Sandpiles on multiplex networks

We introduce the sandpile model on multiplex networks with more than one type of edge and investigate its scaling and dynamical behaviors. We find that the introduction of multiplexity does not alter the scaling behavior of avalanche dynamics; the system is critical with an asymptotic power-law avalanche size distribution with an exponent $\tau = 3/2$ on duplex random networks. The detailed cascade dynamics, however, is affected by the multiplex coupling. For example, higher-degree nodes such as hubs in scale-free networks fail more often in the multiplex dynamics than in the simplex network counterpart in which different types of edges are simply aggregated. Our results suggest that multiplex modeling would be necessary in order to gain a better understanding of cascading failure phenomena of real-world multiplex complex systems, such as the global economic crisis.Comment: 7 pages, 7 figure

A system to enrich for primitive streak-derivatives, definitive endoderm and mesoderm, from pluripotent cells in culture

Two lineages of endoderm develop during mammalian embryogenesis, the primitive endoderm in the pre-implantation blastocyst and the definitive endoderm at gastrulation. This complexity of endoderm cell populations is mirrored during pluripotent cell differentiation in vitro and has hindered the identification and purification of the definitive endoderm for use as a substrate for further differentiation. The aggregation and differentiation of early primitive ectoderm-like (EPL) cells, resulting in the formation of EPL-cell derived embryoid bodies (EPLEBs), is a model of gastrulation that progresses through the sequential formation of primitive streak-like intermediates to nascent mesoderm and more differentiated mesoderm populations. EPL cell-derived EBs have been further analysed for the formation of definitive endoderm by detailed morphological studies, gene expression and a protein uptake assay. In comparison to embryoid bodies derived from ES cells, which form primitive and definitive endoderm, the endoderm compartment of embryoid bodies formed from EPL cells was comprised almost exclusively of definitive endoderm. Definitive endoderm was defined as a population of squamous cells that expressed Sox17, CXCR4 and Trh, which formed without the prior formation of primitive endoderm and was unable to endocytose horseradish peroxidase from the medium. Definitive endoderm formed in EPLEBs provides a substrate for further differentiation into specific endoderm lineages; these lineages can be used as research tools for understanding the mechanisms controlling lineage establishment and the nature of the transient intermediates formed. The similarity between mouse EPL cells and human ES cells suggests EPLEBs can be used as a model system for the development of technologies to enrich for the formation of human ES cell-derived definitive endoderm in the future.Sveltana Vassilieva, Hweee Ngee Goh, Kevin X. Lau, James N. Hughes, Mary Familari, Peter D. Rathjen and Joy Rathje

Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins

Background: The delivery of ubiquitinated proteins to the proteasome for degradation is a key step in the regulation of the ubiquitin-proteasome pathway, yet the mechanisms underlying this step are not understood in detail. The Rad23 family of proteins is known to bind ubiquitinated proteins through its two ubiquitin-associated (UBA) domains, and may participate in the delivery of ubiquitinated proteins to the proteasome through docking via the Rad23 ubiquitin-like (UBL) domain. Results: In this study, we investigate how the interaction between the UBL and UBA domains may modulate ubiquitin recognition and the delivery of ubiquitinated proteins to the proteasome by autoinhibition. We have explored a competitive binding model using specific mutations in the UBL domain. Disrupting the intramolecular UBL-UBA domain interactions in HHR23A indeed potentiates ubiquitin-binding. Additionally, the analogous surface on the Rad23 UBL domain overlaps with that required for interaction with both proteasomes and the ubiquitin ligase Ufd2. We have found that mutation of residues on this surface affects the ability of Rad23 to deliver ubiquitinated proteins to the proteasome. Conclusions: We conclude that the competition of ubiquitin-proteasome pathway components for surfaces on Rad23 is important for the role of the Rad23 family proteins in proteasomal targeting

Single-shot fluctuations in waveguided high-harmonic generation

For exploring the application potential of coherent soft x-ray (SXR) and extreme ultraviolet radiation (XUV) provided by high-harmonic generation, it is important to characterize the central output parameters. Of specific importance are pulse-to-pulse (shot-to-shot) fluctuations of the high-harmonic output energy, fluctuations of the direction of the emission (pointing instabilities), and fluctuations of the beam divergence and shape that reduce the spatial coherence. We present the first single-shot measurements of waveguided high-harmonic generation in a waveguided (capillary-based) geometry. Using a capillary waveguide filled with Argon gas as the nonlinear medium, we provide the first characterization of shot-to-shot fluctuations of the pulse energy, of the divergence and of the beam pointing. We record the strength of these fluctuations vs. two basic input parameters, which are the drive laser pulse energy and the gas pressure in the capillary waveguide. In correlation measurements between single-shot drive laser beam profiles and single-shot high-harmonic beam profiles we prove the absence of drive laser beam-pointing-induced fluctuations in the high-harmonic output. We attribute the main source of high-harmonic fluctuations to ionization-induced nonlinear mode mixing during propagation of the drive laser pulse inside the capillary waveguide

Cluster size dependence of high-order harmonic generation

We investigate high-order harmonic generation (HHG) from noble gas clusters in a supersonic gas jet. To identify the contribution of harmonic generation from clusters versus that from gas monomers, we measure the high-order harmonic output over a broad range of the total atomic number density in the jet (from 3*10^16 cm^{-3} to 3x10^18 cm{-3}) at two different reservoir temperatures (303 K and 363 K). For the firrst time in the evaluation of the harmonic yield in such measurements, the variation of the liquid mass fraction, g, versus pressure and temperature is taken into consideration, which we determine, reliably and consistently, to be below 20% within our range of experimental parameters. By comparing the measured harmonic yield from a thin jet with the calculated corresponding yield from monomers alone, we find an increased emission of the harmonics when the average cluster size is less than 3000. Using g, under the assumption that the emission from monomers and clusters add up coherently, we calculate the ratio of the average single-atom response of an atom within a cluster to that of a monomer and find an enhancement of around 10 for very small average cluster size (~200). We do not find any dependence of the cut-off frequency on the composition of the cluster jet. This implies that HHG in clusters is based on electrons that return to their parent ions and not to neighbouring ions in the cluster. To fully employ the enhanced average single-atom response found for small average cluster sizes (~200), the nozzle producing the cluster jet must provide a large liquid mass fraction at these small cluster sizes for increasing the harmonic yield. Moreover, cluster jets may allow for quasi-phase matching, as the higher mass of clusters allows for a higher density contrast in spatially structuring the nonlinear medium.Comment: 16 pages, 6 figure

Fairness Beyond Disparate Treatment & Disparate Impact: Learning Classification without Disparate Mistreatment

Automated data-driven decision making systems are increasingly being used to assist, or even replace humans in many settings. These systems function by learning from historical decisions, often taken by humans. In order to maximize the utility of these systems (or, classifiers), their training involves minimizing the errors (or, misclassifications) over the given historical data. However, it is quite possible that the optimally trained classifier makes decisions for people belonging to different social groups with different misclassification rates (e.g., misclassification rates for females are higher than for males), thereby placing these groups at an unfair disadvantage. To account for and avoid such unfairness, in this paper, we introduce a new notion of unfairness, disparate mistreatment, which is defined in terms of misclassification rates. We then propose intuitive measures of disparate mistreatment for decision boundary-based classifiers, which can be easily incorporated into their formulation as convex-concave constraints. Experiments on synthetic as well as real world datasets show that our methodology is effective at avoiding disparate mistreatment, often at a small cost in terms of accuracy.Comment: To appear in Proceedings of the 26th International World Wide Web Conference (WWW), 2017. Code available at: https://github.com/mbilalzafar/fair-classificatio

Learning activation functions from data using cubic spline interpolation

Neural networks require a careful design in order to perform properly on a given task. In particular, selecting a good activation function (possibly in a data-dependent fashion) is a crucial step, which remains an open problem in the research community. Despite a large amount of investigations, most current implementations simply select one fixed function from a small set of candidates, which is not adapted during training, and is shared among all neurons throughout the different layers. However, neither two of these assumptions can be supposed optimal in practice. In this paper, we present a principled way to have data-dependent adaptation of the activation functions, which is performed independently for each neuron. This is achieved by leveraging over past and present advances on cubic spline interpolation, allowing for local adaptation of the functions around their regions of use. The resulting algorithm is relatively cheap to implement, and overfitting is counterbalanced by the inclusion of a novel damping criterion, which penalizes unwanted oscillations from a predefined shape. Experimental results validate the proposal over two well-known benchmarks.Comment: Submitted to the 27th Italian Workshop on Neural Networks (WIRN 2017

Patient-Related Barriers to Timely Dialysis Access Preparation: A Qualitative Study of the Perspectives of Patients, Family Members, and Health Care Providers

Rational & Objective A key aspect of smooth transition to dialysis is the timely creation of a permanent access. Despite early referral to kidney care, initiation onto dialysis is still suboptimal for many patients, which has clinical and cost implications. This study aimed to explore perspectives of various stakeholders on barriers to timely access creation. Study Design Qualitative study. Setting & Participants Semi-structured interviews with 96 participants (response rate, 67%), including patients with stage 4 chronic kidney disease (n = 30), new hemodialysis patients with (n = 18) and without (n = 20) permanent access (arteriovenous fistula), family members (n = 19), and kidney health care providers (n = 9). Analytical Approach Thematic analysis. Results Patients reported differential levels of behavioral activation toward access creation: avoidance/denial, wait and see, or active intention. 6 core themes were identified: (1) lack of symptoms, (2) dialysis fear and practical concerns (exaggerated fear, pain, cost, lifestyle disruptions, work-related concerns, burdening their families), (3) evaluating value against costs/risks of access creation (benefits, threat of operation, viability, prompt for early initiation), (4) preference for alternatives, (5) social influences (hearsay, family involvement, experiences of others), and (6) health care provider interactions (mistrust, interpersonal tension, lack of clarity on information). Themes were common to all groups, whereas nuanced perspectives of family members and health care providers were noted in some subthemes. Limitations Response bias. Conclusions Individual, interpersonal, and psychosocial factors compromise dialysis preparation and contribute to suboptimal dialysis initiation. Our findings support the need for interventions to improve patient and family engagement and address emotional concerns and misperceptions about preparing for dialysis