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| 2. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 3. |
- Gandolfi, D., et al.
(författare)
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The Transiting Multi-planet System HD15337: Two Nearly Equal-mass Planets Straddling the Radius Gap
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 876:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a super-Earth and a sub-Neptune transiting the star HD 15337 (TOI-402, TIC 120896927), a bright (V = 9) K1 dwarf observed by the Transiting Exoplanet Survey Satellite (TESS) in Sectors 3 and 4. We combine the TESS photometry with archival High Accuracy Radial velocity Planet Searcher spectra to confirm the planetary nature of the transit signals and derive the masses of the two transiting planets. With an orbital period of 4.8 days, a mass of {7.51}-1.01+1.09 {M}\oplus and a radius of 1.64 ± 0.06 R ⊕, HD 15337 b joins the growing group of short-period super-Earths known to have a rocky terrestrial composition. The sub-Neptune HD 15337 c has an orbital period of 17.2 days, a mass of {8.11}-1.69+1.82 {{{M}}}\oplus , and a radius of 2.39 ± 0.12 R ⊕, suggesting that the planet might be surrounded by a thick atmospheric envelope. The two planets have similar masses and lie on opposite sides of the radius gap, and are thus an excellent testbed for planet formation and evolution theories. Assuming that HD 15337 c hosts a hydrogen-dominated envelope, we employ a recently developed planet atmospheric evolution algorithm in a Bayesian framework to estimate the history of the high-energy (extreme ultraviolet and X-ray) emission of the host star. We find that at an age of 150 Myr, the star possessed on average between 3.7 and 127 times the high-energy luminosity of the current Sun.
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| 4. |
- Kessing, C. F., et al.
(författare)
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High Number of Activated CD8(+) T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
- 2017
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Ingår i: Jaids-Journal of Acquired Immune Deficiency Syndromes. - 1525-4135. ; 75:1, s. 108-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Central nervous system (CNS) infiltration by CD8(+) T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8(+) T cells in the CNS during acute HIV infection (AHI) is unknown. Methods: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8(+) T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8). Results: CSF CD8(+) T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8(+) T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8(+) T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8(+) T cells in AHI exhibited increased functional gene expression profiles associated with CD8(+) T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8(+) T cells directed to unique HIV epitopes compared with the periphery. Conclusions: These results suggest that CSF CD8(+) T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.
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| 5. |
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| 6. |
- Cartwright, S. P., et al.
(författare)
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Constitutively-stressed yeast strains are high-yielding for recombinant Fps1: implications for the translational regulation of an aquaporin
- 2017
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We previously selected four strains of Saccharomyces cerevisiae for their ability to produce the aquaporin Fps1 in sufficient yield for further study. Yields from the yeast strains spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline) that had been transformed with an expression plasmid containing 249 base pairs of 5' untranslated region (UTR) in addition to the primary FPS1 open reading frame (ORF) were 10-80 times higher than yields from wild-type cells expressing the same plasmid. One of the strains increased recombinant yields of the G protein-coupled receptor adenosine receptor 2a (A(2a)R) and soluble green fluorescent protein (GFP). The specific molecular mechanisms underpinning a high-yielding Fps1 phenotype remained incompletely described. Results: Polysome profiling experiments were used to analyze the translational state of spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline); all but gcn5 Delta. were found to exhibit a clear block in translation initiation. Four additional strains with known initiation blocks (rpl31a Delta., rpl22a Delta., ssf1 Delta. and nop1 Delta.) also improved the yield of recombinant Fps1 compared to wild-type. Expression of the eukaryotic transcriptional activator GCN4 was increased in spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline); these four strains also exhibited constitutive phosphorylation of the eukaryotic initiation factor, eIF2 alpha. Both responses are indicative of a constitutively-stressed phenotype. Investigation of the 5' UTR of FPS1 in the expression construct revealed two untranslated ORFs (uORF1 and uORF2) upstream of the primary ORF. Deletion of either uORF1 or uORF1 and uORF2 further improved recombinant yields in our four strains; the highest yields of the uORF deletions were obtained from wild-type cells. Frame-shifting the stop codon of the native uORF (uORF2) so that it extended into the FPS1 ORF did not substantially alter Fps1 yields in spt3. or wild-type cells, suggesting that high-yielding strains are able to bypass 5' uORFs in the FPS1 gene via leaky scanning, which is a known stress-response mechanism. Yields of recombinant A2aR, GFP and horseradish peroxidase could be improved in one or more of the yeast strains suggesting that a stressed phenotype may also be important in high-yielding cell factories. Conclusions: Regulation of Fps1 levels in yeast by translational control may be functionally important; the presence of a native uORF (uORF2) may be required to maintain low levels of Fps1 under normal conditions, but higher levels as part of a stress response. Constitutively-stressed yeast strains may be useful high-yielding microbial cell factories for recombinant protein production.
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| 7. |
- Liu, Chenxiao, et al.
(författare)
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V gamma 9V delta 2 T cells proliferate in response to phosphoantigens released from erythrocytes infected with asexual and gametocyte stage Plasmodium falciparum
- 2018
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Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749 .- 1090-2163. ; 334, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- V gamma 9V delta 2 T cells, the dominant gamma delta T cell subset in human peripheral blood, are stimulated by phosphoantigens, of which (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate, is produced in the apicoplast of malaria parasites. Cell-free media from synchronised Plasmodium falciparum asexual ring, trophozoite, and schizont stage-cultures of high purity as well as media from ruptured schizont cultures, all stimulated V gamma 9V delta 2 T cell proliferation, as did media from pure gametocyte cultures, whereas media from uninfected erythrocytes cultures did not. The media from ruptured schizont cultures and all the asexual and gametocyte stage cultures contained only background iron levels, suggesting that all erythrocyte haemoglobin is consumed as the parasites develop and supporting that the phosphoantigens were released from intact parasitized erythrocytes. The V gamma 9V delta 2 T cell-stimulating agent was not affected by freezing, thawing or heating but was sensitive to phosphatase treatment, confirming its phosphoantigen identity. In summary, phosphoantigens are released from parasitised erythrocytes at all developmental blood stages.
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