Effect of environment on biological burden during spacecraft assembly

Determining effects of environment on accumulation of biological burden on spacecraft during assembl

Human cytomegalovirus US28 facilitates cell-to-cell viral dissemination

Human cytomegalovirus (HCMV) encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs). These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28(YFP) expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAG(YFP) in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28(YFP) protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28(YFP) is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the ΔUS28 virus (TB40/E-FLAG(YFP)) generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAG(YFP) (ΔUS28) displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus

Balanced truncation and singular perturbation approximation model order reduction for stochastically controlled linear systems

When solving linear stochastic differential equations numerically, usually a high order spatial discretisation is used. Balanced truncation (BT) and singular perturbation approximation (SPA) are well-known projection techniques in the deterministic framework which reduce the order of a control system and hence reduce computational complexity. This work considers both methods when the control is replaced by a noise term. We provide theoretical tools such as stochastic concepts for reachability and observability, which are necessary for balancing related model order reduction of linear stochastic differential equations with additive L'evy noise. Moreover, we derive error bounds for both BT and SPA and provide numerical results for a specific example which support the theory

Balanced truncation and singular perturbation approximation model order reduction for stochastically controlled linear systems

When solving linear stochastic differential equations numerically, usually a high order spatial discretisation is used. Balanced truncation (BT) and singular perturbation approximation (SPA) are well-known projection techniques in the deterministic framework which reduce the order of a control system and hence reduce computational complexity. This work considers both methods when the control is replaced by a noise term. We provide theoretical tools such as stochastic concepts for reachability and observability, which are necessary for balancing related model order reduction of linear stochastic differential equations with additive Lévy noise. Moreover, we derive error bounds for both BT and SPA and provide numerical results for a specific example which support the theory

The proteasome cap RPT5/Rpt5p subunit prevents aggregation of unfolded ricin A chain

The plant cytotoxin ricin enters mammalian cells by receptor-mediated endocytosis, undergoing retrograde transport to the endoplasmic reticulum (ER) where its catalytic A chain (RTA) is reductively separated from the holotoxin to enter the cytosol and inactivate ribosomes. The currently accepted model is that the bulk of ER-dislocated RTA is degraded by proteasomes. We show here that the proteasome has a more complex role in ricin intoxication than previously recognised, that the previously reported increase in sensitivity of mammalian cells to ricin in the presence of proteasome inhibitors simply reflects toxicity of the inhibitors themselves, and that RTA is a very poor substrate for proteasomal degradation. Denatured RTA and casein compete for a binding site on the regulatory particle of the 26S proteasome, but their fates differ. Casein is degraded, but the mammalian 26S proteasome AAA-ATPase subunit RPT5 acts as a chaperone that prevents aggregation of denatured RTA and stimulates recovery of catalytic RTA activity in vitro. Furthermore, in vivo, the ATPase activity of Rpt5p is required for maximal toxicity of RTA dislocated from the Saccharomyces cerevisiae ER. Our results implicate RPT5/Rpt5p in the triage of substrates in which either activation (folding) or inactivation (degradation) pathways may be initiated

The use of conceptual components in language production: an ERP study

According to frame-theory, concepts can be represented as structured frames that contain conceptual attributes (e.g., "color") and their values (e.g., "red"). A particular color value can be seen as a core conceptual component for (high color-diagnostic; HCD) objects (e.g., bananas) which are strongly associated with a typical color, but less so for (low color-diagnostic; LCD) objects (e.g., bicycles) that exist in many different colors. To investigate whether the availability of a core conceptual component (color) affects lexical access in language production, we conducted two experiments on the naming of visually presented HCD and LCD objects. Experiment 1 showed that, when naming latencies were matched for colored HCD and LCD objects, achromatic HCD objects were named more slowly than achromatic LCD objects. In Experiment 2 we recorded ERPs while participants performed a picture-naming task, in which achromatic target pictures were either preceded by an appropriately colored box (primed condition) or a black and white checkerboard (unprimed condition). We focused on the P2 component, which has been shown to reflect difficulty of lexical access in language production. Results showed that HCD resulted in slower object-naming and a more pronounced P2. Priming also yielded a more positive P2 but did not result in an RT difference. ERP waveforms on the P1, P2 and N300 components showed a priming by color-diagnosticity interaction, the effect of color priming being stronger for HCD objects than for LCD objects. The effect of color-diagnosticity on the P2 component suggests that the slower naming of achromatic HCD objects is (at least in part) due to more difficult lexical retrieval. Hence, the color attribute seems to affect lexical retrieval in HCD words. The interaction between priming and color-diagnosticity indicates that priming with a feature hinders lexical access, especially if the feature is a core feature of the target object

Model order reduction methods applied to neural network training

Neural networks have emerged as powerful and versatile tools in the field of deep learning. As the complexity of the task increases, so do size and architectural complexity of the network, causing compression techniques to become a focus of current research. Parameter truncation can provide a significant reduction in memory and computational complexity. Originating from a model order reduction framework, the Discrete Empirical Interpolation Method is applied to the gradient descent training of neural networks and analyze for important parameters. The approach for various state-of-the-art neural networks is compared to established truncation methods. Further metrics like L2 and Cross-Entropy Loss, as well as accuracy and compression rate are reported

Clec16a is critical for autolysosome function and Purkinje cell survival

CLEC16A is in a locus genetically linked to autoimmune diseases including multiple sclerosis, but the function of this gene in the nervous system is unknown. Here we show that two mouse strains carrying independent Clec16a mutations developed neurodegenerative disease characterized by motor impairments and loss of Purkinje cells. Neurons from Clec16a-mutant mice exhibited increased expression of the autophagy substrate p62, accumulation of abnormal intra-axonal membranous structures bearing the autophagy protein LC3, and abnormal Golgi morphology. Multiple aspects of endocytosis, lysosome and Golgi function were normal in Clec16a-deficient murine embryonic fibroblasts and HeLa cells. However, these cells displayed abnormal bulk autophagy despite unimpaired autophagosome formation. Cultured Clec16a-deficient cells exhibited a striking accumulation of LC3 and LAMP-1 positive autolysosomes containing undigested cytoplasmic contents. Therefore Clec16a, an autophagy protein that is critical for autolysosome function and clearance, is required for Purkinje cell survival

Tomatoes are red: The perception of achromatic objects elicits retrieval of associated color knowledge

When preparing to name an object, semantic knowledge about the object and its attributes is activated, including perceptual properties. It is unclear, however, whether semantic attribute activation contributes to lexical access or is a consequence of activating a concept irrespective of whether that concept is to be named or not. In this study, we measured neural responses using fMRI while participants named objects that are typically green or red, presented in black line drawings. Furthermore, participants underwent two other tasks with the same objects, color naming and semantic judgment, to see if the activation pattern we observe during picture naming is (a) similar to that of a task that requires accessing the color attribute and (b) distinct from that of a task that requires accessing the concept but not its name or color. We used representational similarity analysis to detect brain areas that show similar patterns within the same color category, but show different patterns across the two color categories. In all three tasks, activation in the bilateral fusiform gyri (“Human V4”) correlated with a representational model encoding the red–green distinction weighted by the importance of color feature for the different objects. This result suggests that when seeing objects whose color attribute is highly diagnostic, color knowledge about the objects is retrieved irrespective of whether the color or the object itself have to be named