Surface flow profiles for dry and wet granular materials by Particle Tracking Velocimetry; the effect of wall roughness

Two-dimensional Particle Tracking Velocimetry (PTV) is a promising technique to study the behaviour of granular flows. The aim is to experimentally determine the free surface width and position of the shear band from the velocity profile to validate simulations in a split-bottom shear cell geometry. The position and velocities of scattered tracer particles are tracked as they move with the bulk flow by analyzing images. We then use a new technique to extract the continuum velocity field, applying coarse-graining with the postprocessing toolbox MercuryCG on the discrete experimental PTV data. For intermediate filling heights, the dependence of the shear (or angular) velocity on the radial coordinate at the free surface is well fitted by an error function. From the error function, we get the width and the centre position of the shear band. We investigate the dependence of these shear band properties on filling height and rotation frequencies of the shear cell for dry glass beads for rough and smooth wall surfaces. For rough surfaces, the data agrees with the existing experimental results and theoretical scaling predictions. For smooth surfaces, particle-wall slippage is significant and the data deviates from the predictions. We further study the effect of cohesion on the shear band properties by using small amount of silicon oil and glycerol as interstitial liquids with the glass beads. While silicon oil does not lead to big changes, glycerol changes the shear band properties considerably. The shear band gets wider and is situated further inward with increasing liquid saturation, due to the correspondingly increasing trend of particles to stick together

Bisphosphonate-Associated Osteonecrosis of the Jaw: Are We Dealing with a Localized Non-Traditional Calciphylaxis?

The bisphosphonate (BP) family of drugs has been used as a vital component in cancer therapy and many other diseases. One of the main adverse effects related to (BP) is BP-associated osteonecrosis of the jaw (ONJ). Although this condition was first recognized in 2003, the pathophysiologic mechanism remains undefined. Our hypothesis is that ONJs clinical course and delayed wound healing is in part correlated to a localized non-traditional calciphylaxis. This effect is identified by the evidence of calcium deposition in the connective tissue and around small blood vessels in the soft tissues immediately adjacent to ONJ lesions. This phenomenon helps to fill gaps in the cascade of events which leads to soft tissue ischemia, necrosis, and non-healing ONJ lesions. Our finding adds to the current knowledge of the potential pathophysiologic mechanisms related to ONJ

High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma

BACKGROUND: HMGA2 expression has been shown to be associated with enhanced selective chemosensitivity towards the topoisomerase (topo) II inhibitor, doxorubicin, in cancer cells. Although the roles of signaling cascades and proteins as regulatory factors in development, neoplasia and adaptation to the environment are becoming well established, evidence for the involvement of regulatory small RNA molecules, such as microRNAs (miRNAs) as important regulators of both transcriptional and posttranscriptional gene silencing is presently mounting. RESULTS: Here we report that HMGA2 expression in head and neck squamous cell carcinoma (HNSCC) cells is regulated in part by miRNA-98 (miR-98). Albeit HMGA2 is associated with enhanced selective chemosensitivity towards topoisomerase (topo) II inhibitor, doxorubicin in HNSCC, the expression of HMGA2 is thwarted by hypoxia. This is accompanied by enhanced expression of miRNA-98 and other miRNAs, which predictably target HMGA2. Moreover, we show that transfection of pre-miR-98™ during normoxia diminishes HMGA2 and potentiates resistance to doxorubicin and cisplatin. These findings implicate the role of a miRNA as a key element in modulating tumors in variable microenvironments. CONCLUSION: These studies validate the observation that HMGA2 plays a prominent role in governing genotoxic responses. However, this may only represent cells growing under normal oxygen tensions. The demonstration that miRNA profiles are altered during hypoxia and repress a genotoxic response indicates that changes in microenvironment in eukaryotes mimic those of lower species and plants, where, for example, abiotic stresses regulate the expression of thousands of genes in plants at both transcriptional and posttranscriptional levels through a number of miRNAs and other small regulatory RNAs

Functional detection of MDR1/P170 and MRP/P190-mediated multidrug resistance in tumour cells by flow cytometry.

Multidrug resistance (MDR) in tumour cells is often caused by the overexpression of the plasma membrane drug transporter P-glycoprotein (P-gp) or the recently discovered multidrug resistance-associated protein (MRP). In this study we investigated the specificity and sensitivity of the fluorescent probes rhodamine 123 (R123), daunorubicin (DNR) and calcein acetoxymethyl ester (calcein-AM) in order to detect the function of the drug transporters P-gp and MRP, using flow cytometry. The effects of modulators on the accumulation and retention of these probes were compared in several pairs of sensitive and P-gp- as well as MRP-overexpressing cell lines. R123, in combination with the modulator PSC833, provided the most sensitive test for detecting P-gp-mediated resistance. Moreover, in a 60 min drug accumulation assay R123 can be regarded as a P-gp-specific probe, since R123 is not very efficiently effluxed by MRP. In contrast to R123, a 60 min DNR or calcein-AM accumulation test could be used to detect MRP-mediated resistance. The MRP-specific modulator genistein could be used in combination with DNR, but not with calcein-AM. Vincristine (VCR) can be used to increase the cellular uptake of calcein-AM in MDR cells, but is not specific for MRP. Thus, although the combination of DNR with genistein appeared to be as sensitive as the combination of calcein-AM with VCR, the former may be used to probe specific MRP activity whereas the latter provides a combined (P-gp + MRP) functional MDR parameter. With these functional assays the role and relative importance of P-gp and MRP can be studied in, for example, haematological malignancies