Settling of cohesive sediment: particle-resolved simulations

We develop a physical and computational model for performing fully coupled, particle-resolved Direct Numerical Simulations of cohesive sediment, based on the Immersed Boundary Method. The model distributes the cohesive forces over a thin shell surrounding each particle, thereby allowing for the spatial and temporal resolution of the cohesive forces during particle-particle interactions. The influence of the cohesive forces is captured by a single dimensionless parameter in the form of a cohesion number, which represents the ratio of cohesive and gravitational forces acting on a particle. We test and validate the cohesive force model for binary particle interactions in the Drafting-Kissing-Tumbling (DKT) configuration. The DKT simulations demonstrate that cohesive particle pairs settle in a preferred orientation, with particles of very different sizes preferentially aligning themselves in the vertical direction, so that the smaller particle is drafted in the wake of the larger one. To test this mechanism in a system of higher complexity, we perform large simulations of 1,261 polydisperse settling particles starting from rest. These simulations reproduce several earlier experimental observations by other authors, such as the accelerated settling of sand and silt particles due to particle bonding. The simulations demonstrate that cohesive forces accelerate the overall settling process primarily because smaller grains attach to larger ones and settle in their wakes. For the present cohesion number values, we observe that settling can be accelerated by up to 29%. We propose physically based parametrization of classical hindered settling functions proposed by earlier authors, in order to account for cohesive forces. An investigation of the energy budget shows that the work of the collision forces can substantially modify the relevant energy conversion processes.Comment: 39 page

Obesity-related perivascular adipose tissue damage is reversed by sustained weight loss in the rat

Objective – Perivascular adipose tissue (PVAT) exerts an anticontractile effect in response to various vasoconstrictor agonists and this is lost in obesity. A recent study reported that bariatric surgery reverses the damaging effects of obesity on PVAT function. However, PVAT function has not been characterised following weight loss induced by caloric restriction, which is often the first line treatment for obesity. Approach and Results – Contractility studies were performed using wire myography on small mesenteric arteries with and without PVAT from control, diet-induced obese, calorie restricted and sustained weight loss rats. Changes in the PVAT environment were assessed using immunohistochemistry. PVAT from healthy animals elicited an anticontractile effect in response to norepinephrine. This was abolished in diet-induced obesity through a mechanism involving increased local TNFα and reduced nitric oxide bioavailability within PVAT. Sustained weight loss led to improvement in PVAT function associated with restoration of adipocyte size, reduced TNFα and increased nitric oxide synthase function. This was associated with reversal of obesity-induced hypertension and normalisation of plasma adipokine levels, including leptin and insulin. Conclusions – We have shown that diet-induced weight loss reverses obesity-induced PVAT damage through a mechanism involving reduced inflammation and increased nitric oxide synthase activity within PVAT. These data reveal inflammation and nitric oxide synthase, particularly eNOS, as potential targets for the treatment of PVAT dysfunction associated with obesity and the metabolic syndrome

High-Throughput Screening for Human Lysosomal β-N-Acetyl Hexosaminidase Inhibitors Acting as Pharmacological Chaperones

SummaryThe adult forms of Tay-Sachs and Sandhoff diseases result when the activity of β-hexosaminidase A (Hex) falls below ∼10% of normal due to decreased transport of the destabilized mutant enzyme to the lysosome. Carbohydrate-based competitive inhibitors of Hex act as pharmacological chaperones (PC) in patient cells, facilitating exit of the enzyme from the endoplasmic reticulum, thereby increasing the mutant Hex protein and activity levels in the lysosome 3- to 6-fold. To identify drug-like PC candidates, we developed a fluorescence-based real-time enzyme assay and screened the Maybridge library of 50,000 compounds for inhibitors of purified Hex. Three structurally distinct micromolar competitive inhibitors, a bisnaphthalimide, nitro-indan-1-one, and pyrrolo[3,4-d]pyridazin-1-one were identified that specifically increased lysosomal Hex protein and activity levels in patient fibroblasts. These results validate screening for inhibitory compounds as an approach to identifying PCs

Fermi surface nesting in several transition metal dichalcogenides

By means of high-resolution angle resolved photoelectron spectroscopy (ARPES) we have studied the fermiology of 2H transition metal dichalcogenide polytypes TaSe2, NbSe2, and Cu0.2NbS2. The tight-binding model of the electronic structure, extracted from ARPES spectra for all three compounds, was used to calculate the Lindhard function (bare spin susceptibility), which reflects the propensity to charge density wave (CDW) instabilities observed in TaSe2 and NbSe2. We show that though the Fermi surfaces of all three compounds possess an incommensurate nesting vector in the close vicinity of the CDW wave vector, the nesting and ordering wave vectors do not exactly coincide, and there is no direct relationship between the magnitude of the susceptibility at the nesting vector and the CDW transition temperature. The nesting vector persists across the incommensurate CDW transition in TaSe2 as a function of temperature despite the observable variations of the Fermi surface geometry in this temperature range. In Cu0.2NbS2 the nesting vector is present despite different doping level, which lets us expect a possible enhancement of the CDW instability with Cu-intercalation in the CuxNbS2 family of materials.Comment: Accepted to New J. Phy

EXOGEN ultrasound bone healing system for long bone fractures with non-union or delayed healing: a NICE medical technology guidance

Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.A routine part of the process for developing National Institute for Health and Care Excellence (NICE) medical technologies guidance is a submission of clinical and economic evidence by the technology manufacturer. The Birmingham and Brunel Consortium External Assessment Centre (EAC; a consortium of the University of Birmingham and Brunel University) independently appraised the submission on the EXOGEN bone healing system for long bone fractures with non-union or delayed healing. This article is an overview of the original evidence submitted, the EAC’s findings, and the final NICE guidance issued.The Birmingham and Brunel Consortium is funded by NICE to act as an External Assessment Centre for the Medical Technologies Evaluation Programme

Recovering the second moment of the strain distribution from neutron Bragg edge data

Point by point strain scanning is often used to map the residual stress (strain) in engineering materials and components. However, the gauge volume and hence spatial resolution is limited by the beam defining apertures and can be anisotropic for very low and high diffraction (scattering) angles. Alternatively, wavelength resolved neutron transmission imaging has a potential to retrieve information tomographically about residual strain induced within materials through measurement in transmission of Bragg edges - crystallographic fingerprints whose locations and shapes depend on microstructure and strain distribution. In such a case the spatial resolution is determined by the geometrical blurring of the measurement setup and the detector point spread function. Mathematically, reconstruction of strain tensor field is described by the longitudinal ray transform; this transform has a non-trivial null-space, making direct inversion impossible. A combination of the longitudinal ray transform with physical constraints was used to reconstruct strain tensor fields in convex objects. To relax physical constraints and generalise reconstruction, a recently introduced concept of histogram tomography can be employed. Histogram tomography relies on our ability to resolve the distribution of strain in the beam direction, as we discuss in the paper. More specifically, Bragg edge strain tomography requires extraction of the second moment (variance about zero) of the strain distribution which has not yet been demonstrated in practice. In this paper we verify experimentally that the second moment can be reliably measured for a previously well characterised aluminium ring and plug sample. We compare experimental measurements against numerical calculation and further support our conclusions by rigorous uncertainty quantification of the estimated mean and variance of the strain distribution

OGA Inhibition By GlcNAc-Selenazoline

The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes. (C) 2010 Elsevier Ltd. All rights reserved

Clinical characteristics and prognosis of cardiac amyloidosis defined by mass spectrometry-based proteomics in an Australian cohort.

Cardiac amyloidosis has a very poor prognosis, but it is the nature of the involved precursor protein that ultimately dictates treatment and survival. We report the clinical characteristics and survival of 47 cardiac amyloid patients across 2 Australian centres including 39 patients evaluated for definitive amyloid subtype utilising laser microdissection and tandem mass spectrometry (LMD-MS). A quarter of patients (n=12) were classified as wild type transthyretin amyloidosis (ATTRwt), 33 patients as light or heavy chain amyloidosis (AL or AH), and 2 as hereditary mutant transthyretin amyloidosis (ATTRv). Greater left ventricular hypertrophy (IV septum 22 vs. 15 mm, p=0.005) and history of cardiac arrhythmia (75% vs. 31%, p=0.016) were significantly associated with ATTRwt patients compared with AL/AH patients. AL patients demonstrated significantly shorter median survival compared to ATTRwt patients (3.5 vs. 37 months, (P=0.007)). New York heart association (NYHA) class III-IV symptoms or plasma cells ≥ 10% at diagnosis, were the only independent predictors of worse survival in AL patients on multivariate analysis. In the era of novel therapies for both AL amyloid and ATTR, identification of the correct amyloid subtype is essential in making therapeutic decisions and providing accurate prognostic information to patients. This article is protected by copyright. All rights reserved

Doping the holographic Mott insulator

Mott insulators form because of strong electron repulsions, being at the heart of strongly correlated electron physics. Conventionally these are understood as classical "traffic jams" of electrons described by a short-ranged entangled product ground state. Exploiting the holographic duality, which maps the physics of densely entangled matter onto gravitational black hole physics, we show how Mott-insulators can be constructed departing from entangled non-Fermi liquid metallic states, such as the strange metals found in cuprate superconductors. These "entangled Mott insulators" have traits in common with the "classical" Mott insulators, such as the formation of Mott gap in the optical conductivity, super-exchange-like interactions, and form "stripes" when doped. They also exhibit new properties: the ordering wave vectors are detached from the number of electrons in the unit cell, and the DC resistivity diverges algebraically instead of exponentially as function of temperature. These results may shed light on the mysterious ordering phenomena observed in underdoped cuprates.Comment: 27 pages, 9 figures. Accepted in Nature Physic