Metastability in better-than-worst-case designs

Abstract Better-Than-Worst-Case-Designs use timing speculation to run with a cycle period faster than the one required for worst-case conditions. This speculation may produce timing violations and metastability that result in failures and non-deterministic timing behavior. The effects of these phenomena are not always well understood by designers and researchers in this area

Convection-enhanced delivery of methotrexate-loaded maghemite nanoparticles

Convection-enhanced delivery (CED) is a novel approach for delivering drugs directly into brain tumors by intracranial infusion, enabling the distribution of high drug concentrations over large tissue volumes. This study was designed to present a method for binding methotrexate (MTX) to unique crystalline, highly ordered and superparamagnetic maghemite nanoparticles via human serum albumin (HSA) coating, optimized for CED treatments of gliomas. Naked nanoparticles and HSA- or polyethylene glycol (PEG)-coated nanoparticles with/without MTX were studied. In vitro results showed no toxicity and a similar cell-kill efficacy of the MTX-loaded particles via HSA coating to that of free MTX, while MTX-loaded particles via PEG coating showed low efficacy. In vivo, the PEG-coated nanoparticles provided the largest distributions in normal rat brain and long clearance times, but due to their low efficacy in vitro, were not considered optimal. The naked nanoparticles provided the smallest distributions and shortest clearance times. The HSA-coated nanoparticles (with/without MTX) provided good distributions and long clearance times (nearly 50% of the distribution volume remained in the brain 3 weeks post treatment). No MTX-related toxicity was noted. These results suggest that the formulation in which HSA was bound to our nanoparticles via a unique precipitation method, and MTX was bound covalently to the HSA, could enable efficient and stable drug loading with no apparent toxicity. The cell-kill efficacy of the bound MTX remained similar to that of free MTX, and the nanoparticles presented efficient distribution volumes and slow clearance times in vivo, suggesting that these particles are optimal for CED

phot1 inhibition of ABCB19 primes lateral auxin fluxes in the shoot apex required for phototropism

It is well accepted that lateral redistribution of the phytohormone auxin underlies the bending of plant organs towards light. In monocots, photoreception occurs at the shoot tip above the region of differential growth. Despite more than a century of research, it is still unresolved how light regulates auxin distribution and where this occurs in dicots. Here, we establish a system in Arabidopsis thaliana to study hypocotyl phototropism in the absence of developmental events associated with seedling photomorphogenesis. We show that auxin redistribution to the epidermal sites of action occurs at and above the hypocotyl apex, not at the elongation zone. Within this region, we identify the auxin efflux transporter ATP-BINDING CASSETTE B19 (ABCB19) as a substrate target for the photoreceptor kinase PHOTOTROPIN 1 (phot1). Heterologous expression and physiological analyses indicate that phosphorylation of ABCB19 by phot1 inhibits its efflux activity, thereby increasing auxin levels in and above the hypocotyl apex to halt vertical growth and prime lateral fluxes that are subsequently channeled to the elongation zone by PIN-FORMED 3 (PIN3). Together, these results provide new insights into the roles of ABCB19 and PIN3 in establishing phototropic curvatures and demonstrate that the proximity of light perception and differential phototropic growth is conserved in angiosperm

Transforming plant biology and breeding with CRISPR/Cas9, Cas12 and Cas13

Currently, biology is revolutionized by ever growing applications of the CRISPR /Cas system. As discussed in this Review, new avenues have opened up for plant research and breeding by the use of the sequence‐specific DN ases Cas9 and Cas12 (formerly named Cpf1) and, more recently, the RN ase Cas13 (formerly named C2c2). Although double strand break‐induced gene editing based on error‐prone nonhomologous end joining has been applied to obtain new traits, such as powdery mildew resistance in wheat or improved pathogen resistance and increased yield in tomato, improved technologies based on CRISPR /Cas for programmed change in plant genomes via homologous recombination have recently been developed. Cas9‐ and Cas12‐ mediated DNA binding is used to develop tools for many useful applications, such as transcriptional regulation or fluorescence‐based imaging of specific chromosomal loci in plant genomes. Cas13 has recently been applied to degrade mRNA s and combat viral RNA replication. By the possibility to address multiple sequences with different guide RNA s and by the simultaneous use of different Cas proteins in a single cell, we should soon be able to achieve complex changes of plant metabolism in a controlled way

A Scalable and License Free 5G Internet of Radio Light Architecture for Services in Homes & Businesses

In this paper we present a 5G Internet Radio-Light (IoRL) architecture for homes that can be readily deployed because it utilizes unlicensed visible light and millimeter wave part of the spectrum, which does not require Mobile Network Operator (MNO) permission to deploy and which is used to provide inhabitants of houses with accurate location, interaction, access to Internet and Cloud based services such as high resolution video on a Tablet PC. The paper describes the home use cases and the IoRL architecture.EU Horizon 202

Assessing the life hazard from burning sandwich panels

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Metastability in Better-Than-Worst-Case Designs

Better-Than-Worst-Case-Designs use timing speculation to run with a cycle period faster than the one required for worst-case conditions. This speculation may produce timing violations and metastability that result in failures and non-deterministic timing behavior. The effects of these phenomena are not always well understood by designers and researchers in this area. This paper analyzes the impact of timing speculation and the reasons why it is difficult to adopt this paradigm in industrial designs