The new Athens center on data processing from the neutron monitor network in real time

International audienceThe ground-based neutron monitors (NMs) record galactic and solar relativistic cosmic rays which can play a useful key role in space weather forecasting, as a result of their interaction with interplanetary disturbances. The Earth's-based neutron monitor network has been used in order to produce a real-time prediction of space weather phenomena. Therefore, the Athens Neutron Monitor Data Processing Center (ANMODAP) takes advantage of this unique multi-directional device to solve problems concerning the diagnosis and forecasting of space weather. At this moment there has been a multi-sided use of neutron monitors. On the one hand, a preliminary alert for ground level enhancements (GLEs) may be provided due to relativistic solar particles and can be registered around 20 to 30 min before the arrival of the main part of lower energy particles responsible for radiation hazard. To make a more reliable prognosis of these events, real time data from channels of lower energy particles and X-ray intensity from the GOES satellite are involved in the analysis. The other possibility is to search in real time for predictors of geomagnetic storms when they occur simultaneously with Forbush effects, using hourly, on-line accessible neutron monitor data from the worldwide network and applying a special method of processing. This chance of prognosis is only being elaborated and considered here as one of the possible uses of the Neutron Monitor Network for forecasting the arrival of interplanetary disturbance to the Earth. The achievements, the processes and the future results, are discussed in this work

Anthropogenic Noise and Its Footprint on ELF Schumann Resonance Recordings

A set of various short artificial disturbances from rifle firings, car engine operation, car radio, shakings of the apparatus, etc., were generated deliberately near our ELF recording stations in order to identify their footprint on the recordings of atmospheric electromagnetic radiation in the Schumann resonance (SR) band (from about 2–50 Hz). Such disturbances simulate anthropogenic noises from hunters, hikers, campers, etc., which may occur in a remote-isolated ELF recording station. We expect that our work will assist fellow scientists to differentiate between artificial signals created from anthropogenic activity and real signals attributable to geophysical phenomena

Antioxidant activity relationship of phenolic compounds in Hypericum perforatum L.

<p>Abstract</p> <p>Background</p> <p>The St John's Wort (<it>Hypericum perforatum</it>; Clusiaceae) has been used in traditional and modern medicine for a long time due to its high content of biologically active phenolics. The purpose of this work was to develop a method for their fractionation and identification, and to determine the most active antioxidant compounds in plant extract.</p> <p>Results</p> <p>An LC-MS method which enables fast qualitative and semiquantitative analysis was developed. The composition determined is in agreement with the previous results, where 6 flavonoids, 4 naphthodianthrones and 4 phloroglucinols have been identified. Significant antioxidant activity was determined for most of the fractions by DPPH assay (the lowest IC₅₀of 0.52 μg/ml), NO scavenging (6.11 μg/ml), superoxide scavenging (1.86 μg/ml), lipid peroxidation (0.0079 μg/ml) and FRAP (the highest reduction capacity of 104 mg Fe equivalents/g) assays.</p> <p>Conclusion</p> <p>LC-MS technique has been successfully applied for a quick separation and identification of the major components of <it>H. perforatum </it>fractions. Majority of the fractions analyzed have expressed a very high antioxidative activity when compared to synthetic antioxidants. The antioxidant activity could be attributed to flavonoids and phenolic acids, while phloroglucinols and naphthodianthrones showed no significant activity. It is demonstrated that it is possible to obtain, by fractionation, <it>H. perforatum </it>preparations with significantly increased phloroglucinols-to-naphthodianthrones ratio (up to 95:5).</p

An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials.

The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The structure of PfATP4 has not been determined. Here, we describe a public competition created to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the synthesis of inactive compounds. Competition participants could see all entries as they were submitted. In the final round, featuring private sector entrants specializing in machine learning methods, the best-performing models were used to predict novel inhibitors, of which several were synthesized and evaluated against the parasite. Half possessed biological activity, with one featuring a motif that the human chemists familiar with this series would have dismissed as "ill-advised". Since all data and participant interactions remain in the public domain, this research project "lives" and may be improved by others

Caveolin-1–eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability

Caveolin-1–mediated inhibition of endothelial nitric oxide synthase signaling is essential for adherens junction integrity and endothelial permeability homeostasis

A Novel Recombinant Peste des Petits Ruminants-Canine Adenovirus Vaccine Elicits Long-Lasting Neutralizing Antibody Response against PPR in Goats

BACKGROUND: Peste des petits ruminants (PPR) is a highly contagious infectious disease of goats, sheep and small wild ruminant species with high morbidity and mortality rates. The Peste des petits ruminants virus (PPRV) expresses a hemagglutinin (H) glycoprotein on its outer envelope that is crucial for viral attachment to host cells and represents a key antigen for inducing the host immune response. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether H can be exploited to generate an effective PPRV vaccine, a replication-competent recombinant canine adenovirus type-2 (CAV-2) expressing the H gene of PPRV (China/Tibet strain) was constructed by the in vitro ligation method. The H expression cassette, including the human cytomegalovirus (hCMV) promoter/enhancer and the BGH early mRNA polyadenylation signal, was inserted into the SspI site of the E3 region, which is not essential for proliferation of CAV-2. Infectious recombinant rCAV-2-PPRV-H virus was generated in transfected MDCK cells and used to immunize goats. All vaccinated animals produced antibodies upon primary injection that were effective in neutralizing PPRV in vitro. Higher antibody titer was obtained following booster inoculation, and the antibody was detectable in goats for at least seven months. No serious recombinant virus-related adverse effect was observed in immunized animals and no adenovirus could be isolated from the urine or feces of vaccinated animals. Results showed that the recombinant virus was safe and could stimulate a long-lasting immune response in goats. CONCLUSIONS/SIGNIFICANCE: This strategy not only provides an effective PPR vaccine candidate for goats but may be a valuable mean by which to differentiate infected from vaccinated animals (the so-called DIVA approach)

Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes

Antibody Responses against Xenotropic Murine Leukemia Virus-Related Virus Envelope in a Murine Model

Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC). Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV.Immunization elicited Env-specific binding and neutralizing antibodies (NAb) against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans

Homology modeling and molecular dynamics simulations of MUC1-9/H-2Kb complex suggest novel binding interactions

International audienceHuman MUC1 is over-expressed in human adenocarcinomas and has been used as a target for immunotherapy studies. The 9-mer MUC1-9 peptide has been identified as one of the peptides which binds to murine MHC class I H-2K. The structure of MUC1-9 in complex with H-2K has been modeled and simulated with classical molecular dynamics, based on the x-ray structure of the SEV9 peptide/H-2K complex. Two independent trajectories with the solvated complex (10 ns in length) were produced. Approximately 12 hydrogen bonds were identified during both trajectories to contribute to peptide/MHC complex, as well as 1-2 water mediated hydrogen bonds. Stability of the complex was also confirmed by buried surface area analysis, although the corresponding values were about 20% lower than those of the original x-ray structure. Interestingly, a bulged conformation of the peptide's central region, partially characterized as a -turn, was found exposed form the binding groove. In addition, P1 and P9 residues remained bound in the A and F binding pockets, even though there was a suggestion that P9 was more flexible. The complex lacked numerous water mediated hydrogen bonds that were present in the reference peptide x-ray structure. Moreover, local displacements of residues Asp4, Thr5 and Pro9 resulted in loss of some key interactions with the MHC molecule. This might explain the reduced affinity of the MUC1-9 peptide, relatively to SEV9, for the MHC class I H-2K