Probabilistic fracture finite elements

The Probabilistic Fracture Mechanics (PFM) is a promising method for estimating the fatigue life and inspection cycles for mechanical and structural components. The Probability Finite Element Method (PFEM), which is based on second moment analysis, has proved to be a promising, practical approach to handle problems with uncertainties. As the PFEM provides a powerful computational tool to determine first and second moment of random parameters, the second moment reliability method can be easily combined with PFEM to obtain measures of the reliability of the structural system. The method is also being applied to fatigue crack growth. Uncertainties in the material properties of advanced materials such as polycrystalline alloys, ceramics, and composites are commonly observed from experimental tests. This is mainly attributed to intrinsic microcracks, which are randomly distributed as a result of the applied load and the residual stress

First passage times and asymmetry of DNA translocation

Motivated by experiments in which single-stranded DNA with a short hairpin loop at one end undergoes unforced diffusion through a narrow pore, we study the first passage times for a particle, executing one-dimensional brownian motion in an asymmetric sawtooth potential, to exit one of the boundaries. We consider the first passage times for the case of classical diffusion, characterized by a mean-square displacement of the form $\sim t$, and for the case of anomalous diffusion or subdiffusion, characterized by a mean-square displacement of the form $\sim t^{\gamma}$ with $0<\gamma<1$. In the context of classical diffusion, we obtain an expression for the mean first passage time and show that this quantity changes when the direction of the sawtooth is reversed or, equivalently, when the reflecting and absorbing boundaries are exchanged. We discuss at which numbers of `teeth' $N$ (or number of DNA nucleotides) and at which heights of the sawtooth potential this difference becomes significant. For large $N$, it is well known that the mean first passage time scales as $N^2$. In the context of subdiffusion, the mean first passage time does not exist. Therefore we obtain instead the distribution of first passage times in the limit of long times. We show that the prefactor in the power relation for this distribution is simply the expression for the mean first passage time in classical diffusion. We also describe a hypothetical experiment to calculate the average of the first passage times for a fraction of passage events that each end within some time $t^*$. We show that this average first passage time scales as $N^{2/\gamma}$ in subdiffusion.Comment: 10 pages, 4 figures We incorporated reviewers' suggestions from Physical Review E. We reformulated a few paragraphs in the introduction and further clarified the issue of the (a)symmetry of passage times. In the results section, we re-expressed the results in a form that manifest the important features. We also added a few references concerning anomalous diffusion. The look (but not the content) of figure 1 was also change

Parallel Computing for Probabilistic Response Analysis of High Temperature Composites

The objective of this Phase I research was to establish the required software and hardware strategies to achieve large scale parallelism in solving PCM problems. To meet this objective, several investigations were conducted. First, we identified the multiple levels of parallelism in PCM and the computational strategies to exploit these parallelisms. Next, several software and hardware efficiency investigations were conducted. These involved the use of three different parallel programming paradigms and solution of two example problems on both a shared-memory multiprocessor and a distributed-memory network of workstations

Abundance of unknots in various models of polymer loops

A veritable zoo of different knots is seen in the ensemble of looped polymer chains, whether created computationally or observed in vitro. At short loop lengths, the spectrum of knots is dominated by the trivial knot (unknot). The fractional abundance of this topological state in the ensemble of all conformations of the loop of $N$ segments follows a decaying exponential form, $\sim \exp (-N/N_0)$, where $N_0$ marks the crossover from a mostly unknotted (ie topologically simple) to a mostly knotted (ie topologically complex) ensemble. In the present work we use computational simulation to look closer into the variation of $N_0$ for a variety of polymer models. Among models examined, $N_0$ is smallest (about 240) for the model with all segments of the same length, it is somewhat larger (305) for Gaussian distributed segments, and can be very large (up to many thousands) when the segment length distribution has a fat power law tail.Comment: 13 pages, 6 color figure

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Study of e+e−→ppˉe^+e^- \rightarrow p\bar{p} in the vicinity of ψ(3770)\psi(3770)

Using 2917 $\rm{pb}^{-1}$ of data accumulated at 3.773~$\rm{GeV}$, 44.5~$\rm{pb}^{-1}$ of data accumulated at 3.65~$\rm{GeV}$ and data accumulated during a $\psi(3770)$ line-shape scan with the BESIII detector, the reaction $e^+e^-\rightarrow p\bar{p}$ is studied considering a possible interference between resonant and continuum amplitudes. The cross section of $e^+e^-\rightarrow\psi(3770)\rightarrow p\bar{p}$, $\sigma(e^+e^-\rightarrow\psi(3770)\rightarrow p\bar{p})$, is found to have two solutions, determined to be ($0.059\pm0.032\pm0.012$) pb with the phase angle $\phi = (255.8\pm37.9\pm4.8)^\circ$ ($<$0.11 pb at the 90% confidence level), or $\sigma(e^+e^-\rightarrow\psi(3770)\rightarrow p\bar{p}) = (2.57\pm0.12\pm0.12$) pb with $\phi = (266.9\pm6.1\pm0.9)^\circ$ both of which agree with a destructive interference. Using the obtained cross section of $\psi(3770)\rightarrow p\bar{p}$, the cross section of $p\bar{p}\rightarrow \psi(3770)$, which is useful information for the future PANDA experiment, is estimated to be either ($9.8\pm5.7$) nb ($<17.2$ nb at 90% C.L.) or $(425.6\pm42.9)$ nb

Cortactin overexpression results in sustained epidermal growth factor receptor signaling by preventing ligand-induced receptor degradation in human carcinoma cells

The chromosome 11q13 region is frequently amplified in human carcinomas and results in an increased expression of various genes including cortactin, and is also associated with an increased invasive potential. Cortactin acts as an important regulator of the actin cytoskeleton. It is therefore very tempting to speculate that cortactin is the crucial gene within the 11q13 amplicon that mediates the invasive potential of these carcinomas. Cortactin also participates in receptor-mediated endocytosis, and recent findings have shown that, during receptor internalization, cortactin overexpression inhibits the ubiquitylation-mediated degradation of the epidermal growth factor receptor, resulting in a sustained ligand-induced epidermal growth factor receptor activity

Nerve Growth Factor Stimulates Interaction of Cayman Ataxia Protein BNIP-H/Caytaxin with Peptidyl-Prolyl Isomerase Pin1 in Differentiating Neurons

Mutations in ATCAY that encodes the brain-specific protein BNIP-H (or Caytaxin) lead to Cayman cerebellar ataxia. BNIP-H binds to glutaminase, a neurotransmitter-producing enzyme, and affects its activity and intracellular localization. Here we describe the identification and characterization of the binding between BNIP-H and Pin1, a peptidyl-prolyl cis/trans isomerase. BNIP-H interacted with Pin1 after nerve growth factor-stimulation and they co-localized in the neurites and cytosol of differentiating pheochromocytoma PC12 cells and the embryonic carcinoma P19 cells. Deletional mutagenesis revealed two cryptic binding sites within the C-terminus of BNIP-H such that single point mutants affecting the WW domain of Pin1 completely abolished their binding. Although these two sites do not contain any of the canonical Pin1-binding motifs they showed differential binding profiles to Pin1 WW domain mutants S16E, S16A and W34A, and the catalytically inert C113A of its isomerase domain. Furthermore, their direct interaction would occur only upon disrupting the ability of BNIP-H to form an intramolecular interaction by two similar regions. Furthermore, expression of Pin1 disrupted the BNIP-H/glutaminase complex formation in PC12 cells under nerve growth factor-stimulation. These results indicate that nerve growth factor may stimulate the interaction of BNIP-H with Pin1 by releasing its intramolecular inhibition. Such a mechanism could provide a post-translational regulation on the cellular activity of BNIP-H during neuronal differentiation. (213 words

Cross-Species Analyses Identify the BNIP-2 and Cdc42GAP Homology (BCH) Domain as a Distinct Functional Subclass of the CRAL_TRIO/Sec14 Superfamily

The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ∼100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs (‘h’ is large and hydrophobic residue and ‘s’ is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding ‘BCH-only’ domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, ‘BCH-like’ and CRAL_TRIO-containing proteins and their significance in regulating signaling events involving small GTPases