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Transforming growth factor-β (TGF-β) and epidermal growth factor (EGF) have critical roles in regulating the metastasis of aggressive breast cancers, yet the impact of epithelial–mesenchymal transition (EMT) induced by TGF-β in altering the response of breast cancer cells to EGF remains unknown. We show in this study that murine metastatic 4T1 breast cancer cells formed compact and dense spheroids when cultured under three-dimensional (3D) conditions, which was in sharp contrast to the branching phenotypes exhibited by their nonmetastatic counterparts. Using the human MCF10A series, we show that epithelial-type and nonmetastatic breast cancer cells were unable to invade to EGF, whereas their mesenchymal-type and metastatic counterparts readily invaded to EGF. Furthermore, EMT induced by TGF-β was sufficient to manifest dense spheroid morphologies, a phenotype that increased primary tumor exit and invasion to EGF. Post-EMT invasion to EGF was dependent on increased activation of EGF receptor (EGFR) and p38 mitogen-activated protein kinase, all of which could be abrogated either by pharmacologic (PF-562271) or by genetic (shRNA) targeting of focal adhesion kinase (FAK). Mechanistically, EMT induced by TGF-β increased cell-surface levels of EGFR and prevented its physical interaction with E-cadherin, leading instead to the formation of oncogenic signaling complexes with TβR-II. Elevated EGFR expression was sufficient to transform normal mammary epithelial cells, and to progress their 3D morphology from that of hollow acini to branched structures characteristic of nonmetastatic breast cancer cells. Importantly, we show that TGF-β stimulation of EMT enabled this EGFR-driven breast cancer model to abandon their inherent branching architecture and form large, undifferentiated masses that were hyperinvasive to EGF and showed increased pulmonary tumor growth upon tail vein injection. Finally, chemotherapeutic targeting of FAK was sufficient to revert the aggressive behaviors of these structures. Collectively, this investigation has identified a novel EMT-based approach to neutralize the oncogenic activities of EGF and TGF-β in aggressive and invasive forms of breast cancer.

Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 10 4 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics 1 – 3 , but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies 4 , 5 . Such measurements were previously limited to especially favourable systems 6 – 8 or to the use of massive statistical averaging 9 , 10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars 11 – 14 . This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission. Lyman-α emission from atomic hydrogen shows the location of warm gas and is ubiquitous around galaxies between redshifts of 3 and 6, thereby covering nearly all the sky.

Cherenkov diffraction radiation is generated when a charged particle beam passes in close proximity to a dielectric target, and is currently being studied and developed for various non-invasive beam instrumentation applications at CERN. One such instrument is a beam position monitor (BPM) composed of four cylindrical dielectric inserts. A challenge of using the conventional stretched wire technique to characterize the BPM up to high frequencies is the coupling of unwanted higher order modes (HOM) into the inserts that are dielectric-loaded circular waveguides. To minimize the generation of HOMs and excite mainly the transverse electromagnetic (TEM) mode as a model of the beam field, a set-up comprising a dielectric insert mounted on a slab line with 50 Ω characteristic impedance was tested. The results and comparison with numerical simulations in CST are be presented.

Temporary hemiepiphysiodesis is a growth-guided surgical technique to address lower limb malalignment in children with remaining growth potential. It is a minimally invasive approach that relies on full standing radiography of the lower limb, resulting in exposure to ionizing radiation. Radiation-free, video-based alternative techniques have recently evolved which seem to have potential to be applied in clinical pathways, but they are still very expensive and have a complex setup. In this prospective pilot study, a low budget and uncomplicated method to assess malalignment of the lower limb was compared to radiologic measurements in 40 children aged from 8 to 16 years with idiopathic genu varum or valgum. Dynamic and static video-based assessments of the children were conducted, during their routine visits provided they had undergone full standing radiographs of the lower limb. Measurements of the primary (HKA = hip-knee angle) and secondary knee angles (e.g. medial proximal tibia angle) were compared. It was observed that the video-based hip-knee-ankle angle correlated very closely with radiographic values, as well as a significant positive correlation ( p  < 0.001) between all techniques (radiographic/dynamic/static). Moreover, the HKA measurements revealed excellent to high inter- and intrarater reliability. Concerning the HKA, this low-budget technique may represent a reliable alternative for longitudinal evaluation of lower limb malalignment in children. Considering the measurement errors in video-based analyses, it may be suggested that radiographic follow-up is only indicated until the target HKA approximates 2°. In summary, this novel technique has the potential to be the first step towards implementing radiation-free setups within clinical routine to evaluate lower limb malalignment. Future studies will need to determine whether the reliability and quality of video-based techniques are high enough to guide operative decision making.

Cellular metastasis is the most detrimental step in carcinoma disease progression, yet the mechanisms that regulate this process are poorly understood. CXCL12 and its receptor CXCR4 are co-expressed in several tissues and cell types throughout the body and play essential roles in development. Disruption of either gene causes embryonic lethality due to similar defects. Post-natally, CXCL12 signaling has a wide range of effects on CXCR4-expressing cells, including the directed migration of leukocytes, lymphocytes and hematopoietic stem cells. Recently, this signaling axis has also been described as an important regulator of directed carcinoma cell metastasis. We show herein that while CXCR4 expression remains consistent, constitutive colonic epithelial expression of CXCL12 is silenced by DNA hypermethylation in primary colorectal carcinomas as well as colorectal carcinoma-derived cell lines. Inhibition of DNA methyltransferase (Dnmt) enzymes with 5-aza-2′-deoxycytidine or genetic ablation of both Dnmt1 and Dnmt3b prevented promoter methylation and restored CXCL12 expression. Re-expression of functional, endogenous CXCL12 in colorectal carcinoma cells dramatically reduced metastatic tumor formation in mice, as well as foci formation in soft agar. Decreased metastasis was correlated with increased caspase activity in cells re-expressing CXCL12. These data constitute the unique observation that silencing CXCL12 within colonic carcinoma cells greatly enhances their metastatic potential.

Human–robot collaborative applications have been receiving increasing attention in industrial applications. The efficiency of the applications is often quite low compared to traditional robotic applications without human interaction. Especially for applications that use speed and separation monitoring, there is potential to increase the efficiency with a cost-effective and easy to implement method. In this paper, we proposed to add human–machine differentiation to the speed and separation monitoring in human–robot collaborative applications. The formula for the protective separation distance was extended with a variable for the kind of object that approaches the robot. Different sensors for differentiation of human and non-human objects are presented. Thermal cameras are used to take measurements in a proof of concept. Through differentiation of human and non-human objects, it is possible to decrease the protective separation distance between the robot and the object and therefore increase the overall efficiency of the collaborative application.

Expression of the chemokine receptor CXCR4 has been linked with increased metastasis and decreased clinical prognosis in breast cancer. The current paradigm dictates that CXCR4 fosters carcinoma cell metastasis along a chemotactic gradient to organs expressing the ligand CXCL12. The present study asked if alterations in autocrine CXCR4 signaling via dysregulation of CXCL12 in mammary carcinoma cells modulated their metastatic potential. While CXCR4 was consistently detected, expression of CXCL12 characteristic of human mammary epithelium was silenced by promoter hypermethylation in breast cancer cell lines and primary mammary tumors. Stable re-expression of functional CXCL12 in ligand null cells increased orthotopic primary tumor growth in the mammary fat-pad model of tumorigenesis. Those data parallel increased carcinoma cell proliferation measured in vitro with little-to-no-impact on apoptosis. Moreover, re-expression of autocrine CXCL12 markedly reduced metastatic lung invasion assessed using in vivo bioluminescence imaging following tail vein injection. Consistent with those data, decreased metastasis reflected diminished intracellular calcium signaling and chemotactic migration in response to exogenous CXCL12 independent of changes in CXCR4 expression. Together these data suggest that an elevated migratory signaling response to ectopic CXCL12 contributes to the metastatic potential of CXCR4-expressing mammary carcinoma cells, subsequent to epigenetic silencing of autocrine CXCL12.

Long-term storage is a necessary unit operation in the biomass feedstock logistics supply chain, enabling biorefineries to run year-round despite daily, monthly, and seasonal variations in feedstock availability. At a minimum, effective storage approaches must preserve biomass. Uncontrolled loss of biomass due to microbial degradation is common when storage conditions are not optimized. This can lead to physical and mechanical challenges with biomass handling, size reduction, preprocessing, and ultimately conversion. This review summarizes the unit operations of dry and wet storage and how they may contribute to preserving or even improving feedstock value for biorefineries.

In many regions of Europe, biogas production is an integral part of farming to generate methane as a sustainable and versatile renewable energy carrier. Besides providing feedstock for ruminants and energy production, grasslands support multiple beneficial ecosystem services, namely diverse flora and habitats that serve as resources for pollinators. The cost‐effective utilization of grassland biomass is mainly determined by the biomass quality, which is highly variable and dependent on the management intensities. Besides chemical analyses, biogas models are usually applied to predict the biogas yield of a specific biomass type and quality. However, available models do not apply to mixed grass stands as they primarily refer to individual grass species and/or are just based on single parameters such as lignin. In this work, we evaluated flower‐rich extensive fen grassland for its biogas yield using a newly created model based on common chemical parameters. Therefore, flower‐rich biomass from a cultivation experiment (n = 48) was analyzed for its biomass yield (average 9.43 ± 1.26 tVS × ha−1), chemical composition by wet chemical analysis and near‐infrared spectroscopy (NIRS), specific methane yield (SMY) potential via batch tests, and methane hectare yield (1505.62 ± 282.86 m3N × ha−1). In the results obtained, we found flower‐rich grassland biomass characterized by high fiber (30.1% ± 1.7%) and high protein content (11.3% ± 1.3%) with reliable determinability of chemical composition by NIRS. The most important predictors on SMY assessed by multiple linear regression were crude ash (XA), crude protein (XP), amylase neutral detergent fiber (aNDFvs), acid detergent fiber (ADFvs), and enzyme‐resistant organic matter (EROM). We conclude that extensive flower‐rich grassland biomass composed of diverse species and different growth and ripening stages provides a suitable feedstock for biogas production despite late harvest dates. NIRS proved capable of analyzing the biomass quality of flower‐rich grassland and thus contributes to optimizing grassland management strategies and provision of demand‐driven feedstock qualities. Biogas production from grasslands in Europe is important for sustainable energy, but predicting biogas yield from mixed, flower‐rich grasslands has been challenging due to variable biomass quality and limitations of existing models. This study analyzed flower‐rich fen grassland biomass, finding it to have high fiber and protein content, and demonstrated that near‐infrared spectroscopy (NIRS) reliably determines its chemical composition. The results show that such diverse grassland biomass is a suitable feedstock for biogas production, and that NIRS can help optimize grassland management and feedstock quality.

This research presents a capacitive displacement sensor concept, designed for integration into a pin array gripper. The sensor employs a plate capacitor structure to measure the displacement of individual pins, with each pin positioned to move between the electrodes. The sensor is designed with sensing, guiding and shielding electrodes to maintain a homogeneous electric field between the capacitor plates and a linear capacitance response. We implemented a shielding strategy with the objective of minimising external interference and reducing mutual interference between individual displacement sensors. This ensures stable operation and reliable measurements, which are crucial for the reliable functioning in dynamic environments. The design is optimised for additive manufacturing, offering advantages in customisation, adaptability to various pin gripping systems and a compact form factor. It also opens up new possibilities for integrating sensing elements directly into the structure of the gripper. A prototype sensor was fabricated using additive manufacturing and tested in an experimental setup to validate its functionality and to enable a comparison of its performance against the results of numerical simulations.