Interaction between the Blasius boundary layer and a free surface

We consider the steady supercritical flow of a fluid layer. The layer is bounded above by a free surface and below by a rigid no-slip base. The base is in two parts: the downstream part of the base is stationary, while the upstream part translates in the streamwise direction with a uniform speed; there is an abrupt transition. At high Reynolds number, a boundary layer forms in the fluid above the base downstream of the transition point. The displacement due to this boundary layer creates a perturbation to the outer flow and therefore to the free surface. We show that the Blasius boundary layer solution, which applies in an infinitely deep fluid, also applies at high Froude numbers. The Blasius solution no longer applies for flows that are just supercritical, as the outer flow is strongly affected by the presence of the boundary layer. We outline possible applications of this work to depth-averaged models of gravity currents.JMFT is funded by an EPSRC Studentship (EP/M508007/1) and NMV is a Royal Society Dorothy Hodgkin Research Fellow (DH120121)

The granular Blasius problem

We consider the steady flow of a granular current over a uniformly sloped surface that is smooth upstream (allowing slip for x<0) but rough downstream (imposing a no-slip condition on x>0), with a sharp transition at $x=0$. This problem is similar to the classical Blasius problem, which considers the growth of a boundary layer over a flat plate in a Newtonian fluid that is subject to a similar step change in boundary conditions. Our discrete particle model simulations show that a comparable boundary-layer phenomenon occurs for the granular problem: the effects of basal roughness are initially localised at the base but gradually spread throughout the depth of the current. A rheological model can be used to investigate the changing internal velocity profile. The boundary layer is a region of high shear rate and therefore high inertial number $I$; its dynamics is governed by the asymptotic behaviour of the granular rheology for high values of the inertial number. The \unicode[STIX]{x1D707}(I) rheology (Jop et al., Nature, vol. 441 (7094), 2006, pp. 727–730) asserts that \text{d}\unicode[STIX]{x1D707}/\text{d}I=O(1/I^{2}) as $I\rightarrow \infty$, but current experimental evidence is insufficient to confirm this. We show that this rheology does not admit a self-similar boundary layer, but that there exist generalisations of the \unicode[STIX]{x1D707}(I) rheology, with different dependencies of \unicode[STIX]{x1D707}(I) on $I$, for which such self-similar solutions do exist. These solutions show good quantitative agreement with the results of our discrete particle model simulations.J.M.F.T. is funded by an EPSRC Studentship (EP/M508007/1) N.M.V. is a Royal Society Dorothy Hodgkin Research Fellow (DH120121)

MiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis

MiR-200 family is an important regulator of epithelial-mesenchymal transition and has been implicated in human carcinogenesis. However, their expression and functions in human cancers remain controversial. In the work presented here, we showed that miR-200 family members were frequently down-regulated in hepatocellular carcinoma (HCC). Although all five members of miR-200 family inhibited ZEB1/2 expression in HCC cell lines, we showed that overexpression only of the miR-200b/200c/429 subfamily, but not the miR-200a/141 subfamily, resulted in impeded HCC cell migration. Further investigations led to the identification of RhoA and ROCK2 as specific down-stream targets of the miR-200b/200c/429 subfamily. We demonstrated that the miR-200b/200c/429 subfamily inhibited HCC cell migration through modulating Rho/ROCK mediated cell cytoskeletal reorganization and cell-substratum adhesion. Re-expression of miR-200b significantly suppressed lung metastasis of HCC cells in an orthotopic liver implantation model in vivo. In conclusion, our findings identified the miR-200b/200c/429 subfamily as metastasis suppressor microRNAs in human HCC and highlighted the functional discrepancy among miR-200 family members.published_or_final_versio

Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome

Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here, we characterize the clinical phenotype of disease caused by variants in CEP78, CEP250, ARSG, and ABHD12. Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease-causing variants in CEP78, CEP250, ARSG, or ABHD12. CEP78-related disease included sensorineural hearing loss (SNHL) in 6/7 patients and demonstrated a broad phenotypic spectrum including: vascular attenuation, pallor of the optic disc, intraretinal pigment, retinal pigment epithelium mottling, areas of mid-peripheral hypo-autofluorescence, outer retinal atrophy, mild pigmentary changes in the macula, foveal hypo-autofluorescence, and granularity of the ellipsoid zone. Nonsense and frameshift variants in CEP250 showed mild retinal disease with progressive, non-congenital SNHL. ARSG variants resulted in a characteristic pericentral pattern of hypo-autofluorescence with one patient reporting non-congenital SNHL. ABHD12-related disease showed rod-cone dystrophy with macular involvement, early and severe decreased best corrected visual acuity, and non-congenital SNHL ranging from unreported to severe. This study serves to expand the clinical phenotypes of atypical USH. Given the variable findings, atypical USH should be considered in patients with peripheral and macular retinal disease even without the typical RP phenotype especially when SNHL is noted. Additionally, genetic screening may be useful in patients who have clinical symptoms and retinal findings even in the absence of known SNHL given the variability of atypical USH

The granular Blasius problem

© 2019 Cambridge University Press. We consider the steady flow of a granular current over a uniformly sloped surface that is smooth upstream (allowing slip for x 0), with a sharp transition at x = 0. This problem is similar to the classical Blasius problem, which considers the growth of a boundary layer over a flat plate in a Newtonian fluid that is subject to a similar step change in boundary conditions. Our discrete particle model simulations show that a comparable boundary-layer phenomenon occurs for the granular problem: The effects of basal roughness are initially localised at the base but gradually spread throughout the depth of the current. A rheological model can be used to investigate the changing internal velocity profile. The boundary layer is a region of high shear rate and therefore high inertial number I; its dynamics is governed by the asymptotic behaviour of the granular rheology for high values of the inertial number. The μ(I) rheology (Jop et al., Nature, vol. 441 (7094), 2006, pp. 727-730) asserts that dμ/dI = O(1=I2) as I → but current experimental evidence is insufficient to confirm this. We show that this rheology does not admit a self-similar boundary layer, but that there exist generalisations of the μ(I) rheology, with different dependencies of μ(I) on I, for which such self-similar solutions do exist. These solutions show good quantitative agreement with the results of our discrete particle model simulations

Proteomics of Macrophage: An Approach to Understand Lipopolysaccharide Challenged Inflammation

Lipopolysaccharide (LPS) has been implicated as one of the major cause of inflammation, sepsis and shock, that are, life-threatening syndromes often occurring in intensive care unit patients. In order to detect diseaserelevant process and biomarkers for alleviating the inflammation or sepsis shock upon bacterial infection, proteome of macrophage cell line RAW 264.7 primed with LPS for 24 hours in vitro was determined using 2DE. Isoelectric focusing was performed on whole cell extracts using 11cm pH 4 –7 IPG strips. Focused proteins were resolved in 12% SDS-polyacrylamide gels and visualized by silver-stain. The proteomes patterns were analyzed by the Melanie III 2D analysis software. Three proteins out of approximately 720 detected were decreased in abundance as a result of the priming with LPS. These proteins were isolated and identified by comparing the masses of their tryptic digested peptides with those of the known proteins, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the SWISSPROT database. The putative identities of these proteins were mitochondrial respiratory chain enzymes, glyceraldehyde-3-phosphate dehydrogenase, putative tumor suppressor molecule, prohibitin, pyrimidine nucleotides synthesis enzymes, and UMP/CMP kinase. Many of these proteins possess important functions in inflammation. This high-resolution 2DE and protein identification technique allows one to rapidly discover new potential candidate proteins which can be used to develop targeted drugs proteins for the prevention and treatment of endotoxemia

Assessing written work by determining competence to achieve the module-specific learning outcomes.

This chapter describes lasers and other sources of coherent light that operate in a wide wavelength range. First, the general principles for the generation of coherent continuous-wave and pulsed radiation are treated including the interaction of radiation with matter, the properties of optical resonators and their modes as well as such processes as Q-switching and mode-locking. The general introduction is followed by sections on numerous types of lasers, the emphasis being on todayʼs most important sources of coherent light, in particular on solid-state lasers and several types of gas lasers. An important part of the chapter is devoted to the generation of coherent radiation by nonlinear processes with optical parametric oscillators, difference- and sum-frequency generation, and high-order harmonics. Radiation in the extended ultraviolet (EUV) and x-ray ranges can be generated by free electron lasers (FEL) and advanced x-ray sources. Ultrahigh light intensities up to 1021 W/cm2 open the door to studies of relativistic laser–matter interaction and laser particle acceleration. The chapter closes with a section on laser stabilization