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驱动基因阴性的转移性非小细胞肺癌最佳免疫治疗方案的选择

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中国肺癌杂志 2022年第7期25卷 555-582页

作者： Michael J.GRANT Roy S.HERbST Sarah b.goldberg 刘明 Department of Medicine (Medical Oncology) Yale School of MediineYale Cancer Center 广州医科大学附属第一医院呼吸科国家呼吸医学中心

驱动基因阴性的非小细胞肺癌(non-small celllung cancer,NSCLC)治疗策略进展迅速。其中,免疫检查点抑制剂,特别是针对程序性死亡受体1 (programmed death 1,PD-1)/程序性死亡配体1 (programmed death-ligand 1,PD-L1)的免疫检查点抑制... 详细信息

驱动基因阴性的非小细胞肺癌(non-small celllung cancer,NSCLC)治疗策略进展迅速。其中,免疫检查点抑制剂,特别是针对程序性死亡受体1 (programmed death 1,PD-1)/程序性死亡配体1 (programmed death-ligand 1,PD-L1)的免疫检查点抑制剂,已在部分NSCLC患者中显示出持久疗效,成为驱动基因阴性NSCLC一线治疗的基石。对于初治患者,目前获批的免疫治疗策略包括免疫单药治疗、免疫联合免疫方案或免疫治疗联合化疗。尽管几项重要临床研究中的长期疗效和安全性数据可以为不同患者亚群的最佳治疗选择提供见解,但鉴于缺乏头对头的前瞻性研究,不同患者亚群的治疗决策仍然十分复杂。事实上,尽管组织学亚型和肿瘤细胞PD-L1表达水平对治疗方案的选择尤为重要,但某些情况下其他临床病理因素和患者意愿也可能影响治疗方案的选择。目前针对新型生物标志物和治疗新策略的研究正在开展,有望进一步完善当前的治疗模式。该综述讨论了现有治疗方案,并详细介绍了驱动基因阴性的晚期NSCLC患者的一线免疫治疗方案的选择。

关键词：基因阴性细胞肺癌免疫治疗

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超越是非之辩:选择调解人

经理人 2006年第5期 74-76页

作者： Stephen b.goldberg

当谈判升级为纠纷时，大多数经理人懂得必须寻求一位调解人，为解决问题提供专业协助。但是该聘用谁，这个问题却不那么清楚易答。调解人应当具备什么样的专业技能，你应当到哪里去找到这样的人士？

关键词：调解人是非专业技能经理人应当

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THE ENERGY SAVINGS POTENTIAL OF OPTIMIZED SLAb-ON-GRADE FOUNDATION INSUL .ATION RETROFITS

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Journal of Green building 2015年第3期10卷 116-136页

作者： Louise F.goldberg Garrett Mosiman Energy Systems Design Program University of Minnesota Lofrango Engineering Center for Sustainable building Research University of Minnesota

A recently developed 3-dimensional earth contact simulation program that operates as a subroutine of the EnergyPlus whole building energy simulation program was used to evaluate the energy performance and cost-effectiveness of retrofit slab-on-grade(SOG)foundation *** optimized retrofit insulation design utiliz-ing hydro-vacuum excavation was developed that generated 8.4%larger metered(or site)energy savings at a$428 lower cost than the IECC 2012 requirement in a Minneapolis,MN climate for a 400 ft2 test *** energy performance and cost effectiveness of single and multi-family buildings was assessed for climate Zones 4–*** reference to the building America b10 benchmark,the highest site energy savings of 5%was realized for a single family home in Duluth,MN,and the lowest savings of 1.4%for a 4-unit townhouse in Richmond,*** foundation insulation retrofit simple paybacks ranged from 18 to 47 *** it is likely that larger energy savings of 10%or more with concomitantly reduced simple paybacks can only be realized in well-insulated buildings.

关键词： slab-on-grade insulation energy cost

Fe Nanoclusters on the Ge（001） Surface Studied by Scanning Tunneling Microscopy, Density Functional Theory Calculations and X-Ray Magnetic Circular Dichroism

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Nano Research 2011年第10期4卷 971-978页

作者： Olaf LUbben Sergey A. Krasnikov Alexei b. Preobrajenski barry E. Murphy Igor V. Shvets Centre for Research on Adaptive Nanostructures and Nanodevices （CRANN） School of Physics Trinity College Dublin Dublin 2 Ireland MAX-lab Lund University Box 118. 22100 Lund Sweden

The growth of Fe nanoclusters oN the Ge（001） surface has been studied using low-temperature scanning tunneling microscopy （STM） and density functional theory （DFT） calculations. STM results indicate that Fe nucleates on the Ge（001） surface, forming well-ordered nanoclusters of uniform size. Depending on the preparation conditions, two types of nanoclusters were observed having either four or sixteen Fe atoms within a nanocluster. The results were confirmed by DFT calculations. Annealing the nanoclusters at 420 K leads to the formation of nanorow structures, due to cluster mobility at such temperature. The Fe nanoclusters and nanorow structures formed on the Ge（001） surface show a superparamagnetic behaviour as measured by X-ray magnetic circular dichroism.

关键词： Ge(001) iron nanoclusters self-assembly scanning tunnelling microscopy X-ray magnetic circular dichroism density functional theory calculations

Outcome of treatment seeking rural gamblers attending a nurse-led cognitive-behaviour therapy service:A pilot study

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International Journal of Nursing Sciences 2016年第1期3卷 89-95页

作者： barry Tolchard School of Nursing University at BuffaloNY 14214USA School of Health University of New EnglandArmidaleNSW 2350Australia

Objectives:Little is known about the differences between urban and rural gamblers in Australia,in terms of comorbidity and treatment *** disparities exist between urban and rural areas in terms of accessibility,availability,and acceptability of treatment programs for problem ***,evidence supporting cognitivebehaviour therapy as the main treatment for problem gamblers is *** pilot study aimed to assess the outcome of a Cognitive-behavioural Therapy(CbT)treatment program offered to urban and rural treatment-seeking ***:People who presented for treatment at a nurse-led Cognitive-behavioural Therapy(CbT)gambling treatment service were invited to take part in this study.A standardised clinical assessment and treatment service was provided to all participants.A series of validated questionnaires were given to all participants at(a)assessment,(b)discharge,(c)at a one-month,and(d)at a 3-month follow-up ***:Differences emerged between urban and rural treatment-seeking *** overall treatment outcomes were much the same at three months after treatment,rural gamblers appeared to respond more rapidly and to have sustained improvements over ***:This study suggests that rural problem gamblers experience different levels of co-morbid anxiety and depression from their urban counterparts,but once in treatment appear to respond *** approach was found to be effective in treating rural gamblers and outcomes were *** better availability and access to such treatment in rural areas is *** are in a position as the majority health professional in rural areas to provide such help.

关键词： Evidence based health care Health program evaluation Models of care Rural health services delivery Rural mental health

Climate change,thermal niches,extinction risk and maternal-effect rescue of toad-headed lizards,Phrynocephalus,in thermal extremes of the Arabian Peninsula to the Qinghai-Tibetan Plateau

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Integrative Zoology 2018年第4期13卷 450-470页

作者： barry SINERVO Donald b.MILES Yayong WU Fausto R.MÉNDEZ-DE LA CRUZ Sebastian KIRCHHOF Yin QI The Institute for the Study of the Ecological and Evolutionary Climate Impacts University of Californiaand Department of Ecology and Evolutionary BiologyUniversity of CaliforniaSanta CruzCaliforniaUSA Department of biological Sciences Ohio UniversityAthensOhioUSA Chengdu Institute of biology Chinese Academy of SciencesChengduSichuanChina Laboratory of Herpetology Institute of BiologyUniversidad Nacional Autónoma de MéxicoMexico CityMexico Museum of Natural History Leibniz-Institute for Evolution and Biodiversity Scienceand Berlin-Brandenburg Institute of Advanced Biodiversity Research(BBIB)BerlinGermany

Determining the susceptibility of species to changing thermal niches is a major goal for *** this paper we develop an eco-physiological model of extinction risk under climate change premised on behavioral *** method downscales operative environmental temperatures,which restrict hours of activity of lizards,hr,for present-day climate(1975)and future climate scenarios(2070).We apply our model using occurrence records of 20 Phrynocephalus lizards(or taxa in species complexes)drawn from literature and museum *** analysis is phylogenetically informed,because some clades may be more sensitive to rising *** limits for computed hr predict local extirpations among Phrynocephalus lizards at continental scales and delineate upper boundaries of thermal niches as defined by Extreme Value *** the 8.5 Representative Concentration Pathway scenario,we predict extirpation of 64%of local populations by 2070 across 20 Phrynocephalus species,and 12 are at high risk of total extinction due to thermal limits being *** tandem with global strategies of lower CO_(2) emissions,we propose regional strategies for establishing new national parks to protect extinction-prone taxa by preserving high-elevation climate refugia within existing sites of species *** propose that evolved acclimatization–maternal plasticity–may ameliorate risk,but is poorly *** studies revealed that adaptive maternal plasticity by thermoregulating gravid females alter progeny thermal preferences by±1℃.We describe plasticity studies for extinction-prone species that could assess whether they might be buffered from climate warming–a *** discuss an epigenetic framework for studying such maternal-effect evolution.

关键词： climate change eco-physiology extinction model maternal effect lizards

A simple umbelliferone based fluorescent probe for the detection of nitroreductase

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Frontiers of Chemical Science and Engineering 2018年第2期12卷 311-314页

作者： Adam C. Sedgwick Alex Hayden barry Hill Steven D. bull Robert b. P. Elmes Tony D. James Department of Chemistry University of Bath Bath BA2 7AY UK Department of Chemistry Maynooth University Maynooth Co. Kildare Ireland

A simple nitrobenzyl-umbelliferone （NCOU1） was synthesised containing a nitroreductase （NTR） trigger moiety. The presence of NTR, resulted in the fragmentation of the parent molecule and release of the highly emissive fluorophore umbelliferone via an NTR-catalyzed reduction of the nitro group. In the presence of the NTR enzyme, NCOU1 gave rise to a 5-fold increase in fluorescence intensity at 455 nm and was selective for NTR over other reductive enzymes. These results indicate that NCOU1 can be used as a simple assay for the detection of NTR.

关键词： NITRO RADICALS NTSR1 gene FLUORESCENT PRObES Skimmetin Nitroreductases noise-temperature ratio

Understanding normal and abnormal development of the Wolffian/epididymal duct by using transgenic mice

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Asian Journal of Andrology 2015年第5期17卷 749-755,I0007页

作者： Aki Murashima bingfang Xu barry T Hinton Department of Developmental Genetics Institute of Advanced Medicine Wakayama Medical University 811-1 Kimiidera Wakayama 641-8509 Wakayama Japan Department of Cell biology University of Virginia School of Medicine Charlottesville VA 22908 USA

The development of the Wolffian/epididymal duct is crucial for proper function and, therefore, male fertility. The development of the epididymis is complex; the initial stages form as a transient embryonic kidney; then the mesonephros is formed, which in turn undergoes extensive morphogenesis under the influence of androgens and growth factors. Thus, understanding of its full development requires a wide and multidisciplinary view. This review focuses on mouse models that display abnormalities of the Wolffian duct and mesonephric development, the importance of these mouse models toward understanding male reproductive tract development, and how these models contribute to our understanding of clinical abnormalities in humans such as congenital anomalies of the kidney and urinary tract （CAKUT）.

关键词： epididymis mesonephros transgenic mice Wolffian duct

Earthworm populations are stable in temperate agricultural soils receiving wood-based biochar

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Pedosphere 2021年第3期31卷 398-404页

作者： Joann KWHALEN Hicham bENSLIM Abdirashid AELMI barry RHUSK Department of Natural Resource Sciences Macdonald Campus of McGill UniversitySte-Anne-de-BellevueQuebec H9X 3V9Canada Department of Environmental Technology Management College of Life SciencesKuwait UniversityP.O.Box 5969Safat 13060Kuwait blueLeaf Inc. DrummondvilleQuebec J2B 5E9Canada

The application of decomposable organic residues such as manure and crop litter is generally beneficial to *** is an emerging interest in applying biochar,a carbonaceous product of pyrolysis,to temperate agricultural *** slow decomposition rate of biochar,which also contains ash and combustion byproducts,could be detrimental to *** objective of this study was to describe the earthworm populations in biochar-amended soils on a dairy farm in the *** River watershed,Quebec,*** were collected from replicated field plots under cereal *** A received three wood-based biochar types at two application rates(5 and 10 t ha^(-1) biochar)plus an unamended control,while Site b received wood-based biochar(7.5 t ha^(-1) biochar),dairy cattle slurry(10 t ha^(-1) manure),or a combination of the biochar and manure rates plus an unamended *** were collected by hand sorting and formaldehyde expulsion from soil *** species,Aporrectodea turgida,Aporrectodea tuberculata,and Lumbricus rubellus,were found at the sites,and Aporrectodea was the dominant *** sources,rates,and application with dairy slurry did not affect the earthworm population,which had 52-218 individuals m^(-2) in 2010 and 4-96 individuals m^(-2) in *** seasonal variation in earthworm population may be due to flooding in the spring of 2011,which apparently interfered with earthworm *** similarity in earthworm abundance and biomass in plots with and without wood-based biochar leads to the conclusion that earthworm populations are stable in biochar-amended soils in this cold,humid temperate region.

关键词： biochar-amended soilcornendogeic earthwormflooded soilpyrolysiswoody feedstock

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