We propose a decentralized variant of Monte Carlo tree search (MCTS) that is suitable for a variety of tasks in multi-robot active perception. Our algorithm allows each robot to optimize its own ...actions by maintaining a probability distribution over plans in the joint-action space. Robots periodically communicate a compressed form of their search trees, which are used to update the joint distribution using a distributed optimization approach inspired by variational methods. Our method admits any objective function defined over robot action sequences, assumes intermittent communication, is anytime, and is suitable for online replanning. Our algorithm features a new MCTS tree expansion policy that is designed for our planning scenario. We extend the theoretical analysis of standard MCTS to provide guarantees for convergence rates to the optimal payoff sequence. We evaluate the performance of our method for generalized team orienteering and online active object recognition using real data, and show that it compares favorably to centralized MCTS even with severely degraded communication. These examples demonstrate the suitability of our algorithm for real-world active perception with multiple robots.
The study of protein localisation has greatly benefited from high-throughput methods utilising cellular fractionation and proteomic profiling. Hyperplexed Localisation of Organelle Proteins by ...Isotope Tagging (hyperLOPIT) is a well-established method in this area. It achieves high-resolution separation of organelles and subcellular compartments but is relatively time- and resource-intensive. As a simpler alternative, we here develop Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) and compare this method to the density gradient-based hyperLOPIT approach. We confirm that high-resolution maps can be obtained using differential centrifugation down to the suborganellar and protein complex level. HyperLOPIT and LOPIT-DC yield highly similar results, facilitating the identification of isoform-specific localisations and high-confidence localisation assignment for proteins in suborganellar structures, protein complexes and signalling pathways. By combining both approaches, we present a comprehensive high-resolution dataset of human protein localisations and deliver a flexible set of protocols for subcellular proteomics.
Discarded plastic wastes in the environment are serious challenges for sustainable waste management and for the delivery of environmental and public health. Plastics in the environment become rapidly ...colonised by microbial biofilm, and importantly this so-called ‘plastisphere’ can also support, or even enrich human pathogens. The plastisphere provides a protective environment and could facilitate the increased survival, transport and dissemination of human pathogens and thus increase the likelihood of pathogens coming into contact with humans, e.g., through direct exposure at beaches or bathing waters. However, much of our understanding about the relative risks associated with human pathogens colonising environmental plastic pollution has been inferred from taxonomic identification of pathogens in the plastisphere, or laboratory experiments on the relative behaviour of plastics colonised by human pathogens. There is, therefore, a pressing need to understand whether plastics play a greater role in promoting the survival and dispersal of human pathogens within the environment compared to other substrates (either natural materials or other pollutants). In this paper, we consider all published studies that have detected human pathogenic bacteria on the surfaces of environmental plastic pollution and critically discuss the challenges of selecting an appropriate control material for plastisphere experiments. Whilst it is clear there is no ‘perfect’ control material for all plastisphere studies, understanding the context-specific role plastics play compared to other substrates for transferring human pathogens through the environment is important for quantifying the potential risk that colonised plastic pollution may have for environmental and public health.
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•Human pathogens can colonise environmental plastic pollution.•Persistence and transport of pathogens can be facilitated on plastics.•Experiments need an appropriate ‘control’ to understand potential risk.•No single control substrate can control for all relevant variables.
Frequent relapse prevents the successful treatment of substance use disorders and is triggered in part by retrieval of drug-associated memories. Drug-conditioned behaviours in rodents are reinstated ...upon drug memory retrieval following re-exposure to cues previously associated with the drug, or the drug itself. Therapies based on mechanistic insights from rodent studies have focused on amnesic procedures of cue-drug associations but with so far limited success. Conversely, more recent studies propose that inhibiting drug memory retrieval offers improved anti-relapse efficacy. However, mechanisms of memory retrieval are poorly understood. Here, we used a conditioned place preference (CPP) procedure in mice to investigate the cellular and molecular underpinnings of drug-induced memory retrieval. After extinction training of CPP, Ca2+-permeable AMPA receptors (CP-AMPARs) accumulated at drug-generated silent synapses of nucleus accumbens (NAc) medium spiny neurons. The NAc CP-AMPARs regulated the retrieval mechanism of drug memories after extinction. Specifically, we used different priming doses of cocaine, fentanyl, or a cue associated with drug exposure to reinstate CPP, providing different memory retrieval conditions. Although both high and low doses of these two drugs induced CPP reinstatement, compromising CP-AMPAR accumulation impaired CPP reinstatement, induced by low doses of each drug or the cue. This threshold effect was mediated by NAc CP-AMPARs as region specific knock-down of PSD-95 prevented low-dose cocaine-induced retrieval selectively. These results demonstrate the NAc as a brain region and CP-AMPARs as key synaptic substrates that govern the threshold for drug-induced retrieval and behavioural expression of drug memories.
Metformin and Aging: A Review Glossmann, Hartmut H; Lutz, Oliver M D
Gerontology (Basel),
10/2019, Letnik:
65, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Metformin is sometimes proposed to be an "anti-aging" drug, based on preclinical experiments with lower-order organisms and numerous retrospective data on beneficial health outcomes for type 2 ...diabetics. Large prospective, placebo-controlled trials are planned, in pilot stage or running, to find a new use (or indication) for an aging population. As one of the metformin trials has "frailty" as its endpoint, similar to a trial with a plant-derived senolytic, the latter class of novel anti-aging drugs is briefly discussed. Concerns exist not only for vitamin B12 and B6 deficiencies, but also about whether there are adverse effects of metformin on individuals who try to remain healthy by maintaining cardiovascular fitness via exercise.
The extracellular matrix (ECM) proteoglycan, versican increases along with other ECM versican binding molecules such as hyaluronan, tumor necrosis factor stimulated gene-6 (TSG-6), and inter alpha ...trypsin inhibitor (IαI) during inflammation in a number of different diseases such as cardiovascular and lung disease, autoimmune diseases, and several different cancers. These interactions form stable scaffolds which can act as "landing strips" for inflammatory cells as they invade tissue from the circulation. The increase in versican is often coincident with the invasion of leukocytes early in the inflammatory process. Versican interacts with inflammatory cells either indirectly via hyaluronan or directly via receptors such as CD44, P-selectin glycoprotein ligand-1 (PSGL-1), and toll-like receptors (TLRs) present on the surface of immune and non-immune cells. These interactions activate signaling pathways that promote the synthesis and secretion of inflammatory cytokines such as TNFα, IL-6, and NFκB. Versican also influences inflammation by interacting with a variety of growth factors and cytokines involved in regulating inflammation thereby influencing their bioavailability and bioactivity. Versican is produced by multiple cell types involved in the inflammatory process. Conditional total knockout of versican in a mouse model of lung inflammation demonstrated significant reduction in leukocyte invasion into the lung and reduced inflammatory cytokine expression. While versican produced by stromal cells tends to be pro-inflammatory, versican expressed by myeloid cells can create anti-inflammatory and immunosuppressive microenvironments. Inflammation in the tumor microenvironment often contains elevated levels of versican. Perturbing the accumulation of versican in tumors can inhibit inflammation and tumor progression in some cancers. Thus versican, as a component of the ECM impacts immunity and inflammation through regulating immune cell trafficking and activation. Versican is emerging as a potential target in the control of inflammation in a number of different diseases.
PSD-95 and SAP97 are scaffolding proteins that have been implicated in regulating AMPA receptor incorporation and function at synapses. Gain- and loss-of-function approaches, however, have generated ...conflicting results. To minimize adaptations during development and potential dominant-negative effects of overexpression, we have combined silencing of endogenous PSD-95 in mature neurons with heterologous expression of specific SAP97 or PSD-95 isoforms. We find that both PSD-95 and SAP97 contain alternative N termini expressing either double cysteines that normally are palmitoylated (α-isoforms) or an L27 domain (β-isoforms). Whereas α-isoforms of PSD-95 and SAP97 influence AMPA receptor-mediated synaptic strength independent of activity, the effects of β-isoforms are regulated by activity in a CaMKII-dependent manner. Importantly, the synaptic effects of the β-isoforms are masked by the endogenous α-isoform of PSD-95. These results demonstrate that the different N termini of the predominant endogenous forms of PSD-95 (α-isoform) and SAP97 (β-isoform) govern their role in regulating synaptic function.
A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term consumption of “red meat” of mammalian origin. Although multiple theories have attempted to explain this ...human-specific association, none have been conclusively proven. We used an improved method to survey common foods for free and glycosidically bound forms of the nonhuman sialic acidN-glycolylneuraminic acid (Neu5Gc), showing that it is highly and selectively enriched in red meat. The bound form of Neu5Gc is bioavailable, undergoing metabolic incorporation into human tissues, despite being a foreign antigen. Interactions of this antigen with circulating anti-Neu5Gc antibodies could potentially incite inflammation. Indeed, when human-like Neu5Gc-deficient mice were fed bioavailable Neu5Gc and challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Such mice are already prone to develop occasional tumors of the liver, an organ that can incorporate dietary Neu5Gc. Neu5Gc-deficient mice immunized against Neu5Gc and fed bioavailable Neu5Gc developed a much higher incidence of hepatocellular carcinomas, with evidence of Neu5Gc accumulation. Taken together, our data provide an unusual mechanistic explanation for the epidemiological association between red meat consumption and carcinoma risk. This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption.
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