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Communicating Science June 25, 2009 RET/REU Professional Development Program R. W. Millard Director, NSF Communicating Science June 25, 2009 RET/REU Professional Development Program R. W. Millard Director, NSF REU/RET in Membrane Applied Science & Technology © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating Science Program – Part 1 Communication Styles (Example Paragraphs): 1. Creative Writing 2. Communicating Science Program – Part 1 Communication Styles (Example Paragraphs): 1. Creative Writing 2. General Science Writing 3. Scientific Technical Writing How to: 1. Write a Scientific Abstract - Guidelines 2. Example of REU Abstracts Received © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating Science Program - Part 2 RET Group Activities (3 teachers per group): 1. Communicating Science Program - Part 2 RET Group Activities (3 teachers per group): 1. Comment on each REU Abstract in Relation to the Guidelines 2. Compose an Abstract for a Science Times Article 3. Present to the Group the Abstract for the Science Times Article © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating Science Program - Part 3 Structuring Slide Presentations: 1. Template of Slides to Communicating Science Program - Part 3 Structuring Slide Presentations: 1. Template of Slides to Presenters (Faculty or Students) 2. Example of Presenters Slide Sets a. Faculty that followed Template b. Faculty that didn’t follow Template How to: 1. Guidelines for an Annotated Bibliography 2. Guidelines Poster Presentation with Template and Example © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating Science Writing Styles and Word Use Part 1 © R. W. Millard 6/25/2009 Communicating Science Writing Styles and Word Use Part 1 © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Written Communication Styles Creative Writing “First, for those familiar with Cincinnati who must be Written Communication Styles Creative Writing “First, for those familiar with Cincinnati who must be asking themselves if I'm an idiot, let me tell you that the Mill Creek did not melt the paint off my boat. The water quality in the Mill Creek is very poor, especially at the downstream end. In fact, it's one of the most polluted streams in the country. On the other hand, I have seen ducks and fish and turtles swimming in it. It's not as bad as people say it is. I found it reasonably clean from Spring Grove Avenue to the Western Hills Viaduct. From then on, it is really bad. I usually take a water bottle with me when I go kayaking, but I didn't this time. I was really careful to stay out of the water as much as possible, and when I was finished I went home and took a shower. Overall, it was a nice trip that few people get to do. The view of the Western Hills Viaduct alone was worth it. The barrier dam was cool, too. ” Excerpted from: “A Trip on the Mill Creek”, Cincinnati, Ohio by: Casey Walter http: //www. geocities. com/caseywalter/millcreek. htm © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Written Communication Styles Popular Science Direct quote from: “Follow the Silt”, by Cornelia Dean, Written Communication Styles Popular Science Direct quote from: “Follow the Silt”, by Cornelia Dean, New York Times, Science Times, June 24, 2008 © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Written Communication Styles Scientific Technical Article … In order to develop highly efficient photocatalytic Written Communication Styles Scientific Technical Article … In order to develop highly efficient photocatalytic Ti. O 2 films and membranes, we have recently investigated a novel chemistry method employing surfactant molecules as a pore directing agent along with acetic acid-based sol–gel route [6, 7]. Controlling materials at the nanolevel makes it possible to develop new types of products with tailordesigned properties for environmental applications [8]. In this study, we have fabricated nano-structured Ti. O 2 films and membranes with enhanced photocatalytic activity to destroy organic pollutants in water such as methylene blue dye, creatinine, and a biological toxin (microcystin-LR MC-LR), as well as to inactivate pathogenic microorganisms such as Escherichia coli (E. coli). The Ti. O 2 membranes were further tested for their water permeability, organic retention, and anti-biofouling properties. Photocatalytic Ti. O 2 films and membranes for the development of efficient wastewater treatment and reuse Systems Desalination, Volume 202, Issues 1 -3, 5 January 2007, Pages 199 -206 Hyeok Choi, Elias Stathatos, Dionysios D. Dionysiou Department of Civil and Environmental Engineering, University of Cincinnati http: //www. sciencedirect. com/science? _ob=Article. URL&_udi=B 6 TFX-4 MG 7 BS 6 - © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Words - Audience Dependent Usage Comparing General Science and Technical Writing “Follow the Silt” Words - Audience Dependent Usage Comparing General Science and Technical Writing “Follow the Silt” (NY Times Science Times 6/24/08) – – – – – geology hydrology silty laminated sediment streamscape millponds rigor streambed model restoration empirical intuitively runoff aesthetic gabions armor geomorpologist shallow channels meandering sandbars multiple threads braided channel stabilizing Debris compensate Accumulated deteriorated agricultural nitrogen phosphorous verbena consultancy disequilibrium aggraded cubic yards prescribes floodplain (These words are found in the entire 2 page article) © R. W. Millard 6/25/2009 “Photocatyltic Ti. O 2 films and membranes for the development of efficient wastewater treatment and reuse systems” Dionysiou et al. – photocatalytic – application – treatment – tailor-designed – structural properties – material – enhance – sol-gel – route – self-assembled – surfactant – pore directing agents – acetic acid-based – fabricated – nano-structured – crystalline – composite membranes – simultaneous A – disinfections – anti-biofouling r m (These words are found in 4 sentences. ) o r RET/REU Workshop @UC

Are You Smarter Than An 8 th Grade Science Student? Science and Non-Science Vocabulary Are You Smarter Than An 8 th Grade Science Student? Science and Non-Science Vocabulary Writing/Reading/Origins/Usage Words Selected from Articles in the New York Times Science Times, May 6, 2008 Science Meaning Non-science physiological (adj. ) underpinning (n. , pl. -s) symptom (n. , pl. -s) measurement (n. , pl. -s) nosology (n. , pl. ) unique (adj. ) genome (n. , pl. ) Meaning unequivocal (adj. ) © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Are You Smarter Than An 8 th Grade Science Student? And Now The Game Are You Smarter Than An 8 th Grade Science Student? And Now The Game REU vs RET! © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating Science Research and Technical Abstracts Program – Part 2 © R. W. Millard Communicating Science Research and Technical Abstracts Program – Part 2 © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Science Project Abstract: Guidelines • Project Title – – • Authors – – • Science Project Abstract: Guidelines • Project Title – – • Authors – – • See next slide for details Key Words – • Your Name, Home Institution, Name of Your UC Summer 2008 Research Program (NSF REU, NSF RET, ASPET SURF) Your Mentor Name(s), Department(s), College(s), and Institution Abstract Narrative -150 words minimum; 200 words maximum – • Be concise. Use important words to convey the scope and specifics of your science project. Example: “Molecular Selectivity of a Membrane Engineered from Banana Polymers” Provide 5 key words that characterize important aspects of your project that are not included in the project title Submission Dates – – Provide date submitted to mentor Provide date submitted to program director Check and Recheck, Read and Re-read for grammar, syntax, spelling – use a dictionary and thesaurus Ask your mentor(s) to preview all writing assignments before submission. This means completing your assignments insufficient time to obtain this feedback. © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Research Project Abstract: Guidelines Abstract Narrative -150 words minimum; 200 words maximum – One Research Project Abstract: Guidelines Abstract Narrative -150 words minimum; 200 words maximum – One general statement of the research field to set up research project context. (Background) – One sentence describing your specific research project. (Your Project) – One sentence describing how the research project will provide new information and advance the field of science or engineering. (Intellectual Merit) – One sentence describing the specific question or hypothesis you will be exploring in your research project. (Question of Hypothesis) – Describe what models and methods will be used to study the research question or hypothesis (Models and Methods) – Describe what specific results are expected and how you will analyze and interpret the results in order to test your hypothesis or answer the question. (Data Collection and Analysis) – What scientific or engineering conclusions do you expect to drawn at the completion of your research project? (Outcomes and Conclusions) – Explain how the results you expect to obtain will shape the field of research to which your research project applies. (Broader Impact) – Describe how your results will be disseminated to others outside your specific research group. (Broader Impact) © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Example Abstract #1 Accuracy of Artificial Neural Networks to Estimate the Permeability of Polymers Example Abstract #1 Accuracy of Artificial Neural Networks to Estimate the Permeability of Polymers REU Trainee Name Mentor Name REU Trainee Home Institution NSF REU UC Summer 2008 Research Program, Department of Chemical Engineering Submitted to Mentor June 23, 2008 Submitted to Program Director June 23, 2008 The ability to reliably predict the properties of novel polymers with a personal computer rather than through synthesis and costly experimental testing would greatly improve the selection of polymers. One suggested method is to use artificial neural networks (ANN). ANN are model-free estimators that “learn” to predict outcomes based upon prior experience. Such a neural network weighs the effect of input values on the outcome in order to estimate output values. Neural networks have been used to predict physical properties of substances based upon their molecular structure. For example, Joyce, et al. used monomer structures to predict the physical properties of polymers through the use of ANN. Problems related to this method include an excess of input values (up to 1000), which increase processing time. Further, none of the input values greatly affected the outcome of the prediction. Wessling, et al. revealed a dependence of permeability on IR spectra for polymers through the use of ANN, though the dependence may at best be described as an order of magnitude approximation. It is thus desirable to find a more accurate method for predicting the properties of polymers. The present work aims to improve estimation methods using ANN by selecting a limited number of criteria which most heavily influence the prediction of permeability. Keywords: semi-empirical methods, node, layer, input, output, backpropagation © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Example Abstract #2 Effects of the Expressed NF-k. B gene from an attached nonviral Example Abstract #2 Effects of the Expressed NF-k. B gene from an attached nonviral polymer to DNA REU Trainee Name and Institution, NSF REU Mentor Names, Pharmocology & Cell Biophysics, University of Cincinnati, In the laboratory we want to create the effects of late phase ischemic preconditioning(IPC). The effects of late phase IPC comes from ischemic stress. This is the process of low blood supply to the heart which causes cardioprotective proteins to protect the heart. The important protein NF-k. B is our focus in the laboratory. The hypothesis is, when attaching a nonviral polymer to the DNA we can automatically cause the effects of ischemic stress. In the laboratory we might deal with attaching the polymer to the DNA samples, as well as study and interpret the data of the processed experiments. By interpreting the results, one can understand the positive and negative effects of the expressed NF k. B gene. Knowing both sides of an experiment can help someone determine what pathway to take in order to succeed in more efficient drug delivery. In Dr. Jones’ lab the heart of a mouse will be used to determine the effect of the hypothesis. Mice are used because it is very cost effective for laboratory purposes, also since they populate so quickly and in great amounts, they are viable candidates for experiments. Once this experiment has passed clinical study, it will be a great achievement for gene therapy. From this experiment a drug will be designed so that it will target only the desired gene NF k. B, which can ultimately stop any type of heart disease. Key Words: ischemic-preconditioning, ischemic stress, cost effective, gene therapy, heart disease © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Example Abstract #3 Synthesis and Application of Photocatyltic. Ti. O 2 Film Membranes For Example Abstract #3 Synthesis and Application of Photocatyltic. Ti. O 2 Film Membranes For the Neutralization and/or Degradation of Amitrole Under the Visible Light Spectrum Trainee and Mentors Names, Trainee Home Institution, Mentor institution National Science Foundation Research Experience for Undergraduates Commonly used pesticides and herbicides in the United States, such as amitrole, leach out of the ground from which they were applied and into public drinking water supplies, forcing the need of new water purification methods. This project will entail manufacturing of film membranes based from Ti. O 2 photocatalyst nanoparticles, which when exposed to visible/solar light, should begin an oxidation process in which the natural or man-made toxins present in the water undergo degradation and neutralization. Through this project we hope to discover and further the knowledge of energy renewable and environment-friendly processes for the aid of purifying drinking water sources. We will attempt to prove that the photocatyltic. Ti. O 2 film membranes will begin oxidation under exposure from visible/solar light, as well as understanding how the toxins and film membranes react. To create the Ti. O 2 membranes, self-assembly surfactants and other modified sol-gel techniques will be utilized as well as also for use of tailoring of the membrane properties. High performance liquid chromatography will be used to determine the contents of the toxins and how much is left after degradation. Different parametric tests will be used in order to determine the best design for the film membranes. The results that are expected are that a Ti. O 2 film membrane will be produced which will possess a very active visible/solar light photocatalyst response and could be modified for enhanced properties. Results of the project will be analyzed by determining how much of the toxins remain in the original water sample after placement of the film membrane for a period of time. Through this project we hope to learn how to more efficiently make film membranes and how Ti. O 2 membranes will react under different conditions. It is anticipated as a long term goal that the technology could be used not only for water purification, but as well for atmospheric air purification. The water purification technology could be economically dispersed to and utilized by developing countries which have an indeterminable amount of problems with drinking water supplies. Keywords: Sol-gel; surfactant; herbicide; nanomaterials; nitrogen-doped nanoparticles Date submitted to mentor: 06/22/08 Date submitted to program director: 06/22/08 © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Critique Abstracts • Each Group of 3 teachers will: – Critique 2 to 3 Critique Abstracts • Each Group of 3 teachers will: – Critique 2 to 3 abstracts against guidelines – Report most common errors to entire group – Recommend changes in guidelines – Offer guidance and advice to authors © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Compose Abstracts • Each Group of 3 teachers will: – Select one Article from Compose Abstracts • Each Group of 3 teachers will: – Select one Article from the June 24 th Science Times, New York Times to Abstract – Construct an Abstract following Guidelines – Present Abstract to entire class – Receive Class Critique © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Science Times Articles June 24 2008 • • Follow the Silt http: //www. nytimes. Science Times Articles June 24 2008 • • Follow the Silt http: //www. nytimes. com/2008/06/24/science/24 stream. html? _r=1&ref=science& oref=slogin For Alien Life-Seekers, New Reason to Hope http: //www. nytimes. com/2008/06/24/science/24 angi. html? ref=science Homecoming of Odysseus May Have Been in Eclipse http: //www. nytimes. com/2008/06/24/science/24 home. html? ref=science Doctors Say Medication Is Overused in Dementia http: //www. nytimes. com/2008/06/24/health/24 deme. html? ref=science Microbes Eating Away at Pieces of History http: //www. nytimes. com/2008/06/24/science/24 micr. html? ref=science From a Prominent Death, Some Painful Truths http: //www. nytimes. com/2008/06/24/health/24 hear. html? ref=science Where the Whole Agenda Is Innovation http: //www. nytimes. com/2008/06/24/science/24 prof. html? ref=science © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating Science Annotated Bibliographies, Slide Sets, and Posters Part 3 © R. W. Millard Communicating Science Annotated Bibliographies, Slide Sets, and Posters Part 3 © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Annotated Bibliography – Guidelines • Provide an annotated working bibliography of 6 sources important Annotated Bibliography – Guidelines • Provide an annotated working bibliography of 6 sources important for your orientation to and conduct of your summer research project. • These primary bibliographic sources should include the following: – One or Two Textbook Chapters that provide background orientation to your research project and mentor’s research program; – One Scientific Review Article published within the past 5 years of the research field to which your research project relates; – One Historical Scientific Article that is the basis of the field in which your research project fits; – One Recent Scientific Article not from your mentor’s laboratory on the field of research that relates most closely to your research project; – One Recent Research Publication from your mentor’s laboratory that most closely relates to your summer research project; and – One Most Recent Scientific Meeting or Article in a Popular Science or Engineering Publication that illustrates the dissemination of new research findings in the research field most closely related to your research project. © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Bibliography Annotations – Guidelines – a general statement to summarize the important content of Bibliography Annotations – Guidelines – a general statement to summarize the important content of the reference source to your research project its science or engineering subject; – examples taken from the body of the reference source illustrating its specific value to you in relation to your summer research project; – any bias or ethical perspectives offered by the authors of the reference; – research sponsors identified in the reference – see footnotes and acknowledgements; (any potential conflicts of interest); and – Identify any undergraduate or graduate student trainees, or K-12 STEM teachers listed as coauthors or credited for contributions in the acknowledgements © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating & Disseminating Science through Slides and Posters • Program Events • Science Fairs Communicating & Disseminating Science through Slides and Posters • Program Events • Science Fairs • Science and Education Conferences • School Hallways © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Communicating & Disseminating Science Slide Set Template © R. W. Millard 6/25/2009 RET/REU Workshop Communicating & Disseminating Science Slide Set Template © R. W. Millard 6/25/2009 RET/REU Workshop @UC

2008 NSF REU Site Program and RET Supplement in Membrane Applied Science & Technology 2008 NSF REU Site Program and RET Supplement in Membrane Applied Science & Technology Core Curriculum 2009 © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Research Program Title Faculty Mentor/Director Presenter Name (if different) Department Graduate Program Affiliation(s) © Research Program Title Faculty Mentor/Director Presenter Name (if different) Department Graduate Program Affiliation(s) © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Research Program Title Background, Rationale, Intellectual Merit, Broader Impacts • Background • Rationale • Research Program Title Background, Rationale, Intellectual Merit, Broader Impacts • Background • Rationale • Intellectual Merit • Broader Impact Faculty Name Presenter Name (if Different) RET/REU Workshop @UC

Research Program Title Overall Hypothesis, Model Systems, Methods, and Current Questions • Overall Hypothesis Research Program Title Overall Hypothesis, Model Systems, Methods, and Current Questions • Overall Hypothesis or Research Question • Model Systems in Use (Approaches) • Major Laboratory Methods and Equipment Resources • Current Questions Under Study Faculty Name Presenter Name (if Different) RET/REU Workshop @UC

Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; 1 of 4) • Recent Discovery/Findings • What Finding Means • Next Steps Faculty Name Presenter Name (if Different) RET/REU Workshop @UC

Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; 2 of 4) • Recent Discovery/Findings • What Finding Means • Next Steps Faculty Name Presenter Name (if Different) RET/REU Workshop @UC

Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; 3 of 4) • Recent Discovery/Findings • What Finding Means • Next Steps Faculty Name Presenter Name (if Different) RET/REU Workshop @UC

Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; Research Program Title Latest Findings, Importance, Next Steps (4 Slides maximum on this part; 4 of 4) • Recent Discovery/Findings • What Finding Means • Next Steps Faculty Name Presenter Name (if Different) RET/REU Workshop @UC

Research Program Title Publications, References, and Contact Information • Most Recent Publication • Most Research Program Title Publications, References, and Contact Information • Most Recent Publication • Most Relevant Recent Subject Review in Literature • Contact Information for Faculty Mentor (email, lab location, etc. ) Faculty Name Presenter Name (if Different) RET/REU Workshop @UC

Communicating & Disseminating Science Slide Set Example 1 Effects of environmental estrogen exposure on Communicating & Disseminating Science Slide Set Example 1 Effects of environmental estrogen exposure on the heart © R. W. Millard 6/25/2009 RET/REU Workshop @UC

Effects of environmental estrogen exposure on the heart June 17, 2008 ASPET Summer Research Effects of environmental estrogen exposure on the heart June 17, 2008 ASPET Summer Research

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that either mimic or block endogenous hormones and Endocrine-disrupting chemicals (EDCs) are exogenous compounds that either mimic or block endogenous hormones and disrupts the body's normal functions. -alter normal hormone levels, halt or stimulate the production of hormones, or change the way hormones travel through the body Estrogenic EDCs are compounds that mimic, or antagonize the effects of endogenous estrogens. -Xenoestrogens are man-made EDCs -Phytoestrogens are naturally occurring estrogenic EDCs

Bisphenol A (BPA) is a man-made environmental estrogen with endocrine-disrupting actions. -used extensively in Bisphenol A (BPA) is a man-made environmental estrogen with endocrine-disrupting actions. -used extensively in the production of consumer goods and products such as polycarbonate plastics, food cans and plastic packaging, dental sealants and water pipes. -There is wide and near ubiquitous human exposure. - Affects reproductive, development, cancer in animal models.

BPA causes arrhythmogenic after-contractions in single cardiac myocytes from female BPA causes arrhythmogenic after-contractions in single cardiac myocytes from female

BPA causes arrhythmias in ex vivo, work performing whole heart from female (but not BPA causes arrhythmias in ex vivo, work performing whole heart from female (but not male) rats

Mechanisms of arrhythmia: triggered activity ■ Unlike automaticity, triggered activity is not a self-generating Mechanisms of arrhythmia: triggered activity ■ Unlike automaticity, triggered activity is not a self-generating rhythm. ■ Triggered activity occurs as a response to a preceding impulse. ■ These are single cell phenomena that can result in cardiac arrhythmias.

Excitation-contraction coupling in cardiac myocytes Excitation-contraction coupling in cardiac myocytes

BPA and Estrogen alter contraction in cardiac myocytes BPA and Estrogen alter contraction in cardiac myocytes

Myocytes from male rats are not affected by E 2 or BPA Myocytes from male rats are not affected by E 2 or BPA

Dose response properties of the effects of estrogen and BPA – inverted U curves Dose response properties of the effects of estrogen and BPA – inverted U curves

Effect of E 2 and BPA on Ca 2+ transient Effect of E 2 and BPA on Ca 2+ transient

BPA and estrogen do not affect SR Ca content BPA and estrogen do not affect SR Ca content

BPA and estrogen increase Ca “leak” from the SR BPA and estrogen increase Ca “leak” from the SR

BPA and estrogen increase Ca “leak” from the SR BPA and estrogen increase Ca “leak” from the SR

Acute exposure to BPA causes arrhythmias in female - but not male - myocytes Acute exposure to BPA causes arrhythmias in female - but not male - myocytes and hearts, particularly in the presence of estrogen; The sex-specific effect of BPA is mediated by increase in SR Ca leak through the ryanodine receptors; Our results have important implication for the cardiac risks associated with BPA and other estrogenic EDC exposure in women, particularly those in the at risk population.

Communicating & Disseminating Science Slide Set Example 2 Role of Fibroblast Growth Factor-2 in Communicating & Disseminating Science Slide Set Example 2 Role of Fibroblast Growth Factor-2 in Ischemia-Reperfusion Injury and Cardioprotection © R. W. Millard 6/25/2009 RET/REU Workshop @UC

ASPET SURF Program Core Curriculum 2009 ASPET SURF Program Core Curriculum 2009

Role of Fibroblast Growth Factor – 2 in Ischemia-Reperfusion Injury and Cardioprotection Jo El Role of Fibroblast Growth Factor – 2 in Ischemia-Reperfusion Injury and Cardioprotection Jo El J. Schultz, Ph. D. Department of Pharmacology and Cell Biophysics Rm 5205, MSB schuljo@email. uc. edu 558 -9754 Graduate Program Affiliations: Molecular, Cellular, Biochemical Pharmacology & Integrative Systems Biology Core Curriculum June 16 -20, 2008

Directions of the Laboratory 1. Role of FGF 2 in Ischemia-Reperfusion Injury of the Directions of the Laboratory 1. Role of FGF 2 in Ischemia-Reperfusion Injury of the Heart 2. 2. Role of Opioids in Heart Failure Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Methods of the Laboratory Animal Models Mouse (Knockout and Transgenic) Hamster (Hypertensive and Cardiomyopathic) Methods of the Laboratory Animal Models Mouse (Knockout and Transgenic) Hamster (Hypertensive and Cardiomyopathic) Physiology and Surgical Procedures Isolated Heart Model In vivo Heart Model (I/R injury, Heart failure models) Echocardiography Catheterizations (vein, artery, left ventricle) Pharmacology (Drug studies, Receptor binding) Cellular and Biochemical Histo- and Immunostaining ELISA, RIA Molecular PCR, DNA microarray analysis Western blots, Proteomic (2 -D gel and MS analysis) Core Curriculum Northern blots June 16 -20, 2008

FGF 2 and Cardiovascular System Prototypic member of fibroblast growth factor family which includes FGF 2 and Cardiovascular System Prototypic member of fibroblast growth factor family which includes 22 different isoforms 12 isoforms expressed in the heart: FGF 1, FGF 2, FGF 6, FGF 7, FGF 8, FGF 9, FGF 10, FGF 12, FGF 13, FGF 16, FGF 18, FGF 20 Localized in heart to gap junctions, extracellular matrix, and cardiac myocytes of atria and ventricles Implicated in: Hematopoiesis Angiogenesis and Vascular Repair Wound Healing Mesoderm Induction & Cardiogenesis Cardiac Hypertrophy Cell Survival/Death Core Curriculum Jo El J. Schultz, Ph. D. June 16 -20, 2008

Role of FGF 2 in Cardioprotection • Administration of recombinant FGF 2 has been Role of FGF 2 in Cardioprotection • Administration of recombinant FGF 2 has been shown to be cardioprotective in many different animal models of I/R injury • This cardioprotection due to: -- Mitogenic/angiogenic effects of FGF 2 -- Non-mitogenic, direct effects on the myocardium • Cardioprotection evaluated as: -- reduction in cell damage -- improvement in post-ischemic cardiac function -- reduction in arrhythmias Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Clinical Significance of FGF 2 Mediated Cardioprotection • Patients with heart disease have increased Clinical Significance of FGF 2 Mediated Cardioprotection • Patients with heart disease have increased FGF 2 levels detectable in urine, pericardial fluid, and serum (~2 -10 fold increase) • Clinical trials are underway to assess the safety and efficacy of FGF 2 for angiogenesis in patients with ischemic heart disease • Understanding the cardioprotective mechanism of FGF 2 may lead to the development of pharmacologic or genetic therapies to protect the heart against contractile dysfunction and myocardial infarction Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Does expression of FGF 2 in the heart provide protection against ischemia-reperfusion injury? Jo Does expression of FGF 2 in the heart provide protection against ischemia-reperfusion injury? Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Phenotypes of FGF 2 Genetically Modified Mice FGF 2 KO mice: Viable and fertile Phenotypes of FGF 2 Genetically Modified Mice FGF 2 KO mice: Viable and fertile Normal cardiac function Thrombocytosis Decreased mean arterial blood pressure (via decreased portal vein vascular smooth muscle tone or baroreceptor impairment) Protected from pressure overload-induced hypertrophy Delayed wound healing Decreased bone mass Impaired cerebral cortex development No effect on vascular growth in hindlimb ischemia Wildtype Fgf 2 KO 22 HMW k. D 21 k. D LMW 18 k. D FGF 2 Tg mice: Normal heart development No spontaneous cardiac hypertrophy Wildtype h. FGF 2 Tg Line 20 h. FGF 2 Tg Line 25 34 k. D 22 k. D 21 k. D 18 k. D 24 k. D 22. 5 k. D 18 k. D

Isolated perfused “work-performing” heart Jo El J. Schultz, Ph. D. Core Curriculum June 16 Isolated perfused “work-performing” heart Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Measurement of Myocardial Infarction Ischemic-reperfused heart stained with 1% triphenyltetrazolium chloride (TTC) Detects viable Measurement of Myocardial Infarction Ischemic-reperfused heart stained with 1% triphenyltetrazolium chloride (TTC) Detects viable tissue (red) vs. necrotic tissue (whitish-yellow) TTC reacts with NADPH to form a red formazan color Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Cardiac-specific overexpression of h. FGF 2 results in an enhanced post-ischemic recovery of contractile Cardiac-specific overexpression of h. FGF 2 results in an enhanced post-ischemic recovery of contractile function 88± 2% 79± 6% 57± 9% House et al. Circulation 108: 3140 -3148, 2003

Cardiac-specific overexpression of h. FGF 2 results in a decrease in myocardial cell damage Cardiac-specific overexpression of h. FGF 2 results in a decrease in myocardial cell damage FGF 2 Tg heart following 60 min Ischemia and 120 min Reperfusion Creatine Kinase Release is Significantly Decreased in h. FGF 2 Tg Hearts During IR 30± 3 13± 6 *p<0. 05 vs. Wildtype 16± 4 * * House et al. Circulation 108: 3140 -3148, 2003 Baseline Isch * * * (Min 0 -14) Reperfusion (Min 114 -120)

stop 951 AUG 486 CUG 319 CUG 346 CUG 361 CUG 86 FGF 2 stop 951 AUG 486 CUG 319 CUG 346 CUG 361 CUG 86 FGF 2 Isoforms 5’ 3’ Translation 18 k. D 21 k. D 22. 5 k. D 24 k. D 34 k. D nuclear localization signals - LMW isoform localized mainly to cytosol (paracrine/autocrine effect) - HMW isoforms localized to nucleus (intracrine function) Different subcellular localizations of FGF 2 isoforms suggest different biological functions Core Curriculum Jo El J. Schultz, Ph. D. June 16 -20, 2008

Phenotypes of FGF 2 Genetically Modified Mice FGF 2 LMW KO mice: Viable and Phenotypes of FGF 2 Genetically Modified Mice FGF 2 LMW KO mice: Viable and fertile Normal cardiac function Normal heart development No difference in vascular density No spontaneous cardiac hypertrophy Wildtype HMW isoforms Fgf 2 KO FGF 2 LMW KO 22 k. D 21 k. D LMW isoform 18 k. D FGF 2 HMW KO mice: Viable and fertile Normal heart development No difference in vascular density No spontaneous cardiac hypertrophy Wildtype HMW 22 k. D isoforms 21 k. D LMW isoform 18 k. D Fgf 2 KO FGF 2 HMW KO

Evidence for the LMW isoform of FGF 2 to protect against cardiac dysfunction 100 Evidence for the LMW isoform of FGF 2 to protect against cardiac dysfunction 100 *p<0. 001 vs. Wildtype * 90 80 Wildtype FGF 2 HMW KO *p<0. 001 vs. Wildtype 70 * * 60 50 40 30 20 66± 4 32± 6 46± 8 10 0 53± 12 85± 2 Liao et al. J Mol Cell Cardiol 42(1): 106 -120, 2007 Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

FGF 2 SIGNALING in CARDIOPROTECTION FGF 2 HS-PG lmw FGF 2 P P P FGF 2 SIGNALING in CARDIOPROTECTION FGF 2 HS-PG lmw FGF 2 P P P MW y L F 2 b ed FG at of i ed m m for iso JNK MAPK RAS- e. NOS an d i. NOS e xpressio modulate n d by FGF 2 PK C mo -a an dul d ate PKC db y F -d act i GF 2 vatio n PKC ERK 1/2 NO ↓Infarction p 38 ↑Recovery of Contractile Function ↓Infarction Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Clinical Significance University of Cincinnati Medical Center Tests Growth Protein By Tim Bonfield The Clinical Significance University of Cincinnati Medical Center Tests Growth Protein By Tim Bonfield The Cincinnati Enquirer March 25, 2004 Three patients at UC and The University Hospital have grown new coronary arteries after receiving a growth factor protein (FGF 1) in November 2003. All three patients showed improved blood flow to the heart three months following the injection. UC Heart & Vascular physicians were the first in the U. S. to inject this protein in heart patients in an attempt to grow new coronary arteries. The procedure is part of a phase I clinical trial, measuring the safety and effectiveness of FGF 1 to grow new arteries, termed angiogenesis, in patients with angina (debilitating chest pain) due to severe coronary artery disease. UC is one of only four sites nationwide to participate in the trial… Jo El J. Schultz, Ph. D. Core Curriculum June 16 -20, 2008

Acknowledgments SCHULTZ LAB Stacey House Siyun Liao Craig Bolte Janet Bodmer Dan Pietras Greg Acknowledgments SCHULTZ LAB Stacey House Siyun Liao Craig Bolte Janet Bodmer Dan Pietras Greg Carpenter Gilbert Newman Angel Whitaker Nick Vatamaniuc Laura Moon Susan Melhorn Kevin Branch Alana Scott Darius Porter James O’Toole Norris Hollie David Palacios Erica Goetz Catherine Post COLLABORATORS Dr. Tom Doetschman (U of AZ) Dr. W. Keith Jones (UC) Funded by NIH/NHLBI, AHA, Ph. RMA

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Please Insert Your Poster Title Here Firstname I. Lastname 1, Firstname I. Lastname 2, Please Insert Your Poster Title Here Firstname I. Lastname 1, Firstname I. Lastname 2, Firstname I. Lastname 3 1 Cincinnati, OH, Department of Medicine; 2 Cincinnati, OH, Department of Health; 3 Cincinnati, OH, Department of Nursing Abstract Methods Results Conclusion Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Donec vitae nunc. Duis arcu. Fusce mattis rutrum dolor. Morbi sed leo sed massa tempor. Aliquam erat volutpat. Quisque rutrum sem sed turpis. In neque risus, scelerisque vel, sodales ut, fringilla eget, ante. Donec facilisis egestas lorem. Aliquam erat volutpat. Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Vivamus et lectus ut sem tempor vehicula. Morbi fringilla tristique sapien. Praesent at mi ac ante pharetra sodales. Fusce ac augue sed neque tempus posuere. Proin tellus. Pellentesque tristique semper urna. Maecenas dictum, turpis vitae placerat gravida, pede velit nonummy pede, id interdum nulla diam sed mauris. In eu neque id ligula euismod pulvinar. Nullam magna mi, facilisis nec, pretium nec, iaculis vitae, diam. Suspendisse vitae sem quis quam tempus accumsan. Morbi eget nunc. Morbi vel erat quis leo pharetra aliquam. Quisque condimentum purus vel elit. In hac habitasse platea dictumst. Nunc in elit a mi pretium interdum. Vestibulum elementum felis vel magna. Aenean hendrerit suscipit neque. Donec id mi a eros egestas. In mi. Nunc diam ante, luctus eget, porta at, porta nec, eros. Integer faucibus tincidunt mi. Donec id ante sed ante lacinia rhoncus. Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Mauris erat. Etiam sollicitudin dignissim purus. Mauris lacus. Maecenas massa nisi, semper non, fringilla at, porta eget, tortor. Phasellus risus nisl, vehicula ac, faucibus ut, sollicitudin quis, tellus. Aliquam sodales. Nullam non felis. Donec eget dui in magna rhoncus eleifend. Curabitur libero tellus, sagittis faucibus, lobortis et, volutpat ac, tellus. Vivamus adipiscing, velit at faucibus sagittis, metus magna condimentum purus, ut vehicula elit purus id massa. Nam accumsan. Vestibulum dui nisl, lobortis non, convallis vitae, tincidunt sit amet, justo. Duis nec tellus eget turpis laoreet accumsan. Maecenas enim. Etiam lacinia, odio at viverra hendrerit, sapien elementum felis, eget pharetra est sapien vel orci. Quisque quis arcu eu lorem accumsan euismod. Vestibulum ante ipsum primis in faucibus orci luctus et ultrices posuere cubilia Curae; Fusce varius risus. Morbi egestas lectus sit amet justo. Vestibulum imperdiet ultrices nisi. Duis id leo non libero accumsan bibendum. Cras ultrices, odio ac faucibus suscipit, orci augue tincidunt arcu, in malesuada massa nisl quis ligula. Sed congue tellus at lectus. Nulla non libero. Sed pretium convallis enim. 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Maecenas dictum, turpis vitae placerat gravida, pede velit nonummy pede, id interdum nulla diam sed mauris. In eu neque id ligula euismod pulvinar. Nullam magna mi, facilisis nec, pretium nec, iaculis vitae, diam. Suspendisse vitae sem quis quam tempus accumsan. Morbi eget nunc. Morbi vel erat quis leo pharetra aliquam. Quisque condimentum purus vel elit. In hac habitasse platea dictumst. Nunc in elit a mi pretium interdum. Vestibulum elementum felis vel magna. Aenean hendrerit suscipit neque. Donec id mi a eros egestas. In mi. Nunc diam ante, luctus eget, porta at, porta nec, eros. Integer faucibus tincidunt mi. Donec id ante sed ante lacinia rhoncus. Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Mauris erat. Etiam sollicitudin dignissim purus. Mauris lacus. Maecenas massa nisi, semper non, fringilla at, porta eget, tortor. Phasellus risus nisl, vehicula ac, faucibus ut, sollicitudin quis, tellus. Aliquam sodales. Nullam non felis. Donec eget dui in magna rhoncus eleifend. Curabitur libero tellus, sagittis faucibus, lobortis et, volutpat ac, tellus. Vivamus adipiscing, velit at faucibus sagittis, metus magna condimentum purus, ut vehicula elit purus id massa. Nam accumsan. Vestibulum dui nisl, lobortis non, convallis vitae, tincidunt sit amet, justo. Duis nec tellus eget turpis laoreet accumsan. Maecenas enim. Etiam lacinia, odio at viverra hendrerit, sapien elementum felis, eget pharetra est sapien vel orci. © R. W. Millard 6/25/2009 habitasse platea dictumst. Nunc in elit a mi pretium interdum. Vestibulum elementum felis vel magna. Aenean hendrerit suscipit neque. Donec id mi a eros egestas. In mi. Nunc diam ante, luctus eget, porta at, porta nec, eros. Integer faucibus tincidunt mi. Donec id ante sed ante lacinia rhoncus. Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Mauris erat. quam tempus accumsan. Morbi eget nunc. Morbi vel erat quis leo pharetra aliquam. Quisque condimentum purus vel elit. In hac habitasse platea dictumst. Nunc RET/REU Workshop @UC

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Molecular Engineering of Porous Membranes for Gas Separations and Biocatalytic Membrane Reactor Applications Andre Molecular Engineering of Porous Membranes for Gas Separations and Biocatalytic Membrane Reactor Applications Andre S. C. Hall 1, Zhenkun Zheng 2, Dr. Vadim V. Guliants 2 1 Tampa, FL, Department of Chemical & Biomedical Engineering ; 2 Cincinnati, OH, Department of Chemical & Materials Engineering Abstract Methods Results This project involves membrane synthesis, characterization, and process engineering, for the optimization of hydrogen purification membranes and membrane supports for biocatalytic membrane reactor applications. In particular, this work is focused on the synthesis of novel zeolitic DD 3 R membranes for economical hydrogen and carbon dioxide separation from syngas and other industrially important process streams. The major goal is to obtain a new chemically and thermally stable decadodecasil 3 R (DD 3 R) membrane with H 2/ CO 2 selectivity greater than 100 and H 2 permeance greater than 5· 10 -7 mol ∙ m- 2 s-1 Pa-1. Current hydrogen production by the water-gas-shift reaction (WGS) is limited by finite equilibrium syngas conversion. The novel DD 3 R membranes promise to deliver enhanced and more economical hydrogen production because they are expected to shift the WGS equilibrium by selectively extracting hydrogen due to the presence of micropores which discriminate between smaller H 2 and bigger CO 2 molecules. Another major advantage of zeolitic DD 3 R membranes is that they can be operated at high temperatures required for the WGS reaction. DD 3 R membrane was made by two processes, in-situ hydrothermal synthesis and secondary growth. In the insitu method, a porous alumina support is brought in direct contact with a synthesis solution so that a zeolite film is grown on the surface under hydrothermal conditions. Secondly, secondary growth method, a support is dipcoated with zeolite seeds, which are small pre-formed DD 3 R crystals, followed by growth of the seeds into a continuous zeolite layer (Verweij et al. 2006). Chemical Vapor Deposition is used to repair defects of the membrane. The permeance and selectivity of the membranes were found using the following formulas: X-Ray diffraction was applied to membrane to give information about the crystalline phase structure, chemical composition, and physical properties of the support material and thin membrane layer. (a)DD 3 R microstructure, (b) X-ray pattern, (c) Permeance of 1. 1· 10 -6 mol ∙ m-2 s-1 Pa-1 at 550 o. C and 30 psi, (d) Increased selectivity of H 2 to CO 2 and N 2 after CVD modification from to 32. 7 and 24. 5 respectively. Introduction Thermally and chemically stable zeolite membranes that have intra-crystalline pores of molecular sizes are ideal for H 2 separation from coal gasification products including syngas (Guliants, 2007). An issue arises when a membrane which possesses the pores larger than the sizes of all molecules in a mixture to be separated; thus, the membrane will not possess molecular sieving properties for CO 2, CO, and H 2 molecules present in coal gasification. The unavailability of specific zeolite membranes represents a major hindrance in the development of novel inorganic membranes for hydrogen separation. The objectives of this current research are (1) developing defect free DD 3 R membranes with improved hydrogen permeance and high chemical and thermal stability because they are believed to possess pores larger than hydrogen molecule but smaller than some other molecules in a syngas mixture; and (2) further repairing defects by a process of thermally activated chemical vapor deposition (CVD) of tetraethyl orthosilicate (TEOS) (Yan et al. 1994). Permeance( F ) : Ideal selectivity = FHydrogen / Fother gas Referenc e Permeation setup Actu al XRD data obtained compared to XRD data from IZA. Conclusion DD 3 R type zeolitic membranes are very effective for the separation of multi-component hydrogen mixtures under harsh conditions, because of their (i) size and shape selective separation behavior and (ii) thermal and chemical stability. Results suggest that DD 3 R membrane can be effectively used for hydrogen separation of various industrial hydrogen mixtures at high temperatures. The DD 3 R membrane becomes permselective for hydrogen over CO 2 and N 2. Reference Chemical Vapor Deposition SEM images of the DD 3 R membranes obtained by (A) in-situ crystallization for 10 days and (B) seeded secondary growth for 2 days at 160 ºC (Left: surface view; Right: cross-sectional view). TEOS (80 o. C) N 2 550 o. C © R. W. Millard 6/25/2009 6 days later RET/REU Workshop @UC Guliants, V. , (2007). SOD-DDR Proposal. Submitted to the D. O. E pp 15 -17 Verweij et al (2006). Microporous Silica and Zeolite Membranes for Hydrogen Purification. MRS Bulletin, Vol. 31, published October 2006 pp 756 -763 Yan et al (1994). Hydrogen-Permselective Si. O 2 Membrane Formed in Pores of Alumina Support Tube by Chemical Vapor Deposition with Tetraethyl Orthosilicate. Industrial and Engineering chemistry Research, 1994, 33, 2096 -2101.