Anholonomic frames in constrained dynamics

We demonstrate the usefulness of anholonomic frames in the contexts of nonholonomic and vakonomic systems. We take a consistently differential-geometric approach. As an application, we investigate the conditions under which the dynamics of the two systems will be consistent. A few illustrative examples confirm the results.Comment: 33 pages, to appear in `Dynamical Systems. An international journal.

Conservation of energy and momenta in nonholonomic systems with affine constraints

We characterize the conditions for the conservation of the energy and of the components of the momentum maps of lifted actions, and of their `gauge-like' generalizations, in time-independent nonholonomic mechanical systems with affine constraints. These conditions involve geometrical and mechanical properties of the system, and are codified in the so-called reaction-annihilator distribution

Reduction of invariant constrained systems using anholonomic frames

We analyze two reduction methods for nonholonomic systems that are invariant under the action of a Lie group on the configuration space. Our approach for obtaining the reduced equations is entirely based on the observation that the dynamics can be represented by a second-order differential equations vector field and that in both cases the reduced dynamics can be described by expressing that vector field in terms of an appropriately chosen anholonomic frame.Comment: 19 page

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

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

The reaction-annihilator distribution and the nonholonomic Noether theorem for lifted actions

We consider nonholonomic systems with linear, time-independent constraints subject to positional conservative active forces. We identify a distribution on the configuration manifold, that we call the reaction-annihilator distribution R degrees, the fibers of which are the annihilators of the set of all values taken by the reaction forces on the fibers of the constraint distribution. We show that this distribution, which can be effectively computed in specific cases, plays a central role in the study of first integrals linear in the velocities of this class of nonholonomic systems. In particular we prove that, if the Lagrangian is invariant under (the lift of) a group action in the configuration manifold, then an infinitesimal generator of this action has a conserved momentum if and only if it is a section of the distribution R degrees. Since the fibers of R degrees contain those of the constraint distribution, this version of the nonholonomic Noether theorem accounts for more conserved momenta than what was known so far. Some examples are given