TerraQSAR - OMAR
Contents
1. Samaad T Backpropagation improvements based on heuristic arguments theory track neural and cognitive sciences Track Int Joint Conf Neural Networks Vol 1 Washington D C 1990 Sarle W S Ed Neural network FAQ part 1 of 7 Introduction 2002 http accpc com nnfaq FAQ html Serra J R P C Jurs and K L E Kaiser Linear regression and computational neural network prediction of Tetrahymena acute toxicity for aromatic compounds from molecular structure Chem Res Toxicol 14 1535 1545 2001 Shanno D F Conjugate gradient methods with inexact searches Math Oper Res 3 244 256 1978 Specht D F Probabilistic neural networks for classification mapping or associative memory ICNN Conference Proc 1988 Yeh Y Y Kuo and D Hsu Building KBES for diagnosis PC pile with artificial neural network J Comp Civil Eng 7 71 93 1993 Acknowledgement TerraBase Inc acknowledges with thanks the contributions of its contractors and associates especially Dr A Krajnc and M B McKinnon to the development of its products Security Features As other software providers TerraBase Inc is interested is preventing un authorized duplication and use of its highly sophisticated software products Therefore all copies of this TerraQSAR program are personalized i e they contain encrypted information of the name and affiliation of the rightful user This information is displayed on the Start up screen2. Ontario L8S 453 CANADA 2 Software License As long as you comply with the terms of this End User License Agreement the Agreement TerraBase grants to you a non exclusive license to Use the Software for the purposes described in the Documentation Some third party materials included in the Software may be subject to other terms and conditions which are typically found in a Read Me file located near such materials 2 1 General Use You may install and Use a copy of the Software solely on your compatible personal computer Server Use You may not install the Software on a computer file server for the purpose of downloading installing or using the Software onto or with other computers 2 3 Backup Copy You may make one backup copy of the Software provided your backup copy is not installed or used on any computer You may not transfer the rights to a backup copy unless you transfer all rights in the Software as provided under Section 4 3 Intellectual Property Rights The Software and any copies that you are authorized by TerraBase to make are the intellectual property of and are owned by TerraBase Incorporated and its suppliers The structure organization and code of the Software are the valuable trade secrets and confidential information of TerraBase Incorporated and its suppliers The Software is protected by copyright including without limitation by Canadian and United States Copyright Law international treaty provisions and
3. The Program Interface as it appears on startup Fi 15 dule TerraQSAR box allows the user to the selected program e g TerraQSAR LC50 estimation mo provides a toggle switch between switch between Manual mode and Batch mode the latter is available in the Professional version only The About box contains important OMAR for the TerraQSAR mouse d rat oral LD50 module etc The second box user information FHM for the TerraQSAR fathead minnow The Program selection In the Manual mode the user enters a SMILES Simplified Molecular Input Line Entry System string either by typing it into the Input field or by pasting it from memory when copied into memory from another source such as a TerraBase Inc database output Please consult the section on SMILES Notation for important advice Example 1 Phenol has the SMILES string clccccc1O Copying this string into memory for example from this text making sure the quotation marks are omitted and pasting it into the Input field will result in the appearance of the chemical structure of phenol in the shaded rectangular field below as shown in Figure 3 TerraQSAR x Program TeraQSAR FHM y Mode m Manual E Batch Input Chemical formula in the SMILES format 8 Calculate Results ar maf mw BH Ext 2 About Fig 3 Result of entering or pasting the SMILES string for
4. bacteria SETAC 99 Europe Leipzig May 1999 poster Martin T M and D M Young Prediction of the acute toxicity 96 hr LC50 of organic compounds to the fathead minnow Pimephales promelas using a group contribution method Chem Res Toxicol 14 1378 1385 2001 http dx doi org 10 1021 tx0155045 Masters T Practical Neural Network Recipes in C San Diego Academic Press 1993 Niculescu S P K L E Kaiser and G Schiiitirmann Influence of data preprocessing and kernel selection on probabilistic neural network modeling of the acute toxicity of chemicals to the fathead minnow and to Vibrio fischeri bacteria Water Quality Res J Canada 33 153 165 1998 http www cciw ca warjc 33 1 33 1 153 htm Niculescu S P and K L E Kaiser Modeling the relative binding affinity of steroids to the progesterone receptor with probabilistic neural networks Quant Struct Act Relat 20 223 226 2001 Niculescu S P K L E Kaiser and T W Schultz Modeling the toxicity of chemicals to Tetrahymena pyriformis using molecular fragment descriptors and probabilistic neural networks Archiv Environ Toxicol Chem 39 289 298 2000 Prechelt L Ed Frequently asked questions FAQ on neural networks 1995 http www ipd uka de prechelt FAQ nn7 html Ramirez M R and D Arghya A faster learning algorithm for back propagation neural networks in NDE applications Proc 2 Int Conf on AI pp 275 283 1991
5. 7 indazolo 2 3 4 fgh acridine 5 10 dione oral LD50 value for rat mouse of 13405 mg kg b w 19 Example 4 Tributyl oleoyloxy stannane CAS 3090 35 5 SMILES string CCCC Sn CCCC CCCC OC O CCCCCCCC C C CCCCCCCC has predicted rat mouse oral LD50 value of 227 mg kg b w pT 0 40 as shown in Figure 7 amp TerraQSAR Program TerraQSAR OMAR x Mode m Manual amp Batch Input ___ Chemical formula in the SMILES format Ccccys nJ CCOCCCCCC OC 0 CCCCCCC C C CCCCCCCC Results pT 0 400 mg kg b w 227 51 74 Mu 571 5 l Ext Fig 7 Result of computation for the SMILES string shown in the input field depicting the organotin compound tributyl oleoyloxy stannane with the computed oral LD50 value for the rat mouse of 227 mg kg b w 20 Example 5 The anti coagulant rodenticide difenacoum CAS 56073 07 5 with the SMILES code O C10c2ccccee2C O C1C3c4ccecc4CC cS5ccc c6ceccc6 cc5 C3 and the structure shown in Figure 8 has the predicted rat mouse oral LDSO of 0 63 mg kg b w pT 2 85 L TerraQSAR Program TerralSAR OMAR Mode m Manual E Batch Input Chemical formula in the SMILES format f 01 De2ccccc2C 0 01C3c4cccccaCClchccclc ccccc lechjC3 al Calculate Results pT 2849 mg kg bw 0 6300 Mw 444 5 Bi Exit About Fig 8 Result of computation for the rodenticide difenacoum CAS 56073 07 5 with the SMILES code O C10c2cccce2
6. Located in Germany and Austria If you purchased a 12 license to the software in Germany or Austria then Section 8 does not apply instead TerraBase may be liable without limitation for damages you have incurred under or in connection with this Agreement only if the damage has been caused by the willful or grossly negligent act of TerraBase or its agents TerraBase is liable only to the extent of the typically foreseeable damage for such damages which have been caused by any other negligent breach of a substantial contractual duty by TerraBase or its agents These aforementioned limitations apply irrespective of their legal basis in particular with regard to any pre contractual or auxiliary contractual claims The limitations shall not apply however to any mandatory liability under the applicable German or Austrian Product Liability Act nor to any damage which is caused due to the breach of an express warranty to the extent that such express warranty was intended to protect the user against the specific damage incurred The obligations under the second sentence shall not apply if any damage is caused by your having altered the Software or if the respective data carriers media have been damaged by accident misuse or inappropriate use or if the damage concerned has been caused by the use of the Software in connection with other software for which the Software was not designated to be used according to the Documentation 14 3 Pre release Product A
7. ca 2 sec at 2 GHz example shows the TerraQSAR FHM program module 17 Example 2 A low complexity molecule the chemical 2 aminothiazole CAS 96 50 4 with the SMILES and structure shown in Figure 5 has a computed iv LD50 value of 576 mg kg b w as shown in Figure 5 computation time lt 5 sec TenaQSAR Ea Program TerradSAR AMIV v Mode m Manual Batch Input Chemical formula in the SMILES format st c Ninccl Results pT 0 760 mg kg b w 576 2628 Mw fi00 1 BL Ext About Fig 5 Result of computation for the insecticide 2 aminothiazole SMILES string shown in the input field depicting the compound 2 aminothiazole with its computed iv LDSO value for rat mouse of 576 mg kg b w 18 Example 3 The compound anthra 2 1 9 mna benz 6 7 indazolo 2 3 4 fgh acridine 5 10 dione CAS 6247 39 8 SMILES string ce12c3c4cS5ccc6C O c7c C8c6cSC N3N C I1clceccc1C O c2cc4 CC 8 cccc7 has a predicted oral LD50 value of 13 405 mg kg b w as shown in Figure 6 Ea TerraQSAR Program TeraQSAR OMAR Mode m Manual amp Batch Input Chemical formula in the SMILES format 6C O e c C8cbceSC N3SN C1cleceec1C O e2ec4 CC 8 eccc Results pt 1 477 mg kg b w 13405 49 Miu 446 5 Fi Exit 2 About Fig 6 Result of computation for the SMILES string shown in the input field depicting the quinone compound anthra 2 1 9 mna benz 6
8. person or entity b you retain no copies including backups and copies stored on a computer and c the receiving party accepts the terms and conditions of this Agreement and any other terms and conditions upon which you legally purchased a license to the Software Notwithstanding the foregoing you may not transfer education pre release or not for resale copies of the Software 5 Updates If the Software is an Update to a previous version of the Software you must possess a valid license to such previous version in order to Use the Update You may continue to Use the previous version of the Software on your computer after you receive the Update to assist you in the transition to the Update provided that the Update and the previous version are installed on the same computer the previous version or copies thereof are not transferred to another party or computer unless all copies of the Update are also transferred to such party or computer and you acknowledge that any obligation TerraBase may have to support the previous version of the Software may be ended upon availability of the Update 6 LIMITED WARRANTY Except as may be otherwise provided in Section 14 TerraBase warrants to the person or entity that first purchases a license for the Software for use pursuant to the terms of this license that the Software will perform substantially in accordance with the Documentation for the ninety 90 day period following receipt of the Software whe
9. phenol c1ccecc10 into the input field the structure of phenol excluding hydrogen atoms will appear in the field below example shows the TerraQSAR FHM program module 16 Once the user has ascertained that the structure of the compound is that of the desired chemical a simple click of the Calculate bar below the structure field will result in the three fields below the bar to be filled with the predicted values for the compound as shown in Figure 4 Field 1 pT is the negative logarithm of the LCS50 concentration in mmol L field 2 mg L in TerraQSAR FHM program module is the LC50 value in mg L in TerraQSAR FHM program module and field 3 MW shows the molecular weight of the compound Computation time varies with the complexity of the structure and the computer specifics ranging from a nearly instantaneous result 1 sec for small structures to minutes for large molecules with highly complex structures TerraQSAR Ea Program TeraQSAR FHM y Mode m Manual Batch Input Chemical formula in the SMILES format et ccccclO Results pT 0 510 mg L 29 0837 Mw 941 Fo Ext 2 About Fig 4 Result of the execution of Calculate The fields show the following values Field 1 pT is the negative logarithm of the millimolar LC50 concentration field 2 mg L is the LC50 value in mg L and field 3 shows the molecular weight of the compound Computation time
10. ste Se see oe Ser Gta E TEAT AEAEE AENEA O EEEE EISEIN SER np tt nde Be se soba aoe 00 shoe sone POE sane POSES ER EEEE EAEEREN OS ERRE OO ennnen ENEN sank shot ERAN ECION OCIO s ih OC IOI EN IEICE E EEES AREER HEEEL ERREEN EAE EENEN OERE RS A LS aS TIS ENS OCS ANS D EREE EAEE AE EEIEIEE SS OSOS SOCIOS seas SS cS E etree ds EEA i eS eS ie 2 eats GS POSI SOS pride SRS 2R 292S 290S 290S 29 PO ESIOSAS TESS RESES ENESES EISES SSE EE EEEREN EEEE ss tee ette SO OO AAN BPRS Se IOI II Eaa aaae aAA IAA tert tects tio EOE NOCION IRIIRI I IOCIS ICI NOCIONI ROS PO PESE O ENS E e ICI RSS IN RR PROS RK RTOS E OS eter EEATT A ESSN tota ets EREE E ICR ONES PE E ESO O IONE OG S EEEE EDUEN DOOR a pete 2 pep 5 Hs 5 A EEIEIEE EAEEREN ETENEE IE O O O EN a A A EE EEEE EEEE ot Se a A E E EERE E DES aE TDN S ROE OEIS RO ES OOO 5 PENETRE EEA pete ESISTESSE SCISCO OTISCI NS ae ES AS E td 3 RE RICO ROHNERT gt beaten PSC SES EEN ES res O sec ence ace relstetatetaretetatersterateraersrterttert satetetatetatetatetatetatetatetetetetetes AEAEE EAEE et CSS TAEAE EAEE AEEA ASES EIL EITTIE PISOS SOS EAS PEO ese SRS ION NONI EEEE EEEE ENERE EEEE EEEE CE Pc Papa ESS PRAEERAT PEREA EIEESE eS Sei 25 OS ptes pup 5 z states CIO PO dto secci PO SOS agta SEELE EOSTO S aos a5 Poche MM RO KF eat O DES AO SR AAA TeralUSAR AMIW 2
11. 3237 3245 1999 http dx doi org 10 1016 S0045 6535 99 00553 6 Kaiser K L E and S P Niculescu Probabilistic neural network PNN methodology for the prediction of acute toxicity of chemicals to fathead minnow based solely on chemical structure derived input parameters National Water Research Institute Contribution No AEP TN99 001 39 p 1999 Kaiser K L E and S P Niculescu Modeling the acute toxicity of chemicals to Daphnia magna a probabilistic neural network approach Environ Toxicol Chem 20 420 431 2001 http etc allenpress com entconline request get abstract amp issn 0730 7268 amp volume 020 amp issue 02 amp page 0420 Kaiser K L E S P Niculescu and T W Schultz Probabilistic neural network modeling of the toxicity of chemicals to Tetrahymena pyriformis with molecular fragment descriptors SAR amp QSAR Environ Res 13 57 67 2002 http taylorandfrancis metapress com link asp id ak 1 1jrbmqqkrnp76 Kaiser K L E and S P Niculescu On the PNN modeling of estrogen receptor binding data for carboxylic acid esters and organochlorine compounds Water Qual Res J Canada 36 619 630 2001 http www cciw ca wqrjc 36 3 36 3 619 htm Kohonen T Self Organization and Associative Memory 2 ed Springer Verlag Berlin 1988 K hne R K L E Kaiser S P Niculescu and G Schiiiirmann Neural network to estimate acute toxicity of chemicals to the fathead minnow and Vibrio fischeri
12. C O C1C3c4ccecc4CC cS5ecc c6ceccc6 cc5 C3 and the structure shown in Figure 8 has the predicted rat mouse oral LD50 of 0 63 mg kg b w 21 Example 6 The natural organohalogen compound aurantoside F from the marine sponge Siliquariaspongia japonica C39H48CI2N2015 with the SMILES string CI C C C C C C C C CI C C C C C C C C C C O C1 C O N C H CC O N C1 O C H 20C C H O C H O C H 20 C H 3 C H O C H O C H O C H 40 C H C C H O C H 40 CO3 and the structure shown in Figure 9 only part of the SMILES string is visible in the TerraQSAR SMILES window has the predicted rat mouse oral LD50 of 1765 mg kg b w pT 0 32 L TerraQSAR Program TerraQSAR OMAR X Mode m Manual amp Batch Input Chemical formula in the SMILES format HIOCEHOCEEHKOICOHICCEGCHIOCE H 40 C03 Results pT 0 315 mg kg b w 1765 747 My 1855 7 Ext About Fig 9 The natural organohalogen compound aurantoside F from the marine sponge Siliquariaspongia japonica C39H48CI2N2015 with the SMILES string CNC C C C C C C C Cl C C C C C C C C C C O C1 C O N C H CC O N C1 O C H 20C C H O C H O C H 20 C H 3 C H O C H O C H O C H 40 C H C C H O C H 40 CO3 and the structure shown in Figure 9 only part of the SMILES string is visible in the TerraQSAR SMILES window has the predicted rat mouse oral LD50 of 1765 mg kg b w 22 Example 7 The compound sax
13. ES code refer to the paragraph on SMILES Notation Computation The computer evaluates the number and type of fragments present in the query string and computes the resulting estimate on the basis of the same types of fragments present in a data set of 2457 compounds for which measured values have been published in the literature Computation time varies with the complexity of the query structure and speed of the computer Typically for compounds without chiral centers and molecular weight of lt 200 computation time on a 2 GHz machine takes lt 5 seconds Results Figure 1 shows the measured vs predicted values for all 2457 compounds used in the development of the TerraQSAR OMAR rat mouse LD50 estimation program as obtained from the program The data cover approximately eight orders of magnitude ranging from approximately pT 2 to pT 6 where pT is the negative logarithm of the millimolar LD50 value per kg body weight b w TerraQSAR OMAR E Qa 0 ao o i Qa measured pT Fig 1 Plot of the measured vs predicted mouse amp rat oral LD50 values for all 10 000 compounds in the training set units are pT equal to log kg b w mmol SMILES Notation The Simplified Molecular Input Line Entry System SMILES has been developed by D Weininger at the beginning of the 1980 s It is far superior to the previously used Wiswesser Line Notation WLN for coding and depicting chemical structures by be
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15. NY WARRANTY OR LIABILITY OBLIGATIONS TO YOU OF ANY KIND INCLUDING WHERE LEGALLY LIABILITY CANNOT BE EXCLUDED FOR PRE RELEASE SOFTWARE BUT IT MAY BE LIMITED TERRABASE S LIABILITY AND THAT OF ITS SUPPLIERS SHALL BE LIMITED TO THE SUM OF FIFTY DOLLARS U S 50 IN TOTAL 15 This concludes the License Agreement for the TerraQSAR software If you have any questions regarding this Agreement or if you wish to request any information from TerraBase please use the address and contact information included with this product to contact TerraBase Gen_WWCombined_USEnglish_8 7 00_11 14 Trademarks and Copyrights Windows 95 Windows 98 Windows NT Windows 2000 Windows ME and Windows XP Windows 7 Windows 8 are trademarks of Microsoft Corporation Redmond Washington USA Other copyrights and trademarks are those of their respective owners 14 le intuitive and highly functional is simp The program interface of the TerraQSAR toxicity prediction modules is shown gure 2 It 1 Program Interface F in caos PCI PO oe sane POE sane seat OO PO CIO IEO O IOO enero A EEEIEE ESS bet oc AEA AEA AEAT PSSST EOCENE SEOSE EISESCNA EEEREN EENEN EAEAN enter ESOS sietetatetetetateteteteteteterstere ed dt pt eat EEEE EEEE ARNES ERAN Hd ENE OSOS ade PERRERA EOS DOE EAEEREN G EEIEIEE EISTO PO O AA PO ok eo eC PO IOO ION haere re trees SS ESA PANES NERO EEE DOS ese ese eset REEE REEE AEI AEEA OS O PS ntc REO rtitetitat pr POSO
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19. TerraQSAR OMAR Mouse amp Rat oral LD50 Estimation Software vs 1 2 User Manual Copyright O 2007 2015 TerraBase Inc Purpose Terra QSAR M OMAR is a holistic probabilistic algorithm based neural network software program designed and optimized solely for the computation of single dose oral route of exposure median lethal dose values LD50 of organic carbon containing substances with a defined chemical structure to the rat and mouse Table of Contents Computation Process 3 25 s seit A A Data OU Pel sasha set Raia aad A ELAMEA SR Mput Que nnna e ect dai e a os das COMPULMIO ei e A A he eee RN RESUS 2 bere eevidiu tence Aue cee read teat arcu urate SMILES Noto e Da A O hie lei RA OE Mee eae Acknowledgement ma na denen a E A E Poems a Sate ets EET Security Feat re A TS Dei EE EE AE A E E ets License Apreement AE Trademarks and Copyrights is i ee ti a BA 14 Program Interface iii ll Aa S AEE anes E a a 15 Teelmical Requirements css e celoso de o jale elote act 24 Installation TOS TU Ons enen oan ek tide eae A a 24 Part 1 Installation of the Accelrys software oooonooccnocononcconcnnncnconncnonccnnn crac ccoo ncnonennnos 24 Part 2 Installation of Terra QSAR ooooccoccccnncnccononononanononcononnnnononononoononnnn nono noncononiannnos 24 Customer SUPppOR iii diia 24 Introduction Welcome to TerraQSAR a breakthrough development in toxicity estimation software developed by TerraBase Inc TerraQSAR predi
20. and can be reviewed at any time by activating the About box prominently displayed on the main program panel see Figure 2 Hence any un authorized propagation of this software can be traced back to the original source Anyone knowing of any such un authorized copies is requested to contact TerraBase Inc We offer generous rewards for information of any illegal duplication or use of this program as described in the About box In order for the TerraQSAR program to function properly the TerraQSAR CD has to be present in a CD ROM drive on the computer system which is used to run the program Other than for archival copies to be used solely for backup and protection against loss by the rightful user duplication of this software is not permitted Legal License Agreement The rightful TerraQSAR user is hereby granted a non exclusive use license subject to the agreement as described in the text below TerraQSAR End User License Agreement NOTICE TO USER PLEASE READ THIS CONTRACT CAREFULLY BY USING ALL OR ANY PORTION OF THE SOFTWARE YOU ACCEPT ALL THE TERMS AND CONDITIONS OF THIS AGREEMENT INCLUDING IN PARTICULAR THE LIMITATIONS ON USE CONTAINED IN SECTION 2 TRANSFERABILITY IN SECTION 4 WARRANTY IN SECTION 6 AND 7 LIABILITY IN SECTION 8 AND SPECIFIC EXCEPTIONS IN SECTION 14 YOU AGREE THAT THIS AGREEMENT IS ENFORCEABLE LIKE ANY WRITTEN NEGOTIATED AGREEMENT SIGNED BY YOU IF YOU DO NOT AGREE DO NOT USE THIS SOFTWARE IF YOU ACQU
21. applicable laws in the country in which it is being used You may not copy the Software except as set forth in Section 2 Software License Any copies that you are permitted to make pursuant to this Agreement must contain the same copyright and other proprietary notices that appear on or in the Software Without exception you agree not to modify adapt or translate the Software You also agree not to reverse engineer decompile disassemble or otherwise attempt to discover the source code of the Software Trademarks shall be used in accordance with accepted trademark practice including identification of trademarks owners names Trademarks can only be used to identify printed output produced by the Software and such use of any trademark does not give you any rights of ownership in that trademark Except as expressly stated above this Agreement does not grant you any intellectual property rights in the Software 4 Transfer You may not rent lease sublicense or authorize all or any portion of the Software to be copied onto another users computer except as may be expressly permitted herein You may however transfer all your rights to Use the Software to another person or legal entity provided that a you also transfer each this Agreement the Software and all other software or hardware bundled or pre installed with the Software including all copies Updates and prior versions and all copies of font software converted into other formats to such
22. ce2ccl1 The SMILES strings shown as not valid are valid per se however the interpretation of these codes are the hydrogen saturated compounds cyclopentane and 3 4 dihydrocoumarin respectively Literature Accelrys Inc 2002 http www accelrys com Carpenter W C and J F Barthelemy Common misconceptions about neural networks as approximators Proc 3rd Int Conf Applic Artificial Intelligence to Civil and Structural Engineering in Neural Networks and Combinatorial Optimization in Civil and Structural Engineering Topping B H V Ed pp 11 18 1993 Daylight Chemical Information Systems Inc 2002 http www daylight com smiles f_smiles html Eldred D V C L Weikel P C Jurs and K L E Kaiser Prediction of fathead minnow acute toxicity of organic compounds from molecular structure Chem Res Toxicol 12 670 678 1999 Grabec I Self organization of neurons described by the maximum entropy principle Biol Cybern 63 403 409 1990 Grabec I Optimization of kernel type density estimator by the principle of maximal self consistency Neural Parallel amp Scientific Computations 1 83 92 1993 Hecht Nielsen R Nearest matched filter classification of spatiotemporal patterns Appl Optics 26 1892 1899 1987 Hecht Nielsen R Neurocomputing Addison Wesley Publishing Co Inc 1990 Hertz J A Rogh and R Palmer Introduction to the Theory of Neural Computation Addison Wesle
23. ction software is based on the probabilistic neural network methodology using the molecular structure of the substances under investigation The TerraQSAR OMAR program computes the oral lethal dose of organic compounds to 50 of a population oral LD50 of the mouse and rat TerraQSAR modules use as input a chemical s SMILES code 2 D or 3 D which is an international code for the representation of chemical structures and amenable to computer analysis The TerraQSAR OMAR module computes the LD50 in both mg L and pT log kg body weight mmole units as well as the molecular weight MW of substances entered Theory The field of artificial intelligence and neural network application is experiencing rapid growth in all aspects of technology From elevator control to drug design neural network methods have lots to contribute to product development operating improvements and frequently enable the customer to tackle problems which were inaccessible hitherto The TerraQSAR products exploit the neural network methodologies developed in recent years by researchers and programmers both within and outside the company In contrast to linear methodologies such as simple regression methods principal components analysis and others neural networks make use of non linear relationships which makes them particularly useful for chemical biological problems where different and or unknown modes of action are known or likely to be present in addition
24. dditional Terms If the product you have received with this license is pre commercial release or beta Software Pre release Software then the following Section applies To the extent that any provision in this Section is in conflict with any other term or condition in this Agreement this Section shall supercede such other term s and condition s with respect to the Pre release Software but only to the extent necessary to resolve the conflict You acknowledge that the Software is a pre release version does not represent final product from TerraBase and may contain bugs errors and other problems that could cause system or other failures and data loss Consequently the Pre release Software is provided to you AS IS and TerraBase disclaims any warranty or liability obligations to you of any kind WHERE LEGALLY LIABILITY CANNOT BE EXCLUDED FOR PRE RELEASE SOFTWARE BUT IT MAY BE LIMITED TERRABASE S LIABILITY AND THAT OF ITS SUPPLIERS SHALL BE LIMITED TO THE SUM OF FIFTY DOLLARS U S 50 IN TOTAL You acknowledge that TerraBase has not promised or guaranteed to you that Pre release Software will be announced or made available to anyone in the future that TerraBase has no express or implied obligation to you to announce or introduce the Pre release Software and that TerraBase may not introduce a product similar to or compatible with the Pre release Software Accordingly you acknowledge that any research or development that you perform regarding the
25. e proper functioning of the TerraQSAR program use the Windows Control Install Remove Software command to run the setup exe in the Accelrys folder and follow the instructions Part 2 Installation of TerraQSAR To install any TerraQSAR module use the Windows Control Install Software command to run the TerraQSAR setup exe in any TerraQSAR folder and follow the instructions Customer Support TerraBase Inc is committed to effective customer support With the rapid change in PC technology operating systems and other software and hardware changes the occasional hiccup is bound to happen We will try our best to help customers with problems related to our products in most cases free of charge Contact our help department with any question and concern about our products either by EMAIL FAX or MAIL TerraBase Inc 1063 King St West Suite 130 Hamilton ON L8S 483 Canada Fax 905 527 0263 Internet http www terrabase inc com Copyright O 2015 TerraBase Inc 24
26. ing simple intuitive and machine readable For an excellent tutorial on the SMILES notation refer to the Daylight Corp web site Recently Accelrys Inc introduced a variety of software modules allowing the visualization of SMILES codes as chemical structure drawings In this process Accelrys introduced changes to the common Daylight Corp interpretation of SMILES codes by their software As a result lower case c formerly only interpreted as sp carbon is now 4 interpreted as either as sp or sp carbon depending on its surrounding and connections to other atoms The determinant here is whether or not the carbon atom is part of an aromatic ring as defined by the Hueckel rules This has ramifications for the correct interpretation of SMILES strings by the TerraQSAR programs as they are built on the backbone of the Accelrys software Therefore all users are cautioned to ascertain that their SMILES codes follow the rules of the Accelrys software 1 e to ascertain that only sp carbons in ring systems which satisfy Hueckel conditions for aromaticity are given in lower case c all other sp carbons whether in rings or not must be entered as capital C Some examples of valid and not valid SMILES strings are listed below in Table 2 Table 2 Valid and not valid examples of Accelrys SMILES code Substance SMILES not valid SMILES valid cyclopentadiene leccCl Cl CC CC1 coumarin clcec20C O cce2ccl clec2O0C O C C
27. itoxin CAS 35523 89 8 with the structure shown in Fig 10 top 2 D and Fig 10 bottom 3 D has the computed rat mouse oral LD50 of 0 37 mg kg b w TerraQSAR Program TerraQSA4R OMAR 7 Mode m Manual Y Batch Input Chemical formula in the SMILES format CN2C N N C Q H COC 0 JN CE S H INSCl NIN C Y1 23 Results pT 2908 mg kg bw 0 3701 Mw 299 3 Bi Ext 2 About Fig 10 Result of computation for the compound saxitoxin CAS 35523 89 8 with the structure shown in Fig 10 top 2 D and Fig 10 bottom 3 D has the computed rat mouse oral LD50 of 0 37 mg kg b w 23 Technical Requirements Operating system PC with Windows 95 98 NT 2000 or ME XP SP2 or Vista Windows 7 or Windows 8 operating system Central processor unit CPU No specific requirement duration of computations will increase with decrease in CPU speed 1 6 GHz or higher recommended Mouse or other pointing device required Screen setting Variable 800 x 640 or higher CD ROM drive required Other Presence of the TerraQSAR CD in the CD ROM drive is required for program execution Installation Instructions The TerraQSAR software is a fully functional stand alone system easy to install or uninstall It consists of two installation parts we recommend installation in the order mentioned Part 1 Installation of the Accelrys software To install un install the Accelrys supporting software necessary for th
28. mmercial Software 14 4 Tryout Product Sampler NFR Additional Terms If the product you have received with this license is a tryout product sampler or NFR copy of the Software Tryout Software then the following Section applies until such time that you purchase a license to the full retail version of such product To the extent that any provision in this Section is in conflict with any other term or condition in this Agreement this Section shall supercede such other term s and 13 condition s with respect to the Tryout Software but only to the extent necessary to resolve the conflict YOU ACKNOWLEDGE THAT THE TRYOUT SOFTWARE CONTAINS LIMITED FUNCTIONALITY AND OR FUNCTIONS FOR A LIMITED PERIOD OF TIME TERRABASE IS LICENSING THE SOFTWARE ON AN AS IS BASIS SOLELY AS A DEMONSTRATION MODEL If the Tryout Software 1s a timeout version then the program will terminate operations after a designated period of time e g 15 30 or 45 days following installation the Time Out Date which is specified in the Software Upon such Time Out Date the license hereunder shall be terminated unless extended by TerraBase upon your purchase of a full retail license from TerraBase You acknowledge that such Tryout Software shall cease operation upon the Time Out Date and accordingly access to any files or output created with such Tryout Software or any product associated with the Tryout Software is done entirely at your own risk TERRABASE DISCLAIMS A
29. n used on the recommended hardware configuration Non substantial variations of performance from the Documentation does not establish a warranty right THIS LIMITED WARRANTY DOES NOT APPLY TO UPDATES FONT SOFTWARE CONVERTED INTO OTHER FORMATS PRE RELEASE BETA TRYOUT PRODUCT SAMPLER OR NOT FOR RESALE NFR COPIES OF SOFTWARE See Section 14 To make a warranty claim you must return the Software to the location where you obtained it along with proof of purchase within such ninety 90 day period If the Software does not perform substantially in accordance with the Documentation the entire liability of TerraBase and your exclusive remedy shall be limited to either at TerraBase s option the replacement of the Software or the refund of the license fee you paid for the Software THE LIMITED WARRANTY SET FORTH IN THIS SECTION GIVES YOU SPECIFIC LEGAL RIGHTS YOU MAY HAVE ADDITIONAL RIGHTS WHICH VARY FROM JURISDICTION TO JURISDICTION For 10 further warranty information please see the jurisdiction specific information at the end of this Agreement if any or contact TerraBase 7 DISCLAIMER THE FOREGOING LIMITED WARRANTY STATES THE SOLE AND EXCLUSIVE REMEDIES FOR TERRABASE S OR ITS SUPPLIER S BREACH OF WARRANTY TERRABASE AND ITS SUPPLIERS DO NOT AND CANNOT WARRANT THE PERFORMANCE OR RESULTS YOU MAY OBTAIN BY USING THE SOFTWARE EXCEPT FOR THE FOREGOING LIMITED WARRANTY AND FOR ANY WARRANTY CONDITION REPRESENTATION OR TERM TO THE EXTENT T
30. or different terms This is the entire agreement between TerraBase and you relating to the Software and it supersedes any prior representations discussions undertakings communications or advertising relating to the Software 12 Notice to U S Government End Users The Software and Documentation are Commercial Items as that term is defined at 48 C F R 2 101 consisting of Commercial Computer Software and Commercial Computer Software Documentation as such terms are used in 48 C F R 12 212 or 48 C F R 227 7202 as applicable Consistent with 48 C F R 12 212 or 48 C F R 227 7202 1 through 227 7202 4 as applicable the Commercial Computer Software and Commercial Computer Software Documentation are being licensed to U S Government end users a only as Commercial Items and b with only those rights as are granted to all other end users pursuant to the terms and conditions herein Unpublished rights reserved under the copyright laws of the United States by TerraBase Incorporated 1363 King St West Suite 130 Hamilton Ontario L8S 483 CANADA 13 Compliance with Licenses If you are a business or organization you agree that upon request from TerraBase or TerraBase s authorized representative you will within thirty 30 days fully document and certify that use of any and all TerraBase Software at the time of the request is in conformity with your valid licenses from TerraBase 14 SPECIFIC EXCEPTIONS 14 1 Limited Warran
31. raud TerraBase is acting on behalf of its suppliers for the purpose of disclaiming excluding and or limiting obligations warranties and liability as provided in this Agreement but in no other respects and for no other purpose For further information please see the jurisdiction specific information at the end of this Agreement if any or contact TerraBase 9 Export Rules You agree that the Software will not be shipped transferred or exported into any country or used in any manner prohibited by the any law governing such activities either in Canada or the United States such as the United States Export Administration Act or any other export laws restrictions or regulations collectively the Export Laws In addition if the Software is identified as export controlled items under the Export Laws you represent and warrant that you are not a citizen or otherwise located within an embargoed nation including without limitation Iran Iraq Syria Sudan Libya Cuba North Korea and Serbia and that you are not otherwise prohibited under the Export Laws from receiving the Software All rights to Use the Software are granted on condition that such rights are forfeited if you fail to comply with the terms of this Agreement 10 Governing Law This Agreement will be governed by and construed in accordance with the substantive laws in force a the Province of Ontario if the license to the Software is purchased when you are in Canada the United
32. to linear relationships Important information on both the theory and specific aspects of this software can be found in the references given in the Literature Computation Process Data Set The TerraQSAR OMAR mouse amp rat LD50 toxicity estimation program is based on a data set of measured values for 10 000 organic carbon containing compounds These data are widely available both from non commercial sources such as the US National Institute of Health s database or from commercial sources such as TerraBase Inc s TerraTox Explorer database Fragments Major fragments used in the TerraQSAR modules have been described in detail in several publications listed in the Literature especially the works by Kaiser et al An overview of basic fragment types considered is given in Table below Table 1 Examples of fragments used in TerraQSAR programs Fragment type Examples C 0 O S O O O Acidity fragment Aliphatic ring fragment Aromatic ring fragment Atom fragment Bond fragment Group fragment Hydrophobicity fragment Ionization fragment Polarity fragment Reactivity fragment Stereo fragment Weight fragment Input Query C1CCCCC1 C1CCCC1 cleececl clececcnl C H N O C C C C C C C O H C O C O C O C C C C C CCCC O Na O N O CC O C CC O CI C H C N Cl C H C N molecular weight All TerraQSAR modules use the SMILES string code as input For additional comments about the SMIL
33. ty for Users Located in Germany or Austria If you purchased a license to the software in Germany or Austria then Section 6 does not apply instead TerraBase warrants to the person or entity that first purchases a license for the Software that the Software will perform substantially in accordance with the Documentation for a period of six 6 months following receipt of the Software when used on the recommended hardware configuration Non substantial variations of performance from the Documentation does not establish a warranty right THIS LIMITED WARRANTY DOES NOT APPLY TO UPDATES FONT SOFTWARE CONVERTED INTO OTHER FORMATS PRE RELEASE TRYOUT PRODUCT SAMPLER NOT FOR RESALE NFR COPIES OF SOFTWARE OR TO SOFTWARE THAT HAS BEEN ALTERED BY YOU TO THE EXTENT SUCH ALTERATIONS CAUSED A DEFECT To make a warranty claim you must return the Software at our expense to the location where you obtained it along with proof of purchase within such six 6 month period If the Software does not perform substantially in accordance with the Documentation the entire liability of TerraBase and your exclusive remedy shall be limited to either at TerraBase s option the replacement of the Software the reduction of the license fee or a refund of the license fee you paid for the Software THE LIMITED WARRANTY SET FORTH IN THIS SECTION GIVES YOU SPECIFIC LEGAL RIGHTS For further warranty information please contact TerraBase 14 2 Limitation of Liability for Users
34. y Redwood City California 1991 Johansson E M F U Dowla and D M Goodman Backpropagation learning for multi layer feed forward neural nets using the conjugate gradient method Lawrence Livermore National Laboratory 1990 Kaiser K L E Neural networks for effect prediction in environmental and health issues using large datasets QSAR Comb Sci 22 185 190 2003 http www wiley vch de 80 contents c_2022 200302 html Kaiser K L E The use of neural networks in QSARs for acute aquatic toxicological endpoints J Mol Struc Theochem 622 85 95 2003 http dx doi org 10 1016 S0166 1280 02 00620 6 Kaiser K L E S P Niculescu and G Schitiirmann Feed forward backpropagation neural networks and their use in predicting the acute toxicity of chemicals to the fathead minnow Water Quality Res J Canada 32 637 657 1997 http www cciw ca wqrjc 32 3 32 3 637 htm Kaiser K L E S P Niculescu and K M Gough Neural network modeling of Vibrio fischeri and fathead minnow acute toxicity data with molecular indicator variables and physico chemical bulk parameters Poster Workshop on Computational Methods in Toxicology Dayton OH April 20 22 1998 http www ccl net ccl toxicology abstracts abs14 html Kaiser K L E and S P Niculescu Using probabilistic neural networks to model the toxicity of chemicals to the fathead minnow Pimephales promelas A study based on 865 compounds Chemosphere 38
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