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Barry Wheeler posted an update 1 year, 5 months ago
Evidence suggests that bacterial community spatial organization affects their ecological function, yet details of the mechanisms that promote spatial patterns remain difficult to resolve experimentally. In contrast to bacterial communities in liquid cultures, surface-attached range expansion fosters genetic segregation of the growing population with preferential access to nutrients and reduced mechanical restrictions for cells at the expanding periphery. Here we elucidate how localized conditions in cross-feeding bacterial communities shape community spatial organization. We combine experiments with an individual based mathematical model to resolve how trophic dependencies affect localized growth rates and nucleate successful cell lineages. The model tracks individual cell lineages and attributes these with trophic dependencies that promote counterintuitive reproductive advantages and result in lasting influences on the community structure, and potentially, on its functioning. We examine persistence of lucky lineages in structured habitats where expansion is interrupted by physical obstacles to gain insights into patterns in porous domains.The filtration performance of soft colloid suspensions suffers from the agglomeration of the colloids on the membrane surface as filter cakes. Backflushing of fluid through the membrane and cross-flow flushing across the membrane are widely used methods to temporally remove the filter cake and restore the flux through the membrane. However, the phenomena occurring during the recovery of the filtration performance are not yet fully described. In this study, we filtrate poly(N-isopropylacrylamide) microgels and analyze the filter cake in terms of its composition and its dynamic mobility during removal using on-line laser scanning confocal microscopy. First, we observe uniform cake build-up that displays highly ordered and amorphous regions in the cake layer. Second, backflushing removes the cake in coherent pieces and their sizes depend on the previous cake build-up. Navitoclax And third, cross-flow flushing along the cake induces a pattern of longitudinal ridges on the cake surface, which depends on the cross-flow velocity and accelerates cake removal. These observations give insight into soft colloid filter cake arrangement and reveal the cake’s unique behaviour exposed to shear-stress.Liver metastasis is a recalcitrant disease that usually leads to death of the patient. The present study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model of a highly aggressive liver metastasis of colon cancer. The aim of the present study was to demonstrate proof-of-concept that candidate drug combinations could significantly inhibit growth and re-metastasis of this recalcitrant tumor. The patient’s liver metastasis was initially established subcutaneously in nude mice and the subcutaneous tumor tissue was then orthotopically implanted in the liver of nude mice to establish a PDOX model. Two studies were performed to test different drugs or drug combination, indicating that 5-fluorouracil (5-FU) + irinotecan (IRI) + bevacizumab (BEV) and regorafenib (REG) + selumetinib (SEL) had significantly inhibited liver metastasis growth (p = 0.013 and p = 0.035, respectively), and prevented liver satellite metastasis. This study is proof of concept that a PDOX model of highly aggressive colon-cancer metastasis can identify effective drug combinations and that the model has future clinical potential.Polycrystalline Lead Oxide (poly-PbO) was considered one of the most promising photoconductors for the direct conversion X-ray medical imaging detectors due to its previous success in optical imaging, i.e., as an optical target in so-called Plumbicon video pick-up tubes. However, a signal lag which accompanies X-ray excitation, makes poly-PbO inapplicable as an X-ray-to-charge transducer in real-time X-ray imaging. In contrast, the recently synthesized Amorphous Lead Oxide (a-PbO) photoconductor is essentially lag-free. Here, we report on our approach to a PbO detector where a thin layer of a-PbO is combined with a thick layer of poly-PbO for lag-free operation. In the presented a-PbO/poly-PbO bilayer structure, the poly-PbO layer serves as an X-ray-to-charge transducer while the a-PbO acts as a lag prevention layer. The hole mobility in the a-PbO/poly-PbO bilayer structure was measured by photo-Charge Extraction by Linearly Increasing Voltage technique at different temperatures and electric fields to investigate charge transport properties. It was found that the hole mobility is similar to that in a-Se-currently the only commercially viable photoconductor for the direct conversion X-ray detectors. Evaluation of the X-ray temporal performance demonstrated complete suppression of signal lag, allowing operation of the a-PbO/poly-PbO detector in real-time imaging.In neuroscience, computational modeling is an effective way to gain insight into cortical mechanisms, yet the construction and analysis of large-scale network models-not to mention the extraction of underlying principles-are themselves challenging tasks, due to the absence of suitable analytical tools and the prohibitive costs of systematic numerical exploration of high-dimensional parameter spaces. In this paper, we propose a data-driven approach assisted by deep neural networks (DNN). The idea is to first discover certain input-output relations, and then to leverage this information and the superior computation speeds of the well-trained DNN to guide parameter searches and to deduce theoretical understanding. To illustrate this novel approach, we used as a test case a medium-size network of integrate-and-fire neurons intended to model local cortical circuits. With the help of an accurate yet extremely efficient DNN surrogate, we revealed the statistics of model responses, providing a detailed picture of model behavior. The information obtained is both general and of a fundamental nature, with direct application to neuroscience. Our results suggest that the methodology proposed can be scaled up to larger and more complex biological networks when used in conjunction with other techniques of biological modeling.

