Study on Tunnelling Radiation in 4 Dimension Black Holes Vector Particles

Recent studies show that the tunnelling radiation of vector particles has been studied successfully by WKB approximation and Hamilton-Jacobi method. In view of this, the main purpose of this paper is to study the Proca equation and the vector particles tunnelling radiation in a 4-dimensional black hole. Finally, the results here show that the temperature of the vector particle is the same as that of the Dirac particle.

Persistent Immunogenicity of Integrase Defective Lentiviral Vectors delivering membrane tethered Native-Like HIV-1 Envelope Trimers

Integrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV-1 immunogen design demonstrated that native-like HIV-1 Envelope (Env) trimers that mimic the structure of virion-associated Env induce neutralization breadth in rabbits and macaques. Here, we describe the development of an IDLV-based HIV-1 vaccine expressing either soluble ConSOSL.UFO.664 or membrane-tethered ConSOSL.UFO.750 native-like Env immunogens with enhanced bNAb epitopes exposure. We show that IDLV can be pseudotyped with properly folded membrane-tethered native-like UFO.750 trimers. After a single IDLV injection in BALB/c mice, IDLV-UFO.750 induced a faster humoral kinetic as well as higher levels of anti-Env IgG compared to IDLV-UFO.664. IDLV-UFO.750 vaccinated cynomolgus macaques developed unusually long-lasting anti-Env IgG antibodies, as underlined by their remarkable half-life both after priming and boost with IDLV. After boosting with recombinant ConM SOSIP.v7 protein, two animals developed neutralization activity against the autologous tier 1B ConS virus mediated by V1/V2 and V3 glycan sites responses. By combining the possibility to display stabilized trimeric Env on the vector particles with the ability to induce sustained humoral responses, IDLVs represent an appropriate strategy for delivering rationally designed antigens to progress towards an effective HIV-1 vaccine.

Tagging and Capturing of Lentiviral Vectors Using Short RNAs

Lentiviral (LV) vectors have emerged as powerful tools for transgene delivery ex vivo but in vivo gene therapy applications involving LV vectors have faced a number of challenges, including the low efficiency of transgene delivery, a lack of tissue specificity, immunogenicity to both the product encoded by the transgene and the vector, and the inactivation of the vector by the human complement cascade. To mitigate these issues, several engineering approaches, involving the covalent modification of vector particles or the incorporation of specific protein domains into the vector’s envelope, have been tested. Short synthetic oligonucleotides, including aptamers bound to the surface of LV vectors, may provide a novel means with which to retarget LV vectors to specific cells and to shield these vectors from neutralization by sera. The purpose of this study was to develop strategies to tether nucleic acid sequences, including short RNA sequences, to LV vector particles in a specific and tight fashion. To bind short RNA sequences to LV vector particles, a bacteriophage lambda N protein-derived RNA binding domain (λN), fused to the measles virus hemagglutinin protein, was used. The λN protein bound RNA sequences bearing a boxB RNA hairpin. To test this approach, we used an RNA aptamer specific to the human epidermal growth factor receptor (EGFR), which was bound to LV vector particles via an RNA scaffold containing a boxB RNA motif. The results obtained confirmed that the EGFR-specific RNA aptamer bound to cells expressing EGFR and that the boxB containing the RNA scaffold was bound specifically to the λN RNA binding domain attached to the vector. These results show that LV vectors can be equipped with nucleic acid sequences to develop improved LV vectors for in vivo applications.

Sensitivity of the SHiP experiment to dark photons decaying to a pair of charged particles

Dark photons are hypothetical massive vector particles that could mix with ordinary photons. The simplest theoretical model is fully characterised by only two parameters: the mass of the dark photon m$$_{\gamma ^{\mathrm {D}}}$$ γ D and its mixing parameter with the photon, $$\varepsilon $$ ε . The sensitivity of the SHiP detector is reviewed for dark photons in the mass range between 0.002 and 10 GeV. Different production mechanisms are simulated, with the dark photons decaying to pairs of visible fermions, including both leptons and quarks. Exclusion contours are presented and compared with those of past experiments. The SHiP detector is expected to have a unique sensitivity for m$$_{\gamma ^{\mathrm {D}}}$$ γ D ranging between 0.8 and 3.3$$^{+0.2}_{-0.5}$$ - 0.5 + 0.2 GeV, and $$\varepsilon ^2$$ ε 2 ranging between $$10^{-11}$$ 10 - 11 and $$10^{-17}$$ 10 - 17 .

Lattice gauge theories: Introduction

Lattice gauge theories are based on the notion of parallel transport. They can be considered as non-perturbative regularizations of the continuum gauge theories in the sense of a low-temperature expansion. The chapter is mainly devoted on a study of matterless lattice gauge theories from the point of view of phase transitions. This means many properties of a realistic theory like quantum chromodynamics (QC) cannot be investigated, but the important question of confinement can still be studied: does the theory generate a force between charged particles increasing at large distances, so that heavy quarks in the fundamental representation cannot be separated? More generally, can one find charged asymptotic states like massless vector particles in the theory? Lattice gauge theories have properties quite different from the ferromagnetic systems. In particular the absence of a local order parameter requires a study of the behaviour of a non-local quantity, a functional of loops generally called Wilson's loop, to distinguish between the confined and deconfined phases, characterized by an area or perimeter law, respectively.

The stability of envelope-pseudotyped lentiviral vectors

Lentiviral vectors have become popular tools for stable genetic modification of mammalian cells. In some applications of lentiviral vector-transduced cells, infectious-lentiviral particles should be absent. Quantification of the free-vector particles that remain from the inoculum can be difficult. Therefore a formula was established that yields an estimation of the ‘Reduction Ratio.’ This ratio represents the loss of titer based on a number of vector-inactivating effects. In this study, we evaluated several parameters and assumptions that were used in the current formula. We generated new data on the stability and trypsin sensitivity of lentiviral vectors pseudotyped with eight heterologous envelope proteins and the loss of vectors by washing or passaging the cell cultures. Our data demonstrate that the loss of virus titer under the influence of trypsin as well as the half-life of the particles in tissue culture medium is dependent on the vector’s envelope protein. While VSV-G-envelope-pseudotyped particles were unsensitive to trypsin, the titer of vectors pseudotyped with other envelope proteins decreased 2–110-fold. The half-life in culture medium ranged from 8 to 40 h for the different envelope-pseudotyped vectors, with 35 h for VSV-G-envelope-pseudotyped vector particles. Additionally, we found that removal of the culture medium from Ø35 mm to Ø10 cm dishes reduces the amount of vector particles in the culture by 50-fold and 20-fold, respectively. Together these data can be used to more precisely estimate the maximum number of free lentiviral vector particles in cell cultures.