A new WPAN Model for NS-3 simulator

International audienceWireless sensor networks are one of the most challenging topics in research world due to the nature of the wireless communication and the constraints related to the sensor’s components. However, this field knows a very fast progress and new technologies are involved. One of the hottest trends of the future WSN is the I/WoT ‘Internet/Web of Things’. For the wireless medium access and radio transmission (MAC and PHY), I/WoT has chosen the IEEE 802.15.4 standard. Some researchers have proposed simulation models to analyze this standard in different simulation environment. In this paper we propose a new WPAN model for the NS-3 simulator. This model implements most of the IEEE 802.15.4 standard feature and modes of operations. Furthermore, a 6LoWPAN Model is used to incorporate the IEEE 802.15.4 into the IPv6 architecture by interfacing the IPv6 model of NS-3 with our new IEEE 802.15.4 standard model. Thus, we believe that this WPAN work can be seen as a foundation for future I/WoT simulation on NS-3

Joint multi-field T1 quantification for fast field-cycling MRI

Acknowledgment This article is based upon work from COST Action CA15209, supported by COST (European Cooperation in Science and Technology). Oliver Maier is a Recipient of a DOC Fellowship (24966) of the Austrian Academy of Sciences at the Institute of Medical Engineering at TU Graz. The authors would like to acknowledge the NVIDIA Corporation Hardware grant support.Peer reviewedPublisher PD

Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling

The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag−/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.National Institutes of Health (U.S.) (NIH grant R01-CA075576)National Institutes of Health (U.S.) (NIH grant R01-CA055042)National Institutes of Health (U.S.) (NIH grant R01-CA149261)National Institutes of Health (U.S.) (NIH grant P30-ES00002)National Institutes of Health (U.S.) (NIH grant P30-ES02109)National Center for Research Resources (U.S.) (grant number M01RR-01066)National Center for Research Resources (U.S.) (grant number UL1 RR025758, Harvard Clinical and Translational Science Center

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated

Operating a full tungsten actively cooled tokamak: overview of WEST first phase of operation

WEST is an MA class superconducting, actively cooled, full tungsten (W) tokamak, designed to operate in long pulses up to 1000 s. In support of ITER operation and DEMO conceptual activities, key missions of WEST are: (i) qualification of high heat flux plasma-facing components in integrating both technological and physics aspects in relevant heat and particle exhaust conditions, particularly for the tungsten monoblocks foreseen in ITER divertor; (ii) integrated steady-state operation at high confinement, with a focus on power exhaust issues. During the phase 1 of operation (2017–2020), a set of actively cooled ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor. Up to 8.8 MW of RF power has been coupled to the plasma and divertor heat flux of up to 6 MW m−2 were reached. Long pulse operation was started, using the upper actively cooled divertor, with a discharge of about 1 min achieved. This paper gives an overview of the results achieved in phase 1. Perspectives for phase 2, operating with the full capability of the device with the complete ITER-grade actively cooled lower divertor, are also described