218 research outputs found
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 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 ∗ = 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
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
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.
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
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
Long-term (> 10 years) clinical outcomes of instrumented posterolateral fusion for spondylolisthesis
PURPOSE: Despite the rapid increase in instrumented spinal fusions for a variety of indications, most studies focus on short-term fusion rates. Long-term clinical outcomes are still scarce and inconclusive. This study investigated clinical outcomes > 10 years after single-level instrumented posterolateral spinal fusion for lumbar degenerative or isthmic spondylolisthesis with neurological symptoms. METHODS: Cross-sectional long-term follow-up among the Dutch participants of an international multicenter randomized controlled trial comparing osteogenic protein-1 with autograft. Clinical outcomes were assessed using the Oswestry Disability Index (ODI), EQ-5D-3L and visual analogue scale (VAS) for leg and back pain, as well as questions on satisfaction with treatment and additional surgery. RESULTS: The follow-up rate was 73% (41 patients). At mean 11.8 (range 10.1-13.7) years after surgery, a non-significant deterioration of clinical outcomes compared to 1-year follow-up was observed. The mean ODI was 20 ± 19, mean EQ-5D-3L index score 0.784 ± 0.251 and mean VAS for leg and back pain, respectively, 34 ± 33 and 31 ± 28. Multiple regression showed that diagnosis (degenerative vs. isthmic spondylolisthesis), graft type (OP-1 vs. autograft) and 1-year fusion status (fusion vs. no fusion) were not predictive for the ODI at long-term follow-up (p = 0.389). Satisfaction with treatment was excellent and over 70% of the patients reported lasting improvement in back and/or leg pain. No revision surgeries for non-union were reported. CONCLUSION: This study showed favourable clinical outcomes > 10 years after instrumented posterolateral spinal fusion and supports spondylolisthesis with neurological symptoms as indication for fusion surgery
Trained innate immunity modulates osteoblast and osteoclast differentiation
Macrophages are key regulators in bone repair and regeneration. Recent studies have shown that long-term epigenetic changes and metabolic shifts occur during specific immune training of macrophages that affect their functional state, resulting in heightened (trained) or reduced (tolerant) responses upon exposure to a second stimulus. This is known as innate immune memory. Here, we study the impact of macrophages’ memory trait on osteoblast differentiation of human mesenchymal stromal cells (hMSCs) and osteoclast differentiation. An in vitro trained immunity protocol of monocyte-derived macrophages was employed using inactivated Candida albicans and Bacillus Calmette–Guérin (BCG) to induce a ‘trained’ state and Pam3CSK4 (PAM) and Lipopolysaccharides (LPS) to induce a ‘tolerance’ state. Macrophages were subsequently cocultured with hMSCs undergoing osteogenic differentiation during either resting (unstimulated) or inflammatory conditions (restimulated with LPS). Alkaline phosphatase activity, mineralization, and cytokine levels (TNF, IL-6, oncostatin M and SDF-1α) were measured. In addition, macrophages underwent osteoclast differentiation. Our findings show that trained and tolerized macrophages induced opposing results. Under resting conditions, BCG-trained macrophages enhanced ALP levels (threefold), while under inflammatory conditions this was found in the LPS-tolerized macrophages (fourfold). Coculture of hMSCs with trained macrophages showed mineralization while tolerized macrophages inhibited the process under both resting and inflammatory conditions. While osteoclast differentiation was not affected in trained-macrophages, this ability was significantly loss in tolerized ones. This study further confirms the intricate cross talk between immune cells and bone cells, highlighting the need to consider this interaction in the development of personalized approaches for bone regenerative medicine. Graphical Abstract: (Figure presented.)
Genes for hereditary sensory and autonomic neuropathies: a genotype–phenotype correlation
Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant (SPTLC1 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP). We performed a systematic mutation screening of the coding sequences of six of these genes on a cohort of 100 familial and isolated patients diagnosed with HSAN. In addition, we screened the functional candidate gene NGFR (p75/NTR) encoding the nerve growth factor receptor. We identified disease-causing mutations in SPTLC1, RAB7, WNK1/HSN2 and NTRK1 in 19 patients, of which three mutations have not previously been reported. The phenotypes associated with mutations in NTRK1 and WNK1/HSN2 typically consisted of congenital insensitivity to pain and anhidrosis, and early-onset ulcero-mutilating sensory neuropathy, respectively. RAB7 mutations were only found in patients with a Charcot-Marie-Tooth type 2B (CMT2B) phenotype, an axonal sensory-motor neuropathy with pronounced ulcero-mutilations. In SPTLC1, we detected a novel mutation (S331F) corresponding to a previously unknown severe and early-onset HSAN phenotype. No mutations were found in NGFB, CCT5 and NGFR. Overall disease-associated mutations were found in 19% of the studied patient group, suggesting that additional genes are associated with HSAN. Our genotype–phenotype correlation study broadens the spectrum of HSAN and provides additional insights for molecular and clinical diagnosis
Microenvironment involved in FPR1 expression by human glioblastomas
Formyl peptide receptor 1 (FPR1) activity in U87 glioblastoma (GBM) cells contributes to tumor cell motility. The present study aimed to evaluate the FPR1 expression in human GBM, the possibility to elicit agonist induced FPR1 activation of GBM cells and inhibit this activation with chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Immunohistochemistry was used to assess FPR1 expression in GBM patient samples, which was present in all 178 samples. Also FPR1 mRNA levels measured with quantitative PCR, could be detected in all 25 GBM patient samples tested. Activation of FPR1 in U87 cells, as measured by human mitochondrial-derived agonists, increased calcium mobilization, AKT and ERK1/2 phosphorylation, and ligand-induced migration. Inhibition of all responses could be achieved with CHIPS. Eight early passage human Groningen Glioma (GG) cell lines, isolated from primary GBM tissue were screened for the presence of FPR1. FPR1 mRNA and protein expression as well as receptor activation could not be detected in any of these early passage GG cell lines. However FPR1 was present in ex vivo tumors formed by the same GG cell lines after being implanted in mouse brains. FPR1 is highly expressed in human GBM specimens, it can be activated by human mitochondrial-derived agonists in U87 and inhibited with CHIPS. FPR1 cannot be detected in early passage GG cell lines in vitro, however when engrafted in the mouse brain these cells show FPR1 expression. These results suggest a role of the brain microenvironment in FPR1 expression in GBM.</p
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