下载文档原格式
Central dogma （中心法则）：DNA 的遗传信息经RNA 一旦进入蛋白质就不能再输出了。
Reductionism （还原论）：把问题分解为各个部分，然后再按逻辑顺序进行安排的研究方法。
Genome （基因组）：单倍体细胞的全部基因。
transcriptome （转录组）：一个细胞、组织或有机体在特定条件下的一组完整基因。
roteome （蛋白质组）：在大规模水平上研究蛋白质特征，获得蛋白质水平上的关于疾病的发生、细胞代谢等过程的整体而全面的认识。
Metabolome （代谢组）：对生物体内所有代谢物进行定量分析并寻找代谢物与生病理变化的相关关系的研究方法。
Gene （基因）：具有遗传效应的DNA 片段。
Epigenetics （表观遗传学现象）：DNA 结构上完全相同的基因，由于处于不同染色体状态下具有不同的表达方式，进而表现出不同的表型。
Cistron （顺反子）：即结构基因，决定一条多肽链合成的功能单位。
Muton （突变子）：顺反子中又若干个突变单位，最小的突变单位被称为突变子。
recon （交换子）：意同突变子。
Z DNA（Z 型DNA）：DNA 的一种二级结构，由两条核苷酸链反相平行左手螺旋形成。
Denaturation （变性）：物质的自然或非自然改变。
Renaturation （复性）：变形的生物大分子恢复成具有生物活性的天然构想的现象。
egative superhelix （负超螺旋）：B-DNA 分子被施加左旋外力，使双螺旋体局部趋向松弛，DNA分子会出现向右旋转的力的超螺旋结构。
C value paradox （C值矛盾）：生物overlapping gene （重叠基因）：不同的基因公用一段相同的DNA序列。
体的大C值与小c 值不相等且相差非常大。
interrupted gene （断裂基因）：由若干编码区和非编码区连续镶嵌而成的基因。
splitting gene （间隔基因）：意思与断裂基因相同。
Asphalt （Bitumen） and Asbestos 沥青和石棉Non-Ferrous Metal 有色金属Anti-Corrosion Materials 防腐蚀材料Drafting 制图方案scheme, draft 草图sketch 服务用房service room 更衣室locker room 厕所lavatory 衣柜间ward robe 暖风间H.V.A.C room 多功能用房utility room 披屋（阁楼） penthousee. ROOFING AND CEILING 屋面及天棚女儿墙parapet 雨蓬canopy 屋脊roof ridge 坡度slope 坡跨比pitch 檐口eave 挑檐overhanging eave 檐沟eave gutter 平屋面flat roof 坡屋面pitched roof 檩条purlin 屋面板roofing board 天花板ceiling board 防水层water-proof course 吊顶suspended ceiling, false ceiling 檐板（窗帘盒） cornicef. WALL （CLADDING）墙体（外墙板）砌块墙block wall 清水砖墙brick wall without plastering 抹灰墙rendered wall 石膏板墙gypsum board, plaster board 纵墙longitudinal wall 横墙transverse wall 填充墙filler wall 防火墙fire wall 窗间墙wall between window 空心墙cavity wall 圈梁gird, girt, girth 玻璃隔断glazed wall 遮阳板sunshade 伸缩缝expansion joint 复合夹心板sandwich board 压型单板corrugatedsingle steel plate 外墙板claddingpanel 复合板composite panelg. FLOOR AND TRENCH 地面及地沟地坪grade 地面和楼面ground andfloor 垫层bedding course, blinding 面层covering, finish 结合层bonding（binding） course 水磨石地面terrazzo flooring 马赛克地面mosaicflooring 瓷砖地面ceramic tile flooring预制水磨石地面precast terrazzoflooring 排水沟drainage trench 沟盖板trench cover 活动盖板removablecover plate 镶板门panelled door 夹板门plywood door 铝合金门aluminumalloy door 卷帘门roller shutter door 弹簧门swing door 推拉门sliding door平开门side-hung door 折叠门foldingdoor玻璃门glazed door 密闭门air-Tightdoor 保温门thermal insulating door 镀锌铁丝网门galvanized steel wiremesh door 防火门fire door（大门上的）小门wicket门框door frame 门扇door leaf 门洞door opening 疏散门emergencydoor 纱门screen door 门槛door sill门边木stile 门樘侧料side jumb 槽口notch 铝合金窗aluminum alloywindow 百叶窗（通风为主） sun-bind, louver（louver, shutter, blind）塑钢窗plastic steel window 空腹钢窗hollowsteel window 固定窗fixed window 平开窗side-hung window 推拉窗sliding window 气窗transom 上悬窗top-hung window 中悬窗center-pivoted window 下悬窗hopperwindow 活动百叶窗adjustable louver天窗skylight 老虎窗dormer window密封双层玻璃sealed double glazing钢筋混凝土过梁reinforced concretelintel 钢筋砖过梁reinforced bricklintel 窗扇casement sash旋转门revolving door窗台window sill窗台板window board窗中梃mullion 窗横木mutin 窗边木stile 压缝条cover mould 窗帘盒curtain box 合页( 铰链) hinge (butts) 转轴pivot 长脚铰链parliament hinge 闭门器door closer 地弹簧floor closer 插销bolt 门锁door lock 拉手pull 链条chain 门钩door hanger 碰球ball latch 窗钩window catch 暗插销insert bolt 电动开关器electric opener 平板玻璃plate glass 夹丝玻璃wire glass 透明玻璃clear glass 毛玻璃(磨砂玻璃) ground glass (frosted glass) 防弹玻璃bullet-proof glass 石英玻璃quartz glass 磨光玻璃polished glass 着色玻璃pigmented glass 玻璃瓦glass tile 玻璃砖glass block 有机玻璃organic glass I. STAIRCASE, LANDING & LIFT (ELEVATOR) 楼梯、休息平台及电梯楼梯间staircase 疏散梯emergency stair 旋转梯spiral stair (circular stair)吊车梯crane ladder直爬梯vertical ladder 踏步step 扇形踏步winder (wheel step) 踏步板tread 档步板riser 踏步宽度tread width 防滑条non-slip insert (strips) 栏杆railing (balustrade) 平台栏杆platform railing 吊装孔栏杆railing around mounting hole 扶手handrail 梯段高度height of flight 防护梯笼protecting cage (safety cage) 平台landing (platform) 楼梯平台stair landing 自动扶梯escalator 观光电梯observation elevator 电梯坑lift pit 电梯井道lift shaftj. BUILDING MATERIAL WORDS AND PHRASES 建筑材料词汇及短语Bricks and Tiles 砖和瓦粘土砖clay brick 瓷砖glazed brick (ceramic tile) 防火砖fire brick 空心砖hollow brick 面砖facing brick 地板砖flooring tile 马赛克mosaic 陶粒混凝土ceramsite concrete 琉璃瓦glazed tile 脊瓦ridge tile 石棉瓦asbestos tile (shingle) 波形石棉水泥瓦corrugated asbestos cement sheetLime, Sand and Stone 灰、砂和石石膏gypsum 汉白玉white marble 碎石crushed stone 毛石rubble 蛭石vermiculite 珍珠岩pearlite 水磨石terrazzo 卵石cobble 砾石gravel 粗砂course sand 中砂medium sand 细砂fine sandCement, Mortar and Concrete 水泥、砂浆和混凝土硅酸盐水泥silicate cement 火山灰水泥pozzolana cement 白水泥white cement水泥砂浆cement mortar 石灰砂浆lime mortar 水泥石灰砂浆( 混合砂浆) cement-lime mortar 保温砂浆thermal mortar 防水砂浆water-proof mortar 耐酸砂浆acid-resistant mortar 耐碱砂浆alkaline-resistant mortar 沥青砂浆bituminous mortar 灰缝mortar joint 钢筋混凝土reinforced concrete 轻质混凝土lightweight concrete 细石混凝土fine aggregate concrete 沥青混凝土asphalt concrete 泡沫混凝土foamed concrete 炉渣混凝土cinder concreteFacing And Plastering Materials 饰面及粉刷材料水刷石granitic plaster斩假石artificial stone刷浆lime wash可赛银casein大白浆white wash麻刀灰打底hemp cuts and lime as base喷大白浆两道sprayed twice with white wash分格抹水泥砂浆cement mortar plaster sectioned板条抹灰lath and plasterAsphalt(Bitumen) and Asbestos 沥青和石棉沥青卷材asphalt felt沥青填料asphalt filler沥青胶泥asphalt grout冷底子油adhesive bitumen primer 沥青玛啼脂asphaltic mastic沥青麻丝bitumastic oakum石棉板asbestos sheet石棉纤维asbestos fiberTimber 木材裂缝crack透裂split环裂shake干缩shrinkage翘曲warping原木log圆木round timber方木square timber板材plank木条batten板条lath木板board红松red pine 白松white pine落叶松deciduous pine云杉spruce柏木cypress白杨white poplar桦木birch 冷杉fir 栎木oak 榴木willow 榆木elm 杉木cedar 柚木teak樟木wood 防腐处理的木材preservative-treated lumber 胶合板plywood 三(五)合板3(5)-plywood 企口板tongued and grooved board 层夹板laminated plank 胶合层夹木材glue-laminated lumber 纤维板fiber-board 竹子bambooMetallic Materials 金属材料黑色金属ferrous metal 圆钢steelbBar 方钢square steel 扁钢steel strap,flat steel 型钢steel section (shape) 槽钢channel 角钢angle steel 等边角钢equal-leg angle不等边角钢unequal-leg angle 工字钢I-beam 宽翼缘工字钢wide flange I-beam丁( 之)字钢T-bar (Z-bar) 冷弯薄壁型钢light gauge cold-formed steel shape 热轧hot-rolled 冷轧cold-rolled合金钢alloy steel 钛合金titanium alloy不锈钢stainless steel 竹节钢筋corrugated steel bar 变形钢筋deformedbar 光圆钢筋plain round bar 钢板steelplate 薄钢板thin steel plate 低碳钢lowcarbon steel 冷弯cold bending 钢管steel pipe (tube) 无缝钢管seamlesssteel pipe 焊接钢管welded steel pipe 黑铁管iron pipe 镀锌钢管galvanized steelpipe 铸铁cast iron 生铁pig iron 熟铁wrought iron 镀锌铁皮galvanized steelsheet 镀锌铁丝galvanized steel wire 钢丝网steel wire mesh 多孔金属网expanded metal 锰钢managanese steel高强度合金钢high strength alloy steelNon-Ferrous Metal 有色金属金gold 白金platinum 铜copper 黄铜brass 青铜bronze 银silver 铝aluminum 铅leadAnti-Corrosion Materials 防腐蚀材料聚乙烯polythene, polyethylene冷拉cold-drawn尼龙nylon冷压cold-pressed聚氯乙烯PVC (polyvinyl chloride) 磁漆enamel paint 轻工业的light industrial聚碳酸酯polycarbonate 干性油drying oil 古代建筑ancient architecture聚苯乙烯polystyrene 稀释剂thinner 现代建筑modern architecture丙烯酸树酯acrylic resin 焦油tar 标准化建筑standardized buildings 乙烯基酯vinyl ester 沥青漆asphalt paint 附属建筑auxiliary buildings橡胶内衬rubber lining 桐油tung oil, Chinese wood oil 城市规划city planning氯丁橡胶neoprene 红丹red lead 厂区内within site沥青漆bitumen paint 铅油lead oil 厂区外offsite环氧树脂漆epoxy resin paint 腻子putty 封闭式closed type氧化锌底漆zinc oxide primerk. OTHER ARCHITECTURAL TERMS 其它开敞式open type防锈漆anti-rust paint建筑术语半开敞式semi-open type耐酸漆acid-resistant paint 模数制modular system耐碱漆alkali-resistant paintDiscipline 专业单位造价unit cost水玻璃sodium silicate建筑architecture概算preliminary estimate树脂砂浆resin-bonded mortar土木civil承包商constructor, contractor环氧树脂epoxy resin给排水water supply and drainage现场siteBuilding Hardware 建筑五金总图plot plan扩建extension钉子nails采暖通风H.V.A.C (heating 、ventilation改建reconstruction螺纹屋面钉spiral-threaded roofing nail and air conditioning)防火fire-prevention环纹石膏板钉annular-ring gypsum 电力供应electric power supply防震aseismatic, quake-proofboard nail电气照明electric lighting防腐anti-corrosion螺丝screws电讯telecommunication 防潮dump-proof平头螺丝flat-head screw仪表instrument 防水water-proof螺栓bolt热力供应heat power supply 防尘dust-proof普通螺栓commercial bolt动力mechanical power防锈rust-proof高强螺栓high strength bolt工艺process technology 车流量traffic volume预埋螺栓insert bolt管道piping 货流量freight traffic volume 胀锚螺栓cinch boltConventional Terms 一般通用名词人流量pedestrian volume垫片washer建筑原理architectonics透视图perspective drawing Paint 油漆建筑形式architectural style 建筑模型building model底漆primer民用建筑civil architectureArchitectural Physics 建筑物理防锈底漆rust-inhibitive primer城市建筑urban architecture 照明illumination防腐漆anti-corrosion paint农村建筑rural architecture 照度degree of illumination调和漆mixed paint农业建筑farm building亮度brightness无光漆flat paint 工业建筑industrial building 日照sunshine透明漆varnish重工业的heavy industrial 天然采光natural lighting 银粉漆aluminum paint光强light intensity 侧光side light 顶光top light 眩光glaze 遮阳sun-shade Name Of Professional role 职务名称项目经理project manager (PM) 设计经理design manager 首席建筑师principal architect 总工程师chief engineer 土木工程师civil engineer 工艺工程师process engineer 电气工程师electrical engineer 机械工程师mechanical engineer 计划工程师planning engineer 助理工程师assistant engineer 实习生probationer 专家specialist, expert 制图员draftsman 技术员technician Drafting 制图总说明general specification 工程说明project specification 采用标准规范目录list of standards and specification adopted 图纸目录list of drawings 平面图plan 局部放大图detail with enlarged scale ．．．平面示意图schematic plan of... ．．．平剖面图sectional plan of... 留孔平面图plan of provision of holes 剖面section 纵剖面longitudinal section 横剖面cross (transverse) section 立面elevation 正立面front elevation侧立面side elevation 背立面back elevation 详图detail drawings 典型节点typical detail 节点号detail No. 首页front page 图纸目录及说明list of contents and description 图例legend 示意图diagram 草图sketch 荷载简图load diagram 流程示意图flow diagram 标准图standard drawing ．．．布置图layout of ... 地形图topographical map 土方工程图earth-work drawing 展开图developed drawing 模板图formworkdrawing 行和栏rows and columns备注remarks 曲线curves -曲折线zigzag line 虚线dotted line实线solid line 影线hatching line 等高线contour Line 环形annular 方形square 矩形rectangle 平行四边形parallelogram 五角形pentagon六角形hexagon 八角形octagon 梯形trapezoid扇形sector 圆锥形cone 椭圆形ellipse, oblong 净高headroom 截面尺寸sectionaldimension 进深depth 单跨single span 双跨double span多跨multi-span 标高elevation,level 室外地面标高groundelevation 室内地面标高floorelevation 柱网column grid 辅助面积service area 通道面积passage area 排水沟drain ditch地漏floor drain 消火栓firehydrant。
Structure and Function of Nucleic Acid1．The primary structure of nucleic acid is the sequence of nucleoside monophosphates from 5’ end to 3’ end in nucleic acid . (usually written as the sequence of bases).2．DNA denaturation：A DNA has lost its’ native conformation and double strand DNA is separated to single strand DNA by exposed to a destabilizing factor such as heat, acid, alkali,urea or amide. (when high temperature is used to denature DNA, the DNA is said to be melted). 3．Tm：is melting temperature at which half (50%) of DNA molecules are denatured.4. Annealing ：The process of renaturation of heat denatured DNA by slowly cooling is called annealing.5．Hyperchromic effect: the absorbance at 260nm of a DNA solution increases when the double helix is melted into single strands.6．Hybridization: when heterogeneous DNA or RNA are put together, they will become to heteroduplex via the base-pairing rules during renaturation if they are complementary in parts (not complete). This is called molecular hybridization.Replication1．The Central Dogma：It described that the flow of genetic information is from DNA to RNA and then to protein. According to the central dogma of molecular biology, DNA directs the synthesis of RNA, and RNA then directs the synthesis of proteins.2．Semiconservative replication：* The two parental strands separate and that each then serves as a template;* 4 kinds of dNTP as the stock;* Catalyzed by DNA polymerase;* Follow the usual base-pairing rules of A with T and G with C;* Each daughter duplex has one parental strand and one newly synthesized strand.3．Okazaki fragments ：The Short segments of DNA (1000－2000 bases in bacteria, 150-200 bases in eukaryotes) formed in the discontinuous lagging strand synthesis of DNA and are rapidly joined by DNA ligase to form a continuous DNA strand.4．Replicon：A unit of DNA that is replicated from one replication origin. 5．Primosome：The protein complex containing DnaB, DnaC, primase (DnaG), DNA oriC sequence and other factors that initiates synthesis of DNA.DNA synthesis proceeds in a 5'→3' direction and is semidiscontinuous. One of the new DNA strands is synthesized continuously and the other discontinuously in short pieces：6．Leading strand ：The strand that is continuously synthesized (in the same direction as replication fork movement).7．Lagging strand：The strand that is synthesized discontinuously in short pieces (Okazaki fragments) in a direction opposite to the direction of replication fork movement. The Okazaki fragments are then spliced together by DNA ligase.8．Telomere：Specialized structure at the end of a linear eukaryotic chromosome, which consists of tandem repeats of a short T,G-rich sequence on the 3’ ending strand and its complementary sequence on the 5' ending strand, allows replication of 5' ends of the DNA without loss of genetic information and maintains the stability of eukaryotic chromosome.9．Telomerase：An RNA-containing reverse transcriptase that using the RNA as a template, adds nucleotides to the 3’ ending strand and thus prevents progressive shortening of eukaryotic linear DNA molecules during replication. Human telomerase contains three parts:Human telomerase RNA, hTRHuman telomerase associated protein 1, hTP1Human telomerase reverse transcriptase, hTRT10．Reverse Transcription：Synthesis of a double-strand DNA from an RNA template. 11．Reverse transcriptase：A DNA polymerase that uses RNA as its template.RNA-dependent DNA polymeraseRNaseDNA-dependent DNA polymeraseGene Recombination and Genetic Engineering1. DNA Cloning:To clone a piece of DNA, DNA is cut into fragments using restriction enzymes. The fragments are pasted into vectors that have been cut by restriction enzyme to form recombinant DNA. The recombinant DNA are needed to transfer and replicate DNA in a host cell.This serial process and related technique are called DNA cloning, also called gene cloning.2. Genomic DNA library:The collection of bacteria clones that contain all the DNA in the organism’s genome on vector of plasmids or bacteriophage.3. α-complementation:some plasmid vectors (eg,pUC19) carry lacZ gene, whose product αfragment is the N-terminal of the β-galactosidase. Whereas, the mutant E.coli strain only synthesize the ω fragment, which is the C-terminal of the enzyme. Eitherα or ω fragment alone is nonfunctional. When the vector containing lacZ is introduced into mutant E.coli, both theαand ωfragments are present. So there is an interaction and a functionally intact β-galactosidase can form. This interaction is called α- complementation.Regulation of Gene Expression1. Housekeeping gene: It is the genes coding for proteins that are needed for basic life processes in all kinds of cells(such as enzymes for citric acid cycle).2. Operon:consists of more than 2 coding sequences, promoter, operator and other regulatory sequences clustered in the genome.3. Promoter: It is the specific DNA sequence binding to RNA-pol to initiate transcription.4. Enhancer: consisting of several functional elements, apart from transcriptional initiation site, enhancing the activity of promoter, determining the stage and spatial specificity, functioning in different direction and distance on upstream or downstream。
Lesson Twenty-fiveNA V AIDS 助航仪器Dialog A: Talking about New Installed ARPA对话1: 谈谈新装的ARPA雷达ed.Mr.Captain.大副：船长先生, 新装的雷达无法使用。
Master: What’s the matter?船长: 是什么问题？Chie.Officer...Th.scannin.lin.i.dar.red.an.th.backgroun.i.black.Sometime.i.i.difficul.t.distinguis.th.scannin.lin.o.th.display.大副: 扫描线是暗红的, 背景是黑色的, 有时很难在屏幕上区分扫描线。
Master......I.mus.b.designedl.defective..wil.sen..cabl.t.th.manufacture.t.as.fo.replacin.th.software.船长：一定是设计缺陷, 我发报给制造商, 要求换软件。
Dialog B: Reporting VHF Defectiveness对话2: 报告VHF故障Secon.Mate....Th.VH.transmitting/receivin.convertio.butto.i.no.working.e.VHF..foun.th.VH.installatio.ca.no.sen.an.message.Th.VH.installatio.stil.work.i.receivin.function.二副: VHF收/发转换按键不好用, 我在要追越前船用它时, 我发现VHF不能发任何信息, VHF仍处于承受功能。
Chie.Mate....Le.m.check.Oh.th.butto.i.ou.o.order.I.ca.no.b.pushe.wit.necessar.tools.大副: 让我检查一下, 噢, 这个按键坏了, 按不下去。
新斯的明拮抗顺阿曲库铵的时机对患者腹腔镜结直肠癌根治术后肌松残留和早期肺功能的影响林 琳 朱 旭厦门市中医院麻醉科（福建厦门 361000）【摘 要】 目的 探究新斯的明拮抗顺阿曲库铵的时机对患者腹腔镜结直肠癌根治术后肌松残留和早期肺功能的影响。
方法 选取于2021年2月—2022年9月在我院行结肠癌根治手术的194例患者为研究对象，以随机数字表法将患者分为空白对照组和试验组，然后结合给予新斯的明治疗时所体现的4个成串刺激（TOF）比值将试验组患者分为试验组A （TOF≤0.1）、试验组B（0.1＜TOF≤0.3）、试验组C（0.3＜TOF≤0.5）、试验组D（0.5＜TOF≤0.8）以及试验组E（TOF ＞0.8）。
对比组间肌松残余情况以及肺功能情况。
结果 插管前，试验组A患者TOF比值低于其他组（P＜0.01），空白对照组患者TOF比值高于其他组（P＜0.01）；空白对照组分别与试验组A~E在复苏室接受观察的时间比较，差异无统计学意义（P＞0.01）；试验组A患者肌松恢复指数低于其他组（P＜0.01），空白对照组患者肌松恢复指数高于其他组（P ＜0.01）。
插管前、拔管0.5 h以及拔管24 h时，组间1秒用力呼气容积（FEV1）、用力肺活量（FVC）和FEV1/FVC比较差异无统计学意义（P＞0.05）。
结论 结直肠癌根治术后给予新斯的明，有助于加快肌松恢复，但不会影响复苏室停留时间与肺功能水平。
【关键词】 新斯的明；顺阿曲库铵；结直肠癌根治术；肌松残留；肺功能DOI：10. 3969 / j. issn. 1000-8535. 2023. 09. 012Effect of neostigmine antagonizing timing of cisatracurium on residual muscle relaxation and early lung function after laparoscopic radical resection of colorectal cancerLIN Lin，ZHU XuAnesthesiology Department of Xiamen Traditional Chinese Medicine Hospital，Xiamen 361000，China【Abstract】 Objective To investigate the effect of timing of neostigmine antagonizing cisatracurium on residual muscle relaxation and early lung function in patients underwent laparoscopic radical resection of colorectal cancer．Methods February 2021 to September 2022，194 patients who underwent radical colon cancer surgery in our hospital were selected as the research subjects．The patients were randomly divided into a blank control group and an experimental group using a random number table method．Then，combined with the train-of-four（TOF）ratios observed during neostigmine treatment，the experimental group patients were divided into experimental group A（TOF≤0.1），experimental group B（0.1＜TOF≤0.3），experimental group C（0.3＜TOF≤0.5）， experimental group D（0.5＜TOF≤0.8）and experimental group E（TOF＞0.8）．The residual muscle relaxation and lung function between groups were compared．Results Before intubation，the TOF ratio of patients in experimental group A was lower than that of other groups（P＜0.01），while the TOF ratio of patients in the blank control group was higher than that of other groups（P＜0.01）．There was no significant difference in the observation time between the blank control group and the experimental group A~E in the postanesthesia care unit（P＞0.01）．The muscle relaxation recovery index of patients in experimental group A was lower than that of other groups（P＜0.01），while the muscle relaxation recovery index of patients in the blank control group was higher than that of other groups（P＜0.01）．There were no significant differences in force expiratory volume in one second（FEV1），forced Vital capacity（FVC）and FEV1/FVC between groups before intubation，0.5 h after extubation and 24 h after extubation（P＞0.05）．Conclusions Administration of neostigmine after radical surgery for colorectal cancer can accelerate muscle relaxation recovery，but it will not affect the residence time of the postanesthesia care unit and lung function levels．【Key words】 neostigmine；cisatracurium；radical resection of colorectal cancer；residual muscle relaxation；lung function结直肠癌（colorectal cancer，CRC）作为好发于患者结肠、直肠部位的恶性肿瘤，其发病率与致死率呈上升趋势，严重威胁患者的生命健康［1］。
Noninvasive Visualization of Retinoblastoma Growth and Metastasis via Bioluminescence ImagingXunda Ji,1Lin Cheng,1Fang Wei,1Huiming Li,1Mengyun Wang,1Yuhua Tian,1 Xiafang Chen,1Yufei Wang,1Frank Wolf,2Chuanyuan Li,*,2and Qian Huang*,1P URPOSE.To establish human retinoblastoma(RB)animal mod-els that allow sensitive,noninvasive and continuous monitor-ing of tumor growth and metastasis in vivo.M ETHODS.The human RB tumor cell lines HXO-Rb44and Y79 were engineered to express a fusion reporter gene allowing for bioluminescence andfluorescence imaging.Intraocular and met-astatic tumors were induced in immunodeficient nude mice by injection of bioluminescent RB cells into eye compartments and into the left ventricle or tail vein.The growth kinetics of intraoc-ular and metastatic tumors was quantitatively and continuously monitored via bioluminescence imaging(BLI).R ESULTS.Intraocular injection of HXO-Rb44-GFP-luc cells re-sulted in100%,80%,and80%successful RB tumor develop-ment in the anterior chamber,vitreal cavity and subretinal space,respectively.The subretinal injection of Y79-GFP-luc cells resulted in100%tumor development.BLI signal intensity correlated with the number of tumor cells injected as well as the weight of the tumor-bearing eyes.After bilateral subretinal injection of HXO-Rb44-GFP-luc cells,one of six RB tumor mice developed brain metastasis.Intracardiac injection of HXO-Rb44-GFP-luc cells resulted in metastatic disease in9of15 nude mice,whereas tail vein injection resulted in metastasis in 1of16.Metastases were developed in multiple organs,includ-ing lymph nodes,bone,and brain,resembling the metastatic profile in patients with RB.C ONCLUSIONS.BLI allowed sensitive,noninvasive,and quantita-tive localization and monitoring of intraocular and metastatic RB tumor growth in vivo and thus may be a useful tool to study RB biology as well as anti-RB therapies.(Invest Ophthalmol Vis Sci.2009;50:5544–5551)DOI:10.1167/iovs.08-3258R etinoblastoma(RB)is the most common primary intraoc-ular malignant tumor in children.RB tumors are generally aggressive and occur in sporadic(mostly unilateral,unifocal), and hereditary(often multifocal and/or bilateral)forms and usually affect children younger than5years.1,2Early diagnosis is crucial for successful treatment of RB.3Enucleation is usually performed for larger RB tumors.Small tumors are treated with conservative therapeutic approaches,including chemother-apy,radiotherapy,laser therapy,and cryotherapy.For large tumors,enucleation is inevitable.The forming of distant me-tastases is the major cause of death.4Therefore,early detection of intraocular tumors and distant metastases is a key prognostic factor for preservation of vision,eye retention,and survival.RB is a prototype of human hereditary tumors,in which one allele of the Rb1tumor suppressor gene is inactivated in all somatic cells.On spontaneous inactivation of the second allele in a retinocyte,RB is formed.The gene product of Rb1is a key regulator of cell cycle progression.5,6Rb1gene mutations are implicated in carcinogenesis of many types of cancer such as breast cancer,ovarian cancer,bladder cancer,and small cell lung cancer.7,8Therefore,RB animal models are important tools for the study of molecular mechanisms of human cancer in general and the investigation of the efficiency of novel treatments for RB in particular.5In the past,various RB animal models have been estab-lished,of which the Y79model and the WERI-Rb model are most widely used.The former closely resembles metastatic human RB,whereas the latter mimics nonmetastatic lesions.9 However,to obtain information about growth dynamics and metastasis,tumor-bearing animals must be killed and subjected to histologic analysis,requiring a large number of animals.In addition,micrometastases and small tumors are difficult to detect histologically,requiring labor intensive screening of thin whole body slice preparations.A variety of methods have been developed that partly overcome these limitations,and some have permitted noninvasive longitudinal studies for or-thotopic tumor growth and distal metastasis.These include microcomputed tomography(microCT),magnetic resonance imaging(MRI),positron emission tomography,andfluores-cence imaging.Bioluminescence imaging(BLI),a newly devel-oped technology,presents several advantages over these meth-ods.Advantages include high sensitivity,high-throughput, short imaging time,ease of operation,and lower cost.10,11All these features make BLI a particularly attractive imaging strat-egy for monitoring intraocular tumor growth and distant me-tastasis.12,13In the present study,we used a dual optical reporter gene, encoding both enhanced greenfluorescence protein(EGFP) and luciferase,to label human RB tumor cell lines,HXO-Rb44 and Y79.The EGFP reporter facilitates the selection of in vitro transduced cell populations by epifluorescent microscopy or fluorescence-activated cell sorting(FACS),whereas luciferase is a sensitive and convenient reporter for noninvasive quanti-tative detection of tumor growth and metastasis in vivo.The new RB-BLI models could serve as useful tools for the under-standing of the early events during RB tumor growth andFrom the1Experimental Center,The First People’s Hospital,Shanghai Jiaotong University,Shanghai,China;and the2Department ofRadiation Oncology,University of Colorado Health Sciences Center,Aurora,Colorado.Supported by Grant2004CB518804from the National Basic Re-search Program of China,Grants30325043and30428015from theNational Natural Science Foundation for outstanding junior investiga-tors,and Shanghai Leading Academic Discipline Project B204.Submitted for publication December5,2008;revised April12andJune19,2009;August31,2009.Disclosure:X.Ji,None;L.Cheng,None;F.Wei,None;H.Li,None;M.Wang,None;Y.Tian,None;X.Chen,None;Y.Wang,None;F.Wolf,None;C.Li,None;Q.Huang,NoneThe publication costs of this article were defrayed in part by pagecharge payment.This article must therefore be marked“advertise-ment”in accordance with18U.S.C.§1734solely to indicate this fact.*Each of the following is a corresponding author:Qian Huang,Experimental Center,The First People’s Hospital,Shanghai JiaotongUniversity,85Wu Jin Road,Shanghai200080,China;qhuang@.Chuanyuan Li,Department of Radiation Oncology,University of Colo-rado Health Sciences Center,12801E17th Street,Aurora,CO80045;chuan.li@.Investigative Ophthalmology&Visual Science,December2009,Vol.50,No.12 5544Copyright©Association for Research in Vision and Ophthalmologymetastasis in vivo as well as for the preclinical assessment of novel anti-RB therapeutics.M ETHODSAnimalsMale BALB/c nude mice were obtained from the Shanghai SLAC Labo-ratory Animal Co.(Shanghai,China).Animals were maintained in accordance with the Statement for the Use of Animals in Ophthalmic and Vision Research,Association for Research in Vision and Ophthal-mology.All mice were6to8weeks of age at the time of tumor cell injection.Generation of Stable Transfectants Expressing Luciferase and EGFP Fusion ProteinThe human RB cell line HXO-Rb44,which was originally established by Hunan Medical University,Xiangya Hospital,Department of Ophthal-mology,and therefore named HXO-Rb44,was isolated from a2.5-year-old patient with bilateral RB with no family history.14The right eye was enucleated because of secondary glaucoma and used for establishment of RB the cell line.The histologic examination revealed that it was poorly differentiated and no Rb protein was detected by immuno-chemical staining.14,15The Y79cell line was obtained from Nanjing KeyGen Biotech.Co.Ltd.,Nanjing,China.Both cell lines were grown in suspension in RPMI-1640medium supplemented with10%fetal bovine serum(FBS)at37°C in a humidified atmosphere containing5% CO2.Cell culture reagents were purchased from Invitrogen(Carlsbad, CA).To obtain bioluminescent cells,we transfected HXO-Rb44and Y79cells with a plasmid carrying an EGFP-luciferase fusion gene, according to manufacturer’s instructions(Lipofectamine;Invitrogen). The transfectants were selected with0.5mg/mL geneticin(G418; Invitrogen).Positive clones were obtained by limiting dilution and detected by GFP and bioluminescence imaging.Stably transfected HXO-Rb44-GFP-luc and Y79-GFP-luc cells maintained GFP and lucif-erase expression when grown in RPMI-1640medium containing10% FBS and reduced geneticin(0.1mg/mL).The growth rate and mor-phology of both HXO-Rb44-GFP-luc and Y79-GFP-luc cells were indis-tinguishable from their parent cells.The clones,HXO-Rb44-GFP-luc-16 and Y79-GFP-luc-F10D10,with stable and high level expression of EGFP and luciferase were selected for further studies in vitro and in vivo.Establishment of RB Orthotopic TumorModels in MiceRB orthotopic tumor models were established by inoculation of biolu-minescent RB cells into the subretinal space,vitreal cavity,or anterior chamber.The mice were anesthetized by intraperitoneal(IP)injection with pentobarbital(50mg/kg body weight)in combination with topical application of0.4%oxybuprocaine hydrochloride(Santen Phar-maceutical,Osaka,Japan).The pupil was dilated with a0.5%/0.5% tropicamide/phenylephrine hydrochloride eye drop(Santen Pharma-ceutical).A plastic ringfilled with2.5%cellulose was placed on the cornea to aid visualization of the fundus.Injection was performed under a binocular surgical microscope.The initial puncture was made through the sclera behind the limbus with a28-gauge beveled needle. 1to2ϫ105bioluminescent RB cells(1ϫ105for HXO-Rb44-GFP-luc cells and2ϫ105for Y79-GFP-luc cells)in2L PBS were injected slowly into the vitreal cavity or subretinal space of the left eye with a 32-gauge needle attached to a10L microsyringe.The right eye received no injection and served as an internal control.To mimic bilateral RB,we subretinally injected a group of six mice bilaterally with1ϫ105HXO-Rb44-GFP-luc cells in each eye.Injection of the tumor cells into the anterior chamber was performed as described by Niederkorn et al.16HXO-Rb44-GFP-luc cells(1ϫ105)in2L PBS were injected into the anterior chamber of the left eye with a32-gauge needle.The growth dynamics of intraocular RB tumor cells in vivo were monitored by BLI.At the end of observation,the animals were imaged and the tumor-bearing eyes were enucleated,weighed,and prepared for histologic analysis.Establishment of a Distant MetastasesModel of RBA model for systemic metastasis of RB was generated by intracardiac injection or tail vein injection of bioluminescent RB tumor cells.A cell suspension of HXO-Rb44-GFP-luc(1ϫ106/100L PBS)was prepared immediately before injection.Mice were anesthetized by IP injection with pentobarbital(50mg/kg body weight).HXO-Rb44-GFP-luc cells (1ϫ106)in100L PBS were inoculated into the left ventricle through the left-front chest according to the method described by Arguello et al.17To maximize efficacy,we completed the nonsurgical injection procedure for each mouse within60seconds,interrupted by three to four short pauses in consideration of the small cardiac size of the mice. To verify whether the injection was successful,we performed BLI immediately after injection.A satisfactory injection was indicated by a thoracic/whole-body(T/WB)ratio less than0.5(see Fig.3A)in accor-dance with Drake and colleagues’criteria.18For tail vein injection, mouse tails were placed in40°C warm water to cause vasodilatation, facilitating injection procedure.HXO-Rb44-GFP-luc cells(1ϫ106)in 100L PBS were injected into the lateral tail vein.BLI was performed immediately after injection.Forming of metastases was evaluated by BLI on thefirst day and once a week for up to5to6weeks after tumor cell injection.Bioluminescence ImagingBLI was performed according to the manufacturer’s instructions (NightOwl LB981Molecular Imaging System;Berthold Technologies, Bad Wildbad,Germany).To illustrate that the luminescence is propor-tional to the number of cells injected and to determine the detection limit,we serially diluted HXO-Rb44-GFP-luc and Y79-GFP-luc cells into 96-well plates.D-luciferin(Molecular Imaging Products,Ann Arbor, MI)at afinal concentration of150g/mL was added to each well,and the plates were imaged for10minutes.In addition,various amounts of HXO-Rb44-GFP-luc cells were injected into the subretinal space to determine the detection limit in vivo.For in vivo imaging,the mice received an IP injection of100mg/kg D-luciferin in100L PBS.After 5minutes,the mice were anesthetized via IP injection of pentobarbital (50mg/kg body weight)or1–3%isoflurane inhalation.The exposure time ranged from1second to10minutes,depending on the intensity of bioluminescence emitting from the tumor cells.For further confir-mation of tumor metastatic foci,ex vivo imaging was performed.Mice with positive metastatic bioluminescence signals were killed,the sus-pected metastatic tissues or organs were removed and placed in indi-vidual wells of a24-well plate containing150g/mL D-luciferin in PBS, and then imaged.Solid tissues with luminescent tumor cells,confirmed by ex vivo BLI,were subsequentlyfixed for histologic evaluation.The bioluminescent images were pseudocolored and superimposed on conventional photographs acquired before BLI.Regions of interest (ROI)were drawn around the tumor sites and quantified as photon counts per second.Histologic AnalysisTo confirm the presence of metastatic RB tumor cells,we excised tissues with detectable BLI emission signals and prepared them for histologic analysis.To harvest metastatic sites in the brain,we killed the mice with positive BLI signals by cardiac perfusion with0.9%saline followed by4%paraformaldehyde.The skull was removed and the brain was plated under afluorescence stereoscope to locate sites with GFP expression.In addition,skull,femur and maxilla werefixed with 4%paraformaldehyde and then decalcified by immersion in10%hy-drochloride for24hours.Other soft tissues including lymph nodes werefixed with4%paraformaldehyde.Other procedures,including paraffin embedding,sectioning,hematoxylin and eosin(H&E)staining, and immunohistochemical staining for GFP,were performed accord-IOVS,December2009,Vol.50,No.12Noninvasive Visualization of Retinoblastoma Growth and Metastasis5545ing to standard protocols.For immunohistochemistry a mouse anti-GFP monoclonal antibody(Santa Cruz Biotechnology,Santa Cruz,CA)was used at a concentration of1:25.Statistical AnalysisRegression plots were used to describe the relationship between bi-oluminescence intensity and the number of tumor cells or the weight of tumor-bearing tissues.The r2values were presented to assess the quality of the regression model.For orthotopic RB models,the growth kinetics of RB tumors were analyzed by ANOVA followed by the post hoc Dunnett’s t-test.PϽ0.05was considered statistically significant (SAS Institute,Cary,NC).R ESULTSStable GFP and Luciferase Expression inHXO-Rb44and Y79CellsHXO-Rb44and Y79cells stably expressed GFP and luciferase after transfection with an EGFP-Luc dual reporter gene con-struct(pCMV-EGFP-Luc)and selection by G418.The propor-tion of GFP-positive cells in a selected clone(denoted HXO-Rb44-GFP-luc-16and Y79-GFP-luc-F10D10),determined by flow cytometry analysis,consistently exceeded98%during in vitro culturing for2months.There were no obvious changes in either growth rate or morphology in comparison with the parental cells.Correlation of Bioluminescent Intensity with the Number of Bioluminescent RB Cells In Vitro and In VivoThe ability to detect bioluminescent tumor cells in vitro and in vivo depends on the following three major factors:(1)intensity of luminescent signal from tumor cells(i.e.,light emission per cell and the total numbers of tested cells),(2)sensitivity of the instru-ment,and(3)signal attenuation through tissue.To determine the efficiency and limitation of BLI both in vitro and in vivo,we plated a series of different numbers of cells into black96-well plates and injected a series of different numbers of cells into the subretinal space.As shown in Figure1,the luminescent emissions from HXO-Rb44-GFP-luc cells and Y79-GFP-luc cells,propagated in black96-well plates,were efficiently detected by the molecular imaging system(NightOwl LB981;Berthold Technologies)allow-ing detection of as few as157cells per well for HXO-Rb44-GFP-luc cells and3125cells per well for Y79-GFP-luc cells.Light emission per cell was127Ϯ44photon counts/s for HXO-Rb44-GFP-luc cells and5.05Ϯ0.74photon counts/s for Y79-GFP-lucF IGURE1.In vitro and in vivo biolu-minescence images of HXO-Rb44-GFP-luc cells and Y79-GFP-luc cells.(A)Bioluminescence image of HXO-Rb44-GFP-luc cells serially diluted intriplicate wells of a black96-wellplate.(B)Luciferase activity of HXO-Rb44-GFP-luc cells,expressed asphoton counts per second,corre-lated in a linear fashion with thenumber of cells in a96-well plate(r2ϭ0.975).(C)Bioluminescence im-ages of mouse eyes after subretinalinjection of different amounts ofHXO-Rb44-GFP-luc cells.The detec-tion limit was10,000cells.(D)Biolu-minescent intensity was proportionalto the number of cells injected intothe subretinal space(r2ϭ0.877).(E)Bioluminescence image of Y79-GFP-luc cells serially diluted in triplicatewells of a black96-well plate.(F)Luciferase activity of Y79-GFP-luccells,expressed as photon countsper second,correlates in a linearfashion with the number of cells in a96-well plate(r2ϭ0.998).5546Ji et al.IOVS,December2009,Vol.50,No.12F IGURE 2.Intraocular RB models of HXO-Rb44-GFP-luc cells.Mice received intraocular injections of HXO-Rb44-GFP-luc cells in the anterior chamber,vitreal cavity,or subretinal space.After inoculation,the mice were observed with BLI.At the end point of the observation period,the tumor-bearing eyes were enucleated and weighed,and the eyes and brains were subjected to histologic examination.(A )Serial images at different time points from a representative mouse in three different intraocular models.(B )Tumor growth curves obtained by quantification of bioluminescent signals in the eyes of individual mice.(C )On day 40,the tumor-bearing eyes were enucleated and weighed.The weight of the tumor-bearing eye (in grams)was correlated with the bioluminescence signal in each subject.(D )A representative photograph of H&E sections from three different intraocular RB models.(E )GFP immunohistochemical staining of three different intraocular RB models.(F )Image of mouse with bilateral RB and metastasis in the brain (arrow :metastatic focus).(G )H&E section from of brain tissue with metastatic RB tumor cells.T,tumor;C,cornea;R,retina;L,lens.IOVS,December 2009,Vol.50,No.12Noninvasive Visualization of Retinoblastoma Growth and Metastasis 5547cells,calculated based on the ratio of detected photons per well to the total number of cells.Linear regression analysis showed a good correlation between the number of cells and photon counts per second(Fig.1).In vivo,similarly encouraging results were obtained for HXO-Rb44-GFP-luc cells,as shown in Figure1C.BLI allowed detection of as few as10,000cells immediately after injection into the subretinal space.Linear regression analysis showed a significant correlation between the bioluminescence intensity of the eye and the number of cells in the subretinal space(r2ϭ0.877;Fig1D).Monitoring Orthotopic Tumor Growth viaIn Vivo BLIAs bioluminescent signals correlated well with the number of cells,we suggested that longitudinal quantification of biolumi-nescent signals emitted from tumor-bearing eyes could be used to determine tumor growth kinetics.Intraocular tumors, formed by inoculation of1ϫ105HXO-Rb44-GFP-luc cells into the anterior chamber,vitreal cavity,and subretinal space, showed generally similar growth dynamics(Figs.2A,2B).A substantial initial reduction in signal intensity was observed in all three intraocular RB models,indicating death or clearance of a large proportion of tumor cells soon after intraocular injection.Thereafter,a steady increase in photon emission was observed,reflecting proliferation of the surviving tumor cells. Successful engraftment of transplanted HXO-Rb44-GFP-luc tu-mor cells was recorded in100%,80%,and80%of recipients in the anterior chamber,vitreal cavity,and subretinal space of nude mice,respectively.After subretinal injection of2ϫ105 Y79-GFP-luc cells,luciferase signals were not detected until2 weeks after injection,when the tumors had already grown to a significant size.However,tumors developed in100%of mice injected with Y79-GFP-luc cells(Fig3).At the end of the observation period,the tumor-bearing eyes were enucleated and weighed.In all intraocular models,the eyeball weight correlated with photon counts per second per eye obtained from in vivo BLI.The presence of human RB tumors was confirmed by histologic analysis and immunochemistry stain-ing,and almost all RB tumor cells showed positive GFP expres-sion(Figs.2,3).Detecting Systemic MetastasesTo establish a model of systemic metastases common in pa-tients with RB,we injected HXO-Rb44-GFP-luc cells into the left ventricle or the tail vein.Satisfactory intracardiac injection was indicated by a thoracic/whole body(T/WB)ratio of less than0.5(Fig.4A)as recommended by Drake et al.18BLI was performed immediately after intracardiac injection,where the luminescent RB cells appeared as diffuse photon accumula-tions throughout the body of the animal,including the abdo-men and testes.Photon emission appeared to be completely abolished24hours after injection.Metastatic tumor growth was tracked by serial imaging at weekly intervals.Nine of15 mice that had received intracardiac injection subsequently developed metastases(Table1,Figs.4A,4B).Although direct invasive spread to the orbital tissue or the surface of the cornea had been observed in both orthotopic HXO-Rb44-GFP-luc and Y79-GFP-luc RB models,only one of six mice with bilateral RB tumors developed brain metastasis10 weeks after subretinal injection of HXO-Rb44-GFP-luc cells,as detected by in vivo BLI and further confirmed by histologic examination(Figs.2F,2G).The growth pattern and metastasis of orthotopic RB tumor models from HXO-Rb44-GFP-luc and Y79-GFP-luc cells is summarized in Table2.Luminescence signals from metastatic foci werefirst de-tected on day22after intracardiac injection and steadily in-creased until the end of the observation period(Fig.4C). Metastatic sites,detected by BLI on day36after injection,were located in the head(brain,maxilla,and skull),hind leg femur, and thoracic sites(Figs.4A,4B).Four mice had multiple met-astatic foci.None of these metastatic foci was superficially palpable.The signal intensities of each separate metastatic focus increased with time(Fig.4C).Ex vivo BLI orfluores-cence stereoscope imaging was conducted with tissues ex-cised from sites where in vivo BLI emission signals had been detected(Fig.4B).The presence of RB tumor cells in these metastatic lesions was further confirmed by H&E and immu-nochemistry staining,and almost all RB tumor cells were GFP positive(Figs.4D,4E).The most common sites of metastatic lesions were the lymph nodes(7/15,47%),bone(6/15,40%), and brain(2/15,13%)(Table1).The intensity of in vivo bioluminescence from living mice and ex vivo biolumines-cence from excised tissues correlated with the size of the metastatic lesions as detected by histologic analysis.The distribution of tumor cells and the rate of metastatic foci formation after tail vein injection was quite different from that after intracardiac injection.Immediately after tail vein injection,bioluminescence signals accumulated in the thorax, indicating that the majority of injected cells became stuck in the lung during theirfirst pass through its circulation(Fig.5A). After24hour,photon emission appeared to be completely abolished.Only1of16mice that had received a tail vein injection showed metastatic signals within the6-week obser-vation period,appearing on day29after injection and steadily increasing thereafter(Figs.5B,5D).Histologic analysis con-firmed that RB tumor cells were present in the mandible(Fig5E).F IGURE3.Intraocular RB models of Y79-GFP-luc cells.Mice received in-traocular injections of Y79-GFP-luc cells in the subretinal space.(A)Se-rial images at different time points from a representative mouse.(B)Tu-mor growth curves obtained by quantification of bioluminescent sig-nals in the eyes of individual mice.(C)On day49,the tumor-bearing eyes were enucleated and weighed. The weight of the tumor-bearing eye (grams)was correlated with the bi-oluminescence signal in each sub-ject.(D)A representative photo-graph of H&E section from Y79 intraocular RB model.T,tumor;R, retina.5548Ji et al.IOVS,December2009,Vol.50,No.12D ISCUSSIONIn this study we describe a new orthotopic and metastatic RB model that combines dual reporter gene luciferase-GFP–la-beled human RB tumor cells with BLI technology and allows sensitive,continuous and noninvasive monitoring of intraocu-lar tumor growth and metastasis in vivo.In the past,efforts have been made to develop animal models for RB.Xenograft models have been created by inject-ing human RB tumor cells subcutaneously or into theeyeF IGURE 4.Systemic metastasis model after intracardiac injection with HXO-Rb44-GFP-luc cells.HXO-Rb44-GFP-luc cells (1ϫ106)were injected into the left ventricle and followed up by BLI.(A )Representative image immediately after injection and on day 36after intracardiac injection.(B )Images acquired with a fluorescence stereoscope or ex vivo BLI from excised tissues to confirm the presence of metastatic lesions.(C )Growth curve of metastatic lesion generated by quantification of bioluminescent signals at various time points.The curves marked with the same superscript letter represent multiple metastatic foci in one mouse.(D )Representative photographs of H&E sections from different metastatic foci.(E )Immunohistochemical staining of different metastatic foci with a GFP antibody.T,tumor;B,bone;Br,brain;LN,lymph node.T ABLE 1.Summary of Metastatic Foci after Intracardiac Injection in Nine Nude Mice Location of Metastatic Foci Metastatic Foci (n )Brain2*†Lymph nodes 7(axillary 2*†;submandibular 2*†;paraaortic 3†)Bone6(maxilla 3*†;skull 1*†;femur 2*†)*Metastasis confirmed by histologic analysis (H&E staining).†Metastasis confirmed by ex vivo BL1.IOVS,December 2009,Vol.50,No.12Noninvasive Visualization of Retinoblastoma Growth and Metastasis 5549compartments of immunodeficient mice or rats.3,9The widely used Y79cell line is capable of developing metastasis in the brain parenchyma after injection into the vitreous.However,it fails to develop distant metastases in other organs commonly affected by human RB.Another widely used model cell line for human RB is WERI-Rb;however,this cell line does not form metastases as well.9We chose HXO-Rb44and Y-79cell lines to generate GFP and luciferase reporter carrying model cell lines for RB.Both of these cell lines are Rb protein negative and exhibit similar morphology and growth dynamics.As the luciferase detection limit for HXO-Rb4cells compared to Y79cells was 20times higher in vitro,we chose to use the HXO-Rb44cell line over the better established Y79cell line for our models for systemic metastases,allowing us to detect very early metastatic foci.We do not know why the rate of brain metastases with the HXO-Rb44cell line was lower than that of Y79model de-scribed by Chevez-Barrios et al.,9but we suspect that it may bedue to different recipient mice.It has been reported that the Rag-2-knockout mice,used by Chevez-Barrios et al.,9lacked NK cells and therefore allowed more efficient metastasis from primary tumors.19In contrast,the nude mice used in this study have been shown to have residual innate immune cells and therefore exhibit a reduced rate of metastasis.Human retinoblastomas exhibit four patterns of invasion and metastasis 9:(1)direct invasive spread along the optic nerve to the brain,the orbital tissue,and adjacent bone;(2)spread via the circulating subarachnoid fluid tumor cells to the spinal cord,distant sites of the brain,and the contralateral optic nerve;(3)hematogenous dissemination causing wide-spread metastasis to the lungs,bones,brain,and other viscera,and (4)lymphatic spread,if the tumor is located anteriorly or massive extraocular invasion has occurred,tumor cells can spread via the lymphatic system.Because our RB cell line failed to form distal metastases after intraocular injection,we in-jected bioluminescent RB cells directly into the systemic cir-culation.Systemic injection of tumor cells resulted in meta-static diseases with a pattern similar to human RB metastatic diseases.However,it has to be noted that,with the injection of tumor cells into the circulation,early steps of metastases such as localized invasion and intravasation are omitted in our mod-els.As mentioned in the results,the majority of mice receiving intracardiac injection developed systemic metastatic disease (9/15)whereas of those mice receiving tail vein injection,only 1mouse (of 16)actually developed metastasis.The most com-mon site of metastases was the lymphatic system (47%),bone (40%),and brain (13%).BLI imaging has some distinct advantages over histopatho-logic analysis for monitoring tumor growth dynamics.These advantages are as follows:(1)Noninvasive in vivo monitoring:BLI allows continuous noninvasive monitoring and precise quantification of in vivo tumor growth and metastasis.Tumor xenografts can be continuously followed up in the living mouse by using multiple imaging time points.In contrast to non–imaging-based methods that require killing the mice for each assessment time point,BLI imaging experiments require fewer animals per experimental group.(2)High sensitivity:BLI is very sensitive and detects a small number of luciferase reporter carrying cells.The metastatic lesion detected in this study was as small as 0.138ϫ0.088mm.Lesions of this size are impossible to detect with other imaging techniques such as CT or MRI.Further improvement in sensitivity and resolution of future BLI devices might allow the detection of smaller micro-metastases in the micrometer range.(3)Good correlation be-tween the signal and the number of cells:There is a good correlation between number of cells and the BLI signal.Changes of the BLI signal over time precisely reflect tumor growth or regression.As only living cells possess luciferase activity,necrotic parts of the tumor will not contribute to the overall BLI signal.(4)High throughput,fast,and easy to use:T ABLE 2.Summary of Intraocular RB Models Site of Injection Number of MiceCell Line and Number of Cells Injected Initial Occurrence of Luc Activity (Signal Intensity)*Observation period (Signal at End of Observation Period)*Metastasis Unilateral subretina 5HXO-Rb44-GFP-luc 1ϫ105Day 0(1e ϩ4.70)Ϯ(1e ϩ0.43)6weeks (1e ϩ6.38)Ϯ(1e ϩ1.59)None Unilateral intravitreous 5HXO-Rb44-GFP-luc 1ϫ105Day 0(1e ϩ5.00)Ϯ(1e ϩ0.67)6weeks (1e ϩ6.08)Ϯ(1e ϩ1.43)None Unilateral anterior chamber5HXO-Rb44-GFP-luc 1ϫ105Day 0(1e ϩ5.18)Ϯ(1e ϩ0.92)6weeks (1e ϩ6.90)Ϯ(1e ϩ0.45)None Bilateral subretina 6HXO-Rb44-GFP-luc 1ϫ105Day 0(1e ϩ5.00)Ϯ(1e ϩ0.44)10weeks (1e ϩ7.73)Ϯ(1e ϩ0.90)1(Brain)Unilateral subretina7Y79-GFP-luc 2ϫ105Day 14(1e ϩ3.68)Ϯ(1e ϩ0.34)7weeks (1e ϩ6.56)Ϯ(1e ϩ0.36)None*Signal intensities are expressed as photon count/second ϮSD.F IGURE 5.Systemic metastasis model after tail vein injection with HXO-Rb44-GFP-luc cells.HXO-Rb44-GFP-luc (1ϫ106)cells were in-jected into the tail vein and followed up by BLI.(A )BLI images taken immediately after injection.(B )Serial images at different time points from the same mouse.(C )Ex vivo BLI of excised tissues to confirm the presence of metastatic lesions.(D )Growth curve of metastatic lesion generated by quantification of bioluminescent signals of various time points.(E )The metastatic lesion identified on H&E section.T,tumor;B,bone.5550Ji et al.IOVS,December 2009,Vol.50,No.12。
想要了解的事物英语作文Things I Yearn to Understand The world is an intricate tapestry woven with threads of knowledge, both known and unknown. While I find myself fascinated by the vast amount of information we’ve accumulated as a species, I am acutely aware of the vast, uncharted territories of understanding that lie before me. There are several key areas that spark a deep curiosity within me, areas I yearn to explore and grasp with greater clarity. Firstly, I am captivated by the complex workings of the human mind. The brain, a three-pound universe contained within our skulls, is a marvel of intricate networks and electrochemical signals that give rise to consciousness, emotion, and behavior. How do neurons fire in symphony to create our perceptions of the world? What are the mechanisms behind memory formation and retrieval? How does our unique blend of genetics and environment shape our personalities and predispositions? Unraveling the mysteries of the mind holds the key to understanding the very essence of what makes us human. The vast universe, with its swirling galaxies, enigmatic black holes, and the tantalizing possibility of life beyond Earth, also ignites my imagination. I long to understand the fundamental laws that govern the cosmos, from the delicate dance of subatomic particles to the majestic movements of celestial bodies. What is the true natureof dark matter and dark energy, the unseen forces shaping the universe's evolution? Are we alone in this vast cosmic expanse, or does life, in all its wondrous forms, exist elsewhere? The pursuit of answers to these questions is a quest to understand our place in the grand scheme of existence. Closer to home, the interconnected web of life on our planet fascinates me. The intricate ecosystems teeming with biodiversity, the delicate balance of predator and prey, theintricate cycles of energy and nutrients - these are all testament to the awe-inspiring power of evolution and adaptation. I yearn to understand the complex interactions within these ecosystems, the delicate balance that sustains them, and the impact of human activities on this delicate web. Understanding these complexities is crucial for our responsible stewardship of the planet and the preservation of its irreplaceable biodiversity. Furthermore, I am drawn to the intricacies of human history and its impact on our present reality. From the rise and fall of civilizations to the struggles for freedom and equality, historyoffers a lens through which we can examine the triumphs and failures of humankind.I crave a deeper understanding of the forces that have shaped our social,political, and economic systems, the ideologies that have fueled conflicts and cooperation, and the enduring legacies of past events. By studying history, wecan learn from our ancestors' mistakes and successes, equipping ourselves to navigate the challenges of the present and build a better future. The ever-evolving world of technology, with its rapid advancements in artificial intelligence, biotechnology, and space exploration, also holds a powerful allure.I am driven to understand the principles behind these innovations, their potential to address global challenges, and the ethical implications that accompany them. How can we harness the power of artificial intelligence for the betterment of society while mitigating potential risks? What are the ethical considerations surrounding genetic engineering and its impact on future generations? How can space exploration contribute to scientific advancements and inspire future generations? Exploring these frontiers of technology is essential for shaping a future where innovation serves humanity and the planet. Finally, I yearn to understand the very essence of creativity and its power to inspire, challenge, and transform. From the evocative brushstrokes of a painter to the soaring melodiesof a composer, creativity speaks a universal language that transcends cultural boundaries. What are the cognitive processes that underpin artistic expression? How does creativity foster innovation and problem-solving across disciplines? How can we nurture and cultivate our own creative potential to contribute to the world in meaningful ways? Understanding the nature of creativity is key to unlockingour own potential and enriching the human experience. In conclusion, the pursuit of knowledge is a lifelong journey, an insatiable thirst for understanding that fuels my curiosity and motivates my exploration. From the inner workings of the human mind to the vast expanses of the cosmos, from the intricate web of life on Earth to the enduring legacies of human history, from the frontiers of technology to the power of creative expression - these are the areas I yearn to understand with greater depth and clarity. This quest for knowledge is not merely an academic pursuit but a fundamental aspect of what makes us human - the desire to learn, grow, and contribute to the betterment of ourselves and the world around us.。
Reconstruction of Illumination Functionsusing Bicubic Hermite InterpolationR UI M ANUEL B ASTOS1A NT´ONIO A UGUSTO DE S OUSA12F ERNANDO N UNES F ERREIRA121INESC–Instituto de Engenharia de Sistemas e ComputadoresLargo Mompiller22–Apartado44334007PORTO CODEX–PORTUGAL2FEUP–Faculdade de Engenharia da Universidade do PortoRua dos Bragas4099PORTO CODEX–PORTUGAL1rmb@bruna.inescn.ptABSTRACT An interpolation technique based on Hermite bicubic surfaces is proposed toimprove the accuracy of the reconstruction of illumination functions and avoid Mach bandartifacts.The information of radiosity at vertices is used to evaluate approximate tangentplanes to the illumination function and determine partials and mixed partials of that function.Typical discontinuities of intensity or derivative in the illumination function are preserved inthe reconstructed image.The additional computation involved is modest and the result of realimportance.1IntroductionThe photorealistic image synthesis has been the aim of much research in Computer Graphics.The main goal is to generate images that evoke the same response that the observer would have when looking at the actual environment.There are many limitations related to physiological cues that hamper the achievement of thefinal purpose[3].A special limitation is the way our eyes respond to changes and discontinuities in magnitude and/or slope of intensity.This is the so called Mach band effect.It is easy to verify that the most of the light we see does not proceed directly from light sources,but from multiple diffuse,specular or intermediate reflections/transmissions.The most accurate way to render a scene is to evaluate the illumination function for each pixel,but for smoothly-varying illumination functions (diffuse surfaces),this is unnecessarily expensive.In this case,it is much more efficient to sample the illumination function in selected points,and then reconstruct a smooth function to approximate the actual illumination function everywhere in the scene.The main cause of the Mach band effect in synthetic images is the discontinuity in the interpolation of the illumination function between patches where only the values in the vertices are known.In addition to the Mach band effect that can be caused by some kinds of interpolation,the loss in accuracy of the interpolated values also can be noted if compared to the ones evaluated using the same method used to compute the illumination function in the vertices.There are some reconstruction models,and the simplest one is the constant or faceted shading-a single value of the illumination function is used to shade each entire polygon.As the name suggests,this model presents images with faceted appearance,caused by intensity discontinuities at the edges of the mesh of ing this model,it is only possible to have intensity and slope continuity at an edge between two patches if these patches have equal values of the illumination function.Otherwise,there is no continuity at each edge between two patches(1-discontinuous in intensity).To reduce discontinuity problems,a bilinear interpolation technique has been introduced by Gouraud [9].A linear interpolation can ensure continuity of intensity,but cannot eliminate derivative discontinuities (0-continuous in intensity,discontinuous in derivative).The discontinuities in intensity and/or in derivative,in places where the illumination function should be smooth,may appear as Mach band effect in the generated images.To obtain reconstruction functions continuously differentiable,higher-order interpolation schemes must be used.Kirk and Voorhies[10]used a quadratic interpolation that avoided Mach band in almost every case, but did not guarantee derivative continuity between adjacent patches.Another quadratic interpolation, described by Powell and Sabin[12]and Cendes and Wong[5],has been used to reconstruct continuously differentiable functions.Although continuity of derivative is desirable to reconstruction functions,care must be taken in some cases where the illumination functions present magnitude and slope discontinuities.Discontinuities in intensity(1)occur,for instance,at regions of contact between surfaces with different orientations or different reflection/emission characteristics.Discontinuities in derivative occur,e.g.,in shadows cast by area light sources at penumbra and umbra boundaries.To be faithful to the illumination function, a reconstruction function should preserve these0and1discontinuities and not smooth them as a continuous differentiable function.Using Powell-Sabin quadratic interpolation looks to be difficult to handle derivative discontinuities, because it imposes a strong connection between neighboring patches.Salesin et al.[14]proposed a bicubic reconstruction scheme that breaks up each triangular patch into three B´e zier subtriangles and introduced discontinuities relaxing constraints on the control points of adjacent triangles.Our approach is similar to the second one,but with a simpler scheme.We propose a bicubic reconstruction scheme based on parametric bicubic Hermite interpolation [7][8].The scheme approximates tangent planes to the illumination function at each vertex of the geo-metrical mesh,and,using the evaluated values of the illumination function at those vertices,associates a reconstruction Hermite patch to each geometrical patch.The consideration of selected discontinuities is done in a natural way,duplicating geometrical vertices and edges where a geometrical or illumination discontinuity exists.This reconstruction scheme can be used to approximate several functions in severalfields.We used and implemented it to achieve a better interpolant in radiosity.Although the radiosity method very accurately evaluates the illumination function of selected points in a scene,the subsequent and traditional bilinear interpolation of those points introduces undesirable inaccuracies.2Mach band effectIt is easy to verify the faceted appearance of any image,when curved objects in the scene are approximated by polygonal meshes where each polygon is shaded individually.This effect occurs if constant or interpolated shading is used and nothing is done to ensure slope continuity across polygon boundaries.The most simple, but expensive,solution of using afiner mesh is not effective,unless all polygons used are smaller than a pixel.This effect of discontinuity is known as Mach band[13][8],and wasfirst reported in1865by the Austrian physicist Ernst Mach.It depends directly on the distribution of the illumination and exaggerates the intensity change at any edge where there is a discontinuity in magnitude or slope of intensity: At the boundary between two polygons,one dark and the other light,the dark one looks darkerand the light one looks lighter.According to Ratliff[13],the basic effect can be verified by holding an opaque card under an ordinary fluorescent desk lamp,preferably in a dark room(figure1).If the shadow is cast on a piece of paper,part of the paper is fully illuminated,and next to that area is a half-shadow(penumbra)that gets progressively darker until a full shadow(umbra)is reached.Ideally,the distribution of light should be uniformly high in the bright area,uniformly low in the dark area,and smoothly graded between the bright and the dark areas. Looking closely at the edges of the penumbra,a narrow bright band at the bright edge and a narrow dark band at the dark edge can be seen.These are the Mach bands.Observing the distribution of intensity along the bright,penumbra and umbra areas,one can verify that the Mach bands appear in regions where there is discontinuity in magnitude or slope of intensity.In the example presented,discontinuities and its associated Mach bands are desired to represent the actual effect. In cases where a smooth illumination function is desired,discontinuities in magnitude or slope of intensityLIGHTOpaque cardI IPenumbra UmbraFully illuminatedDistanceDistancePerceived intensityActual intensityFigure1:Mach band effect in a shadow cast by a linear light source.It can be seen the actual intensity (analogous to a linear interpolation)and the perceived intensity.Also can be seen a representation of the intensity using constant shading and the correspondent perceived intensity.cannot exist.It can be verified that interpolations of order lower than quadratic cannot guarantee continuity of magnitude and slope of intensity.3Definition of the reconstruction problemThe illumination function of a scene returns the spectral sampling at a point,given the spatial coordinates of that point.As said in section1,for smoothly-varying illumination functions(diffuse surfaces)it is much more efficient to sample the illumination function in selected points,and then reconstruct a smooth function to approximate the actual illumination function everywhere in the scene.That reconstructed or interpolated function is called reconstruction function.As it is too difficult tofind an interpolation function for a whole scene,the problem is broken down into small ually,in radiosity algorithms the objects of the scene are tessellated into geometrical patches [6][1].For simplicity,the reconstruction function is tessellated into reconstruction patches associated with the geometrical patches of the scene.Actually,each geometrical patch has more than one associated reconstruction patch-one for each color component(e.g.,red,green and blue),but,since the treatment is the same for each color component,the illumination/reconstruction functions will be analyzed as unidimensional quantities.Each geometrical patch is described by its vertices coordinates and characteristics of reflection and emission.At each vertex of each geometrical patch there exists a geometrical normal vector and an intensity (illumination function at that point)is evaluated.Using the given information,we have tofind a reconstruction function that,at any vertex, returns values equal to the ones calculated,and approximates the illumination function anywhere else over the geometrical patch:geometrical patch andThe same reconstruction function should approximate thefirst derivative,or gradient,of the illumination function everywhere over the geometrical patches,and must preserve the continuity and discontinuities of the illumination function.The simple association of a reconstruction patch with each geometrical patch does not ensure continuity between reconstruction patches.If two patches share an edge where the illumination function continuity is:1,the two reconstruction patches must share,at that edge,the same values and itsfirst derivative.0,the two reconstruction patches must share,at that edge,the same values to approximate theillumination function and the first derivative in the direction of the edge.They do not share the first derivative of the illumination function in any other direction.1,the two reconstruction patches do not share,at that edge,the same values,nor its first derivative.4Bicubic Hermite surfaces to interpolate radiositiesAmong the bicubic surfaces the Hermite form was chosen.The motivation to choose this form was its interpolation of derivative data and that this information is directly available from the tangent planes to the illumination functions.A bicubic patch in Hermite form is given by [8][7]:(1)where 321(2)321(3)2211332100101000(4)and,in the case of radiosity reconstruction functions:00010*******0120111211(5)The input parameters to the Hermite bicubic form,as can be seen in the coefficient matrix,are radiosities(),partials (),shown in figure 2.streconstructionHermitepatchpatch GeometricalPartialsTwistsFigure 2:The shown points and vectors define a bicubic Hermite patch.To guarantee 0continuity at an edge between two Hermite patches,the matching curves of the two patches must be identical,which means that the radiosities and the partials for the two surfaces must be identical along the edge.The necessary conditions for 1continuity are that the radiosities and the partials along the edge and the partials and mixed partials (twists)across the edge be equal.With these equalities the storage requirements may be reduced.5Tangent planes to the illumination functionIt will be assumed that continuity of the geometrical normal vector implies continuity of the reconstruction function.However,an a priori discontinuity meshing algorithm may indicate any kind of discontinuity at any point.In this way,all the reconstruction patches that share a vertex must share a single tangent plane to the illumination function at that point,unless a discontinuity is detected there.A vertex is duplicated if there is any discontinuity that causes a discontinuity in the illumination function at that vertex.In the same way,an edge is duplicated if there is any discontinuity,at least,at one of its vertices.A discontinuity between patches at a vertex/edge occurs if:the geometrical normal vector is discontinuous;the reflectivity is discontinuous;the emissivity is discontinuous;it is a part of the boundary between umbra and penumbra areas;it is a part of the boundary between penumbra and fully illuminated areas.To evaluate an approximate tangent plane to the illumination function,the vertex where the function is tangent,the edges that share that vertex and the corresponding patches,and the radiosities at the verticesof the shared edges must be ing this information (figure 3.a),a coordinate systemis defined for each patch that shares the vertex through the parametric axes and its cross product (radiosity).In this coordinate system (patch),the radiosity variation vector (radiosity linear interpolation between vertices)is evaluated for the two edges of this geometrical patch that share the vertex.The cross product of the two radiosity variation vectors gives the normal vector,,to the radiosity variation plane (radiosity bilinear interpolation)that approximates the normal vector (tangent plane)to the illumination function at the shared vertex.The simple use of bicubic interpolation with the above technique to approximate the illumination function tangent plane at every vertex does not give more accurate results than the bilinear interpolation.But more accurate tangent planes can be used taking the average of the tangent planes at each vertex.This average gives good approximations except at vertices of surface boundary.Geometrical patchradiosity Bt s V2V3V0V1B3B1B0N i variationPlane of sB0B6B4B1V0V1V4V6Patch A Patch B Patch C B(a)(b)Figure 3:Evaluation of the tangent planes (normal vectors)to the illumination function.(a)3D sketch at any vertex of any geometrical patch.(b)Two-dimensional analysis of the normal vectors to the illumination function.If there are more than a patch sharing a vertex (figure 3.b),a normal vector to the reconstruction function is evaluated for each patch at each vertex.The approximate normal vector (tangent plane)to the illumination function at the shared vertex is the average vector of the normal vectors of the patches.Thisassumption ensures1continuity of the reconstruction function for all the patches sharing the vertex and is a good approximation for the illumination function normal vector(figure3.b at1and4).Using just one plane of radiosity variation(figure3.a andfigure3.b at0and6)to evaluate the illumination function normal vector,the tangent plane is undervalued(dotted line)and a correction must be made to improve the results(solid line).The same problem occurs when two radiosity variation planes share a surface boundary vertex,in the direction of the shared edge.6First derivative of the illumination functions-GradientsTo evaluate the partials and mixed partials of the coefficients matrix(5),the approximate normal vectors (tangent planes)to the illumination function are used together with the geometrical normal ing the fact that the slope of a function may be expressed as the height of a right triangle with base length one, the derivatives are evaluated as the tangent of the angle between the geometrical normal vector,,and the normal vector to the illumination function,,at that vertex(figure4):+),and is the projection of the normal vector to the illumination function onto the plane defined by the geometrical normal vector and the given direction.Care must be taken with clockwise/counter clockwise angles,depending on,,and:coscoordinates over that patch are known.Knowing the correspondent reconstruction patches(one for each color component)to that geometrical patch(same parametric coordinates),the bicubic interpolation of the radiosities is evaluated using expression(1)for each color component(e.g.,red,green,blue).8ResultsThe proposed reconstruction technique have been implemented on a SUN Sparc II workstation in C++,as an extension to the radiosity public domain software from India(by Sumant Pattanaik).We have compared a reference solution(a),obtained with afine mesh,since analytic solution are not known for radiosity problems,a bilinear0interpolation(b),and our1bicubic reconstruction technique(c),to show how the accuracy of the reconstruction functions can be improved accumulating more information about the illumination function per vertex/edge and using a higher order interpolation technique(figure6).In(b),a value of intensity per vertex,together with a bilinear interpolation,were used to generate thefinal image.In(a)and(c),a value of intensity per vertex,and partials and mixed partials of the illumination function were used together with a bicubic interpolation to reconstruct improved images.Figure5presents a sketch of the simple geometrical model with136quadrilaterals.The reference solution was generated using a mesh of14080quadrilaterals and the area light source was subdivided in16 by16samples in both cases.Figure5:Simple geometrical model.Figure6shows a simple illumination function of occluded and unoccluded light where can be analysed the continuity and discontinuities of the reconstruction functions.Note the incorrect Mach band artifacts in(b)that are completly eliminated in(a)and(c).Also note the correct Mach bands on the partial occluded surface,due to penumbra edges,appropriatelyflagged in the mesh,not smoothed by the bicubic interpolation.Figure7plots the red component for the horizontal central line of each image andfigure8shows the relative errors between the reference and the interpolated reconstruction functions.The lower relative errors of the bicubic interpolation confirm that the presented technique based on the correlation between the geometrical normal vector and illumination function normal vector is much more accurate than a conventional bilinear interpolation.As presented in section5,the undervalueing of the illumination function normal vector at vertices of surfaces boundary can be seen in the bicubic interpolated image and plots(180),if compared to the reference solution.9Conclusion and further workThe radiosity gradient can be evaluated from the radiosity samples in an environment,using a correlation between the geometrical normal vector and the illumination function normal vector at each vertex.Based on this,we have presented a new bicubic reconstruction technique for illumination functions that allows for selected magnitude and derivative discontinuities.The additional computation involved is negligible,Figure6:(a)(b)compared to the cost of computing the radiosity samples,and the advantage is an improved interpolation accuracy.Compared to a standard radiosity implementation(bilinear interpolation),the described algorithm requires a list of edges(2unsigned-vertices-and6double-2partials per3color components)and12 double per patch-4mixed partials per3color components.To generate the images infigure6.(b)and(c) were used5minutes and45seconds and6minutes and20seconds,respectively,where3minutes and15 seconds is the time for500steps of progressive refinment in both cases.In this way,the rendering took195 seconds for the bilinear interpolation and230seconds for the bicubic interpolation(bicubic=1.18bilinear).Aspects of the presented technique that suggest further research are:A priori and a posteriori adaptive meshing.The a priori meshing is fundamental to indicate the discon-tinuity edges.To more accurately reconstruct the illumination functions,an a posteriori meshing can resample the environment,avoiding great radiosity variations and allowing more accurate tangent planes to the illumination function.More accurate normals at vertices of surface boundary.The simple scheme presented for estimating normals to the illumination function needs a correction at vertices of the boundary of surfaces.It is possible to approximate the derivative of the illumination function at a vertex of the boundary using quadratic interpolation and values of radiosity and derivative at a neighbour vertex out of the boundary.Triangular patches are better suited to describe complex geometries than are rectangular patches.。
