On the validity of entropy production principles for linear electrical circuits

We discuss the validity of close-to-equilibrium entropy production principles in the context of linear electrical circuits. Both the minimum and the maximum entropy production principle are understood within dynamical fluctuation theory. The starting point are Langevin equations obtained by combining Kirchoff's laws with a Johnson-Nyquist noise at each dissipative element in the circuit. The main observation is that the fluctuation functional for time averages, that can be read off from the path-space action, is in first order around equilibrium given by an entropy production rate. That allows to understand beyond the schemes of irreversible thermodynamics (1) the validity of the least dissipation, the minimum entropy production, and the maximum entropy production principles close to equilibrium; (2) the role of the observables' parity under time-reversal and, in particular, the origin of Landauer's counterexample (1975) from the fact that the fluctuating observable there is odd under time-reversal; (3) the critical remark of Jaynes (1980) concerning the apparent inappropriateness of entropy production principles in temperature-inhomogeneous circuits.Comment: 19 pages, 1 fi

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Juergen Ehlers - and the Fate of the Black-Hole Spacetimes

This article -- written in honour of Juergen Ehlers -- consists of two different, though interlocking parts: Section 1 describes my 54 years of perpetual experiences and exchanges with him, both science and episodes, whilst section 2 describes the history of astrophysical black holes, which evolved during the same epoque though largely independently, with its activity centers in other places of the globe, and has by no means terminated.Comment: 12 pages, 2 figures, to be published in General Relativity and Gravitation, Juergen Ehlers Commemorative Issu