BL Lac X-ray Spectra: simpler than we thought

We report results from {\it XMM-Newton} observations of thirteen X-ray bright BL Lacertae objects, selected from the {\it Einstein} Slew Survey sample. The spectra are generally well fit by power-law models, with four objects having hard ($\alpha<1; F_\nu \propto \nu^{-\alpha}$) spectra that indicates synchrotron peaks at $>5$ keV. None of our spectra show line features, indicating that soft X-ray absorption ``notches'' must be rare amongst BL Lacs, rather than common or ubiquitous as had previously been asserted. We find significant curvature in most of the spectra. This curvature is almost certainly intrinsic, as it appears nearly constant from 0.5 to 6 keV, an observation which is inconsistent with the small columns seen in these sources.Comment: 4 pages, 1 figure; to be published in proceedings of the Cozumel meeting on "Multiwavelength Surveys for AGN", Cozumel 200

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

PERCCOM: A Master Program in Pervasive Computing and COMmunications for Sustainable Development

International audienceThis paper presents the Erasmus Mundus Joint Master Degree in Pervasive Computing and Communications for Sustainable Development (PERCCOM). This program brings together 11 academic partners and 8 industry partners to combine advanced Information and Communication Technologies (ICT) with environmental awareness to enable world-class education and unique competences for ICT professionals who can build cleaner, greener, more resource and energy efficient cyber-physical systems. First, this paper describes the rationale and motivations for ICT education for sustainability challenges. It then details the structure and contents of the programs including the courses offered at the three teaching locations (Nancy France, Lappeenranta Finland, and Lulea Sweden). The ways that the program has been running as well as students selection, their thesis works, involvement of industry, are also discussed. The program was built and managed using a solid academic standards and strategies student-centered learning

PERCCOM : A Master Program in Pervasive Computing and COMmunications for Sustainable Development

This paper presents the Erasmus Mundus Joint Master Degree in Pervasive Computing and Communications for Sustainable Development (PERCCOM). This program brings together 11 academic partners and 8 industry partners to combine advanced Information and Communication Technologies (ICT) with environmental awareness to enable world-class education and unique competences for ICT professionals who can build cleaner, greener, more resource and energy efficient cyber-physical systems. First, this paper describes the rationale and motivations for ICT education for sustainability challenges. It then details the structure and contents of the programs including the courses offered at the three teaching locations (Nancy France, Lappeenranta Finland, and Lulea Sweden). The ways that the program has been running as well as students selection, their thesis works, involvement of industry, are also discussed. The program was built and managed using a solid academic standards and strategies student-centered learning.Validerad; 2016; Nivå 1; 2016-11-17 (andbra)PERvasive Computing and COMmunications for sustainable developmen