Error estimation of closed-form solution for annual rate of structural collapse

With the increasing emphasis of performance-based earthquake engineering (PBEE) in the engineering community, several investigations have been presented outlining simplified approaches suitable for performance-based seismic design (PBSD). Central to most of these PBSD approaches is the use of closed-form analytical solutions to the probabilistic integral equations representing the rate of exceedance of key performance measures. Situations where such closed-form solutions are not appropriate primarily relate to the problem of extrapolation outside of the region in which parameters of the closed-form solution are fit. This study presents a critical review of the closed form solution for the annual rate of structural collapse. The closed form solution requires the assumptions of lognormality of the collapse fragility and power model form of the ground motion hazard, of which the latter is more significant regarding the error of the closed-form solution. Via a parametric study, the key variables contributing to the error between the closed-form solution and solution via numerical integration are illustrated. As these key variables can not be easily measured it casts doubt on the use of such closed-form solutions in future PBSD, especially considering the simple and efficient nature of using direct numerical integration to obtain the solution

Frictional Duality Observed during Nanoparticle Sliding

One of the most fundamental questions in tribology concerns the area dependence of friction at the nanoscale. Here, experiments are presented where the frictional resistance of nanoparticles is measured by pushing them with the tip of an atomic force microscope. We find two coexisting frictional states: While some particles show finite friction increasing linearly with the interface areas of up to 310,000nm^2, other particles assume a state of frictionless sliding. The results further suggest a link between the degree of surface contamination and the occurrence of this duality.Comment: revised versio

Pulsed Laser Beam Welding of Pd\u3csub\u3e43\u3c/sub\u3eCu\u3csub\u3e27\u3c/sub\u3eNi\u3csub\u3e10\u3c/sub\u3eP\u3csub\u3e20\u3c/sub\u3e Bulk Metallic Glass

We used pulsed laser beam welding method to join Pd43Cu27Ni10P20 (at.%) bulk metallic glass and characterized the properties of the joint. Fusion zone and heat-affected zone in the weld joint can be maintained completely amorphous as confirmed by X-ray diffraction and differential scanning calorimetry. No visible defects were observed in the weld joint. Nanoindentation and bend tests were carried out to determine the mechanical properties of the weld joint. Fusion zone and heat-affected zone exhibit very similar elastic moduli and hardness when compared to the base material, and the weld joint shows high ductility in bending which is accomplished through the operation of multiple shear bands. Our results reveal that pulsed laser beam welding under appropriate processing parameters provides a practical viable method to join bulk metallic glasses

Recurrence Plot Based Measures of Complexity and its Application to Heart Rate Variability Data

The knowledge of transitions between regular, laminar or chaotic behavior is essential to understand the underlying mechanisms behind complex systems. While several linear approaches are often insufficient to describe such processes, there are several nonlinear methods which however require rather long time observations. To overcome these difficulties, we propose measures of complexity based on vertical structures in recurrence plots and apply them to the logistic map as well as to heart rate variability data. For the logistic map these measures enable us not only to detect transitions between chaotic and periodic states, but also to identify laminar states, i.e. chaos-chaos transitions. The traditional recurrence quantification analysis fails to detect the latter transitions. Applying our new measures to the heart rate variability data, we are able to detect and quantify the laminar phases before a life-threatening cardiac arrhythmia occurs thereby facilitating a prediction of such an event. Our findings could be of importance for the therapy of malignant cardiac arrhythmias

Mechanosensing through talin 1 contributes to tissue mechanical homeostasis.

It is widely believed that tissue mechanical properties, determined mainly by the extracellular matrix (ECM), are actively maintained. However, despite its broad importance to biology and medicine, tissue mechanical homeostasis is poorly understood. To explore this hypothesis, we developed mutations in the mechanosensitive protein talin1 that alter cellular sensing of ECM stiffness. Mutation of a novel mechanosensitive site between talin1 rod domain helix bundles 1 and 2 (R1 and R2) shifted cellular stiffness sensing curves, enabling cells to spread and exert tension on compliant substrates. Opening of the R1-R2 interface promotes binding of the ARP2/3 complex subunit ARPC5L, which mediates the altered stiffness sensing. Ascending aortas from mice bearing these mutations show increased compliance, less fibrillar collagen, and rupture at lower pressure. Together, these results demonstrate that cellular stiffness sensing regulates ECM mechanical properties. These data thus directly support the mechanical homeostasis hypothesis and identify a novel mechanosensitive interaction within talin that contributes to this mechanism

HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Background & aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764). Expression levels of HLA-DP on intestinal epithelial cells (IECs) in individuals with and without UC were quantified. Human intestinal 3-dimensional (3D) organoid cocultures with human NK cells were used to determine functional consequences of interactions between HLA-DP and NKp44.Results: These studies identified HLA-DPA1∗01:03-DPB1∗04:01 (HLA-DP401) as a risk haplotype and HLA-DPA1∗01:03-DPB1∗03:01 (HLA-DP301) as a protective haplotype for UC in European populations. HLA-DP expression was significantly higher on IECs of individuals with UC compared with controls. IECs in human intestinal 3D organoids derived from HLA-DP401pos individuals showed significantly stronger binding of NKp44 compared with HLA-DP301pos IECs. HLA-DP401pos IECs in organoids triggered increased degranulation and tumor necrosis factor production by NKp44+ NK cells in cocultures, resulting in enhanced epithelial cell death compared with HLA-DP301pos organoids. Blocking of HLA-DP401-NKp44 interactions (anti-NKp44) abrogated NK cell activity in cocultures.Conclusions: We identified an UC risk HLA-DP haplotype that engages NKp44 and activates NKp44+ NK cells, mediating damage to intestinal epithelial cells in an HLA-DP haplotype-dependent manner. The molecular interaction between NKp44 and HLA-DP401 in UC can be targeted by therapeutic interventions to reduce NKp44+ NK cell-mediated destruction of the intestinal epithelium in UC

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes