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The PARP-1 Inhibitor Olaparib Causes Retention of γ-H2AX Foci in <i>BRCA</i>1 Heterozygote Cells Following Exposure to Gamma Radiation

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j.urnal of Cancer Therapy 2013年第11期4卷 44-52页

作者： Emma C. Bourton Piers N. Plowman amanda j. harvey Sheba Adam Zahir Christopher N. Parris Brunel Institute of Cancer Genetics and Pharmacogenomics Division of Biosciences School of Health Sciences and Social Care Brunel University Uxbridge UK Department of Radiotherapy St Bartholomew’s Hospital West Smithfield London UK

A novel treatment for cancer patients with homozygous deletions of BRCA1 and BRCA2 is to use drugs that inhibit the enzyme poly(ADP-ribose) polymerase (PARP). Specific inhibition of PARP-1 can induce synthetic lethality in irradiated cancer cells while theoretically leaving normal tissue unaffected. We recently demonstrated in a cell survival assay that lymphoblastoid cells with mono-allelic mutations of BRCA1 were hypersensitive to gamma radiation in the presence of the PARP-1 inhibitor Olaparib compared to normal cells and mono-allelic BRCA2 cells. To determine if the enhanced radiation sensitivity was due to a persistence of DNA strand breaks, we performed γ-H2AX foci analysis in cells derived from two normal individuals, three heterozygous BRCA1 and three heterozygous BRCA2 cell lines. Cells were exposed to 2 Gy gamma radiation in the presence or absence of 5 μM Olaparib. Using immunofluorescence and imaging flow cytometry, foci were measured in untreated cells and at 0.5, 3, 5 and 24 hours post-irradiation. In all lymphoblastoid cells treated with 2 Gy gamma radiation, there was a predictable induction of DNA strand breaks, with a modest but significant retention of foci over 24 hours in irradiated cells treated with Olaparib (ANOVA P < 0.05). However, in mono-allelic BRCA1 cells, there was a failure to fully repair DNA double-strand breaks (DSB) in the presence of Olaparib, evidenced by a significant retention of foci at 24 hours’ post irradiation (t-Test P These data show that the cellular hypersensitivity of mono-allelic BRCA1 lymphoblastoid cells to gamma radiation in the presence of the Olaparib is due to the retention of DNA DSB. These data may indicate that patients with inherited mutations in the BRCA1 gene treated with radiotherapy and PARP-1 inhibitors may experience elevated radiation-associated normal tissue toxicity.

关键词： BRCA1 BRCA2 Heterozygote Radiosensitivity PARP Inhibitor Gamma-H2AX Imaging Flow Cytometry

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The PARP-1 Inhibitor Olaparib Causes Retention of γ-H2AX Foci in BRCA1 Heterozygote Cells Following Exposure to Gamma Radiation

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j.urnal of Cancer Therapy（癌症治疗） 2013年第11期

作者： Emma C. Bourton Piers N. Plowman amanda j. harvey Sheba Adam Zahir Christopher N. Parris

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SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C

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World j.urnal of Pediatrics 2024年第2期20卷 143-152页

作者： Andres F.Moreno Roj.s Emelia Bainto Helen harvey Adriana H.Tremoulet j.ne C.Burns Kirsten B.Dummer Department of Pediatrics Division of Pediatric CardiologyUniversity of California San Diegoand Rady Children’s Hospital3020 Children’s Way MC 5004San DiegoCA 92123USA Kawasaki Disease Research Center La JollaCAUSA Department of Pediatrics Division of Pediatric Critical CareUniversity of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA Department of Pediatrics University of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA

Background Recent infection with SARS‑CoV-2 in children has been associated with multisystem inflammatory syndrome in children(MIS-C).SARS‑CoV-2 has undergone different *** publications exist about specific variants and their correlation with the severity of *** This was a single-center,retrospective study including all patients admitted with MIS-C at Rady Children’s Hospital-San Diego between May 2020 and March *** epidemiologic data,including viral genomic information,were obtained from public ***,clinical presentation,laboratory values,and outcomes were obtained from electronic medical *** The analysis included 104 pediatric *** MIS-C waves were *** variants in San Diego during the first wave included clades 20A to *** the second wave,there were variants from clades 20A to C,20G,21C(Epsilon),20I(Alpha),and 20j.Gamma).The third wave had Delta strains(clades 21A,21I,and 21j.,and the fourth had Omicron variants(clades 21K,21L,and 22C).MIS-C presented with similar symptoms and laboratory findings across all *** patients were admitted to the pediatric intensive care unit(PICU)(74%)and required inotropic support(63%)during the second *** of the patients required mechanical circulatory support,and only two required invasive ventilatory *** was no *** The various strains of SARS-CoV-2 triggered MIS-C with differing severities,with the second wave having a more severe clinical *** the differences in disease severity across variants were due to changes in the virus or other factors remains unknown.

关键词： Complications COVID-19 MIS-C SARS-CoV-2 variants

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Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast cancer and hope for breast tumour kinase targeted therapy

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World j.urnal of Clinical Oncology 2014年第3期5卷 299-310页

作者： Haroon A Hussain amanda j.harvey Brunel Institute for Cancer Genetics and Pharmacogenomics Biosciences Brunel University (London)

There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase(Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metas-tasis and its potential as a therapeutic target in breast cancer.

关键词： Breast tumour kinase Protein tyrosine kinase 6 Breast neoplasms Targeted molecular therapy Intracellular signaling peptides and proteins Protein kinase inhibitors

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Roles of manganese in photosystem II dynamics to irradiations and temperatures

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Frontiers in Biology 2013年第3期8卷 312-322页

作者： Xuej.ng HOU harvey j. M. HOU Department of Chemistry and Biochemistry University of Massachusetts Dartmouth North Dartmouth MA 02747 USA Department of Physical Sciences Alabama State University Montgomery AL 36104 USA

The most amazing chemistry is the light-driven water splitting reaction occurred in the oxygen-evolving complex of phototsystem II in higher plants, green algae, and cyanobacteria. Mn, in the form of Mn4CaOs cluster in photosystem II, is responsible for the catalytic water splitting reaction as well as plays roles in photosystem II dynamics to irradiation and temperatures. Manganese hypothesis of UV-initiated photoinhibition as a direct target is established, and thermal inactivation of photosystem II involves the valence and structural changes of manganese. Recent progresses in understanding the roles of manganese in photoinhibition especially under UV light and in thermal inactivation including elevated temperatures using synthetic models and native PS II complexes are summarized and evaluated. Potential problems and possible solutions are discussed and presented.

关键词： photosynthesis manganese photosystem II irradiation temperature stress

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Structural and Mechanistic Aspects of Mn-oxo and Co-based Compounds in Water Oxidation Catalysis and Potential Applications in Solar Fuel Production

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j.urnal of Integrative Plant Biology 2010年第8期52卷 704-711页

作者： harvey j.M.Hou Department of Chemistry and Biochemistry University of Massachusetts Dartmouth North Dartmouth

To address the issues of energy crisis and global warming, novel renewable carbon-free or carbon-neutral energy sources must be identified and developed. A deeper understanding of photosynthesis is the key to provide a solid foundation to facilitate this transformation. To mimic the water oxidation of photosystem II oxygen evolving complex, Mn-oxo complexes and Co-phosphate catalytic material were discovered in solar energy storage. Building on these discoveries, recent advances in solar energy conversion showed a compelling working principle by combing the active Mn-oxo and Co-based catalysts in water splitting with semiconductor heteronanostructures for effective solar energy harnessing. In this review the appealing systems including Mn-oxo tetramer/Nafion, Mn-oxo dimer/TiO2, Mn-oxo oligomer/WO3, Co-Pi/Fe2O3, and Co-Pi/ZnO are summarized and discussed. These accomplishments offer a promising framework and have a profound impact in the field of solar fuel production.

关键词： Mn Structural and Mechanistic Aspects of Mn-oxo and Co-based Compounds in Water Oxidation Catalysis and Potential Applications in Solar Fuel Production II Figure

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A route to enhanced performance for the petawatt beamlines of the Orion laser facility

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High Power Laser Science and Engineering 2022年第3期10卷 11-18页

作者： E.j.harvey AWE AldermastonReadingRG74PRUK

The Orion laser facility at AWE provides multiple beams to target delivering synchronized pulses at both nanosecond and sub-picosecond *** the latter,the peak power approaches the petawatt *** paper presents a conceptual design for potential development of these *** would deliver a significant enhancement of performance at the fundamental *** addition,a new approach is described for the management of frequency conversion at high intensity,which may allow significantly enhanced performance at the second harmonic also.

关键词： chirped pulse amplification frequency doubling temporal contrast

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Methane production from Sargassum muticum:effects of seasonality and of freshwater washes

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能源与人工环境(英文) 2021年第3期2卷 235-242页

作者： Supattra Maneein j.hn j.Milledge Patricia j.harvey Birthe V.Nielsen Algae Biotechnology University of GreenwichChatham MaritimeME44TBUK

Biogas production from Sargassum muticum,an invasive seaweed species to Europe,is hampered by low methane(CH_(4))yields during anaerobic digestion(AD),but causes are *** research is the first to demonstrate the impact of extensive freshwater washing of spring-and summer-harvested *** on the CH_(4)production rates and the biochemical methane potential(BMP).The findings reveal that the rate profile of CH_(4)production is affected by extensively washing the seaweed and is dependent on ***-harvested *** had higher initial CH_(4)production rates compared to summer-harvested *** spring-harvested ***,the initial rate of CH_(4)production was lowered by extensive *** contrast,extensively washed summer-harvested *** had a higher degradation rate and CH_(4)production rate relative to its non-extensively washed *** highest CH_(4)potentials accumulated by the treated and non-treated *** are,however,statistically similar and not influenced by seasonality or extensive washing(p>0.05).Potential causes for differences in the rate of CH_(4)production between summer-and spring-harvested *** are *** differences in CH_(4)production from treated summer-and spring-harvested *** acts as a stepping stone to understanding the causes for low CH_(4)yields,which could allow for further enhancements in CH_(4)production from ***.

关键词： Seaweed Biogas Biofuels Seasonality Washing

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Resolution beyond classical limits with spatial frequency heterodyning

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Chinese Optics Letters 2006年第3期4卷 148-151页

作者： A.Mudassar A.R.harvey A.H.Greenaway j.D.C.j.nes School of Engineering and Physical Sciences Heriot-Watt UniversityUK

A technique for coherent imaging based on spatial frequency heterodyning is described. Three images corresponding to three physical measurements are recorded. For the first measurement, a scene is simply illuminated with a coherent beam and for measurements 2 and 3, the scene is proj.cted with cosine and sine fringes, respectively. Due to spatial frequency heterodyning, upper and lower side hand information falls in the pass band of the imager. These bands are separated and correct phases and positions are assigned to these bands in the spatial frequency domain. An extension of bandwidth is achieved in the frequency domain and the inverse frequency domain data then give a high resolution coherent image.

关键词： Resolution beyond classical limits with spatial frequency heterodyning

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环氧沥青混合料疲劳衰变特性试验

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中国公路学报 2013年第2期26卷 20-25页

作者：罗桑钱振东 harvey j 东南大学智能运输系统研究中心江苏南京210096 加利福尼亚大学伯克利分校路面研究中心加利福尼亚伯克利ca94804

为获取钢桥面铺装环氧沥青混合料的疲劳衰变特性,首先基于正交异性桥面板-铺装层组成的复合结构模型,计算出标准胎压、超载50%以及超载100%胎压作用下铺装层的最大拉应变,作为疲劳试验应变水平的选取标准;然后,采用小梁四点弯曲疲劳试验... 详细信息

为获取钢桥面铺装环氧沥青混合料的疲劳衰变特性,首先基于正交异性桥面板-铺装层组成的复合结构模型,计算出标准胎压、超载50%以及超载100%胎压作用下铺装层的最大拉应变,作为疲劳试验应变水平的选取标准;然后,采用小梁四点弯曲疲劳试验对3组不同温度和不同应变条件下的环氧沥青混合料疲劳性能进行测试;最后,利用威布尔公式对不同温度与应变条件下的环氧沥青混合料疲劳寿命与疲劳裂纹扩展时的作用次数进行预测。结果表明:环氧沥青混合料初始模量大小仅与温度相关,与应变水平无关;在10℃和20℃时,1.38 MPa以下胎压以及30℃时0.7MPa胎压作用500万次均不发生疲劳破坏;30℃时,1.1 MPa和1.38 MPa胎压分别作用66 833次和35 480次出现疲劳损坏现象;相同应变作用下,试验温度越低,小梁疲劳破坏越快;环氧沥青混合料疲劳曲线可明显分为试验设备稳定、疲劳裂缝启裂、疲劳裂缝扩展3个阶段。研究结果可为环氧沥青混合料铺装疲劳寿命预估以及预防性养护提供理论依据。

关键词：道路工程环氧沥青混合料四点弯曲疲劳试验疲劳衰变威布尔公式

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