On the bend number of circular-arc graphs as edge intersection graphs of paths on a grid

Golumbic, Lipshteyn and Stern \cite{Golumbic-epg} proved that every graph can be represented as the edge intersection graph of paths on a grid (EPG graph), i.e., one can associate with each vertex of the graph a nontrivial path on a rectangular grid such that two vertices are adjacent if and only if the corresponding paths share at least one edge of the grid. For a nonnegative integer $k$, $B_k$-EPG graphs are defined as EPG graphs admitting a model in which each path has at most $k$ bends. Circular-arc graphs are intersection graphs of open arcs of a circle. It is easy to see that every circular-arc graph is a $B_4$-EPG graph, by embedding the circle into a rectangle of the grid. In this paper, we prove that every circular-arc graph is $B_3$-EPG, and that there exist circular-arc graphs which are not $B_2$-EPG. If we restrict ourselves to rectangular representations (i.e., the union of the paths used in the model is contained in a rectangle of the grid), we obtain EPR (edge intersection of path in a rectangle) representations. We may define $B_k$-EPR graphs, $k\geq 0$, the same way as $B_k$-EPG graphs. Circular-arc graphs are clearly $B_4$-EPR graphs and we will show that there exist circular-arc graphs that are not $B_3$-EPR graphs. We also show that normal circular-arc graphs are $B_2$-EPR graphs and that there exist normal circular-arc graphs that are not $B_1$-EPR graphs. Finally, we characterize $B_1$-EPR graphs by a family of minimal forbidden induced subgraphs, and show that they form a subclass of normal Helly circular-arc graphs

Sensitivity Analysis and Quantification of the Role of Governing Transport Mechanisms and Parameters in a Gas Flow Model for Low-Permeability Porous Media

Recent models represent gas (methane) migration in low-permeability media as a weighted sum of various contributions, each associated with a given flow regime. These models typically embed numerous chemical/physical parameters that cannot be easily and unambiguously evaluated via experimental investigations. In this context, modern sensitivity analysis techniques enable us to diagnose the behavior of a given model through the quantification of the importance and role of model input uncertainties with respect to a target model output. Here, we rely on two global sensitivity analysis approaches and metrics (i.e., variance-based Sobol’ indices and moment-based AMA indices) to assess the behavior of a recent interpretive model that conceptualizes gas migration as the sum of a surface diffusion mechanism and two weighted bulk flow components. We quantitatively investigate the impact of (i) each uncertain model parameter and (ii) the type of their associated probability distribution on the evaluation of methane flow. We then derive the structure of an effective diffusion coefficient embedding all complex mechanisms of the model considered and allowing quantification of the relative contribution of each flow mechanism to the overall gas flow

An original deconvolution approach for oil production allocation based on geochemical fingerprinting

We tackle oil commingling scenarios and develop an original deconvolution approach for geochemical production allocation. This yields robust assessment of the proportions of oils forming a mixture originating from commingling oils associated with diverse reservoirs or, wells. Our study starts from considering that production allocation performed by means of geochemical fingerprinting is relevant in the context of modern and sustainable use of georesources, with the added benefit of favoring shared facilities and production equipment. A geochemical production allocation workflow is typically structured according to two steps: (i) determination of the chromatograms associated with the mixture (and eventually with each of the End Members, EMs, constituting the fluids in the mixture), and (ii) the use of a deconvolution algorithm to estimate the mass fraction of each EM. Concerning the latter step, we introduce an original approach and the ensuing deconvolution algorithm (hereafter termed PGM) that does not require additional laboratory efforts in comparison with traditional approaches. We also present extensions of widely used deconvolution algorithms, which we frame in a (stochastic) Monte Carlo context to improve their robustness and reliability. The new PGM approach is assessed jointly with a suite of typically used approaches and algorithms against new laboratory-based commingling scenarios. The latter are based on the design and introduction of a novel and low-cost experimental method. The results of the study (i) constitute a unique and rigorous comparison of the traditionally employed production allocation deconvolution algorithms, (ii) document the critical importance of the number of features of the chromatograms used during a quantitative deconvolution, and (iii) suggest that our new PGM approach is very robust and accurate compared to existing approaches

Isolation and Mechanical Measurements of Myofibrils from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Summary: Tension production and contractile properties are poorly characterized aspects of excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Previous approaches have been limited due to the small size and structural immaturity of early-stage hiPSC-CMs. We developed a substrate nanopatterning approach to produce hiPSC-CMs in culture with adult-like dimensions, T-tubule-like structures, and aligned myofibrils. We then isolated myofibrils from hiPSC-CMs and measured the tension and kinetics of activation and relaxation using a custom-built apparatus with fast solution switching. The contractile properties and ultrastructure of myofibrils more closely resembled human fetal myofibrils of similar gestational age than adult preparations. We also demonstrated the ability to study the development of contractile dysfunction of myofibrils from a patient-derived hiPSC-CM cell line carrying the familial cardiomyopathy MYH7 mutation (E848G). These methods can bring new insights to understanding cardiomyocyte maturation and developmental mechanical dysfunction of hiPSC-CMs with cardiomyopathic mutations. : In this article, Pioner and colleagues reported contractile properties of isolated myofibrils from hiPSC-CMs with highly mature morphology. This approach permits quantitative assessment of maturation and contractile properties of hiPSC-CMs and can be used to study the development of contractile dysfunction in genetically based cardiac diseases. The authors present a patient-derived cell line carrying a novel familial cardiomyopathy MYH7 mutation (E848G)

Measuring the effects through time of the influence of visuomotor and visuotactile synchronous stimulation on a virtual body ownership illusion

Previous studies have examined the experience of owning a virtual surrogate body or body part through specific combinations of cross-modal multisensory stimulation. Both visuomotor (VM) and visuotactile (VT) synchronous stimulation have been shown to be important for inducing a body ownership illusion, each tested separately or both in combination. In this study we compared the relative importance of these two cross-modal correlations, when both are provided in the same immersive virtual reality setup and the same experiment. We systematically manipulated VT and VM contingencies in order to assess their relative role and mutual interaction. Moreover, we present a new method for measuring the induced body ownership illusion through time, by recording reports of breaks in the illusion of ownership ("breaks") throughout the experimental phase. The balance of the evidence, from both questionnaires and analysis of the breaks, suggests that while VM synchronous stimulation contributes the greatest to the attainment of the illusion, a disruption of either (through asynchronous stimulation) contributes equally to the probability of a break in the illusion

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013–2022: Data from the European Registry on H. pylori Management (Hp-EuReg)

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the “most important” variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013–2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin–clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth–quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin–amoxicillin–metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management

Background: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. Aim: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the ‘European Registry on Helicobacter pylori management’ (Hp-EuReg). Methods: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. Results: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. Conclusions: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme

Endogenous Wnt/β-Catenin Signaling Is Required for Cardiac Differentiation in Human Embryonic Stem Cells

Wnt/beta-catenin signaling is an important regulator of differentiation and morphogenesis that can also control stem cell fates. Our group has developed an efficient protocol to generate cardiomyocytes from human embryonic stem (ES) cells via induction with activin A and BMP4.We tested the hypothesis that Wnt/beta-catenin signals control both early mesoderm induction and later cardiac differentiation in this system. Addition of exogenous Wnt3a at the time of induction enhanced cardiac differentiation, while early inhibition of endogenous Wnt/beta-catenin signaling with Dkk1 inhibited cardiac differentiation, as indicated by quantitative RT-PCR analysis for beta-myosin heavy chain (beta-MHC), cardiac troponin T (cTnT), Nkx2.5, and flow cytometry analysis for sarcomeric myosin heavy chain (sMHC). Conversely, late antagonism of endogenously produced Wnts enhanced cardiogenesis, indicating a biphasic role for the pathway in human cardiac differentiation. Using quantitative RT-PCR, we show that canonical Wnt ligand expression is induced by activin A/BMP4 treatment, and the extent of early Wnt ligand expression can predict the subsequent efficiency of cardiogenesis. Measurement of Brachyury expression showed that addition of Wnt3a enhances mesoderm induction, whereas blockade of endogenously produced Wnts markedly inhibits mesoderm formation. Finally, we show that Wnt/beta-catenin signaling is required for Smad1 activation by BMP4.Our data indicate that induction of mesoderm and subsequent cardiac differentiation from human ES cells requires fine-tuned cross talk between activin A/BMP4 and Wnt/beta-catenin pathways. Controlling these pathways permits efficient generation of cardiomyocytes for basic studies or cardiac repair applications