SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Petkov S) "

Search: WFRF:(Petkov S)

  • Result 1-50 of 58
Sort/group result
   
EnumerationReferenceCoverFind
1.
  • Aad, G, et al. (author)
  • 2015
  • swepub:Mat__t
  •  
2.
  • Ahdida, C., et al. (author)
  • Fast simulation of muons produced at the SHiP experiment using Generative Adversarial Networks
  • 2019
  • In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 14
  • Journal article (peer-reviewed)abstract
    • This paper presents a fast approach to simulating muons produced in interactions of the SPS proton beams with the target of the SHiP experiment. The SHIP experiment will be able to search for new long-lived particles produced in a 400 GeV/c SPS proton beam dump and which travel distances between fifty metres and tens of kilometers. The SHiP detector needs to operate under ultra-low background conditions and requires large simulated samples of muon induced background processes. Through the use of Generative Adversarial Networks it is possible to emulate the simulation of the interaction of 400 GeV/c proton beams with the SHiP target, an otherwise computationally intensive process. For the simulation requirements of the SHiP experiment, generative networks are capable of approximating the full simulation of the dense fixed target, offering a speed increase by a factor of O(10(6)). To evaluate the performance of such an approach, comparisons of the distributions of reconstructed muon momenta in SHiP's spectrometer between samples using the full simulation and samples produced through generative models are presented. The methods discussed in this paper can be generalised and applied to modelling any non-discrete multi-dimensional distribution.
  •  
3.
  • Ahdida, C., et al. (author)
  • The magnet of the scattering and neutrino detector for the SHiP experiment at CERN
  • 2020
  • In: Journal of Instrumentation. - 1748-0221. ; 15:01
  • Journal article (peer-reviewed)abstract
    • The Search for Hidden Particles (SHiP) experiment proposal at CERN demands a dedicated dipole magnet for its scattering and neutrino detector. This requires a very large volume to be uniformly magnetized at B > 1.2 T, with constraints regarding the inner instrumented volume as well as the external region, where no massive structures are allowed and only an extremely low stray field is admitted. In this paper we report the main technical challenges and the relevant design options providing a comprehensive design for the magnet of the SHiP Scattering and Neutrino Detector.
  •  
4.
  • Ahdida, C., et al. (author)
  • Sensitivity of the SHiP experiment to Heavy Neutral Leptons
  • 2019
  • In: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :4
  • Journal article (peer-reviewed)abstract
    • Heavy Neutral Leptons (HNLs) are hypothetical particles predicted by many extensions of the Standard Model. These particles can, among other things, explain the origin of neutrino masses, generate the observed matter-antimatter asymmetry in the Universe and provide a dark matter candidate. The SHiP experiment will be able to search for HNLs produced in decays of heavy mesons and travelling distances ranging between O(50 m) and tens of kilometers before decaying. We present the sensitivity of the SHiP experiment to a number of HNL's benchmark models and provide a way to calculate the SHiP's sensitivity to HNLs for arbitrary patterns of flavour mixings. The corresponding tools and data files are also made publicly available.
  •  
5.
  • Ahdida, C., et al. (author)
  • The experimental facility for the Search for Hidden Particles at the CERN SPS
  • 2019
  • In: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 14
  • Journal article (peer-reviewed)abstract
    • The Search for Hidden Particles (SHiP) Collaboration has shown that the CERN SPS accelerator with its 400 GeV/c proton beam offers a unique opportunity to explore the Hidden Sector [1-3]. The proposed experiment is an intensity frontier experiment which is capable of searching for hidden particles through both visible decays and through scattering signatures from recoil of electrons or nuclei. The high-intensity experimental facility developed by the SHiP Collaboration is based on a number of key features and developments which provide the possibility of probing a large part of the parameter space for a wide range of models with light long-lived super-weakly interacting particles with masses up to O(10) GeV/c(2) in an environment of extremely clean background conditions. This paper describes the proposal for the experimental facility together with the most important feasibility studies. The paper focuses on the challenging new ideas behind the beam extraction and beam delivery, the proton beam dump, and the suppression of beam-induced background.
  •  
6.
  • Ahdida, C., et al. (author)
  • Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target
  • 2020
  • In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:3
  • Journal article (peer-reviewed)abstract
    • The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27 +/- 0.07)x1011protons on target was recorded. This amounts to approximatively 1% of a SHiP spill.
  •  
7.
  • Ahdida, C., et al. (author)
  • Sensitivity of the SHiP experiment to dark photons decaying to a pair of charged particles
  • 2021
  • In: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 81:5
  • Journal article (peer-reviewed)abstract
    • 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)D and its mixing parameter with the photon, epsilon. The sensitivity of the SHiP detector is reviewed for dark photons in the mass range between 0.002 and 10 GeV. Different productionmechanisms 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. D ranging between 0.8 and 3.3(-0.5)(+0.2) GeV, and epsilon(2) ranging between 10(-11) and 10(-17).
  •  
8.
  • Ahdida, C., et al. (author)
  • Sensitivity of the SHiP experiment to light dark matter
  • 2021
  • In: Journal of High Energy Physics (JHEP). - : Springer Nature. - 1126-6708 .- 1029-8479. ; :4
  • Journal article (peer-reviewed)abstract
    • Dark matter is a well-established theoretical addition to the Standard Model supported by many observations in modern astrophysics and cosmology. In this context, the existence of weakly interacting massive particles represents an appealing solution to the observed thermal relic in the Universe. Indeed, a large experimental campaign is ongoing for the detection of such particles in the sub-GeV mass range. Adopting the benchmark scenario for light dark matter particles produced in the decay of a dark photon, with αD = 0.1 and mA′ = 3mχ, we study the potential of the SHiP experiment to detect such elusive particles through its Scattering and Neutrino detector (SND). In its 5-years run, corresponding to 2 · 1020 protons on target from the CERN SPS, we find that SHiP will improve the current limits in the mass range for the dark matter from about 1 MeV to 300 MeV. In particular, we show that SHiP will probe the thermal target for Majorana candidates in most of this mass window and even reach the Pseudo-Dirac thermal relic.
  •  
9.
  • Ahdida, C., et al. (author)
  • The SHiP experiment at the proposed CERN SPS Beam Dump Facility
  • 2022
  • In: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 82:5
  • Journal article (peer-reviewed)abstract
    • The Search for Hidden Particles (SHiP) Collaboration has proposed a general-purpose experimental facility operating in beam-dump mode at the CERN SPS accelerator to search for light, feebly interacting particles. In the baseline configuration, the SHiP experiment incorporates two complementary detectors. The upstream detector is designed for recoil signatures of light dark matter (LDM) scattering and for neutrino physics, in particular with tau neutrinos. It consists of a spectrometer magnet housing a layered detector system with high-density LDM/neutrino target plates, emulsion-film technology and electronic high-precision tracking. The total detector target mass amounts to about eight tonnes. The downstream detector system aims at measuring visible decays of feebly interacting particles to both fully reconstructed final states and to partially reconstructed final states with neutrinos, in a nearly background-free environment. The detector consists of a 50m\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm { \,m}$$\end{document} long decay volume under vacuum followed by a spectrometer and particle identification system with a rectangular acceptance of 5 m in width and 10 m in height. Using the high-intensity beam of 400GeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\,\mathrm {GeV}$$\end{document} protons, the experiment aims at profiting from the 4x1019\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4\times 10<^>{19}$$\end{document} protons per year that are currently unexploited at the SPS, over a period of 5-10 years. This allows probing dark photons, dark scalars and pseudo-scalars, and heavy neutral leptons with GeV-scale masses in the direct searches at sensitivities that largely exceed those of existing and projected experiments. The sensitivity to light dark matter through scattering reaches well below the dark matter relic density limits in the range from a few MeV/c2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathrm {\,MeV\!/}c<^>2}$$\end{document} up to 100 MeV-scale masses, and it will be possible to study tau neutrino interactions with unprecedented statistics. This paper describes the SHiP experiment baseline setup and the detector systems, together with performance results from prototypes in test beams, as it was prepared for the 2020 Update of the European Strategy for Particle Physics. The expected detector performance from simulation is summarised at the end.
  •  
10.
  • Ahdida, C., et al. (author)
  • Track reconstruction and matching between emulsion and silicon pixel detectors for the SHiP-charm experiment
  • 2022
  • In: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 17:3
  • Journal article (peer-reviewed)abstract
    • In July 2018 an optimization run for the proposed charm cross section measurement for SHiP was performed at the CERN SPS. A heavy, moving target instrumented with nuclear emulsion films followed by a silicon pixel tracker was installed in front of the Goliath magnet at the H4 proton beam-line. Behind the magnet, scintillating-fibre, drift-tube and RPC detectors were placed. The purpose of this run was to validate the measurement's feasibility, to develop the required analysis tools and fine-tune the detector layout. In this paper, we present the track reconstruction in the pixel tracker and the track matching with the moving emulsion detector. The pixel detector performed as expected and it is shown that, after proper alignment, a vertex matching rate of 87% is achieved.
  •  
11.
  • Akkoyun, S., et al. (author)
  • AGATA - Advanced GAmma Tracking Array
  • 2012
  • In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087 .- 1872-9576. ; 668, s. 26-58
  • Journal article (peer-reviewed)abstract
    • The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation γ-ray spectrometer. AGATA is based on the technique of γ-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a γ ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of γ-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector- response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer. © 2011 Elsevier B.V. All rights reserved.
  •  
12.
  • Blondel, A., et al. (author)
  • The SuperFGD Prototype charged particle beam tests
  • 2020
  • In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:12
  • Journal article (peer-reviewed)abstract
    • A novel scintillator detector, the SuperFGD, has been selected as the main neutrino target for an upgrade of the T2K experiment ND280 near detector. The detector design will allow nearly 47r coverage for neutrino interactions at the near detector and will provide lower energy thresholds, significantly reducing systematic errors for the experiment. The SuperFGD is made of optically-isolated scintillator cubes of size 10 x 10 x 10 mm(3), providing the required spatial and energy resolution to reduce systematic uncertainties for future T2K runs. The SuperFGD for T2K will have close to two million cubes in a 1920 x 560 x 1840 mm(3) volume. A prototype made of 24 x 8 x 48 cubes was tested at a charged particle beamline at the CERN PS facility. The SuperFGD Prototype was instrumented with readout electronics similar to the future implementation for T2K. Results on electronics and detector response are reported in this paper, along with a discussion of the 3D reconstruction capabilities of this type of detector. Several physics analyses with the prototype data are also discussed, including a study of stopping protons.
  •  
13.
  • Abele, H., et al. (author)
  • Particle physics at the European Spallation Source
  • 2023
  • In: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
  • Research review (peer-reviewed)abstract
    • Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
  •  
14.
  • Aguilar, J., et al. (author)
  • Search for Leptonic CP Violation with the ESSnuSBplus Project
  • 2024
  • In: Letters in High Energy Physics. - : Andromeda Publishing And Academic Services LTD. - 2632-2714.
  • Journal article (peer-reviewed)abstract
    • ESSνSB is a design study for a next-generation long-baseline neutrino experiment that aims at the precise measurement of the CP-violating phase, δCP, in the leptonic sector at the second oscillation maximum. The conceptual design report published from the first phase of the project showed that after 10 years of data taking, more than 70% of the possible δCP range will be covered with 5σ C.L. to reject the no-CP-violation hypothesis. The expected value of δCP precision is smaller than 8◦ for all δCP values. The next phase of the project, the ESSνSB+, aims at using the intense muon flux produced together with neutrinos to measure the neutrino-nucleus cross-section, the dominant term of the systematic uncertainty, in the energy range of 0.2–0.6 GeV, using a Low Energy neutrinos from STORed Muons (LEnuSTORM) and a Low Energy Monitored Neutrino Beam (LEMNB) facilities.
  •  
15.
  • Aguilar, J., et al. (author)
  • Study of nonstandard interactions mediated by a scalar field at the ESSnuSB experiment
  • 2024
  • In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 109:11
  • Journal article (peer-reviewed)abstract
    • In this paper, we study scalar mediator induced nonstandard interactions (SNSIs) in the context of the ESSnuSB experiment. In particular, we study the capability of ESSnuSB to put bounds on the SNSI parameters and also study the impact of SNSIs in the measurement of the leptonic CP phase δCP. Existence of SNSIs modifies the neutrino mass matrix and this modification can be expressed in terms of three diagonal real parameters (ηee, ημμ, and ηττ) and three off-diagonal complex parameters (ηeμ, ηeτ, and ημτ). Our study shows that the upper bounds on the parameters ημμ and ηττ depend upon how Δm312 is minimized in the theory. However, this is not the case when one tries to measure the impact of SNSIs on δCP. Further, we show that the CP sensitivity of ESSnuSB can be completely lost for certain values of ηee and ημτ for which the appearance channel probability becomes independent of δCP.
  •  
16.
  • Evangeliou, N., et al. (author)
  • Wildfires in northern Eurasia affect the budget of black carbon in the Arctic - a 12-year retrospective synopsis (2002-2013)
  • 2016
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:12, s. 7587-7604
  • Journal article (peer-reviewed)abstract
    • In recent decades much attention has been given to the Arctic environment, where climate change is happening rapidly. Black carbon (BC) has been shown to be a major component of Arctic pollution that also affects the radiative balance. In the present study, we focused on how vegetation fires that occurred in northern Eurasia during the period of 2002-2013 influenced the budget of BC in the Arctic. For simulating the transport of fire emissions from northern Eurasia to the Arctic, we adopted BC fire emission estimates developed independently by GFED3 (Global Fire Emissions Database) and FEI-NE (Fire Emission Inventory - northern Eurasia). Both datasets were based on fire locations and burned areas detected by MODIS (Moderate resolution Imaging Spectroradiometer) instruments on NASA's (National Aeronautics and Space Administration) Terra and Aqua satellites. Anthropogenic sources of BC were adopted from the MACCity (Monitoring Atmospheric Composition and Climate and megacity Zoom for the Environment) emission inventory. During the 12-year period, an average area of 250aEuro-000aEuro-km(2)aEuro-yr(-1) was burned in northern Eurasia (FEI-NE) and the global emissions of BC ranged between 8.0 and 9.5aEuro-TgaEuro-yr(-1) (FEI-NE+MACCity). For the BC emitted in the Northern Hemisphere (based on FEI-NE+MACCity), about 70aEuro-% originated from anthropogenic sources and the rest from biomass burning (BB). Using the FEI-NE+MACCity inventory, we found that 102aEuro-+/- aEuro-29aEuro-ktaEuro-yr(-1) BC was deposited in the Arctic (defined here as the area north of 67A degrees aEuro-N) during the 12 years simulated, which was twice as much as when using the MACCity inventory (56aEuro-+/- aEuro-8aEuro-ktaEuro-yr(-1)). The annual mass of BC deposited in the Arctic from all sources (FEI-NE in northern Eurasia, MACCity elsewhere) is significantly higher by about 37aEuro-% in 2009 (78 vs. 57aEuro-ktaEuro-yr(-1)) to 181aEuro-% in 2012 (153 vs. 54aEuro-ktaEuro-yr(-1)), compared to the BC deposited using just the MACCity emission inventory. Deposition of BC in the Arctic from BB sources in the Northern Hemisphere thus represents 68aEuro-% of the BC deposited from all BC sources (the remaining being due to anthropogenic sources). Northern Eurasian vegetation fires (FEI-NE) contributed 85aEuro-% (79-91aEuro-%) to the BC deposited over the Arctic from all BB sources in the Northern Hemisphere. We estimate that about 46aEuro-% of the BC deposited over the Arctic from vegetation fires in northern Eurasia originated from Siberia, 6aEuro-% from Kazakhstan, 5aEuro-% from Europe, and about 1aEuro-% from Mongolia. The remaining 42aEuro-% originated from other areas in northern Eurasia. About 42aEuro-% of the BC released from northern Eurasian vegetation fires was deposited over the Arctic (annual average: 17aEuro-%) during spring and summer.
  •  
17.
  • Milham, Michael P., et al. (author)
  • An Open Resource for Non-human Primate Imaging
  • 2018
  • In: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 100:1, s. 61-74
  • Journal article (peer-reviewed)abstract
    • Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.
  •  
18.
  •  
19.
  • de Angelis, G., et al. (author)
  • Coherent proton-neutron contribution to octupole correlations in the neutron-deficient Xe-114 nucleus
  • 2002
  • In: Physics Letters B. - 0370-2693 .- 1873-2445. ; 535:04-jan, s. 93-102
  • Journal article (peer-reviewed)abstract
    • Gamma ray linear polarization and picosecond lifetimes have been measured for levels in the neutron deficient nucleus Xe-114 using the EUROBALL IV spectrometer and the Cologne plunger device. The EUCLIDES Si-ball was used to improve the reaction channel selectivity. The linear polarization results have, for the first time, unambiguously determined the electromagnetic character of the dipole transitions de-exciting the negative parity level sequence, providing clear evidence for enhanced octupole collectivity. The discovery of two E3 transitions and the measurement of the lifetimes of the states depopulated by these transitions have allowed a quantitative determination of the octupole collectivity in the A approximate to 112 mass region. The large measured B(E3) values, close to approximate to 70 W.u., are among the strongest observed hitherto and indicate a coherent proton-neutron contribution to the octupole moment.
  •  
20.
  • Grahn, T., et al. (author)
  • Collectivity and configuration mixing in Pb186,188 and Po194
  • 2006
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:6
  • Journal article (peer-reviewed)abstract
    • Lifetimes of prolate intruder states in Pb186 and oblate intruder states in Po194 have been determined by employing, for the first time, the recoil-decay tagging technique in recoil distance Doppler-shift lifetime measurements. In addition, lifetime measurements of prolate states in Pb188 up to the 8+ state were carried out using the recoil-gating method. The B(E2) values have been deduced from which deformation parameters |β2|=0.29(5) and |β2|=0.17(3) for the prolate and the oblate bands, respectively, have been extracted. The results also shed new light on the mixing between different shapes.
  •  
21.
  •  
22.
  •  
23.
  • Petkov, S, et al. (author)
  • Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
  • 2022
  • In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 965214-
  • Journal article (peer-reviewed)abstract
    • HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.
  •  
24.
  • Petkov, S, et al. (author)
  • Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa
  • 2022
  • In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1009978-
  • Journal article (peer-reviewed)abstract
    • Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcision from 144 young men (72 from Uganda and 72 from South Africa) randomized to one to two doses of either oral tenofovir (TFV) disoproxil fumarate (FTC-TDF) or tenofovir alafenamide (FTC-TAF) or no drug (untreated controls). This novel approach allowed us to examine the impact of short-term oral PrEP on transcriptome of the male genital tract. A single dose of FTC-TDF did not affect the foreskin transcriptome in relation to control arm, however one dose of FTC-TAF induced upregulation of four genes AKAP8, KIAA0141, HSCB and METTL17. Following two doses of either FTC-TDF or FTC-TAF, there was an increase in 34 differentially expressed genes for FTC-TDF and 15 for FTC-TAF, with nine DEGs in common: KIAA0141, SAFB2, CACTIN, FXR2, AKAP8, HSCB, CLNS1A, DDX27 and DCAF15. Functional analysis of differentially expressed genes revealed modulation of biological processes related to mitochondrial stress (KIAA0141, HSCB and METTL17), anti-viral and anti-inflammatory pathways (CACTIN and AKAP8). Our results show that short-course on-demand oral PrEP in men modulates genes in foreskin tissue which are likely unfavorable to HIV acquisition and replication. We also describe an upregulated expression of genes involved in diverse mitochondria biology which may potentially result in worsened mitochondria-related. These results warrant further studies to assess the role of short-course and prolonged oral PrEP on biological processes of the foreskin mucosa.
  •  
25.
  •  
26.
  • Burgman, A., et al. (author)
  • The ESSnuSB Design Study: Overview and Future Prospects
  • 2023
  • In: Universe. - : MDPI. - 2218-1997. ; 9:8
  • Research review (peer-reviewed)abstract
    • ESSnuSB is a design study for an experiment to measure the CP violation in the leptonic sector at the second neutrino oscillation maximum using a neutrino beam driven by the uniquely powerful ESS linear accelerator. The reduced impact of systematic errors on sensitivity at the second maximum allows for a very precise measurement of the CP violating parameter. This review describes the fundamental advantages of measurement at the second maximum, the necessary upgrades to the ESS linac in order to produce a neutrino beam, the near and far detector complexes, and the expected physics reach of the proposed ESSnuSB experiment, concluding with the near future developments aimed at the project realization.
  •  
27.
  •  
28.
  • Latanova, A. A., et al. (author)
  • Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity
  • 2018
  • In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
  • Journal article (peer-reviewed)abstract
    • DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di-GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid ("surrogate challenge"). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-gamma production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+T-cells, targeted epitopes at aa 199-220 and aa 528-543. Drug-resistance mutations disrupted the epitope at aa 205-220, while the CTL epitope at aa 202-210 was not affected. Overall, multiparametric optimization of RT strengthened its Th2- performance. A rapid loss of RT/luciferase-expressing cells in the surrogate challenge experiment revealed a lytic potential of anti-RT response. Such lytic CD4+ response would be beneficial for an HIV vaccine due to its comparative insensitivity to immune escape.
  •  
29.
  •  
30.
  •  
31.
  • Stenler, S, et al. (author)
  • Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses.
  • 2017
  • In: Human Vaccines &amp; Immunotherapeutics. - : Taylor & Francis. - 2164-5515 .- 2164-554X. ; 13:12, s. 2849-2858
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid. In addition, three conventional plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20 in their gp41 sequences were also tested.RESULTS: All combinations induced HIV-specific antibodies and cellular responses. The addition of T20 as a peptide and as an expression cassette in the three DNA vectors enhanced antibody responses. The highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This demonstrates that besides its known antiviral activity, T20 promotes immune responses. We also confirm that the combination of slightly divergent antigens improves immune responses.CONCLUSIONS: The antiretroviral T20 HIV-1 sequence can be used as an immunogen to elicit binding and neutralizing antibodies against HIV-1. These, or similarly modified gp41 genes/peptides, can be used as priming or boosting components for induction of broadly neutralizing anti-HIV antibodies. Future comparative studies will reveal the optimal mode of T20 administration.
  •  
32.
  • Baklaushev, VP, et al. (author)
  • Luciferase Expression Allows Bioluminescence Imaging But Imposes Limitations on the Orthotopic Mouse (4T1) Model of Breast Cancer
  • 2017
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 7715-
  • Journal article (peer-reviewed)abstract
    • Implantation of reporter-labeled tumor cells in an immunocompetent host involves a risk of their immune elimination. We have studied this effect in a mouse model of breast cancer after the orthotopic implantation of mammary gland adenocarcinoma 4T1 cells genetically labelled with luciferase (Luc). Mice were implanted with 4T1 cells and two derivative Luc-expressing clones 4T1luc2 and 4T1luc2D6 exhibiting equal in vitro growth rates. In vivo, the daughter 4T1luc2 clone exhibited nearly the same, and 4T1luc2D6, a lower growth rate than the parental cells. The metastatic potential of 4T1 variants was assessed by magnetic resonance, bioluminescent imaging, micro-computed tomography, and densitometry which detected 100-μm metastases in multiple organs and bones at the early stage of their development. After 3–4 weeks, 4T1 generated 11.4 ± 2.1, 4T1luc2D6, 4.5 ± 0.6; and 4T1luc2, <1 metastases per mouse, locations restricted to lungs and regional lymph nodes. Mice bearing Luc-expressing tumors developed IFN-γ response to the dominant CTL epitope of Luc. Induced by intradermal DNA-immunization, such response protected mice from the establishment of 4T1luc2-tumors. Our data show that natural or induced cellular response against the reporter restricts growth and metastatic activity of the reporter-labelled tumor cells. Such cells represent a powerful instrument for improving immunization technique for cancer vaccine applications.
  •  
33.
  •  
34.
  • Burgman, A., et al. (author)
  • The European Spallation Source neutrino super-beam conceptual design report
  • 2022
  • In: The European Physical Journal Special Topics. - : Springer Nature. - 1951-6355 .- 1951-6401. ; 231:21, s. 3779-3955
  • Research review (peer-reviewed)abstract
    • A design study, named ESSνSB for European Spallation Source neutrino Super Beam, has been carried out during the years 2018–2022 of how the 5 MW proton linear accelerator of the European Spallation Source under construction in Lund, Sweden, can be used to produce the world’s most intense long-baseline neutrino beam. The high beam intensity will allow for measuring the neutrino oscillations near the second oscillation maximum at which the CP violation signal is close to three times higher than at the first maximum, where other experiments measure. This will enable CP violation discovery in the leptonic sector for a wider range of values of the CP violating phase δCPδCP and, in particular, a higher precision measurement of δCPδCP. The present Conceptual Design Report describes the results of the design study of the required upgrade of the ESS linac, of the accumulator ring used to compress the linac pulses from 2.86 ms to 1.2 μs, and of the target station, where the 5 MW proton beam is used to produce the intense neutrino beam. It also presents the design of the near detector, which is used to monitor the neutrino beam as well as to measure neutrino cross sections, and of the large underground far detector located 360 km from ESS, where the magnitude of the oscillation appearance of νe from νμ is measured. The physics performance of the ESSνSB research facility has been evaluated demonstrating that after 10 years of data-taking, leptonic CP violation can be detected with more than 5 standard deviation significance over 70% of the range of values that the CP violation phase angle δCPδCP can take and that δCPδCP can be measured with a standard error less than 8° irrespective of the measured value of δCPδCP. These results demonstrate the uniquely high physics performance of the proposed ESSνSBESSνSB research facility.
  •  
35.
  • Burgman, A., et al. (author)
  • Updated physics performance of the ESSnuSB experiment
  • 2021
  • In: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 81:12
  • Journal article (peer-reviewed)abstract
    • In this paper, we present the physics performance of the ESSnuSB experiment in the standard three flavor scenario using the updated neutrino flux calculated specifically for the ESSnuSB configuration and updated migration matrices for the far detector. Taking conservative systematic uncertainties corresponding to a normalization error of 5% for signal and 10% for background, we find that there is 10 sigma (13 sigma) CP violation discovery sensitivity for the baseline option of 540 km (360 km) at delta(CP) = +/- 90 degrees. The corresponding fraction of delta(CP )for which CP violation can be discovered at more than 5 sigma is 70%. Regarding CP precision measurements, the 1 sigma error associated with delta(CP )= 0 degrees is around 5 degrees and with delta(CP )= -90 degrees is around 14 degrees (7 degrees) for the baseline option of 540 km (360 km). For hierarchy sensitivity, one can have 3 sigma sensitivity for 540 km baseline except delta(CP) = +/- 90 degrees and 5 sigma sensitivity for 360 km baseline for all values of delta(CP). The octant of theta(23) can be determined at 30 for the values of: theta(23) > 51 degrees (theta(23) < 42 degrees and theta(23) > 49 degrees) for baseline of 540 km (360 km). Regarding measurement precision of the atmospheric mixing parameters, the allowed values at 3 sigma are: 40 degrees < theta(23) < 52 degrees (42 degrees < theta(23) < 51.5 degrees) and 2.485 x 10(-3) eV(2) < Delta(2)(m31) < 2.545 x 10(-3) eV(2) (2.49x 10(-3 ) eV(2) < Delta(2)(m31) < 2.54 x 10(-3) eV(2)) for the baseline of 540 km (360 km).
  •  
36.
  •  
37.
  • Gaget, Elie, et al. (author)
  • Protected area characteristics that help waterbirds respond to climate warming
  • 2022
  • In: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 36:4
  • Journal article (peer-reviewed)abstract
    • Protected area networks help species respond to climate warming. However, the contribution of a site's environmental and conservation-relevant characteristics to these responses is not well understood. We investigated how composition of nonbreeding waterbird communities (97 species) in the European Union Natura 2000 (N2K) network (3018 sites) changed in response to increases in temperature over 25 years in 26 European countries. We measured community reshuffling based on abundance time series collected under the International Waterbird Census relative to N2K sites’ conservation targets, funding, designation period, and management plan status. Waterbird community composition in sites explicitly designated to protect them and with management plans changed more quickly in response to climate warming than in other N2K sites. Temporal community changes were not affected by the designation period despite greater exposure to temperature increase inside late-designated N2K sites. Sites funded under the LIFE program had lower climate-driven community changes than sites that did not received LIFE funding. Our findings imply that efficient conservation policy that helps waterbird communities respond to climate warming is associated with sites specifically managed for waterbirds.
  •  
38.
  • Hennig, A., et al. (author)
  • Collective excitations of Ru-96 by means of (p, p 'gamma) experiments
  • 2015
  • In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 92:6
  • Journal article (peer-reviewed)abstract
    • Background: One-phonon mixed-symmetry quadrupole excitations are a well-known feature of near-spherical, vibrational nuclei. Their interpretation as a fundamental building block of vibrational structures is supported by the identification of multiphonon states resulting from a coupling of fully-symmetric and mixed-symmetric quadrupole phonons. In addition, the observation of strong M1 transitions between low-lying 3(-) and 4(+) states has been interpreted as an evidence for one-phonon mixed-symmetry excitations of octupole and hexadecapole character. Purpose: The aim of the present study is to identify collective one-and two-phonon excitations in the heaviest stable N = 52 isotone Ru-96 based on a measurement of absolute M1, E1, and E2 transition strengths. Methods: Inelastic proton-scattering experiments have been performed at the Wright Nuclear Structure Laboratory (WNSL), Yale University, and the Institute for Nuclear Physics (IKP), University of Cologne. From the acquired proton-gamma and gamma gamma coincidence data we deduced spins of excited states, gamma-decay branching ratios, and multipole mixing ratios, as well as lifetimes of excited states via the Doppler-shift attenuation method (DSAM). Results: Based on the new experimental data on absolute transition strengths, we identified the 2(+) and 3(+) members of the two-phonon mixed-symmetry quintuplet (2(1,ms)(+) circle times 2(1,s)(+)). Furthermore, we observed strong M1 transitions between low-lying 3(-) and 4(+) states suggesting one-phonon symmetric andmixed-symmetric octupole and hexadecapole components in their wave functions, respectively. The experimental results are compared to sdg-IBM-2 and shell-model calculations. Conclusions: Both the sdg-IBM-2 and the shell-model calculations are able to describe key features of mixed-symmetry excitations of Ru-96. Moreover, they support the one-phonon mixed-symmetry hexadecapole assignment of the experimental 4(2)(+) state.
  •  
39.
  • Hennig, A., et al. (author)
  • Mixed-symmetry octupole and hexadecapole excitations in N=52 isotones
  • 2015
  • In: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. - 9782759817948 ; 93
  • Conference paper (peer-reviewed)abstract
    • In addition to the well-established quadrupole mixed-symmetry states, octupole and hexadecapole excitations with mixed-symmetry character have been recently proposed for the N = 52 isotones 92Zr and 94Mo. We performed two inelastic proton-scattering experiments to study this kind of excitations in the heaviest stable N = 52 isotone 96Ru. From the combined experimental data of both experiments absolute transition strengths were extracted.
  •  
40.
  • Hennig, A., et al. (author)
  • Mixed-symmetry octupole and hexadecapole excitations in the N=52 isotones
  • 2014
  • In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 90:5, s. Art. no. 051302-
  • Journal article (peer-reviewed)abstract
    • Background: Excitations with mixed proton-neutron symmetry have been previously observed in the N=52 isotones. Besides the well-established quadrupole mixed-symmetry states (MSS), octupole and hexadecapole MSS have been recently proposed for the nuclei Zr92 and Mo94. Purpose: The heaviest stable N=52 isotone Ru96 was investigated to study the evolution of octupole and hexadecapole MSS with increasing proton number. Methods: Two inelastic proton-scattering experiments on Ru96 were performed to extract branching ratios, multipole mixing ratios, and level lifetimes. From the combined data, absolute transition strengths were calculated. Results: Strong M1 transitions between the lowest-lying 3- and 4+ states were observed, providing evidence for a one-phonon mixed-symmetry character of the 32(-) and 42+ states. Conclusions: sdg-IBM-2 calculations were performed for Ru96. The results are in excellent agreement with the experimental data, pointing out a one-phonon hexadecapole mixed-symmetry character of the 42+ state. The 31-||M1||32(-) matrix element is found to scale with the 2s+||M1||2ms+ matrix element.
  •  
41.
  • Hennig, A., et al. (author)
  • Study of mixed-symmetry excitations in Ru-96 via inelastic proton-scattering
  • 2015
  • In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 580:1
  • Conference paper (peer-reviewed)abstract
    • Mixed-symmetry states of octupole (L = 3) and hexadecapole (L = 4) character have been recently proposed in the N = 52 isotones Zr-92 and Mo-94, based on strong M1 transitions to the lowest-lying 3(-) and 4(+) states, respectively. In order to investigate similar excitations in the heaviest stable N = 52 isotone Ru-96, two inelastic proton-scattering experiments have been performed at the Wright Nuclear Structure Laboratory (WNSL), Yale University, USA and the Institute for Nuclear Physics, University of Cologne, Germany. From the combined data of both experiments, absolute E-1, M-1, and E2 transition strengths were extracted, allowing for the identification of candidates for MS octupole and hexadecapole states. The structure of the low-lying 4(+) states is investigated by means of sdg-IBM-2 calculations.
  •  
42.
  • Hinkula, Jorma, et al. (author)
  • HIVIS-DNA or HIVISopt-DNA priming followed by CMDR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV.
  • 2017
  • In: Heliyon. - : Elsevier. - 2405-8440. ; 3:6
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic.METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated. The reverse transcriptase (RT) gene was shortened to contain the most immunogenic N-terminal fragment and fused with an inactivated viral protease vPR gene. HIVISopt-DNA thus contains fewer plasmids but additional PR epitopes compared to the native HIVIS-DNA. DNA components were delivered intradermally to young Balb/c mice once, using a needle-free Biojector® immediately followed by dermal electroporation. Vaccinia-based MVA-CMDR boosts including Env gene E and Gag-RT genes A were delivered intramuscularly by needle, once or twice.RESULTS: Both HIVIS-DNA and HIVISopt-DNA primed humoral and cell mediated responses well. When boosted with heterologous MVA-CMDR (subtypes A and E) virus inhibitory neutralizing antibodies were obtained to HIV-1 subtypes A, B, C and AE. Both plasmid compositions boosted with MVA-CMDR generated HIV-1 specific cellular responses directed against HIV-1 Env, Gag and Pol, as measured by IFNγ ELISpot. It was shown that DNA priming augmented the vector MVA immunological boosting effects, the HIVISopt-DNA with a trend to improved (Env) neutralization, the HIVIS-DNA with a trend to better (Gag) cell mediated immune reponses.CONCLUSIONS: HIVIS-DNA was modified to obtain HIVISopt-DNA that had fewer plasmids, and additional epitopes. Even with one DNA prime followed by two MVA-CMDR boosts, humoral and cell-mediated immune responses were readily induced by priming with either DNA construct composition. Priming by HIV-DNA augmented neutralizing antibody responses revealed by boosting with the vaccinia-based heterologous sequences. Cellular and antibody responses covered selected strains representing HIV-1 subtypes A, B, C and CRF01_AE. We assume this is related to the inclusion of heterologous full genes in the vaccine schedule.
  •  
43.
  • Isaguliants, M, et al. (author)
  • Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells
  • 2021
  • In: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:6
  • Journal article (peer-reviewed)abstract
    • Therapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. INs, overexpressed in mammalian cells from synthetic genes, were assessed for stability, route of proteolytic degradation, and ability to induce oxidative stress. Both were found safe in immunotoxicity tests in mice, with no inherent carcinogenicity: their expression did not enhance tumorigenic or metastatic potential of adenocarcinoma 4T1 cells. DNA-immunization of mice with INs induced potent multicytokine T-cell response mainly against aa 209–239, and moderate IgG response cross-recognizing diverse IN variants. DNA-immunization with IN_in_r1 protected 60% of mice from challenge with 4Tlluc2 cells expressing non-mutated IN, while DNA-immunization with IN_in_r2 protected only 20% of mice, although tumor cells expressed IN matching the immunogen. Tumor size inversely correlated with IN-specific IFN-γ/IL-2 T-cell response. IN-expressing tumors displayed compromised metastatic activity restricted to lungs with reduced metastases size. Protective potential of IN immunogens relied on their immunogenicity for CD8+ T-cells, dependent on proteasomal processing and low level of oxidative stress.
  •  
44.
  •  
45.
  •  
46.
  • Jansons, J, et al. (author)
  • Expression of the Reverse Transcriptase Domain of Telomerase Reverse Transcriptase Induces Lytic Cellular Response in DNA-Immunized Mice and Limits Tumorigenic and Metastatic Potential of Murine Adenocarcinoma 4T1 Cells
  • 2020
  • In: Vaccines. - : MDPI AG. - 2076-393X. ; 8:2
  • Journal article (peer-reviewed)abstract
    • Telomerase reverse transcriptase (TERT) is a classic tumor-associated antigen overexpressed in majority of tumors. Several TERT-based cancer vaccines are currently in clinical trials, but immune correlates of their antitumor activity remain largely unknown. Here, we characterized fine specificity and lytic potential of immune response against rat TERT in mice. BALB/c mice were primed with plasmids encoding expression-optimized hemagglutinin-tagged or nontagged TERT or empty vector and boosted with same DNA mixed with plasmid encoding firefly luciferase (Luc DNA). Injections were followed by electroporation. Photon emission from booster sites was assessed by in vivo bioluminescent imaging. Two weeks post boost, mice were sacrificed and assessed for IFN-γ, interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α) production by T-cells upon their stimulation with TERT peptides and for anti-TERT antibodies. All TERT DNA-immunized mice developed cellular and antibody response against epitopes at the N-terminus and reverse transcriptase domain (rtTERT) of TERT. Photon emission from mice boosted with TERT/TERT-HA+Luc DNA was 100 times lower than from vector+Luc DNA-boosted controls. Bioluminescence loss correlated with percent of IFN-γ/IL-2/TNF-α producing CD8+ and CD4+ T-cells specific to rtTERT, indicating immune clearance of TERT/Luc-coexpressing cells. We made murine adenocarcinoma 4T1luc2 cells to express rtTERT by lentiviral transduction. Expression of rtTERT significantly reduced the capacity of 4T1luc2 to form tumors and metastasize in mice, while not affecting in vitro growth. Mice which rejected the tumors developed T-cell response against rtTERT and low/no response to the autoepitope of TERT. This advances rtTERT as key component of TERT-based therapeutic vaccines against cancer.
  •  
47.
  • Jansons, J, et al. (author)
  • Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer
  • 2021
  • In: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:5
  • Journal article (peer-reviewed)abstract
    • Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, but also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor-associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Additionally, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescence signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.
  •  
48.
  •  
49.
  • Kyuregyan, KK, et al. (author)
  • Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C
  • 2020
  • In: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:4
  • Journal article (peer-reviewed)abstract
    • Direct-acting antivirals (DAAs) revolutionized treatment of hepatitis C virus (HCV) infection. Resistance-associated substitutions (RASs) present at the baseline impair response to DAA due to rapid selection of resistant HCV strains. NS5A is indispensable target of the current DAA treatment regimens. We evaluated prevalence of RASs in NS5A in DAA-naïve patients infected with HCV 1a (n = 19), 1b (n = 93), and 3a (n = 90) before systematic DAA application in the territory of the Russian Federation. Total proportion of strains carrying at least one RAS constituted 35.1% (71/202). In HCV 1a we detected only M28V (57.9%) attributed to a founder effect. Common RASs in HCV 1b were R30Q (7.5%), L31M (5.4%), P58S (4.4%), and Y93H (5.4%); in HCV 3a, A30S (31.0%), A30K (5.7%), S62L (8.9%), and Y93H (2.2%). Prevalence of RASs in NS5A of HCV 1b and 3a was similar to that worldwide, including countries practicing massive DAA application, i.e., it was not related to treatment. NS5A with and without RASs exhibited different co-variance networks, which could be attributed to the necessity to preserve viral fitness. Majority of RASs were localized in polymorphic regions subjected to immune pressure, with selected substitutions allowing immune escape. Altogether, this explains high prevalence of RAS in NS5A and low barrier for their appearance in DAA-inexperienced population.
  •  
50.
  • Lemma, M, et al. (author)
  • Profiling of Inflammatory Proteins in Plasma of HIV-1-Infected Children Receiving Antiretroviral Therapy
  • 2020
  • In: Proteomes. - : MDPI AG. - 2227-7382. ; 8:3
  • Journal article (peer-reviewed)abstract
    • Treatment of HIV-1-infected patients results in improved clinical and immunological conditions, but severe non-AIDS-related conditions still persist. Novel proteomic platforms have identified inflammatory proteins where abundance is dysregulated in adult treated patients, whereas limited data are available in treated HIV-1 infection of children. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we analyzed specimens from 43 vertically HIV-1-infected children receiving antiretroviral treatment (ART) and matched controls in Ethiopia. The infected children were analyzed as a group and separately, according to age of treatment initiation. Proteins displaying a significantly different abundance between groups were hierarchically clustered and presented in heat maps. Random forest analysis was performed to pin-point proteins discriminating between groups; five proteins (STAMBP, CD5, TFG-α, TRANCE, AXIN1) were the strongest prediction factors for treated HIV-1 infection. TRANCE was previously linked to reduced bone mass levels in HIV-1-infected children. CCL4 chemokine, ligand to HIV-1 co-receptor CCR5, was the most critical protein for successful classification between children who initiated ART at different time points. Our data provide evidence that a dysregulated expression of proteins linked to immunological abnormalities and bone metabolism can be found in HIV-1-infected children with prolonged exposure to ART.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-50 of 58
Type of publication
journal article (48)
conference paper (6)
research review (3)
Type of content
peer-reviewed (54)
other academic/artistic (3)
Author/Editor
Petkov, S (27)
Bogomilov, M. (16)
Tsenov, R. (16)
Isaguliants, M (11)
Lopes, L. (10)
Mermod, P. (10)
show more...
Suzuki, Y. (10)
Vannucci, F. (10)
Xella, S. (10)
Petridis, K. (10)
Lee, K. S. (10)
De Roeck, A. (10)
Korol, I. (10)
Treille, D. (10)
Khabibullin, M. (10)
Korzenev, A. (10)
Kudenko, Y. (10)
Brenner, Richard (9)
Battistin, M. (9)
Silverstein, Samuel ... (9)
Betancourt, C. (9)
Campanelli, M. (9)
Casolino, M. (9)
Cristinziani, M. (9)
Golubkov, D. (9)
Hakobyan, H. (9)
Khoriauli, G. (9)
Milstead, D. A. (9)
Silverstein, S. B. (9)
Simoniello, R. (9)
Stramaglia, M. E. (9)
Froeschl, R. (9)
Milstead, David A. (9)
Breton, D. (9)
Kuznetsova, E. (9)
Wurm, M. (9)
Gorbunov, S. (9)
Rademakers, A. (9)
Samsonov, V. (9)
Lamont, M. (9)
Bondarenko, K. (9)
Kadenko, I. (9)
Kovalenko, S. (9)
Sokolenko, A. (9)
Barker, G. J. (9)
Rovelli, T. (9)
Zaytsev, Yu (9)
Osborne, J. (9)
Aoki, S. (9)
Atkin, E. (9)
show less...
University
Karolinska Institutet (27)
Uppsala University (16)
Stockholm University (13)
Royal Institute of Technology (9)
Chalmers University of Technology (7)
Lund University (6)
show more...
Luleå University of Technology (5)
Linköping University (3)
Swedish University of Agricultural Sciences (1)
show less...
Language
English (58)
Research subject (UKÄ/SCB)
Natural sciences (28)
Medical and Health Sciences (6)
Engineering and Technology (2)
Humanities (1)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view