Evan C. Lemley 5473 elemley@ucok.edu Engineering and Physics Mathematics and Science 87 Investigation of the Relationship of Renal Artery Flow to Systemic Hypertension May 1, 2009 NIH - Oklahoma INBRE II Junior Investigator Award 109,663 279,38 0 0 3/24/2008 Nov. 30, 2011 1. Copy of Application Guidelines. Oklahoma INBRE Request for Proposals The Oklahoma IDeA Network of Biomedical Research Excellence (INBRE) will be competing for a five year grant renewal in July of 2008. INBRE is a part of the NIH Institutional Development Award (IDeA) Program, which also includes the Centers of Biomedical Research Excellence (COBRE). The goal of the IDeA Program is to increase the biomedical research capacity of the 23 participating states and Puerto Rico. More information about the Oklahoma INBRE and a copy of this request can be found at www.okinbre.org. A primary focus of the Oklahoma INBRE is to enhance biomedical research at our state s primarily undergraduate institutions (PUIs). This is accomplished through a variety of programs including summer undergraduate research experiences, start-up funds for newly recruited faculty, and by Collaborative and Mini-Grants. INBRE also provides longer term support for selected research projects, designated as Junior Investigator Awards (JIA). It is anticipated that JIA awards, with an annual budget of $85,000 (direct costs), will be made to faculty at the INBRE institutions at the beginning of the grant if the renewal is successful. The awards will be made for the first half of the grant term (2.5 years), with the understanding that these initial awardees as well as other faculty members from the PUIs will be eligible to compete for support for the final 2.5 years of the grant. We are now requesting JIA proposals that will be considered for inclusion in the INBRE grant renewal application. Faculty members from Northeastern State University, Langston University, Southwestern Oklahoma State University, Cameron University, Southeastern Oklahoma State University, and the University of Central Oklahoma are eligible to apply. Full-time, tenured or tenure-track faculty members who hold the rank of Assistant, Associate, or full Professor are eligible. PUI investigators who have already been funded by JIA for 5 years as of the end of the current INBRE grant term are not eligible to re-apply. However, those who have received 2 ½ years or less of JVA funding, as well as those who have received Collaborative or Mini-Grants, without limitation, are eligible to apply. Applicants must submit the grant application using the appropriate NIH form pages (see http://grants1.nih.gov/grants/funding/phs398/phs398.html). The narrative, which includes the Specific Aims, Background & Significance, Preliminary Data (and Progress Report for current or former INBRE JIA investigators), and Experimental Design sections is limited to 7 pages, using 1 inch margins and 12 point font. Illustrations or figures may be included in the text and will be counted against the page limitation. References, vertebrate animals, human subjects, etc. do not count against the page limit. NIH mandates that JIA investigators must devote at least 50% of their time to research and scholarly endeavors and a letter certifying institutional commitment to that effect, signed by a Department Chair or Dean, must be included with all applications. The term of awards will be two years and six months, with a start date of May 1, 2009. The maximum budget is $85,000 (direct costs) per year for the first two years (May 1, 2009 through April 30, 2011) and $42,500 (direct costs) for May 1, 2011 to Oct. 31, 2011. F&A can be added in accordance with your institutional rate. The original and 10 copies of the application must be submitted to Dawn Scott, Oklahoma EPSCoR Office, 655 Research Parkway, Suite 200, Oklahoma City, OK 73104 (dscott@osrhe.edu ph: 405-225-9459). Please be sure to route your applications through the appropriate grants administration office at your institution. Please refer programmatic questions to Darrin Akins (darrin-akins@ouhsc.edu; ph: 405-271-2133 ext. 46640). The deadline for submitting applications is 5:00 pm on March 24, 2008. 2. Abstract of Proposal Proposal Title: Investigation of the Relationship of Renal Artery Flow to Systemic Hypertension Principal Investigator: Evan Lemley, Ph.D., Professor, University of Central Oklahoma Background: A vessel irregularity such as an aneurysm in the human renal artery may cause systemic hypertension by supplying the kidneys with low blood pressure. Baroreceptors in the afferent arterioles of the kidneys function as pressure sensors by detecting the deformation of flow vessels. When flow conditions in the human renal artery lead to low pressure conditions at these baroreceptors, the kidneys release renin which is part of the Renin­Angiotensin­Aldosterone System (RAAS) that regulates systemic arterial vasoconstriction (hence systemic mean blood pressure). In the case of a low pressure signal at the renal baroreceptors the release of Renin leads to an increase in systemic blood pressure. Despite the knowledge that a low pressure signal will engage the RAAS, there has been no flow mechanisms identified by which an aneuysm will generate a low pressure in the kidneys. Hypothesis/Objective: The long­term objective of the proposed research is to establish the connection of renal artery geometry to the appearance of systemic hypertension due to low pressures at the renal baroreceptors. The goal of the research projects in the proposal is to identify aneurysm geometries that cause large pressure losses in terms of size, shape, and location by conducting flow experiments in combination with simulations. Flow and pressure measurements will be made on models of various aneurysm geometries. Specific Aims: (1) To use flow simulations to determine a set of aneurysm geometries that lead to low pressure conditions in the kidneys (2) To perform experiments on models identical to the simulations in (1) with pulsatile flow conditions to measure pressure losses and flow rates at key positions in the models (3) To use flow visualization techniques such as particle image velocimetry (PIV) to confirm the causes for large pressure losses by direct observation of the flow field. Study Design: As part of a ongoing American Chemical Society – Petroleum Research Fund (ACS­ PRF) grant (PI – Evan Lemley) to measure pressure losses in millimeter scale flow junctions, a research group at UCO has developed methods of creating models of flow geometries that are first simulated then made from acrylic for experiments. This project is conducted in collaboration with a research group at OU and related to an initial project to simulate flow in porous media. Another research group at OU has begun to simulate flow in renal artery aneurysms. Physical models of renal aneurysms will be created using the techniques already developed by the group at UCO. The models will be constructed either from acrylic on a computer­controlled milling machine in the UCO Engineering and Physics Department or from silicone from molds made on a 3­D printer that will be obtained by by the UCO Engineering and Physics Department in the next academic year. Measurements will be made by providing pressure, flow, and fluid property matches to OU simulations of renal artery aneurysms. The experimental system to provide the appropriate conditions and ability to measure pressure and flow rates is already under construction at UCO to support measurements needed as part of the ACS­PRF grant. Aneurysm geometries found to create low pressures in simulations by OU collaborative group will be constructed and used in the experimental system currently under construction at UCO. Flow and pressure measurements will be made to validate the simulations that have been conducted. Flow visualization and complete flow field measurements will be performed to gain additional insight into the flow in these low pressure geometries. The flow visualization and complete flow field mapping will be made in collaboration with an OU Mechanical Engineering faculty member that has a PIV system. Collaborations: This proposed research will be conducted with close collaboration between the University of Central Oklahoma (UCO) and the the University of Oklahoma (OU). Initial simulation of renal artery aneurysms has been performed by an existing group at OU in the School of Chemical Engineering and Materials Science (Faculty: Drs. Edgar O'Rear and Dimitrios Papavassiliou) . The OU group will determine additional flow geometries to investigate. The research group at UCO (Faculty: Drs. Evan Lemley and Jaehoon Seong) will simulate flow in these identified geometries and construct replicas of the simulation geometries, which will be used within a test system to measure pressure and flow. Finally, the PIV system in the OU School of Mechanical Engineering (Dr. Ramkumar Parthasarathy) will be used on the system on a small number of aneursym geometries that have demonstrated large pressure losses. 3. Budget (Years 1­3) and Budget Justification Principal Investigator/Program Director (Last, first, middle): Lemley, Evan, C. DD DETAILED BUDGET FOR INITIAL BUDGET PERIOD PERSONNEL (Applicant organization only) NAME Lemley, Evan C. Seong, Jaehoon TBD ROLE ON Cal. PROJECT Mnths Principal Investigator Co­ Investigator Teaching replacement THROUGH 4/30/2010 DOLLAR AMOUNT REQUESTED (omit cents) Months Devoted to Project FROM 05/01/09 DIRECT COSTS ONLY Acad. Summer Institution Base Mnths Mnths Salary SALARY FRINGE REQUESTED BENEFITS TOTALS 5 1 95,303 9,530. 3,240. 12,771. 0 1 70,510 6,700. 2,278. 8,978. 24,000 12,000. 4,080. 16,080. 6 12,000. 960. 12,960. 3 7,200. 576. 7,776. 47,430. 11,134. 58,565. 5 Undergrad TBD TBD Res Assistant Grad Res Assistant SUBTOTALS CONSULTANT COSTS Consultation for Drs. Papavassiliou and O'Rear ($200/month/person) EQUIPMENT (Itemize) Computer and data acquisition hardware 10,000. 5,070. Pressure and flow sensors SUPPLIES (Itemize by category) 4,800. Plastic and acrylic 1,000. Chemicals 750. Consumables 1,815. PATIENT CARE COSTS TRAVEL 3,000. INPATIENT OUTPATIENT ALTERATIONS AND RENOVATIONS (Itemize by category) 0. OTHER EXPENSES (Itemize by category) SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD CONSORTIUM/CONTRACTUAL DIRECT COSTS COSTS FACILITIES AND ADMINISTRATION COSTS (52% salary and wages) TOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD (Item 7a, Face Page) PHS 398 (Rev. 4/98) (Form Page 4) Page Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.. $ 85,000. $ 109,663. 24,664. DD Principal Investigator/Program Director (Last, first, middle): Lemley, Evan C. DD FROM DETAILED BUDGET FOR INITIAL BUDGET PERIOD 05/01/10 4/30/2011 DOLLAR AMOUNT REQUESTED (omit cents) DIRECT COSTS ONLY PERSONNEL (Applicant organization only) Months Devoted to Project Acad. ROLE ON NAME Lemley, Evan C. Seong, Jaehoon TBD PROJECT Cal. Mnths Mnths Principal Investigator Co­ Investigator Teaching Summer Institution Mnths Base SALARY FRINGE Salary REQUESTED BENEFITS TOTALS 5 1 98,162 9,816. 3,338. 13,154. 0 1 72,625 6,901. 2,346. 9,247. 24,000 12,000. 4,080. 16,080. 6 12,000. 960. 12,960. 6 14,400. 1,152. 15,552. 55,117. 11,876. 66,993. 5 replacement THROUGH Undergrad TBD TBD Res Assistant Grad Res Assistant SUBTOTALS CONSULTANT COSTS EQUIPMENT (Itemize) SUPPLIES (Itemize by category) Consultation for Drs. Papavassiliou and O'Rear ($200/month/person) 4,800. Pressure and flow sensors 3,000. Plastic and acrylic Chemicals Consumables 2,000. 1,320. 2,887. 4,000. TRAVEL PATIENT CARE COSTS INPATIENT OUTPATIENT ALTERATIONS AND RENOVATIONS (Itemize by category) 0. OTHER EXPENSES (Itemize by category) SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD CONSORTIUM/CONTRACTUAL DIRECT COSTS COSTS FACILITIES AND ADMINISTRATION COSTS (52% salary and wages) TOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD (Item 7a, Face Page) PHS 398 (Rev. 4/98) (Form Page 4) Page Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.. $ 85,000. 28,661. 113,661. DD Principal Investigator/Program Director (Last, first, middle): Lemley, Evan C. DD DETAILED BUDGET FOR INITIAL BUDGET PERIOD Months Devoted to Project Acad. ROLE ON NAME Lemley, Evan C. Seong, Jaehoon TBD PROJECT Cal. Mnths Principal Investigator Mnths Institution SALARY FRINGE Base Salary REQUESTED BENEFITS TOTALS 0 101,107 0. 0. 0. 0 1 74,804 6,901. 2,346. 9,247. 24,000 6,000. 2,040. 8,040. 3 6,000. 480. 6,480. 3 7,200. 576. 7,776. 26,101. 5,442. 31,543. Investigator replacement Mnths 11/30/2011 DOLLAR AMOUNT REQUESTED (omit cents) 2.5 Co­ Teaching Summer THROUGH 05/01/11 DIRECT COSTS ONLY PERSONNEL (Applicant organization only) FROM 2.5 Undergrad TBD TBD Res Assistant Grad Res Assistant SUBTOTALS CONSULTANT COSTS Consultation for Drs. Papavassiliou and O'Rear ($200/month/person) 2,400. Plastic and acrylic Chemicals Consumables 2,000. 2,160. 2,397. EQUIPMENT (Itemize) SUPPLIES (Itemize by category) 2,000. TRAVEL PATIENT CARE COSTS INPATIENT OUTPATIENT ALTERATIONS AND RENOVATIONS (Itemize by category) 0. OTHER EXPENSES (Itemize by category) SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD CONSORTIUM/CONTRACTUAL DIRECT COSTS COSTS FACILITIES AND ADMINISTRATION COSTS (52% salary and wages) TOTAL DIRECT COSTS FOR INITIAL BUDGET PERIOD (Item 7a, Face Page) PHS 398 (Rev. 4/98) (Form Page 4) Page Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.. $ 42,500. 13,573. $ 56,073. DD JUSTIFICATION: FOLLOW THE BUDGET JUSTIFICATION INSTRUCTIONS EXACTLY. USE CONTINUATION PAGES AS NEEDED. PERSONNEL Dr. Evan C. Lemley, Principal Investigator Dr. Evan Lemley is a mechanical engineer with a strong background in fluid dynamics. He currently is a Professor of Engineering and Physics at the University of Central Oklahoma (UCO). He has recently been awarded a grant by the American Chemical Society Petroleum Research fund to perform simulations and experiments in arbitrary flow bifurcations at a small scale. His research group has written computer programs to create three-dimensional models, perform fluid flow simulations, and construct physical models of arbitrary flow bifurcations, which are similar to the networks proposed here. Dr. Lemley's research group has also begun construction of a low pressure measurement system that may be used for the proposed project. Dr. Lemley will lead the research effort by coordinating the research effort of all investigators. He will also perform the experiments on selected high pressure loss renal aneurysm geometries. He will coordinate efforts with collaborators at the University of Oklahoma, who will be running flow simulations on various renal aneurysm geometries. Dr. Lemley will devote 50% of his time to the project during the academic year and in the summer. Dr. Lemley will only receive salary for the project at 50% during the summer. The amounts shown on the budget reflect a 3% increase from Dr. Lemley's current base salary per year of the project and 34% fringe benefits. Dr. Jaehoon Seong, Co-Investigator Dr. Seong is a biomedical engineer and new faculty member and Assistant Professor in the Department of Engineering and Physics at the University of Central Oklahoma. He is an expert in experimental fluid dynamics in biological systems, and in biofluid flows near brain aneurysms. Dr. Seong has significant recent experience in design of experiments to measure and observe flow near brain aneurysms including use of particle image velocimetry (PIV) systems to directly observe the flow field. He will advise the research team on the design and implementation of the experimental system and the use of PIV to observe flow. Dr. Seong will also participate in all experimental data analysis. Dr. Seong will serve as a consultant throughout the academic year and be committed for one month during the summer. The amounts shown on the budget reflect a 3% increase from Dr. Seong's current base salary per year of the project and 34% fringe benefits. Dr. Dimitrios V. Papavassiliou, consultant Dr. Papavassiliou is a chemical engineer with over 10 years experience in computational fluid dynamics (CFD) applied to numerous flow problems such as bio-flow, porous media, and flow in carbon nanotubes. He has extensive experience with flow modeling and the interpretation of CFD results and comparison to experimental results. He is presently an Associate Professor in the School of Chemical, Biological, and Materials Engineering at the University of Oklahoma. He has been collaborating with the PI on flow in porous media and laminar flow in microtubes for the past three years. He will serve as a consultant to Dr. Lemley s research team, providing service for the proposed experiments and comparison of experimental results to CFD studies along with guidance on appropriate experiments. The requested consulting fee for Dr. Papavassiliou is $200/month throughout the period of the project. Dr. Edgar J. O'Rear, consultant Dr. O'Rear is a chemical engineer with experience in biotransport phenomena, biorheology, and surfactant science. He has extensive experience with bio-flow modeling and the interpretation of CFD results and comparison to experimental results. He is presently the Francis W. Winn Professor for Chemical, Biological, and Materials Engineering and the Director of the Bioengineering Center at the University of Oklahoma. He has been collaborating with the Dr. Papavassiliou on simulations of flow in renal artery aneurysm geometries for the past two years. He will serve as a consultant to Dr. Lemley s research team, providing service for the proposed experiments and comparison of experimental results to CFD studies along with guidance on appropriate experiments. The requested consulting fee for Dr. O'Rear is $200/month throughout the period of the project. To Be Determined, Teaching Replacement Teaching replacement is needed for the reduced teaching duties of the PI. The requested funding is for the replacement salary of $12,000/year for Year 1 and Year 2 (each five months) and $6,000 for Year 3 (2.5 months), plus 34% benefits. To Be Determined, Undergraduate Research Assistant The planned experiments require an undergraduate student research assistant on the research team. This person will have experience in basic fluid mechanics, and computer acquisition of pressure and flow data. He/she will be identified when the proposal is funded. He/she will assist the PI in all aspects of the experiments and simulations. He/she will devote 50% (20 hours per week) of his/her time during the academic year and summer. The required funds are to provide part of his/her stipend and benefits. To Be Determined, Graduate Research Assistant The planned experiments require a graduate student research assistant on the research team. This person will have experience in fluid mechanics and computational engineering. He/she will be identified when the proposal is funded. He/she will assist the PI in all aspects of the simulations and will assist as necessary with experiments. He/she will devote 25% (10 hours per week) of his/her time during the academic year and summer. The required funds are to provide part of his/her stipend and benefits. MATERIALS AND SUPPLIES MATERIALS Computer and data acquisition hardware Sensors and related electronics and accessories ($5070 year 1, $3,000 year 2) SUPPLIES Acrylic, Plastic, Aluminum for experimental system structure ($1,000 year 1, $2,000 year 2, and $2,000 year 3) Chemicals - fluids for experiments ($750 year 1, $1,320 year 2, and $2,160 for year 3) Consumables tubing, fittings, pumps, etc. ($1,815 year 1, $2,887 year 2, and $2,397 year 3) $18,070 $10,000 $8,070 $16,429 $5,000 $4,230 $7,099 TRAVEL $9,000 The requested travel funds are for the PI to attend the American Society for Mechanical Engineers (ASME) Annual Fluids Engineering Conference, the Biomedical Engineering Society (BMES) Annual Fall Meeting, and other related professional research conferences. $3,000 is requested for year 1, $4,000 for year 2, and $2,000 for year 3. 4. UCO Commitments ● Space for Experiments ○ may require some remodeling of Howell 111 – currently being considered by Dept. of Engineering and Physics ● Teaching Replacement – (Lemley will have 50% release during academic year) – grant will supply funding for the teaching replacement. ● Use of Dept. of Engr. and Phys. facilities such as computer­ controlled milling machine and shop. 5. IRB – Not Applicable