Fabric anisotropy & DEM informed two-surface hyperplasticity : constitutive formulation, asymptotic states & experimental validation.

In geotechnical analysis continuum idealisations of the bulk material still provide the most appropriate approach for engineers designing large-scale structures. In this area, the most successful framework for describing the behaviour of soils is Critical State (CS) soil mechanics. However, the findings from discrete element method (DEM) analysis, such as the uniqueness of the CS, can provide invaluable information in the development such models. This paper details the key concepts behind a two-surface hyperplasticity model (?) whose development was informed by recent DEM findings on the uniqueness of the CS. Asymptotic states of the model will be confirmed and the DEM-continuum-experimental loop will be closed through comparison of the developed model with experimental data on coarse-grained particulate media. This will demonstrate, that providing the previous stress history is accounted for, the proposed model is suitable for a variety of particulate media

Simple Model of the Transduction of Cell-Penetrating Peptides

Cell-penetrating peptides (CPPs) such as HIV's trans-activating transcriptional activator (TAT) and polyarginine rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction. They may be medically useful when fused to well-chosen chains of fewer than about 35 amino acids. I offer a simple model of transduction in which phosphatidylserines and CPPs effectively form two plates of a capacitor with a voltage sufficient to cause the formation of transient pores (electroporation). The model is consistent with experimental data on the transduction of oligoarginine into mouse C2-C12 myoblasts and makes three testable predictions.Comment: Seven pages. For a more complete version including the effects of counterions, see arXiv:0810.2358v3 [q-bio.BM

Diagnosis / Intervention criteria in damaged slabs by severe corrosion of prestressed joists

This research defines diagnosis criteria in R/C one-way slabs with severe corrosion at the lower prestressed reinforcement of the joists and proposes specific actuation criteria and constructive recommendations to increase the safety. The corrosion of this reinforcement is the most common damage in building structures, and the use of aluminous cement in the precast joists can aggravate the corrosion. The usual cases of entire residential buildings with different degrees of damage and with a few or all joists affected in a slab have been simulated. ACI-318 is used as an acceptance criterion for existing structures in the simulations, and a ratio between the ultimate load and the service load is defined as valuation coefficient. By this way, the residual safety for a damaged structure is known. Results are in accordance with the extensive experience in real intervention cases, which often still have high safety reserves.Vercher Sanchis, JM.; Gil Benso, E.; Mas Tomas, MDLA.; Lerma Elvira, C. (2013). Diagnosis / Intervention criteria in damaged slabs by severe corrosion of prestressed joists. Journal of Performance of Constructed Facilities. (04014040). doi:10.1061/(ASCE)CF.1943-5509.0000515S0401404

Model comparisons for estimating carbon emissions from North American wildland fire

Research activities focused on estimating the direct emissions of carbon from wildland fires across North America are reviewed as part of the North American Carbon Program disturbance synthesis. A comparison of methods to estimate the loss of carbon from the terrestrial biosphere to the atmosphere from wildland fires is presented. Published studies on emissions from recent and historic time periods and five specific cases are summarized, and new emissions estimates are made using contemporary methods for a set of specific fire events. Results from as many as six terrestrial models are compared. We find that methods generally produce similar results within each case, but estimates vary based on site location, vegetation (fuel) type, and fire weather. Area normalized emissions range from 0.23 kg C m−2 for shrubland sites in southern California/NW Mexico to as high as 6.0 kg C m−2 in northern conifer forests. Total emissions range from 0.23 to 1.6 Tg C for a set of 2003 fires in chaparral-dominated landscapes of California to 3.9 to 6.2 Tg C in the dense conifer forests of western Oregon. While the results from models do not always agree, variations can be attributed to differences in model assumptions and methods, including the treatment of canopy consumption and methods to account for changes in fuel moisture, one of the main drivers of variability in fire emissions. From our review and synthesis, we identify key uncertainties and areas of improvement for understanding the magnitude and spatial-temporal patterns of pyrogenic carbon emissions across North America

Renal tubular HIF-2α expression requires VHL inactivation and causes fibrosis and cysts.

The Hypoxia-inducible transcription Factor (HIF) represents an important adaptive mechanism under hypoxia, whereas sustained activation may also have deleterious effects. HIF activity is determined by the oxygen regulated α-subunits HIF-1α or HIF-2α. Both are regulated by oxygen dependent degradation, which is controlled by the tumor suppressor "von Hippel-Lindau" (VHL), the gatekeeper of renal tubular growth control. HIF appears to play a particular role for the kidney, where renal EPO production, organ preservation from ischemia-reperfusion injury and renal tumorigenesis are prominent examples. Whereas HIF-1α is inducible in physiological renal mouse, rat and human tubular epithelia, HIF-2α is never detected in these cells, in any species. In contrast, distinct early lesions of biallelic VHL inactivation in kidneys of the hereditary VHL syndrome show strong HIF-2α expression. Furthermore, knockout of VHL in the mouse tubular apparatus enables HIF-2α expression. Continuous transgenic expression of HIF-2α by the Ksp-Cadherin promotor leads to renal fibrosis and insufficiency, next to multiple renal cysts. In conclusion, VHL appears to specifically repress HIF-2α in renal epithelia. Unphysiological expression of HIF-2α in tubular epithelia has deleterious effects. Our data are compatible with dedifferentiation of renal epithelial cells by sustained HIF-2α expression. However, HIF-2α overexpression alone is insufficient to induce tumors. Thus, our data bear implications for renal tumorigenesis, epithelial differentiation and renal repair mechanisms

Potent and selective chemical probe of hypoxic signaling downstream of HIF-α hydroxylation via VHL inhibition

Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling