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Cancer Drug Resistance 2022年第2期5卷 424-435页

作者： Michael J.Flynn jonathan A.Ledermann Department of Oncology University College London HospitalLondon NW12PGUnited Kingdom. UCL Cancer Institute University College LondonLondon WC1E 6DDUnited Kingdom.

Definitions of platinum resistance have been questioned and changed over the last five years,even though no predictive biomarker of resistance *** have sculpted how we approach platinum retreatment and,consequently,how we devise new treatment strategies for those patients with tumour progression on platinum ***-non-eligible ovarian cancer is treated with single-agent non-platinum *** bevacizumab can be added to chemotherapy,progression-free survival improves *** patients with a BRCA mutation,PARP inhibitor monotherapy is an option compared to *** is currently no clearly identified role for immune-checkpoint inhibition in this patient *** review describes some of the challenges in treating patients with platinum resistance and suggests refinements in the selection of patients most likely to benefit from targeting a DNA damage response,angiogenesis or immune *** also describes novel agents of interest and possible mechanisms of the synergy of therapeutic combinations.

关键词： Platinum resistance PARP inhibitors VeGF inhibitors immune checkpoint inhibitors DNA damage response

Assessing Agricultural Sustainable Development Based on the DPSIR Approach: Case Study in Jiangsu, China

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Journal of Integrative Agriculture 2013年第7期12卷 1292-1299页

作者： ZHOU Shu-dong Felix mueller Benjamin Burkhard CAO Xing-jin HOU Ying Jiangsu Research Base of Rural Development and Land Policy Nanjing Agricultural University Institute for Natural Resource Conservation Department of Ecosystem Management University of Kiel

According to the contemporary ecosystem approach, the linkages of human actions with their environment have to be assessed in an integrative manner. The Driver-Pressure-State-Impact-Response （DPSIR） model is applied to identify and describe processes and interactions in human-environmental systems. An example application from a research project dealing with the development of sustainable management strategies for the agriculture in Jiangsu, China, illustrates the potentials and limitations of its sustainable development. The concept and indicators of ecological integrity are used to assess the indicators in the dimensions of DPSIR between 2003 and 2006. The main drivers included population growth which caused increasing demand for food, growing environmental demands, and rapidly decreasing of land and other natural resources. The main environmental problem was water pollution. The results show that in the dimension of driver, total grain output and agricultural land productivity both increased. Labor intensive agriculture has been promoted to increase agricultural land productivity. In the dimension of pressure, on the positive side, infrastructure got greatly improved, the input level such as total power of machinery, and level of fertilizer use increased, and level of pesticides use decreased, but on the negative side, cultivated land per capita and irrigation rate decreased, natural resources keep decreased. environmental pollution indicators such as industrial wastewater discharge and acid rain rate increased in Jiangsu Province. In the aspect of state, ecosystem state was improved, plant coverage index increased, biological abundance index increased, fertilizer productivity increased, eco-environmental quality index increased, but land degradation index also increased. In the aspect of impact, output level increased, output efficiency enhanced, farmer＇s social economic benefit improved. In the aspect of response, social support was greatly improved, input for e

关键词： agricultural sustainable development DPSIR ecosystem China

Current taxane formulations and emerging cabazitaxel delivery systems

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Nano Research 2018年第10期11卷 5193-5218页

作者： Boyang Sun Robert M. Straubinger jonathan F. Lovell Department of Biomedical engineering University at Buffalo State University of New York Buffalo NY 14260 USA Department of Chemical and Biological engineering University at Buffalo State University of New York Buffalo NY 14260 USA Department of Pharmaceutical Sciences University at Buffalo State University of New York Buffalo NY 14214 USA

Cabazitaxel is a second-generation taxane with promising anti-tumor activity and is approved for treating hormone-refractory metastatic prostate cancer previously treated with docetaxel. Although first-generation taxanes （i.e. paclitaxel and docetaxel） have sparked broad interest in a variety of drug delivery vehicles, fewer have yet been developed for cabazitaxel. This review summarizes several clinical-stage approaches for taxane formulation and recent efforts to develop novel cabazitaxel delivery systems.

关键词： cabazitaxel Jevtana taxanes drug delivery systems nanocarriers

Artificial Intelligence and the Future of education： Big Promises -Bigger Challenges

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学术界 2017年第4期 257-265页

作者： jonathan Michael Spector Du Jing University of North Texas USA Beijing Normal University Beijing 100875

The history of educational technology in the last 50 years contains few instances of dramatic improvements in learning based on the adoption of a particular *** example involving artificial intelligence occurred in the 1990s with the development of intelligent tutoring systems( ITSs). What happened with ITSs was that their success was limited to well-defined and relatively simple declarative and procedural learning tasks(e. g.,learning how to write a recursive function in LISP; doing multi-column addition),and improvements that were observed tended to be more limited than promised(e. g.,one standard deviation improvement at best rather than the promised standard deviation improvement).Still,there was some progress in terms of how to conceptualize learning. A seldom documented limitation was the notion of only viewing learning from only content and cognitive perspectives( i. e.,in terms of memory limitations,prior knowledge,bug libraries,learning hierarchies and sequences etc.). Little attention was paid to education conceived more broadly than developing specific cognitive skills with highly constrained problems. New technologies offer the potential to create dynamic and multi-dimensional models of a particular learner,and to track large data sets of learning activities,resources,interventions,and outcomes over a great many learners. Using those data to personalize learning for a particular learner developing knowledge,competence and understanding in a specific domain of inquiry is finally a real possibility. While the potential to make significant progress is clearly possible,the reality is less not so promising. There are many as yet unmet challenging some of which will be mentioned in this paper. A persistent worry is that educational technologists and computer scientists will again promise too much,too soon at too little cost and with too little effort and attention to the realities in schools and universities.

关键词：智能教学系统认知技能教育技术人员中国

Upper risk bounds in internal factor models with constrained specification sets

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Probability, Uncertainty and Quantitative Risk 2020年第1期5卷 38-67页

作者： jonathan Ansari Ludger Ruschendorf Department of Quantitative Finance Albert-Ludwigs University of FreiburgPlatz der Alten Synagoge 1KG II79098 Freiburg i.Br.Germany Department of Mathematical Stochastics Albert-Ludwigs University of FreiburgErnst-Zermelo-Straße 179104 FreiburgGermany

For the class of(partially specified)internal risk factor models we establish strongly simplified supermodular ordering results in comparison to the case of general risk factor *** allows us to derive meaningful and improved risk bounds for the joint portfolio in risk factor models with dependence information given by constrained specification sets for the copulas of the risk components and the systemic risk *** proof of our main comparison result is not *** is based on grid copula approximation of upper products of copulas and on the theory of mass *** application to real market data shows considerable improvement over the standard method.

关键词： Risk bounds Risk factor model Supermodular order Convex order Convex risk measure Upper product of bivariate copulas Comonotonicity

AGRONOMIC AND eNVIRONMeNTAL BeNeFITS OF ReINTRODUCING HeRB-AND LeGUMe-RICH MULTISPeCIeS LeYS INTO ARABLe ROTATIONS:A ReVIeW

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Frontiers of Agricultural Science and engineering 2022年第2期9卷 245-271页

作者： emily C.COOLeDGe David R.CHADWICK Lydia M.J.SMITH jonathan R.LeAKe Davey L.JONeS School of Natural Sciences Bangor UniversityGwyneddLL572UWUK National Institute of Agricultural Botany Huntingdon RoadCambridgeCB 3 OLEUK Plants Photosynthesis and SoilUniversity of SheffieldSheffieldS102TNUK Centre for Sustainable Farming Systems Food Futures InstituteMurdochWA 6150Australia

Agricultural intensification and the subsequent decline of mixed farming systems has led to an increase in continuous cropping with only a few fallow or break years,undermining global soil ***-ley rotations incorporating temporary pastures(leys) lasting 1–4 years may alleviate soil degradation by building soil fertility and improving soil ***,the majority of previous research on arable-ley rotations has utilized either grass or grassclover leys within ungrazed *** leys,containing a mix of grasses,legumes,and herbs,are rapidly gaining popularity due to their promotion in agri-environment schemes and potential to deliver greater ecosystem services than conventional grass or grass-clover *** grazing in arable-ley rotations may increase the economic resilience of these systems,despite limited research of the effects of multispecies leys on ruminant health and greenhouse gas *** review aims to evaluate previous research on multispecies leys,highlighting areas for future research and the potential benefits and disbenefits on soil quality and livestock *** botanical composition of multispecies leys is crucial,as legumes,deep rooted perennial plants(e.g.,Onobrychis viciifolia and Cichorium intybus) and herbs(e.g.,Plantago lanceolata) can increase soil carbon,improve soil structure,reduce nitrogen fertilizer requirements,and promote the recovery of soil fauna(e.g.,earthworms) in degraded arable soils while delivering additional environmental benefits(e.g.,biological nitrification inhibition and enteric methane reduction).Multispecies leys have the potential to deliver biologically driven regenerative agriculture,but more long-term research is needed to underpin evidence-based policy and farmer guidance.

关键词： bioactive forages integrated crop-livestock systems nitrogen cycling plant secondary metabolites soil carbon soil quality

Light-Absorbing Products Form during the Aqueous Phase Reaction of Phenolic Compounds in the Presence of Nitrate and Nitrite with UV Illumination

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Open Journal of Air Pollution 2012年第2期1卷 13-21页

作者： Hao Tang jonathan e. Thompson Department of Chemistry & Biochemistry Texas Tech University Lubbock TX 79409-1061

Phenolic compounds are emitted into earth’s atmosphere through industry and biomass burning events. These compounds may react in the gas or particle phase to form additional airborne pollutants. In this work, the aqueous phase chemical reactions of syringol, guaiacol, and catechol were studied in the presence of nitrate (NO-3 ) or nitrite ( NO-2) with and without UV illumination. The reactions were found to yield light absorbing products and electrospray ionization mass spectrometry (eSI-MS) experiments indicate some of the compounds formed may be the nitrated analogues of the starting organic compounds. However, infrared absorption data suggests the reaction products are composed of a complicated mixture. This suggests additional reactions occur simultaneously in solution. Treatment of the isolated reaction products with ozone (O3) suggest they are unstable and will eventually chemically decompose if/when formed in the atmosphere.

关键词： Air Pollution Biomass Burning Nitration Aerosol Airborne Particulate Matter Secondary Organic Aerosol

Affinity-induced covalent protein-protein ligation via the SpyCatcherSpyTag interaction

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Green Carbon 2023年第1期1卷 33-42页

作者： Jacob O.Fierer Omar e.Tovar-Herrera jonathan Y.Weinstein Amaranta Kahn Sarah Moraïs Itzhak Mizrahi edward A.Bayer Department of Biomolecular Sciences the Weizmann Institute of ScienceRehovot 7610001Israel Department of Life Sciences Ben-Gurion University of the NegevBeer Sheva 84105Israel National Institute of Biotechnology in the Negev Ben-Gurion University of the NegevBe’er Sheva 84105Israel The Goldman Sonnenfeldt School of Sustainability and Climate Change Ben-Gurion University of the NegevBeer Sheva 84105Israel

Production of economically viable bioethanol is potentially an environmentally and financially worthwhile *** major source for fermentable sugars is ***,lignocellulosic biomass is difficult to degrade,owing to its inherent structural *** are complexes of cellulases and associated polysaccharide-degrading enzymes bound to a protein scaffold that can efficiently degrade *** of the enzyme subunits into the complex depends on intermodular cohesin-dockerin interactions,which are robust but nonetheless *** modular architecture of these complexes can be used to assemble artificial designer cellulosomes for advanced nanotechnological *** that promote lignocellulose degradation involve high temperatures and acidic or alkaline conditions that could dismember designer cellulosomes,thus requiring separation of reaction steps,thereby increasing overall process *** overcome these challenges,we developed a means of covalently locking cohesin-dockerin interactions by integrating the chemistry of SpyCatcher-SpyTag approach to target and secure the *** resultant cohesin-conjugated dockerin complex was resistant to high temperatures,SDS,and urea while high affinity and specificity of the interacting modular components were *** this approach,a covalently locked,bivalent designer cellulosome complex was produced and demonstrated to be enzymatically active on cellulosic *** combination of affinity systems with SpyCatcher-SpyTag chemistry may prove of general use for improving other types of protein ligation systems and creating unconventional,biologically active,covalently locked,affinity-based molecular architectures.

关键词： Synthetic Biology Protein Ligation Cellulosomes Cohesin Dockerin Protein engineering Cellulose Degradation

Spatio-temporal patterns of satellite-derived grassland vegetation phenology from 1998 to 2012 in Inner Mongolia, China

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Journal of Arid Land 2016年第3期8卷 462-477页

作者： SHA Zongyao ZHONG Jialin BAI Yongfei TAN Xicheng jonathan LI International Software School Wuhan University Department of Geography & environmental Management University of Waterloo Institute of Botany Chinese Academy of Sciences

Spatio-temporal variations of vegetation phenology, e.g. start of green-up season（SOS） and end of vegetation season（eOS）, serve as important indicators of ecosystems. Routinely processed products from remotely sensed imagery, such as the normalized difference vegetation index（NDVI）, can be used to map such variations. A remote sensing approach to tracing vegetation phenology was demonstrated here in application to the Inner Mongolia grassland, China. SOS and eOS mapping at regional and vegetation type（meadow steppe, typical steppe, desert steppe and steppe desert） levels using SPOT-VGT NDVI series allows new insights into the grassland ecosystem. The spatial and temporal variability of SOS and eOS during 1998–2012 was highlighted and presented, as were SOS and eOS responses to the monthly climatic fluctuations. Results indicated that SOS and eOS did not exhibit consistent shifts at either regional or vegetation type level; the one exception was the steppe desert, the least productive vegetation cover, which exhibited a progressive earlier SOS and later eOS. Monthly average temperature and precipitation in preseason（February, March and April） imposed most remarkable and negative effects on SOS（except for the non-significant impact of precipitation on that of the meadow steppe）, while the climate impact on eOS was found to vary considerably between the vegetation types. Results showed that the spatio-temporal variability of the vegetation phenology of the meadow steppe, typical steppe and desert steppe could be reflected by the monthly thermal and hydrological factors but the progressive earlier SOS and later eOS of the highly degraded steppe desert might be accounted for by non-climate factors only, suggesting that the vegetation growing period in the highly degraded areas of the grassland could be extended possibly by human interventions.

关键词： phenological timing degradation harmonic analysis human activity climate restoration

A CK2-RNF4 interplay coordinates non-canonical SUMOylation and degradation of nuclear receptor FXR

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Journal of Molecular Cell Biology 2017年第3期9卷 195-208页

作者： Stephanie Bilodeau Veronique Caron jonathan Gagnon Alexandre Kuftedjian Andre Tremblay Research Center CHU Sainte-Justine Montreal Quebec H3T 1C5 Canada Department of Biochemistry and Molecular Medicine Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada Department of Obstetrics & Gynecology Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada

Farnesoid X 受体(FXR ) 是在调整涉及胆汁酸动态平衡，和脂肪和葡萄糖新陈代谢的基因起一个中央作用的激活 ligand 的原子受体。这里，我们表明在在 hepatocytes 指导受体进一条激活降级小径的 FXR phosphorylation， SUMOylation，和 ... 详细信息

Farnesoid X 受体(FXR ) 是在调整涉及胆汁酸动态平衡，和脂肪和葡萄糖新陈代谢的基因起一个中央作用的激活 ligand 的原子受体。这里，我们表明在在 hepatocytes 指导受体进一条激活降级小径的 FXR phosphorylation， SUMOylation，和 ubiquitination 之间的 translational 以后相互影响。我们识别一个不在经典中的 SUMOylation 主题在酷蛋白 kinase 的直接控制下面在 FXR 的 Lys-325 结合 SUMO2 的称为的 pSuM 2 (CK2 ) ，它提供要求的否定费用让 Ubc9 和 PIAS1 执行 SUMOylation，由 phosphorylating Ser-327。Lys-325 SUMOylation 对有效 ligand 激活的提升和 FXR 的 transcriptional coactivation 不可缺少。用 phospho 模仿 Ser-327 变异或催化的 CK2 表情的组成的 pSuM 激活强烈导致 SUMO2 变化形式，它指导 FXR ubiquitination 和 proteasome 依赖的降级。我们也决定 FXR 的如此的 SUMOylation 依赖的 ubiquitination 被 e3 ubiquitin ligase RNF4 调停，它被要求完成 FXR 的最大的正式就职并且在上面最佳 -- 或涉及胆汁酸动态平衡和肝新生的应答的基因的 downregulation。我们的调查结果识别服务协调 FXR transcriptional 胜任的一个高度调整的不正常的相扑变化形式主题，从而扩展到来的信号过去常管理新陈代谢的基因规定的 SUMOylation 过程的复杂动力学。

关键词： SUMO 降解途径核受体动坐标有功功率直接控制酪蛋白激酶泛素连接酶