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Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date

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World Journal of Clinical Cases 2015年第8期3卷 694-704页

作者： Kyle Crassini Stephen P Mulligan O giles best Northern Blood Research Centre and CLL Australian Research Consortium Kolling Institute of Medical Research Royal North Shore Hospital

Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor(BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents.

关键词： Chronic lymphocytic leukemia Therapy Microenvironment Leukemia Novel

Detection and Localization of Load Redistribution Attacks on Large-scale Systems

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Journal of Modern Power Systems and Clean Energy 2022年第2期10卷 361-370页

作者： Andrea Pinceti Lalitha Sankar oliver Kosut the School of Electrical Computer and Energy EngineeringArizona State UniversityTempeUSA

A nearest-neighbor-based detector against load redistribution attacks is *** detector is designed to scale from small-scale to very large-scale systems while guaranteeing consistent detection *** testing is performed on a realistic large-scale system to evaluate the perfor-mance of the proposed detector against a wide range of attacks,from simple random noise attacks to sophisticated load redistribution *** detection capability is analyzed against different attack parameters to evaluate its sensitivity.A statistical test that leverages the proposed detector is introduced to identify which loads are likely to have been maliciously modified,thus,localizing the attack *** test is based on ascribing to each load a risk measure(probability of being attacked)and then computing the best posterior likelihood that minimizes log-loss.

关键词： Attack detection cyber-security false data injection(FDI)attack load redistribution attack machine learning nearest neighbor

Complementary and alternative medicines in irritable bowel syndrome: An integrative view

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World Journal of Gastroenterology 2014年第2期20卷 346-362页

作者： oliver Grundmann Saunjoo L Yoon Department of Medicinal Chemistry College of PharmacyUniversity of FloridaFL 32610United States Department of Adult and Elderly Nursing College of NursingUniversity of FloridaFL 32610United States

Irritable bowel syndrome(IBS)is a common gastrointestinal disorder with a high incidence in the general *** diagnosis of IBS is mainly based on exclusion of other intestinal conditions through the absence of inflammatory markers and specific *** current pharmacological treatment approaches available focus on reducing symptom severity while often limiting quality of life because of significant side *** has led to an effectiveness gap for IBS patients that seek further relief to increase their quality of *** and alternative medicines(CAM)have been associated with a higher degree of symptom management and quality of life in IBS *** the past decade,a number of important clinical trials have shown that specific herbal therapies(peppermint oil and Iberogast?),hypnotherapy,cognitive behavior therapy,acupuncture,and yoga present with improved treatment outcomes in IBS *** propose an integrative approach to treating the diverse symptoms of IBS by combining the benefits of and need for pharmacotherapy with known CAM therapies to provide IBS patients with the best treatment outcome *** steps in this direction are already being considered with an increasing number of practitioners recommending CAM therapies to their patients if pharmacotherapy alone does not alleviate symptoms sufficiently.

关键词： Irritable bowel syndrome Complementary and alternative medicine Hypnotherapy Cognitive behavioral therapy Herbal therapy Peppermint

Controlling the reaction network of Ni/silica derived conversion of bio-oil surrogate guaiacol

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Carbon Resources Conversion 2024年第1期7卷 39-60页

作者： Nils Kretzschmar oliver Busse Markus Seifert Technische Universität Dresden Faculty of Chemistry and Food Chemistry01062 DresdenGermany

Replacing fossil carbon sources with green bio-oils is a promising route to switch to a sustainable chemical industry,although their high oxygen contents are *** hydrodeoxygenation is a favored route to upgrade bio-oils to renewable fuels and basic *** this work,we investigated Ni/SiO2 catalysts with differing metal dispersity in continuous mode conversion of guaiacol with a statistical experimental design for 250℃to 400℃,2 h up to 5 h time on stream(ToS)and subsequently different residence time besides other *** low temperature(250℃)promotes cyclohexanol formation from guaiacol,high temperature(400℃)inhibits hydrogenation,leading to phenol and *** medium temperature(340℃),the selectivity for cyclohexanone *** and cyclohexanone(KA-oil)are the industrial basis for polyamide ***,we clarified the role of 2-methoxycyclohexanol(2MC)in the reaction network towards KA-oil for continuous-mode *** analysis was used to predict and optimize product selectivity and yield,leading to the best yield of cyclohexanone/-ol at 327.5℃,low ToS,medium residence time,high particle dispersity,and medium hydrogen pressure(15 bar(g)).

关键词： Hydrodeoxygenation Design of experiments Bio-oil Nickel silica catalyst Continuous mode flow reactor KA-oil Cyclohexanol Cyclohexanone

ENERGY EMBODIED IN,AND TRANSMITTED THROUGH,WALLS OF DIFFERENT TYPES WHEN ACCOUNTING FOR THE DYNAMIC EFFECTS OF THERMAL MASS

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Journal of Green Building 2020年第4期15卷 43-66页

作者： Aidan Reilly oliver Kinnane Richard O’Hegarty UCD School of Architecture Planning and Environmental PolicyCollege of Engineering and ArchitectureUniversity College DublinIreland

Embodied energy is a measure of the energy used in producing,transporting and assembling the materials for a *** energy is the energy used to moderate the indoor environment to make it functional or comfortable-primarily,to heat or cool the *** many building geometries,the walls make the most significant contribution to the embodied energy of the building,and they are also the path of greatest heat loss or gain through the fabric,as they often have a greater surface area than the roof or *** insulation reduces the heat flow through the wall,reducing the energy used during operation,but this adds to the embodied *** operational energy is not only a function of the wall buildup,but also depends on the climate,occupancy pattern,and heating strategy,making an optimisation for minimum overall energy use *** study presents a comparison of typical wall construction types and heating strategies in a temperate maritime *** transient energy ratio method is a means to abstract the heat flow through the walls(operational energy for heating),allowing assessment of the influence of walls in isolation(*** a general sense,without being restricted to particular building geometries).Three retrofit scenarios for a solid wall are *** very low U-values,overall energy use can increase as the embodied energy can exceed the operational energy;current best practice walls coupled with low building lifetimes mean that this point may be reached in the near *** uncertainty is present in existing embodied energy data,and given its contribution to total energy use,this is a topic of urgent concern.

关键词： energy use lifetime energy use embodied energy operational energy thermal mass heating intermittent occupancy transient energy ratio uncertainty

Alpine Activity Patterns of Mitopus morio(Fabricius, 1779) are Induced by Variations in Temperature and Humidity at Different Scales in Central Norway

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Journal of Mountain Science 2014年第3期11卷 644-655页

作者： Nils HEIN Roland PAPE oliver-D. FINCH Jorg LOFFLER Department of C-eography University of Bonn Meckenheimer AUee 166 D-53115 Bonn Germany Achtern Nordpol 8 D-26180 Rastede Germany

Our research addresses questions about how micro-climate affects activity abundance of a common and widespread harvestman in an alpine ecosystem. Activity patterns of the Harvestman Mitopus morio(Fabricius, 1779) were studied along different alpine gradients in the central Norwegian Scandes. Within a nested design, we surveyed 18 alpine habitats with pitfall traps and microclimatological equipment along oceanic-continental, two elevational, and(fine-scaled) microtopographic gradients. Sites in the oceanic region of the Scandes showed generally higher abundance of M. morio than sites in the continental region. Furthermore, along the elevational gradient, middle-alpine sites showed higher abundances than low-alpine sites. These general patterns are best explained by higher humidity in the oceanic region and in the middlealpine belt. Focusing at a finer scale, i.e. one elevational level within each region, revealed partly opposing activity patterns within relatively short distances. While in the western middle-alpine belt these patterns were best explained by humidityrelated measures but now with higher activity abundance during drier conditions, in the drier eastern middle-alpine belt heat sums rather than humidity were found to be the best explanatoryvariables for the observed patterns. Hence, our results imply a pronounced different reaction of the two populations towards climatic variables that partly even contradict the previously described general pattern. Regardless whether these differences in activity abundance in M. morio are a form of phenotypic plasticity or adaptation, our findings stress the importance of detailed autecological knowledge combined with fine-scaled climatic measurements when aiming at predictions about possible future ecosystem structures and spatiotemporal phenomena. M. morio proves to be an ideal biogeographic model organism for understanding spatio-temporal responses of alpine ecosystems under modified climatic conditions.

关键词： Climate gradients Opiliones Arctic-alpine ecosystems High mountains Scandinavia

Design and optimization of electrochemical cell potential for hydrogen gas production

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Journal of Energy Chemistry 2021年第1期30卷 421-427,I0013页

作者： Nawar KAl-Shara Farooq Sher Sania ZIqbal oliver Curnick George ZChen Department of Chemical and Environmental Engineering Faculty of EngineeringUniversity of NottinghamUniversity ParkNottingham NG72RDUK School of Mechanical Aerospace and Automotive EngineeringFaculty of EngineeringEnvironmental and ComputingCoventry UniversityCoventry CV12JHUK Department of Biochemistry University of AgricultureFaisalabad 38000Pakistan Institute for Future Transport and Cities Coventry UniversityCoventry CV15FBUK Department of Chemical and Environmental Engineering Faculty of Science and EngineeringUniversity of Nottingham Ningbo ChinaUniversity ParkNingbo 315100China

This study deals with the optimization of best working conditions in molten melt for the production of hydrogen(H2) *** research has been carried out on how electrochemical process occurs through steam splitting via molten hydroxide.54 combinations of cathode,anode,temperature and voltage have been investigated for the optimization of best working conditions with molten hydroxide for hydrogen gas *** these electrochemical investigations were carried out at 225 to 300℃ temperature and 1.5 to 2.5 V applied voltage *** current efficiency of 90.5,80.0 and 68.6% has been achieved using stainless steel anodic cell with nickel,stainless steel and platinum working cathode *** nickel cathode,an increase in the current directly affected the hydrogen gas flow rate at *** can be hypothesized from the noted results that increase in current is directly proportional to operating temperature and applied *** values were noted when the applied voltages increased from 1.5 to 2.5 V at 300℃,the flow rate of hydrogen gas increased from 1.5 to 11.3 cm^(3) min^(-1),1.0 to 13 cm^(3) min^(-1) in case of electrolysis@stainless steel and@graphite anode *** is observed that the current efficiency of stainless steel anodic cell was higher than the graphite anodic ***,steam splitting with the help of molten salts has shown an encouraging alternate to current methodology for H2 fuel production.

关键词： Sustainable energy Splitting steam Electrolysis Hydrogen gas production Electrochemical cell and Variable cathodes

Review of different fault detection methods and their impact on pre-emptive VSC-HVDC dc protection performance

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High Voltage 2017年第4期2卷 211-219页

作者： Bin Chang oliver Cwikowski Mike Barnes Roger Shuttleworth Antony Beddard Paul Coventry Global Energy Interconnection Research Institute Future Science ParkBeijing 102209People's Republic of China The University of Manchester Oxford RoadManchester M139PLUK National Grid National Grid HouseWarwick CV346DAUK

Multi-terminal voltage-sourced converters(VSC)high-voltage direct current(HVDC)transmission system is expected to play a vital role in future power *** with ac power transmission,dc transmission is more vulnerable to faults due to low dc-side impedances and sensitive power electronics in the *** protection issues must be tackled before any multi-terminal VSC-HVDC grid can be *** multi-terminal VSC-HVDC system is studied in detail using switching models for two-level converters,detailed equivalent models for the modular multi-level converters,detailed hybrid circuit breaker switching models and frequency-dependent phase models for dc *** such high-fidelity system models,a systematic study of HVDC fault protection methodologies in more detail than previous studies is *** is the first comprehensive study that includes pre-emptive circuit breaker *** results presented in this study underline the benefits of such a detailed treatment of the breaker,and of considering it as part of a fast power electronics system rather than isolated dc *** study identifies the best existing fault detection method and tests it *** order to further improve post-fault system recovery response,which is a key but often neglected part of previous studies,a novel bump-less transfer control has been implemented in the converters.

关键词： fault system power

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欧洲主权债务问题

新金融 2011年第10期 4-9页

作者：胡妍斌王辰 oliver Adler giles Keating Daniel Davies Christine Schmid William Porter Vaérie Plagnol Giovanni Zanni 瑞信私人银行研究部私人银行及资产管理研究部瑞信投资银行部瑞信私人银行部

次贷危机爆发之后、特别是雷曼破产后,各国政府推出了许多政策措施,目的在于重建市场信心,最明显的途径是向系统重要银行提供正式或非正式的担保。但当银行负债不得不成为政府的或有负债时,就会彻底改变市场对政府自身信用的评价。在希... 详细信息

次贷危机爆发之后、特别是雷曼破产后,各国政府推出了许多政策措施,目的在于重建市场信心,最明显的途径是向系统重要银行提供正式或非正式的担保。但当银行负债不得不成为政府的或有负债时,就会彻底改变市场对政府自身信用的评价。在希腊等体质较弱的欧洲外围国家,会把政府和银行一道带入恶性循环。不过,欧元的结构比通常理解的更为坚固,脱离欧元是一种代价昂贵的违约方式,相信这是最不可能发生的;相比之下,政府债务重组对经济的负面影响较小,因而更可能被采用。

关键词：国际金融主权债务金融危机银行业