On the elastic moduli of three-dimensional assemblies of spheres: characterization and modeling of fluctuations in the particle displacement and rotation

The elastic moduli of four numerical random isotropic packings of Hertzian spheres are studied. The four samples are assembled with different preparation procedures, two of which aim to reproduce experimental compaction by vibration and lubrication. The mechanical properties of the samples are found to change with the preparation history, and to depend much more on coordination number than on density. Secondly, the fluctuations in the particle displacements from the average strain are analysed, and the way they affect the macroscopic behavior analyzed. It is found that only the average over equally oriented contacts of the relative displacement these fluctuations induce is relevant at the macroscopic scale. This average depends on coordination number, average geometry of the contact network and average contact stiffness. As far as the separate contributions from particle displacements and rotations are concerned, the former is found to counteract the average strain along the contact normal, while the latter do in the tangential plane. Conversely, the tangential components of the center displacements mainly arise to enforce local equilibrium, and have a small, and generally stiffening effect at the macro-scale. Finally, the fluctuations and the shear modulus that result from two approaches available in the literature are estimated numerically. These approaches are both based on the equilibrium of a small-sized representative assembly. The improvement of these estimate with respect to the average strain assumption indicates that the fluctuations relevant to the macroscopic behavior occur with short correlation length.Comment: Submitted to IJS

Frictionless bead packs have macroscopic friction, but no dilatancy

The statement of the title is shown by numerical simulation of homogeneously sheared packings of frictionless, nearly rigid beads in the quasistatic limit. Results coincide for steady flows at constant shear rate γ in the limit of small γ and static approaches, in which packings are equilibrated under growing deviator stresses. The internal friction angle ϕ, equal to 5.76 $\pm$ 0.22 degrees in simple shear, is independent on the average pressure P in the rigid limit. It is shown to stem from the ability of stable frictionless contact networks to form stress-induced anisotropic fabrics. No enduring strain localization is observed. Dissipation at the macroscopic level results from repeated network rearrangements, like the effective friction of a frictionless slider on a bumpy surface. Solid fraction Φ remains equal to the random close packing value ≃ 0.64 in slowly or statically sheared systems. Fluctuations of stresses and volume are observed to regress in the large system limit, and we conclude that the same friction law for simple shear applies in the large psystem limit if normal stress or density is externally controlled. Defining the inertia number as I = γ m/(aP), with m the grain mass and a its diameter, both internal friction coefficient $\mu$∗ = tan ϕ and volume 1/Φ increase as powers of I in the quasistatic limit of vanishing I, in which all mechanical properties are determined by contact network geometry. The microstructure of the sheared material is characterized with a suitable parametrization of the fabric tensor and measurements of connectivity and coordination numbers associated with contacts and near neighbors.Comment: 19 pages. Additional technical details may be found in v

A unique small cell lung carcinoma disease progression model shows progressive accumulation of cancer stem cell properties and CD44 as a potential diagnostic marker

OBJECTIVES: Cancer stem cells (CSCs) have been implicated in disease progression of aggressive cancers including small cell lung carcinoma (SCLC). Here, we have examined the possible contribution of CSCs to SCLC progression and aggressiveness. MATERIALS AND METHODS: GLC-14, GLC-16 and GLC-19 SCLC cell lines derived from one patient, representing increasing progressive stages of disease were used. CSC marker expressions was determined by RT-qPCR and western blotting analyses, and heterogeneity was studied by CSC marker expression by immunofluorescence microscopy and flow cytometry. Colony formation assays were used to assess stem cell properties and therapy sensitivity. RESULTS: Increasing expression of stem cell markers MYC, SOX2 and particularly CD44 were found in association with advancing disease. Single and overlapping expression of these markers indicated the presence of different CSC populations. The accumulation of more homogeneous double- and triple-positive CSC populations evolved with disease progression. Functional characterization of CSC properties affirmed higher proficiency of colony forming ability and increased resistance to γ-irradiation in GLC-16 and GLC-19 compared to GLC-14. GLC-19 colony formation was significantly inhibited by a human anti-CD44 antibody. CONCLUSION: The progressive increase of MYC, SOX2 and particularly CD44 expression that was accompanied with enhanced colony forming capacity and resistance in the in vitro GLC disease progression model, supports the potential clinical relevance of CSC populations in malignancy and disease relapse of SCLC

Memory of the Unjamming Transition during Cyclic Tiltings of a Granular Pile

Discrete numerical simulations are performed to study the evolution of the micro-structure and the response of a granular packing during successive loading-unloading cycles, consisting of quasi-static rotations in the gravity field between opposite inclination angles. We show that internal variables, e.g., stress and fabric of the pile, exhibit hysteresis during these cycles due to the exploration of different metastable configurations. Interestingly, the hysteretic behaviour of the pile strongly depends on the maximal inclination of the cycles, giving evidence of the irreversible modifications of the pile state occurring close to the unjamming transition. More specifically, we show that for cycles with maximal inclination larger than the repose angle, the weak contact network carries the memory of the unjamming transition. These results demonstrate the relevance of a two-phases description -strong and weak contact networks- for a granular system, as soon as it has approached the unjamming transition.Comment: 13 pages, 15 figures, soumis \`{a} Phys. Rev.

Solid behavior of anisotropic rigid frictionless bead assemblies

We investigate the structure and mechanical behavior of assemblies of frictionless, nearly rigid equal-sized beads, in the quasistatic limit, by numerical simulation. Three different loading paths are explored: triaxial compression, triaxial extension and simple shear. Generalizing recent results [1], we show that the material, despite rather strong finite sample size effects, is able to sustain a finite deviator stress in the macroscopic limit, along all three paths, without dilatancy. The shape of the yield surface is adequately described by a Lade-Duncan (rather than Mohr-Coulomb) criterion. While scalar state variables keep the same values as in isotropic systems, fabric and force anisotropies are each characterized by one parameter and are in one-to-one correspondence with principal stress ratio along all three loading paths.The anisotropy of the pair correlation function extends to a distance between bead surfaces on the order of 10% of the diameter. The tensor of elastic moduli is shown to possess a nearly singular, uniaxial structure related to stress anisotropy. Possible stress-strain relations in monotonic loading paths are also discussed

Force transmission in a packing of pentagonal particles

We perform a detailed analysis of the contact force network in a dense confined packing of pentagonal particles simulated by means of the contact dynamics method. The effect of particle shape is evidenced by comparing the data from pentagon packing and from a packing with identical characteristics except for the circular shape of the particles. A counterintuitive finding of this work is that, under steady shearing, the pentagon packing develops a lower structural anisotropy than the disk packing. We show that this weakness is compensated by a higher force anisotropy, leading to enhanced shear strength of the pentagon packing. We revisit "strong" and "weak" force networks in the pentagon packing, but our simulation data provide also evidence for a large class of "very weak" forces carried mainly by vertex-to-edge contacts. The strong force chains are mostly composed of edge-to-edge contacts with a marked zig-zag aspect and a decreasing exponential probability distribution as in a disk packing

Rheophysics of dense granular materials : Discrete simulation of plane shear flows

We study the steady plane shear flow of a dense assembly of frictional, inelastic disks using discrete simulation and prescribing the pressure and the shear rate. We show that, in the limit of rigid grains, the shear state is determined by a single dimensionless number, called inertial number I, which describes the ratio of inertial to pressure forces. Small values of I correspond to the quasi-static regime of soil mechanics, while large values of I correspond to the collisional regime of the kinetic theory. Those shear states are homogeneous, and become intermittent in the quasi-static regime. When I increases in the intermediate regime, we measure an approximately linear decrease of the solid fraction from the maximum packing value, and an approximately linear increase of the effective friction coefficient from the static internal friction value. From those dilatancy and friction laws, we deduce the constitutive law for dense granular flows, with a plastic Coulomb term and a viscous Bagnold term. We also show that the relative velocity fluctuations follow a scaling law as a function of I. The mechanical characteristics of the grains (restitution, friction and elasticity) have a very small influence in this intermediate regime. Then, we explain how the friction law is related to the angular distribution of contact forces, and why the local frictional forces have a small contribution to the macroscopic friction. At the end, as an example of heterogeneous stress distribution, we describe the shear localization when gravity is added.Comment: 24 pages, 19 figure

The Summer School Oncology Groningen:Improving a Successful International Course by Refining the Old, Maintaining What's Good

For more than two decades, the International Summer School Oncology for Medical Students (ISOMS) has organized a biennial 2-week international summer school program in Groningen, the Netherlands. The summer school aims to increase knowledge about general cancer care, reduce fear of talking to cancer patients, and expose students to cancer-related problems. After 22 years, there was a need to improve the summer school format, the application procedure, and the intensity of the course. Here, we describe and evaluate these and additional changes that were made to the program. Several changes were made to the summer school format. The course was shortened from 10 days to a more intensive 7 days. The scientific program was integrated with the clinical program and students were taught scientific writing and presentation skills. The application process involved a personal video pitch. Importantly, the new summer school format was organized by a committee in which medical students had the lead. To evaluate the changes to the summer school, we conducted knowledge tests and regularly obtained feedback. There was a high overall student satisfaction, with a median score of a 9 out of 10. Students appreciated the interactive sessions and practicals and the scientific program, and were satisfied with the course level. All students had improved test scores. Improvement points highlighted the need for a less packed schedule and more lectures on basic oncology principles, or were related to specific lectures. The student-led innovation and adaptation of the ISOMS has been successful

Comparison of Outcomes Following Thrombolytic Therapy Among Patients With Prior Stroke and Diabetes in the Virtual International Stroke Trials Archive (VISTA)

OBJECTIVE - The use of alteplase in patients who have had a prior stroke and concomitant diabetes is not approved in Europe To examine the influence of diabetes and prior stroke on outcomes we compared data on thrombolysed patients with nonthrombolysed comparators RESEARCH DESIGN AND METHODS - We selected patients with ischemic stroke on whom we had data on age pretreatment baseline National Institutes of Health Stroke Scale (b-NIHSS) and 90-day outcome measures (functional modified Rankin score [mRS]) and neurological measures [NIHSS]) in the Virtual International Stroke Trials Archive We compared outcomes between thrombolysed patients and nonthrombolysed comparators in those with and without diabetes those who have had a prior stroke or both and report findings using the Cochran Mantel-Haenszel (CMH) test and proportional odds logistic regression analyses We report an age adjusted and b NIHSS adjusted CMH P value and odds ratio (OR) RESULTS - Rankin data were available for 5 817 patients 1 585 thrombolysed patients and 4 232 nonthrombolysed comparators A total 1 334 (24 1%) patients had diabetes 1 898 (33 7%) patients have had a prior stroke and 491 (8%) patients had both Diabetes and non-diabetes had equal b-NIHSS (median 13 P = 0 3) but patients who have had a prior stroke had higher b-NIHSS than patients who have not had a prior stroke (median 13 vs 12 P < 0 0001) Functional outcomes were better for thrombolysed patients versus nonthrombolysed comparators among both nondiabetic (P < 0 0001 OR 1 4 vertical bar 95% CI 1 3-1 6]) and diabetic (P = 0 1 1 3 [1 05-1 6 ]) subjects Similarly outcomes were better for thrombolysed patients versus nonthrombolysed comparators among who have not had a prior stroke (P < 0 0001 1 4 [1 2-1 6]) and those who have (P = 002 1 3 [1 04-1 6]) There was no interaction of diabetes and prior stroke with treatment (P = 0 8) Neurological outcomes were consistent with the mRS CONCLUSIONS - Outcomes from thrombolysis are better among patients with diabetes and/or those who have had a prior stroke than in control subjects Withholding thrombolytic treatment from otherwise eligible patients may not be justifie