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Estimates for Lyme borreliosis infections based on models using sentinel canine and human seroprevalence data

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Infectious Disease Modelling 2020年第1期5卷 871-888页

作者： Michael j.cook Basant K.Puri Vis a Vis Symposiums Bury St EdmundsUK CAR CambridgeUK

Two models were developed to estimate Lyme borreliosis(LB)*** was based on the seroprevalence of Borrelia infections in human *** model used corrections for false negative and false positive results from published test sensitivity and specificity measures.A second model based on Borrelia infections in sentinel dogs was used to quantify the prevalence of Lyme disease Borrelia infections in humans;the reference baseline for this model was human and canine infections in Germany.A comparison of the two models is shown and differences *** relationships between incidence,prevalence and total infection burden for LB were derived from published data and these were used in both models to calculate annual incidence,prevalence and total LB *** modelling was conservative and based on medical insurance records coded for erythema *** model growth rates were used in place of the commonly adopted exponential *** mean of the two models was used to create estimates for various countries and *** from the analyses for LB estimated for 2018 include:incidence e USA 473,000/year,Germany 471,000/year,France 434,000/year and UK 132,000/year;prevalence e USA 2.4 million,Germany 2.4 million,France 2.2 million and UK 667,000;total infections e USA 10.1 million,Germany 10.0 million,France 9.3 million and UK 2.8 *** for the world for 2018 are:incidence 12.3 million/year;prevalence 62.1 million;and total infection burden 262.0 *** figures are far higher than officially published data and reflect not only the underestimation of diagnosed cases,which is acknowledged by health agencies,but also undiagnosed and misdiagnosed cases.

关键词： Lyme disease Borreliosis Linear regression models Seropositive Companion animals Sentinel animals

Resistance to ERK1/2 pathway inhibitors;sweet spots,fitness deficits and drug addiction

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Cancer Drug Resistance 2019年第2期2卷 365-380页

作者： Matthew j.Sale Kathryn Balmanno Simon j.cook Signalling Programme The Babraham InstituteBabraham Research CampusCambridge CB223ATUK

MEK1/2 inhibitors are clinically approved for the treatment of BRAF-mutant melanoma,where they are used in combination with BRAF inhibitors,and are undergoing evaluation in other *** resistance to MEK1/2 inhibitors,including selumetinib(AZD6244/ARRY-142866),can arise through amplification of BRAF^(V600E) or KRAS^(G13D) to reinstate ERK1/2 *** have found that BRAF^(V600E) amplification and selumetinib resistance are fully reversible following drug *** is because resistant cells with BRAF^(V600E) amplification become addicted to selumetinib to maintain a precise level of ERK1/2 signalling(2%-3%of total ERK1/2 active),that is optimal for cell proliferation and *** withdrawal drives ERK1/2 activation outside of this critical“sweet spot”(~20%-30%of ERK1/2 active)resulting in a p57^(KIP2)-dependent G1 cell cycle arrest and senescence or expression of NOXA and cell death with features of autophagy;these terminal responses select against cells with amplified BRAF^(V600E).ERK1/2-dependent p57^(KIP2) expression is required for loss of BRAF^(V600E) amplification and determines the rate of reversal of selumetinib *** of selumetinib-resistant cells with BRAF^(V600E) amplification as tumour xenografts also requires the presence of selumetinib to“clamp”ERK1/2 activity within the sweet ***,BRAF^(V600E) amplification confers a selective disadvantage or“fitness deficit”during drug withdrawal,providing a rationale for intermittent dosing to forestall ***,selumetinib resistance driven by KRAS^(G13D) amplification/upregulation is not *** these cells ERK1/2 reactivation does not inhibit proliferation but drives a ZEB1-dependent epithelial-to-mesenchymal transition that increases cell motility and promotes resistance to traditional chemotherapy *** results reveal that the emergence of drug-addicted,MEKi-resistant cells,and the opportunity this may afford for intermittent dosing

关键词： BRAF CDKN1C/p57^(KIP2) EMT ERK KRAS MEK MEK inhibitor resistance selumetinib

Muscadine or amla extracts standardized to ellagic acid content ameliorate glucolipotoxicity associatedβ-cell dysfunction via inhibition of IL-1βand improved insulin secretion

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Food Production, Processing and Nutrition 2020年第1期2卷 91-101页

作者： Srikanth Earpina Karen McDonough Millicent Yeboah-Awudzi Kristina j.cook Sita Aggarwal jack N.Losso Chronic Degenerative Disease Prevention Laboratory School of Nutrition and Food ScienceLouisiana State University AgCenterLouisiana State University SystemBaton RougeLA 70803USA School of Animal Science Louisiana State University AgCenterLouisiana State University SystemBaton RougeLA 70803USA William Hansel Cancer Prevention Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeLA 70808USA Louisiana State University System Baton RougeLA 70803USA

Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin *** acid and urolithin A have strong anti-inflammatory effect on *** and amla are very good sources of ellagic *** present study examined the effect of ellagic acid,ellagic acid-rich muscadine or amla extract,or urolothin A on inflammation inβcells under glucolipotoxic *** NIT-1βcells were incubated in glucolipotoxic conditions(33.3 mM glucose,250μM palmitic acid or 33.3 mM glucose+250μM palmitic acid with or without ellagic acid,ellagic acid-rich muscadine or amla extracts standardized to its ellagic acid content,or urolithin A).Inflammatory status was evidenced by ELISA analysis of insulin and IL-1β*** acid-rich muscadine or amla extracts dose-dependently stimulated insulin secretion and down-regulated IL-1βbetter than pure ellagic acid,or urolithin *** A did not statistically stimulate insulin secretion and did not inhibit IL-1β.

关键词： Muscadine Amla Ellagic acid NIT-1 pancreaticβ-cells glucose,Palmitic acid Glucolipotoxicity IL-1β Inflammation Inflammasome Insulin secretion

Detecting subtle yet fast skeletal muscle contractions with ultrasoft and durable graphene-based cellular materials

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National Science Review 2022年第4期9卷 105-115页

作者： Zijun He Zheng Qi Huichao Liu Kangyan Wang Leslie Roberts jefferson Z.Liu Yilun Liu Stephen j.Wang Mark j.cook George P.Simon Ling Qiu Dan Li Department of Chemical Engineering The University of Melbourne Department of Materials Science and Engineering Monash University Department of Chemical Engineering Monash University State Key Laboratory for Strength and Vibration of Mechanical Structures School of Aerospace EngineeringXi'an Jiaotong University Neurophysiology Department Department of Neurology and Neurological ResearchSt Vincent's Hospital Department of Medicine St.Vincent's HospitalUniversity of Melbourne Department of Mechanical Engineering University of Melbourne Department of Design Monash University School of Design The Hong Kong Polytechnic University Shenzhen Geim Graphene Center Tsinghua-Berkeley Shenzhen InstituteTsinghua University

Human bodily movements are primarily controlled by the contractions of skeletal muscles. Unlike joint or skeletal movements that are generally performed in the large displacement range, the contractions of the skeletal muscles that underpin these movements are subtle in intensity yet high in frequency. This subtlety of movement makes it a formidable challenge to develop wearable and durable so?t materials to electrically monitor such motions with high fidelity for the purpose of, for example, muscle/neuromuscular disease diagnosis. Here we report that an intrinsically fragile ultralow-density graphene-based cellular monolith sandwiched between silicone rubbers can exhibit a highly effective stress and strain transfer mechanism at its interface with the rubber, with a remarkable improvement in stretchability(>100%). In particular, this hybrid also exhibits a highly sensitive, broadband-frequency electrical response(up to 180 Hz) for a wide range of strains. By correlating the mechanical signal of muscle movements obtained from this hybrid material with electromyography, we demonstrate that the strain sensor based on this hybrid material may provide a new, so?t and wearable mechanomyography approach for real-time monitoring of complex neuromuscular–skeletal interactions in a broad range of healthcare and human–machine interface applications. This work also provides a new architecture-enabled functional so?t material platform for wearable electronics.

关键词： cellular graphene strain sensors high-frequency electromechanical property surface mechanomyography skeletal muscle activity

Stable diffusion gradients in microfluidic conduits bounded by fluid walls

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Microsystems & Nanoengineering 2024年第3期10卷 357-367页

作者： Federico Nebuloni Cyril Deroy peter R.cook Edmond j.Walsh Department of Engineering Science Osney Thermo-Fluids InstituteUniversity of OxfordOxford OX20ESUK Sir William Dunn School of Pathology University of OxfordOxford OX13REUK

Assays mimicking in vitro the concentration gradients triggering biological responses like those involved in fighting infections and blood clotting are essential for biomedical *** assays prove especially attractive as they allow precise control of gradient shape allied to a reduction in *** microfluidic devices are fabricated using solid plastics that prevent direct access to responding ***-walled microfluidics allows the manufacture of circuits on standard Petri dishes in seconds,coupled to simple operating methods;cell-culture medium sitting in a standard dish is confined to circuits by fluid walls made of an immiscible *** develop and experimentally validate an analytical model of diffusion between two or more aqueous streams flowing at different rates into a fluid-walled conduit with the cross-section of a circular *** solid walls,fluid walls morph during flows as pressures fall,with wall shape changing down the *** model is validated experimentally for Fourier numbers<0.1 using fluorescein diffusing between laminar *** enables a priori prediction of concentration gradients throughout a conduit,so allowing rapid circuit design as well as providing bioscientists with an accurate way of predicting local concentrations of bioactive molecules around responsive and nonresponsive cells.

关键词： walls diffusion attractive

Evaluation of an automated spike-and-wave complex detection algorithm in the EEG from a rat model of absence epilepsy

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Neuroscience Bulletin 2015年第5期31卷 601-610页

作者： Sebastien H.Bauquier Alan Lai jonathan L.jiang Yi Sui Mark j.cook Faculty of Veterinary and Agricultural Sciences The University of Melbourne Department of Electrical and Electronic Engineering The University of Melbourne Department of Clinical Neurosciences St Vincent's Hospital Faculty of Medicine The University of Melbourne Department of Neurology Shenyang First People's Hospital

The aim of this prospective blinded study was to evaluate an automated algorithm for spike-andwave discharge（SWD） detection applied to EEGs from genetic absence epilepsy rats from Strasbourg（GAERS）.Five GAERS underwent four sessions of 20-min EEG *** EEG was manually analyzed for SWDs longer than one second by two investigators and automatically using an algorithm developed in MATLAB（？）.The sensitivity,specificity,positive predictive value（PPV）,and negative predictive value（NPV） were calculated for the manual（reference） versus the automatic（test） *** results showed that the algorithm had specificity,sensitivity,PPV and NPV 〉94%,comparable to published methods that are based on analyzing EEG changes in the frequency *** provides a good alternative as a method designed to mimic human manual marking in the time domain.

关键词： GAERS seizure detection epilepsy

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CCS Research Development and Deployment in a Clean Energy Future： Lessons from Australia over the Past Two Decades

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Engineering 2017年第4期3卷 477-484页

作者： peter j. cook CO2CRC Ltd.& peter cook Centre for Carbon Capture and Storage Research The University of Melbourne Melbourne VIC 2010 Australia

There is widespread, though by no means universal, recognition of the importance of carbon capture and storage （CCS） as a carbon mitigation technology. However, the rate of deployment does not match what is required for global temperatures to stay well below 2℃. Although some consider the hurdles to achieving the widespread application of CCS to he almost insurmountable, a more optimistic view is that a great deal is now known about CCS through research, demonstration, and deployment. We know how to do it; we are confident it can be done safely and effectively; we know what it costs; and we know that costs are decreasing and will continue to do so. We also know that the world will need CCS as long as countries, companies, and communities continue to use fossil fuels for energy and industrial processes. What is lacking are the necessary policy drivers, along with a technology-neutral approach to decrease carbon emissions in a cost-effective and timely manner while retaining the undoubted benefits of ready access to reliable and secure electricity and energy-intensive industrial products. In this paper, Australia is used as an example of what has been undertaken in CCS over the past 20 years, particularly in research and demonstration, hut also in international collaboration. Progress in the large-scale deployment of CCS in Australia has been too slow. However, the world＇s largest storage project will soon be operational in Australia as part of the Gorgon liquefied natural gas （LNG） project, and investigations are underway into several large-scale CCS Flagship program opportunities. The organization and progress of the Cooperative Research Centre for Greenhouse Gas Technologies （CO2CRC） Otway Project, which is currently Australia＇s only operational storage project, is discussed in some detail because of its relevance to the commercial deployment of CCS. The point is made that there is scope for building on this Otway activity to investigate more broadly （through the p

关键词： Carbon dioxide Carbon capture and storage Otway Australia

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Predicting flows through microfluidic circuits with fluid walls

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Microsystems & Nanoengineering 2021年第6期7卷 119-127页

作者： Cyril Deroy Nicholas Stovall-Kurtz Federico Nebuloni Cristian Soitu peter R.cook Edmond j.Walsh Department of Engineering Science Osney Thermo-Fluids LaboratoryUniversity of OxfordOxford OX20ESUK Sir William Dunn School of Pathology University of OxfordOxford OX13REUK Cold Spring Harbor Laboratory Cold Spring HarborNYUSA

The aqueous phase in traditional microfluidics is usually confined by solid walls;flows through such systems are often predicted *** solid walls limit access,open systems are being developed in which the aqueous phase is partly bounded by fluid walls(interfaces with air or immiscible liquids).Such fluid walls morph during flow due to pressure gradients,so predicting flow fields remains *** recently developed a version of open microfluidics suitable for live-cell biology in which the aqueous phase is confined by an interface with an immiscible and bioinert fluorocarbon(FC40).Here,we find that common medium additives(fetal bovine serum,serum replacement)induce elastic no-slip boundaries at this interface and develop a semi-analytical model to predict flow *** experimentally validate the model’s accuracy for single conduits and fractal vascular trees and demonstrate how flow fields and shear stresses can be controlled to suit individual applications in cell biology.

关键词： walls flows flow

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常见硫化物矿物中不可见金的富集

黄金地质科技 1991年第4期 63-72页

作者： NIGEL j.cook 金洪良

常见硫化物矿物晶格中的金及粒径小于1000埃的分散金均称为不可见金,它们无法用矿相显微镜和扫描电镜测到。离子探针微量分析(次级离子质谱法)表明,12个矿床硫化物矿物颗粒中不可见金的含量为0.5至1000ppm之间。不同矿床,或一个矿床中... 详细信息

常见硫化物矿物晶格中的金及粒径小于1000埃的分散金均称为不可见金,它们无法用矿相显微镜和扫描电镜测到。离子探针微量分析(次级离子质谱法)表明,12个矿床硫化物矿物颗粒中不可见金的含量为0.5至1000ppm之间。不同矿床,或一个矿床中不同矿石相间不可见金含量变化很大。最主要的载金矿物为毒砂和富砷黄铁矿。黄铁矿中金与砷含量呈正相关,表明种促进了金进入黄铁矿晶格。当两种或差别大的毒砂共生时,细粒毒砂更富含不可见金。磁黄铁矿、黄铜矿、斑铜矿、方铅矿和黝铜矿中不可见金的含量通常较低。

关键词：硫化物金富集黄铁矿

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