31,201 research outputs found

    A factor graph description of deep temporal active inference

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    Active inference is a corollary of the Free Energy Principle that prescribes how self-organizing biological agents interact with their environment. The study of active inference processes relies on the definition of a generative probabilistic model and a description of how a free energy functional is minimized by neuronal message passing under thatmodel. This paper presents a tutorial introduction to specifying active inference processes by Forney-style factor graphs (FFG). The FFG framework provides both an insightful representation of the probabilistic model and a biologically plausible inference scheme that, in principle, can be automatically executed in a computer simulation. As an illustrative example, we present an FFG for a deep temporal active inference process. The graph clearly shows how policy selection by expected free energy minimization results from free energy minimization per se, in an appropriate generative policy model

    Constraints for the nuclear parton distributions from Z and W production at the LHC

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    The LHC is foreseen to finally bring also the nuclear collisions to the TeV scale thereby providing new possibilities for physics studies, in particular related to the electro-weak sector of the Standard Model. We study here the Z and W production in proton-lead and lead-lead collisions at the LHC, concentrating on the prospects of testing the factorization and constraining the nuclear modifications of the parton distribution functions (PDFs). Especially, we find that the rapidity asymmetries in proton-nucleus collisions, arising from the differences in the PDFs between the colliding objects, provide a decisive advantage in comparison to the rapidity-symmetric nucleus-nucleus case. We comment on how such studies will help to improve our knowledge of the nuclear PDFs.Comment: The version accepted for publication in JHEP. New figures has been added, and we also discuss the single charged lepton productio

    DNA methylation profiling to assess pathogenicity of BRCA1 unclassified variants in breast cancer

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    Germline pathogenic mutations in BRCA1 increase risk of developing breast cancer. Screening for mutations in BRCA1 frequently identifies sequence variants of unknown pathogenicity and recent work has aimed to develop methods for determining pathogenicity. We previously observed that tumor DNA methylation can differentiate BRCA1-mutated from BRCA1-wild type tumors. We hypothesized that we could predict pathogenicity of variants based on DNA methylation profiles of tumors that had arisen in carriers of unclassified variants. We selected 150 FFPE breast tumor DNA samples [47 BRCA1 pathogenic mutation carriers, 65 BRCAx (BRCA1-wild type), 38 BRCA1 test variants] and analyzed a subset (n=54) using the Illumina 450K methylation platform, using the remaining samples for bisulphite pyrosequencing validation. Three validated markers (BACH2, C8orf31, and LOC654342) were combined with sequence bioinformatics in a model to predict pathogenicity of 27 variants (independent test set). Predictions were compared with standard multifactorial likelihood analysis. Prediction was consistent for c.5194-12G>A (IVS 19-12 G>A) (P>0.99); 13 variants were considered not pathogenic or likely not pathogenic using both approaches. We conclude that tumor DNA methylation data alone has potential to be used in prediction of BRCA1 variant pathogenicity but is not independent of estrogen receptor status and grade, which are used in current multifactorial models to predict pathogenicity

    Application of a sustainability index for integrated urban water management in Southern African cities: Case study comparison – Maputo and Hermanus

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    Poor service provision in developing countries, and particularly the provision of water-related services, present serious challenges to urban development. It is estimated that 300 m. people in Africa do not have access to safe drinking water and 313 m. have limited access to adequate sanitation. The critical situation in the water sector continues to undermine strategies for poverty eradication and retards development. It is possible that the failure in service provision can in part be attributed to an inability by policy makers to address urban water management in a holistic  manner. In this study, a systems approach has been adopted to develop a composite index that could be used to assess the potential of a town or city to be sustainable. This index, the Sustainability Index for Integrated Urban Water Management (SIUWM) is composed of 5 components which disaggregate into 20 indicators and ultimately into 64 variables. Two Southern African urban centres, Hermanus and Maputo, were selected as initial case studies to test the applicability and validity of the index and to compare their sustainability index scores. Results of the SIUWM  application demonstrate that the index could highlight areas for  improvement and ultimately guide appropriate action and policy-making towards better service delivery and improved resource management

    Compatibility of neutrino DIS data and global analyses of parton distribution functions

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    Neutrino\antineutrino deep inelastic scattering (DIS) data provide useful constrains for the flavor decomposition in global fits of parton distribution functions (PDF). The smallness of the cross-sections requires the use of nuclear targets in the experimental setup. Understanding the nuclear corrections is, for this reason, of utmost importance for a precise determination of the PDFs. Here, we explore the nuclear effects in the neutrino\antineutrino-nucleon DIS by comparing the NuTeV, CDHSW, and CHORUS cross-sections to the predictions derived from the latest parton distribution functions and their nuclear modifications. We obtain a good description of these data and find no apparent disagreement between the nuclear effects in neutrino DIS and those in charged lepton DIS. These results also indicate that further improvements in the knowledge of the nuclear PDFs could be obtained by a more extensive use of these sets of neutrino data.Comment: 16 pages, 8 figure

    Geometric control of myogenic cell fate.

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    This work combines expertise in stem cell biology and bioengineering to define the system for geometric control of proliferation and differentiation of myogenic progenitor cells. We have created an artificial niche of myogenic progenitor cells, namely, modified extracellular matrix (ECM) substrates with spatially embedded growth or differentiation factors (GF, DF) that predictably direct muscle cell fate in a geometric pattern. Embedded GF and DF signal progenitor cells from specifically defined areas on the ECM successfully competed against culture media for myogenic cell fate determination at a clearly defined boundary. Differentiation of myoblasts into myotubes is induced in growth-promoting medium, myotube formation is delayed in differentiation-promoting medium, and myogenic cells, at different stages of proliferation and differentiation, can be induced to coexist adjacently in identical culture media. This method can be used to identify molecular interactions between cells in different stages of myogenic differentiation, which are likely to be important determinants of tissue repair. The designed ECM niches can be further developed into a vehicle for transplantation of myogenic progenitor cells maintaining their regenerative potential. Additionally, this work may also serve as a general model to engineer synthetic cellular niches to harness the regenerative potential of organ stem cells

    Modelling the Physics of Bubble Nucleation in Histotripsy

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    This work aims to establish a theoretical framework for the modeling of bubble nucleation in histotripsy. A phenomenological version of the classical nucleation theory was parametrized with histotripsy experimental data, fitting a temperature-dependent activity factor that harmonizes theoretical predictions and experimental data for bubble nucleation at both high and low temperatures. Simulations of histotripsy pressure and temperature fields are then used in order to understand spatial and temporal properties of bubble nucleation at varying sonication conditions. This modeling framework offers a thermodynamic understanding on the role of the ultrasound frequency, waveforms, peak focal pressures, and duty cycle on patterns of ultrasound-induced bubble nucleation. It was found that at temperatures lower than 50 °C, nucleation rates are more appreciable at very large negative pressures such as -30 MPa. For focal peak-negative pressures of -15 MPa, characteristic of boiling histotripsy, nucleation rates grow by 20 orders of magnitude in the temperature interval 60 °C-100 °C

    Exposure of tropical ecosystems to artificial light at night: Brazil as a case study

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    Artificial nighttime lighting from streetlights and other sources has a broad range of biological effects. Understanding the spatial and temporal levels and patterns of this lighting is a key step in determining the severity of adverse effects on different ecosystems, vegetation, and habitat types. Few such analyses have been conducted, particularly for regions with high biodiversity, including the tropics. We used an intercalibrated version of the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS) images of stable nighttime lights to determine what proportion of original and current Brazilian vegetation types are experiencing measurable levels of artificial light and how this has changed in recent years. The percentage area affected by both detectable light and increases in brightness ranged between 0 and 35% for native vegetation types, and between 0 and 25% for current vegetation (i.e. including agriculture). The most heavily affected areas encompassed terrestrial coastal vegetation types (restingas and mangroves), Semideciduous Seasonal Forest, and Mixed Ombrophilous Forest. The existing small remnants of Lowland Deciduous and Semideciduous Seasonal Forests and of Campinarana had the lowest exposure levels to artificial light. Light pollution has not often been investigated in developing countries but our data show that it is an environmental concern

    Mechanisms of nuclei growth in ultrasound bubble nucleation

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    This paper interrogates the intersections between bubble dynamics and classical nucleation theory (CNT) towards constructing a model that describes intermediary nucleation events between the extrema of cavitation and boiling. We employ Zeldovich's hydrodynamic approach to obtain a description of bubble nuclei that grow simultaneously via hydrodynamic excitation by the acoustic field and vapour transport. By quantifying the relative dominance of both mechanisms, it is then possible to discern the extent to which viscosity, inertia, surface tension and vapour transport shape the growth of bubble nuclei through non-dimensional numbers that naturally arise within the theory. The first non-dimensional number Φ12/Φ2 is analogous to the Laplace number, representing the balance between surface tension and inertial constraints to viscous effects. The second non-dimensional number δ represents how enthalpy transport into the bubble can reduce nucleation rates by cooling the surrounding liquid. This formulation adds to the current understanding of ultrasound bubble nucleation by accounting for bubble dynamics during nucleation, quantifying the physical distinctions between “boiling” and “cavitation” bubbles through non-dimensional parameters, and outlining the characteristic timescales of nucleation according to the growth mechanism of bubbles throughout the histotripsy temperature range. We observed in our simulations that viscous effects control the process of ultrasound nucleation in water-like media throughout the 0–120 °C temperature range, although this dominance decreases with increasing temperatures. Enthalpy transport was found to reduce nucleation rates for increasing temperatures. This effect becomes significant at temperatures above 30 °C and favours the creation of fewer nuclei that are larger in size. Conversely, negligible enthalpy transport at lower temperatures can enable the nucleation of dense clusters of small nuclei, such as cavitation clouds. We find that nuclei growth as modelled by the Rayleigh-Plesset equation occurs over shorter timescales than as modelled by vapour-dominated growth. This suggests that the first stage of bubble nuclei growth is hydrodynamic, and vapour transport effects can only be observed over longer timescales. Finally, we propose that this framework can be used for comparison between different experiments in bubble nucleation, towards standardisation and dosimetry of protocols
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