The Prince and the Pauper: Evidence for the early high-redshift formation of the Galactic α\alpha-poor disc population

Context. The presence of [$\alpha$/Fe]-[Fe/H] bi-modality in the Milky Way disc has animated the Galactic archaeology community since more than two decades. Aims. Our goal is to investigate the chemical, temporal, and kinematical structure of the Galactic discs using abundances, kinematics, and ages derived self-consistently with the new Bayesian framework SAPP. Methods. We employ the public Gaia-ESO spectra, as well as Gaia EDR3 astrometry and photometry. Stellar parameters and chemical abundances are determined for 13 426 stars using NLTE models of synthetic spectra. Ages are derived for a sub-sample of 2 898 stars, including subgiants and main-sequence stars. The sample probes a large range of Galactocentric radii, $\sim$ 3 to 12 kpc, and extends out of the disc plane to $\pm$ 2 kpc. Results. Our new data confirm the known bi-modality in the [Fe/H] - [$\alpha$/Fe] space, which is often viewed as the manifestation of the chemical thin and thick discs. The over-densities significantly overlap in metallicity, age, and kinematics, and none of these is a sufficient criterion for distinguishing between the two disc populations. Different from previous studies, we find that the $\alpha$-poor disc population has a very extended [Fe/H] distribution and contains $\sim$ 20$\%$ old stars with ages of up to $\sim$ 11 Gyr. Conclusions. Our results suggest that the Galactic thin disc was in place early, at look-back times corresponding to redshifts z $\sim$ 2 or more. At ages $\sim$ 9 to 11 Gyr, the two disc structures shared a period of co-evolution. Our data can be understood within the clumpy disc formation scenario that does not require a pre-existing thick disc to initiate a formation of the thin disc. We anticipate that a similar evolution can be realised in cosmological simulations of galaxy formation.Comment: 14 pages, 10 figures, re-submitted to A&

Acceptance of technology-enhanced learning for a theoretical radiological science course: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Technology-enhanced learning (TEL) gives a view to improved education. However, there is a need to clarify how TEL can be used effectively. The study compared students' attitudes and opinions towards a traditional face-to-face course on theoretical radiological science and a TEL course where students could combine face-to-face lectures and e-learning modules at their best convenience.</p> <p>Methods</p> <p>42 third-year dental students were randomly assigned to the traditional face-to-face group and the TEL group. Both groups completed questionnaires before the beginning and after completion of the course on attitudes and opinions towards a traditional face-to-face lectures and technology-enhanced learning. After completion of the course both groups also filled in the validated German-language TRIL (Trierer Inventar zur Lehrevaluation) questionnaire for the evaluation of courses given at universities.</p> <p>Results</p> <p>Both groups had a positive attitude towards e-learning that did not change over time. The TEL group attended significantly less face-to-face lectures than the traditional group. However, both groups stated that face-to-face lectures were the basis for education in a theoretical radiological science course.</p> <p>The members of the TEL group rated e-mail reminders significantly more important when they filled in the questionnaire on attitudes and opinions towards a traditional face-to-face lectures and technology-enhanced learning for the second time after completion of the course.</p> <p>The members of the technology-enhanced learning group were significantly less confident in passing the exam compared to the members of the traditional group. However, examination results did not differ significantly for traditional and the TEL group.</p> <p>Conclusions</p> <p>It seems that technology-enhanced learning in a theoretical radiological science course has the potential to reduce the need for face-to-face lectures. At the same time examination results are not impaired. However, technology-enhanced learning cannot completely replace traditional face-to-face lectures, because students indicate that they consider traditional teaching as the basis of their education.</p

PDGF-C Induces Maturation of Blood Vessels in a Model of Glioblastoma and Attenuates the Response to Anti-VEGF Treatment

Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy.We first showed that PDGF-C is present in human GBMs. Then, we overexpressed or downregulated PDGF-C in a human GBM cell line, U87MG, and grew them in cranial windows in nude mice to assess vessel structure and function using intravital microscopy. PDGF-C overexpressing tumors had smaller vessel diameters and lower vascular permeability compared to the parental or siRNA-transfected tumors. Furthermore, vessels in PDGF-C overexpressing tumors had more extensive coverage with NG2 positive perivascular cells and a thicker collagen IV basement membrane than the controls. Treatment with DC101, an anti-VEGFR-2 antibody, induced decreases in vessel density in the parental tumors, but had no effect on the PDGF-C overexpressing tumors.These results suggest that PDGF-C plays an important role in glioma vessel maturation and stabilization, and that it can attenuate the response to anti-VEGF therapy, potentially contributing to escape from vascular normalization

Exploring the mechanisms of renoprotection against progressive glomerulosclerosis

In this review, I introduce the strategy developed by our laboratory to explore the mechanisms of renoprotection against progressive glomerulosclerosis leading to renal death. First, I describe the experimental rat model in which disturbances of vascular regeneration and glomerular hemodynamics lead to irreversible glomerulosclerosis. Second, I discuss the possible mechanisms determining the progression of glomerulosclerosis and introduce a new imaging system based on intravital confocal laser scanning microscopy. Third, I provide an in-depth review of the regulatory glomerular hemodynamics at the cellular and molecular levels while focusing on the pivotal role of Ca2+-dependent gap junctional intercellular communication in coordinating the behavior of mesangial cells. Last, I show that local delivery of renoprotective agents, in combination with diagnostic imaging of the renal microvasculature, allows the evaluation of the therapeutic effects of angiotensin II receptor and cyclooxygenase activity local blockade on the progression of glomerulosclerosis, which would otherwise lead to renal death

Post-Infection Immunodeficiency Virus Control by Neutralizing Antibodies

BACKGROUND: Unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (NAbs), primary HIV infections are not met with such potent and early antibody responses. This brings into question if or how the presence of potent antibodies can contribute to primary HIV control, but protective efficacies of antiviral antibodies in primary HIV infections have remained elusive; and, it has been speculated that even NAb induction could have only a limited suppressive effect on primary HIV replication once infection is established. Here, in an attempt to answer this question, we examined the effect of passive NAb immunization post-infection on primary viral replication in a macaque AIDS model. METHODS AND FINDINGS: The inoculums for passive immunization with simian immunodeficiency virus mac239 (SIVmac239)-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC)-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced T cell priming. CONCLUSIONS: Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for sterile HIV protection by prophylactic vaccination has been suggested, this study points out a possibility of non-sterile HIV control by prophylactic vaccine-induced, sub-sterile titers of NAbs post-infection, providing a rationale of vaccine-based NAb induction for primary HIV control

The GALAH Survey : Non-LTE departure coefficients for large spectroscopic surveys

19 pages, 25 figures, 2 tables, arXiv abstract abridged; accepted for publication in A&AMassive sets of stellar spectroscopic observations are rapidly becoming available and these can be used to determine the chemical composition and evolution of the Galaxy with unprecedented precision. One of the major challenges in this endeavour involves constructing realistic models of stellar spectra with which to reliably determine stellar abundances. At present, large stellar surveys commonly use simplified models that assume that the stellar atmospheres are approximately in local thermodynamic equilibrium (LTE). To test and ultimately relax this assumption, we have performed non-LTE calculations for $13$ different elements (H, Li, C, N, O, Na, Mg, Al, Si, K, Ca, Mn, and Ba), using recent model atoms that have physically-motivated descriptions for the inelastic collisions with neutral hydrogen, across a grid of $3756$ 1D MARCS model atmospheres that spans $3000\leq T_{\mathrm{eff}}/\mathrm{K}\leq8000$, $-0.5\leq\log{g/\mathrm{cm\,s^{-2}}}\leq5.5$, and $-5\leq\mathrm{[Fe/H]}\leq1$. We present the grids of departure coefficients that have been implemented into the GALAH DR3 analysis pipeline in order to complement the extant non-LTE grid for iron. We also present a detailed line-by-line re-analysis of $50126$ stars from GALAH DR3. We found that relaxing LTE can change the abundances by between $-0.7\,\mathrm{dex}$ and $+0.2\,\mathrm{dex}$ for different lines and stars. Taking departures from LTE into account can reduce the dispersion in the $\mathrm{[A/Fe]}$ versus $\mathrm{[Fe/H]}$ plane by up to $0.1\,\mathrm{dex}$, and it can remove spurious differences between the dwarfs and giants by up to $0.2\,\mathrm{dex}$. The resulting abundance slopes can thus be qualitatively different in non-LTE, possibly with important implications for the chemical evolution of our Galaxy.Peer reviewe