BACKGROUND

INCA is a MATLAB-based software package for isotopomer network modeling and metabolic flux analysis (MFA). The software can simulate both steady-state and transient isotope labeling experiments using the elementary metabolite unit (EMU) method. It can also estimate pathway fluxes based on extracellular flux measurements, pool size measurements, and/or mass isotopomer measurements supplied to the program. The software can perform a variety of statistical tests to determine goodness-of-fit, to compute parameter confidence intervals (i.e., uncertainty), and to assess model identifiability. It can also perform constraint-based analysis of metabolic networks (e.g., flux balance analysis, flux coupling analysis, etc.) and optimize the design of isotope labeling experiments using computational search algorithms. Licensors seeks to advance this research and to publish and enable adoption of research codes in furtherance of its public interest mission. Distribution of research codes as a research courtesy is facilitated by licensing these codes for development and use. Development of these codes was supported, in part, by the following sponsors: the National Institutes of Health, Grant Number DK072856.

DEFINITIONS

1. "Agreement" means this Non-Exclusive Software Site License Agreement.
2. "Effective Date" means the latest date upon which this Agreement is either entered into or renewed.
3. “Licensors” in this agreement means Vanderbilt University and Massachusetts Institute of Technology.
4. "Licensing Contact" means the individual identified on the Registration Page and who shall be responsible for administering this Agreement on behalf of the Licensee.
5. "Modifications" mean any changes or extensions introduced into the Software or otherwise based on or derived from the Software source statements by Licensors. Modifications include, but are not limited to, corrections of program errors, translations and stylistic restructuring of the Software, addition or deletion of functions or enhancement of existing functions of the Software, changes or additions required to integrate the Software into other applications or to allow the Software to run under alternative operating systems or computer hardware configurations, and other adaptations of the Software.
6. "Registration Page" means the portion of the web site used by Licensees to enter information permitting the licensing of the Software.
7. "Site" means a single personal computer on which the Software will be used and maintained. Site(s) authorized to maintain the Software is (are) are those designated on the Registration Page.
8. "Software" means the current version of the INCA software package as available on the Effective Date and listed on Attachment A.
9. "Technical Contact" means the individual authorized by Licensee to receive the Software and conduct all technical correspondence with Licensors as listed on the Registration Page.

GRANT

Commencing on the Effective Date, and provided that Licensee abides by the terms of this Agreement including, but not limited to, the provisions of Section 7, Licensors hereby grants, and Licensee accepts, a limited, non-exclusive, non-transferable license to use the Software and any Modification provided by Licensors, at the Site(s), and to make such copies of the Software in original or modified form as are necessary for such use at the Site(s). Licensee shall under no circumstances make any modifications to the Software itself, or analyze for composition, structure, reverse engineer or decompile the Software or attempt to do so. These Grants are limited to Licensee’s use at the Site and do not authorize use of the Software by third parties at the Site or by anyone not located at the Site via the Internet or any other means. Licensee shall obtain no ownership in the Software under this Agreement, and with the exception of applying Licensors-provided Modifications (or "updates"), shall not modify the Software or the accompanying documentation in any way, for any reason. Licensee shall retain in the Software the proprietary notices and legends as provided by Licensors, including without restriction any and all copyright, trademark, patent notices and legends pertaining to attribution, source of developments, funding sources, and disclaimer of risk and, at the request of Licensors, shall promptly modify such proprietary notices and legends to conform to Licensors’ reasonable requirements. Licensee shall not distribute, publish, or otherwise transfer or allow to be transferred, the Software or copies thereof, in whole or in part, without prior written permission of Licensors. Licensee acknowledges and agrees that Licensors Software (including Modifications) contains valuable proprietary information and trade secrets developed, licensed or acquired by Licensors.

USE OF NAMES

Licensee shall not use the name "Vanderbilt University" or any abbreviation thereof, or the names of any Vanderbilt personnel or identifiers of the Software without prior written approval from Vanderbilt. In addition, Licensee shall not use the name of "Massachusetts Institute of Technology," "Lincoln Laboratory" or any variation, adaptation, or abbreviation thereof, or of any of MIT’s or Lincoln Laboratory’s trustees, officers, faculty, students, employees, or agents, or any trademark owned by M.I.T., in any promotional material or other public announcement or disclosure without the prior written consent of M.I.T., which consent M.I.T. may withhold in its sole discretion.

DELIVERY

Licensors shall provide Licensee access to the Software by means of an internet transmission (HTTP download) following execution of this Agreement. Licensee authorizes delivery of the Software to be made to the Technical Contact.

UPDATES

Licensors will provide updates to the Software, in Licensors’ sole discretion, on an "as available" basis during the term of this Agreement. Upon delivery, all such updates shall thereafter be considered part of the Software.

TERM

This Agreement shall remain effective for a term of up to twelve (12) months from the Effective Date or any anniversary date upon which this Agreement has been renewed ("Termination Date", which due to system constraints shall be December 31 or otherwise the last day of any given calendar year) unless sooner terminated as provided herein. Licensee may renew the Agreement on or before any Termination Date. If Licensee does not renew this before the Termination Date, the license granted herein shall terminate in its entirety.

TERMINATION

This Agreement will terminate without further action by or notice from Licensors for any future period for which Licensee has not abided by the terms of this Agreement including, but not limited to, the provisions of Section 7. Licensee may terminate this Agreement at any time upon written notice to Licensors. Licensors may terminate this Agreement immediately upon notice if Licensee is in material breach of this Agreement. The provisions under which this Agreement may be terminated will be in addition to any and all other legal remedies which either party may have for the enforcement of any and all terms hereof, and do not in any way limit any other legal remedy such party may have. Termination of this Agreement will terminate all rights and licenses granted to Licensee relating to the Software. Licensee shall certify in writing to Licensors within ten (10) days after Termination that the Software has been destroyed.

LICENSEE STATUS AND OBLIGATIONS

1. This "Non-Exclusive Software Site License Agreement" shall be available to any academic or otherwise not-for-profit institution that uses the Software solely for research purposes and provided that such Licensee abides by the terms of this Agreement including, but not limited to, the provisions of this Section 7.
2. If Licensee wishes to use or make available the Software for any commercial purposes, including fee-based service projects, Licensee shall need to enter into a separate license agreement with Licensors and pay a licensing fee. In the event Licensee wishes to obtain such a commercial use license, Licensee must contact Vanderbilt’s Center for Technology Transfer and Commercialization, 1207, 17th Avenue South, Suite 105, Nashville, Tennessee 37212 Attn: INCA Licensing. Furthermore, licensee shall not modify the Software or written materials or documentation related to the Software in any way. In particular, all Licensors’ copyright, trademark, or other notices contained in the Software or written materials or documentation must be maintained by Licensee. Licensee hereby agrees to provide the developers of the Software in the Jamey Young Laboratory at Vanderbilt with comprehensive feedback on the use of the Software in Licensee’s research which information Vanderbilt shall be permitted to use in evaluating and making changes to the Software. All bug reports and technical questions shall be sent via the VU e-Innovations contact form [http://vueinnovations.com/contact].
3. Licensors and Licensee will each acknowledge in their respective publications relating to their research utilizing the Software the contributions made by the other party.

AMENDMENT OF THIS AGREEMENT

Licensors may amend this Agreement, in its sole and absolute discretion, at any time or from time-to-time during the Term or after a Termination Date. Such amendments may include, but not be limited to, the assessment of a license fee for use of the Software.

LIMITED SUPPORT; UPDATES

Licensee shall receive reasonable assistance by email and access to updates and new releases of the Software, which Licensors may make available from time to time within its sole discretion ("Limited Support"). Limited Support is provided by queries sent via the VU e-Innovations contact form [http://vueinnovations.com/contact] or other contact point as may be designated by Licensors from time to time. In order for Licensee to receive the Limited Support set forth herein, Licensee must be using the latest version and all current releases and updates of the Software. If Licensors generally makes available new versions of the Software, the new versions will be available to Licensee at the discretion of Licensors. Limited Support does not include responding to Licensee if, in Licensors’ reasonable opinion, Licensee fails to provide sufficient information, as reasonably requested by Licensors, to enable Licensors to identify, reproduce and analyze the reported problem; Licensors reserves the right to charge additional fees for such support.

DISCLAIMERS

The Software has been developed as part of research conducted at Vanderbilt University and Massachusetts Institute of Technology. The Software is experimental in nature and is available "AS IS," without obligation by Licensors to provide Licensee services or support except as specified in this Agreement. The entire risk as to the quality and performance of the Software is with Licensee. TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, LICENSORS DOES NOT MAKE AND EXPRESSLY DISCLAIMS ALL WARRANTIES WITH RESPECT TO THE SOFTWARE AND SUPPORT, INCLUDING, WITHOUT LIMITATION, THE IMPLIED WARRANTIES OF TITLE, NON-INFRINGEMENT (OF BOTH LICENSORS’ INTELLECTUAL PROPERTY RIGHTS AND THIRD PARTY INTELLECTUAL PROPERTY RIGHTS), VALIDITY, ENFORCEABILITY AND SCOPE OF THE INTELLECTUAL PROPERTY RIGHTS ASSOCIATED WITH THE SOFTWARE, THE ABSENCE OF LATENT OR OTHER DEFECTS, MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE, REGARDLESS OF WHETHER LICENSORS KNOWS OR HAD REASON TO KNOW OF LICENSEE’S PARTICULAR NEEDS. NO EMPLOYEE, AGENT, DEALER OR DISTRIBUTOR OF LICENSORS IS AUTHORIZED TO MODIFY THE LIMITED WARRANTY, OR TO MAKE ANY ADDITIONAL WARRANTIES. SOME COUNTRIES AND STATES DO NOT ALLOW THE EXCLUSION OF IMPLIED WARRANTIES, SO THE ABOVE EXCLUSION MAY NOT APPLY. THIS WARRANTY GIVES LICENSEE SPECIFIC LEGAL RIGHTS, AND LICENSEE MAY ALSO HAVE OTHER RIGHTS WHICH VARY FROM COUNTRY TO COUNTRY OR STATE TO STATE Licensors’ entire liability and Licensee’s exclusive remedy for a breach of this Agreement shall be termination of this Agreement by returning or destroying the Software. Licensors shall have no liability for consequential, exemplary, indirect, special, punitive or incidental damages whether based on contract, tort or any other legal theory, arising out of or related to this Agreement or the inability to use the Software or Limited Support, nor shall Licensors be liable for any loss of data or lost profits of Licensee, even if Licensors is apprised of the likelihood of such damages occurring. SOME COUNTRIES OR STATES DO NOT ALLOW THE LIMITATION OR EXCLUSION OF LIABILITY FOR INCIDENTAL OR CONSEQUENTIAL DAMAGES, SO THE ABOVE LIMITATION MAY NOT APPLY IN THOSE JURISDICTIONS.

INDEMNIFICATION

Licensee shall indemnify, defend and hold harmless Licensors and its officers, trustees, faculty, staff, employees, students, agents and their respective successors or assigns against any and all claims, suits, losses, damages, costs, fees and expenses resulting from Licensee’s possession and/or use of the Software (including any Modifications), including by not limited to any damages, losses or liabilities whatsoever with respect to death or injury to any person and damage to any property. This indemnification clause shall survive the termination of this Agreement.

COMPLIANCE WITH LAWS

Vanderbilt and Licensee will comply with all federal, state and local laws and regulations, as amended from time to time, applicable to such party’s performance of its obligations under this Agreement, including all applicable export controls and economic sanctions laws and regulations of the United States and other applicable jurisdictions. Further, because the provision of a “service” under U.S. economic sanctions is generally prohibited without a license, Vanderbilt will block the IP addresses of persons located in Iran, Syria, Republic of Sudan, Cuba, North Korea or any other country to which the provision of such services is prohibited and will take reasonable steps to exclude participation of persons identified on the U.S. Treasury Department’s List of Specially Designated Nationals, Blocked Persons and Foreign Sanction Evaders, except as licensed otherwise authorized by the U.S. Government.

NOTICES

All notices required or permitted relating to a claim or breach of this Agreement shall be in writing and sent to: (i) if to the Licensee: to the Licensing Contact; and (ii) if to Licensors: Center for Technology Transfer and Commercialization, 1207 17th Avenue South, Suite 105, Nashville, Tennessee 37027, Attn: INCA Software. Either party may change their address from time to time by written notice to the other and shall be deemed validly given upon receipt of such notice given by certified mail, postage prepaid, or personal or courier delivery. All Limited Support or other notices relating to the usage of the Software will be provided by Licensors either via telephone or e-mail.

GENERAL

This Agreement will be construed in accordance with, and its performance will be governed by, the laws of the State of Tennessee, excluding its conflict of laws principles. Any suit, action, or proceeding arising out of or relating to this Agreement will be decided in Davidson County, Tennessee. Licensee accepts the venue and jurisdiction of the Federal District Court of Middle Tennessee or the state courts in Davidson County, Tennessee. Headings are provided for convenience only. No omission or delay of either party hereto in requiring due and punctual fulfillment of the obligations of any other party hereto shall be deemed to constitute a waiver by such party of its rights to require such due and punctual fulfillment, or of any other of its remedies hereunder. Licensee shall not assign or transfer this Agreement or any of its rights or obligations hereunder, whether by operation of law or otherwise, without the prior written consent of Licensors. Licensors may assign its rights or obligations hereunder without the consent of or notice to Licensee. This Agreement shall inure to the benefit of and bind successors and permitted assigns of Licensors and Licensee. If any provision of this Agreement shall be held to be invalid, illegal or unenforceable, the validity, legality, and enforceability of the remaining provisions will not be in any way affected or impaired thereby. In the event either party hereto is prevented from or delayed in the performance of any of its obligations hereunder by reason of acts of God, war, strikes, riots, storms, fires or any other cause whatsoever beyond the reasonable control of the non-performing party, the non-performing party shall be excused from the performance of any such obligation to the extent and during the period of such prevention or delay. This Agreement embodies the entire understanding of the parties and supersedes all previous communications, representations, or understandings, either oral or written, between the parties relating to the subject matter hereof.

ATTACHMENT A — SOFTWARE DESCRIPTION

INCA is a MATLAB-based software package for isotopomer network modeling and metabolic flux analysis (MFA). The software can simulate both steady-state and transient isotope labeling experiments using the elementary metabolite unit (EMU) method [1,2]. It can also estimate pathway fluxes based on extracellular flux measurements, pool size measurements, and/or mass isotopomer measurements supplied to the program. The software can perform a variety of statistical tests to determine goodness-of-fit, to compute parameter confidence intervals (i.e., uncertainty), and to assess model identifiability. It can also perform constraint-based analysis of metabolic networks (e.g., flux balance analysis, flux coupling analysis, etc.) and optimize the design of isotope labeling experiments using computational search algorithms.

The software provides a framework for comprehensive analysis of metabolic networks using mass balances and isotopomer balances. The generation of balance equations and their computational solution is completely automated and can be performed on networks of arbitrary complexity. The graphical user interface (GUI) allows the user to input reaction information and experimental data in a simple format, while offering a variety of powerful analysis tools to design and interpret isotope labeling experiments. All INCA data objects can be loaded and manipulated from the MATLAB command line, and the driver routines can be called directly from the command line or invoked within custom MATLAB scripts. INCA also offers built-in parallelization capabilities for running certain functions within a distributed computing environment.

Licensees and users of INCA are hereby informed that the operation of INCA requires the operation of “FindJObj”, a third party code. A license for this “FindJObj” code is included as Attachment B herein.

Further information about projects and publications related to this software can be found at www.Vanderbilt.edu/younglab.

ATTACHMENT B — LICENSE FOR “FINDJOBJ”

Copyright (c) 2009, Yair Altman All rights reserved.

Redistribution and use in source and binary forms, with or without modification, are permitted provided that the following conditions are met:

1. Redistributions of source code must retain the above copyright notice, this list of conditions and the following disclaimer.
2. Redistributions in binary form must reproduce the above copyright notice, this list of conditions and the following disclaimer in the documentation and/or other materials provided with the distribution

THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.