Recombinant Flag-tagged E1E2 glycoproteins from three hepatitis C virus genotypes are biologically functional and elicit cross-reactive neutralizing antibodies in mice

Hepatitis C virus (HCV) is a globally disseminated human pathogen for which no vaccine is currently available. HCV is highly diverse genetically and can be classified into 7 genotypes and multiple sub-types. Due to this antigenic variation, the induction of cross-reactive and at the same time neutralizing antibodies is a challenge in vaccine production. Here we report the analysis of immunogenicity of recombinant HCV envelope glycoproteins from genotypes 1a, 1b and 2a, with a Flag tag inserted in the hypervariable region 1 of E2. This modification did not affect protein expression or conformation or its capacity to bind the crucial virus entry factor, CD81. Importantly, in immunogenicity studies on mice, the purified E2-Flag mutants elicited high-titer, cross-reactive antibodies that were able to neutralize HCV infectious particles from two genotypes tested (1a and 2a). These findings indicate that E1E2-Flag envelope glycoproteins could be important immunogen candidates for vaccine aiming to induce broad HCV-neutralizing responses

Green-Schwarz Formulation of Self-Dual Superstring

The self-dual superstring has been described previously in a Neveu-Schwarz-Ramond formulation with local N=2 or 4 world-sheet supersymmetry. We present a Green-Schwarz-type formulation, with manifest spacetime supersymmetry.Comment: 11 pg., (uuencoded dvi file) ITP-SB-92-5

New approach to the conceptual design of STUMM: A module dedicated to the monitoring of neutron and gamma radiation fields generated in IFMIF-DONES

International Fusion Materials Irradiation Facility — DEMOsingle bondOriented Neutron Source (IFMIF-DONES) is a planned powerful neutron source, which will generate an intense flux of neutrons (up to ∼1015n/s/cm2) with a fusion-relevant energy spectrum. It will be an accelerator source based on deuteron beam - lithium target reactions. The engineering design of IFMIF-DONES is elaborated in the frame of the Early Neutron Source work package of the EUROfusion consortium. The facility will be dedicated to the irradiation of suitable structural materials planned for the construction of future fusion reactors such as DEMO (Demonstration Fusion Power Plant). Start-up Monitoring Module (STUMM) is designed to monitor radiation and thermal conditions during the commissioning phase of IFMIF-DONES, characterize the produced neutron flux and validate neutronic modeling of the facility. The conceptual design of STUMM is prepared by a team of physicists and engineers from the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) and the National Centre for Nuclear Research (NCBJ), Poland. This paper presents the concept of STUMM, the proposed design of the module, and selected measuring systems

Varicellovirus UL49.5 Proteins Differentially Affect the Function of the Transporter Associated with Antigen Processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

The trace fossil Lepidenteron lewesiensis: a taphonomic window on diversity of Late Cretaceous fishes

The trace fossil Lepidenteron lewesiensis (Mantell 1822) provides an exceptional taphonomic window to diversity of fishes as shown for the Upper Cretaceous of Poland, in the Middle Turonian–Lower Maastrichtian deposits of the Opole Trough, Miechów Trough, Mazury-Podlasie Homocline, and SE part of the Border Synclinorium. Lepidenteron lewesiensis is an unbranched burrow lined with small fish scales and bones, without a constructed wall. It contains scales, vertebrae, and bones of the head belonging to ten taxa of teleostean fishes: two undetermined teleosteans, six undetermined Clupeocephala, one Dercetidae, and one undetermined euteleostean. The preservation of fish remains suggests that fishes were pulled down into the burrow by an animal, probably by eunicid polychaetes.Das Spurenfossil Lepidenteron lewesiensis (Mantell 1822) ermöglicht einen biostratinomischen Einblick in die Diversität von Fischen, wie Fossilmaterial aus der Oberkreide von Polen zeigt. Es stammt aus dem Mittelturonium bis Untermaastrichtium des südöstlichen Abschnittes der Grenz-Synklinale, dem Opolen-Trog, dem Miechów-Trog und der Masuren-Podlachien-Homoklinale. L. lewesiensis ist ein unverzweigter Grabgang ohne ausgekleidete Wände, dessen Ränder von kleinen Fischschuppen und—knochen gebildet werden. Diese setzen sich aus Schuppen, Wirbel und Schädelknochen von zehn Teleostei-Taxa zusammen und zwar aus zwei unbestimmte Teleosteer, sechs unbestimmten Clupeocephala, einem Dercetidae und einem unbestimmten Euteleostei. Die Erhaltung der Fischüberreste deutet darauf hin, dass die Fische von einem Tier, wahrscheinlich einem Polychaeten der Familie Eunicidae, in den Bau gezogen wurden.We are very grateful to Dr. Lionel Cavin (Geneva) and the anonymous reviewer for constructive comments on an earlier version of the manuscript. Additional support was provided by the Jagiellonian University (DS funds), National Science Center (Grant Number: PRO-2011/01/N/ST10/07717), and the Laboratory of Geology (University of Lodz) BSt Grant No. 560/844. We are grateful to Dr. Johann Egger (Wien) and Kilian Eichenseer M.Sc. (Erlangen) for help with translating the abstract into German. We are grateful to Dr. Ursula Göhlich (Wien) for access to the Dercetis specimen

Oligocene bivalve faunas from the Silesian Nappe, Polish Outer Carpathians: Evidence for the early history of the Paratethys

The study is focused on the taxonomic inventory of an intriguing bivalve fauna from the Lower Oligocene Menilite Beds (Dynów Marls) within the Silesian Nappe, Polish Outer Carpathians. Sixteen bivalve species have been identified within the material collected in two small quarries in Jabłonica Polska near Krosno. Stratigraphic and geographic distributions of all recognized species are considered. This assemblage, the first of this kind in Poland and one of three recognized in the Outer Carpathians, shows clear affinities to coeval typical Solenovian faunas from Ukraine to Kazakhstan, with particular comparison made to bivalve faunas from the Menilite Formation (Subchert Member) within the Boryslav-Pokuttya Nappe, Ukrainian Outer Carpathians. Moreover, this study presents an overview of the main aspects and definitions of the date of the Paratethys origin. The main criterion used to define the time of the Paratethys birth is the distinct faunal turnover from the moderately diverse boreal or Tethyan bivalve faunas populating particular basins of the Northern Peri-Tethys in the earliest Oligocene to the uniform, highly endemic fauna inhabiting the newly formed semi-closed basin. This vast inland sea, named Paratethys, was populated by representatives of eight euryhaline bivalve families. They are characterized by extinct Paratethyan genera, such as Bessia Kojumdgieva et Sapungieva, Merklinicardium Popov, Korobkoviella Merklin, Urbnisia Goncharova, Ergenica G. Popov and Janschinella Merklin

Status of a mega-joule scale Plasma-Focus experiments

This paper presents results of the recent plasma-focus (PF) experiments carried out with PF facilities, which was operated at energies ranging from 0.5 MJ to about 1 MJ. Particular attention has been paid to pinch evolution, the emission of pulsed X-ray, fast electron beams, and fusion produced neutrons. Some theoretical models of the initial breakdown, which occurs at the insulator surface, are compared. It is pointed out that modeling of the breakdown is sensitive to kinetics of ionization processes and transport coefficients. Progress in experimental studies of the axial acceleration phase is unsatisfactory. Important experimental data have been collected, but new measurements are still needed. For the radial collapse phase, it was shown that the MHD modeling is efficient until the maximum compression, but plasma instabilities require more sophisticated approaches. The pinch phase was investigated by means of different diagnostics. Fusion neutron yields were measured in different experiments, but some discrepancies in scaling must still be explained. The conclusions concern directions for further studies and optimization of large-scale high-current PF facilities