Effective conductivity of inertial flows through porous media

We study two-dimensional incompressible inertial flows through porous media. At core (small) scale, we prove that the constitutive, nonlinear model can be rewritten into a linear one by means of a new parameter K* which encompasses all the inertial effects. In natural (large-scale) formations, K* is erratically changing, and we analytically compute its counterpart, which is coined generalized effective conductivity, by the self-consistent approach (SCA). In spite of its approximate nature, the SCA leads to simple results that are in good agreement with Monte Carlo simulations

Mathematical modelling and numerical bifurcation analysis of inbreeding and interdisciplinarity dynamics in academia

We address a mathematical model to approximate in a coarse qualitative the interaction between inbreeding-lobbying and interdisciplinarity in academia and perform a one and two-parameter numerical bifurcation analysis to analyse its dynamics. Disciplinary diversity is a necessary condition for the development of interdisciplinarity, which is being recognized today as the key to establish a vibrant academic environment with bigger potential for breakthroughs/innovation in research and technology. However, the interaction of several factors including institutional policies, and behavioural attitudes put significant barriers on advancing interdisciplinarity. A “cognitive rigidity” may rise due to reactive academic lobby behaviours favouring inbreeding. The proposed model consists of four coupled non-linear Ordinary Differential Equations simulating the interaction between certain types of academic behaviour and the rate of knowledge advancement which is related to the level of disciplinary diversity. The effect of a control policy that inhibits inbreeding-lobbying is also investigated. The numerical bifurcation analysis reveals a rich nonlinear behaviour including multistability, sustained oscillations, limit points of limit cycles, homoclinic bifurcations as well as codimension-two bifurcations and in particular Bogdanov–Takens and Bautin bifurcations

Spatial analysis of phylogenetic community structure: New version of a classical method

The increasing availability of phylogenetic information facilitates the use of evolutionary methods in community ecology to reveal the importance of evolution in the species assembly process. However, while several methods have been applied to a wide range of communities across different spatial scales with the purpose of detecting non-random phylogenetic patterns, the spatial aspects of phylogenetic community structure have received far less attention. Accordingly, the question for this study is: can point pattern analysis be used for revealing the phylogenetic structure of multi-species assemblages? We introduce a new individual-centered procedure for analyzing the scale-dependent phylogenetic structure of multi-species point patterns based on digitized field data. The method uses nested circular plots with increasing radii drawn around each individual plant and calculates the mean phylogenetic distance between the focal individual and all individuals located in the circular ring delimited by two successive radii. This scale-dependent value is then averaged over all individuals of the same species and the observed mean is compared to a null expectation with permutation procedures. The method detects particular radius values at which the point pattern of a single species exhibits maximum deviation from the expectation towards either phylogenetic aggregation or segregation. Its performance is illustrated using data from a grassland community in Hungary and simulated point patterns. The proposed method can be extended to virtually any distance function for species pairs, such as functional distances

Thermally stable external cavity laser based on silicon nitride periodic nanostructures

In this paper we demonstrate a thermally stable silicon nitride external cavity (SiN EC) laser based on a 250 μm sized Reflective Semiconductor Optical Amplifier (RSOA) butt-coupled to a series of Si 3 N 4 Bragg gratings acting as wavelength selective reflectors. The laser shows power outputs over 3 mW, a very low lasing threshold of 12 mA and with a typical Side-Mode Suppression Ratio of 45 dB. In this configuration a mode-hop free lasing regime over a range of 47 mA has been achieved (from 15 mA to 62 mA). Thermal stability of the lasing wavelength at temperatures up to 80°C is demonstrated. Further on, experimental results on a passive chip based on new 1D photonic crystal cavities are shown to have higher Q-Factors. This paves the way to avoiding thermal wavelength drifts and unlocks the possibility for these devices to be integrated in Dense WDM and optical-interconnect technologies, where transceivers must operate over a wide temperature range without active cooling

Energy, forest, and indoor air pollution models for Sagarmatha National Park and Buffer Zone, Nepal

This paper presents the results of management-oriented research on energy, forest, and human health issues in a remote mountain area, the Sagarmatha National Park and Buffer Zone (SNPBZ), Nepal. The research was based on a broader, integrated participatory framework ultimately intended for use in adaptive management. The present study focused on the application of a participatory modeling framework to address problems related to energy demand and consumption, forest condition, and indoor air pollution, which were defined by the stakeholders as important issues to be addressed. The models were developed using a generalizing design that allows for user-friendly adaptation to other contexts (free download at http://hkkhpartnership.org). Moreover, we simulated management scenarios in collaboration with all modeling actors with the aim of building consensus on the understanding of the system as well as supporting decision-makers' capacity not only to respond to changes, but also to anticipate them. Importantly, the system dynamics assessment found that the SNPBZ forests are affected by an increasing demand for fuelwood (occurring due to tourism growth), as one of the main sources of energy. Selected forests show an average reduction of 38 in forest biomass from 1992 to 2008. This shows that the business-as-usual scenario is unlikely to result in the preservation of the current forest status; in fact, such preservation would require 75 of fuelwood to be replaced with alternative energy sources. At the same time, a 75 reduction of fuelwood use (and an 80 reduction of dung use) would reduce indoor carbon monoxide (CO) concentrations to the standard limits for CO exposure set by the World Health Organization

Mutant p53 as a guardian of the cancer cell

Forty years of research have established that the p53 tumor suppressor provides a major barrier to neoplastic transformation and tumor progression by its unique ability to act as an extremely sensitive collector of stress inputs, and to coordinate a complex framework of diverse effector pathways and processes that protect cellular homeostasis and genome stability. Missense mutations in the TP53 gene are extremely widespread in human cancers and give rise to mutant p53 proteins that lose tumor suppressive activities, and some of which exert trans-dominant repression over the wild-type counterpart. Cancer cells acquire selective advantages by retaining mutant forms of the protein, which radically subvert the nature of the p53 pathway by promoting invasion, metastasis and chemoresistance. In this review, we consider available evidence suggesting that mutant p53 proteins can favor cancer cell survival and tumor progression by acting as homeostatic factors that sense and protect cancer cells from transformation-related stress stimuli, including DNA lesions, oxidative and proteotoxic stress, metabolic inbalance, interaction with the tumor microenvironment, and the immune system. These activities of mutant p53 may explain cancer cell addiction to this particular oncogene, and their study may disclose tumor vulnerabilities and synthetic lethalities that could be exploited for hitting tumors bearing missense TP53 mutations

Translational control of cardiac fibrosis

Background Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global post-transcriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored. Methods Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used miRNA-and RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. To reveal post-transcriptional mechanisms in the human fibrotic heart, we then integrated our findings with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients. Results We generated nucleotide-resolution translatome data during the TGFβ1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in post-transcriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested an extensive post-transcriptional regulatory network underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as PUM2 and QKI that work in concert to regulate the translation of target transcripts in human diseased hearts. Conclusions We reveal widespread translational effects of TGFβ1 and define novel post-transcriptional events that control the fibroblast-to-myofibroblast transition. Regulatory networks that affect ribosome occupancy in fibroblasts are paralleled in human heart disease. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies