330 research outputs found
A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus
No full textIInfluenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for influenza A virus rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type influenza A virus by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited influenza A virus infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds
Controlling Factors of Cell Design on Large-format Li-ion Battery Safety During Nail Penetration
No full textIn this paper we investigate the controlling design parameters of large-format Li-ion batteries on safety while undergoing nail penetration. We have identified three critical design parameters that control the safety during the nail penetration process: nail diameter, single sheet foil area, and cell capacity.Using commercial AutoLion software, we have investigated two typical design problems related to the selection of cell thickness and aspect ratio, namely: (1) the safety ramifications of increasing cell capacity via greater cell thickness for a fixed footprint, and (2) the effect of aspect ratio, or single sheet foil size, on safety at a given capacity. For a fixed footprint, our results indicate that the safety of the cell can be predicted by (Qcell Dnail^-0.5). For a given cell capacity, our results indicate that typically a larger single sheet foil area leads to a greater likelihood for thermal runaway due to its effect of making the heating more local in nature; however, for small cells (~ 5Ah) and large nails (~ 20mm), the greater aspect ratio can lead to a safer cell, as the greater surface area strongly cools the global heating of the cell
Recent Advances on the Understanding of Structural and Composition Evolution of LMR Cathode for Li ion Batteries
No full textLithium-rich, magnesium-rich (LMR) cathode materials have been regarded as very promising for lithium (Li-ion battery applications. However, their practical application is still limited by several barriers such as their limited electrochemical stability and rate capability. In this work, we present recent progress on the understanding of structural and compositional evolution of LMR cathode materials, with an emphasis being placed on the correlation between structural/chemical evolution and electrochemical properties. In particular, using Li[Li0.2Ni0.2Mn0.6]O2 as a typical example, we clearly illustrate the structural characteristics of pristine materials and their dependence on the material-processing history, cycling-induced structural degradation/chemical partition, and their correlation with electrochemical performance degradation. The fundamental understanding that resulted from this work may also guide the design and preparation of new cathode materials based on the ternary system of transitional metal oxides
Interfacial Reaction Dependent Performance of Hollow Carbon NanoSphere – Sulfur composite as a cathode for Li-S battery
No full textLithium-sulfur (Li-S) battery is a promising energy storage system due to its high energy density, cost effectiveness and environmental friendliness of sulfur. However, there are still a number of technical challenges, such as low Coulombic efficiency and poor long-term cycle life, impeding the commercialization of Li-S battery. The electrochemical performance of Li-S battery is closely related with the interfacial reactions occurring between hosting substrate and active sulfur species which are poorly conducting at fully oxidized and reduced states. Here, we correlate the relationship between the performance and interfacial reactions in the Li-S battery system, using a hollow carbon nanosphere (HCNS) with highly graphitic character as hosting substrate for sulfur. With an appropriate amount of sulfur loading, HCNS/S composite exhibits excellent electrochemical performance because of the fast interfacial reactions between HCNS and the polysulfides. However, further increase of sulfur loading leads to increased formation of highly resistive insoluble reaction products (Li2S2/Li2S) which limits the reversibility of the interfacial reactions and results in poor electrochemical performances. These findings demonstrate the importance of the interfacial reaction reversibility in the whole electrode system on achieving high capacity and long cycle life of sulfur cathode for Li-S batteries
lamivudine inhibits the replication of ALV-J associated acutely transforming virus, its helper virus and tumor growth in vitro and in vivo
No full textTo study the antiviral effects of lamivudine on avian leukosis virus subgroup J (ALV-J) and its inhibitory effect on the growth of fibrosarcomas caused by acute transforming ALV, a series of experiments were performed in chicken embryo fibroblast cultures and 1-day-old chickens inoculated with an acutely transforming viral stock Fu-J (SDAU1005). This stock was prepared from an acutely fibrosarcoma of field cases in chicken farms and contained both the replication-defective virus Fu-J carrying v-fps oncogene and its helper virus ALV-J strain SDAU1005. The results from 3 different assays in cell cultures demonstrated the significant inhibitory effect of lamivudine on the replication of both SDAU1005 and Fu-J viruses. Furthermore, the effect was dose dependent in the concentration range of 1–4 μg/ml. In chicken experiments, lamivudine could decrease the viral loads of SDAU1005 and Fu-J in the plasma of inoculated chickens, delay the appearance of acute sarcomas, and decrease chicken mortality in the early stage. This model may be used to directly evaluate the inhibitory effects of lamivudine on such tumors and to understand the relationship between the replication-defective virus and its helper virus while also assessing tumor processes
Modulation of antigen-specific T-cells as immune therapy for chronic infectious diseases and cancer
Get PDFCopyright: © 2014 Li, Symonds, Miao, Sanderson and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.This article has been made available through the Brunel Open Access Publishing Fund.T-cell responses are induced by antigen presenting cells (APC) and signals from the microenvironment. Antigen persistence and inflammatory microenvironments in chronic infections and cancer can induce a tolerant state in T-cells resulting in hyporesponsiveness, loss of effector function, and weak biochemical signaling patterns in response to antigen stimulation. Although the mechanisms of T-cell tolerance induced in chronic infection and cancer may differ from those involved in tolerance to self-antigen, the impaired proliferation and production of IL-2 in response to antigen stimulation are hallmarks of all tolerant T cells. In this review, we will summarize the evidence that the immune responses change from non-self to “self”-like in chronic infection and cancer, and will provide an overview of strategies for re-balancing the immune response of antigen-specific T cells in chronic infection and cancer without affecting the homeostasis of the immune system.Arthritis Research UK and Medical Research Council UK
Community-onset Klebsiella pneumoniae pneumonia in Taiwan: clinical features of the disease and associated microbiological characteristics of isolates from pneumonia and nasopharynx
No full textKlebsiella pneumoniae is an important cause of community-onset pneumonia in Asian countries and South Africa. We investigated the clinical characteristics of K. pneumoniae causing community-onset pneumonia, and the associated microbiological features between K. pneumoniae isolates from pneumonia and those from the nasopharynx in Taiwan. This study was conducted at the Taipei Veterans General Hospital during July 2012 to February 2014. The clinical characteristics in patients with community-onset K. pneumoniae pneumonia were analysed. K. pneumoniae isolates from the nasopharynx of adults attending otorhinolaryngology outpatient clinics were collected to compare their microbiological features with those from pneumonia. Capsular genotypes, antimicrobial susceptibility, and multilocus sequence type (MLST) were determined among these strains. Ninety-one patients with community-onset K. pneumoniae pneumonia were enrolled. We found a high mortality (29.7%) among these patients. Capsular types K1, K2, K5, K20, K54 and K57 accounted for ~70% of the K. pneumoniae isolates causing pneumonia, and ~70% of all the K. pneumoniae strains isolated from the nasopharynx of patients in outpatient clinics. The MLST profiles further demonstrated the genetic relatedness between most pneumonia isolates and those from the nasopharynx. In conclusion, our results show that community-onset pneumonia caused by K. pneumoniae was associated with high mortality and could have a reservoir in the nasopharynx. To tackle this high-mortality disease, the distribution of capsular types and the common virulent clones in the nasopharynx might have implications for future vaccine development
Criteria for assessing the cooperative extension program planning process in the West central district of Virginia
No full textThe success of cooperative extension depends on the knowledge of how to apply the principles of extension education to situations where the activities are to be performed. The cooperative extension services dynamic localized approach to the solution of the common persons problem has stood the test of time. It is not necessary to establish a new system, but what is needed is to increase accountability and efficiency in the way programs are planned and developed.
The overall purpose of this study was to develop criteria for assessing the local cooperative extension program planning process in Virginia. Specific objectives that served as a basis for accomplishing the overall purpose of the study were:
1. To identify principles that are basic for planning an effective local extension program.
2. To verify these principles with a panel of experts.
3. To formulate criteria, based on the verified principles, to assess if on-going local extension programs were developed following the accepted programming principles.
4. To field test the criteria to determine the degree to which the criteria are used as guides during the local extension program planning process.
This study was a qualitative study. The principles identified and the criteria developed were reviewed by a panel of eight experts, then field tested in randomly selected extension units in the West Central Extension District of Virginia. Using personal interview methodology, unit directors of the randomly selected units were used for the field testing stage of this study.
Six of the seven principles identified as basic for planning/developing effective local extension programs were accepted by the panel of experts. Eighteen criteria were formulated based on the accepted principles. Criteria as used in this study implies an overall description of a set of related actions and/or operations which will be called standards of the planning process. It was found that most of the unit directors in the West-Central Extension District of Virginia interviewed for this study use the criteria as guides during their respective programming process. The panel of experts and unit directors agreed that the criteria were important as guides for local extension programming processes.
Based on the findings the author concluded that: (a) there are six essential principles for planning effective social extension programs; (b) that there are 18 criteria that can be used as guides for assessing if local extension programs are planned/developed using the essential extension program planning principles; and (c) that it is possible to assess local program planning activities in extension.
A recommendation made from the study that the process of assessing local program planning activities be tested statewide to increase the usability potential of the criteria and give possible directions for statewide in-service needs of unit directors and extension agents.Ed. D.incomplete_metadat
Insights into auxin signaling in plant–pathogen interactions
No full textThe phytohormone auxin has been noted as a regulator of plant growth and development ever since its discovery. Recent studies on plant–pathogen interactions make auxin a key character in pathogenesis and plant defense. In addition to plants, diverse pathogens possess the capacity to synthesize indole-3-acetic acid (IAA), the major form of auxin in plants. The emerging knowledge on auxin signaling components, auxin metabolic processes, and indole-derived phytoalexins in plant responses to pathogen invasion has provided putative mechanisms of IAA in plant susceptibility and resistance to non–gall- or tumor-inducing pathogens
Actor-recipient role affects neural responses to self in emotional situations
No full textPeople often take either the role of an actor or that of recipient in positive and negative interpersonal events when they interact with others. The present study investigated how the actor-recipient role affected the neural responses to self in emotional situations. Twenty-five participants were scanned while they were presented with positive and negative interpersonal events and were asked to rate the degree to which the actor/the recipient was that kind of person who caused the interpersonal event. Half of the trials were self-relevant events and the other half were other-relevant events. Results showed that people were more likely to isolate self from negative events when they played the role of actor relative to recipient. Pregenual anterior cingulate cortex (pgACC) and posterior dorsal anterior cingulate cortex (pdACC) were more active for self than other only in negative events. More importantly, also in negative interpersonal events, dorsal medial prefrontal cortex (dmPFC) showed greater self-related activations (self - other) when participants played the role of recipient relative to actor, while activities in orbitofrontal cortex (OFC) were greater for self than other only when the evaluation target played the role of recipient. These results showed that the actor-recipient role affected neural responses to self in emotional situations, especially when a recipient role was played in negative situations
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