1,581 research outputs found

    Analogies between geminivirus and oncovirus: Cell cycle regulation

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    Geminiviruses are a large family of plant viruses whose genome is composed of one or two circular and single strand of DNA. They replicate in the cell nucleus being Rep protein, the only viral protein necessary for their replication process. Geminiviruses as same as animal DNA oncoviruses, like SV40, adenovirus and papillomavirus, use the host replication machinery to replicate their DNA. Consequently, they alter host cell cycle regulation to create a suitable environment for their replication. One of the events involved in this alteration would be the inactivation of the retinoblastoma protein (pRb) that negatively regulates the G1/S transition in cells. The discovery of one homologue of the pRb in plants and the finding that Rep protein of some geminiviruses interacts with human retinoblastoma protein, as well as animal virus oncoproteins, is very interesting. This finding laid the groundwork for subsequent detection of analogies between geminiviruses and animal DNA tumor viruses, especially in their interaction with pRb. Moreover, the finding allowed the determination of how this interaction affects the regulation of the cell cycle in plants and animals. Accumulated knowledge generates new interesting questions and possible implications, and so, in this document, we dare to watch in that direction.Key words: Geminivirus, oncovirus, retinoblastoma protein, cell cycle regulation, endoreduplication

    Mass hierarchy, mass gap and corrections to Newton's law on thick branes with Poincare symmetry

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    We consider a scalar thick brane configuration arising in a 5D theory of gravity coupled to a self-interacting scalar field in a Riemannian manifold. We start from known classical solutions of the corresponding field equations and elaborate on the physics of the transverse traceless modes of linear fluctuations of the classical background, which obey a Schroedinger-like equation. We further consider two special cases in which this equation can be solved analytically for any massive mode with m^2>0, in contrast with numerical approaches, allowing us to study in closed form the massive spectrum of Kaluza-Klein (KK) excitations and to compute the corrections to Newton's law in the thin brane limit. In the first case we consider a solution with a mass gap in the spectrum of KK fluctuations with two bound states - the massless 4D graviton free of tachyonic instabilities and a massive KK excitation - as well as a tower of continuous massive KK modes which obey a Legendre equation. The mass gap is defined by the inverse of the brane thickness, allowing us to get rid of the potentially dangerous multiplicity of arbitrarily light KK modes. It is shown that due to this lucky circumstance, the solution of the mass hierarchy problem is much simpler and transparent than in the (thin) Randall-Sundrum (RS) two-brane configuration. In the second case we present a smooth version of the RS model with a single massless bound state, which accounts for the 4D graviton, and a sector of continuous fluctuation modes with no mass gap, which obey a confluent Heun equation in the Ince limit. (The latter seems to have physical applications for the first time within braneworld models). For this solution the mass hierarchy problem is solved as in the Lykken-Randall model and the model is completely free of naked singularities.Comment: 25 pages in latex, no figures, content changed, corrections to Newton's law included for smooth version of RS model and an author adde

    Management of SARS-CoV-2 Infection: Key Focus in Macrolides Efficacy for COVID-19

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    Macrolides (e.g., erythromycin, fidaxomicin, clarithromycin, and azithromycin) are a class of bacteriostatic antibiotics commonly employed in medicine against various gram-positive and atypical bacterial species mostly related to respiratory tract infections, besides they possess anti-inflammatory and immunomodulatory effects. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). It was first detected in Wuhan, Hubei, China, in December 2019 and resulted in a continuing pandemic. Macrolides have been extensively researched as broad adjunctive therapy for COVID-19 due to its immunostimulant abilities. Among such class of drugs, azithromycin is described as azalide and is well-known for its ability to decrease the production of pro-inflammatory cytokines, including matrix metalloproteinases, tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8. In fact, a report recently published highlighted the effectiveness of combining azithromycin and hydroxychloroquine for COVID-19 treatment. Indeed, it has been underlined that azithromycin quickly prevents SARS-CoV-2 infection by raising the levels of both interferons and interferon-stimulated proteins at the same time which reduces the virus replication and release. In this sense, the current review aims to evaluate the applications of macrolides for the treatment of COVID-19.NC-M acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

    Learning Interpretable Rules for Multi-label Classification

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    Multi-label classification (MLC) is a supervised learning problem in which, contrary to standard multiclass classification, an instance can be associated with several class labels simultaneously. In this chapter, we advocate a rule-based approach to multi-label classification. Rule learning algorithms are often employed when one is not only interested in accurate predictions, but also requires an interpretable theory that can be understood, analyzed, and qualitatively evaluated by domain experts. Ideally, by revealing patterns and regularities contained in the data, a rule-based theory yields new insights in the application domain. Recently, several authors have started to investigate how rule-based models can be used for modeling multi-label data. Discussing this task in detail, we highlight some of the problems that make rule learning considerably more challenging for MLC than for conventional classification. While mainly focusing on our own previous work, we also provide a short overview of related work in this area.Comment: Preprint version. To appear in: Explainable and Interpretable Models in Computer Vision and Machine Learning. The Springer Series on Challenges in Machine Learning. Springer (2018). See http://www.ke.tu-darmstadt.de/bibtex/publications/show/3077 for further informatio

    Improving Editorial Workflow and Metadata Quality at Springer Nature

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    Identifying the research topics that best describe the scope of a scientific publication is a crucial task for editors, in particular because the quality of these annotations determine how effectively users are able to discover the right content in online libraries. For this reason, Springer Nature, the world's largest academic book publisher, has traditionally entrusted this task to their most expert editors. These editors manually analyse all new books, possibly including hundreds of chapters, and produce a list of the most relevant topics. Hence, this process has traditionally been very expensive, time-consuming, and confined to a few senior editors. For these reasons, back in 2016 we developed Smart Topic Miner (STM), an ontology-driven application that assists the Springer Nature editorial team in annotating the volumes of all books covering conference proceedings in Computer Science. Since then STM has been regularly used by editors in Germany, China, Brazil, India, and Japan, for a total of about 800 volumes per year. Over the past three years the initial prototype has iteratively evolved in response to feedback from the users and evolving requirements. In this paper we present the most recent version of the tool and describe the evolution of the system over the years, the key lessons learnt, and the impact on the Springer Nature workflow. In particular, our solution has drastically reduced the time needed to annotate proceedings and significantly improved their discoverability, resulting in 9.3 million additional downloads. We also present a user study involving 9 editors, which yielded excellent results in term of usability, and report an evaluation of the new topic classifier used by STM, which outperforms previous versions in recall and F-measure

    Adjustable Gastric Banding Conversion to One Anastomosis Gastric Bypass: Data Analysis of a Multicenter Database

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    Introduction: One anastomosis gastric bypass (OAGB) has been proposed as a rescue technique for laparoscopic adjustable gastric banding (LAGB) poor responders. Aim: We sought to analyze, complications, mortality, and medium-term weight loss results after LAGB conversion to OAGB. Methods: Data analysis of an international multicenter database. Results: One hundred eighty-nine LAGB-to-OAGB operations were retrospectively analyzed. Eighty-seven (46.0%) were converted in one stage. Patients operated on in two stages had a higher preoperative body mass index (BMI) (37.9 vs. 41.3 kg/m2, p = 0.0007) and were more likely to have encountered technical complications, such as slippage or erosions (36% vs. 78%, p < 0.0001). Postoperative complications occurred in 4.8% of the patients (4.6% and 4.9% in the one-stage and the two-stage group, respectively). Leak rate, bleeding episodes, and mortality were 2.6%, 0.5%, and 0.5%, respectively. The final BMI was 30.2 at a mean follow-up of 31.4 months. Follow-up at 1, 3, and 5 years was 100%, 88%, and 70%, respectively. Conclusion: Conversion from LAGB to OAGB is safe and effective. The one-stage approach appears to be the preferred option in non-complicate cases, while the two-step approach is mostly done for more complicated cases.info:eu-repo/semantics/publishedVersio

    Covalently bonded three-dimensional carbon nanotube solids via boron induced nanojunctions

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    The establishment of covalent junctions between carbon nanotubes (CNTs) and the modification of their straight tubular morphology are two strategies needed to successfully synthesize nanotube-based three-dimensional (3D) frameworks exhibiting superior material properties. Engineering such 3D structures in scalable synthetic processes still remains a challenge. This work pioneers the bulk synthesis of 3D macroscale nanotube elastic solids directly via a boron-doping strategy during chemical vapour deposition, which influences the formation of atomic-scale “elbow” junctions and nanotube covalent interconnections. Detailed elemental analysis revealed that the “elbow” junctions are preferred sites for excess boron atoms, indicating the role of boron and curvature in the junction formation mechanism, in agreement with our first principle theoretical calculations. Exploiting this material’s ultra-light weight, super-hydrophobicity, high porosity, thermal stability, and mechanical flexibility, the strongly oleophilic sponge-like solids are demonstrated as unique reusable sorbent scaffolds able to efficiently remove oil from contaminated seawater even after repeated use

    A retrospective analysis of the change in anti-malarial treatment policy: Peru

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    <p>Abstract</p> <p>Background</p> <p>National malaria control programmes must deal with the complex process of changing national malaria treatment guidelines, often without guidance on the process of change. Selecting a replacement drug is only one issue in this process. There is a paucity of literature describing successful malaria treatment policy changes to help guide control programs through this process.</p> <p>Objectives</p> <p>To understand the wider context in which national malaria treatment guidelines were formulated in a specific country (Peru).</p> <p>Methods</p> <p>Using qualitative methods (individual and focus group interviews, stakeholder analysis and a review of documents), a retrospective analysis of the process of change in Peru's anti-malarial treatment policy from the early 1990's to 2003 was completed.</p> <p>Results</p> <p>The decision to change Peru's policies resulted from increasing levels of anti-malarial drug resistance, as well as complaints from providers that the drugs were no longer working. The context of the change occurred in a time in which Peru was changing national governments, which created extreme challenges in moving the change process forward. Peru utilized a number of key strategies successfully to ensure that policy change would occur. This included a) having the process directed by a group who shared a common interest in malaria and who had long-established social and professional networks among themselves, b) engaging in collaborative teamwork among nationals and between nationals and international collaborators, c) respect for and inclusion of district-level staff in all phases of the process, d) reliance on high levels of technical and scientific knowledge, e) use of standardized protocols to collect data, and f) transparency.</p> <p>Conclusion</p> <p>Although not perfectly or fully implemented by 2003, the change in malaria treatment policy in Peru occurred very quickly, as compared to other countries. They identified a problem, collected the data necessary to justify the change, utilized political will to their favor, approved the policy, and moved to improve malaria control in their country. As such, they offer an excellent example for other countries as they contemplate or embark on policy changes.</p
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