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African Americans,hypertension and the renin angiotensin system

World Journal of Cardiology 2014年第9期6卷 878-889页

作者： sandra f williams Susanne B Nicholas Nosratola D Vaziri Keith C Norris Department of Endocrinology Cleveland Clinic Department of Clinical Biomedical Science Charles E Schmidt College of MedicineFlorida Atlantic University Division of Nephrology and Division of Endocrinology Diabetes and HypertensionDepartment of Medicine David Geffen School of MedicineUniversity of California Division of Nephrology and Hypertension Departments of MedicinePhysiology and BiophysicsUniversity of California Division of General Internal Medicine and Health Services Research Los AngelesCA 90024United States Department of Medicine David Geffen School of Medicine University of California

African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system(RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans.

关键词： African American Blood pressure Ethnicity Hypertension Renin Angiotensin

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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.williams Department of Biology University of PisaPisaItaly Department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon C.Smith Jessica L.williams Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

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4-Amino-1,8-naphthalimide based fluorescent photoinduced electron transfer (PET) pH sensors as liposomal cellular imaging agents: The effect of substituent patterns on PET directional quenching

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frontiers of Chemical Science and Engineering 2020年第1期14卷 61-75页

作者： Miguel Martinez-Calvo sandra A.Bright Emma B.Veale Adam f.Henwood D.Clive williams Thorfinnur Gunnlaugsson School of Chemistry and Trinity Biomedical Sciences Institute(TBSI) Trinity College DublinThe University of DublinDublin 2Ireland School of Biochemistry and Immunology and Trinity Biomedical Sciences Institute(TBSI) Trinity College DublinThe University of DublinDublin 2Ireland Centro Singular de Investigacion en Quimica Bioloxica e Materiais Moleculares(CIQUS)and Departamento de Quimica Organica Universidade de Santiago de Compostela Rua Jenaro de la Fuente s/n15782Santiago de CompostelaSpain

four new fluorescent sensors(1-4)based on the 4-amino-1,8-naphthalimide fluorophores(Naps)have been synthesized based on the classical fluorophore-spacer-receptor *** four compounds all gave rise to emission bands centred at ca.535 nm,which were found to be highly pH dependent,the emission being‘switched on’in acidic media,while being quenched due to PET from the amino moieties to the excited state of the Nap at more alkaline *** luminescent pH dependence for these probes was found to be highly dependent on the substitution on the imide site,as well as the polyamine chain attached to the position 4-amino *** the case of sensor 2 the presence of the 4-amino-aniline dominated the pH dependent ***,at higher pH,PET quenching was also found to occur from the polyamine ***,2 is better described as a receptor1-spacer1-fluorophore-spacer2-receptor2 system,where the dominant PET process is due to(normally less favourable)‘directional’PET quenching from the 4-amino-aniline unit to the Nap *** trends and pH fluorescence dependences were also seen for 3 and *** compounds were also tested for their imaging potential and toxicity against HeLa cells(using DRAQ5 as nuclear stain which does now show pH dependent changes in acidic and neutral pH)and the results demonstrated that these compounds have reduced cellular viability at moderately high concentrations(with IC50 values between ca.8-30μmol?L^?1),but were found to be suitable for intracellular pH determination at 1μmol?L^?1 concentrations,where no real toxicity was *** allowed us to employ these as lysosomal probes at sub-toxic concentrations,where the Nap based emission was found to be pH depended,mirroring that seen in aqueous solution for 1-4,with the main fluorescence changes occurring within acidic to neutral pH.

关键词： sensors pH photoinduced electron transfer cellular imaging confocal microscopy

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Anosov and expanding attractors

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Science China Mathematics 2020年第9期63卷 1929-1934页

作者： Robert f.williams Department of Mathematics University of Texas at AustinAustinTX 78705USA Institute for Advanced Study PrincetonNJ 08540USA

An earlier conjecture is settled with an immersion of a 2-dimensional branched *** obstructions in linear algebra and tiling theory are studied rst.

关键词： Anosov expanding attractor Cantor set ber bundle

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Biocompatibility pathways and mechanisms for bioactive materials:The bioactivity zone

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Bioactive Materials 2022年第4期7卷 306-322页

作者： David f.williams Wake forest Institute of Regenerative Medicine 391 Technology Way.Winston-SalemNorth Carolina27101USA

This essay analyzes the scientific evidence that forms the basis of bioactive materials,covering the fundamental understanding of bioactivity phenomena and correlation with the mechanisms of biocompatibility of *** is a detailed assessment of performance in areas such as bone-induction,cell adhesion,immunomodulation,thrombogenicity and antimicrobial *** is the modulation of biological activity by characteristics of the interfacial region that incorporates the material surface and the immediate local host *** the term‘bioactive material’is widely used and has a well understood general meaning,it would be useful now to concentrate on this interfacial region,considered as‘the bioactivity zone’.Bioactivity phenomena are either due to topographical/micromechanical characteristics,or to biologically active species that are presented in the bioactivity *** of topographical/micromechanical effects are the modulation of the osteoblast-osteoclast balance,nanotopographical regulation of cell adhesion,and bactericidal *** of bioactivity by biologically active species include their influence,especially of metal ions,on signaling pathways in bone formation,the role of cell adhesion molecules and bioactive peptides in cell attachment,macrophage polarization by immunoregulatory molecules and antimicrobial *** much experimental data exists to demonstrate the potential of such phenomena,there are considerable barriers to their effective clinical *** essay shows that there is solid scientific evidence of the existence of bioactivity mechanisms that are associated with some types of biomaterials,especially when the material is modified in a manner designed to specifically induce that activity.

关键词： Bioactivity Host response Biomaterial Medical technology Cell signaling

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COMPUTATION Of STRESS INTENSITY fACTORS BY THE SUB-REGION MIXED fINITE ELEMENT METHOD Of LINES

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Acta Mechanica Solida Sinica 2007年第2期20卷 149-162页

作者： Yuan Si Xu Yongjun williams f W Department of Civil Engineering Tsinghua University Beijing 100084 China Institute of Mechanics Chinese Academy of Sciences Beijing 100080 China Structural Engineering Division Cardiff University Cardiff CF2 3TB UK

Based on the sub-region generalized variationM principle, a sub-region mixed version of the newly-developed semi-analytical ＇finite element method of lines＇（fEMOL） is proposed in this paper for accurate and efficient computation of stress intensity factors （SIfs） of two-dimensional notches/cracks. The circular regions surrounding notch/crack tips are taken as the complementary energy region in which a number of leading terms of singular solutions for stresses are used, with the sought SIfs being among the unknown coefficients. The rest of the arbitrary domain is taken as the potential energy region in which fEMOL is applied to obtain approximate displacements. A mixed system of ordinary differential equations （ODEs） and algebraic equations is derived via the sub-region generalized variational principle. A singularity removal technique that eliminates the stress parameters from the mixed equation system eventually yields a standard fEMOL ODE system, the solution of which is no longer singular and is simply and efficiently obtained using a standard general-purpose ODE solver. A number of numerical examples, including bi-material notches/cracks in anti-plane and plane elasticity, are given to show the generally excellent performance of the proposed method.

关键词： stress intensity factors finite element method of lines sub-region generalized variational principle ordinary differential equation solver

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ORIGIN Of CARBONATE MATERIALS IN THE NORTHERN BASIN Of LAKE BAIKAL AND ITS RELATIONSHIP TO HOLOCENE PALEOCLIMATE

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Chinese Journal of Oceanology and Limnology 1993年第1期11卷 57-69页

作者：邱林青 f.williams Dept of Geological Sciences University of South Carolina Columbia SC 29208 U.S.A

fine-grained disseminated carbonate was found in Holocene sediments in a core taken from the northern basin of Lake Baikal. The core had two distinct facies. a terrigenous blue-clay overlain by a diatomaceous silt. Oxygen and carbon stable isotope analyses, combined with SEM , X-ray diffraction and .palynology, show that the carbonate in the blue-clay layer is pedogenic in origin, rather than biogenic or authigenic . The S C values in the blue clay suggest that the carbonate is derived from a single source , while the carbonate in the diatom-rich layer might be transported by winds from different sources. On the assumption that the carbonate was formed during the post-glacial age and was transported primarily by river runoff, the 18O isotopic values suggest that the annual temperature in the northern Baikal drainage area was about 3℃ warmer during the middle Holocene (8500-7000 a, B. P.) than during the early Holocene (11 000-8 500a, B.P.) when the blue clay was being deposited . This interpretation

关键词： Lake Baikal carbonate oxygen isotopes carbon isotopes paleoclimate

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MODAL SYNTHESIS METHOD fOR NORM COMPUTATION Of H_∞ DECENTRALIZED CONTROL SYSTEMS (II)

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Applied Mathematics and Mechanics(English Edition) 2004年第2期25卷 123-134页

作者：钟万勰吴志刚高强梁以德 f.W.williams State Key Laboratory of Structural Analysis for Industrial Equipment Dalian University of Technology Department of Building and Construction City University of Hong Kong

When using H_∞ techniques to design decentralized controllers for large systems, the whole system is divided into subsystems, which are analysed using H_∞ control theory before being recombined. An analogy was established with substructural analysis in structural mechanics, in which H_∞ decentralized control theory corresponds to substructural modal synthesis theory so that the optimal H_∞ norm of the whole system corresponds to the fundamental vibration frequency of the whole structure. Hence, modal synthesis methodology and the extended Wittrick_williams algorithm were transplanted from structural mechanics to compute the optimal H_∞ norm of the control system. The orthogonality and the expansion theorem of eigenfunctions of the subsystems H_∞ control are presented in part (Ⅰ) of the paper. The modal synthesis method for computation of the optimal H_∞ norm of decentralized control systems and numerical examples are presented in part (Ⅱ).

关键词： H_∞ control decentralized control modal synthesis generalized Rayleigh quotient extended Wittrick-williams algorithm

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Hubble telescope 30 years in orbit:personal reflections

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Research in Astronomy and Astrophysics 2020年第4期20卷 1-6页

作者： Robert williams Space Telescope Science Institute&University of California/Santa Cruz CA 95064USA

With an initial requirement to make observations a minimum of 5–10 years,Hubble Space Telescope(HST)has continued to operate well for 30 *** has relied upon five servicing missions to repair and replace essential *** the final Space Shuttle mission 10 years ago,it has avoided major breaks in its operation,with the only serious effects of aging in space being a progressive deterioration in the performance of the gyroscopes and sensitivity of the instrument detectors.A number of factors were important in making HST a scientific ***-breaking discoveries have been made with HST-the most important being the discovery of cosmic *** HST operation ceases,future observations in space should be assured with successful operation of major missions now planned by NASA,ESA,and the Chinese and Japanese Space Agencies.

关键词： HST cosmic acceleration Hubble constant supernovae

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