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Universal adaptive optics for microscopy through embedded neural network control

Light(Science & Applications) 2023年第12期12卷 2597-2609页

作者： Qi Hu martin Hailstone Jingyu Wang matthew Wincott Danail Stoychev Huriye Atilgan Dalia Gala Tai Chaiamarit Richard m.Parton Jacopo Antonello Adam m.Packer Ilan Davis martin J.Booth Department of Engineering Science University of OxfordOxfordUK Department of Biochemistry University of OxfordOxfordUK Department of Physiology Anatomyand GeneticsUniversity of OxfordOxfordUK

The resolution and contrast of microscope imaging is often affected by aberrations introduced by imperfect optical systems and inhomogeneous refractive structures in *** optics(AO)compensates these aberrations and restores diffraction limited performance.A wide range of AO solutions have been introduced,often tailored to a specific microscope type or *** now,a universal AO solution-one that can be readily transferred between microscope modalities-has not been *** propose versatile and fast aberration correction using a physics-based machine learning assisted wavefront-sensorless AO control(mLAO)*** previous mL methods,we used a specially constructed neural network(NN)architecture,designed using physical understanding of the general microscope image formation,that was embedded in the control loop of different microscope *** approach means that not only is the resulting NN orders of magnitude simpler than previous NN methods,but the concept is translatable across microscope *** demonstrated the method on a two-photon,a three-photon and a widefield three-dimensional(3D)structured illumination *** showed that the method outperformed commonly-used modal-based sensorless AO *** also showed that our mL-based method was robust in a range of challenging imaging conditions,such as 3D sample structures,specimen motion,low signal to noise ratio and activity-induced fluorescence ***,as the bespoke architecture encapsulated physical understanding of the imaging process,the internal NN configuration was no-longer a"black box",but provided physical insights on internal workings,which could influence future designs.

关键词： optics illumination correction

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The role of mT1-mmP in the progression and metastasis of osteosarcoma

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Journal of Cancer metastasis and Treatment 2022年第1期8卷 564-578页

作者： Hannah L.m.Spencer Steven D.Shnyder Paul m.Loadman Robert A.Falconer Institute of Cancer Therapeutics Faculty of Life SciencesUniversity of BradfordBradford BD71DPUK

The dysregulation of membrane-type 1 matrix metalloproteinase(mT1-mmP)has been extensively studied in numerous cancer types,and plays key roles in angiogenesis,cancer progression,and ***1-mmP is a predictor of poor prognosis in osteosarcoma(OS),yet the molecular mechanisms of disease progression are *** review provides a summary of the literature relating to the gene and protein expression of mT1-mmP(mmP-14)in OS clinical samples,evaluates the expression in cell lines and experimental models,and analyses its potential role in the progression and metastasis of *** addition,the therapeutic potential of mT1-mmP as a drug target has been *** to the biological complexity of mmPs,inhibition has proven to be ***,exploiting the expression and proteolytic capacity of mT1-mmP could open new avenues in the search for novel,safer and selective drugs for use in OS.

关键词： matrix metalloproteinase membrane-type osteosarcoma mT1-mmP

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Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encepha-lopathy

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World Journal of Gastroenterology 2006年第19期12卷 2969-2978页

作者： VP Bob Graver m Alex Dresner Daniel m Forton Serena Counsell David J Larkman Nayna Patel Howard C Thomas Simon D Taylor-Robinson Hepatology Section Division of medicine A St Mary's CampusFaculty of MedicineImperial College LondonSouth Wharf StreetLondon W2 1NYUnited Kingdom Imaging Sciences DepartmentClinical Sciences DivisionFaculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W12 0HSUnited Kingdom Imaging Sciences Department Clinical Sciences Division Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W12 0HSUnited Kingdom Hepatology Section Division of medicine A St Mary's CampusFaculty of MedicineImperial College LondonSouth Wharf StreetLondon W2 1NYUnited Kingdom

Hepatic encephalopathy （HE） is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging （mRI） techniques provide a non-invasive means of assessment of changes in brain volume （coregistered mRI） and impaired brain function （fmRI）, while proton magnetic resonance spectroscopy （^1H mRS） detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. mRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since mR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.

关键词： Hepatic encephalopathy magnetic resonance imaging magnetic resonance spectroscopy Diffusion weighted imaging Arterial spin labeling Functional mRI

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Using compositional data analysis to explore accumulation of sedentary behavior,physical activity and youth health

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Journal of Sport and Health Science 2022年第2期11卷 234-243页

作者： Simone J.J.m.Verswijveren Karen E.Lamb Josep A.martín-Fernández Elisabeth Winkler Rebecca m.Leech Anna Timperio Jo Salmon Robin m.Daly Ester Cerin David W.Dunstan Rohan m.Telford Richard D.Telford Lisa S.Olive Nicola D.Ridgers Institute for Physical Activity and Nutrition School of Exercise and Nutrition SciencesDeakin UniversityGeelongVIC 3216Australia melbourne School of Population and Global Health University of MelbourneParkvilleVIC 3053Australia Department of Computer Science Applied Mathematics and StatisticsUniversity of GironaGirona 17003Spain School of Public Health University of QueenslandHerstonQLD 4006Australia mary macKillop Institute for Health Research Australian Catholic UniversityFitzroyVIC 3065Australia School of Public Health University of Hong KongHong KongChina Baker Heart and Diabetes Institute MelbourneVIC 3004Australia Research Institute for Sport and Exercise University of CanberraBruceACT 2617Australia School of Psychology Deakin UniversityBurwoodVIC 3125Australia ImPACT Research Institute Deakin UniversityBurwoodVIC 3125Australia ANU medical School Australian National UniversityGarranACT 2605Australia

Purpose:The study aimed to describe youth time-use compositions,focusing on time spent in shorter and longer bouts of sedentary behavior and physical activity(PA),and to examine associations of these time-use compositions with cardiometabolic ***:Accelerometer and cardiometabolic biomarker data from 2 Australian studies involving youths 7-13 years old were pooled(complete cases with accelerometry and adiposity marker data,n=782).A 9-component time-use composition was formed using compositional data analysis:time in shorter and longer bouts of sedentary behavior;time in shorter and longer bouts of light-,moderate-,or vigorous-intensity PA;and"other time"(i.e.,non-wear/sleep).Shorter and longer bouts of sedentary time were defined asmin and>5 min,*** bouts of light-,moderate-,and vigorous-intensity PA were defined asmin;longer bouts were defined as≥1 *** models examined associations between overall time-use composition and cardiometabolic ***,associations were derived between ratios of longer activity patterns relative to shorter activity patterns,and of each intensity level relative to the other intensity levels and"other time",and cardiometabolic ***:Confounder-adjusted models showed that the overall time-use composition was associated with adiposity,blood pressure,lipids,and the summary ***,more time in longer bouts of light-intensity PA relative to shorter bouts of light-intensity PA was significantly associated with greater body mass index z-score(zBmI)(β=1.79;SE=0.68)and waist circumference(β=18.35,SE=4.78).When each activity intensity was considered relative to all higher intensities and"other time",more time in light-and vigorous-intensity PA,and less time in sedentary behavior and moderate-intensity PA,were associated with lower waist ***:Accumulating PA,particularly light-intensity PA,in frequent short bursts may be more beneficial for limiting adi

关键词： Accumulation patterns Cardiometabolic health Children Compositional data analysis Time-use

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Glutaminase inhibition in renal cell carcinoma therapy

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Cancer Drug Resistance 2019年第2期2卷 356-364页

作者： Aleksandra m.Raczka Paul A.Reynolds School of medicine University of St AndrewsSt Andrews KY169TFUK Biomedical Sciences Research Complex University of St AndrewsSt AndrewsUK.

Receptor tyrosine kinase inhibitors have been a standard first-line therapy for renal cell carcinoma(RCC)for over a *** they stabilize the disease,they are unable to remove all tumor cells,leading to ***,both intrinsic and acquired resistance to therapy are a significant health *** order to overcome resistance,several combination therapies have been recently approved by the *** approach takes advantage of altered metabolism in tumor cells,which switch to alternative metabolic pathways to sustain their rapid growth and ***-839 is a small molecule inhibitor of kidney type glutaminase(GLS).GLS is often upregulated in glutamine addicted cancers,enhancing glutamine metabolism for the production of energy and the biosynthesis of various cellular building ***-839 is currently in clinical trials for several tumors,including clear cell(cc)RCC,both as monotherapy and in combination with the approved therapeutic agents everolimus,cabozantinib and *** results of Phase 1/2 clinical trials look promising,especially for CB-839 plus cabozantinib,and all combinations seem to be well ***,cancer cells can activate compensatory pathways to overcome glutaminolysis ***,genetic and metabolomic studies are crucial for the successful implementation of CB-839 alone or in combination in subgroups of ccRCC patients.

关键词： Glutamine addiction renal cell carcinoma combination therapy metabolism

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management of metabolic-associated fatty liver disease: The diabetology perspective

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World Journal of Gastroenterology 2023年第1期29卷 126-143页

作者： mohammad Sadiq Jeeyavudeen Shahanas K A Khan Sherouk Fouda Joseph m Pappachan Department of Endocrinology and metabolism University Hospitals of EdinburghEdinburgh EH42XUUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom School of Health and Biomedical Sciences RMIT UniversityMelbourneVIC 3046Australia Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology University of ManchesterManchester M139PLUnited Kingdom

The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(mAFLD)and type 2 diabetes mellitus(T2Dm).Because of the similarity in pathobiology shared between T2Dm and mAFLD,both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual *** fact,awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and *** of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and,when necessary,liaising with dieticians and *** comprehensive review is to compile the current evidence from a diabetologist's perspective on mAFLD and T2Dm and to suggest optimal management strategies.

关键词： metabolic syndrome metabolic-associated fatty liver disease Type 2 diabetes mellitus Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Diabetology perspective Obesity

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Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now

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World Journal of Diabetes 2024年第5期15卷 797-809页

作者： Joseph m Pappachan Cornelius James Fernandez Ambika P Ashraf Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Division of Pediatric Endocrinology and Diabetes Department of PediatricsUniversity of Alabama at BirminghamBirminghamAL 35233United States

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic *** has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and *** looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most *** there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this *** article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity.

关键词： Childhood obesity Diabesity Type 2 diabetes mellitus Adolescence Cardiovascular disease Pharmacotherapy

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Individualized diabetes care:Lessons from the real-world experience

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World Journal of Clinical Cases 2023年第13期11卷 2890-2902页

作者： Xiao Ying Khor Joseph m Pappachan mohammad Sadiq Jeeyavudeen Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29UTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology and metabolism University Hospitals of EdinburghEdinburgh EH164SAUnited Kingdom

Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles,and medication doses to optimise glycaemic *** clinical guidelines on the management of diabetes mellitus(Dm)provide only broad principles on diabetes care,and the blind follow-up of such principles without a proper review and consideration of patient characteristics often results in inadequate glycaemic control and diabetes complications ***,a proper understanding of the pathobiology,clinical situation,and comorbidities of the individual case is of paramount importance to tailoring the most appropriate management strategy in real-world diabetes *** the aid of five unique cases of Dm[(1)medically managed type 2 diabetes mellitus(T2Dm)with severe obesity;(2)management of T2Dm with unreliable glycated haemoglobin(HbA1c);(3)Obesity in a patient with type 1 diabetes mellitus(T1Dm);and(4)Late diagnosis and subsequent management of monogenic diabetes and *** worsening of well-controlled T2Dm)]we elaborate on the importance of individualised diabetes care and the practicalities in these *** review also provides an evidence update on the management of different forms of Dm to guide physicians in optimising the care of their patients in day-to-day clinical practice.

关键词： Individualised diabetes care Diabesity Double diabetes monogenic diabetes Diabetes in pancreatic cancer

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An Optimized Novel trust-Based Security mechanism Using Elephant Herd Optimization

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Computer Systems Science & Engineering 2023年第3期44卷 2489-2500页

作者： Saranya Veerapaulraj m.Karthikeyan S.Sasipriya A.S.Shanthi Tamilnadu College of Engineering CoimbatoreIndia Krishna College of Engineering CoimbatoreIndia

Routing strategies and security issues are the greatest challenges in Wireless Sensor Network(WSN).Cluster-based routing Low Energy adaptive Clustering Hierarchy(LEACH)decreases power consumption and increases net-work lifetime *** WSN is a challenging issue faced by *** systems are very helpful in detecting interfering nodes in *** have successfully applied Nature-inspired metaheuristics Optimization Algorithms as a decision-making factor to derive an improved and effective solution for a real-time optimization *** metaheuristic Elephant Herding Optimizations(EHO)algorithm is formulated based on ele-phant herding in their *** considers two herding behaviors to solve and enhance optimization *** on Elephant Herd Optimization,a trust-based security method is built in this *** proposed routing selects routes to destination based on the trust values,thus,finding optimal secure routes for transmitting *** results have demonstrated the effectiveness of the proposed EHO based *** Average Packet Loss Rate of the proposed trust Elephant Herd Optimization performs better by 35.42%,by 1.45%,and by 31.94%than LEACH,Elephant Herd Optimization,and trust LEACH,respec-tively at Number of Nodes *** the proposed routing is efficient in selecting secure routes,the average packet loss rate is significantly reduced,improving the network’s *** is also observed that the lifetime of the network is enhanced with the proposed trust Elephant Herd Optimization.

关键词： Wireless sensor network low energy adaptive clustering hierarchy trust systems elephant herding optimizations algorithm trust-based elephant herd optimization

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major,trace element and Sr-Nd isotope evidence for a sublithospheric mantle source for the Umkondo large igneous province

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Geoscience Frontiers 2024年第1期15卷 263-285页

作者： Ben Hayes Lewis D.Ashwal Khulekani B.Khumalo Linda m.Iaccheri School of Geosciences University of the WitwatersrandJohannesburg2050South Africa

The mesoproterozoic(1.11 Ga)Umkondo large igneous province(LIP)in southern Africa and Antarctica was emplaced in<5 myr and is dominated by low-Ti tholeiitic doleritic-gabbroic *** is of particular interest because it ... 详细信息

The mesoproterozoic(1.11 Ga)Umkondo large igneous province(LIP)in southern Africa and Antarctica was emplaced inmyr and is dominated by low-Ti tholeiitic doleritic-gabbroic *** is of particular interest because it is the least studied LIP in southern Africa with both sublithospheric and lithospheric mantle sources proposed and it coincides with the early assembly of Rodinia,so it has importance in understanding the nature of magmatism and tectonics in and around the Kalahari craton during the *** this study,we compiled a large database of existing(~750)and new(~100)major and trace element data for the Umkondo province,as well as 42 new Sr-Nd isotopic measurements,to provide constraints on its magma sources and geochemical *** element compositional variations in the low-Ti tholeiites are explained by low-pressure(1 kbar)three-phase fractional crystallisation(olivine,clinopyroxene and plagioclase)of a parent magma with~10 wt.%mgO in oxidising conditions(QFm+1).Inverse models show that the low-Ti tholeiitic magmas were derived as residual melts after the crystallization of 12%-33%olivine from primary komatiitic-basaltic magmas(up to~20 wt.%mgO)in equilibrium with mantle olivine(Fo90).Low Sm/Yb and TiO2/Yb-Nb/Yb indicate that the primary magmas were derived by 2%-20%shallow(40-50 km)partial melting of spinel *** Sm/Yb is restricted to dyke swarms and may imply limited magma production from deeper(up to~70 km)garnet lherzolite-like *** low-Ti tholeiites of the Umkondo province are enriched in large ion lithophile elements(Rb-Sr-Cs-K)and depleted in high-field strength elements(Zr-Hf-Nb-Ta),indicating the involvement of crustal material and/or the subcontinental lithospheric *** is supported by covariations in Th/Nb,Nb/Yb,Nb/La and Ce/Sm with generally negativeΔ***-Nd isotopes lend support to the notion that the Umkondo magmas were derived from depleted and/or enriched sublithospheric mantle sources and subs

关键词： Umkondo large igneous province Low-Ti magma Continental tholeiites Sublithospheric mantle sources Kalahari craton Rodinia

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