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Better together? Treating traumatic brain inj.ry with minocycline plus N-acetylcysteine

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Neural Regeneration Research 2022年第12期17卷 2589-2592页

作者： Siobhán Lawless peter j.Bergold Graduate Program in Neural and Behavioral Sciences State University of New York-Downstate Health Sciences UniversityBrooklynNYUSA Department of Physiology and Pharmacology State University of New York-Downstate Health Sciences UniversityBrooklynNYUSA

Traumatic brain inj.ry has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after inj.ry. Treatment of traumatic brain inj.ry is typically delayed many hours, thus only delayed damage can be targeted with drugs. Delayed traumatic brain inj.ry includes neuroinflammation, oxidative damage, apoptosis, and glutamate toxicity. Both the speed and complexity of traumatic brain inj.ry pathophysiology present large obstacles to drug development. Repurposing of Food and Drug Administration-approved drugs may be a highly efficient approach to get therapeutics to the clinic. This review examines the preclinical outcomes of minocycline and N-acetylcysteine as individual drugs and compares them to the minocycline plus N-acetylcysteine combination. Both minocycline and N-acetylcysteine are Food and Drug Administration-approved drugs with pleiotropic therapeutic effects. As individual drugs, minocycline and N-acetylcysteine are well tolerated, with known pharmacokinetics, and enter the brain through an intact blood-brain barrier. At concentrations greater than needed for antimicrobial action, minocycline is a potent anti-inflammatory minocycline, also acts as an antioxidant and inhibits multiple enzymes that promote brain inj.ry including metalloproteases, caspases, and polyADP-ribose-polymerase-1. N-acetylcysteine alone is also an antioxidant. It increases brain glutathione, prevents lipid oxidation, and protects mitochondria. N-acetylcysteine also acts as an anti-inflammatory as well as increases extracellular glutamate by activating the X;cystine-glutamate antitransporter. These multiple actions of minocycline and N-acetylcysteine have made them attractive candidates to treat traumatic brain inj.ry. When first dosed within the one hour after inj.ry, either minocycline or N-acetylcysteine improves a diverse set of therapeutic outcome measures in multiple traumatic brain inj.ry animal models. A small number of clinical

关键词： clinical trial outcome measures preclinical testing rodent models of traumatic brain inj.ry therapeutic time window

Optimizing laser coupling,matter heating,and particle acceleration from solids using multiplexed ultraintense lasers

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Matter and Radiation at Extremes 2024年第4期9卷 16-28页

作者： Weipeng Yao Motoaki Nakatsutsumi Sébastien Buffechoux Patrizio Antici Marco Borghesi Andrea Ciardi Sophia N.Chen Emmanuel d’Humières Laurent Gremillet Robert Heathcote Voj.ech Horny Paul McKenna Mark N.Quinn Lorenzo Romagnani Ryan Royle Gianluca Sarri Yasuhiko Sentoku Hans-peter Schlenvoigt Toma Toncian Olivier Tresca Laura Vassura Oswald Willi j.lien Fuchs LULI-CNRS CEASorbonne UniversitéEcole PolytechniqueInstitut Polytechnique de ParisF-91128 Palaiseau CedexFrance Sorbonne Université Observatoire de ParisUniversité PSLCNRSLERMAF-75005 ParisFrance INRS-EMT 1650 BoulLionel-BouletVarennesQuebec J3X 1S2Canada Center for Plasma Physics School of Mathematics and PhysicsQueen’s University BelfastBelfast BT71NNUnited Kingdom “Horia Hulubei”National Institute for Physics and Nuclear Engineering 30 Reactorului StreetRO-077125 Bucharest-MagureleRomania University of Bordeaux Centre Lasers Intenses et ApplicationsCNRSCEAUMR 5107F-33405 TalenceFrance CEA DAMDIFF-91297 ArpajonFrance Université Paris-Saclay CEALMCE91680 Bruyères-le-ChatelFrance Central Laser Facility STFC Rutherford Appleton LaboratoryDidcotUnited Kingdom SUPA Department of PhysicsUniversity of StrathclydeGlasgow G40NGUnited Kingdom Department of Physics University of NevadaRenoNevada 89557USA Institute of Laser Engineering Osaka University2-6 YamadaokaSuitaOsaka 565-0871Japan Institut fur Laser und Plasmaphysik Heinrich Heine Universitat DusseldorfDusseldorfGermany

Realizing the full potential of ultrahigh-intensity lasers for particle and radiation generation will require multi-beam arrangements due to technology ***,we investigate how to optimize their coupling with solid ***,we show that overlapping two intense lasers in a mirror-like configuration onto a solid with a large preplasma can greatly improve the generation of hot electrons at the target front and ion acceleration at the target *** underlying mechanisms are analyzed through multidimensional particle-in-cell simulations,revealing that the self-induced magnetic fields driven by the two laser beams at the target front are susceptible to reconnection,which is one possible mechanism to boost electron *** addition,the resistive magnetic field generated during the transport of the hot electrons in the target bulk tends to improve their *** simulations also indicate that such effects can be further enhanced by overlapping more than two laser beams.

关键词： laser acceleration particle

A-posteriori error estimation for second order mechanical systems

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Acta Mechanica Sinica 2012年第3期28卷 854-862页

作者： Thomas Ruiner j.rg Fehr Bernard Haasdonk peter Eberhard Institute of Engineering and Computational Mechanics University of StuttgartPfaffenwaldring 970569 StuttgartGermany Institute of Applied Analysis and Numerical Simulation University of StuttgartPfaffenwaldring 5770569 StuttgartGermany

One important issue for the simulation of flexible multibody systems is the reduction of the flexible bodies de- grees of freedom. As far as safety questions are concerned knowledge about the error introduced by the reduction of the flexible degrees of freedom is helpful and very important. In this work, an a-posteriori error estimator for linear first order systems is extended for error estimation of me- chanical second order systems. Due to the special second order structure of mechanical systems, an improvement of the a-posteriori error estimator is achieved. A maj.r advan- tage of the a-posteriori error estimator is that the estimator is independent of the used reduction technique. Therefore, it can be used for moment-matching based, Gramian matrices based or modal based model reduction techniques. The capability of the proposed technique is demon- strated by the a-posteriori error estimation of a mechanical system, and a sensitivity analysis of the parameters involved in the error estimation process is conducted.

关键词： A-posteriori error estimator. Flexible multibodysystems Model reduction

Word Embeddings and Semantic Spaces in Natural Language Processing

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International j.urnal of Intelligence Science 2023年第1期13卷 1-21页

作者： peter j. Worth Dept. of Computer Science and Electrical Engineering Florida Atlantic University Boca Raton FL USA

One of the critical hurdles, and breakthroughs, in the field of Natural Language Processing (NLP) in the last two decades has been the development of techniques for text representation that solves the so-called curse of dimensionality, a problem which plagues NLP in general given that the feature set for learning starts as a function of the size of the language in question, upwards of hundreds of thousands of terms typically. As such, much of the research and development in NLP in the last two decades has been in finding and optimizing solutions to this problem, to feature selection in NLP effectively. This paper looks at the development of these various techniques, leveraging a variety of statistical methods which rest on linguistic theories that were advanced in the middle of the last century, namely the distributional hypothesis which suggests that words that are found in similar contexts generally have similar meanings. In this survey paper we look at the development of some of the most popular of these techniques from a mathematical as well as data structure perspective, from Latent Semantic Analysis to Vector Space Models to their more modern variants which are typically referred to as word embeddings. In this review of algoriths such as Word2Vec, GloVe, ELMo and BERT, we explore the idea of semantic spaces more generally beyond applicability to NLP.

关键词： Natural Language Processing Vector Space Models Semantic Spaces Word Embeddings Representation Learning Text Vectorization Machine Learning Deep Learning

Direct Load Control of Thermostatically Controlled Loads Based on Sparse Observations Using Deep Reinforcement Learning

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CSEE j.urnal of Power and Energy Systems 2019年第4期5卷 423-432页

作者： Frederik Ruelens Bert j.Claessens peter Vrancx Fred Spiessens Geert Deconinck Department of Electrical Engineering KU Leuven/EnergyVille3001 LeuvenBelgium REstore Centrica2600 AntwerpBelgium AI-lab Vrije Universiteit Brussel1050 BrusselsBelgium Vito/EnergyVille 2600 MolBelgium

This paper considers a demand response agent that must find a near-optimal sequence of decisions based on sparse observations of its *** a relevant set of features from these observations is a challenging task and may require substantial domain *** way to tackle this problem is to store sequences of past observations and actions in the state vector,making it high dimensional,and apply techniques from deep *** paper investigates the capabilities of different deep learning techniques,such as convolutional neural networks and recurrent neural networks,to extract relevant features for finding near-optimal policies for a residential heating system and electric water heater that are hindered by sparse *** simulation results indicate that in this specific scenario,feeding sequences of time-series to an Long Short-Term Memory(LSTM)network,which is a specific type of recurrent neural network,achieved a higher performance than stacking these time-series in the input of a convolutional neural network or deep neural network.

关键词： Convolutional networks deep reinforcement learning long short-term memory residential demand response

Molecular Analysis of Legume Nodule Development and Autoregulation

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j.urnal of Integrative Plant Biology 2010年第1期52卷 61-76页

作者： Brett j. Ferguson Arief Indrasumunar Satomi Hayashi Yu-Hsiang Lin Dugald E. Reid peter M. Gresshoff ARC Centre of Excellence for Integrative Legume Research The University of Queensland

Legumes are highly important food, feed and biofuel crops. With few exceptions, they can enter into an intricate symbiotic relationship with specific soil bacteria called rhizobia. This interaction results in the formation of a new root organ called the nodule in which the rhizobia convert atmospheric nitrogen gas into forms of nitrogen that are useable by the plant. The plant tightly controls the number of nodules it forms, via a complex root-to-shoot-to-root signaling loop called autoregulation of nodulation （AON）. This regulatory process involves peptide hormones, receptor kinases and small metabolites. Using modern genetic and genomic techniques, many of the components required for nodule formation and AON have now been isolated. This review addresses these recent findings, presents detailed models of the nodulation and AON processes, and identifies gaps in our understanding of these process that have yet to be fully explained.

关键词： Molecular Analysis of Legume Nodule Development and Autoregulation

Dietary Lectin exclusion: The next big food trend?

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World j.urnal of Gastroenterology 2019年第24期25卷 2973-2976页

作者： Kirpal Panacer peter j.Whorwell University of Manchester Medical Student Stopford BuildingUniversity of ManchesterManchester M13 9PGUnited Kingdom Neurogastroenterology Unit Wythenshawe HospitalManchester M23 9LTUnited Kingdom

Until recently,with the exception of coeliac disease,gastroenterologists have not been particularly interested in the role of diet in the management of gastrointestinal ***,patients have always felt that diet must play a part in their symptoms and,in the absence of any medical interest,have turned to alternative dietary practitioners for help,which can often have no evidence ***,with the advent of the FODMAP diet(fermentable oligosaccharides,disaccharides,monosaccharides,and polyols)and the realisation that diet can have a profound effect on the microbiome,medical opinion is now ***,research on the various diets that are now available is often completely *** are carbohydrate binding proteins which are widely distributed in nature and are found in a whole variety of commonly consumed *** seems likely that the exclusion of lectins from the diet could become the next“food fashion”for alternative practitioners to promote,especially as there is some evidence to suggest that certain lectins may be harmful to *** is,therefore,the purpose of this viewpoint to try and stimulate research on the dietary effects of lectins,which is currently minimal,so that we can pre-empt a situation where we are unable to give patients or the public evidence based advice on this topic.

关键词： Dietary lectins Exclusion diets Gastrointestinal system Harm Carbohydrate

ON AN EXTENSION OF ABEL-GONTSCHAROFF'S EXPANSION FORMULA

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Analysis in Theory and Applications 2005年第4期21卷 359-369页

作者： Tianxiao He Leetsch C. Hsu peter j. S. Shiue Illinois Wesleyan University USA Dalian University of Technology China University of Nevada Las Vegas USA

We present a constructive generalization of Abel-Gontscharoff＇s series expansion to higher dimensions. A constructive application to a problem of multivariate interpolation is also investigated. In addition, two algo... 详细信息

关键词： Abel-Gontscharoff's Expansion Formula Abel-Gontscharoff-Gould polynomial multivariate Abel-Gontscharoff interpolation higher dimensional dot product annihilation coefficients

Metallacycles,metallacages,and their aggregate/optical behavior

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Aggregate

Aggregate 2021年第5期2卷 1-21页

作者： Yan Sun peter j.Stang Department of Chemistry University of UtahSalt Lake CityUtahUSA

Since the first metallacycle was prepared by Verkade in 1983,various metallacycles and metallacages with controllable nanoscale shapes and sizes have been created by modular design and synthesis,showing unique properties that enable applications in catalysis,sensors,and *** from their photophysical properties to their antitumor activities and catalysis was found to be influenced by their ***,it is necessary and helpful to develop a systematic understanding of the relationships among the micro/nanostructures,the resultant photophysical/chemical properties,and the corresponding *** this review,we summarized the latest progress in this area in approximately the past 5 years.

关键词： aggregation coordination-driven assembly emission