Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals

BackgroundInfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.MethodsWe enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC.ResultsDuring the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular.ConclusionsWe found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC

Focusing on Students: Librarians and Writing Tutors Working Together

The aim of this presentation is to highlight and reflect on the advantages of collaboration between librarians and writing tutors, as well as to give three examples of fruitful collaboration at the Karolinska Institutet University Library. Librarians and writing tutors have different competencies and can help students with different aspects of their work. This specialization is however not obvious to students, which may lead to them approaching the wrong person, or focusing on tangible and specific details instead of the big picture.Collaboration between librarians and writing tutors has many advantages, both for students and staff. Firstly, it enables an overall view of the student’s working process and a contextualization of their work in a way that each group cannot achieve on their own. When the students understand the context of their assignments and theses, they are able to assume greater responsibility for their work, act more independently, and develop their critical thinking. Secondly, collaboration leads to a development of the staff’s competencies as we learn from each other, but we also get a deeper and more nuanced understanding of each other’s competencies, and can therefore plan teaching in a more efficient way.During our presentation, we will present and reflect on three activities on which we have collaborated: a lecture which addresses all the aspects of writing a thesis: searching, collecting, writing, and sharing; a seminar which aims to deepen the understanding for why and how sources are used, as well as how they are indicated in the text; and an online self-correcting test which highlights all aspects of thesis writing.The collaboration has been successful and motivated us to find new areas of collaboration. The next planned step is to offer students joint appointments with librarians and writing tutors to discuss their assignments

Electromigration Modelling of Void Nucleation in Open Cu-TSVs Christian Doppler Laboratory for Reliability Issues in Microelectronics at the

Abstract Recently, Through Silicon Vias (TSVs) have attracted much attention in three-dimensional (3D) integration technology due to their function as vertical connections of the different stacked semiconductor dies. Since electromigration (EM) will continue to be a key reliability issue in modern structures, the prediction of the EM failure behavior is a crucial necessity. Traditionally, Black's equation has been used from the early times of EM investigations for the estimation of the interconnect time to failure. In this work we investigate the applicability of Black's equation to open copper TSV structures using TCAD. TCAD can significantly contribute to the comprehension of EM failure mechanisms, in particular for the understanding of the early failure mode dominated by the void nucleation mechanism. The simulation procedure is applied to an open copper TSV technology in order to find the sites where void formation is most likely to occur. The time to failure is determined as the time needed to reach the stress threshold for void nucleation. Simulations are carried out for different current densities and successfully fitted to Black's equation. In this way, we have shown that failure development in studied TSV structures obeys Black's equation

The drug diazaborine blocks ribosome biogenesis by inhibiting the AAA-ATPase Drg1

Contains fulltext : 136109.pdf (publisher's version ) (Open Access)The drug diazaborine is the only known inhibitor of ribosome biogenesis and specifically blocks large subunit formation in eukaryotic cells. However, the target of this drug and the mechanism of inhibition were unknown. Here we identify the AAA-ATPase Drg1 as a target of diazaborine. Inhibitor binding into the second AAA domain of Drg1 requires ATP loading and results in inhibition of ATP hydrolysis in this site. As a consequence the physiological activity of Drg1, i.e. the release of Rlp24 from pre-60S particles, is blocked, and further progression of cytoplasmic preribosome maturation is prevented. Our results identify the first target of an inhibitor of ribosome biogenesis and provide the mechanism of inhibition of a key step in large ribosomal subunit formation