A&A 666, A124 (2022) Young massive stellar clusters are extreme environments and potentially
provide the means for efficient particle acceleration. Indeed, they are
increasingly considered as being ...responsible for a significant fraction of
cosmic rays (CRs) accelerated within the Milky Way. Westerlund 1, the most
massive known young stellar cluster in our Galaxy is a prime candidate for
studying this hypothesis. While the very-high-energy $\gamma$-ray source HESS
J1646-458 has been detected in the vicinity of Westerlund 1 in the past, its
association could not be firmly identified. We aim to identify the physical
processes responsible for the $\gamma$-ray emission around Westerlund 1 and
thus to better understand the role of massive stellar clusters in the
acceleration of Galactic CRs. Using 164 hours of data recorded with the High
Energy Stereoscopic System (H.E.S.S.), we carried out a deep
spectromorphological study of the $\gamma$-ray emission of HESS J1646-458. We
furthermore employed H I and CO observations of the region to infer the
presence of gas that could serve as target material for interactions of
accelerated CRs. We detected large-scale ($\sim 2^\circ$ diameter) $\gamma$-ray
emission with a complex morphology, exhibiting a shell-like structure and
showing no significant variation with $\gamma$-ray energy. The combined energy
spectrum of the emission extends to several tens of TeV, and is uniform across
the entire source region. We did not find a clear correlation of the
$\gamma$-ray emission with gas clouds as identified through H I and CO
observations. We conclude that, of the known objects within the region, only
Westerlund 1 can explain the bulk of the $\gamma$-ray emission. Several CR
acceleration sites and mechanisms are conceivable, and discussed in detail.
(abridged)
Direct sequencing of polymerase chain reaction (PCR)-generated templates is a commonly used technique in molecular biology laboratories. We describe an improved method for direct sequencing of PCR ...fragments longer than 20 kb obtained with a commercial mixture of Taq and Pwo DNA polymerases. The sequencing protocol was optimized for an automated infrared DNA sequencer, consistently yielding long reads (500-600 bases).
We report on the observations of four well-localized binary black hole (BBH) mergers by the High Energy Stereoscopic System (H.E.S.S.) during the second and third observing runs of Advanced LIGO and ...Advanced Virgo, O2 and O3. H.E.S.S. can observe \(\mathrm{20\,deg^2}\) of the sky at a time and follows up gravitational-wave (GW) events by ``tiling'' localization regions to maximize the covered localization probability. During O2 and O3, H.E.S.S. observed large portions of the localization regions, between 35\% and 75\%, for four BBH mergers (GW170814, GW190512\_180714, GW190728\_064510, and S200224ca). For these four GW events, we find no significant signal from a pointlike source in any of the observations, and set upper limits on the very high energy (\(>\)100 GeV) \(\gamma\)-ray emission. The 1-10 TeV isotropic luminosity of these GW events is below \(10^{45}\) erg s\(^{-1}\) at the times of the H.E.S.S. observations, around the level of the low-luminosity GRB 190829A. Assuming no changes are made to how follow-up observations are conducted, H.E.S.S. can expect to observe over 60 GW events per year in the fourth GW observing run, O4, of which eight would be observable with minimal latency.
Clinical and laboratory procedures to fabricate a transitional prosthesis for patients treated with laryngofissure surgery have been described. Hard resin promoted healing of the surgical area and ...maintained the opening because of its stiffness. The prosthesis, which can be highly polished, was easily removed by the patient for proper hygiene and was fabricated to accurately fit the inside margins of the wound. All these factors were important for a good clinical result.
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Young massive stellar clusters are extreme environments and potentially provide the means for efficient particle acceleration. Indeed, they are increasingly considered as being responsible for a ...significant fraction of cosmic rays (CRs) accelerated within the Milky Way. Westerlund 1, the most massive known young stellar cluster in our Galaxy is a prime candidate for studying this hypothesis. While the very-high-energy \(\gamma\)-ray source HESS J1646-458 has been detected in the vicinity of Westerlund 1 in the past, its association could not be firmly identified. We aim to identify the physical processes responsible for the \(\gamma\)-ray emission around Westerlund 1 and thus to better understand the role of massive stellar clusters in the acceleration of Galactic CRs. Using 164 hours of data recorded with the High Energy Stereoscopic System (H.E.S.S.), we carried out a deep spectromorphological study of the \(\gamma\)-ray emission of HESS J1646-458. We furthermore employed H I and CO observations of the region to infer the presence of gas that could serve as target material for interactions of accelerated CRs. We detected large-scale (\(\sim 2^\circ\) diameter) \(\gamma\)-ray emission with a complex morphology, exhibiting a shell-like structure and showing no significant variation with \(\gamma\)-ray energy. The combined energy spectrum of the emission extends to several tens of TeV, and is uniform across the entire source region. We did not find a clear correlation of the \(\gamma\)-ray emission with gas clouds as identified through H I and CO observations. We conclude that, of the known objects within the region, only Westerlund 1 can explain the bulk of the \(\gamma\)-ray emission. Several CR acceleration sites and mechanisms are conceivable, and discussed in detail. (abridged)
Rett's syndrome (RTT) is a severe hereditary disorder of the nervous system. MECP2 gene mutations are considered as a primary cause of the disease. In the present study, we have found MECP2 mutations ...in 33 (84.6%) out of 39 RTT females. We have also studied X-inactivation patterns in 70 girls with RTT. A frequency of skewed X-inactivation was 37% (26 patients), being significantly higher (p < 0.001) than that in the controls. The investigation of inactivated X chromosome origin revealed that about 33% pairs had preferentially the inactivated maternal X chromosome. An abnormal type of chromosome X inactivation was observed in all RTT females. Thus, we conclude that skewed X-inactivation may be considered as a common feature of RTT. There is unambiguous evidence that epigenetic alterations in RTT are associated with MECP2 mutations. MeCP2 protein also appears to be involved in transcriptional regulation of chromosome X genes. RTT in females without MECP2 mutations is related to the epigenetic alterations. We suggest X chromosome inactivation study in RTT females and their mothers to be informative for investigation of genetic processes in RTT girls, even in case MECP2 mutations have not been found. RTT could be considered as an appropriate model for studying epigenetic abnormalities in relation to autistic spectrum disorders.
Human mesenchymal stem cells (hMSCs) suppress T-cell and dendritic-cell function and represent a promising strategy for cell therapy of autoimmune diseases. Nevertheless, no information is currently ...available on the effects of hMSCs on B cells, which may have a large impact on the clinical use of these cells. hMSCs isolated from the bone marrow and B cells purified from the peripheral blood of healthy donors were cocultured with different B-cell tropic stimuli. B-cell proliferation was inhibited by hMSCs through an arrest in the G0/G1 phase of the cell cycle and not through the induction of apoptosis. A major mechanism of B-cell suppression was hMSC production of soluble factors, as indicated by transwell experiments. hMSCs inhibited B-cell differentiation because IgM, IgG, and IgA production was significantly impaired. CXCR4, CXCR5, and CCR7 B-cell expression, as well as chemotaxis to CXCL12, the CXCR4 ligand, and CXCL13, the CXCR5 ligand, were significantly down-regulated by hMSCs, suggesting that these cells affect chemotactic properties of B cells. B-cell costimulatory molecule expression and cytokine production were unaffected by hMSCs. These results further support the potential therapeutic use of hMSCs in immune-mediated disorders, including those in which B cells play a major role.
Gene therapy with adeno-associated viral (AAV) vectors is limited by AAV cargo capacity that prevents their application to the inherited retinal diseases (IRDs), such as Stargardt disease (STGD) or ...Usher syndrome type IB (USH1B), which are due to mutations in genes larger than 5 kb. Trans-splicing or hybrid dual AAV vectors have been successfully exploited to reconstitute large gene expression in the mouse retina. Here, we tested them in the large cone-enriched pig retina that closely mimics the human retina. We found that dual AAV trans-splicing and hybrid vectors transduce pig photoreceptors, the major cell targets for treatment of IRDs, to levels that were about two- to threefold lower than those obtained with a single AAV vector of normal size. This efficiency is significantly higher than that in mice, and is potentially due to the high levels of dual AAV co-transduction we observe in pigs. We also show that subretinal delivery in pigs of dual AAV trans-splicing and hybrid vectors successfully reconstitute, albeit at variable levels, the expression of the large genes ABCA4 and MYO7A mutated in STGD and USH1B, respectively. Our data support the potential of dual AAV vectors for large gene reconstitution in the cone-enriched pig retina that is a relevant preclinical model.
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