Stress response function of a two-dimensional ordered packing of frictional beads

We study the stress profile of an ordered two-dimensional packing of beads in response to the application of a vertical overload localized at its top surface. Disorder is introduced through the Coulombic friction between the grains which gives some indeterminacy and allows the choice of one constrained random number per grain in the calculation of the contact forces. The so-called `multi-agent' technique we use, lets us deal with systems as large as $1000\times1000$ grains. We show that the average response profile has a double peaked structure. At large depth $z$, the position of these peaks grows with $cz$, while their widths scales like $\sqrt{Dz}$. $c$ and $D$ are analogous to `propagation' and `diffusion' coefficients. Their values depend on that of the friction coefficient $\mu$. At small $\mu$, we get $c_0-c \propto \mu$ and $D \propto \mu^\beta$, with $\beta \sim 2.5$, which means that the peaks get closer and wider as the disorder gets larger. This behavior is qualitatively what was predicted in a model where a stochastic relation between the stress components is assumed.Comment: 7 pages, 7 figures, accepted version to Europhys. Let

Contractile deficits in engineered cardiac microtissues as a result of MYBPC3 deficiency and mechanical overload.

The integration of in vitro cardiac tissue models, human induced pluripotent stem cells (hiPSCs) and genome-editing tools allows for the enhanced interrogation of physiological phenotypes and recapitulation of disease pathologies. Here, using a cardiac tissue model consisting of filamentous three-dimensional matrices populated with cardiomyocytes derived from healthy wild-type (WT) hiPSCs (WT hiPSC-CMs) or isogenic hiPSCs deficient in the sarcomere protein cardiac myosin-binding protein C (MYBPC3-/- hiPSC-CMs), we show that the WT microtissues adapted to the mechanical environment with increased contraction force commensurate to matrix stiffness, whereas the MYBPC3-/- microtissues exhibited impaired force development kinetics regardless of matrix stiffness and deficient contraction force only when grown on matrices with high fibre stiffness. Under mechanical overload, the MYBPC3-/- microtissues had a higher degree of calcium transient abnormalities, and exhibited an accelerated decay of calcium dynamics as well as calcium desensitization, which accelerated when contracting against stiffer fibres. Our findings suggest that MYBPC3 deficiency and the presence of environmental stresses synergistically lead to contractile deficits in cardiac tissues

Augmenting human memory using personal lifelogs

Memory is a key human facility to support life activities, including social interactions, life management and problem solving. Unfortunately, our memory is not perfect. Normal individuals will have occasional memory problems which can be frustrating, while those with memory impairments can often experience a greatly reduced quality of life. Augmenting memory has the potential to make normal individuals more effective, and those with significant memory problems to have a higher general quality of life. Current technologies are now making it possible to automatically capture and store daily life experiences over an extended period, potentially even over a lifetime. This type of data collection, often referred to as a personal life log (PLL), can include data such as continuously captured pictures or videos from a first person perspective, scanned copies of archival material such as books, electronic documents read or created, and emails and SMS messages sent and received, along with context data of time of capture and access and location via GPS sensors. PLLs offer the potential for memory augmentation. Existing work on PLLs has focused on the technologies of data capture and retrieval, but little work has been done to explore how these captured data and retrieval techniques can be applied to actual use by normal people in supporting their memory. In this paper, we explore the needs for augmenting human memory from normal people based on the psychology literature on mechanisms about memory problems, and discuss the possible functions that PLLs can provide to support these memory augmentation needs. Based on this, we also suggest guidelines for data for capture, retrieval needs and computer-based interface design. Finally we introduce our work-in-process prototype PLL search system in the iCLIPS project to give an example of augmenting human memory with PLLs and computer based interfaces

The C++0x "Concepts" Effort

C++0x is the working title for the revision of the ISO standard of the C++ programming language that was originally planned for release in 2009 but that was delayed to 2011. The largest language extension in C++0x was "concepts", that is, a collection of features for constraining template parameters. In September of 2008, the C++ standards committee voted the concepts extension into C++0x, but then in July of 2009, the committee voted the concepts extension back out of C++0x. This article is my account of the technical challenges and debates within the "concepts" effort in the years 2003 to 2009. To provide some background, the article also describes the design space for constrained parametric polymorphism, or what is colloquially know as constrained generics. While this article is meant to be generally accessible, the writing is aimed toward readers with background in functional programming and programming language theory. This article grew out of a lecture at the Spring School on Generic and Indexed Programming at the University of Oxford, March 2010

Dynamic Effects Increasing Network Vulnerability to Cascading Failures

We study cascading failures in networks using a dynamical flow model based on simple conservation and distribution laws to investigate the impact of transient dynamics caused by the rebalancing of loads after an initial network failure (triggering event). It is found that considering the flow dynamics may imply reduced network robustness compared to previous static overload failure models. This is due to the transient oscillations or overshooting in the loads, when the flow dynamics adjusts to the new (remaining) network structure. We obtain {\em upper} and {\em lower} limits to network robustness, and it is shown that {\it two} time scales $\tau$ and $\tau_0$, defined by the network dynamics, are important to consider prior to accurately addressing network robustness or vulnerability. The robustness of networks showing cascading failures is generally determined by a complex interplay between the network topology and flow dynamics, where the ratio $\chi=\tau/\tau_0$ determines the relative role of the two of them.Comment: 4 pages Latex, 4 figure

Models of stress fluctuations in granular media

We investigate in detail two models describing how stresses propagate and fluctuate in granular media. The first one is a scalar model where only the vertical component of the stress tensor is considered. In the continuum limit, this model is equivalent to a diffusion equation (where the r\^ole of time is played by the vertical coordinate) plus a randomly varying convection term. We calculate the response and correlation function of this model, and discuss several properties, in particular related to the stress distribution function. We then turn to the tensorial model, where the basic starting point is a wave equation which, in the absence of disorder, leads to a ray-like propagation of stress. In the presence of disorder, the rays acquire a diffusive width and the angle of propagation is shifted. A striking feature is that the response function becomes negative, which suggests that the contact network is mechanically unstable to very weak perturbations. The stress correlation function reveals characteristic features related to the ray-like propagation, which are absent in the scalar description. Our analytical calculations are confirmed and extended by a numerical analysis of the stochastic wave equation.Comment: 32 pages, latex, 18 figures and 6 diagram

Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes.

Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylcholine, and biogenic amines are reported in WD; however, less is known about their circulating precursors. We aimed to study choline, methionine, aromatic amino acids, and phospholipids in serum of WD subjects. Hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry was employed to profile serum of WD subjects categorized as hepatic, neurologic, and pre-clinical. Hepatic transcript levels of genes related to choline and methionine metabolism were verified in the Jackson Laboratory toxic milk mouse model of WD (tx-j). Compared to healthy subjects, choline, methionine, ornithine, proline, phenylalanine, tyrosine, and histidine were significantly elevated in WD, with marked alterations in phosphatidylcholines and reductions in sphingosine-1-phosphate, sphingomyelins, and acylcarnitines. In tx-j mice, choline, methionine, and phosphatidylcholine were similarly dysregulated. Elevated choline is a hallmark dysregulation in WD interconnected with alterations in methionine and phospholipid metabolism, which are relevant to hepatic steatosis. The elevated phenylalanine, tyrosine, and histidine carry implications for neurologic manifestations and are worth further investigation