46 research outputs found
Absorbing boundary conditions for granular acoustics
The boundary conditions of soft-sphere DEM are usually perfect reflectors of acoustic waves, leading to an unrealistic accumulation of energy. This situation is usually dealt with by global damping. In some situations, this solution is undesirable, so we present an alternative. If the grain-wall contact is made soft and dissipative, most acoustic energy incident on the boundary will be trapped and dissipated there. We show that these boundary conditions can efficiently damp both high and low frequency waves
Measurement of Indeterminacy in Packings of Perfectly Rigid Disks
Static packings of perfectly rigid particles are investigated theoretically
and numerically. The problem of finding the contact forces in such packings is
formulated mathematically. Letting the values of the contact forces define a
vector in a high-dimensional space enable us to show that the set of all
possible contact forces is convex, facilitating its numerical exploration. It
is also found that the boundary of the set is connected with the presence of
sliding contacts, suggesting that a stable packing should not have more than
2M-3N sliding contacts in two dimensions, where M is the number of contacts and
N is the number of particles.
These results were used to analyze packings generated in different ways by
either molecular dynamics or contact dynamics simulations. The dimension of the
set of possible forces and the number of sliding contacts agrees with the
theoretical expectations. The indeterminacy of each component of the contact
forces are found, as well as the an estimate for the diameter of the set of
possible contact forces. We also show that contacts with high indeterminacy are
located on force chains. The question of whether the simulation methods can
represent a packing's memory of its formation is addressed.Comment: 12 pages, 13 figures, submitted to Phys Rev
Quasi-rigidity: some uniqueness issues
Quasi-rigidity means that one builds a theory for assemblies of grains under
a slowly changing external load by using the deformation of those grains as a
small parameter. Is quasi-rigidity a complete theory for these granular
assemblies? Does it provide unique predictions of the assembly's behavior, or
must some other process be invoked to decide between several possibilities? We
provide evidence that quasi-rigidity is a complete theory by showing that two
possible sources of indeterminacy do not exist for the case of disk shaped
grains. One possible source of indeterminacy arises from zero-frequency modes
present in the packing. This problem can be solved by considering the
conditions required to obtain force equilibrium. A second possible source of
indeterminacy is the necessity to choose the status (sliding or non-sliding) at
each contact. We show that only one choice is permitted, if contacts slide only
when required by Coulomb friction.Comment: 14 pages, 3 figures, submitted to Phys Rev E (introduction and
conclusion revised
Energy flows in vibrated granular media
We study vibrated granular media, investigating each of the three components
of the energy flow: particle-particle dissipation, energy input at the
vibrating wall, and particle-wall dissipation. Energy dissipated by
interparticle collisions is well estimated by existing theories when the
granular material is dilute, and these theories are extended to include
rotational kinetic energy. When the granular material is dense, the observed
particle-particle dissipation rate decreases to as little as 2/5 of the
theoretical prediction. We observe that the rate of energy input is the weight
of the granular material times an average vibration velocity times a function
of the ratio of particle to vibration velocity. `Particle-wall' dissipation has
been neglected in all theories up to now, but can play an important role when
the granular material is dilute. The ratio between gravitational potential
energy and kinetic energy can vary by as much as a factor of 3. Previous
simulations and experiments have shown that E ~ V^delta, with delta=2 for
dilute granular material, and delta ~ 1.5 for dense granular material. We
relate this change in exponent to the departure of particle-particle
dissipation from its theoretical value.Comment: 19 pages revtex, 10 embedded eps figures, accepted by PR
Energy non-equipartition in systems of inelastic, rough spheres
We calculate and verify with simulations the ratio between the average
translational and rotational energies of systems with rough, inelastic
particles, either forced or freely cooling. The ratio shows non-equipartition
of energy. In stationary flows, this ratio depends mainly on the particle
roughness, but in nonstationary flows, such as freely cooling granular media,
it also depends strongly on the normal dissipation. The approach presented here
unifies and simplifies different results obtained by more elaborate kinetic
theories. We observe that the boundary induced energy flux plays an important
role.Comment: 4 pages latex, 4 embedded eps figures, accepted by Phys Rev
Fragmentation of a Circular Disc by Impact on a Frictionless Plate
The break-up of a two-dimensional circular disc by normal and oblique impact
on a hard frictionless plate is investigated by molecular dynamics simulations.
The disc is composed of numerous unbreakable randomly shaped convex polygons
connected together by simple elastic beams that break when bent or stretched
beyond a certain limit. It is found that for both normal and oblique impacts
the crack patterns are the same and depend solely on the normal component of
the impact velocity. Analysing the pattern of breakage, amount of damage,
fragment masses and velocities, we show the existence of a critical velocity
which separates two regimes of the impact process: below the critical point
only a damage cone is formed at the impact site (damage), cleaving of the
particle occurs at the critical point, while above the critical velocity the
disc breaks into several pieces (fragmentation). In the limit of very high
impact velocities the disc suffers complete disintegration (shattering) into
many small fragments. In agreement with experimental results, fragment masses
are found to follow the Gates-Gaudin-Schuhmann distribution (power law) with an
exponent independent of the velocity and angle of impact. The velocity
distribution of fragments exhibit an interesting anomalous scaling behavior
when changing the impact velocity and the size of the disc.Comment: submitted to J. Phys: Condensed Matter special issue on Granular
Medi
Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death
Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocyte-specific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD. The increase in SCD in CYB5R3-KO mice is associated with calcium mishandling, ventricular fibrillation, and cardiomyocyte hypertrophy. Molecular studies reveal that CYB5R3-KO hearts display decreased adenosine triphosphate (ATP), increased oxidative stress, suppressed coenzyme Q levels, and hemoprotein dysregulation. Finally, from a translational perspective, we reveal that the high-frequency missense genetic variant rs1800457, which translates into a CYB5R3 T117S partial loss-of-function protein, associates with decreased event-free survival (~20%) in Black persons with HF with reduced ejection fraction (HFrEF). Together, these studies reveal a crucial role for CYB5R3 in cardiomyocyte redox biology and identify a genetic biomarker for persons of African ancestry that may potentially increase the risk of death from HFrEF.These studies were supported by NIH grants R35 HL 161177 (to ACS), R01 HL 133864 (to ACS), R01 HL 128304 (to ACS), R41 HL15098 (to GS), R01 GM 122091 (to PHT), GM125944 (to FJS), R01 DK112854 (to FJS), R21 NS112787 (to MF), NS121706 (to YLW), EB023507 (to YLW), F31 HL149241 (to HMS), and F31 HL151173 (to JCG). Support was also provided by American Heart Association grants 19EIA34770095 (to ACS), AHA 18CDA34140024 (to YLW), and 19PRE34380152 (to NTC); the Spanish Ministry of Health (grant FIS PI17-01286); Junta de Andalucía BIO-177 and the FEDER Funding Program from the European Union and CIBERER (U729)-ISCIII (to PN); Department of Defense W81XWH1810070 (to YLW); and Vitalant. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Specifically, this work used the HTC cluster, which is supported by NIH award number S10OD028483.Peer reviewe
Approximating Optimal Behavioural Strategies Down to Rules-of-Thumb: Energy Reserve Changes in Pairs of Social Foragers
Functional explanations of behaviour often propose optimal strategies for organisms to follow. These ‘best’ strategies could be difficult to perform given biological constraints such as neural architecture and physiological constraints. Instead, simple heuristics or ‘rules-of-thumb’ that approximate these optimal strategies may instead be performed. From a modelling perspective, rules-of-thumb are also useful tools for considering how group behaviour is shaped by the behaviours of individuals. Using simple rules-of-thumb reduces the complexity of these models, but care needs to be taken to use rules that are biologically relevant. Here, we investigate the similarity between the outputs of a two-player dynamic foraging game (which generated optimal but complex solutions) and a computational simulation of the behaviours of the two members of a foraging pair, who instead followed a rule-of-thumb approximation of the game's output. The original game generated complex results, and we demonstrate here that the simulations following the much-simplified rules-of-thumb also generate complex results, suggesting that the rule-of-thumb was sufficient to make some of the model outcomes unpredictable. There was some agreement between both modelling techniques, but some differences arose – particularly when pair members were not identical in how they gained and lost energy. We argue that exploring how rules-of-thumb perform in comparison to their optimal counterparts is an important exercise for biologically validating the output of agent-based models of group behaviour
Pharmacokinetics and pharmacodynamics of clofazimine for treatment of cryptosporidiosis
Infection with Cryptosporidium spp. can cause severe diarrhea leading to long-term adverse impacts and even death in malnourished children and immunocompromised patients. The only FDA-approved drug for treating cryptosporidiosis, nitazoxanide, has limited efficacy in the populations impacted the most by the diarrheal disease, and safe, effective treatment options are urgently needed. Initially identified by a large-scale phenotypic screening campaign, the antimycobacterial therapeutic clofazimine demonstrated great promise in both in vitro and in vivo preclinical models of Cryptosporidium infection. Unfortunately, a Phase 2a clinical trial in HIV infected adults with cryptosporidiosis did not identify any clofazimine treatment effect on Cryptosporidium infection burden or clinical outcomes. To explore whether clofazimine's lack of efficacy in the Phase 2a trial may have been due to subtherapeutic clofazimine concentrations, a pharmacokinetic/pharmacodynamic modeling approach was undertaken to determine the relationship between clofazimine in vivo concentrations and treatment effects in multiple preclinical infection models. Exposure-response relationships were characterized using Emax and logistic models which allowed predictions of efficacious clofazimine concentrations for the control and reduction of disease burden. After establishing exposure-response relationships for clofazimine treatment of Cryptosporidium infection in our preclinical model studies, it was unmistakable that the clofazimine levels observed in the Phase 2a study participants were well below concentrations associated with anti-Cryptosporidium efficacy. Thus, despite a dosing regimen above the highest doses recommended for mycobacterial therapy, it is very likely the lack of treatment effect in the Phase 2a trial was at least partially due to clofazimine concentrations below those required for efficacy against cryptosporidiosis. It is unlikely that clofazimine will provide a remedy for the large number of cryptosporidiosis patients currently without a viable treatment option unless alternative, safe clofazimine formulations with improved oral absorption are developed