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Is COX-2 a perpetrator or a protector? Selective COX-2 inhibitors remain controversial~1

Acta Pharmacologica Sinica 2005年第8期26卷 926-933页

作者： lars BOHLIN Department of Medicinal Chemistry Biomedical Center Uppsala University Sweden

Aim: COX-2(cyclooxygenase-2) has sparked a surge in pharmaceutical interest since its discovery at the beginning of the 1990s. Several COX-2 selective inhibi- tors that avoid gastrointestinal side effects have been successfully launched into the market in recent years. The first selective COX-2 inhibitor, celecoxib, enteredthe market in December 1999. However, there are a few organs that physiologi-cally and functionally express COX-2, particularly the glomeruli of the kidney and the cortex of the brain. Inhibition of COX-2 expression in these organs possibly causes heart attack and stroke in long-term COX-2 inhibitor users. Recently, a USA Food and Drug Agency (FDA) advisory panel re-evaluated COX-2 inhibitors and unanimously concluded that the entire class of COX-2 inhibitors increase the risk of cardiovascular problems. Thus the use of COX-2 inhibitors is still controversial, and there is a challenge for not only pharmacologists, but also the pharmaceutical industry, to develop improved painkilling and anti-inflammatory drugs. This may involve exploring a new generation of COX-2 inhibitors with different inhibitory mechanisms through computer-aided design, screening differ-ent sources of inhibitors with lower Selectivity, or seeking completely new targets. Synthetic COX-2 inhibitors have high selectivity and the advantage of irrever-sible inhibition, whereas naturally derived COX-2 inhibitors have lower selectivity and fewer side effects, with the medical effects in general not being as striking as those achieved using synthetic inhibitors. This review discusses the mechanism of COX-2 inhibitor therapy and a possible new way of exploration in the develop-ment of anti-inflammatory, analgetic, and antipyretic drugs.

关键词： COX-2 inhibitor nonsteroidal anti-inflammatory drug prostanoids cardiovascular disease

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An overview of various control benchmarks with a focus on automotive control

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Control Theory and Technology 2019年第2期17卷 121-130页

作者： lars ERIKSSON Vehicular Systems Department of Electrical EngineeringLinkoping UniversitySE-581 83 LinkopingSweden

There exists a gap between control theory and control practice,i.e.,all control methods suggested by researchers are not implemented in real systems and,on the other hand,many important in dustrial problems are not studied in the academic *** problems can help close this gap and provide many opportunities for members in both the controls theory and application *** goal is to survey and give pointers to different general controls and modeling related benchmark problems that can serve as inspiration for future benchmarks and then specifically focus the benchmark coverage on automotive control engineering *** the paper reflections are given on how different categories of benchmark designers,benchmark solvers and third part users can benefit from providing,solving,and studying benchmark *** paper also collects information about several benchmark problems and gives pointers to papers than give more detailed information about different problems that have been presented.

关键词： Benchmark automotive control robust control robotics engine control powertrain control system identification

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Production of hybrid aspen on agricultural land during one rotation in southern Sweden

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Journal of Forestry Research 2021年第1期32卷 181-189页

作者： Nils Fahlvik lars Rytter lars-Goran Stener The Forestry Research Institute of Sweden(Skogforsk) Ekebo 225026890 SvalovSweden

High potential productivity together with short rotation periods have made hybrid aspen an interesting option for wood production on former arable land in Nordic *** this study,some of the oldest active experimental plots with hybrid aspen in Sweden were remeasured at 23–30 years of age.A main aim was to assess age and productivity at the time of maximum mean annual volume *** addition,the infl uence of commercial thinning on stand development and diff erences in genetic gain among clones were *** from fi ve experiments in southern Sweden were used,including three genetic trials,one demonstration stand with a clone mixture and one stand regenerated from root *** three genetic trials were treated as single plot experiments,subject to a standard thinning *** the remaining experiments,diff erent thinning strategies were tested in a balanced block *** growth had culminated or was close to maximum at age 25–30 *** annual stem volume increment at culmination was 20–22 m 3 ha^−1 a^−*** height reached 30–35 m at 28–30 years of *** diameter at breast height was 27–29 cm after 29–30 years in the genetic *** ranking based on diameter at age 7–9 years was positively correlated with the ranking at the fi nal measurement in the genetic trials,20 years *** indicates that clones can be selected for superior growth based on results from young *** intense thinning programs increased the mean diameter compared to light *** study indicates that one or two early and relatively heavy thinnings can promote the development of crop trees,without jeopardizing total volume production during a rotation of 25–30 years.

关键词： Populus tremula×Populus tremuloides Rotation length Thinning Biomass

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The usefulness and significance of assessing rapidly progressive spermatozoa

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Asian Journal of Andrology 2010年第1期12卷 33-35页

作者： lars Bjorndahl Centre for Andrology and Sexual Medicine Clinic of Endocrinology Karolinska University Hospital Huddinge M52Stockholm Sweden Department of Medicme Karolinska Institutet Huddinge S-141 86 Stockholm Sweden

It is possible and clinically relevant to distinguish between slow and rapid progressive spermatozoa in basic semen analysis. This is discussed in light of the different purposes of semen analysis for the subfertile couple and the male patient. The two groups of progressive spermatozoa should be distinguished to help ensure that pertinent information available in the semen sample is not neglected.

关键词： male factor infertility manual sperm motility assessment quality control rapidly progressive spermatozoa referencevalues semen analysis staff training

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A new hadron spectroscopy

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Frontiers of physics 2015年第2期10卷 1-34页

作者： Stephen lars Olsen Center for Underground Physics Institute of Basic Science Daejeon 305-811 Korea

QCD-motivated models for hadrons predict an assortment of ＂exotic＂ hadrons that have structures that are more complex than the quark-antiquark mesons and three-quark baryons of the original quark-parton model. These include pentaquark baryons： the six-quark H-dibaryon~ and tetraquark, hybrid and glueball mesons. Despite extensive experimental searches, no unambiguous candidates for any of these exotic configurations have been identified. On the other hand, a number of meson states, one that seems to be a proton-antiproton bound state, and others that contain either charmed- anticharmed quark pairs or bottom-antibottom quark pairs, have been recently discovered that neither fit into the quark-antiquark meson picture nor match the expected properties of the QCD- inspired exotics. Here I briefly review results from a recent search for the H-dibaryon, and discuss some properties of the newly discovered states -the proton-antiproton state and the so-called XYZ mesons- and compare them with expectations for conventional quark-antiquark mesons and the predicted QCD-exotic states.

关键词： quarks charmonium pentaquarks di-baryons baryonium tetraquarks

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Sphingosine signaling and atherogenesis

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Acta Pharmacologica Sinica 2004年第7期25卷 3-8页

作者： Jacob HANSEN-SCHWARTZ,lars EDVINSSON Department of Clinical Experimental Research Glostrup University Hospital Glostrup Denmark Division of Experimental Vascular Research Institute of Medicine Lund University Sweden

Sphingosine-1-phosphate (S1P) has diverse biological functions acting inside cells as a second messenger toregulate cell proliferation and survival, and extracellularly, as a ligand for a group of G protein-coupled receptors(GPCRs) named the endothelial differentiation gene (EDG) family. Five closely related GPCRs of EDG family(EDG1, EDG3, EDG5, EDG6, and EDG8) have recently been identified as high-affinity S1P receptors. Thesereceptors are coupled via Gi, Gq, G12/13, and Rho. The signaling pathways are linked to vascular cell migration,proliferation, apoptosis, intracellular Ca2+ mobilization, and expression of adhesion molecules. The formation of anatherosclerotic lesion occurs through activation of cellular events that include monocyte adhesion to the endothe-lium and vascular smooth muscle cell (VSMC) migration and proliferation. Thus, S1P signaling may play animportant role in the pathogenesis of atherosclerotic vascular disease. This review highlights S1P signalling invascular cells and its involvement in the formation of atherosclerotic lesions.

关键词： sphingosine 1-phosphate sphingosine kinase sphingosine-1-phosphate receptors endothelium myocardium smooth muscle arteriosclerosis

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Flow-Field Analysis of Anti-Kidney Vortex Film Cooling

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Journal of Thermal Science 2012年第1期21卷 66-76页

作者： lars Grf Leonhard Kleiser Institute of Fluid Dynamics

Film cooling is an important measure to enable an increase of the inlet temperature of a gas turbine and, thereby, to improve its overall efficiency. The coolant is ejected through spanwise rows of holes in the blades or endwalls to build up a film shielding the material. The holes often are inclined in the downstream direction and give rise to a kidney vortex. This is a counter-rotating vortex pair, with an upward flow direction between the two vortices, which tends to lift off the surface and to locally feed hot air towards the blade outside the pair. Reversing the rotational sense of the vortices reverses these two drawbacks into advantages. In the considered case, an anti-kidney vortex is generated using two subsequent rows of holes both inclined downstream and yawed spanwise with alternating angles. In a previous study, we performed large-eddy simulations (which focused on the fully turbulent boundary layer) of this anti-kidney vortex film-cooling and compared them to a corresponding physical experiment. The present work analyzes the simulated flow field in detail, beginning in the plenum (inside the blade or endwall) through the holes up to the mixture with the hot boundary layer. To identify the vortical structures found in the mean flow and in the instantaneous flow, we mostly use the λ 2 criterion and the line integral convolution (LIC) technique indicating sectional streamlines. The flow regions (coolant plenum, holes, and boundary layer) are studied subsequently and linked to each other. To track the anti-kidney vortex throughout the boundary layer, we propose two criteria which are based on vorticity and on LIC results. This enables us to associate the jet vortices with the cooling effectiveness at the wall, which is the key feature of film cooling.

关键词： Film cooling anti-kidney vortex vortex identification trajectory tracking large-eddy simulation LES compound angle double row kidney vortex jet in cross-flow.

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Identification of digital technologies and digitalisation trends in the mining industry

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International Journal of Mining Science and Technology 2020年第6期30卷 747-757页

作者： lars Barnewold Bernd G.Lottermoser Institute of Mineral Resources Engineering RWTH Aachen University52062 AachenGermany

Digitalisation in mining refers to the use of computerised or digital devices or systems and digitised data that are to reduce costs,improve business productivity,and transform mining ***,it remains increasingly difficult for mining companies to decide which digital technologies are most relevant to their needs and individual *** paper provides an overview of digital technologies currently relevant to mining companies as presented and discussed by mining journals,the media and insight reports of leading consultancy *** technologies were systematically identified using text-mining techniques,and network analyses established the relations between significant *** demonstrated that currently 107 different digital technologies are pursued in the mining ***,an analysis of the actual implementation of digital technologies in 158 active surface and underground mines reveals a limited uptake of digital technologies in general and that the uptake increases with the run-of-mine ***-scale mining operations appear to select and apply digital technologies suitable to their needs,whereas operations with lower production rates do not implement the currently available digital technologies to the same *** minor producers may require other digital transformation solutions tailored to their capabilities and needs and applicable to their scale of operations.

关键词： Diffusion of digital technologies Automation Internet of things Big data Machine learning Artificial intelligence

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从模型到应用:基于生态系统服务权衡的乡村生态修复规划工具研究

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园林 2024年第3期41卷 4-12页

作者：董楠楠王怡琪 Harald Zepp lars Gruenhagen Malte Bührs Christin Busch 魏维轩同济大学建筑与城市规划学院上海200092 波鸿鲁尔大学地理学系波鸿44801 ILS-国家和城市发展研究所有限公司多特蒙德D-44135

在全球范围内的气候变化背景下,具有多种功能和服务价值的乡村生态空间成为当下国际生态规划研究与合作的关注热点之一。为实现乡村生态空间的精准管理与规划,中德双方围绕联合课题“生态系统服务概念在德国鲁尔与中国大都市区韧性发展... 详细信息

在全球范围内的气候变化背景下,具有多种功能和服务价值的乡村生态空间成为当下国际生态规划研究与合作的关注热点之一。为实现乡村生态空间的精准管理与规划,中德双方围绕联合课题“生态系统服务概念在德国鲁尔与中国大都市区韧性发展模式下的绿色基础设施规划应用”进行了深入探索。在土地利用与土地覆盖类型的基础上,进一步识别了生物群落类型,并基于调节、供给、文化三大生态系统服务类型,选取了评估生态系统服务供需权衡的指标和对应权重,构建了乡村生态空间规划场景下的生态系统服务价值评测模型。以上海市水库村为例,运用该课题的评测模型,初步评估了典型乡村生态规划场景下的生态系统服务价值。最后,从应用尺度、研究范围以及操作流程三个方面总结了该评测模型的优化方向。

关键词：乡村生态修复生态系统服务供需权衡决策辅助工具

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A Structural Bisulfite Assay to Identify DN Cruciforms

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Molecular Plant 2016年第9期9卷 1328-1336页

作者： Matthew Gentry lars Hennig Department of Plant Biology Uppsala BioCenter Swedish University of Agricultural Sciences and Linnean Center for Plant Biology 75007 Uppsala Sweden

In the half century since the discovery of the double-helix structure of DNA, it has become increasingly clear that DNA functionality is based on much more than its sequence in a double-helical structure. Further advances have highlighted the importance of additional aspects of DNA structure： its packaging in the higher order chromatin structure, positioning of nucleosomes along the DNA, and the occurrence of non-helical DNA structures. Of these, the latter has been problematic to prove empirically. Here, we describe a method that uses non-denaturing bisulfite sequencing on isolated Arabidopsis thaliana nuclei to determine the location of cytosines positioned outside the double helix as a result of non-B-form DNA structures. We couple this with computational methods and S1 nuclease digest to reliably identify stable, non-B-form, cruciform structures. This enables us to identify a palindrome in the promoter of FLOWERING LOCUS T that forms a stable non-B-form structure. The stronger conservation of the ability to form a nonhelical secondary structure than of the sequence suggests that this structure is biologically relevant.

关键词： DNA structure cruciform DNA genome organization

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