Slow relaxation in granular compaction

Experimental studies show that the density of a vibrated granular material evolves from a low density initial state into a higher density final steady state. The relaxation towards the final density value follows an inverse logarithmic law. We propose a simple stochastic adsorption-desorption process which captures the essential mechanism underlying this remarkably slow relaxation. As the system approaches its final state, a growing number of beads have to be rearranged to enable a local density increase. In one dimension, this number grows as $N=\rho/(1-\rho)$, and the density increase rate is drastically reduced by a factor $e^{-N}$. Consequently, a logarithmically slow approach to the final state is found $\rho_{\infty}-\rho(t)\cong 1/\ln t$.Comment: revtex, 4 pages, 3 figures, also available from http://arnold.uchicago.edu/~ebn

Quantum Kinetic Theory III: Quantum kinetic master equation for strongly condensed trapped systems

We extend quantum kinetic theory to deal with a strongly Bose-condensed atomic vapor in a trap. The method assumes that the majority of the vapor is not condensed, and acts as a bath of heat and atoms for the condensate. The condensate is described by the particle number conserving Bogoliubov method developed by one of the authors. We derive equations which describe the fluctuations of particle number and phase, and the growth of the Bose-Einstein condensate. The equilibrium state of the condensate is a mixture of states with different numbers of particles and quasiparticles. It is not a quantum superposition of states with different numbers of particles---nevertheless, the stationary state exhibits the property of off-diagonal long range order, to the extent that this concept makes sense in a tightly trapped condensate.Comment: 3 figures submitted to Physical Review

Emerging immunotherapies for metastasis

Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours. We also present a list of challenges in treating metastatic disease with immunotherapy that must be considered in order to move laboratory observations into clinical practice and maximise patient benefit

Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis

Background: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. Methods: We conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966–2014), EMBASE (1947–2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults. Results: Nineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (−5.7 [−9.0, −2.3] mmHg), diastolic blood pressure (−1.7 [−3.4, −0.1] mmHg) and glomerular filtration rate (−3.2 [−5.4, −1.0] mL/min/1.73 m2). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse. Conclusions: Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit

A microscopic 2D lattice model of dimer granular compaction with friction

We study by Monte Carlo simulation the compaction dynamics of hard dimers in 2D under the action of gravity, subjected to vertical and horizontal shaking, considering also the case in which a friction force acts for horizontal displacements of the dimers. These forces are modeled by introducing effective probabilities for all kinds of moves of the particles. We analyze the dynamics for different values of the time $\tau$ during which the shaking is applied to the system and for different intensities of the forces. It turns out that the density evolution in time follows a stretched exponential behavior if $\tau$ is not very large, while a power law tail develops for larger values of $\tau$. Moreover, in the absence of friction, a critical value $\tau^*$ exists which signals the crossover between two different regimes: for $\tau < \tau^*$ the asymptotic density scales with a power law of $\tau$, while for $\tau > \tau^*$ it reaches logarithmically a maximal saturation value. Such behavior smears out when a finite friction force is present. In this situation the dynamics is slower and lower asymptotic densities are attained. In particular, for significant friction forces, the final density decreases linearly with the friction coefficient. We also compare the frictionless single tap dynamics to the sequential tapping dynamics, observing in the latter case an inverse logarithmic behavior of the density evolution, as found in the experiments.Comment: 10 pages, 15 figures, to be published in Phys. Rev.

Urinary active transforming growth factor ß in feline chronic kidney disease

The cytokine transforming growth factor beta 1 (TGF-β1) has been widely implicated in the development and progression of renal fibrosis in chronic kidney disease (CKD) in humans and in experimental models. The aims of this study were to assess the association between urinary active TGF-β1 and (a) development of CKD in a cross-sectional study, (b) deterioration of renal function over 1 year in a longitudinal study, and (c) renal histopathological parameters in cats. A human active TGF-β1 ELISA was validated for use in feline urine. Cross-sectional analysis revealed no significant difference in urinary active TGF-β1:creatinine ratio (aTGF-β1:UCr) between groups with differing renal function. Longitudinally, non-azotaemic cats that developed CKD demonstrated a significant (P = 0.028) increase in aTGF-β1:UCr approximately 6 months before the development of azotaemia, which remained elevated (P = 0.046) at diagnosis (approximately 12 months prior, 8.4 pg/mg; approximately 6 months prior, 22.2 pg/mg; at CKD diagnosis, 24.6 pg/mg). In the histopathology study, aTGF-β1:UCr was significantly higher in cats with moderate (P = 0.02) and diffuse (P = 0.005) renal fibrosis than in cats without fibrosis. Cats with moderate renal inflammation had significantly higher urinary active aTGF-β1 concentrations than cats with mild (P = 0.035) or no inflammatory change (P = 0.004). The parameter aTGF-β1:UCr was independently associated with Log urine protein:creatinine ratio in a multivariable analysis of clinicopathological parameters and interstitial fibrosis score in a multivariable analysis of histopathological features. These results suggest that urinary aTGF-β1 reflects the severity of renal pathology. Increases in urinary aTGF-β1 followed longitudinally in individual cats may indicate the development of CKD

Phenomenological glass model for vibratory granular compaction

A model for weakly excited granular media is derived by combining the free volume argument of Nowak et al. [Phys. Rev. E 57, 1971 (1998)] and the phenomenological model for supercooled liquids of Adam and Gibbs [J. Chem. Phys. 43, 139 (1965)]. This is made possible by relating the granular excitation parameter \Gamma, defined as the peak acceleration of the driving pulse scaled by gravity, to a temperature-like parameter \eta(\Gamma). The resulting master equation is formally identical to that of Bouchaud's trap model for glasses [J. Phys. I 2, 1705 (1992)]. Analytic and simulation results are shown to compare favourably with a range of known experimental behaviour. This includes the logarithmic densification and power spectrum of fluctuations under constant \eta, the annealing curve when \eta is varied cyclically in time, and memory effects observed for a discontinuous shift in \eta. Finally, we discuss the physical interpretation of the model parameters and suggest further experiments for this class of systems.Comment: 2 references added; some figure labels tweaked. To appear in PR

Compaction of Rods: Relaxation and Ordering in Vibrated, Anisotropic Granular Material

We report on experiments to measure the temporal and spatial evolution of packing arrangements of anisotropic, cylindrical granular material, using high-resolution capacitive monitoring. In these experiments, the particle configurations start from an initially disordered, low-packing-fraction state and under vertical vibrations evolve to a dense, highly ordered, nematic state in which the long particle axes align with the vertical tube walls. We find that the orientational ordering process is reflected in a characteristic, steep rise in the local packing fraction. At any given height inside the packing, the ordering is initiated at the container walls and proceeds inward. We explore the evolution of the local as well as the height-averaged packing fraction as a function of vibration parameters and compare our results to relaxation experiments conducted on spherically shaped granular materials.Comment: 9 pages incl. 7 figure

Mechanisms for slow strengthening in granular materials

Several mechanisms cause a granular material to strengthen over time at low applied stress. The strength is determined from the maximum frictional force F_max experienced by a shearing plate in contact with wet or dry granular material after the layer has been at rest for a waiting time \tau. The layer strength increases roughly logarithmically with \tau -only- if a shear stress is applied during the waiting time. The mechanisms of strengthening are investigated by sensitive displacement measurements and by imaging of particle motion in the shear zone. Granular matter can strengthen due to a slow shift in the particle arrangement under shear stress. Humidity also leads to strengthening, but is found not to be its sole cause. In addition to these time dependent effects, the static friction coefficient can also be increased by compaction of the granular material under some circumstances, and by cycling of the applied shear stress.Comment: 21 pages, 11 figures, submitted to Phys. Rev.