1,148 research outputs found
Improved algorithm for neuronal ensemble inference by Monte Carlo method
Neuronal ensemble inference is one of the significant problems in the study
of biological neural networks. Various methods have been proposed for ensemble
inference from their activity data taken experimentally. Here we focus on
Bayesian inference approach for ensembles with generative model, which was
proposed in recent work. However, this method requires large computational
cost, and the result sometimes gets stuck in bad local maximum solution of
Bayesian inference. In this work, we give improved Bayesian inference algorithm
for these problems. We modify ensemble generation rule in Markov chain Monte
Carlo method, and introduce the idea of simulated annealing for hyperparameter
control. We also compare the performance of ensemble inference between our
algorithm and the original one.Comment: 14 pages, 3 figure
Mapping the Distribution of Invasive Staphylococcus aureus across Europe
Franklin Lowy discusses a new study in PLoS Medicine in which the investigators developed an interactive tool for analyzing the spatial distribution of invasive Staphylococcus aureus
Holographic Reconstruction and Renormalization in Asymptotically Ricci-flat Spacetimes
In this work we elaborate on an extension of the AdS/CFT framework to a
subclass of gravitational theories with vanishing cosmological constant. By
building on earlier ideas, we construct a correspondence between Ricci-flat
spacetimes admitting asymptotically hyperbolic hypersurfaces and a family of
conformal field theories on a codimension two manifold at null infinity. By
truncating the gravity theory to the pure gravitational sector, we find the
most general spacetime asymptotics, renormalize the gravitational action,
reproduce the holographic stress tensors and Ward identities of the family of
CFTs and show how the asymptotics is mapped to and reconstructed from conformal
field theory data. In even dimensions, the holographic Weyl anomalies identify
the bulk time coordinate with the spectrum of central charges with
characteristic length the bulk Planck length. Consistency with locality in the
bulk time direction requires a notion of locality in this spectrum.Comment: 44 pages, 4 figures. v2: minor changes in section
High-throughput spheroid screens using volume, resazurin reduction and acid phosphatase activity
Mainstream adoption of physiologically-relevant three-dimensional models has been slow in the last 50 years due to long, manual protocols with poor reproducibility, high price and closed commercial platforms. This chapter describes high-throughput, low-cost, open methods for spheroid viability assessment which use readily-available reagents and open-source software to analyse spheroid volume, metabolism and enzymatic activity. We provide two ImageJ macros for automated spheroid size determination - for both single images and for images in stacks. We also share an Excel template spreadsheet allowing users to rapidly process spheroid size data, analyse plate uniformity (such as edge effects and systematic seeding errors), detect outliers and calculate dose-response. The methods would be useful to researchers in preclinical and translational research planning to move away from simplistic monolayer studies and explore 3D spheroid screens for drug safety and efficacy without substantial investment in money or time
Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids
Multicellular tumor spheroids are an important {\it in vitro} model of the
pre-vascular phase of solid tumors, for sizes well below the diagnostic limit:
therefore a biophysical model of spheroids has the ability to shed light on the
internal workings and organization of tumors at a critical phase of their
development. To this end, we have developed a computer program that integrates
the behavior of individual cells and their interactions with other cells and
the surrounding environment. It is based on a quantitative description of
metabolism, growth, proliferation and death of single tumor cells, and on
equations that model biochemical and mechanical cell-cell and cell-environment
interactions. The program reproduces existing experimental data on spheroids,
and yields unique views of their microenvironment. Simulations show complex
internal flows and motions of nutrients, metabolites and cells, that are
otherwise unobservable with current experimental techniques, and give novel
clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The
published version contains links to a supplementary text and three video
file
Information transmission in oscillatory neural activity
Periodic neural activity not locked to the stimulus or to motor responses is
usually ignored. Here, we present new tools for modeling and quantifying the
information transmission based on periodic neural activity that occurs with
quasi-random phase relative to the stimulus. We propose a model to reproduce
characteristic features of oscillatory spike trains, such as histograms of
inter-spike intervals and phase locking of spikes to an oscillatory influence.
The proposed model is based on an inhomogeneous Gamma process governed by a
density function that is a product of the usual stimulus-dependent rate and a
quasi-periodic function. Further, we present an analysis method generalizing
the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the
information content in such data. We demonstrate these tools on recordings from
relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic
Spheroid arrays for high-throughput single-cell analysis of spatial patterns and biomarker expression in 3D
We describe and share a device, methodology and image analysis algorithms, which allow up to 66 spheroids to be arranged into a gel-based array directly from a culture plate for downstream processing and analysis. Compared to processing individual samples, the technique uses 11-fold less reagents, saves time and enables automated imaging. To illustrate the power of the technology, we showcase applications of the methodology for investigating 3D spheroid morphology and marker expression and for in vitro safety and efficacy screens. Firstly, spheroid arrays of 11 cell-lines were rapidly assessed for differences in spheroid morphology. Secondly, highly-positive (SOX-2), moderately-positive (Ki-67) and weakly-positive (βIII-tubulin) protein targets were detected and quantified. Third, the arrays enabled screening of ten media compositions for inducing differentiation in human neurospheres. Lastly, the application of spheroid microarrays for spheroid-based drug-screens was demonstrated by quantifying the dose-dependent drop in proliferation and increase in differentiation in etoposide-treated neurospheres
Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report
<p>Abstract</p> <p>Introduction</p> <p>Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously.</p> <p>Case presentation</p> <p>We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later.</p> <p>Conclusion</p> <p>Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma.</p
Whole-body integration of gene expression and single-cell morphology
Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets
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