scholarly journals Perspectives for the Treatment of Infections withFlaviviridae

2000 ◽  
Vol 13 (1) ◽  
pp. 67-82 ◽  
Author(s):  
Pieter Leyssen ◽  
Erik De Clercq ◽  
Johan Neyts
Keyword(s):  
Cell Uptake ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Ongoing Research ◽  
Disease Spectrum ◽  
Viral Proteases ◽  
Tick Borne Encephalitis ◽  
Recent Developments ◽  
Prevention Of Infections ◽  
The Impact

SUMMARY The family Flaviviridae contains three genera: Hepacivirus, Flavivirus, and Pestivirus. Worldwide, more than 170 million people are chronically infected with Hepatitis C virus and are at risk of developing cirrhosis and/or liver cancer. In addition, infections with arthropod-borne flaviviruses (such as dengue fever, Japanese encephalitis, tick-borne encephalitis, St. Louis encephalitis, Murray Valley encephalitis, West Nile, and yellow fever viruses) are emerging throughout the world. The pestiviruses have a serious impact on livestock. Unfortunately, no specific antiviral therapy is available for the treatment or the prevention of infections with members of the Flaviviridae. Ongoing research has identified possible targets for inhibition, including binding of the virus to the cell, uptake of the virus into the cell, the internal ribosome entry site of hepaciviruses and pestiviruses, the capping mechanism of flaviviruses, the viral proteases, the viral RNA-dependent RNA polymerase, and the viral helicase. In light of recent developments, the prevalence of infections caused by these viruses, the disease spectrum, and the impact of infections, different strategies that could be pursued to specifically inhibit viral targets and animal models that are available to study the pathogenesis and antiviral strategies are reviewed.

scholarly journals Silencing and Oblivion of Psychological Trauma, Its Unconscious Aspects, and Their Impact on the Inflation of Vajrayāna. An Analysis of Cross-Group Dynamics and Recent Developments in Buddhist Groups Based on Qualitative Data

Religions ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 622 ◽  
Author(s):  
Anders
Keyword(s):  
Group Dynamics ◽  
Interdisciplinary Approach ◽  
Psychological Trauma ◽  
Ongoing Research ◽  
Psychological Mechanisms ◽  
Teacher Student ◽  
New Concepts ◽  
Recent Developments ◽  
Student Relationship ◽  
The Impact

The commercialization of Buddhist philosophy has led to decontextualization and indoctrinating issues across groups, as well as abuse and trauma in that context. Methodologically, from an interdisciplinary approach, based on the current situation in international Buddhist groups and citations of victims from the ongoing research, the psychological mechanisms of rationalizing and silencing trauma were analyzed. The results show how supposedly Buddhist terminology and concepts are used to rationalize and justify economic, psychological and physical abuse. This is discussed against the background of psychological mechanisms of silencing trauma and the impact of ignoring the unconscious in that particular context. Inadequate consideration regarding the teacher–student relationship, combined with an unreflective use of Tibetan honorary titles and distorted conceptualizations of methods, such as the constant merging prescribed in so-called 'guru yoga', resulted in giving up self-responsibility and enhanced dependency. These new concepts, commercialized as 'karma purification' and 'pure view', have served to rationalize and conceal abuse, as well as to isolate the victims. Therefore, we are facing societal challenges, in terms of providing health and economic care to the victims and implementing preventive measures. This use of language also impacts on scientific discourse and Vajrayāna itself, and will affect many future generations.

scholarly journals Discovery of Structurally Diverse Small-Molecule Compounds with Broad Antiviral Activity against Enteroviruses

2015 ◽  
Vol 60 (3) ◽  
pp. 1615-1626 ◽  
Author(s):  
Jun Zuo ◽  
Steve Kye ◽  
Kevin K. Quinn ◽  
Paige Cooper ◽  
Robert Damoiseaux ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Internal Ribosome Entry Site ◽  
Viral Proteins ◽  
Molecular Screening ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Viral Proteases ◽  
Life Threatening ◽  
Infected Cells ◽  
Resistant Mutants

Antiviral drugs do not currently exist for the treatment of enterovirus infections, which are often severe and potentially life-threatening. We conducted high-throughput molecular screening and identified a structurally diverse set of compounds that inhibit the replication of coxsackievirus B3, a commonly encountered enterovirus. These compounds did not interfere with the function of the viral internal ribosome entry site or with the activity of the viral proteases, but they did drastically reduce the synthesis of viral RNA and viral proteins in infected cells. Sequence analysis of compound-resistant mutants suggests that the viral 2C protein is targeted by most of these compounds. These compounds demonstrated antiviral activity against a panel of the most commonly encountered enteroviruses and thus represent potential leads for the development of broad-spectrum anti-enteroviral drugs.

scholarly journals IRES Trans-Acting Factors, Key Actors of the Stress Response

2019 ◽  
Author(s):  
Anne-Claire Godet ◽  
Florian David ◽  
Fransky Hantelys ◽  
Florence Tatin ◽  
Eric Lacazette ◽  
...  
Keyword(s):  
Stress Response ◽  
Network Formation ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Cellular Stress Response ◽  
Cell Physiology ◽  
Entry Site ◽  
Viral Mrnas ◽  
Internal Ribosome Entry ◽  
The Impact

The cellular stress response corresponds to the molecular changes that cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression, at transcriptional and post-transcriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support translation of specific mRNAs. One of the major mechanisms involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Importantly, cellular mRNA IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents an update of the reported ITAFs regulating cellular mRNA translation and of the different mechanisms allowing them to control translation initiation in specific conditions. The impact of ITAFs on coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.

Theory and Method and the Stakes of a Fragmented Discipline: Or, What Economics Taught Me About the Study of Religion

2020 ◽  
Author(s):  
Thomas A Lewis
Keyword(s):  
Religious Studies ◽  
The Public ◽  
Global Pandemic ◽  
Recent Developments ◽  
The Common ◽  
The Impact ◽  
Academic Study

Abstract As a discipline, the academic study of religion is strikingly fragmented, with little engagement or shared criteria of excellence across subfields. Although important recent developments have expanded the traditions and peoples studied as well as the methods used, the current extent of fragmentation limits the impact of this diversification and pluralization. At a moment when the global pandemic is catalyzing profound pressures on our universities and disciplines, this fragmentation makes it difficult to articulate to the public, to non-religious studies colleagues, and to students why the study of religion matters. We therefore too often fall back on platitudes. I argue for a revitalized methods and theories conversation that connects us even as it bears our arguments and disagreements about what we do and how. Courses in methods and theories in the study of religion represent the most viable basis we have for bringing the academic study of religion into the common conversation or argument that constitutes a discipline without sacrificing our pluralism.

scholarly journals A Reference Framework to Combine Model-Based Design and AR to Improve Social Sustainability

2021 ◽  
Vol 13 (4) ◽  
pp. 2031
Author(s):  
Fabio Grandi ◽  
Riccardo Karim Khamaisi ◽  
Margherita Peruzzini ◽  
Roberto Raffaeli ◽  
Marcello Pellicciari
Keyword(s):  
Positive Impact ◽  
Cost Effective ◽  
Digital Models ◽  
Model Based ◽  
Digital Contents ◽  
Recent Developments ◽  
Virtual Simulations ◽  
Product And Process ◽  
The Impact ◽  
Time Information

Product and process digitalization is pervading numerous areas in the industry to improve quality and reduce costs. In particular, digital models enable virtual simulations to predict product and process performances, as well as to generate digital contents to improve the general workflow. Digital models can also contain additional contents (e.g., model-based design (MBD)) to provide online and on-time information about process operations and management, as well as to support operator activities. The recent developments in augmented reality (AR) offer new specific interfaces to promote the great diffusion of digital contents into industrial processes, thanks to flexible and robust applications, as well as cost-effective devices. However, the impact of AR applications on sustainability is still poorly explored in research. In this direction, this paper proposed an innovative approach to exploit MBD and introduce AR interfaces in the industry to support human intensive processes. Indeed, in those processes, the human contribution is still crucial to guaranteeing the expected product quality (e.g., quality inspection). The paper also analyzed how this new concept can benefit sustainability and define a set of metrics to assess the positive impact on sustainability, focusing on social aspects.

scholarly journals Assessing the Potential of Catch-Only Models to Inform on the State of Global Fisheries and the UN’s SDGs

2021 ◽  
Vol 13 (11) ◽  
pp. 6101
Author(s):  
Rishi Sharma ◽  
Henning Winker ◽  
Polina Levontin ◽  
Laurence Kell ◽  
Dan Ovando ◽  
...  
Keyword(s):  
Stock Assessment ◽  
Fishing Effort ◽  
The State ◽  
Sources Of Information ◽  
Ongoing Research ◽  
Traditional Assessment ◽  
Stock Status ◽  
Stock Assessments ◽  
Recent Developments ◽  
Measure Of Performance

Catch-only models (COMs) have been the focus of ongoing research into data-poor stock assessment methods. Two of the most recent models that are especially promising are (i) CMSY+, the latest refined version of CMSY that has progressed from Catch-MSY, and (ii) SRA+ (Stock Reduction Analysis Plus) a recent developments in field. Comparing COMs and evaluating their relative performance is essential for determining the state of regional and global fisheries that may be lacking necessary data that would be required to run traditional assessment models. In this paper we interrogate how performance of COMs can be improved by incorporating additional sources of information. We evaluate the performance of COMs on a dataset of 48 data-rich ICES (International Council for the Exploration of Seas) stock assessments. As one measure of performance, we consider the ability of the model to correctly classify stock status using FAO’s 3-tier classification that is also used for reporting on sustainable development goals to the UN. Both COMs showed notable bias when run with their inbuilt default heuristics, but as the quality of prior information increased, classification rates for the terminal year improved substantially. We conclude that although further COM refinements show some potential, most promising is the ongoing research into developing biomass or fishing effort priors for COMs in order to be able to reliably track stock status for the majority of the world’s fisheries currently lacking stock assessments.

scholarly journals Recent Developments in Coatings for Orthopedic Metallic Implants

Coatings ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 791
Author(s):  
Muzamil Hussain ◽  
Syed Hasan Askari Rizvi ◽  
Naseem Abbas ◽  
Uzair Sajjad ◽  
Muhammad Rizwan Shad ◽  
...  
Keyword(s):  
Stress Shielding ◽  
Orthopedic Implant ◽  
Coating Materials ◽  
Implant Materials ◽  
Metallic Implants ◽  
Common Causes ◽  
Recent Developments ◽  
Orthopedic Applications ◽  
The Impact ◽  
Cocrmo Alloys

Titanium, stainless steel, and CoCrMo alloys are the most widely used biomaterials for orthopedic applications. The most common causes of orthopedic implant failure after implantation are infections, inflammatory response, least corrosion resistance, mismatch in elastic modulus, stress shielding, and excessive wear. To address the problems associated with implant materials, different modifications related to design, materials, and surface have been developed. Among the different methods, coating is an effective method to improve the performance of implant materials. In this article, a comprehensive review of recent studies has been carried out to summarize the impact of coating materials on metallic implants. The antibacterial characteristics, biodegradability, biocompatibility, corrosion behavior, and mechanical properties for performance evaluation are briefly summarized. Different effective coating techniques, coating materials, and additives have been summarized. The results are useful to produce the coating with optimized properties.

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