D) translation and 1D rotation. This constraint is suitable to align scan pairs acquired using modern terrestrial Light Detection and Ranging (LiDAR) scanners, the scans of which can share the direction of gravity as the Z-axis due to such scanners using tripods or internal inclinometers. We propose a fast convergence method for global optimal 4DoF registration. The proposed method consists of (i) our newly developed 4DoF registration model formulated as an optimization problem involving the cylindrical norm to measure the distance between two points, and (ii) a fast convergence algorithm to find a global optimal solution of the model. We experimentally demonstrated that the proposed method reduced the number of iterations to convergence and computation time compared with a current 4DoF registration method, especially when the given scan pairs are similar but cannot be aligned, which often appears in registration of multiple point clouds.

Background Contraceptive discontinuation for reasons other than the desire for pregnancy is associated with a high rate of unintended pregnancies leading to unsafe abortions, maternal morbidity and mortality. In Nigeria, little is known about modern contraceptive discontinuation using the calendar data. Methods A cross-sectional research design from the 2018 Nigeria Demographic and Health Surveys (NDHS) women’s dataset was used to examine the prevalence and associated factors of modern contraceptive discontinuation among sexually active married women in Nigeria. A weighted sample size of 3,353 currently sexually active married or in union women who have ever used a modern contraceptive 5 years before the survey and with complete reproductive histories and are not sterilised or declared infecund was analysed. Data were analysed and displayed using frequency tables and charts, chi-square test, and binary logistic regression model at 5% level of significance. Results The prevalence of modern contraceptive discontinuation was 35.8% (1199) with 45.8% (549) of the women discontinuing using modern contraceptives while at risk of pregnancy. The most modern method discontinued was Injectables (25.2%) while the commonest reason for modern method discontinuation was because they wanted to become pregnant (36.1%). Associated factors of modern contraceptive discontinuation among sexually active married women in Nigeria were: marital duration (aOR = 3.0; 95%CI: 1.5–6.2), visitation to a health facility in the last 12 months before the survey (aOR = 0.6; 95%CI: 0.4–0.8), education (aOR = 2.0; 95%CI: 1.2–3.4) and region of residence (aOR = 2.7; 95%CI: 1.6–4.7). Conclusion Modern contraceptive discontinuation among the study respondents was high. Region of residence, health facility visitation and marital duration were significantly associated with modern contraceptive discontinuation . The study suggests that health care providers should address the discontinuation of contraception through counselling, particularly among women who reside in the region of high prevalence of contraceptive discontinuation, short-term users as well as strengthen the use of contraception among those who are still at risk of becoming pregnant. Governments and stakeholders should also partner with private sectors to make health care accessible to women by bring health facilities closer to them to improve facility visitation. 

We have developed an automatic detection method for metallic corrosion in facilities by using a LiDAR point cloud. While visual inspections for monitoring facilities are widely conducted, the inspection result depends on human skill, and there is currently a shortage of inspectors. While automatic detection methods using an RGB image have been developed, such methods cannot be applied to inspections at night. Therefore, we propose a robust detection method that utilizes both 3D shapes and intensities in a LiDAR point cloud instead of RGB information. The proposed method segments the point cloud into a basic building material by using the 3D shape and then recognizes a point cloud with an abnormal intensity in each material as the corrosion area. We demonstrate through experiments that the proposed method can robustly detect corrosion spots in aging facilities during detection conducted both during the day and at night.

One of the identified shortcomings militating against the widespread application of Ti6Al4V alloy in the aerospace sector of the economy includes its unsatisfactory hardness and proneness to high-temperature oxidation which in turn adversely impact its abrasion resistance properties in certain service conditions. The work reported in this paper forms an important aspect of the effort put together in addressing these composite issues. Precisely, the effects of the nano-reinforcements of aluminum nitride (AlN) and hexagonal boron nitride ( h -BN) on the microstructure, phase contents, hardness, and oxidation resistance of Ti6Al4V-based composites were considered. The prepared powders were sintered by spark plasma sintering (SPS), an innovative sintering method which enables the implementation of fast heating and cooling rates. Thereafter, scanning electron microscopy, optical microscopy, and X-ray diffractometry were employed to observe and study the microstructure and phase contents, Archimedes’ principle was applied to evaluate the densification, Vickers’ microhardness test was used to measure the hardness values, and thermogravimetric analysis technique was used to study the oxidation resistance of the sintered composites. A homogeneous blend of the nano-reinforcements of 1.5 wt% each of AlN and h -BN gave the highest relative densification value of 99.77% while the hardness value (656.01 HV) was less than that of Ti6Al4V-3 h -BN (716.80 HV) which gave more credence to the phase contents in the microstructure as the most influencing factor determining the hardness property of the composites than ordinary relative densification. Meanwhile, Ti6Al4V-1.5AlN-1.5 h -BN with the minimum positive weight change (0.36 mg/cm 2 ) exhibited the greatest thermal oxidation resistance in air.

BACKGROUND AND AIMS: Understanding the genetic basis underlying domestication-related traits (DRTs) is important in order to use wild germplasm efficiently for improving yield, stress tolerance and quality of crops. This study was conducted to characterize the genetic basis of DRTs in soybean (Glycine max) using quantitative trait locus (QTL) mapping. METHODS: A population of 96 recombinant inbred lines derived from a cultivated (ssp. max) x wild (ssp. soja) cross was used for mapping and QTL analysis. Nine DRTs were examined in 2004 and 2005. A linkage map was constructed with 282 markers by the Kosambi function, and the QTL was detected by composite interval mapping. KEY RESULTS: The early flowering and determinate habit derived from the max parent were each controlled by one major QTL, corresponding to the major genes for maturity (e1) and determinate habit (dt1), respectively. There were only one or two significant QTLs for twinning habit, pod dehiscence, seed weight and hard seededness, which each accounted for approx. 20-50 % of the total variance. A comparison with the QTLs detected previously indicated that in pod dehiscence and hard seededness, at least one major QTL was common across different crosses, whereas no such consistent QTL existed for seed weight. CONCLUSIONS: Most of the DRTs in soybeans were conditioned by one or two major QTLs and a number of genotype-dependent minor QTLs. The common major QTLs identified in pod dehiscence and hard seededness may have been key loci in the domestication of soybean. The evolutionary changes toward larger seed may have occurred through the accumulation of minor changes at many QTLs. Since the major QTLs for DRTs were scattered across only six of the 20 linkage groups, and since the QTLs were not clustered, introgression of useful genes from wild to cultivated soybeans can be carried out without large obstacles.

The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear. We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation. Our findings demonstrate that laminar flow (L-flow) induces phosphorylation of SENP2 at S344 through the activation of checkpoint kinase 1 (CHK1), leading to the inhibition of ERK5 and p53 SUMOylation and subsequent suppression of EC activation. We observed a significant increase in lipid-laden lesions in both the aortic arch (under D-flow) and descending aorta (under L-flow) of female hypercholesterolemic SENP2 S344A KI mice. In male hypercholesterolemic SENP2 S344A KI mice, larger lipid-laden lesions were only observed in the aortic arch area, suggesting a weaker HC-mediated atherogenesis in male mice compared to females. Ionizing radiation (IR) reduced CHK1 expression and SENP2 S344 phosphorylation, attenuating the pro-atherosclerotic effects observed in female SENP2 S344A KI mice after bone marrow transplantation (BMT), particularly in L-flow areas. The phospho-site mutation SENP2 S344A upregulates processes associated with EC activation, including inflammation, migration, and proliferation. Additionally, fibrotic changes and up-regulated expression of EC marker genes were observed. Apoptosis was augmented in ECs derived from the lungs of SENP2 S344A KI mice, primarily through the inhibition of ERK5-mediated expression of DNA damage-induced apoptosis suppressor (DDIAS). In this study, we have revealed a novel mechanism underlying the suppressive effects of L-flow on EC inflammation, migration, proliferation, apoptosis, and fibrotic changes through promoting CHK1-induced SENP2 S344 phosphorylation. The phospho-site mutation SENP2 S344A responds to L-flow through a distinct mechanism, which involves the upregulation of both mesenchymal and EC marker genes.

Previously, we reported that post-translational modifications (PTMs) of MAGI1, including S741 phosphorylation and K931 de-SUMOylation, both of which are regulated by p90RSK activation, lead to endothelial cell (EC) activation. However, roles for p90RSK and MAGI1-PTMs in regulating EC permeability remain unclear despite MAGI1 being a junctional molecule. Here, we show that thrombin (Thb)-induced EC permeability, detected by the electric cell-substrate impedance sensing (ECIS) based system, was decreased by overexpression of dominant negative p90RSK or a MAGI1-S741A phosphorylation mutant, but was accelerated by overexpression of p90RSK, siRNA-mediated knockdown of magi1 , or the MAGI1-K931R SUMOylation mutant. MAGI1 depletion also increased the mRNA and protein expression of the large tumor suppressor kinases 1 and 2 (LATS1/2), which inhibited YAP/TAZ activity and increased EC permeability. Because the endothelial barrier is a critical mediator of tumor hypoxia, we also evaluated the role of p90RSK activation in tumor vessel leakiness by using a relatively low dose of the p90RSK specific inhibitor, FMK-MEA. FMK-MEA significantly inhibited tumor vessel leakiness at a dose that does not affect morphology and growth of tumor vessels in vivo . These results provide novel insights into crucial roles for p90RSK-mediated MAGI1 PTMs and the Hippo pathway in EC permeability, as well as p90RSK activation in tumor vessel leakiness.