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Dabrafenib,an inhibitor of RIP3 kinase-dependent necroptosis,reduces ischemic brain injury

Neural Regeneration Research 2018年第2期13卷 252-256页

作者： Shelly A.Cruz Zhaohong Qin Alexandre E R.stewart Hsiao-Huei Chen Ottawa Hospital Research Institute OttawaCanada University of Ottawa Brain and Mind InstituteOttawaCanada University of Ottawa Heart Institute OttawaCanada Canadian Partnership for Storke Recovery OttawaCanada

Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases （RIPK） associated with the tumor necrosis factor-alpha （TNF-a）/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and al- leviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar con- centrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/ kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-u. However, subsequent lower doses （5 mg/kg/day） failed to sustain this neuroprotective effect after 4 days. Dabrafenib bl ocked lipopolysaccharides-induced activation of TNF-ct in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-ct-induced necroptotic pathway after ischemic brain injury. Since Dab- rafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.

关键词： ischemic brain injury inflammation macrophage Dabrafenib tumor necrosis factor-alpha photothrombosis receptor-interacting protein kinases necroptosis microgIia stroke neural regeneration

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High-g Shocking Testing of the Martlet Wireless Sensing System

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Sound & Vibration 2018年第3期52卷 6-11页

作者： Xi Liu Xinjun Dong Yang Wang Lauren stewart Jacob Dodson Bryan Joyce School of Civil and Environmental Engineering Georgia Inst.of TechnologyAtlantaGAUSA Air Force Research Laboratory Munitions DirectorateEglin AFBFLUSA Energy Technology and Materials Division University of Dayton Research Inst.Eglin AFBFLUSA

This article reports the latest development of a wireless sensing system,named Martlet,on high-g shock acceleration *** Martlet sensing node design is based on a Texas Instruments Piccolo microcontroller,with clock frequency programmable up to 90 *** high clock frequency of the microcontroller enables Martlet to support high-frequency data acquisition and high-speed onboard *** addition,the extensible design of the Martlet node conveniently allows incorporation of multiple sensor *** this study,a high-g accelerometer interface board is developed to allow Martlet to work with the selected microelectromechanical system(MEMS)high-g *** low-pass and highpass filters,amplification gains are also implemented on the high-g accelerometer interface *** impact experiments are conducted to validate the performance of the Martlet wireless sensing system with the high-g accelerometer *** results of this study show that the performance of the wireless sensing system is comparable to the cabled system.

关键词： Shock test wireless sensors data acquisition system hydraulic blast actuator Martlet wireless sensing unit

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Premotor biomarkers for Parkinson's disease-a promising direction of research

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Translational Neurodegeneration 2012年第1期1卷 81-91页

作者： Brian R Haas Tessandra H stewart Jing Zhang Department of Pathology University of Washington School of MedicineHMC Box 3596353259th AvenueSeattleWA98104USA

The second most serious neurodegenerative disease is Parkinson’s disease(PD).Over the past several decades,a strong body of evidence suggests that PD can begin years before the hallmark clinical motor symptoms *** for PD are urgently needed to differentiate between neurodegenerative disorders,screen novel therapeutics,and predict eventual clinical PD before the onset of *** clinical evaluations and neuroimaging techniques have been developed in the last several years with some success in this ***,other strategies have been utilized to identify biochemical and genetic markers associated with PD leading to the examination of PD progression and pathogenesis in cerebrospinal fluid,blood,or ***,interesting results are surfacing from preliminary studies using known PD-associated genetic mutations to assess potential premotor PD *** current review highlights recent advances and underscores areas of potential advancement.

关键词： Parkinson’s disease Biochemical markers LRRK2 GBA α-synuclein DJ-1 Clinical biomarkers Premotor,Neuroimaging parkin CSF

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Stepping up to meet the challenge of freezing of gait in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 589-600页

作者： Simon Lewis stewart Factor Nir Giladi Alice Nieuwboer John Nutt Mark Hallett ForeFront Parkinson’s Disease Research Clinic Brain and Mind CentreSchool of Medical SciencesUniversity of SydneySydneyNSWAustralia Jean and Paul Amos Parkinson’s Disease and Movement Disorders Program Emory University School of MedicineAtlantaGAUSA Movement Disorders Unit Department of NeurologyTel-Aviv Sourasky Medical CenterSackler School of Medicine and Sagol School of NeuroscienceTel Aviv UniversityTel AvivIsrael Department of Rehabilitation Sciences KU LeuvenLeuvenBelgium Movement Disorder Section Department of NeurologyOregon Health&Science UniversityPortlandORUSA Human Motor Control Section National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMDUSA.

There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie the phenomenon, but these reductionist approaches have yet to lead to a paradigm shift resulting in the development of novel treatment strategies. Addressing this issue will require greater integration of multi-modal data with complex computational modeling, but there are a number of critical aspects that need to be considered before embarking on such an approach. This paper highlights where the field needs to address current gaps and shortcomings including the standardization of definitions and measurement, phenomenology and pathophysiology, as well as considering what available data exist and how future studies should be constructed to achieve the greatest potential to better understand and treat this devastating symptom.

关键词： Freezing of gait Computational modeling Standardized definitions and assessments Novel paradigms Phenomenology Pathophysiology Treatment

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Diffusion tensor imaging in the courtroom:Distinction between scientific specificity and legally admissible evidence

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World Journal of Clinical Cases 2023年第19期11卷 4477-4497页

作者： Jennifer Christine van Velkinburgh Mark D Herbst stewart M Casper Science Communication Filipodia Publishing LLCSanta FeNM 87505United States Diagnostic Radiology Independent Diagnostic Radiology IncSt PetersburgFL 33711United States Personal Injury Law Casper&DeToledo LLCStamfordCT 06905United States

Interest and uptake of science and medicine peer-reviewed literature by readers outside of a paper’s topical subject,field or even discipline is *** the application of knowledge from one field or discipline to others can stimulate innovative solutions to problems facing modern society,it is also fraught with danger for *** the practice of law in the United States,academic papers are submitted to the courts as evidence in personal injury litigation from both the plaintiff(complainant)and *** transcendence of an academic publication over disciplinary boundaries is immediately met with the challenge of application by a group that inherently lacks in-depth knowledge on the scientific method,the practice of evidence-based medicine,or the publication process as a structured and internationally synthesized process involving peer review and guided by ethical standards and norms.A modern-day example of this is the ongoing conflict between the sensitivity of diffusion tensor imaging(DTI)and the legal standards for admissibility of evidence in litigation cases of mild traumatic brain injury(mTBI).In this review,we amalgamate the peer-reviewed research on DTI in mTBI with the court’s rationale underlying decisions to admit or exclude evidence of DTI abnormalities to support claims of brain *** found that the papers which are critical of the use of DTI in the courtroom reflect a primary misunderstanding about how diagnostic biomarkers differ legally from relevant and admissible *** clinical use of DTI to identify white matter abnormalities in the brain at the chronic stage is a valid methodology both clinically as well as forensically,contributes data that may or may not corroborate the existence of white matter damage,and should be admitted into evidence in personal injury trials if supported by a *** also delve into an aspect of science publication and peer review that can be manipulated by scientists and clinicians to

关键词： Diffuse axonal injury Mild brain injury Magnetic resonance imaging Neuroimaging Medicolegal Litigation Medical jurisprudence Ethics Peer review Publishing

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FUNDAMENTALS OF CORPORATE FINANCE / 4th ed.

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丛书名： McGraw-Hill/Irwin series in finance, insurance, and real estate

2004年

作者： richard A. BREALEY stewart C. MYERS ALAN J. MARC

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Comparison of Two Novel MRAS Based Strategies for Identifying Parameters in Permanent Magnet Synchronous Motors

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International Journal of Automation and computing 2010年第4期7卷 516-524页

作者： Kan Liu Qiao Zhang Zi-Qiang Zhu Jing Zhang An-Wen Shen Paul stewart School of Electrical and Information Engineering Hunan University Changsha 410082 PRC Department of Electronic and Electrical Engineering University of Sheffield Shettleld S1 3JD UK Department of Control Science and Engineering Huazhong University of Science and Technology Wuhan 430074 PRC Department of Aeronautical and Automotive Engineering University of Salford Greater Manchester M5 4WT UK

Two model reference adaptive system （MRAS） estimators are developed for identifying the parameters of permanent magnet synchronous motors （PMSM） based on the Lyapunov stability theorem and the Popov stability criterion, respectively. The proposed estimators only need online measurement of currents, voltages, and rotor speed to effectively estimate stator resistance, inductance, and rotor flux-linkage simultaneously. The performance of the estimators is compared and verified through simulations and experiments, which show that the two estimators are simple, have good robustness against parameter variation, and are accurate in parameter tracking. However, the estimator based on the Popov stability criterion, which can overcome parameter variation in a practical system, is superior in terms of response speed and convergence speed since there are both proportional and integral units in the estimator, in contrast to only one integral unit in the estimator based on the Lyapunov stability theorem. In addition, the estimator based on the Popov stability criterion does not need the expertise that is required in designing a Lyapunov function.

关键词： Permanent magnet synchronous motors (PMSM) model reference adaptive system (MRAS) Lyapunov stability theorem Popov stability criterion parameter identification.

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The friction of diamond-like carbon coatings in a water environment

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Friction 2013年第3期1卷 210-221页

作者： D.C.SUTTON G.LIMBERT D.stewart R.J.K.WOOD National Centre for Advanced Tribology at Southampton(nCATS) Engineering SciencesFaculty of Engineering and the EnvironmentUniversity of SouthamptonSouthamptonSO171BJUK Bioengineering Science Research Group Engineering SciencesFaculty of Engineering and the EnvironmentUniversity of SouthamptonSouthamptonSO171BJUK Materials Chemistry and CorrosionRolls-RoyceDerbyDE217XXUK

Diamond-like carbon(DLC)coatings are known to provide beneficial mechanical and tribological properties in harsh *** combination of high wear resistance and low friction has led to their extensive use in any number of *** tribological performance of a DLC coating is varied however,and the frictional response is known to be strongly dependent on the surrounding environment,as well as the material composition and bonding structure of the DLC *** paper presents an up-to-date review on the friction of DLC coatings in a water environment,with a special focus on transfer layer formation and tribochemistry.

关键词： friction diamond-like carbon(DLC) water transfer layer tribochemistry review

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Adjusting to climate:Acclimation,adaptation and developmental plasticity in physiological traits of a tropical rainforest lizard

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Integrative Zoology 2018年第4期13卷 411-427页

作者： John LLEWELYN stewart L.MACDONALD Craig MORITZ Felipe MARTINS AmberleeHATCHER Ben L.PHILLIPS Centre for Tropical Biodiversity and Climate Change James Cook UniversityTownsvilleQueenslandAustralia CSIRO Land and Water TownsvilleQueenslandAustralia Centre for Biodiversity Analysis Australian National UniversityCanberraAustralia School of BioSciences University of MelbourneMelbourneAustralia

The impact of climate change may be felt most keenly by tropical *** these taxa,it is argued,thermal specialization means a given shift in temperature will have a larger effect on *** species with limited dispersal ability,the impact of climate change depends on the capacity for their climate-relevant traits to *** shifts can occur through genetic adaptation,various forms of plasticity,or a combination of these *** we assess the extent and causes of shifts in 7 physiological traits in a tropical lizard,the rainforest sunskink(Lampropholis coggeri).Two populations were sampled that differ from each other in both climate and physiological *** compared trait values in each animal soon after field collection versus following acclimation to laboratory *** also compared trait values between populations in:(i)recently field-collected animals;(ii)the same animals following laboratory acclimation;and(iii)the laboratory-reared offspring of these *** results reveal high trait lability,driven primarily by acclimation and local *** contrast,developmental plasticity,resulting from incubation temperature,had little to no effect on most *** results suggest that,while specialized,tropical ectotherms may be capable of rapid shifts in climate-relevant traits.

关键词： acclimation adaptation climate change ectotherm reptile

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Measuring episodic abdominal pain and disability in suspected sphincter of Oddi dysfunction

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World Journal of Gastroenterology 2010年第35期16卷 4416-4421页

作者： Valerie Durkalski Walter stewart Paulette MacDougall Patrick Mauldin Joseph Romagnuolo Olga Brawman-Minzter Peter Cotton Division of Biostatistics and Epidemiology Medical University of South Carolina Center for Health Research Geisinger Health System Digestive Diseases Center Medical University of South Carolina Department of Pharmacy Medical University of South Carolina Department of Psychiatry Medical University of South Carolina

AIM:To evaluate the reliability of an instrument that measures disability arising from episodic abdominal pain in patients with suspected sphincter of Oddi dysfunction(SOD).METHODS:Although several treatments have been utilized to reduce pain and associated disability,measurement tools have not been developed to reliably track *** pilot studies were conducted to assess test-retest reliability of a newly developed instrument,the recurrent abdominal pain intensity and disability(RAPID) *** RAPID score is a 90-d summation of days where productivity for various daily activities is reduced as a result of abdominal pain episodes,and is modeled after the migraine disability assessment instrument used to measure headache-related *** was administered by telephone on 2 consecutive occasions in 2 consenting populations with suspected SOD:a pre-sphincterotomy population(Pilot Ⅰ,n = 55) and a post-sphincterotomy population(Pilot Ⅱ,n = 70).RESULTS:The average RAPID scores for Pilots Ⅰ and Ⅱ were:82 d(median:81.5 d,SD:64 d) and 48 d(median:0 d,SD:91 d),*** concordance between the 2 assessments for both populations was very good:0.81 for the pre-sphincterotomy population and 0.95 for the post-sphincterotomy ***:The described pilot studies suggest that RAPID is a reliable instrument for measuring disability resulting from abdominal pain in suspected SOD patients.

关键词： Sphincter of Oddi Abdominal pain Disability measurement Reproducibility of results Pain measurement Episodic pain

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