Dale Baker - US grants

DESCRIPTION (Adapted from the Applicant's Abstract): The goal of this project is to develop an implantable combination lactate/oxygen sensor that can continuously and simultaneously monitor blood lactate and oxygen concentration. This project will use and integrated approach of engineering and physiological techniques aimed t development of an acceptable biosensor that can be used for basic research applications and for clinical m monitoring in critical care units. There is a need in research and clinical medicine for an implantable lactate/oxygen sensor which can continuously monitor lactate and oxygen concentration at specific sits in the body. Hypoxic and ischemic conditions cause significant changes in blood lactate concentration. The role of lactate concentration as indicator in these labile conditions can be investigated dynamically with the combination in vivo lactate/oxygen sensor as proposed here. This sensor has potential diagnostic, prognostic and therapeutic value for myocardial ischemia, circulatory shock, acidosis, exercise physiology, cardiac rehabilitation, surgery and neonatal monitoring. A systematic approach of theoretical modeling, in vivo experiments will be used to develop a reliable lactate sensor. A mathematical model that describes the physical and chemical process within the sensor will be use for sensor design and signal interpretation. This model will predict the influence of pertinent sensor parameters (geometric, diffusive, kinetic, and equilibrium) on the sensor response. This direct modeling approach for sensor design and signal interpretation avoids the time consuming trial and error approach commonly used in biosensor development. In vitro experiments will be conducted with sensors that are fabricated having the design features suggested from the modeling studies, the purpose of the in vitro experiments is to completely characterize the sensor response and validate the sensor design before the sensor is implanted, After the sensor design is refined by the modeling and in vitro experiments, the sensor will be assessed for their performance in blood during intravascular implantation in dogs and rats. These implant studies will allow evaluation of the enzyme catalytic lifetime chemical interference, biocompatibility and overall sensor reliability. The fully characterized sensor will then be used in studies of myocardial ischemia and in the evaluation of blood substitutes.

The WISE Investments project is multifaceted and is designed to encourage females in middle, high school and community colleges to pursue engineering and related careers by: 1) teaching middle and high school math and science teachers to help students understand engineering as a helping profession; 2) teaching middle and high school guidance counselors to support and encourage pre-college young women to pursue engineering and related careers; 3) teaching community college math and science faculty to include gender-inclusive engineering applications of math and science, along with engineering career information, in their classrooms; 4) teaching community college advisors and counselors to support and encourage community college women to pursue engineering and related fields; 5) educating parents (or another significant adult) of young women in middle and high school about educational and career opportunities in engineering, and by assisting parents to encourage their daughters' continued enrollment in higher-level precollege math and science courses; and 6) giving young women in middle and high school a single sex environment to explore engineering, providing them with engineering mentors, and giving them exposure to higher education and engineering-related industries.
Middle and high school math and science teachers, along with a district representative from each of the six participating school districts, will participate in a two-week summer workshop. Middle and high school counselors will be teamed with teachers from their school and will participate in an abbreviated workshop. Community college faculty and advisors, who will also be placed in same-school teams, will participate in their own two-week summer workshop. Educator and counselor participants will also participate in a two-week internship with an engineering-related company.
Educators and counselor/advisors workshops will include hands-on engineering labs, exposure to engineering-related industry through tours and speakers, opportunity to develop engineering applications and outreach activities for their classrooms/campuses, and gender-equity training. The two-week internship will allow participants to gain an understanding of engineering in a real-world setting. Participants will be involved in an electronic forum throughout the duration of the project and will participate in follow-up activities, including dissemination activities. A mentor team consisting of an engineering faculty member, an industry representative, and an engineering student will be paired with each educator/counselor team.
Middle and high school girls will participate in hands-on engineering applications developed by the teacher teams, gain exposure to engineers and engineering-related industry through tours and speakers, and be paired with a trained female undergraduate engineering student mentor, who in turn will have her own mentor. Parents will receive information about engineering and how to encourage their daughters in math and science, and will gain exposure to engineers and engineering-related industry.
An end-of-the-year banquet will pull the various components together and celebrate the participant's accomplishments. A poster session of the educators teams' efforts will be displayed, and one team will be selected to present on their involvement at a regional or national education conference.
These project components will give women and girls more information about, and create a positive affective response to, engineering. The project will also develop a support network for their pursuit of engineering and related fields. The interventions will serve to ultimately increase the number of women pursuing degrees in engineering and related fields. Outcomes for the project will include: 1) an increased knowledge of engineering careers and activities by each of the six target groups (listed above), 2) an increased interest in engineering and related fields by precollege and community college student participants, 3) an increase in plans to pursue engineering and related fields by precollege and community college student participants, 4) a greater likelihood for precollege student participants to enroll in higher-level precollege math and science courses than members of a control group, 5) improved teacher's efforts to create a gender-inclusive classroom atmosphere, 6) an integration of engineering information and activities into teacher participants' classrooms, 7) an increased number of outreach programs for middle and high school girls interested in engineering and related fields, and 8) an increase in interest and knowledge of engineering for students in participating teachers' classrooms and students participating in counselors' outreach programs.
The project is a collaboration of the Arizona State University College of Engineering and Applied Sciences and College of Education; Northern Arizona University's Institute for Future Workforce Development; Chandler-Gilbert, South Mountain and Glendale Community Colleges; Phoenix Union High School District, Tempe Union High School District, Chandler Unified School District, Kyrene, Creighton and Roosevelt School Districts; Intel Corporation, Motorola, Lockheed Martin-Andersen Consulting, Honeywell, Boeing, Medtronic Micro-Rel, and Salt River Project; the Phoenix Urban Systemic Initiative, Arizona State Public Information Network (ASPIN), and other existing programs which will greatly enhance the impact of the WISE Investments project in terms of recruiting quality participants, informing project development, and providing dissemination outlets. The nature of this collaboration allows for the enhancement of the pipeline that creates women engineers.
Each year this comprehensive project will include 24 teachers, 6 district-level representatives, 12 counselors, 20 community college faculty, 10 community college advisors, 40 middle and high school girls and 40-80 parents. Aside from those individuals directly participating in the WISE Investments project, through the engineering applications developed by teachers and community college faculty for their classrooms, and outreach projects developed by counselors and community college advisors, the impact of the project will be felt by thousands of students over time.

NSF Proposal 9987273
Development of a Pyruvate Sensor and Instrumentation
Dale A. Baker, Ph.D.

Project Abstract

Pyruvate is a chemical, which is involved in many biological pathways and their regulation. The knowledge of its concentration is important not only in studies of human and animal physiology, but also in the control of industrial processes, such as fermentations. Currently, pyruvate is most often measured by a chemical procedure that takes several minutes to complete and requires pretreatment of turbid samples, e.g. blood, microbial growth media or food samples, in order to remove particulate matter for accurate measurement. Furthermore, the chemicals used in this method are washed away and cannot be re-used after this single measurement. Continuous measurements are not possible with this technique. To overcome these disadvantages, the pyruvate sensor in this project will use a membrane that embeds (immobilizes) an enzyme, and in conjunction with an electrode, measures the concentration of pyruvate.
A pyruvate sensor will be developed that can quantitatively and continuously monitor pyruvate concentration by using the immobilized enzyme, pyruvate oxidase, in a membrane, which is coupled to an oxygen sensitive electrode. A mathematical model that describes the chemical processes within the sensor and subsequent simulations will be used to design the sensor and better understand its operation. Experiments will be conducted with sensors that are fabricated having the design features suggested from the modeling studies. The purpose of the initial experiments is to characterize the sensor response to changes in pyruvate concentration under well-controlled conditions. These experiments will also allow validation of the sensor performance before the sensor can be considered for use in more demanding physiology studies or in bioreactors. Additionally, the role of the two major properties of the enzyme membrane, the enzyme reaction kinetics and the substrate transport, will be investigated with an experimental apparatus for membrane characterization. An engineering analysis of the predominant mechanisms affecting the enzyme performance can be completed from the data collected with this apparatus.
The pyruvate sensor will be used for basic biological research applications and has potential for studies of physiology in animals and humans. Many bacterial cultures depend on the level or control of pyruvate concentration to enhance growth or augment the production of valuable chemicals or enzyme products. In mammalian physiology, conditions of low blood flow (ischemia) or lowered oxygen levels (hypoxia) can cause significant changes in blood pyruvate concentration. The sensor will dynamically indicate any accumulation in pyruvate, which can reflect a transition from normal (aerobic) metabolism during these pathological conditions. It is anticipated that an acceptable biosensor can be developed to continuously monitor pyruvate concentration. These research studies will provide a systematic way to enhance the enzyme membrane, which is an essential component of the sensor used to detect and quantify the pyruvate. Improvements in the membrane will refine the sensitivity and stability of the complete sensor.

DESCRIPTION (provided by applicant): This application is a request for R24 funding through the National Center for Research Resources (NCRR) of the project entitled "Characterization of Defective Gamma-Glutamyl Carboxylase in Rambouillet Sheep." Human patients with hereditary deficiencies of gamma-glutamyl carboxylase have severe bleeding clinically, but more recently, acquired defects of carboxylation have been implicated in degenerative diseases of the aged such as vascular mineralization and osteoporosis. While hereditary deficiency of gamma-glutamyl carboxylase is uncommon, atherosclerosis and osteoporosis are significant diseases of the aged. A model of defective gamma-glutamyl carboxylation does not exist despite previous efforts to produce one through knockout mouse technology. The Specific Aims of this project are: (1) Develop and maintain a flock of sheep with defective gamma-glutamyl carboxylase activity equivalent to human gamma-glutamyl carboxylase deficiency, and provide affected lambs and tissue to investigators of gamma-glutamyl carboxylase; (2) verify that the genetic defects identified in the gamma-glutamyl carboxylase gene is responsible for diminished function, and develop a heterozygous carrier detection test for identification of carrier animals; (3) characterize the skeletal phenotype in defective gamma-glutamyl carboxylase of homozygous affected lambs; and (4) develop an in vitro gene therapy technique that may eventually be applied in vivo to this and other models of defective coagulation. Specific Aims 1, 2, and 4 will be performed at CSU under the supervision of Drs. Baker and Jennifer MacLeay, and Specific Aim 3 will be carried out at Yale University by Dr. Caren Gundberg. Preliminary studies in these sheep have identified the coagulation defect that occurs in homozygous affected lambs, and the underlying cause of this coagulopathy is markedly decreased gamma-glutamyl carboxylase activity. Genetic mutations of the gamma-glutamyl carboxylase gene have also been identified. These sheep represent the only known model of this defect in existence, but much of the underlying genetic and functional aspects of the abnormalities other than defective hemostasis are unknown. One ram and seven ewes are known heterozygous carriers of the gene. The investigators plan to identify and increase the numbers of known carrier rams to three and ewes to 24 to produce six homozygous affected lambs per year, and make rams and ewes available to investigators of gamma-glutamyl carboxylase.

DESCRIPTION (provided by applicant): This application is a request for R24 funding through the National Center for Research Resources (NCRR) of the project entitled "Characterization of Defective Gamma-Glutamyl Carboxylase in Rambouillet Sheep." Human patients with hereditary deficiencies of gamma-glutamyl carboxylase have severe bleeding clinically, but more recently, acquired defects of carboxylation have been implicated in degenerative diseases of the aged such as vascular mineralization and osteoporosis. While hereditary deficiency of gamma-glutamyl carboxylase is uncommon, atherosclerosis and osteoporosis are significant diseases of the aged. A model of defective gamma-glutamyl carboxylation does not exist despite previous efforts to produce one through knockout mouse technology. The Specific Aims of this project are: (1) Develop and maintain a flock of sheep with defective gamma-glutamyl carboxylase activity equivalent to human gamma-glutamyl carboxylase deficiency, and provide affected lambs and tissue to investigators of gamma-glutamyl carboxylase; (2) verify that the genetic defects identified in the gamma-glutamyl carboxylase gene is responsible for diminished function, and develop a heterozygous carrier detection test for identification of carrier animals; (3) characterize the skeletal phenotype in defective gamma-glutamyl carboxylase of homozygous affected lambs; and (4) develop an in vitro gene therapy technique that may eventually be applied in vivo to this and other models of defective coagulation. Specific Aims 1, 2, and 4 will be performed at CSU under the supervision of Drs. Baker and Jennifer MacLeay, and Specific Aim 3 will be carried out at Yale University by Dr. Caren Gundberg. Preliminary studies in these sheep have identified the coagulation defect that occurs in homozygous affected lambs, and the underlying cause of this coagulopathy is markedly decreased gamma-glutamyl carboxylase activity. Genetic mutations of the gamma-glutamyl carboxylase gene have also been identified. These sheep represent the only known model of this defect in existence, but much of the underlying genetic and functional aspects of the abnormalities other than defective hemostasis are unknown. One ram and seven ewes are known heterozygous carriers of the gene. The investigators plan to identify and increase the numbers of known carrier rams to three and ewes to 24 to produce six homozygous affected lambs per year, and make rams and ewes available to investigators of gamma-glutamyl carboxylase.

Arizona State University (ASU) in collaboration with Arizona Science Center, Boeing, Intel, Microchip, Motorola, Salt River Project, AZ Foundation for Resource Education, AZ Game & Fish Department, US Partnership for the Decade of Education for Sustainable Development, Mesa Public Schools, and Boys & Girls Clubs of the East Valley, offer a three-year extracurricular project resulting in IT/STEM-related learning outcomes for 96 participants in grades 7, 8, and 9. The project targets and engages female and minority youth traditionally under-represented in IT/STEM fields in multi-year out-of-school technological design and problem solving experiences. These include summer internships/externships and university research in the science center and industrial settings where participants develop socially responsible solutions for challenging real world problems. The program includes cognitive apprenticeships with diverse mentors, opportunities to practice workplace skills such as leadership, teamwork, time management, creativity and reporting, and use of technological tools to gather and analyze complex data sets. Participants simulate desert tortoise behaviors, research and develop designs to mitigate the urban heat island, build small-scale renewable energy resources, design autonomous rovers capable of navigating Mars-like terrain, and develop a model habitat for humans to live on Mars. Together with their families participants gain first-hand knowledge of IT/STEM career and educational pathways.

In addition to youth outcomes, the adults associated with this project are better prepared to positively influence IT/STEM learning experiences for under-represented youth. The evaluation measures participant content knowledge, attitudes and interest in IT/STEM subjects, workplace skills and intentions to pursue IT/STEM educational and career pathways to understand participant reactions, learning, transfer and results. Informal curricula developed through this project, field-tested with youth at Boys & Girls Clubs and youth at Arizona Science Center will be available on the project website.

Interdisciplinary (99)
This project (SEMI-STEM) is creating instructional materials in the "science and engineering of musical instruments" (SEMI) in order to connect student learning in each of: science, technology, engineering, and math (STEM). The project is developing and implementing a freshman math-science block course that uses science, math, engineering, and technology as a means to understand music, particularly the design of musical instruments. Although there have been courses for decades that connect science, technology, math, and music theoretically, this project is adding design and development components that culminate in the building of musical instruments. With these additions, this course is being created as a large "block" course sized at 7-credit hours. The learning context is inquiry-based. Students are learning to use engineering techniques as well as the underlying science to design, construct, and demonstrate musical instruments. The course development and instruction is being guided by an interdisciplinary team consisting of a physicist, mathematician, engineer, educator, musician, and science teacher.

Intellectual Merit: The merit of this project rests is derived from improvements that are expected to occur in the technical literacy, problem solving ability, creative thinking, and STEM self-efficacy of first-year undergraduates who complete this SEMI-STEM course. Criteria are being developed for a general approach to developing coordinated math-science-engineering courses, especially for diverse populations, by monitoring student outcomes. This entails modifying, developing, and testing assessment tools to measure changes in students' affective attributes and cognitive skills. Ways are also being created to measure each student's prior knowledge and misconceptions, and subsequent conceptual changes as the course proceeds.

Broader Impact: This project is developing a prototype methodology for integrating STEM with the fine arts and developing assessment tools to judge the effectiveness of prototype courses.

In the Phoenix metropolitan area, high-need schools often experience on-going vacancies in the teaching staff and a high turnover rate of qualified teachers. This project attempts to identify and support up to 60 qualified secondary science teachers who will persist in high-need environments. Using different methods of recruitment, in conjunction with a marketing plan, science students are being identified and recruited to participate in undergraduate or post-baccalaureate programs that have extensive field experiences with diverse students, strong content knowledge requirements, and on-going opportunities to build their understanding of science as inquiry instruction. While students are completing their initial certification course work, field placements are being arranged in high need settings that consist of students who are Native American, Latina/o, or African American. Upon graduation, STARR Noyce teachers participate in science-focused induction programs, which specifically support their use of science as inquiry in diverse classrooms, their development as science teachers, and their socialization into the school community.
Ultimately, the dissemination of these findings is expected to direct future recruitment endeavors in this area.

This project will develop an understanding of the progression of student learning in materials courses achieved through conceptual change of concept models of materials (CONCOMM). A learning progression of student conceptual knowledge and change for the topics covered across a semester would be developed, and using this progression would foster new strategies for materials teaching and learning strategies, as well as improve the effectiveness of student learning in materials classes. New misconception-compensated instructional materials would be developed to address students' misconception related issues. This approach would be not be limited to materials courses in the materials discipline, but could be used in materials courses for other disciplines as well as new types of nanotechnology courses now being created and taught. The CONCOMM approach will utilize rapid feedback technological tools of Just-in-Time-Teaching and Personal Response Systems to quickly characterize and address misconceptions. It could also be used to study and characterize potential differences of conceptual change for diverse populations which would allow the modification to instructional materials for more effective learning for diverse student populations. A final point is that a general toolkit of misconception-eliciting-methods will be defined which could be used by any engineering discipline to explore students' prior knowledge and misconceptions and then address them to improve teaching effectiveness.

Nanotechnology is one of the leading edge technologies that must be effectively taught to engineering students who will be ready to compete in the global economy. This research will create a framework and instructional materials for the CONCOMM technique which uses rapid accommodation of misconceptions in materials instruction to promote more effective conceptual change, improve the effectiveness of teaching and learning of materials, and build a general model that would have potential for broader application. Effective implementations and assessment and will be developed to measure the effect of the CONCOMM technique on student learning and the instructional materials will be widely disseminated.

Engineering - Materials Science (57)

The project is combining the Just-in-Time-Teaching (JiTT) approach, which uses student responses to web-based, pre-class study question sets to frame the day's classroom inquiry activities, with Inquiry Learning Lesson (ILL) activities. The integration of JiTT and ILL as a teaching, learning, and monitoring strategy is referred to as JiTTILL. To implement this strategy in an introductory material science and engineering course, the investigators are creating modules that consist of pre-class concept questions, typical student response misconceptions, content for informational mini-lectures, follow-on classroom inquiry learning activities, closure, and question sets to be completed later on-line. In this approach they intend to reveal prior knowledge, monitor student understanding, enhance learning skills, and promote student learning of material science and engineering content through conceptual change. The dissemination effort includes establishing website resource portals, distributing a CD containing the material, presenting and publishing papers at conferences and in journals, and offering faculty workshops. Project evaluation involves experienced evaluators and is determining the impact of the JiTTILL approach on student learning and conceptual understanding using a material concept inventory, student interviews, and focus groups. The broader impacts include the broad dissemination of the approach, the modules, and the material concept inventory, particularly through the faculty workshop.

The Just-in-Time-Teaching with Interactive Frequent Formative Feedback (JiTTIFFF or JTF) project uses engagement, assessment, and reflection tools developed in a prior NSF project and adapts them to an interactive cyber-enabled web environment. Using the tools in and out of class has the potential to increase the effectiveness and efficiency of learning using frequent formative feedback to students. New strategies include: 1) instruction informed by a multi-level, assessment-driven frequent formative feedback loops; 2) formative feedback from pre-class class preparation problems, 3) feedback during in-class engagement activities; 4) next class feedback discussion on confusing points from the previous class and 5) contextualization of activities and assessments with real-world applications. Compared to lecture-based pedagogy, constructivist pedagogy: increased average conceptual gain (measured by the Materials Concept Inventory) from 18% to 42%; increased class persistence from 85% to 95%; and decreased female withdrawal rate from 40% to 10%. The web environment facilitates ease of implementation and creates the potential for broad dissemination of instructional strategies and tools developed. The project is also investigating issues in implementation and how instructors use assessment results to adjust instruction. Such knowledge and insight is shaping the development of tutorials, workshops, webinars and you-tube videos for instruction for faculty interested in adapting the JTF pedagogy in their own instruction. The JTF pedagogy is being implemented and assessed in four settings with diverse populations: Arizona State University, North Carolina A&T, Oregon Institute of Technology, and Oregon State University.

This project is producing 1) an updated sets of instructional resources in the web-based JTF Learning Tool Kit; 2) an understanding of the barriers and benefits of JTF implementation in diverse settings; 3) an understanding of how instructors use results of multi-level assessment to adjust instruction to address student learning issues; and 4) an assessment of the impact of JTF on student attitude, learning and retention, and differences arising from use in different settings and diverse populations. It is also investigating the potential for broad application of the general features of JTF strategies and tools in other engineering domains through dissemination and diffusion of JTF strategies, findings, and products to a wide audience. This study is informing the engineering education community of the potential for use of the types of JTF strategies and learning tools in other engineering domains. This project is testing the effectiveness of the JTF pedagogy in different settings with diverse populations when implemented on the cyber-enabled web platforms