ORIGINAL ARTICLES Interictal to Ictal Transition in Human Temporal Lobe Epilepsy Insights F
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21 CFR Part 11 联邦法规21章第11款主要规定内容涉及电子记录和电子签名适用范围(a) 本条款的规则提供了标准,在此标准之下FDA将认为电子记录、电子签名、和在电子记录上的手签名是可信赖的、可靠的并且通常等同于纸制记录和在纸上的手写签名。
(b) 本条款适用于在FDA规则中阐明的在任何记录的要求下,以电子表格形式建立、修改、维护、归档、检索或传送的记录。
本条款同样适用于在《联邦食品、药品和化妆品法案》和《公众健康服务法案》要求下的呈送给FDA的电子记录,即使该记录没有在FDA规则下明确识别。
然而,本条款不适用于现在和已经以电子的手段传送的纸制记录。
(c) 一旦电子签名和与它相关的电子记录符合本条款的要求,FDA将会认为电子签名等同于完全手签名、缩写签名、和其他的FDA规则所求的一般签名。
除非被从1997年8月20日起(包括该日)生效后的规则明确地排除在外。
(d) 依照本条款11.2,除非纸制记录有特殊的要求,符合本条款要求的电子记录可以代替纸制记录使用。
(e) 在本条款下维护计算机系统(包括硬件和软件)、控制权、和随附的文件应便于被FDA用到,和服从于FDA的监管。
履行(a) 需要维护,但不提交给FDA的记录,如果符合本条款的要求,人们可以使用全部或部分电子记录代替纸制记录或用电子签名代替传统签名。
(b)提交给FDA的电子记录,人们可以使用全部或部分电子记录代替纸制记录或电子签名代替传统签名(手签名)假如:(1) 符合条款的要求(2) 提交的文件或部分文件,作为FDA以电子形式接收的提交物的类型已经被编号为92S-0251公共摘要识别出来。
这个摘要将明确地识别出,何种类型文件或部分文件在没有纸制记录和FDA接收单位(举例来说,特定的中心,办公室,部门、分支机构)时的电子形式提交物是可接受的。
如果没有在公共摘要上明确出来,他们以电子形式提交给FDA接收单位的文件将不被认为是正式的;这种文件的书面形式将被认为是正式的但必须伴有电子记录。
Product Change Notification# 1252-00Information in this document is provided in connection with Intel® products. No license, express or implied, by estoppel or otherwise, to any intellectual property rights is granted by this document. Except as provided in Intel’s Terms and Conditions of Sale for such products, Intel assumes no liability whatsoever, and Intel disclaims any express or implied warranty, relating to sale and/or use of Intel® products including liability or warranties relating to fitness for a particular purpose, merchantability, or infringement of any patent, copyright or other intellectual property right. Intel® products are not intended for use in medical, life saving, or life sustaining applications. Intel may make changes to specifications and product descriptions at any time, without notice.Copyright © Intel Corporation 2001. Third-party brands and names are the property of their respective owners. Intel, Insight960, Intel386, Intel486, Intel740, IntelDX2, IntelDX4, IntelSX2, Intel GigaBlade, Intel StrataFlash, Intel Xeon, Intel XScale, Itanium, OverDrive, Pentium, Pentium II Xeon, Pentium lll Xeon, Solutions960, LANDesk, Celeron, FlashFile, i386, i486, i960, iCAT, iCOMP, Intel SingleDriver technology, EtherExpress, AnyP oint is a trademark or registered trademark of Intel Corporation or its subsidiaries in the United States and other countries.Change Notification #: 1252-00Change Title: FYI Intel ® Mobile Processors, Chipsets, HandheldComponent, Flash Memory, Embedded, Platform, andOptical Networking Components New Moisture BarrierBag and JEDEC Standard Humidity Indicator Cards Date of PCN Publication: September 26, 2001Type of Change Notification:FYI (for-your-information)Key Characteristics of the Change:Transport MediaForecasted Key Milestones:Humidity Indicator Cards:Date Customer Must be Ready to Receive Post-Conversion Material: October 22, 2001October 22, 2001 Date of First Availability of Post-Conversion Material:The date of "First Availability of Post-Conversion Material" is the projected date that acustomer may expect to receive the Post-Conversion Materials. This date is determined by theprojected depletion of inventory at the time of the PCN publication. The depletion of inventorymay be impacted by fluctuating supply and demand, therefore, although customers should beprepared to receive the Post-Converted Materials on this date, Intel will continue to ship andcustomers may continue to receive the pre-converted materials until the inventory has beendepleted.Moisture Barrier Bags:Date Customer Must be Ready to Receive Post-Conversion Material: January 7, 2002January 7, 2002Date of First Availability of Post-Conversion Material:The date of "First Availability of Post-Conversion Material" is the projected date that acustomer may expect to receive the Post-Conversion Materials. This date is determined by theprojected depletion of inventory at the time of the PCN publication. The depletion of inventorymay be impacted by fluctuating supply and demand, therefore, although customers should beprepared to receive the Post-Converted Materials on this date, Intel will continue to ship andcustomers may continue to receive the pre-converted materials until the inventory has beendepleted.Description of Change to the Customer:• Intel will be changing from a white to a silver foil moisture barrier bag (MBB)• The current Humidity Indicator (HIC) cards have humidity level indicators of 10-20-30%. To comply with the new JEDEC requirements, JEDEC standard J-STD-033, the new HIC cards will have humidity level indicators of 5-10-15%. The current rebake criteria on the HIC’s of 10% will not change. The cards only reflect a higher resolution of humidity detection.Customer Impact of Change and Recommended Action:• Intel does not anticipate any changes to customers operations or applications.• There will be no change to the package sizes or materials and all products will continue to meet Intel’s stringent quality requirements.Products Affected / Intel Ordering Codes:Embedded and Networking Products:Product Code Spec/ROM MM#KU80C186EC20 802933KU80960CF33 803114TN87C51RA1 807001S80C188EB25 803598SB87C196KD20 802938N87C196KD20 802914TN80C251SQ16 804487KU80960CF16 802993N80C188XL20 803820TS80C188XL20 803878SB80C188EA13 803473S87C42 804133TS80C51RA24 804603N80C188XL25 803895TN80C186XL20 803212S80C196KB16 804079N87C251SQ16 804054SB87C196KC20 802774KU80C188EC25 803656SB80C186EC25 802965SB80L188EC13 806197TS80C186EC20 802945NG80386SXLP25 800134S80C188XL20 803850FA80386EXTB25 807257N87C196KC20 802695NG80386DX20 807082S80C196NU40 804302SB80C186EB20 802869KU80386EXTC33 807277SB80C188XL20 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S87C196MC R 9091 803454 S87C196MC R 9094 803475 N87C196MC R 9099 808528 N83C196MC R 9099 830280 S87C196MC R 9101 809229 S87C196MC R 9110 809991 S87C196MC R 9118 803494 S87C196MC R 9121 814599 S87C196MC R 9126 803519 S87C196MC R 9132 803525 S87C196MC R 9133 816153 N8QC196MC R 9134 821654 N8QC196MC R 9135 821655 N8QC196MC R 9139 821635 N8QC196MC R 9142 822533 N8QC196MC R 9144 822793 N80C52 R 9154 804737 N8QC196MC R 9181 828175 N83C51FA R 9187 800519 TN80C52 R 9190 805274 N87C196MC R 9190 830046S87C196MC R 9191 830047 N80C5224 R 9208 807757 N80C521 R 9209 805374 N80C52 R 9213 804787 N80C52 R 9263 804798 N80C5220 R 9268 805577 N80C52 R 9271 804804 N80C52 R 9273 821162 N80C52 R 9286 804808 N80C52 R 9289 804814 N80C521 R 9342 808002 N83C51FA R 9346 808056 N83C51FA24 R 9363 808149 N80C52 R 9367 808471 N80C5224 R 9418 809622 TN80C52 R 9426 808867 S83C51FA R 9493 810053 N83C51FA1 R 9497 821908 N83C51FA R 9509 810298 N83C51FA1 R 9512 810374 N83C51FA1 R 9537 811645 N83C51FA R 9538 811649 N83C51FA R 9539 811647 N83C51FA R 9552 812075 N80C52 R 9605 816942 N83C51FA1 R 9647 818840 N80C52 R 9674 820823 N80C52 R 9678 820825 N83C51FA R 9699 822914 N80C521 R 9702 824896 N83C51FA1 R 9762 831488 N83C51FA R 9806 800534 N80C188XL20 S C06 823072 N80C31BH1 S C06 804799 N87C51RC1 S C06 800202 TN80C31BH S C06 804733 N80C31BH S C06 804610 N80C186XL16 S C06 803122 N80C321 S C06 805115 N80C186XL10 S C06 802994 TN80C188XL10 S C06 803683 N80C186XL20 S C06 822594 N80C32 S C06 805028 N80C186XL12 S C06 803028 N80C188XL12 S C06 803704 TN80C186XL12 S C06 803083N80C51RA1 S C06 804503 N80C51FA S C06 804146 N80C31BH1 S C28 804805 N80C31BH S C28 804616 TN87C196KC20 S F01 802821 N87C196KB16 S F01 812010 N87C196KC20 S F01 802738 TN87C196KB16 S F01 809971 N87C51FA S F01 804285 TN80C196KC20 S F12 804161 N80C188XL20 S F12 803826 N80C188XL12 S F12 803712 TN80C188EB20 S F12 803575 N80C186XL25 S F12 815333 N80C186XL20 S F12 803151 TN80C186XL20 S F12 803227 TN80C188XL20 S F12 812057 TN80C186EA20 S F12 802810 N87C196KC20 S F12 802748 TN80C186EB13 S F12 809397 TN80C186XL12 S F12 810359 N87C251SB16 S F12 803913 N87C196KD20 S F12 802921 TN87C251SB16 S F12 803965 TN80C196KB16 S F12 809439 TN87C196KC20 S F12 802827 TN80C186EB20 S F12 802881 TN80C188EB13 S F12 803543 N80C251SB16 S F12 804414 N80C196NT S F12 809446 TN80C188XL12 S F12 803793 TN80C186EA13 S F12 802775 N80C186XL12 S F12 803038 N80C188XL25 S F12 828628 N80C196KB16 S F12 809438 N80C196KC20 S F12 804105 N80C251TB24 S F12 829880 N80C186XL20 S F33 803156 N80C188XL20 S F33 809170 N80C186XL12 S F33 803045 N87C5224 S F75 811696 N87C51FA1 S F75 811697 TN87C521 S F76 810688 TN87C5224 S F76 819853 S87C581 S F76 810734 S87C51FC1 S F76 806104TN87C5124 S F76 810989 TN87C51FC1 S F76 812059 TN87C51FA24 S F76 810975 N87C541 S F76 810719 TN87C51FB1S F76 812042 S87C521 S F76 810770 TN87C511 S F76 811004 N87C5224 S F76 810752 N87C51FC33 S F76 811090 N87C5424 S F76 810720 N87C51FB20 S F76 810972 N87C51FA1 S F76 810760 N87C51FC20 S F76 811088 TN87C51FC24 S F76 811071 N87C51FC1 S F76 811087 N87C5833 S F76 810725 N87C51FA33 S F76 810753 N87C51FA24 S F76 810758 LN87C51FC20 S F76 811064 N87C511 S F76 810977 N87C51FC24 S F76 811089 N87C51FB1 S F76 812060 LN87C511 S F76 823401 N87C51FB33 S F76 811022 N87C5433 S F76 810721 LN87C51FA1 S F76 823334 N87C581 S F76 810724 TN87C51FB20 S F76 810996 N87C5124 S F76 810976 N87C51FB24 S F76 811012 N87C5233 S F76 810763 TN87C51FB24 S F76 812495 TS87C51FA24 S F76 810982 TS87C51FA1 S F76 811518 TS87C51FB1 S F76 812058 N87C521 S F76 810755 S87C51FB24 S F76 811017 TN87C51FA1S F76 810774 S87C51FC24 S F76 811081 S87C51FB33 S F76 811019 S87C5424 S F76 810712 S87C51FA24 S F76 810749 S87C541 S F76 810369 S87C51FB1S F76 805377 TS87C51FC S F76 812079 LN87C51FC24 S F76 812078S87C51FA1S F76 804439 S87C511 S F76 823331 S87C196MH S F81 803697 S87C196MC S F81 803538 N87C251SB16 S F87 803916 N80C251SB16 S F87 804421 TN80C51FA1S F88 809574 S80C51FA24 S F88 809582 TN80C31BH1 S F88 810026 N80C31BH1 S F88 809480 N80C3224 S F88 809521 N80C51FA24 S F88 809581 LN80C51FA1 S F88 811045 TN80C321 S F88 809517 N80C51FA33 S F88 810981 S80C31BH24 S F88 811520 N80C321 S F88 809512 N80C51FA1 S F88 809568 TN80C51FA24 S F88 809583 TS80C321 S F88 809519 TS80C31BH1 S F88 809489 TN80C3224 S F88 809524 S80C321 S F88 809516 S80C51FA1S F88 809572 S80C3224 S F88 810024 N80C31BH24 S F88 809494 S80C31BH1 S F88 809486 LN80C31BH1 S F88 809475 TN80C31BH1 S F89 823320 N80C51FA1 S F89 809569 TN80C3224 S F89 833125 TN80C321 S F89 823319 N80C3224 S F89 809522 N80C31BH1 S F89 809481 TN80C51FA1S F89 809575 N80C321 S F89 809513 N87C51FA S W30 825231 FC80960HD32 S L2GL 815243 FC80960HD50 S L2GM 815241 FC80960HD66 S L2GN 815238 FC80960HT75 S L2GT815234 FC80960HA25 S L2GU 813626 FC80960HA33 S L2GV 813627 FC80960HA40 S L2GW 813625 FC80960HD80 S L2LZ815242 FC80486DX4WB100 S L2M9 816435AN87C196KDF8 S L2N8 820753 N81C66 S L2RN 816815 AN87C196CA20F8 S L2TE 820751 AN87C196KC16F8 S L2ZU 820745 AN87C196CB S L34F 820087 AN87C196KTF8 S L34F 820757 AN87C196CA18F8 S L37J 820750 AS83C196EA S L3BU 821714 AN87C51FC20F8 S L47Y 828719 FW80960VH100 S L4PH 831141 NG80960JF3V33 S L4PJ 831158 NG80960JC66 S L4PJ 831159 FW80960VH100 S L5P6 836378 NG80386SX25 S N177 800333 KU80960CA25 S N181 802907 N87C51 S N219 806809 N80C186XL20 S N220 803184 N80C188XL12 S N221 803736 N80C196NT S N236 809172 N87C196KC20 S N237 810294 AN82527F8 S T111 820733 AN82527F8 S T125 820734 AN82527F8 S T130 820736 AN82527F8 S T131 820738 AN87C196KRF8 S T147 820755 AN82527F8 S T174 820739 N8065 S T183 802062 AN80C196KBSF8 S T187 820740 S82C42PE S U007 812437 NG8037616 S V816 806931 TN87C51FA S W061 804358 NG8037616 S W076 806946 N80C188XL10 S W149 803670 N80960SA10 S W225 810287 N80960SA16 S W226 803835 N80960SA20 S W227 803859 N80C31BH S W230 809459 N80960SB16 S W232 803890 S80C196KB S W237 804008 N80C188XL10 S W244 803676 N87C51 S W270 806817 KU80960CA25 S W271 814046 KU80960CA16 S W316 802864 SB80C196KC20 S W335 804149 KU80960CF25 S W344 803056 KU80960CF16 S W344 802999TN80C51FA1S W400 804307 NG80386SX25 S X701 800341 NG80386SX33 S X702 800367 NG80386SX16 S X711 800236 NG80386SX20 S X712 800286 NG80386SXLP20 S X713 800127 SB80486DX2SC40 S X913 808893 SB80486DX2SC50 S X920 800952 KU80486SXSA25 S X934 801281 KU80486SXSA33 S X935 801318 FW82439TX S L28T813149 KC80524KX266256 S L32Q 820516 KC80524KX333256 S L32S 820520 GC80503CSM66166 S L388 821225 GC80503CSM66266 S L389 821226 GC80503CS166EXT S L3B8 822631 FW82439TX S L3BT 821840 KC80524KX366128 S L3C7 822451 KC80526GY650256 S L4JJ 830973 KC80526LY500256 S L4JP 830978 FW82439HX S L5M2 835654 FW82439TX S L5M3 835656 SB82371SB S U093 805436 FW82439HX S U115 807787Platform Networking Products: Product Code Spec/ROM MM#21154AC821305 821305 21154BC821308 821308 21285AB 821310 821310 21554AA 821311 821311 FW21154AE 834404 834404 FW21154BE 834405 834405 FW82544EI 834735 834735 21154BC835219 835219 FW21555AA 836622 836622 FW21555BA 836624 836624 FW82544EI 838209 838209 FW80200M400 S L589 834495 FW80200M600 S L58B 834496 FW80200M733 S L58C 834497 FW82544EI S L5EU 834734 FW82544EI S L5XV 838208Handheld Component Products: Product Code Spec/ROM MM#FW88386VXSE 818138 818138 FW88386VXSD 818974 818974 FW88386VXSG 827000 827000 FW88386VXST837572 837572Chipset Products:Product Code Spec/ROM MM# FW82443LX S L2QY 816316 FW82452NX S L2RW 817126 FW82453NX S L2RX 817125 FW82443GX S L2TF 817749 FW82443BX S L2VH 818428 FW82452NX S L2XA 818751 FW82443DX S L33J 819899 FW82443ZX S L33W 820228 FW82805AA S L377 825089 FW82443ZX66 S L37A 820575 FW82443MX S L37L 822867 FW82371EB S L37M 820763 FW82801AA S L38Q 822704 FW82801AA S L38R 823031 FW82371EB S L3AU 821640FW82371MB S L3CG 822036 FW82820 S L3FT825078 FW82443MX S L3J3 822889 FW82443ZX66M S L3M5 824458 FW82801AA S L3MA 825015 FW82801AB S L3MB 824956 FW82810E S L3MD 825101 FW82803AA S L3ML 824975 FW82803AA S L3MT824976 FW82803AA S L3MU 824655 FW82801AA S L3MZ 824957 FW82801AB S L3N2 825014 FW82443MX100 S L3N4 824918 FW82801AB S L3NZ824958 FW82810DC100 S L3P6 825103 FW82810 S L3P7 825102 FW82804AA S L3PT 825090 FW82804AA S L3PU 825136 FW82804AA S L3R6 826053 FW82804AA S L3R7 826056 FW82840 S L3TA 826059 FW82840 S L3TB 826060 FW82443ZXM S L3VP 827137 FW82806AA S L3VZ 827923 FW82801AA S L3Z2 827769 FWPRFPB64 S L44M 828250 FWPRFPB64 S L44N 828251 FWPRFDIB S L44P 828252 FWPRFPID S L44R 828249 FW82801BA S L45H 828277 FW82820 S L47D 828640 FW82820DP S L47F 828979 FW82801AA S L47Z828722 FW82372FB S L489 829956 FW82815 S L4DF 829512 FW82463GX S L4DH 830227 FW82804AA S L4FR 829978 FW82804AA S L4FS 829979 FW82805AA S L4G8 830052 FW82468GX S L4GJ 830184 FW82804AA S L4GK 830101 FW82804AA S L4GL 830107 FW82805AA S L4GP 830316 FW82801BA S L4HM 830246 FW82801BAM S L4HN 830247 FW82815EM S L4MP 830995FW82805AA S L4MW 830834 FW82805AA S L4MX830833 FW82805AA S L4MY 830829 FW82805AA S L4MZ830832 FW82805AA S L4NZ830830 FW82807AA S L4QZ833240 FW82801BAM S L4R6 831303 FW82804AA S L4RS 831687 FW82804AA S L4RT831688 FW82804AA S L4RU 831689 FW82805AA S L4S6 831975 FW82805AA S L4WA 833011 FW82805AA S L4WB 833010 FW82805AA S L4WC 833009 FW82805AA S L4WD 833008 FW82808AA S L4WQ 833088 FW82801BA S L4YG 833232 FW82815EP S L552 833766 FW82807AA S L55P 833722 FW82801BA S L59Z834062 FW82801BA S L5FC 834769 FW82464GX S L5L6 835339 FW82801CAM S L5LF 835551 FW82815 S L5NQ 836138 FW82815EP S L5NR 836139 FW82830MP S L5P7 836388 FW82830M S L5P8 836387 FW82830MG S L5P9 836386 FW82801BA S L5PN 836419 FW82801BAM S L5PP 836420 FW82801BA S L5WK 838027 FW82801CAM S L5X7 838033 FW82815G S L5XP 838228 FW82830MP S L5YG 839414 FW82815 S L5YN 838983 FW82801CAM S L5YP 838981 FW82801AA S LM3A 824955Flash Memory Products:Product Code Spec/ROM MM#E28F008SA120 801050 PA28F008S585 808715 PA28F008SA85 801480 PA28F008S5120 808708 TP28F010150 802096 E28F008S585 808711 E28F008S5120 808704 TE28F008SA100 811350 TE28F008B3B150 814161 814161 TE28F800B3T120 814164 814164 TE28F008B3T120 814166 814166 TE28F008B3B120 814169 814169 TE28F800B3B120 814172 814172 GT28F800B3T120 814193 814193 GT28F800B3B120 814196 814196 GT28F008B3B120 814484 814484 GT28F008B3T120 814485 814485 N28F512120 815135 815135 N28F512150 815136 815136 TP28F512120 815146 815146 TB28F008SA100 816471 816471 TE28F400B3T120 816771 816771 TE28F400B3B120 816778 816778 TE28F008B3B90 817563 817563 TE28F008B3T90 817564 817564 TE28F008B3B110 817565 817565 TE28F008B3T110 817574 817574 TE28F800B3B90 817578 817578 TE28F800B3T90 817579 817579 TE28F800B3B110 817585 817585 TE28F800B3T110 817587 817587 GT28F008B3B90 817719 817719 GT28F008B3T90 817722 817722 GT28F008B3B110 817734 817734 GT28F008B3T110 817735 817735 GT28F800B3T90 817747 817747 GT28F800B3B90 817748 817748 GT28F800B3T110 817752 817752 GT28F800B3B110 817754 817754 TE28F400B3T110 817791 817791 TE28F400B3B110 817818 817818 DT28F160S3100 818821 818821 DT28F160S570 818823 818823 DT28F160S5100 818833 818833 TE28F160S5100 818839 818839 TE28F160S570 818845 818845。
Minimum-Security Criteria for C-TPAT Foreign Manufacturers in English(04/28/2008)Business Partner RequirementContainer and Trailer SecurityPhysical Access ControlsPersonnel SecurityProcedural SecurityPhysical SecurityInformation Technology SecuritySecurity Training and Threat AwarenessThese minimum security criteria are fundamentally designed to be the building blocks for foreign manufacturers to institute effective security practices designed to optimize supply chain performance to mitigate the risk of loss, theft, and contraband smuggling that could potentially introduce terrorists and implements of terrorism into the global supply chain. The determination and scope of criminal elements targeting world commerce through internal conspiracies requires companies, and in particular, foreign manufacturers to elevate their security practices.At a minimum, on a yearly basis, or as circumstances dictate such as during periods of heightened alert, security breach or incident, foreign manufacturers must conduct a comprehensive assessment of their international supply chains based upon the following C-TPAT security criteria. Where a foreign manufacturer out-sources or contracts elements of their supply chain, such as another foreign facility, warehouse, or other elements, the foreign manufacturer must work with these business partners to ensure that pertinent security measures are in place and are adhered to throughouttheir supply chain. The supply chain for C-TPAT purposes is defined from point of origin (manufacturer/supplier/vendor) through to point of distribution –and recognizes the diverse business models C-TPAT members employ.C-TPAT recognizes the complexity of international supply chains and security practices, and endorses the application and implementation of security measures based upon risk1. Therefore, the program allows for flexibility and the customization of security plans based on the member’s business model.Appropriate security measures, as listed throughout this document, must be implemented and maintained throughout the Foreign manufacturer’s supply chains - based on risk2.back totopBusiness Partner RequirementForeign manufacturers must have written and verifiable processes for the selection of business partners including, carriers, other manufacturers, product suppliers and vendors (parts and raw material suppliers, etc).Security proceduresFor those business partners eligible for C-TPAT certification (carriers, importers, ports, terminals, brokers, consolidators, etc.) the foreign manufacturer must have documentation (e.g., C-TPAT certificate, SVI number, etc.) indicating whether these business partners are or are not C-TPAT certified.For those business partners not eligible for C-TPAT certification, the foreign manufacturer must require that their business partners to demonstrate that they are meeting C-TPAT security criteria via written/electronic confirmation (e.g., contractual obligations; via a letter from a senior business partner officer attesting to compliance; a written statement from the business partner demonstrating their compliance withC-TPAT security criteria or an equivalent World Customs Organization (WCO) accredited security program administered by a foreign customs authority; or, by providing a completed foreign manufacturer security questionnaire). Based upon a documented risk assessment process, non-C-TPAT eligible business partners must be subject to verification of compliance with C-TPAT security criteria by the foreign manufacturer.Point of OriginForeign manufacturers must ensure that business partners develop security processes and procedures consistent with the C-TPAT security criteria to enhance the integrity of the shipment at point of origin, assembly or manufacturing. Periodic reviews ofbusiness partners’processes and facilities should be conducted based on risk, and should maintain the security standards required by the foreign manufacturer. Participation/Certification in a Foreign Customs Administration Supply Chain Security ProgramCurrent or prospective business partners who have obtained a certification in a supply chain security program being administered by foreign Customs Administration should be required to indicate their status of participation to the foreign manufacturer. Security ProceduresOn U.S. bound shipments, foreign manufacturers should monitor that C-TPAT carriers that subcontract transportation services to other carriers use other C-TPAT approved carriers, or non-C-TPAT carriers that are meeting the C-TPAT security criteria as outlined in the business partner requirements.As the foreign manufacturer is responsible for loading trailers and containers, they should work with the carrier to provide reassurance that there are effective security procedures and controls implemented at the point-of-stuffing.back totopContainer and Trailer SecurityContainer and trailer integrity must be maintained to protect against the introduction of unauthorized material and/or persons. At the point-of-stuffing, procedures must be in place to properly seal and maintain the integrity of the shipping containers and trailers. A high security seal must be affixed to all loaded containers and trailers bound for the U.S. All seals must meet or exceed the current PAS ISO 17712 standard for high security seals.In those geographic areas where risk assessments warrant checking containers or trailers for human concealment or smuggling, such procedures should be designed to address this risk at the manufacturing facility or point-of-stuffing.Container InspectionProcedures must be in place to verify the physical integrity of the container structure prior to stuffing, to include the reliability of the locking mechanisms of the doors. A seven-point inspection process is recommended for all containers:•Front wall•Left side•Right side•Floor•Ceiling/Roof•Inside/outside doors•Outside/UndercarriageTrailer InspectionProcedures must be in place to verify the physical integrity of the trailer structure prior to stuffing, to include the reliability of the locking mechanisms of the doors. The following ten-point inspection process is recommended for all trailers: •Fifth wheel area - check natural compartment/skid plate•Exterior - front/sides•Rear - bumper/doors•Front wall•Left side•Right side•Floor•Ceiling/Roof•Inside/outside doors•Outside/UndercarriageContainer and Trailer SealsThe sealing of trailers and containers, to include continuous seal integrity, are crucial elements of a secure supply chain, and remains a critical part of a foreign manufacturers’commitment to C-TPAT. The foreign manufacturer must affix a high security seal to all loaded trailers and containers bound for the U.S. All seals must meet or exceed the current PAS ISO 17712 standards for high security seals.Written procedures must stipulate how seals are to be controlled and affixed to loaded containers and trailers, to include procedures for recognizing and reporting compromised seals and/or containers/trailers to US Customs and Border Protection or the appropriate foreign authority. Only designated employees should distribute seals for integrity purposes.Container and Trailer StorageContainers and trailers under foreign manufacturer control or located in a facility of the foreign manufacturer must be stored in a secure area to prevent unauthorized access and/or manipulation. Procedures must be in place for reporting and neutralizing unauthorized entry into containers/trailers or container/trailer storage areas.back totopPhysical Access ControlsAccess controls prevent unauthorized entry to facilities, maintain control of employees and visitors, and protect company assets. Access controls must include the positive identification of all employees, visitors, and vendors at all points of entry.EmployeesAn employee identification system must be in place for positive identification and access control purposes. Employees should only be given access to those secure areas needed for the performance of their duties. Company management or security personnel must adequately control the issuance and removal of employee, visitor and vendor identification badges. Procedures for the issuance, removal and changing of access devices (e.g. keys, key cards, etc.) must be documented.VisitorsVisitors must present photo identification for documentation purposes upon arrival. All visitors should be escorted and should visibly display temporary identification. Deliveries (including mail)Proper vendor ID and/or photo identification must be presented for documentation purposes upon arrival by all vendors. Arriving packages and mail should be periodically screened before being disseminated.Challenging and Removing Unauthorized PersonsProcedures must be in place to identify, challenge and addressunauthorized/unidentified persons.back totopPersonnel SecurityProcesses must be in place to screen prospective employees and to periodically check current employees.Pre-Employment VerificationApplication information, such as employment history and references must be verified prior to employment.Background Checks / InvestigationsConsistent with foreign regulations, background checks and investigations should be conducted for prospective employees. Once employed, periodic checks and reinvestigations should be performed based on cause, and/or the sensitivity of the employee’s position.Personnel Termination ProceduresCompanies must have procedures in place to remove identification, facility, and system access for terminated employees.back totopProcedural SecuritySecurity measures must be in place to ensure the integrity and security of processes relevant to the transportation, handling, and storage of cargo in the supply chain. Documentation ProcessingProcedures must be in place to ensure that all information used in the clearing of merchandise/cargo, is legible, complete, accurate, and protected against the exchange, loss or introduction of erroneous information. Documentation control must include safeguarding computer access and information.Manifesting ProceduresTo help ensure the integrity of cargo, procedures must be in place to ensure that information received from business partners is reported accurately and timely. Shipping and ReceivingDeparting cargo being shipped should be reconciled against information on the cargo manifest. The cargo should be accurately described, and the weights, labels, marks and piece count indicated and verified. Departing cargo should be verified against purchase or delivery orders. Drivers delivering or receiving cargo must be positively identified before cargo is received or released. Procedures should also be established to track the timely movement of incoming and outgoing goods.Cargo DiscrepanciesAll shortages, overages, and other significant discrepancies or anomalies must be resolved and/or investigated appropriately. Customs and/or other appropriate law enforcement agencies must be notified if anomalies, illegal or suspicious activities are detected - as appropriate.back totopPhysical SecurityCargo handling and storage facilities in international locations must have physical barriers and deterrents that guard against unauthorized access. Foreign manufacturer should incorporate the following C-TPAT physical security criteria throughout their supply chains as applicable.FencingPerimeter fencing should enclose the areas around cargo handling and storage facilities. Interior fencing within a cargo handling structure should be used to segregate domestic, international, high value, and hazardous cargo. All fencing must be regularly inspected for integrity and damage.Gates and Gate HousesGates through which vehicles and/or personnel enter or exit must be manned and/or monitored. The number of gates should be kept to the minimum necessary for proper access and safety.ParkingPrivate passenger vehicles should be prohibited from parking in or adjacent to cargo handling and storage areas.Building StructureBuildings must be constructed of materials that resist unlawful entry. The integrity of structures must be maintained by periodic inspection and repair.Locking Devices and Key ControlsAll external and internal windows, gates and fences must be secured with locking devices. Management or security personnel must control the issuance of all locks and keys.LightingAdequate lighting must be provided inside and outside the facility including the following areas: entrances and exits, cargo handling and storage areas, fence lines and parking areas.Alarms Systems and Video Surveillance CamerasAlarm systems and video surveillance cameras should be utilized to monitor premises and prevent unauthorized access to cargo handling and storage areas.back totopInformation Technology SecurityPassword ProtectionAutomated systems must use individually assigned accounts that require a periodic change of password. IT security policies, procedures and standards must be in place and provided to employees in the form of training.AccountabilityA system must be in place to identify the abuse of IT including improper access, tampering or the altering of business data. All system violators must be subject to appropriate disciplinary actions for abuse.back totopSecurity Training and Threat AwarenessA threat awareness program should be established and maintained by security personnel to recognize and foster awareness of the threat posed by terrorists and contraband smugglers at each point in the supply chain. Employees must be made aware of the procedures the company has in place to address a situation and how to report it. Additional training should be provided to employees in the shipping and receiving areas, as well as those receiving and opening mail.Additionally, specific training should be offered to assist employees in maintaining cargo integrity, recognizing internal conspiracies, and protecting access controls. These programs should offer incentives for active employee participation.1Foreign manufacturers shall have a documented and verifiable process for determining risk throughout their supply chains based on their business model (i.e., volume, country of origin, routing, C-TPAT membership, potential terrorist threat via open source information, having inadequate security, past security incidents, etc.).2Foreign manufacturer shall have a documented and verifiable process for determining risk throughout their supply chains based on their business model (i.e., volume, countryof origin, routing, potential terrorist threat via open source information, etc.)。
Bankruptcy in IndiaThe business of going bustA long-awaited bankruptcy code should help owners and lendersNov 21st 2015 | MUMBAI| From the print editionIN THE 19th century, when a Hindu merchant could not pay his debts, he would announce his insolvency by burning a lamp of ghee (clarified butter) at his doorstep. Unable to face the ignominy of default, he would flee by night, never to return. The morning after, villagers would mourn the loss of a friend and watch creditors swoop in to confiscate his house. India’s modern-day bankruptcy procedures are not as brutal and certainly not as swift.The World Bank estimates that it takes about 4.3 years, on average, to resolve a bankruptcy case in India, more than twice as long as in China. The recovery of debts is just 25.7 cents on the dollar, one of the worst rates among developing countries. Take Kingfisher, once India’s second-biggest airline, which was grounded in 2012 with debts of more than $1.5 billion. Only this year did its creditor banks manage to seize its former headquarters in Mumbai. Unlike most other countries, India has no unified bankruptcy code, and its courts have to interpret a variety of sometimes conflicting laws that touch on insolvency.Earlier this month the finance ministry floated proposals for a bankruptcy law that would set a hard deadline of 180 days to decide the fate of a sick firm, plus a 90-day extension if creditors agree. Bahram Vakil of AZB & Partners, a law firm, who sits on a committee advising the ministry on the reforms, says thereis a “crying need” for them. At the moment, creditors cannot take any legal action against a defaulter until a restructuring plan is in place, which usually takes between three and ten years. In the mean time, the owners of sick firms retain day-to-day management control; and while they drag out court proceedings, creditors see their assets dwindle. In many cases, says a lawyer who works on such cases, the owners start up a fresh company in the name of a relative, and siphon off business from the old one.The reform bill proposes to replace the current legal mess with a clear and rapid resolution process, designed to reduce conflicts among creditors. Now, it can take up to two years just to get a dozen or more banks to agree a common approach, says Abizer Diwanji of EY, an accounting firm. Unusually, the new law would put even unsecured creditors in front of official ones in the queue for repayment, with the intention of encouraging the development of a market in unsecured loans.Though some current laws work in their favour, the owners of failing firms do not have it all easy. To be declared sick, and qualify for court protection, firms have to apply to the Board for Industrial and Financial Reconstruction, a government agency, which will not act until the firm has frittered away half of its net worth in losses. By then it may be too late to save it. Somecreditor-friendly laws result in firms being liquidated when they could have been restructured. And some labour and land laws stop firms selling property or trimming their workforce to stay in business.If the law is passed, more sickly firms would be revived instead of being left to die slowly; and India’s banks—whose portfolio of troubled loans has quintupled to $133 billion since 2011—should get more of their money back, sooner. However, the governing Bharatiya Janata Party may struggle to get much done in the next few months, following the walloping it has just received in state-assembly elections in populous Bihar. The law should bring benefits to both business owners and their lenders. But as ever, politics may get in the way of sensible reform.Sex educationDream of the bed chamberNov 21st 2015 | BEIJING| From the print edition“SEX, sex, sexual intercourse, penis, penis, vagina.” More than 150 undergraduates are sitting in a lecture hall at China Agricultural University in Beijing, shouting loudly. Many are sexually active, or soon will be. Yet for most it is the first sex education class they have attended.Their instructor hopes that shouting such words will help youngsters talk more openly about sex. Lu Zhongbao, a 24-year-old forestry student, says he was told as a child that he “emerged from a rock”. When he started having sex with his university girlfriend he had little idea about contraception. This evening he arrived an hour early armed with another question: will masturbating damage his health?It is not just China’s economy that has loosened up since 1979. The country is in the midst of a sexual revolution. A 2012 study found that more than 70% of Chinese people have sex before marriage. Other polls put that figure lower but consistently indicate that over the past 30 years, more young Chinese are doing it, with more partners, at a younger age. But a lack of sex education means that many are not protecting themselves, resulting in soaring abortion rates and a rise in sexually transmitted diseases.The Communist Party has stuck its nose into people’s bedrooms for 30 years through its harsh family-planning policies. Yet taboos on sex before marriage prevailed, the result of paternalistic—not religious—values about femalechastity, with a dose of Communist asceticism thrown in. Pre-marital sex fell foul of a range of laws, including the catch-all charge of “hooliganism”, only scrapped in 1997.The social climate remains chilly. Most news items about sex involve scandals or crimes. Schools b an pupils from dating and many deploy “morality patrols” to root out flirting or frolicking couples. Sex outside wedlock is not illegal but children born to unmarried mothers face obstacles obtaining a hukou, or household residency, that entitles them to subsidised education and welfare. Yet with greater freedom from their parents, more money and increasing exposure to permissive influences from abroad, China’s youth are clearly separating sex from procreation.Education on the subject is compulsory in Japan, South Korea and Taiwan—societies that have some cultural similarities with China. But most Chinese schools teach only basic anatomy.This is not entirely for lack of trying. Pilot campaigns in Shanghai and Beijing schools in the 1980s were incorporated into a nationwide programme in 1988 but it was never implemented. In 2008 the Ministry of Education included sex education in the national health and hygiene curriculum. The barriers are not just prudery. Like football, fashion and other teenage pastimes, sex (and learning about it) is seen as a distraction from studies. “Sex is not an exam subject,” says Sheng Yingyi, a 21-year-old student.Where classes happen, most students are merely given a textbook. “Happy Middle School Students”, written for 12- to 15-year-olds in 2006 and still widely used, refers to sperm meeting egg without describing the mechanics of intercourse. A more explicit volume for primary-school pupils published in 2011, which did explain how sperm were delivered, was criticised for being pornographic.The dominant message is to abstain. A 2013 review by UNESCO and Beijing Forestry University noted the prevalence of “terror-based” sex education, with content largely focused on the horrors of pregnancy, abortion and HIV. Earlier this month a university in Xi’an in central China ran a course entitled “No Regrets Youth” where students received a “commitment card”, essentially a pledge to remain a virgin until marriage.We need to talkThere is almost no discussion in Chinese schools about love, communication or trust, how to say no or to deal with harassment or abuse. Homosexuality is not discussed, and Chinese parents rarely talk with their children about sex. Peng Xiaohui of Central China Normal University, who runs sex-education classes (including the one at China Agricultural University), had excrement thrown at him last year because of the work he does. Several Chinese and foreign NGOs have tried to fill the gap, but many are now wary after themonth-long detention this year of five feminists who had launched a campaign against sexual harassment. Most Chinese youths find out about sex from the internet and online pornography.That does not work well. Because of the mismatch between lust and learning, around a quarter of all sexually active women under 24 get pregnant by mistake. Half of them do not use prophylactics, some because they know little about them, others because of insufficient access.The pill is not widely used in China, even by married women. The government encourages the use of intra-uterine devices which provide less chance of human error. Until last year advertising condoms on television was banned (abortion, by contrast, is widely promoted). Convenience stores sell condoms, but they are not always available near college campuses.Those who do use prophylactics often use them wrongly: a 2014 study found that a quarter of under-17s who got pregnant had used some form of birth control. There is also a flourishing trade in “counterfeit condoms”, shoddily made sheaths being passed off as popular name brands. As a result sexually transmitted diseases are on the rise; 91% of new HIV cases are from sexual contact.Dirty secretsIt is hardly surprising that the abortion rate is so high. The one-child policy has made termination a normal phenomenon. Most clinics, private or state, put a premium on speed and offer no advice on how to avoid getting pregnant again. So repeat abortions are common: a study of nearly 80,000 Chinese women who terminated pregnancies in 2013, published in October by the Lancet, a British journal, found that 37% were doing so for the second time, and 29% for a third time or more. Unmarried women account for a rising share of these—and are a significant reason why, after an extended period of decline, terminations have been increasing in number since 2003.Although China has no national system for counting abortions (official statistics include only state facilities), a researcher from the National Health and Family Planning Commission reckons there could be 13m terminations or more a year, a figure widely quoted in state media. But Marie Stopes, an international reproductive-health agency, reckons that figure could be as high as 40m, given domestic sales for pharmaceutical companies selling drugs used in terminations. If that number is correct, around half of all abortions worldwide are in China. The high number of terminations is in marked contrast to the low birth rate. If Marie Stopes is correct, 2.5 babies are aborted in China for every one born, compared with about two live births per termination in Russia and five births to one abortion in America. Even using the widely cited 13m figure, there are nearly as many abortions as births in China each year. That, and not frank talk about sex, is China’s shame.。
VEEG对难治性非惊厥发作癫痫的诊断及致痫灶术前定位价值李哲贤;毓青;杨卫东;陈英;陈旨娟;郝志东【摘要】Objective: To explore the significance of long time Video-EEG in the diagnosis of non-convulsive seizure and preoperative localization of refractory epilepsy. Methods:22 patients with intractable non-convulsive seizure epilepsy were checked by VEEG, all of them were checked by MRI, 17 patients were checked by interictal PCT-CT.8 patients were checked by MEG. All patients did the preoperative evaluation on epileptogenic zone, then in half of them with surgical treatment,the accuracy of epileptogenic zone was validated with intraoperative electrocorticography (ECoG). Results: 22 patients were monitored by VEEG for 24-48 h, 83 non-convulsive seizures were observed in which unknown seizure type in past medical history was found in the 5 patients. In all patients clinically seizures and ictal discharge (2 -20 times) were watched.18 ictal EEG prompted discharge area:frontal(6),temporal(7),frontal-temporalarea(5).The seizure onset zone was consistent with symplomatogenic zone in 12 patients. Tne coincidence rates of VEEG methods on localizing epileptogenic zone with the abnormal MRI and with MEG were 100% respectively,and with PET-CT was 82.35% .VEEG was consistent with ECoG in the 11 patients who with surgical treatment. Conclusion: VEEG can improve the detection rate of non-convulsive seizure and also has a notable value in diagnosis classification. Meanwhile, it has significance in preoperative localization of epilepsy surgery. VEEG is an essentialexamination on presurgical evaluation in intractable epilepsy.%目的:探讨长程视频脑电图(VEEG)对非惊厥发作癫痫的诊断价值及对难活性癫痫术前定位的意义.方法:对22例难治性非惊厥发作性癫痫患者行VEEG监测,22例行头MRI检查,17例行发作间期PET-CT检查,8例行脑磁图(MEG)检查.对所有患者进行致痫灶术前定位评估后11例行手术治疗,术中皮层脑电图(ECoG)监测结果验证VEEG定位的准确性.结果:22倒VEEG监测时间24~48h,共监测到83次非惊厥发作,其中5例(22.72%)监测到既往未曾发现的发作类型.每例均记录到临床发作和相应的发作期脑电异常(2~20次),18例(69次)提示局灶起源(额叶起源6例,颞叶起源7例,额颞叶起源5例),其中12倒(54次,占78.26%)发作起始区与症状产生区一致.VEEG定位的致痫灶区与头MRI有结构异常者符合率为100%,与PETCT符合率为82.35%,与MEG符合率为100%,与11例手术治疗患者的ECoG监测结果一致(符合率100%).结论:VEEG可提高癫痫患者非惊厥类发作的检出率,有助于癫痫的分类,比较准确地定位致痫灶,是难治性癫痫术前评估必不可少的检查.【期刊名称】《天津医科大学学报》【年(卷),期】2011(017)003【总页数】3页(P367-369)【关键词】非惊厥发作:视频脑电图:难治性癫痫;术前评估【作者】李哲贤;毓青;杨卫东;陈英;陈旨娟;郝志东【作者单位】天津医科大学总医院神经内科;天津医科大学总医院神经内科;天津医科大学总医院神经外科,天津300052;天津医科大学总医院神经内科;天津医科大学总医院神经外科,天津300052;天津医科大学总医院神经外科,天津300052【正文语种】中文【中图分类】R742.1以非惊厥发作为主的癫痫发作往往症状不典型,其与肢体或面部强直阵挛发作的惊厥类发作相比不容易被识别或感知到。
J. Microelectron. Manuf. 2, 19020205 (2019)doi: 10.33079/jomm.19020205Editorial Introduction:China's IC industry has been flourishing in recent years, huge market demand together with government investments are the major driving forces for this development. The status and development momentum of the Chinese IC industry also attracted wide interest and attention of international counterparts. A group of domestic IC experts are invited by the JoMM to write a series of articles about China's IC industry, including the history, current status, development, and related government policies. Information in these articles is all from public data from recent years. The purpose of these articles is to enhance mutual understanding between the Chinese domestic IC industry and international IC ecosystem.The following article is the third one of this series, the status quo of China's IC industry. The IC industry chain is very long including design, manufacturing, special equipment, materials, packaging and testing. The article series are arranged in accordance with this scope.Current Status of the Integrated Circuit Industry in China― IC Manufacturing Industry1.IntroductionThe integrated circuit is a product featured with fast revolution and high technologies. Speaking of the current international market structure, IC companies are struggling with intellectual property dominance, the key IC industrial product global organizations presents the characteristics of multinational monopoly. Integrated circuit multinational companies’ sales, manufacturing and R & D strategies are in the direction of globalization.As the largest integrated circuit market in the world, the self-sufficient ability of integrated circuits in China is low, and the pain of lacking core needs to be addressed urgently. With the rapid development of automotive electronics, smart phones and other cutting-edge applications, the domestic integrated circuit market has expanded rapidly.At present, integrated circuits are still among the cores of communication, multimedia and computer technology. High added value, technology intensive, strong competitiveness and huge output value are the advantages of integrated circuit industry. Integrated circuit industry has great potential and vitality, and it is a well-deserved high-growth industry. Therefore, we must vigorously develop the integrated circuit industry, so as to promote the progress of economic construction in China and accelerate the process of information industrialization.The integrated circuit design industry in China is highly market-oriented. On the one hand, there are many domestic enterprises engaged in integrated circuit design, and the competition is fierce; on the other hand, many IC design enterprises from abroad have poured into the Chinese market, among which there are plenty of well-known design companies with strong capital and technical strength, which further intensified the competition in Chinese market.As the foundation and core of the information industry, the integrated circuit is the basic, leading and strategic industry of the whole world of the national economy and the society. In recent years, China's electronic industry has continued to grow at a high speed, and the integrated circuit industry has experienced a period of rapid development.2. A Survey of Domestic Integrated Circuit ManufacturersThe followings are brief review of the major leading manufacturers that representing the development of integrated circuits in China:2.1.Semiconductor Manufacturing International Corporation (SMIC)Semiconductor Manufacturing International Corporation (''SMIC", NYSE code: SMI, HK Ex stock code: 981), SMIC was established in 2000. Its headquarters is located in Shanghai, China. It is one of the leading IC chip contract manufacturers in the world, and it is also the largest and most advanced integrated circuit chip manufacturing enterprise in mainland China. Its main business is to manufacture integrated circuit chips for customers according to the integrated circuit design of the customer or the third party. The founder of the company is Dr. RujingZhang who used to work for Taiwan Semiconductor Manufacturing Company(TSMC). At present, the vast majority of the company's executives are Taiwanese. It is one of the world's leading integrated circuit wafer contract manufacturers, SMIC provides 0.35μm~28nm wafer foundry and technical services to global customers.SMIC has a 300mm chip factory and three 200mm chip factories in Shanghai. There are two 300mm chip factories in Beijing, a 200mm chip factory in Tianjin, a 200mm chip factory in Shenzhen and a packaging and testing plant in Chengdu. SMIC also provides customer service and marketing offices in the United States, Europe and Japan, as well as representative offices in Hong Kong. In addition, SMIC International manages a 200mm chip factory on behalf of Chengdu Cension Semiconductor Manufacturing Corporation Ltd., and also manages a 300mm chip factory on behalf of Wuhan Xinxin Semiconductor Manufacturing Co., Ltd. (XMC).Semiconductor manufacturing is a capital expenditure industry, the lack of capital expenditure capacity can easily lead to the company gradually fall behind the advanced process competitors. The company's R & D investment has continued to grow, with R & D spending of $318 million in 2016, R & D investment accounting for 10.92 percent of revenue, and R & D investment of $219 million in 2017, accounting for 14.18 percent of revenue. SMIC continues to increase R & D investment, 28nm process will gradually release, meanwhile it has started the development of 14nm process. SMIC is expected to start trial production in 2019, and the technological gap with international factories will gradually narrow.In the whole production process and the whole service from R & D to mass production, SMIC integrates a comprehensive quality and control system. In addition, its diverse laboratories and tools can be used for chemical and raw material analysis, product failure analysis, yield improvement, reliability inspection and monitoring, and equipment calibration.In order to ensure the consistency of product quality and the customer flexibility of different customers, SMIC adopts the concept of "one big factory", that is, in all SMIC factories, each chip factory optimizes the equipment and process parameters in order to meet the standard and yield requirement of testing (WAT) for the same wafer acceptance.2.2.Shanghai Huahong (Group) Co., Ltd.Shanghai Huahong (Group) Co., Ltd. was established in 1996, the company is the result and carrier the national "909" project.While constructing and operating the first deep submicron ultra-large-scale 8-inch integrated circuit production line in China, Huahong Group gradually becomes the core of chip manufacturing business. It has gradually become an integrated circuit industry group with the common development of integrated circuit system integration and application services, chip manufacturing process research and development, chip design, electronic component trade, venture capital at home and abroad and other business platforms.With the mission of "building the '909' project and promoting the development of the information industry", Huahong Group is committed to playing the main role of the state-owned industrial group in the fields of 8-inch characteristic process chip manufacturing, integrated circuit process research and development public platform, AFC and RFID system application, integrated circuit design service and so on. Huahong Group is a senior sponsor of World Expo 2010 in Shanghai, successfully realizing the largest application of RFID technology in the field of tickets in the world, and has been well received by all parties. At present, Huahong Group is actively promoting the "909" project upgrade-12-inch integrated circuit production line project construction.After years of construction and development, Huahong Group has not only promoted the development of integrated circuit industry in China, but also made remarkable achievements in chip manufacturing, chip design, system and application services, process research and development, electronic component trade and venture capital (including overseas investment). It offers contract (foundry) technology, product process, chip design, AFC system and other products and services to the society and users.2.3.China Resources Microelectronics Limited (“CR Micro”)China Resources Microelectronics Limited (“CR Micro”) is a high-tech enterprise belonging to China Resources (Holdings) Co., Ltd. (CR) which is engaged in investment, development and operations management of microelectronics business,and it is also one of the largest and most influential comprehensive microelectronics enterprises in China, been included in the top 100 electronic information enterprises continuously by the Ministry of Industry and Information Technology since 2004.CR Micro takes it as its own responsibility to revitalize the national microelectronics industry and focuses on the fields of simulation, power semiconductors and the like, and is dedicated to becoming a leading enterprise embracing a culture of innovative spirit, excellent performance and industrial leadership in the Chinese semiconductor industry, to provide products and systematic solutions of extraordinary quality to the benefit of a harmonious and efficient society.CR Micro operates a business of integrated circuit design, mask manufacture, wafer fabrication, package testing and discrete devices, currently holding 5 production lines of 6-8 inch wafer fabrication, 2 production lines of package testing, 1 production of mask manufacture and 3 design companies, and it is the only enterprise possessing the complete semiconductor industry chain in China.With the increase of the enterprise scale, CR Micro also values its social responsibility, continuously carrying out environmental protection as well as energy-saving and emission-reducing measures. It has been awarded titles such as Advanced Unit of Energy-saving in “Eleventh Five-Year Plan” by Jiangsu Province, Category II Enterprise of “Resources-saving Type and Environment-friendly Type” by Wuxi City Government, and has been elected a top “Green” enterprise for four successive years according to the Environmental Behavior rating of The Yangtze River Delta region.2.4.Hynix-STMicroelectronics Co., Ltd. (Wuxi)Hynix Semiconductor was founded in 1983 as a modern electronics industry co., Ltd., officially listed in Korea in 1996, acquired LG Semiconductor in 1999, and changed its name to Hercules Semiconductor in 2001, which was separated from Hyundai Group. In October 2004, the system IC business was sold to Citigroup as a professional memory manufacturer. It is the world's second-largest DRAM manufacturer.Hynix-STMicroelectronics Co., Ltd. is a wholly foreign-owned world-class memory company established by the joint venture of the South Korean (strain) Hynix semiconductor and the European STMicroelectronics Co., Ltd. in the export processing zone of Wuxi New Area of Jiangsu. Its main product includes 8-inch and 12-inch integrated circuit wafer, the application range covers memory, consumer products, mobile devices, SOC and system IC and other fields. The company will use the world's most advanced technology to produce DRAM and NAND flash memory.The project is the only industrial project approved by the State Council in Wuxi. The total investment is 3.5 billion dollars. This project has the largest domestic semiconductor monomer investment and the most advanced technology, as well it’s the largest wholly foreign-owned project in Jiangsu Province. As a joint venture between two important groups in the semiconductor industry, Hynix-STMicroelectronics Co., Ltd. is bound to take a steady pace and move forward on the road of prosperity.2.5.HeJian Technology (Suzhou) Co., Ltd.HeJian Technology (Suzhou) Co., Ltd. is located in Suzhou Industrial Park. It is a first-class wafer manufacturer with strong foreign capital and manufacturing cutting-edge integrated circuits. The first 8-inch wafer plant was officially put into production in May 2003 with a total investment of more than $1.2 billion and a maximum monthly output of 60,000 tablets. At present, HeJian technology is the fastest in the same industry in China to achieve monthly, quarterly profit and loss balance, and employ high efficiency production capacity and high level of process technology to create a sustained profit and excellent performance of wafer industry enterprises. It has introduced the upstream and downstream industries into Suzhou Industrial Park to form a clustering effect, completed the first step in the layout of integrated circuit industry in China, and planned to establish a number of wafer manufacturing plants.HeJian Technology adheres to the business philosophy of customer satisfaction and growing together with customers, and provides customers with comprehensive and competitive services, including multi-project wafer (MPW) services, IP services, BOAC, Mini-library and so on. Senior, professional technical and business team in new product development, scheme design, delivery time, quality improvement and good rate to provide strong support to customers. The long-term commitment to promote the overall development of the Chinese semiconductor industry has established a cooperative relationship with a number of design companies. Through cooperation with the technical production of HeJian technology, these design companies have made significant achievements in the marketdevelopment and the operation of the company. Lili also provides preferential MPW services for industrialization bases, and signs school-enterprise cooperation agreements with many famous universities in China to implement the strategy of localization of talents and provide perfect training programs for employees. At the same time, HeJian technology also actively practices social responsibility, actively participates in social public welfare activities, and supports the education of vulnerable groups and poor areas.In the future, HeJian technology will actively expand the mainstream product market, develop more advanced and special application technology, and continue to expand capacity to meet the expanding market demand. At the same time, HeJian technology cooperates with the head office UMC to carry out business promotion in the mainland to facilitate customers to obtain the 6-inch, 8-inch and 12-inch full-range customer-oriented wafer solutions provided by the group in a timely manner.2.6.Shougang NEC Electronics Co., Ltd.Shougang NEC Electronics Co., Ltd. (SGNEC) is a joint venture of Shougang and NEC Electronics Corporation. It is committed to semiconductor integrated circuit manufacturing and sales manufacturers. The company was founded in December 1991, the assembly line was put into production in April 1994 and the diffusion line was put into operation in April 1995.The company has a complete production line of semiconductor integrated circuit production (including wafer manufacturing and IC packaging). Its main products are MCU (microcomputer control unit) circuit, remote control circuit, display drive circuit, general LIC and so on. At the same time, the company targets at domestic customers to carry out the labor business of foundry products. Manufacturing level: 6-inch wafer 0.35 μm, can handle 15,000 pieces per month. IC package: QFP series and many other package types, totaling 200 million pieces/year.2.7.Advanced Semiconductor Manufacturing Corporation Limited (ASMC)Shanghai Advanced Semiconductor is a leading manufacturer of analog chips. It mainly produces imitating-true semiconductors and bipolar high-content mixed-signal semiconductors, and has a leading position in automotive electronics, MEMS and IGBT. ASMC’s customers include some of the world's leading manufacturers of integrated devices and non-production line semiconductor companies. Shanghai advanced semiconductor production standards and special semiconductors, designed by the company's customers, products for a variety of end-market applications, including computers, communications and consumer electronics. In 2009, Shanghai Advanced Semiconductor obtained VDA6.3 quality system certification, now has an "A" qualified supplier to provide services for the international automotive market.The company provides customers with a wide range of processing technologies. Comprises the following steps of: simulating a bipolar, BICMOS and HVMOS processing technology of a semiconductor, and a non-volatile storage memory technology for manufacturing an intelligent ID card. With the flexible manufacturing mode of various processing technologies, ASMC can support the customer's specific manufacturing requirements. At present, there are one 5-inch, 6-inch, 8-inch and MEMS independent production lines in Shanghai Pudong New River Basin.2.8.TSMC (Shanghai) China Company LimitedTSMC (Shanghai) China Company Limited (TSMC Shanghai) is located in Songjiang Science and Technology Park of Shanghai. It is a wholly owned subsidiary of TSMC, and it is also an important part of its global layout. TSMC will use its rich success experience to help customers eliminate all kinds of difficulties from design to final listing, provide customers with the most complete product solutions, and establish a long-term and deep partnership with customers. TSMC is the largest and most trusted wafer manufacturing service partner in the world, and is also the best pipeline for obtaining the best wafer manufacturing service in China and the world. TSMC Shanghai is facing the mainland domestic customers, providing high-quality production, operation and design services, and the antenna of its business team has spread throughout the country.TSMC is the world's leading and largest professional integrated circuit manufacturing service company. In the generation of advanced process technology, it has become a trend for many companies to produce and manufacture outside the company. When the development of integrated circuit industry begins to enter such a new model, TSMC undoubtedly has an excellent strategic position and the best profit advantage.TSMC was established in Xinzhu ScienceIndustrial Park on February 21, 1987. It is the first professional integrated circuit manufacturing service company in the world. As a global leader, TSMC provides the most advanced process technology in the industry and has the most complete component database (Library), intelligent (IP), design tool (Design Tools) and design reference process (Reference Flow). In the field of professional wafer manufacturing services.In 2004, TSMC and its investment, the total capacity of the joint venture, has reached 4.8 million pieces of eight-inch wafer (estimated) for the whole year. The plant area in Taiwan includes a six-inch wafer factory (fab2), five eight-inch wafer factories (fab2, fab5, fab6, fab7 and fab8), two twelve-inch wafer factories (fab12, fab14).2.9.Shanghai Huahong Grace Semiconductor Manufacturing Co., Ltd.Shanghai Huahong Grace Semiconductor Manufacturing Co., Ltd. opened on September 23, 2003. The total investment for the first phase of the project was $1.63 billion. At present, it has built two 12-inch factory buildings, one of which has been put into production at the A line (8-inch line). By the end of 2004, it produced 27,000 pieces of 8-inch silicon wafers. It is available in 0.25/0.22/0.18/0.15/0.12 μm processes, including: logic, mixed-signal, RF, high-voltage devices, and mask memory, static memory, flash memory, embedded flash memory, and more.Shanghai Huahong Grace Semiconducor Manufacturing Co., Ltd. ("Huahong Grace"), formed by the new merger of Shanghai Huahong NEC Electronics Co., Ltd. and Shanghai Grace Semiconductor Manufacturing Co., Ltd., is the world's leading 8-inch foundry. HuaHong Grace has three 8-inch integrated circuit production lines in Zhangjiang and Jinqiao, Shanghai, with a monthly capacity of 124,000. The company is headquartered in Shanghai, China, providing sales and technical support in Taiwan, Japan, North America and Europe.HuaHong and Grace signed a legally binding merger agreement on September 13, 2011. The trading structure of the merger is all-stock trading. Under the terms of the merge agreement, HuaHong issued new shares to Grace's existing shareholders in exchange for all Grace's issued shares.Grace Semiconductor Manufacturing Co., Ltd. is a leader in advanced 8-inch semiconductor production technology in China, focusing on high-quality manufacturing services and high value-added technologies. It has an 8-inch chip-generation factory with world-class leadership in NOR flash technology, and provides advanced technology platform for logic, non-volatile memory, mixed signal, radio-frequency, high-voltage device and static memory, and the capacity of the wafer is 44,000 per month.2.10.Jilin Sino-Microelectronics Co., Ltd. (JSMC)Jilin Sino-Microelectronics Co., Ltd. is located in Jilin High-tech Industrial Development Zone, which is a national key high-tech enterprise, and is established as a national enterprise technology center and a national post-doctoral research work station. The company now has nearly 2000 employees, R & D personnel account for 20% of the company's total number. The company's total assets are 2.7 billion yuan, more than 2,000 employees, R & D personnel accounted for more than 30% of the company's total number, covers an area of nearly 400,000 square meters, construction area of 135,000 square meters, purification area of 17,000 square meters, the main purification level is 0.3 microns Hundreds of levels. The company was listed on the Shanghai Stock Exchange in March 2001 with stock code 600360 and total share capital of 521.6 million shares.Jilin Sino-Microelectronics Co., Ltd is a high-tech enterprise which integrates power semiconductor device design and research, chip processing, packaging testing and product marketing. Demonstrated by the Ministry of Science and Technology, the Chinese Academy of Sciences and other national institutions, it is listed as the national enterprise technology center, the national postdoctoral research workstation, and the national innovative enterprise.Jilin Sino-Microelectronics Co., Ltd. has 3-inch, 4-inch, 5-inch and 6-inch power semiconductor discrete devices and IC chip production lines, chip processing capacity of more than 3 million chips per year, packaging capacity of 3 billion pieces per year. The company has a number of patents in terminal design, process manufacturing and product design. Each series of products adopt bipolar, MOS technology and integrated circuit and other core manufacturing technologies. The company mainly produces power semiconductor devices and IC, applications in consumer electronics, energy-saving lighting, computer, PC, automotive electronics, communication protection and industrial control. The trademark has been recognized as a "well-known trademark in China". The company has formed a series of products such as VDMOS, IGBT, FRED, SBD, BJT as the main line of marketing, and hasTable 1. Top 10 pure wafer foundries in 2016 (million dollars).become a manufacturer of solutions for customers in the field of power semiconductor devices.Jilin Sino-Microelectronics Co., Ltd. has more than 40 years of production and operation history of power semiconductor device design and development, chip processing, packaging and sales. The company has a 4-inch,5-inch and 6-inch power semiconductor wafer production line. The chip processing capacity is more than 2.2 million chips per year, and the packaging capacity is 2.2 billion pieces per year. The main products of organic box power transistor, color TV line output tube and power tube, energy saving lamp, ballast, transformer Bipolar power transistor, VDMOS field effect power transistor, semiconductor discharge tube, single/bidirectional thyristor, Schottky, fast recovery diode and other products. Products are widely used in all kinds of household appliances, green lighting, computer, automotive electronics, network communication, industrial control and other fields. Through a good joint venture and cooperation with PHILIPS, FAIRCHILD, China Microelectronics has become one of the largest semiconductor power device manufacturing bases in China.2.11.Foundry Top Three: SMIC, HuaHong Semiconductor, Huali MicroelectronicsIn the foundry market, mainland companies faced with challenges and opportunities. On the one hand, mainland China design company in the fast-growing, local design companies have a natural tendency to support local manufacturers; on the other hand, the manufacturing sector entrance barrier for funds, human and knowledge accumulated has increased, and Chinese manufacturers in these areas are seeing a larger gap between the world's leading manufacturers are widening trend. How to moving steadily on the existing basis and gradually narrow the gap is a great challenge to the viability of SMIC, HuaHong, Huali Microelectronics represented continent foundries.The global wafer industry has steadily increased and the industry is concentrated. ICInsight expects the pure wafer replacement plant to be 7.5% a year from 2016 to 2021. Compound growth of 6 percent rose from $50 billion in 2016 to $72.1 billion in 2021. The concentration pure-wafer foundry industry is very high, and the top four pure wafer-generation plants account for 85% of the global share, of which the TSMC has a market share of nearly 60%. Based on the threshold of high technology and high investment in wafer contract industry, it can be inferred that the pattern of wafer contract industry will not change much in the short term, but SMIC may be the fastest growing foundry in the near future.Compared with the international giants, it still takes a long time to catch up for the domestic top three. From the perspective of the mainland market, because of the rise of the domestic market, especially the rapid development of the design company, the sales of the pure fabs in the country are growing rapidly. According to ICInsight, the mainland wafer contract industry market reached $7 billion in 2017, a jump of 16 percent from a year earlier, significantly higher than the global average. TSMC is still a dominant family, accounting for as much as 47%.The domestic advanced process falls behind by more than two generations. Semiconductor manufacturing market concentration keeps onTable 2. Major pure wafer foundries in China market forecast (million dollars).Figure 1. The concentration of wafer manufacturing is increasing.climbing, only giants can continue to develop and promote the development of technology. The 28-14 nm process node of the global integrated circuit industry is mature, and the 14/10 nm process has entered mass production, and Intel, Samsung and TSMC have announced that the sub-10nm chip production has been realized, and the production line of 7 nm and 5 nm is prepared to continue to invest. However, the domestic 28nm process only achieved mass production in 2015, and 28nm is still the main process.The most advanced manufacturing process of the local fab is still in the 28 nm Poly/SiON scheme, although it has achieved good results in the 28-nm revenue-making ratio and the 28-nm-HKMG mass-production process. SMIC is the leader of domestic pure wafer manufacturing plants. SMIC has a considerable comparative advantage in the traditional。
13576fbT YPICAL APPLICATIONF EATURESA PPLICATIONSD ESCRIPTION with USB On-the-Go + TripleStep-Down DC/DCsnHDD-Based Media Playersn GPS, PDAs, Digital Cameras, Smart Phones n Automotive Compatible Portable ElectronicsL , L T , L TC, L TM, Linear Technology and the Linear logo are registered trademarks of Linear Technology Corporation. Bat-T rack and PowerPath are trademarks of Linear TechnologyCorporation. All other trademarks are the property of their respective owners. Protected by U.S. Patents, including 6522118, 6404251.High Effi ciency PowerPath Manager with Overvoltage Protectionand T riple Step-Down RegulatorPowerPath Switching Regulator Effi ciencyto System Load (P VOUT /P VBUS )nBidirectional Switching Regulator with Bat-T rack™ Adaptive Output Control Provides Effi cient Charging and a 5V Output for USB On-The-Go n Bat-T rack Control of External High Voltage Step-Down Switching Regulatorn Overvoltage Protection Guards Against Damage n Instant-On Operation with Discharged Battery n T riple Step-Down Switching Regulators with I 2C Adjustable Outputs (1A/400mA/400mA I OUT )n 180mΩ Internal Ideal Diode + External Ideal Diode Controller Powers the Load in Battery Mode n Li-Ion/Polymer Battery Charger (1.5A Max I CHG )n Battery Float Voltage: 4.2V (L TC3576), 4.1V (L TC3576-1)n Compact (4mm × 6mm × 0.75mm) 38-Pin QFN PackageThe L TC ®3576/L TC3576-1 are highly integrated power management and battery charger ICs for Li-Ion/Polymer battery applications. They each include a high effi ciency, bidirectional switching PowerPath™ manager with auto-matic load prioritization, a battery charger , an ideal diode, a controller for an external high voltage switching regulator and three general purpose step-down switching regulators with I 2C adjustable output voltages. The internal switch-ing regulators automatically limit input current for USB compatibility and can also generate 5V at 500mA for USB on-the-go applications when powered from the battery. Both the USB and external switching regulator power paths feature Bat-T rack optimized charging to provide maximum power to the application from supplies as high as 38V . An overvoltage circuit protects the L TC3576/L TC3576-1 from damage due to high voltage on the V BUS or WALL pins with just two external components. The L TC3576/L TC3576-1 are available in a low profi le 38-pin (4mm × 6mm × 0.75mm) QFN package.LOAD CURRENT (mA)100E F F I C I E N C Y (%)2040608010010003576 TA01b1001030507090/23576fbP IN CONFIGURATIONA BSOLUTE MAXIMUM RATINGS V BUS , WALL (T ransient) t < 1ms,Duty Cycle < 1% ..........................................–0.3V to 7V V BUS , WALL (Static), BAT , V IN1, V IN2, V IN3, V OUT , ENOTG, NTC, SDA, SCL, DV CC ,RST3, CHRG ................................................–0.3V to 6V I LIM0, I ILIM1 ........–0.3V to Max(V BUS , V OUT , BAT) + 0.3V EN1, EN2, EN3 ..............................–0.3V to V OUT + 0.3V FBx (x = 1, 2, 3) ..............................–0.3V to V INx + 0.3V I OVSENS ...................................................................10mA I CLPROG ....................................................................3mA I CHRG , I RST3............................................................50mA I PROG ........................................................................2mA I LDO3V3 ...................................................................30mA I SW1, I SW2 (Continuous) .......................................600mA I SW , I SW3, I BAT , I VOUT (Continuous) ..............................2A Maximum Junction Temperature...........................125°C Operating Temperature Range..................–40°C to 85°C Storage Temperature Range ...................–65°C to 125°C(Notes 1, 2, 3)13141516TOP VIEW39UFE PACKAGE38-LEAD (4mm s 6mm) PLASTIC QFN17181938373635343332242526272829303187654321CLPROG LDO3V3NTCBIAS NTC OVGATE OVSENS FB1V IN1SW1EN1ENOTG DV CC IDGATE CHRG PROG ACPR WALLV C FB2V IN2SW2EN2RST3FB3I L I M 1I L I M 0S WV B U SV B U SV O U TB A TS C LS D A N CV I N 3S W 3N CE N 3232221209101112T JMAX = 125°C, θJA = 34°C/WEXPOSED PAD (PIN 39) IS GND, MUST BE SOLDERED TO PCBSYMBOL PARAMETER CONDITIONS MIN TYP MAX UNITSPowerPath Switching Regulator—Step-Down ModeV BUS Input Supply Voltage 4.35 5.5V I VBUS(LIM)Total Input Current1× Mode 5× Mode 10× ModeLow Power Suspend Mode High Power Suspend Mode l l l l l824408000.321.6904728800.392.0510050010000.52.5mA mA mA mA mA I VBUSQ (Note 4)Input Quiescent Current1× Mode5×, 10× ModesLow/High Power Suspend Modes7170.045mA mA mAORDER INFORMATIONLEAD FREE FINISH TAPE AND REEL PART MARKING PACKAGE DESCRIPTIONTEMPERATURE RANGE L TC3576EUFE#PBF L TC3576EUFE#TRPBF 357638-Lead (4mm × 6mm) Plastic QFN –40°C to 85°C L TC3576EUFE-1#PBFL TC3576EUFE-1#TRPBF3576138-Lead (4mm × 6mm) Plastic QFN–40°C to 85°CConsult L TC Marketing for parts specifi ed with wider operating temperature ranges.Consult L TC Marketing for information on non-standard lead based fi nish parts.For more information on lead free part marking, go to: http://www.linear .com/leadfree/ For more information on tape and reel specifi cations, go to: http://www.linear .com/tapeandreel/E LECTRICAL CHARACTERISTICS The l denotes the specifi cations which apply over the full operatingtemperature range, otherwise specifi cations are at T A = 25°C. V BUS = 5V , BAT = 3.8V , DV CC = 3.3V , R CLPROG = 3.01k, unless otherwise noted./E LECTRICAL CHARACTERISTICSThel denotes the specifi cations which apply over the full operating temperature range, otherwise specifi cations are at T A = 25°C. V BUS = 5V, BAT = 3.8V, DV CC = 3.3V, R CLPROG = 3.01k, unless otherwise noted.SYMBOL PARAMETER CONDITIONS MIN TYP MAX UNITSh CLPROG (Note 4)Ratio of Measured V BUS Current toCLPROG Program Current1× Mode5× Mode10× ModeLow Power Suspend ModeHigh Power Suspend Mode210116022009.656mA/mAmA/mAmA/mAmA/mAmA/mAI VOUT(POWERPATH)V OUT Current Available BeforeDischarging Battery 1× Mode, BAT = 3.3V5× Mode, BAT = 3.3V10× Mode, BAT = 3.3VLow Power Suspend ModeHigh Power Suspend Mode0.261.612166712170.3120.412.4mAmAmAmAmAV CLPROG CLPROG Servo Voltage in Current Limit Switching ModesSuspend Modes 1.18100VmVV UVLO V BUS Undervoltage Lockout Rising ThresholdFalling Threshold 3.954.304.004.35VVV DUVLO V BUS to BAT Differential UndervoltageLockout Rising ThresholdFalling Threshold20050mVmVV OUT V OUT Voltage1×, 5×, 10× Modes, 0V < BAT < 4.2V,I VOUT = 0mA, Battery Charger Off USB Suspend Modes, I VOUT = 250μA 3.44.5BAT + 0.34.64.74.7VVf OSC Switching Frequency 1.8 2.25 2.7MHz R PMOS_POWERPATHPMOS On-Resistance0.18ΩR NMOS_POWERPATHNMOS On-Resistance0.30ΩI PEAK_POWERPATH Peak Inductor Current Limit1× Mode (Note 5)5× Mode (Note 5)10× Mode (Note 5)123AAAR SUSP Suspend LDO Output Resistance Closed Loop10ΩPowerPath Switching Regulator—Step-Up Mode (USB On-the-Go)V BUS Output Voltage0mA ≤ I VBUS ≤ 500mA, V OUT > 3.2V 4.75 5.25V V OUT Input Voltage 2.9 5.5V I VBUS Output Current Limit l550680mA I PEAK Peak Inductor Current Limit(Note 5) 1.8A I OTGQ V OUT Quiescent Current V OUT = 3.8V, I VBUS = 0mA (Note 6) 1.38mA V CLPROG Output Current Limit Servo Voltage 1.15VV OUT(UVLO)V OUT UVLO—V OUT FallingV OUT UVLO—V OUT Rising 2.5 2.62.8 2.9VVt SCFAUL T Short-Circuit Fault Delay V BUS < 4V and PMOS Switch Off7.2ms Bat-T rack Switching Regulator ControlV WALL Absolute WALL Input Threshold Rising ThresholdHysteresis 4.2 4.31.14.4VVΔV WALL Differential WALL Input Threshold WALL-BAT FallingHysteresis 0306045mVmVV OUT Regulation Target Under V C Control 3.55BAT + 0.3VI WALLQ WALL Quiescent Current400μAR ACPR ACPR Pull-Down Strength150ΩV H ACPR ACPR High Voltage V OUT V V L ACPR ACPR Low Voltage0Vh t t p://o n e i c.c o m/33576fbE LECTRICAL CHARACTERISTICSThel denotes the specifi cations which apply over the full operating temperature range, otherwise specifi cations are at T A = 25°C. V BUS = 5V, BAT = 3.8V, DV CC = 3.3V, R CLPROG = 3.01k, unless otherwise noted.SYMBOL PARAMETER CONDITIONS MIN TYP MAX UNITS Overvoltage ProtectionV OVCUTOFF Overvoltage Protection Threshold With 6.2k Series Resistor 6.1 6.35 6.7VV OVGATE OVGATE Output Voltage V OVSENS < V OVCUTOFFV OVSENS > V OVCUTOFF 1.88•V OVSENS12VVt RISE OVGATE Time to Reach Regulation OVGATE C LOAD = 1nF 2.2ms Battery ChargerV FLOAT BAT Regulated Output Voltage L TC3576l 4.1794.1654.2004.2004.2214.235VVL TC3576-1l 4.0794.0654.1004.1004.1214.135VVI CHG Constant Current Mode Charger Current R PROG = 1kR PROG = 5k 98018510302061065223mAmAI BAT Battery Drain Current V BUS > V UVLO, Suspend Mode,I VOUT = 0μA3.66μAV BUS = 0V, I VOUT = 0μA(Ideal Diode Mode)2845μA V PROG PROG Pin Servo Voltage 1.000V V PROG_TRKL PROG Pin Servo Voltage in T rickle Charge BAT < V TRKL0.100V V C/10C/10 Threshold Voltage at PROG100mV h PROG Ratio of I BAT to PROG Pin Current1030mA/mA I TRKL T rickle Charge Current BAT < V TRKL, R PROG = 1k100mA V TRKL T rickle Charge Threshold Voltage BAT Rising 2.7 2.85 3.0V ΔV TRKL T rickle Charge Hysteresis Voltage135mV ΔV RECHRG Recharge Battery Threshold Voltage Threshold Voltage Relative to V FLOAT–75–100–125mV t TERM Safety Timer Termination Period Timer Starts When V BAT = V FLOAT 3.345Hour t BADBAT Bad Battery Termination Time BAT < V TRKL0.40.50.6Hour h C/10End of Charge Current Ratio(Note 7)0.0850.10.112mA/mA V CHRG CHRG Pin Output Low Voltage I CHRG = 5mA65100mV I CHRG CHRG Pin Leakage Current V CHRG = 5V1μA R ON_CHG Battery Charger Power FET On-Resistance (Between V OUT and BAT)0.18ΩT LIM Junction Temperature in ConstantTemperature Mode110°C NTCV COLD Cold Temperature Fault Threshold Voltage Rising ThresholdHysteresis 7576.51.678%NTCBIAS%NTCBIASV HOT Hot Temperature Fault Threshold Voltage Falling ThresholdHysteresis 33.434.91.536.4%NTCBIAS%NTCBIASV DIS NTC Disable Threshold Voltage Falling ThresholdHysteresis 0.7 1.7502.7%NTCBIASmVI NTC NTC Leakage Current NTC = NTCBIAS = 5V–5050nAIdeal DiodeV FWD Forward Voltage I VOUT = 10mA15mV R DROPOUT Internal Diode On-Resistance Dropout I VOUT = 200mA0.18ΩI MAX_DIODE Diode Current Limit2A /43576fbE LECTRICAL CHARACTERISTICSThel denotes the specifi cations which apply over the full operating temperature range, otherwise specifi cations are at T A = 25°C. V BUS = 5V, BAT = 3.8V, DV CC = 3.3V, R CLPROG = 3.01k, unless otherwise noted.SYMBOL PARAMETER CONDITIONS MIN TYP MAX UNITS Always On 3.3V LDO SupplyV LDO3V3Regulated Output Voltage0mA < I LDO3V3 < 20mA 3.1 3.3 3.5V R CL_LDO3V3Closed-Loop Output Resistance 2.7ΩR OL_LDO3V3Dropout Output Resistance23ΩLogic (I LIM0, I LIM1, EN1, EN2, EN3, ENOTG, and SCL, SDA when DV CC = 0V)V IL Logic Low Input Voltage0.4V V IH Logic High Input Voltage 1.2V I PD1I LIM0, I LIM1, EN1, EN2, EN3, ENOTG, SCL,SDA Pull-Down Current2μAI2C PortDV CC Input Supply 1.6 5.5V I DVCC DV CC Current SCL/SDA = 0kHz, DV CC = 3.3V0.5μA V DVCC(UVLO)DV CC UVLO 1.0V ADDRESS I2C Address0001001[0]V IH, SDA, SCL Input High Threshold70%DV CC V IL, SDA, SCL Input Low Threshold30%DV CC I PD2, SDA, SCL Pull-Down Current2μA V OL Digital Output Low (SDA)I SDA = 3mA0.4V f SCL Clock Operating Frequency400kHz t BUF Bus Free Time Between Stop and StartCondition1.3μst HD_STA Hold Time After (Repeated) StartCondition0.6μs t SU_STA Repeated Start Condition Setup Time0.6μs t SU_STO Stop Condition Setup Time0.6μs t HD_DAT(O)Data Hold Time Output0900ns t HD_DAT(I)Data Hold Time Input0ns t SU_DAT Data Setup Time100ns t LOW SCL Low Period 1.3μs t HIGH SCL High Period0.6μs t f SDA/SCL Fall Time20300ns t r SDA/SCL Rise Time20300ns t SP Input Spike Suppression Pulse Width50ns General Purpose Switching Regulators 1, 2 and 3V IN1,2,3Input Supply Voltage(Note 8) 2.7 5.5VV OUT(UVLO)V OUT UVLO—V OUT FallingV OUT UVLO—V OUT Rising V IN1,2,3 Connected to V OUT ThroughLow Impedance. SwitchingRegulators are Disabled in UVLO2.5 2.62.8 2.9VVf OSC Switching Frequency 1.8 2.25 2.7MHzI FB1,2,3FBx Input Current V FB1,2,3 = 0.85V–5050nAD1,2,3Maximum Duty Cycle100% R SW1,2,3_PD SWx Pull-Down in Shutdown10kΩ/53576fbE LECTRICAL CHARACTERISTICSThel denotes the specifi cations which apply over the full operating temperature range, otherwise specifi cations are at T A = 25°C. V BUS = 5V, BAT = 3.8V, DV CC = 3.3V, R CLPROG = 3.01k, unless otherwise noted.SYMBOL PARAMETER CONDITIONS MIN TYP MAX UNITS I VIN1,2,3Pulse-Skipping Mode Input Current I OUT1,2,3 = 0μA (Note 9)90μABurst Mode® Input Current I OUT1,2,3 = 0μA (Note 9)2035μALDO Mode Input Current I OUT1,2,3 = 0μA (Note 9)1525μAShutdown Input Current Limit I OUT1,2,3 = 0μA, FB1,2,3 = 0V1μA V FBHIGH1,2,3Maximum Servo Voltage Full Scale (1,1,1,1) (Note 10)l0.780.800.82V V FBLOW1,2,3Minimum Servo Voltage Zero Scale (0,0,0,0) (Note 10)0.4050.4250.445V V LSB1,2,3V FB1,2 Servo Voltage Step Size25mV R LDO_CL1,2,3LDO Mode Closed-Loop R OUT V FB1,2,3 = V OUT1,2 3 = 0.8V0.25ΩR LDO_OL1,2,3LDO Mode Open-Loop R OUT(Note 11) 2.5ΩGeneral Purpose Switching Regulator 1 and 2I LIM1,2PMOS Switch Current Limit Pulse-Skipping/Burst ModeOperation (Note 5)6009001300mA I OUT1,2Available Output Current LDO Mode50mA R P1,2PMOS R DS(ON)0.6ΩR N1,2NMOS R DS(ON)0.7ΩGeneral Purpose Switching Regulator 3I LIM3PMOS Switch Current Limit Pulse-Skipping/Burst ModeOperation (Note 5)130018002800mA I OUT3Available Output Current LDO Mode50mA R P3PMOS R DS(0N)0.18ΩR N3NMOS R DS(ON)0.3Ωt RST3Power-On Reset Time for SwitchingRegulator V FB3 Within 92% of Final Value toRST3 Hi-Z230msBurst Mode is a registered trademark of Linear Technology Corporation.Note 1: Stresses beyond those listed under Absolute Maximum Ratings may cause permanent damage to the device. Exposure to any Absolute Maximum Rating condition for extended periods may affect device reliability and lifetime.Note 2: The L TC3576E/L TC3576E-1 are guaranteed to meet performance specifi cations from 0°C to 85°C. Specifi cations over the –40°C to 85°C operating temperature range are assured by design, characterization and correlation with statistical process controls.Note 3: The L TC3576E/L TC3576E-1 include overtemperature protection that is intended to protect the device during momentary overload conditions. Junction temperature will exceed 125°C when overtemperature protection is active. Continuous operation above the specifi ed maximum operating junction temperature may impair device reliability.Note 4: Total input current is the sum of quiescent current, I VBUSQ, and measured current given by V CLPROG/R CLPROG • (h CLPROG + 1).Note 5: The current limit features of this part are intended to protect the IC from short term or intermittent fault conditions. Continuous operation above the maximum specifi ed pin current rating may result in device degradation or failure.Note 6: The bidirectional switcher’s supply current is bootstrapped to V BUS and in the application will refl ect back to V OUT by (V BUS/V OUT) •1/effi ciency. Total quiescent current is the sum of the current into theV OUT pin plus the refl ected current.Note 7: h C/10 is expressed as a fraction of the measured full charge current with indicated PROG resistor.Note 8: V OUT not in UVLO.Note 9: FBx above regulation such that regulator is in sleep. Specifi cation does not include resistive divider current refl ected back to V INx.Note 10: Applies to pulse-skipping and Burst Mode operation only.Note 11: Inductor series resistance adds to open-loop R OUT./63576fb73576fbT YPICAL PERFORMANCE CHARACTERISTICS Ideal Diode V-I CharacteristicsIdeal Diode Resistance vs Battery VoltageV OUT Voltage vs Load Current (Battery Charger Disabled)USB Limited Load Current vs Battery Voltage (Battery Charger Disabled)Battery and V BUS Currents vs Load CurrentBattery Charge Current vs TemperaturePowerPath Switching Regulator T ransient ResponsePowerPath Switching Regulator Effi ciency vs Load CurrentBattery Charging Effi ciencyvs Battery Voltage with No External Load (P BAT /P VBUS )FORWARD VOLTAGE (V)C U R R E N T (A )0.60.81.00.163576 G010.40.20.040.080.120.20BATTERY VOL TAGE (V)2.7R E S I S T A N C E (Ω)0.150.200.253.93576 G020.100.050 3.03.33.64.2TEMPERATURE (°C)–400C H A R G E C U R R E N T (m A )10020030040040801203576 G06500600–202060100LOAD CURRENT (A)V O U T (V )4.004.254.500.83576 G033.753.503.250.10.20.30.40.50.60.70.91.0BATTERY VOL TAGE (V)2.70L O A D C U R R E N T (m A )100300400500 3.33.94.29003576 G04200 3.03.6600700800LOAD CURRENT (mA)0C U R R E N T (m A )2505007508003576 G05–250–5001002003004005006007009001000V OUT 50mV/DIV AC COUPLEDI VOUT 500mA/DIV0mA20μs/DIV3576 G07V BUS = 5V V OUT = 3.65V CHARGER OFF 10s MODELOAD CURRENT (mA)306050401009080703576 G08E FF I C I E N C Y (%)101000100BATTERY VOL TAGE (V)2.750E F F I C I E N C Y (%)55657075 3.33.94.2953576 G09603.03.6808590T A = 25°C unless otherwise specifi ed./83576fbV BUS Quiescent Currentvs V BUS Voltage (Suspend)V OUT Voltagevs Load Current in SuspendV BUS Currentvs Load Current in SuspendBattery Charge Current vs V OUT VoltageNormalized Battery Charger Float Voltage vs TemperatureV OUT Voltage vs Battery Voltage (Charger Overprogrammed)V BUS Quiescent Current vs TemperatureBattery Drain Current vs TemperatureV BUS Quiescent Current in Suspend vs TemperatureBUS VOL TAGE (V)00Q U I E S C E N T C U R R E N T (μA )10203040506012343576 G105LOAD CURRENT (mA)V O U T (V )4.04.55.02.03576 G113.53.02.50.51.01.52.5LOAD CURRENT (mA)0V B U S C U R R E N T (m A )1.52.02.52.03576 G121.00.500.51.01.52.5V OUT (V)3.400B A T T E R YC U R R E N T (m A )1002003004003.50 3.60 3.70 3.803576 G13500600 3.45 3.55 3.65 3.75BATTERY VOLTAGE (V)2.7V O U T (V )3.94.34.7 3.93576 G143.53.13.74.14.53.32.92.7 3.03.33.64.2TEMPERATURE (°C)–40N O R M A L I Z E D F L O A T V O L T A G E0.9980.9991.000603576 G150.9970.996–151035851.001TEMPERATURE (°C)–40Q U I E S C E N T C U R R E N T (m A )152025603576 G161050–15103585TEMPERATURE (°C)–400Q U I E S C E N T C U R R E N T (μA )102030405060–151035603576 G1785TEMPERATURE (°C)–40253035603576 G182015–151035851050B A T T E R YC U R R E N T (μA )T YPICAL PERFORMANCE CHARACTERISTICS T A = 25°C unless otherwise specifi ed./93576fbOTG Boost Quiescent Currentvs V OUT VoltageOTG Boost V BUS Voltage vs Load CurrentOTG Boost Effi ciency vs Load CurrentOTG Boost Effi ciency vs V OUT VoltageOTG Boost Start-Up Time into Current Source Load vs V OUT VoltageOTG Boost Burst Mode OperationOTG Boost T ransient ResponseOTG Boost Burst Mode Current Threshold vs V OUT VoltageOTG Boost Start-Up into Current Source LoadV OUT (V)2.900.5Q U I E S C E N T C U R R E N T (m A )0.71.11.31.52.51.93.554.203576 G190.92.12.31.7 4.855.50LOAD CURRENT (mA)1003.0V B U S (V )4.05.52004005003576 G203.55.04.5300600700LOAD CURRENT (mA)140E F F I C I E N C Y (%)80901001010010003576 G21706050V OUT (V)2.90E F F I C I E N C Y (%)80855.503576 G227570 3.55 4.20 4.859590V OUT (V)2.91.50T I M E (m s )1.752.002.252.503.43.94.4 4.93576 G235.4V OUT (V)2.90L O A D C U R R E N T (m A )2003005.503576 G241003.554.20 4.85400V BUS 50mV/DIV AC COUPLEDI VBUS 200mA/DIV0mA20μs/DIV3576 G25VOUT = 3.8VI VBUS 200mA/DIVV BUS 2V/DIV0V0mA200μs/DIV3576 G26V OUT = 3.8VILOAD = 500mAV BUS 50mV/DIV AC COUPLEDV SW 1V/DIV0V50μs/DIVV OUT = 3.8V I LOAD = 10mA3576 G27T YPICAL PERFORMANCE CHARACTERISTICS T A = 25°C unless otherwise specifi ed./103576fbBattery Charging from USB-HVBUCK-USBUSB OTG from BAT-HV BUCK-BATOscillator Frequency vs TemperatureOVP Connect WaveformOVP Disconnect WaveformRising OVP Threshold vs TemperatureOVGATE vs OVSENSOVGATE Quiescent Current vs TemperatureRST3, CHRG Pin Current vs Voltage (Pull-Down State)V OUT 1V/DIV AC COUPLEDV BUS 100mV/DIV AC COUPLEDV SW 5V/DIVHVOK 5V/DIV0V0V500μs/DIV3576 G28V BUS = 5V HV IN = 12V USING LT3653V OUT 1V/DIV AC COUPLEDV BUS 200mV/DIV AC COUPLEDI BAT 1A/DIV HVOK 5V/DIV0V500μs/DIV3576 G29V BAT = 3.8V I BUS = 285mA HV IN = 12V USING LT36530ATEMPERATURE (°C)–40F R E Q U E N C Y (M H z )2.202.252.30603576 G302.152.102.05–15103585VBUS 5V/DIVOVGATE 5V/DIV 500μs/DIV3576 G31OVP INPUT VOL TAGE 0V TO 5V STEP 5V/DIVV BUS 5V/DIVOVGATE 5V/DIV 500μs/DIV3576 G32OVP INPUT VOL TAGE 5V TO 10V STEP 5V/DIVTEMPERATURE (°C)–40O V P T H R E S H O LD (V )6.2706.2756.280603576 G336.2656.2606.255–15103585INPUT VOL TAGE (V)00O V G A T E (V )2468101224683576 G34TEMPERATURE (°C)–40Q U I E S C E N T C U R R E N T (μA )333537603576 G35312927–15103585RST3, CHRG PIN VOL TAGE (V)R S T 3,C H R G P I N C U R R E N T (m A )608010043576 G3640201235T YPICAL PERFORMANCE CHARACTERISTICS T A = 25°C unless otherwise specifi ed./分销商库存信息:LINEAR-TECHNOLOGYLTC3576EUFE-1#PBF LTC3576EUFE#TRPBF LTC3576EUFE-1#TRPBF LTC3576EUFE#PBF。
浙江临床医学202丨年5月第23卷第5期• 751••中医论坛•中医“治未病”理论防治糖尿病探讨郭欣艳黄琦*随着人们生活水平的提高及生活方式的改变,我国糖尿 病人群逐年上升,研究显示,至2018年,中国成人2型糖尿 病患病率已升至12.8% "I。
糖尿病是一种以持续高血糖为表 现的代谢性疾病,属中医“消渴”范畴,其演变经历郁热虚 损,基本病机不离阴虚燥热〜。
长期血糖控制不佳,会导致 多种并发症的发生。
“治未病”理论及中医药特色疗法在糖尿 病不同阶段发挥重要作用。
1“治未病”理论指导糖尿病防治1.1注重养慎,未病先防“消渴病”病因涉及先天禀赋不 足,后天外感邪气、食饮不节、情志失调、劳欲过度等,最终导致机体阴虚燥热。
糖尿病家族史、肥胖或超重、运动量 缺乏等属于高危因素[3]。
《素问•上古天真论》云:“其知道 者,法于阴阳,和于术数,食饮有节,起居有常,不妄作劳,故能形与神俱,而尽终其天年……”。
未病先防应注重摄生养 慎,饮食有节、起居有常,避免过食膏粱厚味而致聚痰生湿;七情合宜、调摄精神,谨防情志过极而损耗阴液。
劳逸有度,以摄神形;调养五脏,以和为先;坚持锻炼,增强体魄,防止外邪内侵伤正。
从而预防糖尿病的发生。
1.2既病早治,防其传变医家叶天士所云“务必先安未 受邪之地”,意指不同疾病有不同的发生发展规律及传变方 式,内伤杂病的主要传变方式是循五行生克规律传变及经络 传变。
故要阻止疾病进一步发展,就需正确推断疾病的传变 规律,保护未病脏腑使其不受侵袭,以此切断疾病传变途径,使其向愈。
“消渴”晚期常合并胸痹病、中风病、水肿病、雀肓病、耳聋病、疮毒病、痈疽病等。
既病防变即需采取相应 治疗方法,如可以在辨证施治的基础上加用补肾活血通络之 品ul,并辅以针刺、艾灸、熏蒸、足浴等中医特色疗法,尽早干预糖尿病本病,延缓或防止变病的发生。
1.3瘥后调摄,防其复发瘥后防复意指,一为原病再发,二为复患它病。
ISO9000and the U.S.Construction IndustryAbdol R.Chini1and Hector E.Valdez2Abstract:ISO9000,the series of quality management standards issued by the International Organization for Standardization,is being used by organizations involved in construction all over the world.The construction industry in the United States has generally lagged behind other industries and other countries in the acceptance and implementation of ISO9000standards.Differing opinions surround the issue of ISO9000in the U.S.construction industry;it has received either the support or the criticism of experts,who weigh the effects of ISO9000as a matter of real improvements in quality against competitiveness and specific requirements at a domestic and international level.This paper attempts to determine the applicability and effectiveness of ISO9000in U.S.constructionfirms and the barriers that hinder its acceptance.The methodology used consists of a literature review and a survey distributed to a sample offirms that have or have not received ISO9000certification.After analyzing the gathered data,it was concluded that ISO9000is an appropriate and effective tool for constructionfirms in the United States,although several obstacles affect its implementation and acceptance among construction organizations.DOI:10.1061/͑ASCE͒0742-597X͑2003͒19:2͑69͒CE Database subject headings:Construction industry;Quality control;Standards.IntroductionThe building construction industry is evolving at a rapid pace. Construction-relatedfirms recognize the need for providing a quality product that will both satisfy the customer and maintain their competitiveness in an ever-changing and demanding market. In this context,quality is considered one of the key transforma-tion elements of project management techniques,deemed neces-sary for success in the21st century market place͑Kini2000͒. Companies are being persuaded to adopt quality management sys-tems in order to meet the demands of customers in a globalized market.ISO9000,a series of international quality management standards,has emerged during the last two decades as a system that can be applied to different types of companies in order to obtain improvements in quality procedures and products.ISO9000is being implemented all over the world as a system of standards related to quality assurance management and control for companies and institutions.These standards were developed by ISO,the International Organization for Standardization,as part of this institution’s efforts to promote uniformity and facilitate international exchange between nations.ISO9000has gained popularity and is being applied to companies and institutions all over the world due to its generic nature.ISO9000certification in the construction industry has been widely accepted in many coun-tries,and the number of certifications for general,heavy and spe-cialty contracting companies is growing considerably.Some in-vestigators͑Kubal1994͒associate ISO9000with multiple advantages and with positive changes in internal procedures of constructionfirms.Yet others͑Anitfos1996͒argue that these standards do not apply directly to the construction industry and cannot be associated with a substantial improvement in the deliv-ery of a quality construction product.In a different study͑Yates and Anitfos1997b͒,construction companies in the United States have generally stated that compli-ance with ISO9000is positive and would increase the industry’s competitiveness in local and foreign markets.However,only rela-tively few constructionfirms in the United States have adapted these standards to their management systems and received ISO 9000certification.The main objective of this paper is to deter-mine whether ISO9000is an applicable tool for construction companies in the United States.If the answer is positive,the barriers for acceptance must be identified.This goal requires re-search in order to provide a theoretical background on the issue of quality in construction,on the application of ISO9000in the construction industry,and on the current status and application of ISO9000as part of the management systems of construction firms in the United States.A literature review was performed to shape a theoretical background for ISO9000in construction.An-other part of the research performed is the analysis of data col-lected from a survey mailed to different construction companies in the United States that have or have not achieved ISO9000 certification.All this information led to conclusions supporting or discouraging the application of these standards in the U.S.con-struction industry,as well as to recommendations for removing barriers that limit their acceptance.Research has been performed on the application of ISO9000 in constructionfirms of countries in Europe,Asia,and Oceania. Yates and Aniftos͑1997a,b͒have performed research about the role of the U.S.construction industry in standards development and implementation.However,no specific research has been per-formed on the current status of the standards in the U.S.construc-tion industry from the perspective of certified constructionfirms. In addition,no study has been able to demonstrate the advantages and disadvantages of applying ISO9000in this industry,or the1Holland Associate Professor,Rinker School of Building Construc-tion,University of Florida,FAC101,Gainesville,FL32611-5703.2Project Engineer,DPR Construction,Inc.,10900Nuckols Rd.,Ste.200,Richmond,V A23060.Note.Discussion open until September1,2003.Separate discussionsmust be submitted for individual papers.To extend the closing date byone month,a written request must befiled with the ASCE ManagingEditor.The manuscript for this paper was submitted for review and pos-sible publication on September25,2001;approved on July11,2002.Thispaper is part of the Journal of Management in Engineering,V ol.19,No.2,April1,2003.©ASCE,ISSN0742-597X/2003/2-69–77/$18.00.JOURNAL OF MANAGEMENT IN ENGINEERING©ASCE/APRIL2003/69reasons why acceptance of these quality management standardshas been so gradual and unsteady.Quality in Construction IndustryQuality can be defined in several ways.A definition proposed byArditi and Gunaydin͑1999͒defines quality in terms of conform-ance to the agreed requirements of the customer and a product orservice free of deficiencies.The term‘‘quality’’should not beused as an expression of degree of excellence,as may be impliedby a dictionary definition.This term should be used and definedas‘‘a measure offitness for purpose,in the sense of meeting theneeds of a customer,at a price commensurate with the extent ofthose needs.’’ISO defines quality as the totality of characteristicsof an entity that bear on its ability to satisfy stated or impliedneeds͑ISO2000͒.The construction end product is not a repetitive unit,but anendeavor that may be unique in its design and composition.In-ternal and external factors such as community response,construc-tion cost,and time of delivery must be addressed in the designand construction of a building.Quality in construction can beviewed as part of a triangle in which the contractor must attain thecost level as planned,meet the schedule deadlines,and achievethe required quality level.An equitative balance among thesethree aspects is considered as ideal.However,quality may be thefirst of these components to be disregarded or sacrificed in favorof increased cost savings and time reductions.The assessment of quality in a construction project involvestwo components:quality assurance and quality control.Qualityassurance is considered as a‘‘system of controlling the provisionof a product or service so as to satisfy the needs of the customer’’͑Chini1999͒;it is identified as an external quality system,cover-ing activities aimed at inspiring confidence in the client regardingthe product or service being provided.Quality control is the‘‘spe-cific implementation of the quality assurance program and relatedactivities’’͑Arditi and Gunaydin1999͒.Several approaches to quality assurance and control in con-struction have been proposed and adopted in recent years.Theseinclude;͑1͒partnering,which attempts to improve the communi-cationflow on a specific construction project;͑2͒business processreengineering,which is a fundamental and radical approach toprocess redesign in terms of meeting customer demands͑Jaafari2000͒;͑3͒constructibility reviews,which consist in a review ofthe project plans and specifications in an effort to improve thequality of the construction process and the completed product;͑4͒value engineering,which attempts to improve the value and op-timize the life-cycle costs of a facility from the preconstructionphase;and͑5͒total quality management͑TQM͒,which is an op-erational philosophy that emphasizes continuous improvement ofall facets of an organization.ISO9000is a set of defined standards,rather than a manage-ment philosophy,that was created to provide uniform quality as-surance standards for product manufacturing and service provid-ers in a globalization perspective and has been adopted bynumerous organizations all over the world.ISO9000The ISO9000family of standards was launched to the worldcommunity in1987,after a process of consensus handled by ISOTechnical Committee176.ISO9000was widely accepted fromthe start;at the end of1999,at least343,643certificates had been awarded in150countries,representing an increase of26.4%over the total number of certificates awarded up to1998.A large per-centage of the certificates͑56%͒correspond to Europeanfirms, where acceptance has been widespread due to European Union standardization policies.The United States had33,054certified organizations at the end of1999͑Jaafari2000͒,has experienced a high growth in the number of certificates͑second only to Austra-lia in1999͒,and has experienced a32%increase in its number of certificates from1998to1999.With the feedback of members of the ISO,the standards underwent a series of revisions in1994and another in2000.ISO9000in ConstructionApplication in ConstructionDue to the generic nature of ISO9000,it has also been imple-mented in the construction industry.Specifically,and following the1994revisions scheme,ISO9001and9002can be applied to construction-relatedfirms.The former standard addresses design, development,and servicing capabilities,whereas the latter ad-dresses the same elements except for design control.The twenty elements required of an organization certified to ISO9000have continuously been identified with manufacturing procedures. Nevertheless,they have been adapted for construction procedures and are believed by some parties to cover a wide scope of quality-related activities of construction-relatedfirms.Both Chung͑1999͒and Nee͑1996͒have illustrated the interaction and application of the twenty requirements of ISO9000in construction activities.Constructionfirms for a variety of reasons pursue ISO9000. Ideally,the main motivator for certification should be the achieve-ment of quality in a company’s internal procedures in order to optimize resources and better satisfy customers’requirements. Many organizations are pursuing certification in order to satisfy specific requirements from one or more customers.This is true for firms working or targeting projects for owners that are either cer-tified to ISO9000or require certifications for their suppliers. Other organizations at a worldwide level are obtaining certifica-tion due to increasing government requirements.This is true for local and internationalfirms working in Asian markets,where ISO9000is increasingly becoming a mandatory requirement for bidding in public projects.Otherfirms take advantage of ISO 9000as an effective marketing tool through an improved com-pany reputation.The application of ISO9000in construction has its advocates and opponents.Supporters believe that ISO9000can be applied successfully in construction and can generate substantial benefits. It is believed that a construction company’s operations can im-prove through the establishment of a quality system designed to standardize corporate procedures͑Chung1999͒.ISO9000is also considered as an effective control mechanism that seeks to reduce waste and labor inefficiencies in a process so that quality in the production and delivery process can be ensured.From another point of view,ISO9000certification provides proof that an opti-mal level of quality is being obtained throughout all stages of the product’s quality cycle͑Love and Li2000͒,therefore expanding a company’s marketing opportunities.ISO9000certification in constructionfirms has been strongly debated and consistently criticized by other parties.They state that the interface of the standards with the special characteristics and properties of the construction industry can generate problems. It is arguable whether construction procedures can be standard-ized at all͑as it can in the manufacturing industry͒,knowing that the product of construction is in a sense always unique,the pro-70/JOURNAL OF MANAGEMENT IN ENGINEERING©ASCE/APRIL2003cesses of construction involve a variety of professionals andtradesmen,and the environment where these processes are carriedout is often exposed to aggressive elements͑Chung1999͒.Be-sides,the generic nature of the standards often leads to differ-ences in interpretations,and the implementation,use,and impactof ISO9000can vary between companies and countries͑Bubshaitand Al-Atiq1999͒,being difficult to measure and u-ally a contractor is required tofinish a project within a specifiedtime frame,at an agreed price,and at a certain standard of work-manship in order to maintain the required quality.These are con-sidered conflicting goals running in three different directions,andusually quality is thefirst to be sacrificed͑Tam et al.2000͒.Anincreased emphasis in fast tracking can also hinder quality effortsbecause of unclear specifications,insufficient specification re-views,mistakes made early in the project,and problems of con-structibility͑Low1997͒.ISO9000has gained wide acceptance in the global construc-tion market.Construction has the third highest number of certifi-cates of all industrial sectors at a worldwide level,behind onlyelectrical and optical equipment and basic metal/fabricated metalproducts.According to data published by the International Orga-nization for Standardization͑ISO2000͒,approximately25,273construction-relatedfirms had achieved certification up to1999.This accounts for7%of the total number of certified companiesin all industrial sectors.Far East countries rank among the mostvehement advocates of standardization in the construction indus-try;in fact,Korea͑with4,096certificates in1999͒and China ͑with2,051certificates in the same time period͒rankfirst and third in the list of countries with the highest number of ISO9000certificates in the construction industry.In countries like Austra-lia,certification is becoming mandatory for all construction orga-nizations wishing to do business with government agencies andmajor private companies.Europe is increasingly requiring knowl-edge of ISO9000for construction companies,with support fromthe European Union.Countries such as Italy,the Netherlands,andSwitzerland have the most certifications in the construction sectorfor the European continent;they rank second,seventh,and eighthin the world,respectively.However,acceptance of the standardsin Europe still experiences problems,especially since the Euro-pean construction industry is traditionally fragmented.Current Status in U.S.Construction IndustryISO9000has gained acceptance in many industrial sectors in theUnited States.However,acceptance of these standards in the U.S.construction industry is limited when compared with statisticsfrom construction organizations in Europe,Asia,and Oceania.The U.S.construction industry has lagged behind other industriesin the application of ISO9000and in the number of organizationscertified for these standards.According to the‘‘ISO9000Regis-tered Company Directory for North America,’’published by theMcGraw-Hill Company in2000,there are114construction-related organizations certified for ISO9000.These companieshave received certification under three scopes,or Standard Indus-try Codes͑SIC͒:•1500,for general building͑building construction͒;•1600,for heavy construction;and•1700,for special trade contractors.The number of construction-related organizations certified forISO9000in the United States represents about0.004%of allcertifiedfirms in the nation͓which amounted to33,054at the endof1999͑ISO2000͔͒.The scope of work of most of these com-panies is special trade contracting.More than66%of the certifiedfirms perform this type of work.Building constructionfirms͑in-cluding general contractors͒account for16%,and heavy con-structionfirms account for18%.This may be due to the stan-dard’s emphasis on quality requirements for certified companies’suppliers and subcontractors.Another fact that can be observedfrom the list of certifiedfirms is their geographic location.36%ofthesefirms are located in the state of Michigan,followed by Ohio ͑with14%͒.This distribution seems to indicate that many com-panies have pursued certification as a requirement for performingwork with the three major U.S.automakers͑Ford Motor Com-pany,General Motors Corporation,and Daimler-Chrysler͒.Thesethree industrial giants,which to a great extent are headquarteredin the states of Michigan and neighboring Ohio,have all adoptedISO9000͑customized as QS-9000͒and are requiring certificationfrom their contractors and suppliers.The analysis of more datasupports the premise of ISO9000certification among construc-tionfirms being offset by U.S.automakers.From the list of topconstruction companies performing work for auto plants͑ENR2000a͒,at least eight of the top12are certified for ISO9000,ascan be seen in Table1.From these eight companies,five of themperform more than25%of their annual volume for the automo-bile industry;it can be inferred that thesefirms are highly depen-dent on automobile manufacturing customers.This is not unusual,since General Motors and Ford alone had more than5.8billiondollars worth of construction in progress during1999͑ENR2000b͒.However;it has not been determined whether thesefirmsalso perform work for foreign-owned corporations with manufac-turing plants in the United States that may or may not require ISO9000certification for their suppliers.Other important data can be obtained from the list of certifiedconstructionfirms.Many of the U.S.based construction compa-nies with the highest level of international involvement have ob-tained certification for ISO9000.From the list of top ten U.S.contractors performing work abroad in1999͑ENR2000a͒,atleast eightfirms are known to be certified for ISO9000.Three ofTable1.Top U.S.Construction Organizations Performing Work for Auto Plants͑ENR2000a͒Ranking͑top in auto plants͒Ranking͑top in U.S.contractors͒FirmRevenue in auto plants͑U.S.$million͒Total revenue͑U.S.$million͒145Walbridge Aldinger450.0775.0 255J.S.Alberici Construction283.0672.9 338Barton Malow Co.242.4969.572Fluor Corporation71.08,707.0 911J.A.Jones,Inc.47.02,165.4 10392DeMaria Building Co.,Inc.42.094.6 1164Angelo Iafrate Construction40.0601.6 12221Industrial Contractors,Inc.38.0166.3JOURNAL OF MANAGEMENT IN ENGINEERING©ASCE/APRIL2003/71thesefirms rank among the six largest construction organizations in the world.This supports the premise that companies can be motivated to pursue certification in order to be competitive in foreign markets.On the other hand,many foreign construction firms with U.S.subsidiaries are certified for ISO9000in their international operations but lack certification for their U.S.opera-tions.These include Skanska USA͑a subsidiary of Skanska AB͒, Turner Construction͑a subsidiary of Hotchtief AG,from Ger-many͒and Bovis Lend Lease͑a subsidiary of Bovis Lend Lease, from the United Kingdom/Australia͒.This may reflect the rela-tively low acceptance of ISO9000in the U.S.construction indus-try.Table2shows the distribution of U.S.international contrac-tors certified for ISO9000.Survey of U.S.Construction Firms Certified for ISO 9000Survey MethodologyA survey was distributed to U.S.constructionfirms to determine their motivations for certification,the applicability of the stan-dards inside construction organizations,and the barriers that limit the acceptance of ISO9000in U.S.constructionfirms.The sur-vey consisted of two different questionnaires.Thefirst one was mailed to companies in the construction industry that have ob-tained certification for the ISO9000series of standards.The sec-ond was mailed to a sample offirms that have not pursued or achieved certification͑see Appendix͒.Survey DescriptionThe certifiedfirms survey consisted of two different sections.The first section dealt withfinancial and operative information about the responding company.The second section contained specific questions regarding the applicability of the ISO9000series of standards in thesefirms.The names of the certified companies and contact information were obtained from two ISO9000direc-tories,found at and http:// .These sources are relatively accurate,al-though they fall short of including all the certifiedfirms.A more complete list can be obtained in the‘‘ISO9000Registered Com-pany directory,North America,’’published by the McGraw-Hill Company.The respondent from each company was selected from the names provided in the directories and by direct contact with the companies,either by e-mail or by telephone. Characteristics of SampleFifty-four surveys were mailed out to companies certified for ISO 9000.Thirty-six of these companies responded,yielding a re-sponse rate of67%.This response rate is considered satisfactory for the required purposes,since the sample represents approxi-mately29%of the total number of certifiedfirms in the United States.Of the respondents,eight companies perform general contracting/construction management,11are in heavy construc-tion,and17are special trade contractors.This can be observed in Fig.1.More than half of the surveys͑21͒were completed by each company’s quality control or assurance manager.Others were completed by such officers as management representatives and members of top management͑vice presidents and presidents͒.The annual volume of the responding companies varies,al-though it can be observed that none of the respondingfirms has an annual volume smaller than$3million in performed work. This supports the premise that ISO9000has not been pursued by or that ultimately is not appropriate for small companies.The range with the highest frequency of companies is that between$3 and50million.Five of the respondingfirms perform more than $1billion in volume and rank among the top ten contractors in the United States.The distribution can be observed in Fig.2.Seven of the respondingfirms self-perform between0and 40%of their total work;four self-perform between40and60%; 13self-perform between80and100%,and six companies did not provide a response.Therefore,more than50%of the respondents self-perform more than60%of their work.This is expected due to the fact that many of the respondents are specialtycontractors;pany’s primary scope of workTable2.Top U.S.International Contractors Certified for ISO9000in1999͑ENR2000b͒Ranking͑international U.S.contractors͒Ranking͑international global contractors͒FirmInternational revenue͑U.S.$million͒Total revenue͑U.S.$million͒11Bechtel Group Inc.7,442.011,240.025Kellogg,Brown,&Root4,721.06,399.036Fluor Corporation4,669.08,707.0 414Foster Wheeler Corp.2,240.02,884.0 629Parsons Corporation1,032.71,599.6 833McDermott International883.81,850.2 949ABB Lummus Global649.41,089.9 1050Black&Veatch637.01,720.0Fig.2.Annual volume of respondingfirmsthis type offirm tends to self-perform much of its work and tends to hire sub-subcontractors to a relatively limited extent.Building and heavy constructionfirms generally account for smaller per-centages of performed work.Regarding the percentage of work performed domestically and internationally,80%of the respon-dents perform between0and40%of their work abroad.In fact, 16firms do not perform any work͑0%͒at an international level. Only seven respondents͑20%of the total͒perform more than 40%of their work abroad.Two of thesefirms perform between80 and100%of their work internationally.These results seem to contradict the premise that a major driving force for ISO9000 certification in the U.S.construction industry is competitiveness at an international level.Motivators for CertificationKnowledge about each company’s motivation for certification was a key component of the survey.Several options were pro-vided,and each respondent was asked to rank these according to importance.This information presents an interesting picture of the motivation of companies for becoming ISO9000certified and seemingly contradicts some of the preestablished assumptions about ISO9000certification in the U.S.construction industry. Many experts argue that certification is being pursued mainly to obtain access to international markets or for marketing and cus-tomer requirement reasons.However,the survey results show that the respondents acknowledge the establishment and maintenance of a quality system like ISO9000as an effective tool for improv-ing their internal quality management procedures.The second and third highest ranking motivating factors,competitiveness for U.S. markets and requirements by U.S.customers,are both related. Nine of the respondingfirms mentioned customer requirements as their main reason for obtaining certification.Four of thesefirms specifically referred to the automotive industry’s quality require-ments as a major factor for making the decision.Other companies mentioned that certification has become a bidding requirement and that most of their customers are certified,thus urging them to take the same path.If the responses are classified according to company scope of work,volume,and percentage of volume performed internation-ally,the responses differ from those obtained for all respondents in general.If classified by scope of work,building construction firms͑SIC code1500͒ranked obtaining a competitive edge for U.S.markets as their most important reason for obtaining certifi-cation,followed by obtaining improvement in the company’s quality management system.Results for heavy constructionfirms, certified under SIC1600,present a different pattern.Access to Asian markets ranksfirst,followed by access to European mar-kets and the improvement of the company’s quality management system.This shows that heavy constructionfirms have recognized the importance of ISO9000certification for international projects.Three of the heavy constructionfirms included in the survey rank among the top U.S.contractors performing work at an international level;therefore,access to European and Asian markets might be a priority for thesefirms.Responses for spe-cialty contractors͑SIC code1700͒follow the trend of the original ranking of allfirms.Improvement of the company’s quality man-agement system ranksfirst,followed by obtaining a competitive edge for U.S.markets.This distribution is displayed in Fig.3.It is also important to analyze the motivation for certification according to percentage of work performed internationally.The responses of thefirms that perform more than50%of their vol-ume internationally were tabulated.It can be expected that pursu-tor for certification among thesefirms.However,the results indicate that these companies have achieved certification mostly to improve their quality management systems.This result is dis-played in Fig.4.Application of ISO9000Another part of the survey was dedicated to analyzing the imple-mentation process and application of ISO9000in the responding companies.Two of these aspects are the duration of the certifica-tion process and the cost of ISO9000certification.Regarding time dedicated to the process,there seems to be no direct rela-tionship between the size and volume of a company and the du-ration of the certification process.Seventeen companies͑46%͒dedicated less than one year to the process;another15͑40%͒dedicated between one and2years;andfive companies͑14%͒dedicated more than2years to becoming ISO9000certified. Firms that have taken from one to6months for certification range from the smallest in the sample͑with$10million in volume͒to global giants performing billions of U.S.dollars in work.On the other hand,firms that have taken more than2years to become certified range from medium sizefirms with$50million in vol-ume to giants with billions of dollars in volume and multiple international operations.Regarding cost of certification,14companies stated that they spent more than$100,000in the certification process͑onefirm spent up to$1million͒;12companies spent between$50,000and $100,000;and nine companies spent less than$50,000in the whole initial process.There is a visible pattern regarding the cost of certification and the duration of the process.In general,a shorter process of certification implies fewer costs for a company.A pattern can also be observed when comparing the cost of cer-tification with the volume of thefipanies that perform large amounts of work and have multiple office and project sites usually have a higher cost of certification.This can be observed in Table3,which compares costs with duration of the certificationprocess.Fig.3.Initial motivation for certification by scope of work of re-spondents͑by points according to rankings͒Fig.4.Initial motivation for certification of companies performing more than50%of their volume at international level͑by points ac-cording to rankings͒。
O RIGINAL A RTICLESInterictal to Ictal Transition in Human Temporal Lobe Epilepsy:Insights From a Computational Model ofIntracerebral EEGFabrice Wendling,*Alfredo Hernandez,*Jean-Jacques Bellanger,*Patrick Chauvel,†and Fabrice Bartolomei†Summary:In human partial epilepsies and in experimental modelsof chronic and/or acute epilepsy,the role of inhibition and therelationship between the inhibition and excitation and epileptogen-esis has long been questioned.Besides experimental methods carriedout either in vitro(human or animal tissue)or in vivo(animals),pathophysiologic mechanisms can be approached by direct record-ing of brain electrical activity in human epilepsy.Indeed,in someclinical presurgical investigation methods like stereoelectroencepha-lography,intracerebral electrodes are used in patients suffering fromdrug resistant epilepsy to directly record paroxysmal activities withexcellent temporal resolution(in the order of1millisecond).Thestudy of neurophysiologic mechanisms underlying such depth-EEGactivities is crucial to progress in the understanding of the interictalto ictal transition.In this study,the authors relate electrophysiologicpatterns typically observed during the transition from interictal toictal activity in human mesial temporal lobe epilepsy(MTLE)tomechanisms(at a neuronal population level)involved in seizuregeneration through a computational model of EEG activity.Intra-cerebral EEG signals recorded from hippocampus infive patientswith MTLE during four periods(during interictal activity,justbefore seizure onset,during seizure onset,and during ictal activity)were used to identify the three main parameters of a model ofhippocampus EEG activity(related to excitation,slow dendriticinhibition and fast somatic inhibition).The identification procedureused optimization algorithms to minimize a spectral distance be-tween real and simulated signals.Results demonstrated that themodel generates very realistic signals for automatically identifiedparameters.They also showed that the transition from interictal toictal activity cannot be simply explained by an increase in excitationand a decrease in inhibition but rather by time-varying ensembleinteractions between pyramidal cells and local interneurons project-ing to either their dendritic or perisomatic region(with slow and fastGABAA kinetics).Particularly,during preonset activity,an increas-ing dendritic GABAergic inhibition compensates a gradually in-creasing excitation up to a brutal drop at seizure onset when fasteroscillations(beta and low gamma band,15to40Hz)are observed.These faster oscillations are then explained by the model feedbackloop between pyramidal cells and interneurons targeting their peri-somatic region.Thesefindings obtained from model identification inhuman temporal lobe epilepsy are in agreement with some resultsobtained experimentally,either on animal models of epilepsy or onthe human epileptic tissue.Key Words:Human TLE—Hippocampus—Intracerebral EEG—Neuronal population model—Parameter identification—Ictogen-esis mechanisms.(J Clin Neurophysiol2005;22:343–356)In human partial epilepsies and in experimental modelsof chronic and/or acute epilepsy,the role of inhibition and therelationship between the inhibition and excitation and epilep-togenesis has long been questioned(Dalby and Mody,2001;Dichter,1997).Recent advances have suggested that differenttypes of inhibition(depending on the location of synapses/receptors,for example)are present in a given neuronal tissueand that they may be differently involved in epileptic pro-cesses.Particularly,in experimental focal models(kainate orpilocarpine-treated rat),it has been shown that GABAergicinhibition is impaired,but not uniformly:dendritic inhibitionis reduced whereas somatic inhibition is preserved(Cossart etal.,2001;Houser and Esclapez,1996).This intact inhibitioncould be due to selective survival of perisomatic inhibitoryinterneurons,as shown in human epileptogenic tissue(scle-rotic hippocampus in temporal lobe epilepsy[TLE])(Wittneret al.,2001;Wittner et al.,2005).Besides experimental methods carried out either invitro(human or animal tissue)or in vivo(animals),patho-physiologic mechanisms can be approached by direct record-ing of brain electrical activity in human epilepsy.Indeed,insome clinical presurgical investigation methods like stereo-electroencephalography(SEEG)(Bancaud and Talairach,1973),intracerebral electrodes are used in patients withdrug-resistant epilepsy to directly record paroxysmal activi-ties with excellent temporal resolution(in the order of1millisecond).The study of neurophysiologic mechanismsunderlying such depth-EEG activities is crucial to progress inthe understanding of the interictal to ictal transition.Here,we*Laboratoire Traitement du Signal et de L’Image,INSERM Universite´deRennes1,Campus de Beaulieu,Rennes Cedex,France;and†Laboratoirede Neurophysiologie et Neuropsychologie,INSERM Universite´de laMe´diterrane´e,Marseille Cedex,FranceAddress correspondence and reprint requests to F.Wendling,LaboratoireTraitement du Signal et de L’Image Universite´de Rennes1,INSERMU642Campus de Beaulieu,Bat.22-35042Rennes Cedex,France;e-mail:fabrice.wendling@univ-rennes1.fr.Copyright©2005by Lippincott Williams&WilkinsISSN:0736-0258/05/2205-0343Journal of Clinical Neurophysiology•Volume22,Number5,October2005343propose to perform this study using not only descriptive signal analysis techniques but also computational modeling,a research methodology that has been largely developed for the study of various(patho)physiologic mechanisms and that attracts growing interest in neuroscience.We address the question whether EEG dynamics observed during the transi-tion from interictal to ictal activity could result from variable global interactions between populations of pyramidal cells and inhibitory interneurons,and whether these interactions could be revealed by appropriate model-based processing of intracerebral EEG signals.Hence,we relate electrophysi-ologic patterns of seizure generation in human hippocampus to excitatory and inhibitory interactions in a neuronal popu-lation model of hippocampal EEG activity.This type of computational model(also referred to as “neuronal rate model”or“neuronal population dynamics”; Wilson and Cowan,1972)has been demonstrated to produce realistic epileptiform activities(Wendling et al.,2000).Re-cently,it has provided a means for linking some pathophys-iologic characteristics of hippocampus at a neuronal popula-tion level to the fast oscillations observed at seizure onset at the EEG level(Wendling et al.,2002).Here,we report results about identification of the three main parameters of this model(namely excitation,slow dendritic inhibition,and fast somatic inhibition)from record-ings performed in patients with mesial TLE(inverse prob-lem).Parameter identification(based on evolutionary algo-rithms)is performed to produce signals that match those actually recorded during interictal to ictal transition.From the analysis of parameters evolution during this transition,hy-potheses are generated about excitatory and inhibitory inter-actions that take place between subsets of cells represented within the modeled hippocampal neuronal population.In particular,we found that during preonset activity(a few tens of seconds before seizure),an increasing dendritic inhibition (produced by interneurons mediating slow GABA A inhibitory postsynaptic currents[IPSCs])compensates a gradually in-creasing excitation up to a brutal drop at seizure onset.Faster ictal oscillations(beta and low-gamma band)are then ex-plained by the model feedback loop involving pyramidal cellsand interneurons targeting their perisomatic region(mediat-ing fast GABA A IPSCs).As described in the discussion,these findings obtained from model identification in human TLE are in agreement with some experimental studies conducted in animal models of epilepsy.MATERIALS AND METHODS Intracerebral EEG Signals Recorded FromHippocampus in Patients With Mesial Temporal Lobe EpilepsyFive patients undergoing presurgical evaluation of drug-resistant mesial temporal lobe epilepsy(MTLE)were selected.All patients had a comprehensive evaluation includ-ing detailed history and neurologic examination,neuropsy-chological testing,routine MRI,surface EEG,and SEEG.As illustrated in Fig.1,SEEG recordings were performed using intracerebral electrodes placed intracranially according to Talairach’s stereotactic method(Bancaud and Talairach, 1973).These patients were selected for the present study because they satisfied the following criteria:(1)seizures involved the mesial temporal regions at the onset;(2)MRI was normal or suggestive of hippocampal sclerosis(hip-pocampal atrophy and increased T2signal);(3)one electrode was placed in the hippocampus;and(4)the electrophysi-ologic pattern during the transition to seizure was character-ized by the emergence of a low-frequency,high-amplitude spiking activity followed by a so-called rapid discharge in the hippocampus.This pattern has been reported to be typical in MTLE(Bartolomei et al.,2004;Engel et al.,1989;Spencer et al.,1992;Velasco et al.,2000).Analyzed signals were recorded on a128-channel Del-tamed system.They were sampled at256Hz and recordedon FIGURE1.Depth electrodes implanted for SEEG in temporal lobe epilepsy.(a)coronal view of a preoperative plan in which electrode#1records electrophysiologic activity within the hippocampal head(internal contacts)and the middle part of the middle temporal gyrus(external contacts)and in which electrode#2records the activity within the entorhinal cortex (internal contacts)and the anterior part of the inferior tempo-ral gyrus(external contacts).Generally,five to eight electrodes are used to spatially sample the temporal region.The implan-tation accuracy is per-operatively controlled by telemetric x-ray imaging.A postoperative computed tomography(CT) scan without contrast is then used to verify the absence of bleeding and the precise location of each recording lead. Intracerebral electrodes were then removed and an MRI per-formed,permitting visualization of the trajectory of each elec-trode.Finally,CT-scan/MRI data fusion can be performed to anatomically locate each contact along the electrode trajec-tory.(b)Electrodes include10to15contacts2mm long,0.8 mm in diameter,and1.5mm apart.F.Wendling et al.Journal of Clinical Neurophysiology•Volume22,Number5,October2005a hard disk(16bits/sample)using no digitalfilter.Two hardwarefilters are present in the acquisition procedure.The first one is a high-passfilter(cut-off frequency equal to0.16 Hz at–3dB)used to remove very slow variations that sometimes contaminate the baseline.The second one is a first-order low-passfilter(cut-off frequency equal to97Hz at –3dB)to avoid aliasing.Definition of Periods of InterestFor thefive patients,signals recorded from the hip-pocampus during the transition from interictal to ictal activity were visually analyzed.In each patient,four seg-ments of EEG activity(10seconds duration)were defined at different stages of this transition using visual criteria (Figs.2and3),as follows.During the interictal period (“intICTAL”segment,chosen1minute before seizure onset at least),EEG signals do not exhibit high amplitude transient spikes.The preonset period(preceding seizure onset)is marked by the appearance of high amplitude spikes(“preONSET”segments,from10to50seconds before seizure onset).The electrical onset of the seizure (“ONSET”segment)is characterized by the appearance of the rapid discharge reflecting faster oscillations,typically in the beta and low-gamma frequency bands(15to40Hz). Finally,as seizure develops,the rapid discharge slows down and changes into a more rhythmic activity(“ICTAL”segment),typically in the theta or alpha frequency band(4 to10Hz).Computational Model of Hippocampus Neuronal Population and Simulation of EEG SignalsA macroscopic approach(neuronal population,adapted to the macroscopic size of SEEG electrodes)was used to build the EEG model,which has been detailed in previous reports(Wendling et al.,2002).Briefly,this model is based on the global cellular organization of the hippocampus. Firstly,recurrent excitatory connections from pyramidal cells to pyramidal cells have been demonstrated to occur in CA1 (Thomson and Radpour,1991;Whittington et al.,1997). Secondly,a series of studies based on a variety of techniques (Miles et al.,1996)demonstrated that there are two types of GABA A synaptic responses in CA1pyramidal neurons:a fast one near the soma and a slow one at the dendrites.Thefirst one—GABA A,fast—is a rapidly activated and decaying IPSC mediated by somatic synapses and the second one—GABA A,slow—is a slowly rising and decaying IPSC mediated by dendritic synapses.More recent works(Banks et al.,1998; White et al.,2000)suggested that two separate classes of interneurons(possibly basket cells and interneurons in stra-tum lacunosum-moleculare respectively called,for simplic-ity,GABA A,fast interneurons and GABA A,slow interneurons) give rise to these two IPSCs.Moreover,as suggested in Banks et al.(2000),both classes interact:GABA A,slow cells inhibit not only pyramidal cells but also GABA A,fast inter-neurons.The model was designed to represent this functional organization of interacting subsets of principal cells andinter-FIGURE2.Intracerebral EEG signals recorded from hippocampus during the transition from interictal activity to ictal activity in five patients with mesial temporal lobe epilepsy.Solid line rectangles correspond to segments of EEG signal(10seconds duration)on which model parameters were identified.intICTAL,interictal activity;preONSET,mixing of interictal activity and high-amplitude spikes that arise before seizure onset;ONSET,rapid discharge occurring at the electrical onset of the seizure and in which faster oscillations are observed;ICTAL,activity observed after the rapid discharge period as seizure develops.intICTAL segments were chosen1minute(at least)before seizure onset(note that high-amplitude epileptic spikes are not present in these segments). Journal of Clinical Neurophysiology•Volume22,Number5,October2005Interictal to Ictal Transition in TLEneurons,as summarized in Fig.4a.It consists in three subsets of neurons,namely the main cells (i.e.,pyramidal cells),the slow dendritic-projecting inhibitory interneurons (GABA A,slow recep-tors),and the fast somatic-projecting inhibitory interneurons (GABA A,fast receptors).Interneurons receive an excitatory input (AMPA receptor-mediated)from pyramidal cells.The influence from neighboring or more distant populations is represented by an excitatory input n ͑t ͒(modeled by a positive mean gaussian white noise)that globally describes the average density of afferent action potentials.The model output corresponds to the postsynaptic activity of the subset of pyramidal cells that mainly contributes to the EEG signal (field potential).In each subset,a linear transfer function is used to trans-form the average presynaptic pulse density of afferent action potentials (the input)into an average postsynaptic membrane potential (the output).This transfer function is of order 2.Theassociated impulse response h EXC ͑t ͒ϭEXC.a .t .e Ϫat ,h SDI ͑t ͒ϭSDI.b .t .e Ϫbt ,and h FSI ͑t ͒ϭFSI.g .t .e Ϫgt ,respectively,deter-mines the excitatory,slow dendritic inhibitory,and fast somatic inhibitory average postsynaptic membrane potentials,where EXC,SDI,and FSI represent the synaptic gains (Fig.4c).In this work,these key parameters are automatically identified from real EEG signals recorded in the hippocampus.The inhibitory feedback loop from the subset of fast somatic-projecting inhibitory interneurons uses a faster impulse response h FSI ͑t ͒(i.e.,producing faster IPSP)than h SDI ͑t ͒.Here,the important parameter is the average somatic time constant 1/g,which was chosen lower than the average dendritic time constant 1/b,consistently with data provided in Traub et al.(1999a)(see model parameter values given in Table 1as well as average postsynaptic potentials displayed in Fig.4c).FIGURE 3.(a )Intracerebral EEG sig-nals recorded from hippocampus during the transition from interictal activity to ictal activity in patient 2and (b )time-frequency distribution of its energy (spectrogram,red color indicates higher energy).This se-quence of electrophysiologic pat-terns is characteristic of the hip-pocampus activity observed in temporal lobe epilepsy of mesial or-igin.(c )Normalized power spectral densities computed on segments of EEG activity during the interictal pe-riod (intICTAL),before the begin-ning of seizure (preONSET),during the rapid discharge at seizure onset (ONSET),and finally after the rapid discharge (ICTAL)during seizure spread show that frequency con-tents of intICTAL and preONSET segments are quite similar.The ON-SET period is marked by the redistri-bution of signal energy in higher frequency band (15to 30Hz,in this case)whereas the ICTAL period is characterized by the appearance of a narrow band activity (around 5Hz,EEG theta band).F.Wendling et al.Journal of Clinical Neurophysiology •Volume 22,Number 5,October 2005In each subset,in turn,a static nonlinear function (asym-metric sigmoid curve S ͑v ͒ϭ2e 0⁄͓1ϩe r ͑v 0Ϫv ͔͒)is also used to model threshold and saturation effects in the relationship be-tween the average postsynaptic potential of a given subset and the average pulse density of potentials fired by the neurons.Finally,interactions between main cells and local neu-rons are summarized in the model by seven connectivity constants C 1to C 7,which account for the average number of synaptic contacts.Each impulse response h EXC ͑t ͒,h SDI ͑t ͒and h FSI ͑t ͒intro-duces a pair of first-order ordinary differential equation.Consequently,the model can be represented by a set of 14first-order ordinary differential equations,which can be re-duced to an equivalent set of 10equations (Wendling et al.2002).This set must be solved by numerical integration methods adapted to its stochastic nature.We used the Euler method with a time step equal to 1/256milliseconds (corre-sponding to the sampling period of real signals).Model output can be represented as:X s ϭMn r ,Pwhere M denotes the function operated by the model to produce Xs (the simulated EEG signal)from a realization n r of input noise n(t)and for given vector P of modelparameters.FIGURE 4.Neuronal population model based on the cellular organization of the hippocampus.(a )Schematic representation.A whole population of neurons is considered inside which a subset of principal cells (pyramidal cells)project to and receive feedback from other local cells.Input to interneurons is excitatory (AMPA receptor-mediated).Feedback to pyramidal cells is either excitatory (recurrent excitation)or inhibitory (dendritic-projecting interneurons with slow synaptic kinetics—GABA A,slow —and somatic-projecting interneurons (gray rectangle)with faster synaptic kinetics—GABA A,fast ).As described in Banks et al.(2000),dendritic interneurons project to somatic ones.(b )Corresponding block diagram representation.In each subset,the average pulse density of afferent action potentials is changed into an average inhibitory or excitatory postsynaptic membrane potential using a linear dynamic transfer function of impulse response h EXC ͑t ͒,h SDI ͑t ͒,and h FSI ͑t ͒while this potential is converted into an average pulse density of potentials fired by the neurons using a static nonlinear function (asymmetric sigmoid curve,S(v )).The subset of somatic-projecting interneurons (gray rectangle)receives input from both subsets of pyramidal and dendritic interneurons.One of the model outputs represents the summated average postsynaptic potentials on pyramidal cells.It reflects an EEG signal.The three main parameters of the model respectively correspond to the average excitatory synaptic gain (EXC),to the average slow inhibitory synaptic gain (SDI),and to the average fast inhibitory synaptic gain (FSI).These three parameters are automatically identified.Other parameters are detailed in Table 1.(c )Time-course of average postsynaptic membrane potentials:excitatory,slow inhibitory,and fast inhibitory,respectively,obtained from h EXC ͑t ͒,h SDI ͑t ͒,and h FSI ͑t ͒for standard values of EXC (3.25mV),SDI (22mV),and FSI (10mV).Journal of Clinical Neurophysiology •Volume 22,Number 5,October 2005Interictal to Ictal Transition in TLEIdentification of Model Parameters EXC,SDI, and FSI Using Evolutionary Algorithms Problem StatementModel-based interpretation requires identification of model parameters that can be formalized as an optimization problem(Hernandez et al.,2002).Because model parameters are based on physiologic considerations,hypotheses for the interpretation of real EEG activity could be obtained from the optimal set of parameters Pˆϭ͓EXC,SDI,FSI͔,i.e.,the one that minimizes an error function͑Fˆo,FˆS͑P͒͒,where Fˆo and FˆS͑P͒are estimators of a feature vector F,respectively, computed on the observed EEG(X O)and synthesized EEG (X S)using parameter vector P.In the present study,F was primary based on spectral properties of the EEG signal.More precisely,the power within specific frequency bands B1(0–4Hz,delta),B2 (4–12Hz,theta and alpha),and B3(12–64Hz,beta and gamma)was retained as threefirst features.Because these spectral features did not distinguish well between interictal activity and interictal activity mixed with high-amplitude spikes,we added a fourth feature based on a morphologic criterion indicating the presence of sporadic high extrema values.It is simply defined as the difference between thefirst and last␣-order quantiles.The four features were computed on simulated and real signals normalized by their standard deviation(this provides invariance with respect to different amplitude scale factors in the model and in reality).In the expression of the error function,we use an estimation FˆS͑P͒instead of the exact value F S͑P͒that cannotbe analytically computed as a function of P because of the nonlinear nature of the model.This estimation is computed over afinite duration⌬and consequently is dependant on realization n r of model input noise.We are facing an optimization problem presenting multiple local optima in which the error function(1)is not deterministic and(2)is not computable(and thus not differ-entiable).Consequently,deterministic optimization algo-rithms,such as those based on gradient descent,do not apply.Two types of optimization methods are well suited to this problem:combinatory and exhaustive search methods on the one hand and stochastic search methods on the other hand.As the former present prohibitive computational costs, we used a particularly interesting family of stochastic searchTABLE1.Model Paremeters,Interpretation and Values Used to Produce EEG Signals With the ModelParameter Interpretation ValueEXC Average excitatory synaptic gain Determined from identification procedureSDI Average inhibitory synaptic gain(slow dendritic inhibitionloop)Determined from identification procedureFSI Average inhibitory synaptic gain(fast somatic inhibitionloop)Determined from identification procedure1/a Average time constant of excitatory postsynapticpotentials atthe dendrites of pyramidal cellsaϭ100s–11/b Average time constant of inhibitory postsynapticpotentials atthe dendrites of pyramidal cellsbϭ50s–11/g Average time constant of inhibitory postsynapticpotentials atthe soma of pyramidal cellsgϭ350s–1C1,C2Average number of synaptic contacts in the feedbackexcitatory loopC1ϭC,C2ϭ0.8C(with Cϭ135)C3,C4Average number of synaptic contacts in the slowfeedback inhibitory loopC3ϭC4ϭ0.25CC5,C6Average number of synaptic contacts in the fast feedbackinhibitory loopC5ϭC6ϭ0.1CC7Average number of synaptic contacts in the connectionbetween slowand fast inhibitory interneuronsC7ϭ0.8Cv0,e0,r Parameters of the asymmetric sigmoid function S(transforming an averagePSP into an average density of action potentials)v0ϭ6mV e0ϭ2.5s–1rϭ0.56mV–1n(t)Excitatory input noise(positive mean gaussian whitenoise)Meanϭ90pulses•s–1SDϭ30pulses•s–1Standard values(except g,C5,C6,and C7)were established in(Jansen and Rit,1995).Main parameters(EXC,SDI,and FSI)are automatically identified from real intracerebral EEG signals.F.Wendling et al.Journal of Clinical Neurophysiology•Volume22,Number5,October2005methods,known as evolutionary algorithms(EAs).EAs have been the subject of intensive research during the last decade and have shown to be useful in the solution of hard identifi-cation problems,including different biomedical applications (Hernandez et al.,2002;Pena–Reyes and Sipper,2000).The optimization procedure using EAs is detailed in appendix. Variance of Identified Parameters and Significance of Parameter ChangesTo evaluate the dispersion of triplets of identified val-ues,the whole identification procedure was applied30times to the same segment,leading to a set of30solutions for the optimal parameter set Pˆϭ͓EXC,SDI,FSI͔.The distribu-tions of parameter EXC,SDI,and FSI values obtained for the thirty iterations were represented in a so-called boxplot form for statistical analysis and comparison.This compact graph-ical display provides a way to picture how parameter values are distributed relative to defined percentiles,to identify if a distribution is skewed and if outliers or unusual data values are present.They are used to graphically determine if signif-icant statistical differences do exist between sets of parameter values.This graphical test consists in comparing boxes rep-resenting the lower and upper percentiles.If boxes do not overlap,parameter values are significantly different.RESULTSFrequency Content of Segments of EEG Activity Chosen During intICTAL,preONSET, ONSET,and ICTAL PeriodsFor each patient,segments of EEG activity chosen during the interictal period(“intICTAL”segment),during the period preceding the onset rapid discharge(“preONSET”segment),during the rapid discharge itself that typically occurs at seizure onset(“ONSET”segment),and during the period that follows this rapid discharge as seizure develops (“ICTAL”segment)were analyzed for their frequency con-tent.These segments are shown in Fig.2.Normalized power spectral densities(PSDs)were computed using the standard periodogram method over10-second-duration segments in both the real and simulated case.PSDs were found to be very typical with respect to the analyzed period.The frequency content of intICTAL and preONSET segments was found to be relatively similar.Indeed,high-amplitude sporadic spikes that appear during the preONSET period do not affect sig-nificantly the global spectral energy distribution.For thefive patients,thefirst major change in PSDs is observed at seizure onset,during the rapid discharge,which is marked by the redistribution of signal energy in a higher frequency band, typically from15to40Hz(EEG beta and low-gamma bands).The second major change corresponds to the slow-down of the rapid discharge during the ictal activity,charac-terized by a transition from broadband to narrowband activity ranging from3to10Hz(mostly within the EEG theta band). Results are exemplified in Fig.3,which also provides a time-frequency representation(spectrogram,Fig.3b)of the SEEG signal recorded during the transition from interictal to ictal activity in patient2(Fig.3a).In this case,the rapid discharge observed at seizure onset is relatively stationary with a maximum energy located in a frequency band ranging from20to30Hz.One can also notice the periodical aspect (around5Hz)of the signal recorded during ictal activity(Fig. 3c,bottom right).Identification of Model Parameters and Simulation of EEG ActivityFor each patient,the model parameter identification procedure wasfirstly applied on each segment of EEG activ-ity,tofind appropriate parameter setting for the evolutionary algorithm.Several tests were performed to analyze the mean error value for each generation and the convergence rate of the EA,as a function of the main algorithm parameters.The best results were obtained with a mutation probability of p m ϭ0.2and a crossover probability of p cϭ0.9.The error function was computed for each individual by comparing spectral and morphologic features computed on simulated and real signal segments,as described in Materials and Methods.The size of the population has beenfixed to200 individuals.The stopping criterion of the EA is met if no solution improvement is found during10consecutive gener-ations,or if the maximum number of iterations(fixed to200) is reached.The best individual of the last population was chosen as the identified solution,leading,in each case,to a triplet of values for the three model parameters:EXC(exci-tation),SDI(slow dendritic inhibition),and FSI(fast somatic inhibition).Some identification results found during this step are presented in Fig.5,which displays four examples of simu-lated signals identified from real EEG signals along with their corresponding PSDs and error values.It can be observed that identified parameters lead the model to generate EEG signals that are close(in terms of morphologic and spectral content) to real EEG signals.One can notice that signals produced by the model are very realistic:waveforms are qualitatively similar to real ones and PSDs are quantitatively comparable (as exemplified by epileptic spikes in Fig.5,preONSET period).At this step,we also observed some common ten-dencies(among patients)in the evolution of model parame-ters for transitions of dynamics.To check whether these tendencies were significant or only due to the variability of identified parameters related to the randomness inherent to this identification procedure and to the randomness of the observed data,we conducted an analysis of the dispersion of estimated parameters EXC,SDI,and FSI for each type of activity in each patient.Dispersion of Identified ParametersThe identification procedure was repeated thirty times with random initialization on each segment of activ-ity leading,in each case,to thirty triplets of values(EXC, SDI,FSI)for each patient(P1to P5)and for each period (intICTAL,preONSET,ONSET,ICTAL).These results are displayed in Fig.6,in the compact form of so-called boxplots(see Materials and Methods,“Variance of Iden-tified Parameters”).Taken as a whole,the evolution ofJournal of Clinical Neurophysiology•Volume22,Number5,October2005Interictal to Ictal Transition in TLE。