Integrated Systems Pharmacology Analysis of Clinical Drug‐Induced Peripheral Neuropathy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109792/1/psp4201411.pd

Cyclic deformation characteristics of S355 and S690 steels under different loading protocols

Despite of excellent high strength to self-weight ratios of the S690 steels, when compared with the S355 steels, there is a widespread concern regarding the ductility of the S690 steels. It is generally considered that the ductility of the S690 steels is significantly lower than that of the S355 steels – this is the general understandings the authors attempt to investigate. This paper presents an experimental investigation into cyclic deformation characteristics of both S355 and S690 steels through low-cycle high-strain cyclic tests with two different loading protocols. A detailed account of the results of 32 cyclic tests on both the S355 and the S690 funnel-shaped coupons is presented. Effects of four different target strains and two different loading frequencies are also examined in details. For the ranges of loading protocols, strain amplitudes, and frequencies considered, the hysteretic responses of these coupons of the two steels are compared directly in terms of engineering stress–strain curves based on their nominal diameters. Microstructures of the fractured coupons of the two steels are also identified for comparison. Contrary to the general understandings, it is demonstrated that the high strength S690 steels do have a good ductility under both monotonic and cyclic actions. Moreover, depending on specific loading protocols and target strains, the cyclic deformation characteristics of the S690 steels are demonstrated to be superior to those of the S355 steels in terms of the number of cycles completed prior to failure and their corresponding energy dissipation characteristic under various target strains up to ±10.0%. The findings of this experimental investigation highlight the importance of establishing ductility requirements and cyclic deformation characteristics for the high strength S690 steels in accordance with specifically designed cyclic tests rather than relying solely on conventional monotonic tensile tests

Axial and bending behaviour of steel tubes infilled with rubberised concrete

This paper presents an experimental and numerical study into the behaviour of rubberised concrete-filled steel tubes (RuCFST), incorporating concrete with relatively high rubber replacements of up to 60% of mineral aggregates by volume. Axial compression, eccentric compression, and three-point bending tests on circular specimens are carried out and the results are used to validate the nonlinear procedures adopted in continuum finite element (FE) models of RuCFST members. A constitutive material model specific for confined rubberised concrete and associated modelling techniques, developed from existing procedures for concrete-filled steel tubes (CFST), is proposed for RuCFST members. The modelling techniques involve different damage definitions including low strength concrete with high rubber replacements in compression and bending. It is shown that the proposed modelling procedures can predict reliably the structural behaviour of circular RuCFST members under combined axial-bending conditions. The numerical procedures are then employed in undertaking a detailed parametric assessment for RuCFST cross-sections. The results are used to appraise current design procedures and to propose modifications that provide improved capacity predictions for a wide range of properties and loading conditions

Experimental cyclic response of rubberised concrete-filled steel tubes

This paper examines the behaviour of circular steel tubes infilled with concrete incorporating recycled rubber particles. The rubberised concrete-filled steel tubes are tested under lateral cyclic deformations with and without co-existing axial loading. A detailed account of the cyclic tests on twelve specimens is provided together with complementary material and section tests. The rubber replacement ratio is varied up to a relatively high value of 60%, under axial loads reaching up to 30% of the nominal capacity. Hollow steel members are also tested for comparison purposes. The experimental results are discussed in detail with respect to the member stiffness, capacity, ductility, energy dissipation and failure mechanisms. Although high rubber ratios lead to a considerable loss in concrete strength, the test results show that the corresponding reduction in member capacity is much less significant due to the contribution of the steel tube and the comparatively high confinement effects mobilised within the rubberised concrete. In comparison with the members incorporating normal concrete, the rubberised concrete members are found to exhibit up to about 10% and 17% increase in ductility and energy dissipation, respectively, depending on the rubber content. Analytical treatments are then used to suggest simplified relationships for predicting the stiffness, moment-axial strength interaction, plastic hinge length and local ductility criteria. Overall, the test results demonstrate the favourable inelastic cyclic performance of circular steel tubes infilled with rubberised concrete and provide valuable experimental data. The proposed expressions for key response parameters also offer the basis for developing practical assessment and design methods

Monitoring iron chelation effect in hearts of thalassaemia patients with improved sensitivity using reduced transverse relaxation rate (RR2)

Posters - Myocardial Viability: Human Models: No. 3660Accurate MRI characterization of myocardial iron is needed to improve the diagnosis and management of thalassaemia patients with transfusional iron overload. This study aimed to demonstrate that a new transverse relaxation index, the reduced R2 (RR2) that is estimated from non-monoexponential multi-echo CPMG signal decay and sensitive to ferritin iron, could detect the myocardial iron changes immediately following 1-week iron chelation suspension in thalassaemia patients at 3T.postprin

Relations among neutrino observables in the light of a large theta_13 angle

The recent T2K and MINOS indications for a "large" theta_13 neutrino mixing angle can be accommodated in principle by an infinite number of Yukawa flavour structures in the seesaw model. Without considering any explicit flavour symmetry, there is an instructive exercise one can do: to determine the simplest flavour structures which can account for the data with a minimum number of parameters, simply assuming these parameters to be uncorrelated. This approach points towards a limited number of simple structures which show the minimum complexity a neutrino mass model must generally involve to account for the data. These basic structures essentially lead to only 4 relations between the neutrino observables. We emphasize that 2 of these relations, |sin theta_13|=(tan theta_23/cos delta)*(1-tan theta_12)/(1+tan theta_12) and |sin theta_13| = sin theta_12 R^1/4, with R= Delta m^2_21/Delta m^2_32, have several distinctive properties. First, they hold not only with a minimum number of parameters, but also for complete classes of more general models. Second, any value of theta_13 within the T2K and MINOS ranges can be obtained from these relations by taking into account small perturbations. Third, they turn out to be the pivot relations of models with approximate conservation of lepton number, which allow the seesaw interactions to induce observable flavour violating processes, such as mu -> e gamma and tau -> mu gamma. Finally, in specific cases of this kind, these structures have the rather unique property to allow a full reconstruction of the seesaw Lagrangian from low energy data.Comment: 13 pages, 3 figure

The underpotential deposition that should not be : Cu(1x1) on Au(111)

Peer reviewedPostprin

Fully gapped topological surface states in Bi2_2Se3_3 films induced by a d-wave high-temperature superconductor

Topological insulators are a new class of materials, that exhibit robust gapless surface states protected by time-reversal symmetry. The interplay between such symmetry-protected topological surface states and symmetry-broken states (e.g. superconductivity) provides a platform for exploring novel quantum phenomena and new functionalities, such as 1D chiral or helical gapless Majorana fermions, and Majorana zero modes which may find application in fault-tolerant quantum computation. Inducing superconductivity on topological surface states is a prerequisite for their experimental realization. Here by growing high quality topological insulator Bi$_2$Se$_3$ films on a d-wave superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ using molecular beam epitaxy, we are able to induce high temperature superconductivity on the surface states of Bi$_2$Se$_3$ films with a large pairing gap up to 15 meV. Interestingly, distinct from the d-wave pairing of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$, the proximity-induced gap on the surface states is nearly isotropic and consistent with predominant s-wave pairing as revealed by angle-resolved photoemission spectroscopy. Our work could provide a critical step toward the realization of the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274

When do myopia genes have their effect? Comparison of genetic risks between children and adults

Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged 25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10–25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; β = 0.0016 per risk allele (P = 2 × 10–8) in <10 years, 0.0033 (P = 5 × 10–15) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10–72) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH