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Radiotherapy and the cellular DNA damage response: current and future perspectives on head and neck cancer treatment

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Cancer Drug Resistance 2020年第4期3卷 775-790页

作者： Maria Rita Fabbrizi Jason l.parsons Cancer Research Centre Department of Molecular and Clinical Cancer MedicineUniversity of LiverpoolLiverpool L39TAUnited Kingdom Clatterbridge Cancer Centre NHS Foundation Trust Clatterbridge RoadBebington CH634JYUnited Kingdom

Incidences of head and neck squamous cell carcinoma(HNSCC)have been on the rise in the last few decades,with a significant risk factor being human papillomavirus(HPV)type-16/18 infection,particularly in the development of oropharyngeal ***(RT)is an important treatment modality for HNSCC,where it promotes extensive cellular DNA damage leading to the therapeutic *** has been well-established that HPV-positive HNSCC display better response rates and improved survival following RT compared to HPV-negative *** differential radiosensitivity has been largely associated with altered cellular DNA damage response mechanisms in HPV-positive HNSCC,and particularly with the signaling and repair of DNA double strand ***,other factors,particularly hypoxia present within the solid cancer,have a major impact on relative ***,recent approaches aimed at enhancing the radiosensitivity of HNSCC have largely centered on targeting key proteins involved in DNA repair,DNA damage checkpoint activation,and hypoxia *** studies have utilised in vitro and in vivo models of HPV-positive and HPV-negative HNSCC and examined the impact of specific inhibitors against the targets in combination with radiation in suppressing HNSCC cell growth and ***,accumulating evidence has shown that targeting enzymes including poly(ADP-ribose)polymerase,ataxia telangiectasia and Rad-3 related,DNA-dependent protein kinase catalytic subunit,and checkpoint kinase 1 can radiosensitise HNSCC cells which should be taken forward in further preclinical studies,with the goal of optimizing the future effective RT treatment of HNSCC.

关键词： DNA damage DNA repair head and neck cancer ionising radiation proton beam therapy radiobiology radiotherapy

A systematic review of patient reported outcome measures (PROMs) and quality of life reporting in patients undergoing laparoscopic cholecystectomy

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 228-245页

作者： Prita Daliya Elizabeth H.Gemmill Dileep N.lobo Simon l.parsons Gastrointestinal Surgery Nottingham Digestive Diseases Centre and National Institute for Health Research(NIHR)Nottingham Biomedical Research CentreNottingham University Hospitals NHS Trust and University of NottinghamQueen’s Medical CentreNottingham NG72UHUK Department of General Surgery Sherwood Forest Hospitals NHS TrustKing’s Mill HospitalSutton-in-Ashfield NG174JLUK MRC/ARUK Centre for Musculoskeletal Ageing Research School of Life SciencesUniversity of NottinghamQueen’s Medical CentreNottingham NG72UKUK Trent Oesophago-Gastric Unit City Hospital CampusNottingham University Hospitals NHS TrustNottingham NG51PBUK

Patient reported outcome measures(PROMs)provide a valuable means of measuring outcomes subjectively from a patient's perspective,facilitating the assessment of service quality across healthcare providers,and assisting patients and clinicians in shared decision *** primary aim of this systematic review was to critically appraise all historic studies evaluating patient reported quality of life,in adult patients undergoing laparoscopic cholecystectomy for symptomatic *** secondary aim was to perform a quality assessment of cholecystectomy-specific PROM-validation studies.A literature review was performed in PubMed,Google ScholarTM,the Cochrane library,Medline,CINAHl,EMBASE and PsychINFO databases up to September *** characteristics,PROM-specific details and a bias assessment were summarised for non-validation studies.A COnsensus-based Standards for the selection of health Measurement INstruments(COSMIN)analysis was performed to assess the methodological quality of identified PROM-validation *** one studies were found to evaluate health-related quality of life(HRQol)after laparoscopic *** 94.1%of these studies included PROMs as a primary outcome measure,level 1 evidence through randomised controlled trials(RCTs).There was significant variation in the selection and reporting of PROMs,with no studies declaring patient involvement in PROM selection,and 88.2%of studies failing to document the management of missing data points,or non-returned surveys(33.3%).In the 6 PROM-validation studies identified,only 5 psychometric properties were evaluated,the findings of which were limited due to the small number of *** systematic review identifies a lack in consistency of study design and PRO reporting in clinical *** an increasing number of studies are being performed to evaluate PROs,a lack of adherence to existing PRO administration and reporting guidelines is continuing to negatively affect st

关键词： Cholecystectomy patient reported outcomes(PROs) patient reported outcome measures(PROMs) quality of life(Qol) COnsensus-based Standards for the selection of health Measurement INstruments(COSMIN)

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用于飞机货舱防火的热监视系统

红外 1994年第3期15卷 31-38页

作者： Michael l.parsons 顾聚兴 SPIE会员

现在飞机货舱配置的火灾探测系统并不符合目前联邦航空管理局的要求,其中有一条技术规定,即在火灾发生后一分钟内将其探测出来。联邦航空管理局关于适航性的新规定要求改进由波音公司和麦克道耐尔道格拉斯公司生产的所有客货飞机上的火... 详细信息

现在飞机货舱配置的火灾探测系统并不符合目前联邦航空管理局的要求,其中有一条技术规定,即在火灾发生后一分钟内将其探测出来。联邦航空管理局关于适航性的新规定要求改进由波音公司和麦克道耐尔道格拉斯公司生产的所有客货飞机上的火灾探测系统。人们研制了一种符合联邦航空管理局新规定的热监视/火灾探测系统。它基于同菲涅耳扫描光学系统耦合起来的红外探测技术,并且使用双重的计算机控制装置,这使得该系统能够对货舱进行全面的热监视。系统对过热和火灾状态敏感,它具有三种火警信号电平,包含完整的光学视界和电路,能够提供有关火焰位置的信息。它可靠性高,不会产生误警。每个传感器都被设计得能够复盖高度为12英尺的一部分货舱。本文介绍该系统对火灾和过热状态的敏感特性,并且讨论它对误警的免疫能力。

关键词：飞机火灾监测防火系统红外成象

SO(n)-Invariant Special lagrangian Submanifolds of C^(n+1) with Fixed loci

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Chinese Annals of Mathematics,Series B 2006年第1期27卷 95-112页

作者： robert l. BRYANT Dedicated to the memory of Shiing-Shen Chern

let SO（n） act in the standard way on C^n and extend this action in the usual way to C^n＋l = C＋ C^n. It is shown that a nonsingular special lagrangian submanifold l→∪ C^n＋l that is invariant under this SO（n）-action intersects the fixed C→∪ C^n＋1 in a nonsingular real-analytic arc A （which may be empty）. If n 〉 2, then A has no compact component. Conversely, an embedded, noncompact nonsingular real-analytic arc A→∪ C lies in an embedded nonsingular special lagrangian submanifold that is SO（n）-invariant. The same existence result holds for compact A if n =2. nonsingular SO（n）-invariant special lagrangian nonsingular SO（n）-invariant special lagrangian extensions in some open neighborhood of A. If A is connected, there exist n distinct extensions of A such that any embedded extension of A agrees with one of these n The method employed is an analysis of a singular nonlinear PDE and ultimately calls on the work of Gerard and Tahara to prove the existence of the extension.

关键词： Calibrations Special lagrangian submanifolds

Boundary element method (BEM) applied to the rough surface contact vs. BEM in computational mechanics

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Friction 2019年第4期7卷 359-371页

作者： Yang XU robert l.JACKSON Mechanical Engineering Department Auburn University

In the numerical study of rough surfaces in contact problem, the flexible body beneath the roughness is commonly assumed as a half-space or a half-plane. The surface displacement on the boundary, the displacement components and state of stress inside the half-space can be determined through the convolution of the traction and the corresponding influence function in a closed-form. The influence function is often represented by the Boussinesq-Cerruti solution and the Flamant solution for three-dimensional elasticity and plane strain/stress, respectively. In this study, we rigorously show that any numerical model using the above mentioned half-space solution is a special form of the boundary element method(BEM). The boundary integral equations(BIEs) in the BEM is simplified to the Flamant solution when the domain is strictly a half-plane for the plane strain/stress condition. Similarly, the BIE is degraded to the Boussinesq-Cerruti solution if the domain is strictly a half-space. Therefore, the numerical models utilizing these closed-form influence functions are the special BEM where the domain is a half-space(or a half-plane). This analytical work sheds some light on how to accurately simulate the non-half-space contact problem using the BEM.

关键词： boundary element method rough surface contact half-space half-plane Flamant solution Boussinesq-Cerruti solution

Genetic and molecular changes in ovarian cancer

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Cancer Biology & Medicine 2016年第2期13卷 236-247页

作者： robert l Hollis Charlie Gourley Edinburgh Cancer Research UK Centre MRC Institute of Genetics and Molecular Medicine University of Edinburgh

Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical ***, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

关键词： ovarian cancer molecular genetics histological subtypes molecular subgrouping ovary

Assessment of portable FTIR and Raman spectroscopy for the detection of 2,3-dimethyl-2,3-dinitrobutane(DMDNB)in plastic explosives

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Defence Technology（防务技术） 2024年第4期34卷 11-18页

作者： Jacky Cailes robert Dunsmore Kathryn l.linge ChemCentre PO Box 1250PerthAustralia

The Marplex Convention was established to prevent the manufacture of unmarked plastic explosives and stipulates that a volatile detection agent must be added at the time of ***,to-date,laboratory testing remains the internationally accepted practice for identifying and quantifying the taggants stipulated in the *** this project,portable FTIR and Raman instruments were tested for their ability to detect 2,3-dimethyl-2,3-dinitrobutane(DMDNB),the chemical marker incorporated in plastic explosives that are manufactured within *** both FTIR and Raman instruments detected solid DMDNB(98%purity),field analysis of plastic explosives at an Australian Defence establishment showed that both FTIR and Raman spectra were matched the relevant explosive(RDX or PETN),rather than the DMDNB *** all three plastic explosives tested,the concentration of DMDNB was measured by SPME-GC-MS to be between 1.8 and 2%,greater than the minimum 1%concentration stipulated by the Marplex *** testing with a plastic explosive analogue confirmed that the minor absorption peaks that would characterize low concentrations of DMDNB were masked by absorption bands from other compounds within the ***,while both FTIR and Raman spectroscopy are suitable for detection of plastic explosives,neither rely on the presence of DMDNB for *** is likely that similar results would be found for other taggants stipulated by the Marplex Convention,given they are also present in concentrations less than 1%.

关键词： Explosive ICAO taggants 2,3-Dimethyl-2,3-dinitrobutane(DMDNB) Fourier transform infrared(FTIR) Raman

The influence of various grease compositions and silver nanoparticle additives on electrically induced rolling-element bearing damage

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Friction 2024年第4期12卷 796-811页

作者： Samuel BOND robert l.JACKSON German MIllS Department of Chemistry and Biochemistry Auburn UniversityAuburn 36849-5412USA Department of Mechanical Engineering Auburn UniversityAuburn 36849-5412USA

leakage currents accelerate surface degradation of metal contacts via small scale arcing across lubricating films,but recent observations suggest that metallic nanoparticle additives in lubricants may be useful to improve contact *** findings prompted a study that examined electrically induced surface pitting of steel contacts in the presence of several lubricating greases including some containing nanometer-sized colloidal silver(Ag)*** rolling sphere-on-disk experiments were conducted under electro-tribological loads employing polyurea greases derived from mineral and synthetic base oils with and without *** forces and electrical resistance were monitored continuously during the tests;surface changes were characterized by means of optical spectroscopy,stylus profilometry,and scanning electron microscopy(SEM)including compositional analysis using energy dispersive spectroscopy(EDS).The observations demonstrate that surface pitting induced by arcing occurs mainly at the points were the rolling motion changes direction and that eroded metal is deposited along the wear ***-sized pits are formed which contain carbon and oxygen indicating that arcing causes decomposition of the hydrocarbon *** findings indicate a significant inhibition of pitting is induced by the Ag nanoparticles;some greases containing other additives exhibit a similar,although less pronounced,effect.

关键词： electric motor bearings wheel bearings electric vehicles arcing electrically induced bearing damage pitting leakage current stray current

Approaches to antiretroviral therapy in China

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Cell Research 2005年第Z1期15卷 895-902页

作者： Bruce l GIllIAM robert R REDFIElD Division of Clinical Care and Research Institute of Human Virology University of Maryland Baltimore MD 21201 USA

China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment (ART) program. However, high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide. Concepts which will define treatment success and local and national programmatic goals are 1) access to ART, 2) durability of ART at the patient level, 3) scalability of treatment modalities, and the 4) sustainability of the program at the community or national level. In the face of limited resources, China must also consider when to start ARV therapy, which agents to use, when to switch them, and how to treat highly experienced patients with drug resistance. The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data. Currently, a regimen including tenofovir, emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV/AIDS in China. However, critical to all of these choices is the evaluation of programs implemented to insure wide scale success. China has wisely begun this process of evaluating the perfor- mance of local programs through systematic monitoring and evaluation of treatment outcomes. This will allow regi- mens and programs that work to be expanded, and programs with high failure rates to be eliminated. In the end, evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences

关键词： antiretroviral therapy scalability HIV/AIDS.