Special Safeguard Mechanisms for the Agricultural Sector: The GATT Negotiations

The Uruguay Round of the General Agreement on Tariffs and Trade (GATT) negotiations is deadlocked on the issue of agricultural policy reform. Although broad consensus has been reached regarding replacing all nontariff trade barriers with equivalent tariffs, agreement on the questions of domestic farm policy reforms and access to domestic markets by exporting countries has not yet been reached. Arthur Dunkel, Director General of the GATT, has put forward a compromise proposal that seeks to ensure minimum access to the domestic markets of all countries while providing importing countries with special safeguard mechanisms to protect their domestic markets against large price declines and import surges. Within this context, we analyze and compare safeguard mechanisms activated either by prices declining below some benchmark level or by imports surging above a prespecified level

Role of c-Jun N-Terminal Protein Kinase 1/2 (JNK1/2) in Macrophage-Mediated MMP-9 Production in Response to Moraxella catarrhalis Lipooligosaccharide (LOS)

Moraxella catarrhalis is a Gram negative bacterium and a leading causative agent of otitis media (OM) in children. Recent reports have provided strong evidence for the presence of high levels of matrix metalloproteinase (MMPs) in effusion fluids from children suffering with OM, however, the precise mechanisms by which MMPs are generated are currently unknown. We hypothesized that MMPs are secreted from macrophages in the presence of M. catarrhalis lipooligosaccharide (LOS). In this report, we demonstrate that in vitro stimulation of murine macrophage RAW 264.7 cells with LOS leads to secretion of MMP-9 as determined by ELISA and zymogram assays. We have also shown that inhibition of ERK1/2 and p38 kinase completely blocked LOS induced MMP-9 production. In contrast, inhibition of JNK1/2 by the specific inhibitor SP600125 actually increased the level of expression and production of MMP-9 at both mRNA and protein levels, respectively by almost five fold. This latter result was confirmed by knocking down JNK1/2 using siRNA. Similar results have been observed in murine bone marrow derived macrophages in vitro. In contrast to and in parallel with the LOS-induced increased levels of MMP-9 in the presence of SP600125, we found a corresponding dose-dependent inhibition of TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) secretion. Results of subsequent in vitro studies provided evidence that when JNK1/2 was inhibited prior to stimulation with LOS, it significantly increased both the extent of macrophage cell migration and invasion compared to control cells or cells treated with LOS alone. The results of these studies contribute to an increased understanding of the underlying pathophysiology of OM with effusion in children

Enterovirus D68 outbreak detection through a syndromic disease epidemiology network

BACKGROUND: In 2014, enterovirus D68 (EV-D68) was responsible for an outbreak of severe respiratory illness in children, with 1,153 EV-D68 cases reported across 49 states. Despite this, there is no commercial assay for its detection in routine clinical care. BioFire® Syndromic Trends (Trend) is an epidemiological network that collects, in near real-time, deidentified. BioFire test results worldwide, including data from the BioFire® Respiratory Panel (RP). OBJECTIVES: Using the RP version 1.7 (which was not explicitly designed to differentiate EV-D68 from other picornaviruses), we formulate a model, Pathogen Extended Resolution (PER), to distinguish EV-D68 from other human rhinoviruses/enteroviruses (RV/EV) tested for in the panel. Using PER in conjunction with Trend, we survey for historical evidence of EVD68 positivity and demonstrate a method for prospective real-time outbreak monitoring within the network. STUDY DESIGN: PER incorporates real-time polymerase chain reaction metrics from the RPRV/EV assays. Six institutions in the United States and Europe contributed to the model creation, providing data from 1,619 samples spanning two years, confirmed by EV-D68 gold-standard molecular methods. We estimate outbreak periods by applying PER to over 600,000 historical Trend RP tests since 2014. Additionally, we used PER as a prospective monitoring tool during the 2018 outbreak. RESULTS: The final PER algorithm demonstrated an overall sensitivity and specificity of 87.1% and 86.1%, respectively, among the gold-standard dataset. During the 2018 outbreak monitoring period, PER alerted the research network of EV-D68 emergence in July. One of the first sites to experience a significant increase, Nationwide Children's Hospital, confirmed the outbreak and implemented EV-D68 testing at the institution in response. Applying PER to the historical Trend dataset to determine rates among RP tests, we find three potential outbreaks with predicted regional EV-D68 rates as high as 37% in 2014, 16% in 2016, and 29% in 2018. CONCLUSIONS: Using PER within the Trend network was shown to both accurately predict outbreaks of EV-D68 and to provide timely notifications of its circulation to participating clinical laboratories

Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide

BACKGROUND: Recently it has been reported that, toll-like receptors (TLRs) are expressed on a series of tumor cells, such as colon cancer, breast cancer, prostate cancer, melanoma and lung cancer. Although some cancer cells like melanoma cells are known to respond to lipopolysaccharide (LPS) via TLR4, not all cancer cells are positive for TLR4. There is little information on the expression and function of TLR4 in neuroblastoma cells. In this study, we investigated the expression of TLR4 in human neuroblastoma NB-1 cell line. METHODS: Expression and localization of TLR4 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis, respectively. Activation of nuclear factor (NF)-κB by LPS was detected by degradation of IκB-α and NF-κB luciferase assay. Activation and expression of mitogen-activated protein (MAP) kinase and interferon regulatory factor (IRF)-3 was detected by immunoblot analysis. RESULTS: Human NB-1 neuroblastoma cells expressed intracellular form of TLR4, but not the cell surface form. Further, NB-1 cells express CD14, MD2 and MyD88, which are required for LPS response. However, LPS did not significantly induce NF-κB activation in NB-1 cells although it slightly degraded IκB-α. NB-1 cells expressed no IRF-3, which plays a pivotal role on the MyD88-independent pathway of LPS signaling. Collectively, NB-1 cells are capable to avoid their response to LPS. CONCLUSION: Although human NB-1 neuroblastoma cells possessed all the molecules required for LPS response, they did not respond to LPS. It might be responsible for intracellular expression of TLR4 or lack of IRF-3

The impact of the COVID-19 pandemic on the education of medical, dental and non-medical healthcare professionals in Bangladesh : findings and connotation

Lockdown measures in response to the COVID-19 pandemic had an appreciable impact on the education of all medical, dental, and non-medical healthcare professional (HCP) students. These included the closure of universities necessitating a rapid move to e-learning and new approaches to practical’s. However initially, there was a lack of knowledge and expertise regarding e-learning approaches and the affordability of internet bundles and equipment. We initially con-ducted two pilot studies to assess such current challenges, replaced by a two-stage approach including a full investigation involving 32 private and public universities during the early stages of the pandemic followed by a later study assessing the current environment brought about by the forced changes. Top challenges at the start of the pandemic included a lack of familiarity with e-learning approaches, cost of the internet, lack of IT equipment and the quality of the classes. Universities offered support to staff and students to a varying degree to address identified challenges. Since then, e-learning approaches have widened the possibilities for teaching and learning at convenient times. However, challenges remain. In conclusion, there were considerable challenges at the start of them pandemic. Several key issues have been addressed with hybrid learning here to stay. Remaining challenges include a lack of ICT equipment. However, new innovations will continue

Special Safeguard Mechanisms for the Agricultural Sector: The GATT Negotiations

The Uruguay Round of the General Agreement on Tariffs and Trade (GATT) negotiations is deadlocked on the issue of agricultural policy reform. Although broad consensus has been reached regarding replacing all nontariff trade barriers with "equivalent tariffs," agreement on the questions of domestic farm policy reforms and access to domestic markets by exporting countries has not yet been reached. Arthur Dunkel, Director General of the GATT, has put forward a compromise proposal that seeks to ensure minimum access to the domestic markets of all countries while providing importing countries with special safeguard mechanisms to protect their domestic markets against large price declines and import surges. Within this context, we analyze and compare safeguard mechanisms activated either by prices declining below some benchmark level or by imports surging above a prespecified level.</p

Optimal design of magneto-rheological damper comparing different configurations by finite element analysis

Magnetorheological (MR) damper is one of the most advanced applications of semi active damper in controlling vibration. Due to its continuous controllability in both on and off state its practice is increasing day by day in the vehicle suspension system. MR damper’s damping force can be controlled by changing the viscosity of its internal magnetorheological fluids (MRF). But still there are some problems with this damper such as MR fluid’s sedimentation, optimal design configuration considering all components of the damper. In this paper both 2-D Axisymmetric and 3-D model of MR Damper is built and finite element analysis is done for design optimization. Different configurations of MR damper piston, MR fluid gap, air gap and Dampers housing are simulated for comparing the Dampers performance variation. From the analytical results it is observed that among different configurations single coil MR damper with linear plastic air gap, top and bottom chamfered piston end and medium MR fluid gap shows better performance than other configurations by maintaining the same input current and piston velocity. Further an experimental analysis is performed by using RD-8041-1 MR Damper. These results are compared with the optimized MR Damper’s simulation results, which are clearly validating the simulated results

Moraxella catarrhalis activates murine macrophages through multiple toll like receptors and has reduced clearance in lungs from TLR4 mutant mice.

Moraxella catarrhalis is a gram negative bacterium and a leading causative agent of otitis media (OM) in children. Several recent reports have provided strong evidence for an association between toll like receptors and OM. It has been found that both Streptococcus pneumoniae and nontypeable Haemophilus influenzae activate host protective immune responses through toll like receptors (TLRs), however, the precise mechanism by which Moraxella catarrhalis initiates the host immune response is currently unknown. In this report, using murine macrophages generated from a series of knock-out mice, we have demonstrated that M. catarrhalis lipooligosaccharide (LOS) and either heat killed or live bacteria are recognized by one or more TLRs. LOS activates the host immune response through a membrane bound CD14-TLR4 complex, while both heat killed and live M.cat require recognition by multiple toll like receptors such as TLR2, TLR4 and TLR9 without the requirement of CD14. We have also shown that M.cat stimuli are capable of triggering the host innate immune response by both MyD88- and TRIF- dependent signaling pathways. We further showed that M.cat induced activation of mitogen activated protein kinase (MAPK) is essential in order to achieve optimal secretion of pro-inflammatory cytokine TNF-α. We finally showed that TLR4 mutant C3H/HeJ mice produce significantly lower levels of pro-inflammatory cytokines TNF-α and IL-6 in vivo, An increased bacterial loads at 12 and 24 hours (P<0.001) in their lungs upon challenge with live M.cat in an aerosol chamber compared to wild-type (WT) control mice. These data suggest that TLRs are crucial for an effective innate immune response induced by M.cat. The results of these studies contribute to an increased understanding of molecular mechanism and possible novel treatment strategies for diseases caused by M.cat by specifically targeting TLRs and their signaling pathways

Biochemical Constituent of Ginkgo biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias javanicus) Model

Background. Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed. Methods. The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka (Oryzias javanicus). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC). Results. The result shows activities with high significant differences at P<0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method. Conclusion. The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements