Survivability study of a Water Cleaning Facility using Fluid Stochastic Petri Nets

This paper investigates the survivability of a water cleaning facility using Fluid Stochastic Petri Nets (FSPNs). Water cleaning facilities are responsible for providing drinking water to a specific district. The provided service is very important and makes such facilities belong to a nation's critical infrastructures. Therefore, such a facility should be able to recover in a timely manner after the occurrence of disasters. The use of FSPNs in survivability research is new and promising due to its general applicability. In this paper we model and analyze the survivability of of the last phases of the water cleaning process in a Dutch water company. Analysis results identify the weaknesses of the process and redundancy is suggested to improve the survivability

Region-Based Analysis of Hybrid Petri Nets with a Single General One-Shot Transition

Recently, hybrid Petri nets with a single general one-shot transition (HPnGs) have been introduced together with an algorithm to analyze their underlying state space using a conditioning/deconditioning approach. In this paper we propose a considerably more efficient algorithm for analysing HPnGs. The proposed algorithm maps the underlying state-space onto a plane for all possible firing times of the general transition s and for all possible systems times t. The key idea of the proposed method is that instead of dealing with infinitely many points in the t-s-plane, we can partition the state space into several regions, such that all points inside one region are associated with the same system state. To compute the probability to be in a specific system state at time τ, it suffices to find all regions intersecting the line t = τ and decondition the firing time over the intersections. This partitioning results in a considerable speed-up and provides more accurate results. A scalable case study illustrates the efficiency gain with respect to the previous algorithm

Nitrogen deposition and grass encroachment in calcareous and acidic Grey dunes (H2130) in NW-Europe

We present an overview of high nitrogen deposition effects on coastal dune grasslands in NW-Europe (H2130), especially concerning grass encroachment in calcareous and acidic Grey Dunes. The problem is larger than previously assumed, because critical loads are still too high, and extra N-input from the sea may amount to 10 kg ha−1 yr−1. Grass encroachment clearly leads to loss of characteristic plant species, from approximately 16 in open dune grassland to 2 in tall-grass vegetation. Dune zones differ in grass encroachment, due to the chemical status of the soil. In calcareous and iron-rich dunes (Renodunal district), grass encroachment showed a clear gradient over the dune area. Grass encroachment is low in calcareous foredunes, due to low P-availability, and large grazers were not needed to counteract grass encroachment after 2001. In partly decalcified middle dunes, P-availability and grass encroachment are high due to dissolution of calcium phosphates, and grazing only partially helped to control this. In acidic, iron-rich hinterdunes, grass encroachment gradually increased between 1990 and 2014, possibly because P-availability increased with time due to increased soil organic matter content. In acidic, iron-poor dunes (Wadden district), grass encroachment is a large problem, because chemical P-fixation with Ca or Fe does not occur. Large grazers may however reduce tall-grass cover. High cumulative N-deposition could theoretically lead to increased N-storage and N-mineralization in the soil. Mineralization indeed increased with N-deposition, but in 15N experiments, most ammonium was converted to nitrate, and storage in soil organic matter was low. Soil N-storage is probably reduced by high nitrate leaching, which will favour dune restoration when N-deposition levels decrease

A MicroRNA-1280/JAG2 Network Comprises a Novel Biological Target in High-Risk Medulloblastoma

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target

N-Myc-induced metabolic rewiring creates novel therapeutic vulnerabilities in neuroblastoma

N-Myc is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of Myc family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of Myc proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of N-Myc overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of N-Myc induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of N-Myc. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of N-Myc overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered N-Myc induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation

Impact of grazing management on hibernating caterpillars of the butterfly melitaea cinxia in calcareous grasslands

Contains fulltext : 103431.pdf (publisher's version ) (Open Access)12 p

Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses

The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations