Probabilistic Spatial Transformers for Bayesian Data Augmentation

High-capacity models require vast amounts of data, and data augmentation is a common remedy when this resource is limited. Standard augmentation techniques apply small hand-tuned transformations to existing data, which is a brittle process that realistically only allows for simple transformations. We propose a Bayesian interpretation of data augmentation where the transformations are modelled as latent variables to be marginalized, and show how these can be inferred variationally in an end-to-end fashion. This allows for significantly more complex transformations than manual tuning, and the marginalization implies a form of test-time data augmentation. The resulting model can be interpreted as a probabilistic extension of spatial transformer networks. Experimentally, we demonstrate improvements in accuracy and uncertainty quantification in image and time series classification tasks.Comment: Submitted to the International Conference on Machine Learning (ICML), 202

Wirkung carcinostatischer äthylenimin-verbindungen auf den DPN-gehalt therapieresistener tumoren

Preliminary experiments with the ascites form of the relatively therapeutic-resistant DS-tumour demonstrated that the decrease in DPN content and the inhibition of glycolysis in the neoplastic cells under the influence of ethylenimine compounds were delayed, in comparison with the rapid changes observed in Ehrlich-ascites carcinomas. Extending these observations, the therapeutic effect of carcinostatic ethylenimine compounds was studied in rats bearing solid forms of either the Jensen sarcoma or the therapeutic-resistant DS-tumour. During the course of the experiments the DPN content of the tumours was followed. In the Jensen sarcoma the DPN content decreased sharply as early as the first day following administration of the carcinostatic, while the DS-tumour, in contrast, showed no clear change during the first six days. A cure was obtained in nine out of thirteen cases of the Jensen-sarcoma rats, while no cure was observed in six DS-tumour-bearing rats. These experiments further support our hypothesis, that carcinostatic ethylenimine compounds are therapeutically effective though they depress the DPN content in the tumour

Sub-Sets of Cancer Stem Cells Differ Intrinsically in Their Patterns of Oxygen Metabolism

PMCID: PMC3640080This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Quiescience as a mechanism for cyclical hypoxia and acidosis

Tumour tissue characteristically experiences fluctuations in substrate supply. This unstable microenvironment drives constitutive metabolic changes within cellular populations and, ultimately, leads to a more aggressive phenotype. Previously, variations in substrate levels were assumed to occur through oscillations in the hæmodynamics of nearby and distant blood vessels. In this paper we examine an alternative hypothesis, that cycles of metabolite concentrations are also driven by cycles of cellular quiescence and proliferation. Using a mathematical modelling approach, we show that the interdependence between cell cycle and the microenvironment will induce typical cycles with the period of order hours in tumour acidity and oxygenation. As a corollary, this means that the standard assumption of metabolites entering diffusive equilibrium around the tumour is not valid; instead temporal dynamics must be considered

Precursors of Cytochrome Oxidase in Cytochrome-Oxidase-Deficient Cells of Neurospora crassa

Three different cell types of Neurospora crassa deficient in cytochrome oxidase were studied: the nuclear mutant cni-1, the cytoplasmic mutant mi-1 and copper-depleted wild-type cells. * 1. The enzyme-deficient cells have retained a functioning mitochondrial protein synthesis. It accounted for 12–16% of the total protein synthesis of the cell. However, the analysis of mitochondrial translation products by gel electrophoresis revealed that different amounts of individual membrane proteins were synthesized. Especially mutant cni-1 produced large amounts of a small molecular weight translation product, which is barely detectable in wild-type. * 2. Mitochondrial preparations of cytochrome-oxidase-deficient cells were examined for precursors of cytochrome oxidase. The presence of polypeptide components of cytochrome oxidase in the mitochondria was established with specific antibodies. On the other hand, no significant amounts of heme a could be extracted. * 3. Radioactively labelled components of cytochrome oxidase were isolated by immunoprecipitation and analysed by gel electrophoresis. All three cell types contained the enzyme components 4–7, which are translated on cytoplasmic ribosomes. The mitochondrially synthesized components 1–3 were present in mi-1 mutant and in copper-depleted wild-type cells. In contrast, components 2 and 3 were not detectable in the nuclear mutant cni-1. Both relative and absolute amounts of these polypeptides in the enzyme-deficient cells were quite different from those in wild-type cells. * 4. The components of cytochrome oxidase found in the enzyme-deficient cells were tightly associated with the mitochondrial membranes. * 5. Processes, which affect and may control the production of enzyme precursors or their assembly to a functional cytochrome oxidase are discussed

Dynamic interplay between tumour, stroma and immune system can drive or prevent tumour progression

In the tumour microenvironment, cancer cells directly interact with both the immune system and the stroma. It is firmly established that the immune system, historically believed to be a major part of the body's defence against tumour progression, can be reprogrammed by tumour cells to be ineffective, inactivated, or even acquire tumour promoting phenotypes. Likewise, stromal cells and extracellular matrix can also have pro-and anti-tumour properties. However, there is strong evidence that the stroma and immune system also directly interact, therefore creating a tripartite interaction that exists between cancer cells, immune cells and tumour stroma. This interaction contributes to the maintenance of a chronically inflamed tumour microenvironment with pro-tumorigenic immune phenotypes and facilitated metastatic dissemination. A comprehensive understanding of cancer in the context of dynamical interactions of the immune system and the tumour stroma is therefore required to truly understand the progression toward and past malignancy.Comment: 36 pages, 4 figures, 1 tabl

Dynamic Phase Transition in a Time-Dependent Ginzburg-Landau Model in an Oscillating Field

The Ginzburg-Landau model below its critical temperature in a temporally oscillating external field is studied both theoretically and numerically. As the frequency or the amplitude of the external force is changed, a nonequilibrium phase transition is observed. This transition separates spatially uniform, symmetry-restoring oscillations from symmetry-breaking oscillations. Near the transition a perturbation theory is developed, and a switching phenomenon is found in the symmetry-broken phase. Our results confirm the equivalence of the present transition to that found in Monte Carlo simulations of kinetic Ising systems in oscillating fields, demonstrating that the nonequilibrium phase transition in both cases belongs to the universality class of the equilibrium Ising model in zero field. This conclusion is in agreement with symmetry arguments [G. Grinstein, C. Jayaprakash, and Y. He, Phys. Rev. Lett. 55, 2527 (1985)] and recent numerical results [G. Korniss, C.J. White, P. A. Rikvold, and M. A. Novotny, Phys. Rev. E (submitted)]. Furthermore, a theoretical result for the structure function of the local magnetization with thermal noise, based on the Ornstein-Zernike approximation, agrees well with numerical results in one dimension.Comment: 16 pp. RevTex, 9 embedded ps figure

Diffuse-Charge Dynamics in Electrochemical Systems

The response of a model micro-electrochemical system to a time-dependent applied voltage is analyzed. The article begins with a fresh historical review including electrochemistry, colloidal science, and microfluidics. The model problem consists of a symmetric binary electrolyte between parallel-plate, blocking electrodes which suddenly apply a voltage. Compact Stern layers on the electrodes are also taken into account. The Nernst-Planck-Poisson equations are first linearized and solved by Laplace transforms for small voltages, and numerical solutions are obtained for large voltages. The ``weakly nonlinear'' limit of thin double layers is then analyzed by matched asymptotic expansions in the small parameter $\epsilon = \lambda_D/L$, where $\lambda_D$ is the screening length and $L$ the electrode separation. At leading order, the system initially behaves like an RC circuit with a response time of $\lambda_D L / D$ (not $\lambda_D^2/D$), where $D$ is the ionic diffusivity, but nonlinearity violates this common picture and introduce multiple time scales. The charging process slows down, and neutral-salt adsorption by the diffuse part of the double layer couples to bulk diffusion at the time scale, $L^2/D$. In the ``strongly nonlinear'' regime (controlled by a dimensionless parameter resembling the Dukhin number), this effect produces bulk concentration gradients, and, at very large voltages, transient space charge. The article concludes with an overview of more general situations involving surface conduction, multi-component electrolytes, and Faradaic processes.Comment: 10 figs, 26 pages (double-column), 141 reference