On the damped oscillations of an elastic quasi-circular membrane in a two-dimensional incompressible fluid

We propose a procedure - partly analytical and partly numerical - to find the frequency and the damping rate of the small-amplitude oscillations of a massless elastic capsule immersed in a two-dimensional viscous incompressible fluid. The unsteady Stokes equations for the stream function are decomposed onto normal modes for the angular and temporal variables, leading to a fourth-order linear ordinary differential equation in the radial variable. The forcing terms are dictated by the properties of the membrane, and result into jump conditions at the interface between the internal and external media. The equation can be solved numerically, and an excellent agreement is found with a fully-computational approach we developed in parallel. Comparisons are also shown with the results available in the scientific literature for drops, and a model based on the concept of embarked fluid is presented, which allows for a good representation of the results and a consistent interpretation of the underlying physics.Comment: in press on JF

The hematopoietic stem-cell niche in health and leukemia

Research in the last decade has shown that hematopoietic stem cells (HSCs) interact with and are modulated by a complex multicellular microenvironment in the bone marrow, which includes both the HSC progeny and multiple non-hematopoietic cell types. Intense work is gradually throwing light on the composition of the HSC niche and the molecular cues exchanged between its components, which has implications for HSC production, maintenance and expansion. In addition, it has become apparent that bidirectional interactions between leukemic cells and their niche play a previously unrecognized role in the initiation and development of hematological malignancies. Consequently, targeting of the malignant niche holds considerable promise for more specific antileukemic therapies. Here we summarize the latest insights into HSC niche biology and recent work showing multiple connections between hematological malignancy and alterations in the bone marrow microenvironment.We thank members of the SM-F group for helpful discussions. This work was supported by core support grants from the Wellcome Trust and MRC to the Cambridge Stem Cell Institute, the Spanish Ministry of Economy and Competitiveness (SAF-2011-30308), Pro-CNIC Foundation, Severo Ochoa Center of Excellence award SEV-2015-0505 to CNIC, TerCel (Spanish Cell Therapy Network), Ramon y Cajal Program grants RYC-2011-09726 to AS-A and RYC-2009-04703 to SM-F), Marie Curie Career Integration Program grants (FP7-PEOPLE-2011-RG-294262/294096) to AS-A and SM-F; and a ConSEPOC-Comunidad de Madrid grant (S2010/BMD-2542) and Horizon2020 (ERC-2014-CoG-64765 grant to SM-F. This research was partly funded by a European Hematology Association Research Fellowship awarded to AS-A and an International Early Career Scientist Grant from the Howard Hughes Medical Institute to SM-F.S

Generalizing to New Tasks via One-Shot Compositional Subgoals

The ability to generalize to previously unseen tasks with little to no supervision is a key challenge in modern machine learning research. It is also a cornerstone of a future "General AI". Any artificially intelligent agent deployed in a real world application, must adapt on the fly to unknown environments. Researchers often rely on reinforcement and imitation learning to provide online adaptation to new tasks, through trial and error learning. However, this can be challenging for complex tasks which require many timesteps or large numbers of subtasks to complete. These "long horizon" tasks suffer from sample inefficiency and can require extremely long training times before the agent can learn to perform the necessary longterm planning. In this work, we introduce CASE which attempts to address these issues by training an Imitation Learning agent using adaptive "near future" subgoals. These subgoals are recalculated at each step using compositional arithmetic in a learned latent representation space. In addition to improving learning efficiency for standard long-term tasks, this approach also makes it possible to perform one-shot generalization to previously unseen tasks, given only a single reference trajectory for the task in a different environment. Our experiments show that the proposed approach consistently outperforms the previous state-of-the-art compositional Imitation Learning approach by 30%.Comment: Present at ICRA 2022 "Compositional Robotics: Mathematics and Tools

Light-Dependent Translocation of Arrestin in the Absence of Rhodopsin Phosphorylation and Transducin Signaling

Visual arrestin plays a crucial role in the termination of the light response in vertebrate photoreceptors by binding selectively to light-activated, phosphorylated rhodopsin. Arrestin localizes predominantly to the inner segments and perinuclear region of dark-adapted rod photoreceptors, whereas light induces redistribution of arrestin to the rod outer segments. The mechanism by which arrestin redistributes in response to light is not known, but it is thought to be associated with the ability of arrestin to bind photolyzed, phosphorylated rhodopsin in the outer segment. In this study, we show that light-driven translocation of arrestin is unaffected in two different mouse models in which rhodopsin phosphorylation is lacking. We further show that arrestin movement is initiated by rhodopsin but does not require transducin signaling. These results exclude passive diffusion and point toward active transport as the mechanism for light-dependent arrestin movement in rod photoreceptor cells

A new look at blood shear-thinning

Blood viscosity decreases with shear stress, a property essential for an efficient perfusion of the vascular tree. Shear-thinning is intimately related to the dynamics and mutual interactions of red blood cells (RBCs), the major constituents of blood. Our work explores RBCs dynamics under physiologically relevant conditions of flow strength, outer fluid viscosity and volume fraction. Our results contradict the current paradigm stating that RBCs should align and elongate in the flow direction thanks to their membrane circulation around their center of mass, reducing flow-lines disturbances. On the contrary, we observe both experimentally and with simulations, rich morphological transitions that relate to global blood rheology. For increasing shear stresses, RBCs successively tumble, roll, deform into rolling stomatocytes and finally adopt highly deformed and polylobed shapes even for semi-dilute volume fractions analogous to microcirculatory values. Our study suggests that any pathological change in plasma composition, RBCs cytosol viscosity or membrane mechanical properties will impact the onset of shape transitions and should play a central role in pathological blood rheology and flow behavior

Speech can produce jet-like transport relevant to asymptomatic spreading of virus

Many scientific reports document that asymptomatic and presymptomatic individuals contribute to the spread of COVID-19, probably during conversations in social interactions. Droplet emission occurs during speech, yet few studies document the flow to provide the transport mechanism. This lack of understanding prevents informed public health guidance for risk reduction and mitigation strategies, e.g. the "six-foot rule". Here we analyze flows during breathing and speaking, including phonetic features, using order-of-magnitudes estimates, numerical simulations, and laboratory experiments. We document the spatio-temporal structure of the expelled air flow. Phonetic characteristics of plosive sounds like 'P' lead to enhanced directed transport, including jet-like flows that entrain the surrounding air. We highlight three distinct temporal scaling laws for the transport distance of exhaled material including (i) transport over a short distance ($<$ 0.5 m) in a fraction of a second, with large angular variations due to the complexity of speech, (ii) a longer distance, approximately 1 m, where directed transport is driven by individual vortical puffs corresponding to plosive sounds, and (iii) a distance out to about 2 m, or even further, where sequential plosives in a sentence, corresponding effectively to a train of puffs, create conical, jet-like flows. The latter dictates the long-time transport in a conversation. We believe that this work will inform thinking about the role of ventilation, aerosol transport in disease transmission for humans and other animals, and yield a better understanding of linguistic aerodynamics, i.e., aerophonetics.Comment: 14 pages, 6 figure

Twin-width IV: ordered graphs and matrices

We establish a list of characterizations of bounded twin-width for hereditary, totally ordered binary structures. This has several consequences. First, it allows us to show that a (hereditary) class of matrices over a finite alphabet either contains at least $n!$ matrices of size $n \times n$, or at most $c^n$ for some constant $c$. This generalizes the celebrated Stanley-Wilf conjecture/Marcus-Tardos theorem from permutation classes to any matrix class over a finite alphabet, answers our small conjecture [SODA '21] in the case of ordered graphs, and with more work, settles a question first asked by Balogh, Bollob\'as, and Morris [Eur. J. Comb. '06] on the growth of hereditary classes of ordered graphs. Second, it gives a fixed-parameter approximation algorithm for twin-width on ordered graphs. Third, it yields a full classification of fixed-parameter tractable first-order model checking on hereditary classes of ordered binary structures. Fourth, it provides a model-theoretic characterization of classes with bounded twin-width.Comment: 53 pages, 18 figure

Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium

Clinical trials; Liver transplant; Quality of lifeEnsayos clínicos; Trasplante de hígado; Calidad de vidaAssaigs clínics; Trasplantament de fetge; Qualitat de vidaManagement of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis