Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis.

Recent studies have established cell type- specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-kappaB. In each of these studies, inhibitors of NF-kappaB activity have been present before the apoptotic stimulus, and so the role of stimulus- induced NF-kappaB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-kappaB activation and apoptosis in cultured cell lines. To address whether Sindbis virus- induced NF-kappaB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-kappaB activity. Complete suppression of virus-induced NF-kappaB activity neither prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition of NF-kappaB activity before infection inhibits Sindbis virus-induced apoptosis. Our results demonstrate that suppression of steady-state, but not stimulus-induced NF-kappaB activity, regulates expression of gene products required for Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF-kappaB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-kappaB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-kappaB activity relative to the death stimulus

Multi-copy and stochastic transformation of multipartite pure states

Characterizing the transformation and classification of multipartite entangled states is a basic problem in quantum information. We study the problem under two most common environments, local operations and classical communications (LOCC), stochastic LOCC and two more general environments, multi-copy LOCC (MCLOCC) and multi-copy SLOCC (MCSLOCC). We show that two transformable multipartite states under LOCC or SLOCC are also transformable under MCLOCC and MCSLOCC. What's more, these two environments are equivalent in the sense that two transformable states under MCLOCC are also transformable under MCSLOCC, and vice versa. Based on these environments we classify the multipartite pure states into a few inequivalent sets and orbits, between which we build the partial order to decide their transformation. In particular, we investigate the structure of SLOCC-equivalent states in terms of tensor rank, which is known as the generalized Schmidt rank. Given the tensor rank, we show that GHZ states can be used to generate all states with a smaller or equivalent tensor rank under SLOCC, and all reduced separable states with a cardinality smaller or equivalent than the tensor rank under LOCC. Using these concepts, we extended the concept of "maximally entangled state" in the multi-partite system.Comment: 8 pages, 1 figure, revised version according to colleagues' comment

SECaps: A Sequence Enhanced Capsule Model for Charge Prediction

Automatic charge prediction aims to predict appropriate final charges according to the fact descriptions for a given criminal case. Automatic charge prediction plays a critical role in assisting judges and lawyers to improve the efficiency of legal decisions, and thus has received much attention. Nevertheless, most existing works on automatic charge prediction perform adequately on high-frequency charges but are not yet capable of predicting few-shot charges with limited cases. In this paper, we propose a Sequence Enhanced Capsule model, dubbed as SECaps model, to relieve this problem. Specifically, following the work of capsule networks, we propose the seq-caps layer, which considers sequence information and spatial information of legal texts simultaneously. Then we design a attention residual unit, which provides auxiliary information for charge prediction. In addition, our SECaps model introduces focal loss, which relieves the problem of imbalanced charges. Comparing the state-of-the-art methods, our SECaps model obtains 4.5% and 6.4% absolutely considerable improvements under Macro F1 in Criminal-S and Criminal-L respectively. The experimental results consistently demonstrate the superiorities and competitiveness of our proposed model.Comment: 13 pages, 3figures, 5 table

Effect of methylation of adenine N6 on kink turn structure depends on location

N6-methyladenine is the most common covalent modification in cellular RNA species, with demonstrated functional consequences. At the molecular level this methylation could alter local RNA structure, and/or modulate the binding of specific proteins. We have previously shown that trans-Hoogsteen-sugar (sheared) A:G base pairs can be completely disrupted by methylation, and that this occurs in a sub-set of human box C/D k-turn structures. In this work we have investigated to what extent sequence context affects the severity with which inclusion of N6-methyladenine into different A:G base pairs of a standard k-turn affects RNA folding and L7Ae protein binding. We find that local sequence has a major influence, ranging from complete absence of folding and protein binding to a relatively mild effect. We have determined the crystal structure of one of these species both free and protein-bound, showing the environment of the methyl group and the way the modification is accommodated into the k-turn structure

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. <p/>Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. <p/>Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Hepatic fibrogenesis requires sympathetic neurotransmitters

Background and aims: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. Methods: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. Results: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by α- and β-adrenoceptor antagonists. HSC from dopamine β-hydroxylase deficient (Dbh(−/−)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(−/−) mice, as evidenced by reduced hepatic accumulation of α-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor β1 (TGF-β1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-β1 and collagen, and increased liver fibrosis. Conclusions: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis

Operator theory and function theory in Drury-Arveson space and its quotients

The Drury-Arveson space $H^2_d$, also known as symmetric Fock space or the $d$-shift space, is a Hilbert function space that has a natural $d$-tuple of operators acting on it, which gives it the structure of a Hilbert module. This survey aims to introduce the Drury-Arveson space, to give a panoramic view of the main operator theoretic and function theoretic aspects of this space, and to describe the universal role that it plays in multivariable operator theory and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page

Topological Schr\"odinger cats: Non-local quantum superpositions of topological defects

Topological defects (such as monopoles, vortex lines, or domain walls) mark locations where disparate choices of a broken symmetry vacuum elsewhere in the system lead to irreconcilable differences. They are energetically costly (the energy density in their core reaches that of the prior symmetric vacuum) but topologically stable (the whole manifold would have to be rearranged to get rid of the defect). We show how, in a paradigmatic model of a quantum phase transition, a topological defect can be put in a non-local superposition, so that - in a region large compared to the size of its core - the order parameter of the system is "undecided" by being in a quantum superposition of conflicting choices of the broken symmetry. We demonstrate how to exhibit such a "Schr\"odinger kink" by devising a version of a double-slit experiment suitable for topological defects. Coherence detectable in such experiments will be suppressed as a consequence of interaction with the environment. We analyze environment-induced decoherence and discuss its role in symmetry breaking.Comment: 7 pages, 4 figure

Cognitive appraisal of environmental stimuli induces emotion-like states in fish

The occurrence of emotions in non-human animals has been the focus of debate over the years. Recently, an interest in expanding this debate to non-tetrapod vertebrates and to invertebrates has emerged. Within vertebrates, the study of emotion in teleosts is particularly interesting since they represent a divergent evolutionary radiation from that of tetrapods, and thus they provide an insight into the evolution of the biological mechanisms of emotion. We report that Sea Bream exposed to stimuli that vary according to valence (positive, negative) and salience (predictable, unpredictable) exhibit different behavioural, physiological and neuromolecular states. Since according to the dimensional theory of emotion valence and salience define a two-dimensional affective space, our data can be interpreted as evidence for the occurrence of distinctive affective states in fish corresponding to each the four quadrants of the core affective space. Moreover, the fact that the same stimuli presented in a predictable vs. unpredictable way elicited different behavioural, physiological and neuromolecular states, suggests that stimulus appraisal by the individual, rather than an intrinsic characteristic of the stimulus, has triggered the observed responses. Therefore, our data supports the occurrence of emotion-like states in fish that are regulated by the individual's perception of environmental stimuli.European Commission [265957 Copewell]; Fundacao para a Ciencia e Tecnologia [SFRH/BD/80029/2011, SFRH/BPD/72952/2010]info:eu-repo/semantics/publishedVersio