Intra-host evolution of multiple genotypes of hepatitis C virus in a chronically infected patient with HIV along a 13-year follow-up period

AbstractThe intra-host evolutionary process of hepatitis C virus (HCV) was analyzed by phylogenetic and coalescent methodologies in a patient co-infected with HCV-1a, HCV-2a, HCV-3a and human immunodeficiency virus (HIV) along a 13-year period.Direct sequence analysis of the E2 and NS5A regions showed diverse evolutionary dynamics, in agreement with different relationships between these regions and the host factors.The Bayesian Skyline Plot analyses of the E2 sequences (cloned) yielded different intra-host evolutionary patterns for each genotype: a steady state of a “consensus” sequence for HCV-1a; a pattern of lineage splitting and extinction for HCV-2a; and a two-phase (drift/diversification) process for HCV-3a.Each genotype evolving in the same patient and at the same time presents a different pattern apparently modulated by the immune pressure of the host.This study provides useful information for the management of co-infected patients and provides insights into the mechanisms behind the intra-host evolution of HCV

Using discrete simulation to support internal logistics process design

The objective of this paper is to present the developments of an ongoing project that aims at implementing an internal materials movement system using autonomous vehicles for supporting logistics processes. In particular the project focus on the movement of final products, from assembly lines to the expedition warehouse and the supply of packaging materials (customer packages), from the raw materials warehouse to the assembly lines. This process is currently carried out by two stackers, in a milk-run environment and, in the context of this project, an innovative solution is proposed to improve the performance of the supply and pickup processes, transforming and optimizing an entirely manual process into an automated one. The main challenge was to investigate the impact on the existing internal logistic system of the new solution and, simultaneously, to explore if new management strategies are needed to satisfy both throughput levels and overall supply chain needs. A simulation model was developed using ARENA Simulation Software to get insights concerning the new challenges posed by the solution to be adopted. Results have revealed that the use of simulation allowed the assessment of the impact of the new internal logistics solution and played a critical role to identify the best dispatching rules to schedule transportation orders in such a complex system. This research shows the flexibility of the simulation tool to address several complex management issues simultaneously that arises in the context of innovative solutions aligned with industry 4.0 challenges.This work has been financially supported by the Portugal Incentive System for Research and Technological Development in scope of the projects in co-promotion nº 002814/2015 (iFACTORY 20152018).info:eu-repo/semantics/publishedVersio

Gut microbiota, diet, and chronic diseases: the role played by oxidative stress

The authors gratefully acknowledge the Espirito Santo Research Foundation (FAPES) (Grant CNPq/FAPES No. 24/2018; Termo Outorga 569/2018) and the Brazilian National Council for Research and Development (CNPq) (CNPq Grant Bolsa Produtividade 2015-2019) for the financial support to our research projectS

Testing Anomalous Higgs Couplings in Triple Photon Production at the Tevatron Collider

We derive bounds on Higgs and gauge--boson anomalous interactions using the CDF data for the process $p \bar{p} \to \gamma\gamma\gamma + X$. We use a linearly realized $SU_L(2) \times U_Y(1)$ invariant effective Lagrangian to describe the bosonic sector of the Standard Model, keeping the fermionic couplings unchanged. All dimension--six operators that lead to anomalous Higgs interactions involving $\gamma$ and $Z$ are considered. We also show the sensitivity that can be achieved for these couplings at Fermilab Tevatron upgrades.Comment: 13 pages, RevTeX, 2 figures included using epsfi

Quantum optical coherence tomography with dispersion cancellation

We propose a new technique, called quantum optical coherence tomography (QOCT), for carrying out tomographic measurements with dispersion-cancelled resolution. The technique can also be used to extract the frequency-dependent refractive index of the medium. QOCT makes use of a two-photon interferometer in which a swept delay permits a coincidence interferogram to be traced. The technique bears a resemblance to classical optical coherence tomography (OCT). However, it makes use of a nonclassical entangled twin-photon light source that permits measurements to be made at depths greater than those accessible via OCT, which suffers from the deleterious effects of sample dispersion. Aside from the dispersion cancellation, QOCT offers higher sensitivity than OCT as well as an enhancement of resolution by a factor of 2 for the same source bandwidth. QOCT and OCT are compared using an idealized sample.Comment: 19 pages, 4 figure

Inhibition Of Epithelial-mesenchymal Transition And Metastasis By Combined Tgfbeta Knockdown And Metformin Treatment In A Canine Mammary Cancer Xenograft Model

Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-β, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-β1. This was combined with metformin treatment, to look at effects on cell migration and the expression of EMT markers. For in vivo study, unmodified or TGF-β1sh cells were injected in the inguinal region of nude athymic female mice followed by metformin treatment. The mice’s lungs were collected and metastatic nodules were subsequently assessed for EMT markers expression. The migration rate was lower in TGF-β1sh cells and when combined with metformin treatment. Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-β1sh cells. Was demonstrated that metformin treatment reduced the number of lung metastases in animals bearing TGF-β1sh tumors. This paralleled a decreased N-cadherin and vimentin expression, and increased E-cadherin and claudin-7 expression in lung metastases. This study confirms the benefits of TGF-β1 silencing in addition to metformin as potential therapeutic agents for breast cancer patients, by blocking EMT process. To the best of our knowledge, we are the first to report metformin treatment in cells with TGF-β1 silencing and their effect on EMT. © 2017, Springer Science+Business Media New York.221274

A coordination model for interactive components

Although presented with a variety of ‘flavours’, the notion of an interactor, as an abstract characterisation of an interactive com- ponent, is well-known in the area of formal modelling techniques for interactive systems. This paper replaces traditional, hierarchical, ‘tree-like’ composition of interactors in the specification of complex interactive sys- tems, by their exogenous coordination through general-purpose software connectors which assure the flow of data and the meet of synchronisation constraints. The paper’s technical contribution is twofold. First a modal logic is defined to express behavioural properties of both interactors and connectors. The logic is new in the sense that its modalities are indexed by fragments of sets of actions to cater for action co-occurrence. Then, this logic is used in the specification of both interactors and coordination layers which orchestrate their interconnection