Introduction to modeling viral infections and immunity

Copyright © 2018 John Wiley & Sons, Inc. All rights reserved.Infectious agents, such as HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), malaria, and influenza remain significant public health threats, with ~41 million people chronically infected by HIV, ~331 million infected by HBV, ~148 million infected by HCV, and ~351 million cases of malaria, according to the Global Burden of Disease 2013 study. In addition, threats of new influenza pandemics or emerging viruses, such as Ebola and Zika, have created alarm in the United States and in many parts of the world. Despite intensive research efforts by public and private institutions, there are still no vaccines for HIV, HCV, malaria, Ebola, Zika, and many other pathogens. Even though there has been enormous progress with antiviral therapies for chronic infections, we are still unable to cure HIV and HBV, and life‐long treatment is needed.info:eu-repo/semantics/publishedVersio

The role of infected cell proliferation in the clearance of acute HBV Infection in humans

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection data together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. In conclusion, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.This work was funded by National Institutes of Health grants R01-AI116868 (RMR), R01-AI028433 (ASP) and R01-OD011095 (ASP). Portions of this work were performed under the auspices of the U.S. Department of Energy under contract DE-AC52-06NA25396.info:eu-repo/semantics/publishedVersio

Inverse semigroup actions as groupoid actions

To an inverse semigroup, we associate an \'etale groupoid such that its actions on topological spaces are equivalent to actions of the inverse semigroup. Both the object and the arrow space of this groupoid are non-Hausdorff. We show that this construction provides an adjoint functor to the functor that maps a groupoid to its inverse semigroup of bisections, where we turn \'etale groupoids into a category using algebraic morphisms. We also discuss how to recover a groupoid from this inverse semigroup.Comment: Corrected a typo in Lemma 2.14 in the published versio

Methodology for the characterization of elastic constants of wood from tree branches

In biomechanical analyses, computational models are essential tools for simulating the behavior of a tree subjected to a load. However, such models allow only approximation of the actual behavior of the tree if the elastic parameters of the wood in different tree parts (stem, branches, and roots) and at least orthotropic behavior are not considered. In addition, as the wood is green, the parameters of strength and stiffness must be adequate for this level of moisture. However, even for stem wood, knowledge of elastic properties is not available for most species used in urban tree planting, and this scarcity of information is even greater for wood branches. The objective of this research was to evaluate methodology, based on wave propagation, in characterizing the 12 elastic constants of wood from branches. Complementarily, compression tests were performed to characterize the strength. The obtained elastic parameters using ultrasound tests were comparable with the values expected based on theoretical aspects related to the behavior of the wood. The results of the compression test complemented the ultrasound characterization, but the application of this method for the complete characterization of the elastic parameters is not feasible for tree branches because of their small size.1448439845

Probabilistic control of HIV latency and transactivation by the Tat gene circuit

Copyright © 2020 National Academy of Sciences.The reservoir of HIV latently infected cells is the major obstacle for eradication of HIV infection. The “shock-and-kill” strategy proposed earlier aims to reduce the reservoir by activating cells out of latency. While the intracellular HIV Tat gene circuit is known to play important roles in controlling latency and its transactivation in HIV-infected cells, the detailed control mechanisms are not well understood. Here we study the mechanism of probabilistic control of the latent and the transactivated cell phenotypes of HIV-infected cells. We reconstructed the probability landscape, which is the probability distribution of the Tat gene circuit states, by directly computing the exact solution of the underlying chemical master equation. Results show that the Tat circuit exhibits a clear bimodal probability landscape (i.e., there are two distinct probability peaks, one associated with the latent cell phenotype and the other with the transactivated cell phenotype). We explore potential modifications to reactions in the Tat gene circuit for more effective transactivation of latent cells (i.e., the shock-and-kill strategy). Our results suggest that enhancing Tat acetylation can dramatically increase Tat and viral production, while increasing the Tat–transactivation response binding affinity can transactivate latent cells more rapidly than other manipulations. Our results further explored the “block and lock” strategy toward a functional cure for HIV. Overall, our study demonstrates a general approach toward discovery of effective therapeutic strategies and druggable targets by examining control mechanisms of cell phenotype switching via exactly computed probability landscapes of reaction networks.info:eu-repo/semantics/publishedVersio

Forecasting Large Realized Covariance Matrices: The Benefits of Factor Models and Shrinkage

We propose a model to forecast large realized covariance matrices of returns, applying it to the constituents of the S\&P 500 daily. To address the curse of dimensionality, we decompose the return covariance matrix using standard firm-level factors (e.g., size, value, and profitability) and use sectoral restrictions in the residual covariance matrix. This restricted model is then estimated using vector heterogeneous autoregressive (VHAR) models with the least absolute shrinkage and selection operator (LASSO). Our methodology improves forecasting precision relative to standard benchmarks and leads to better estimates of minimum variance portfolios

Surface resonant modes in colloidal photonic crystals

Herein we report an experimental and theoretical optical analysis of the effect of growing a dielectric slab on the surface of photonic colloidal crystals. Optical spectroscopy shows an enhancement of the transmitted intensity for certain frequencies within the photonic pseudogap. Simulations based on a scalar wave approximation fairly reproduce the experimental results and provide a description of the interplay between the features arising from the presence of the surface slab and the finite size of the photonic crystal. The experimental observations are explained by the excitation of photon resonant states at the crystal boundary. Our work demonstrates that the amplitude of light waves penetrating the crystal with frequencies lying within the pseudogap range can be greatly modified by rather simple means

Use of the video transect method for characterizing the Itacolomis reefs, eastern Brazil

O método do vídeo-transecto consiste em uma filmagem do fundo marinho ao longo de uma seção linear, e as imagens são posteriormente analisadas, em laboratório, na tela de um computador. Este método foi aplicado pela primeira vez no Brasil nos recifes do interior da Baía de Todos os Santos, com resultados satisfatórios. O objetivo deste trabalho foi determinar qual seria o menor esforço amostral na aplicação do vídeo transecto para avaliar a comunidade de coral do recife Pedra do Silva, no complexo de recifes dos Itacolomis, na Reserva Extrativista Marinha de Corumbau, no sul do estado da Bahia. Cada transécto foi analisado em toda a sua extensão em quadros sucessivos gerados com o congelamento da imagem na tela de um computador. Os resultados obtidos apontam o número de seis transéctos de 20 m de comprimento para uma análise de vinte pontos por quadro como adequada para a identificação taxonômica das principais categorias dos corais construtores e dos componentes da biota bentônica dos recifes, podendo toda a operação ser executada durante apenas um mergulho por local de amostragem.The video-transect method consists of a field survey performed with a video-camera along a line of fixed length, with the registered images further analyzed using a computer. This method was successfully applied in Brazil for the first time in the coral reefs of Todos os Santos Bay. The main goal of this work was to define the minimum sampling effort needed to describe the coral community when the video-transect method was applied to a selected reef site, namely the Pedra do Silva Reef in the Itacolomis reef complex, inside the Corumbau Marine Extractive Reserve, in Southern Bahia. Each transect was analyzed throughout its length, in successive captured video frames. The findings revealed that six 20 m long transects with an analysis of twenty points per image (frame) was sufficient for sampling the broad taxonomic categories of hard corals and major reef benthos, and that the whole field operation could be performed during one dive per station