Studies on processing, particle formation, and immunogenicity of the HIV-1 gag gene product: a possible component of a HIV vaccine

Antigens in a particulate conformation were shown to be highly immunogenic in mammals. For this reason, the particle forming capacity of derivatives of the HIV-1 group specific core antigen p55 gag was assayed and compared dependent on various expression systems: recombinant bacteria, vaccinia- and baculoviruses were established encoding the entire core protein p55 either in its authentic sequence or lacking the myristylation consensus signal. Moreover, p55 gag was expressed in combination with the protease (p55-PR) or with the entire polymerase (p55-pol), respectively. Budding of 100-160 nm p55 core particles, resembling immature HIV-virions, was observed in the eucaryotic expression systems only. In comparison to the vaccinia virus driven expression of p55 in mammalian cells, considerably higher yields of particulate core antigen were obtained by infection of Spodoptera frugiperda (Sf9) insect cells with the recombinant Autographa californica nuclear polyhedrosis (AcMNPV) baculovirus. Mutation of the NH2-terminal myristylation signal sequence prevented budding of the immature core particles. Expression of the HIV p55-PR gene construct by recombinant baculovirus resulted in complete processing of the p55 gag precursor molecule in this system. The introduction of an artificial frameshift near the natural frameshift site resulted in constitutive expression of the viral protease and complete processing of p55, both in Escherichia coli and in vaccinia virus infected cells. Interestingly, significant processing of p55 resembling that of HIV infected H9 cells could also be achieved in the vaccinia system by fusing the entire pol gene to the gag gene. Moreover, processing was not found to be dependent on amino-terminal myristylation of the gag procursor molecule, which is in contrast to observations with type C and type D retrovirus. However, complete processing of p55 into p24, p17, p9 and p6 abolished particle formation. Purified immature HIV-virus like particles were highly immunogenic in rabbits, leading to a strong humoral immune response after immunization. Empty immature p55 gag particles represent a noninfectious and attractive candidate for a basic vaccine component

Validity of Wearable Activity Monitors for Estimation of Resting Energy Expenditure in Adults

• Wearable accelerometers have become the standard method for assessing physical activity for both individuals and field-based research [1]. These new devices allow consumers to have the ability to estimate total energy expenditure and track it over time. • Resting Energy Expenditure plays a critical role in estimating daily total energy expenditure as it contributes 60-70% of total energy expenditure [2,3]. • Little to no information is available to substantiate the validity of these consumer-based activity monitors under free-living conditions

Coherent radiation of an ultra-relativistic charged particle channeled in a periodically bent crystal

We suggest a new type of the undulator radiation which is generated by an ultra-relativistic particle channeled along a periodically bent crystallographic plane or axis. The electromagnetic radiation arises mainly due to the bending of the particle's trajectory, which follows the shape of the channel. The parameters of this undulator, which totally define the spectrum and the angular distribution of the radiation (both spontaneous and stimulated), depend on the type of the crystal and the crystallographic plane (axis), on the type of a projectile and its energy, and on the shape of the bent channel, and, thus, can be varied significantly by varying these characteristics. As an example, we consider the acoustically induced radiation (AIR) which is generated by ultra-relativistic particles channeled in a crystal which is bent by a transverse acoustic wave. The AIR mechanism allows to make the undulator with the main parameters varying in wide ranges, which are inaccessible in the undulators based on the motion of particles in the periodic magnetic fields and also in the field of the laser radiation. The intensity of AIR can be easily made larger than the intensity of the radiation in a linear crystal and can be varied in a wide range by varying the frequency and the amplitude of the acoustic wave in the crystal. A possibility to generate stimulated emission of high-energy photons (in keV - MeV region) is also discussed.Comment: published in J. Phys. G: Nucl. Part. Phys. 24 (1998) L45-L53, http://www.iop.or

T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression.

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR

Photon emission by an ultra-relativistic particle channeling in a periodically bent crystal

This paper is devoted to a detailed analysis of the new type of the undulator radiation generated by an ultra-relativistic charged particle channeling along a crystal plane, which is periodically bent by a transverse acoustic wave, as well as to the conditions limiting the observation of this phenomenon. This mechanism makes feasible the generation of electromagnetic radiation, both spontaneous and stimulated, emitted in a wide range of the photon energies, from X- up to gamma-rays

Technical enhancement of TMA sites for data safety & cost efficiency

Current developments of deep sea data telemetry system (capsules, inductive, acoustics) will be reviewed and further developments performed. Technical enhancement will be demonstrated at selected sites and with different platforms (e.g. Myrtle-X lander

Development of an acoustic transceiver for the KM3NeT positioning system

[EN] In this paper we describe an acoustic transceiver developed for the KM3NeT positioning system. The acoustic transceiver is composed of a commercial free flooded transducer, which works mainly in the 20-40 kHz frequency range and withstands high pressures (up to 500 bars). A sound emission board was developed that is adapted to the characteristics of the transducer and meets all requirements: low power consumption, high intensity of emission, low intrinsic noise, arbitrary signals for emission and the capacity of acquiring the receiving signals with very good timing precision. The results of the different tests made with the transceiver in the laboratory and shallow sea water are described, as well as, the activities for its integration in the Instrumentation Line of the ANTARES neutrino telescope and in a NEMO tower for the in situ tests. © 2012 Elsevier B.V. All rights reserved.This work has been supported by the Ministerio de Ciencia e Innovacion (Spanish Government), Project references FPA2009-13983-C02-02, ACI2009-1067, AIC10-D-00583, and Consolider-Ingenio Multidark (CSD2009-00064). It has also been funded by Generalitat Valenciana, Prometeo/2009/26, and the European 7th Framework Programme, Grant no. 212525.Larosa, G.; Ardid Ramírez, M.; Llorens Alvarez, CD.; Bou Cabo, M.; Martínez Mora, JA.; Adrián Martínez, S.; KM3NeT Consortium (2013). Development of an acoustic transceiver for the KM3NeT positioning system. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 725:215-218. https://doi.org/10.1016/j.nima.2012.11.167S21521872

White dwarf spins from low mass stellar evolution models

The prediction of the spins of the compact remnants is a fundamental goal of the theory of stellar evolution. Here, we confront the predictions for white dwarf spins from evolutionary models including rotation with observational constraints. We perform stellar evolution calculations for stars in the mass range 1... 3\mso, including the physics of rotation, from the zero age main sequence into the TP-AGB stage. We calculate two sets of model sequences, with and without inclusion of magnetic fields. From the final computed models of each sequence, we deduce the angular momenta and rotational velocities of the emerging white dwarfs. While models including magnetic torques predict white dwarf rotational velocities between 2 and 10 km s$^{-1}$, those from the non-magnetic sequences are found to be one to two orders of magnitude larger, well above empirical upper limits. We find the situation analogous to that in the neutron star progenitor mass range, and conclude that magnetic torques may be required in order to understand the slow rotation of compact stellar remnants in general.Comment: Accepted for A&A Letter