122,961 results on '"Department of Biomedical Engineering"'
Search Results
2. Quantum Techniques and Technologies for Cybersecurity in Healthcare
- Author
-
Florence D. Hudson, Founder and CEO, FDHint, LLC, Executive Director, Northeast Big Data Innovation Hub at Columbia University, IEEE Engineering in Medicine and Biology Society Standards Committee, Former IBM VP & CTO, and Special Advisor – NSF Cybersecur and Shantanu Chakrabortty, Founder, Free Dynamics, Clifford Murphy Professor, Preston M. Green Department of Electrical and Systems Engineering, Department of Computer Science and Engineering, Department of Biomedical Engineering, Washington University, St. L
- Subjects
blockchain trusted platform modules ,low resource platforms ,ip protection ,exploiting quantum primitives for healthcare ,blockchain in healthcare today ,low computational footprint for healthcare ,end to end security solutions for healthcare ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Quantum based security solutions for low resource platforms. Learn and prepare for breaches with a pre-emptive stance and not just when there is an imminent threat.
- Published
- 2022
- Full Text
- View/download PDF
3. Analysis of Myocardial Layer Specific Systolic and Diastolic Function During and After PCI (PCI-Strain)
- Author
-
Department of Biomedical Engineering, Technion, Haifa, Israel
- Published
- 2015
4. Euphorbia hirta Leaves Extracts for Removal of Warts and Skin Diseases
- Author
-
Kripa, N.; Department of Biomedical Engineering, Bharath Institute of Higher Education and Research, Chennai – 600073, Kishore Kanna, R.; Department of Biomedical Engineering, Bharath Institute of Higher Education and Research, Chennai – 600073, Kripa, N.; Department of Biomedical Engineering, Bharath Institute of Higher Education and Research, Chennai – 600073, and Kishore Kanna, R.; Department of Biomedical Engineering, Bharath Institute of Higher Education and Research, Chennai – 600073
- Abstract
Euphorbia hirta is a a medicinal plant which is been widely used from olden days as a herbal medicine for various purposes for mankind. Our country is known for its medical and Ayurvedic treatments. Various parts of the plant is been used for various uses, and here the leaves are been used for the treatment of warts and skin diseases. Questionnaire was prepared and the feedback was collected before the usage of this medicinal plant. The latex or the sap of the plant was collected from Euphorbia hirta and it has been used for the treatment. After the completion of the treatment again questionnaire was given and the feedback was collected for the group of people. This research describes about the medicinal properties, the days of treatment, the feedback and the other important aspects of Euphorbia hirta. The research enlightens on how efficient the leaf extracts of Euphorbia hirta totally irradiated the warts and the fungal diseases totally without any pain and side effects. Moreover, the availability of the leaves are abundant and easily available, hence economical. There are many medicinal plants around us like this each having its own chemical composition which can be used in our daily life without any side effects instead of going for synthetic drugs.
- Published
- 2022
5. Elemental analysis of Chinese and Japanese tea and tea leaf by ICP-MS
- Author
-
Jun, Naohara, Yuto, Yamashita, and Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science
- Published
- 2018
6. Reduction effect of powered air purifying respirator on physical load : Measurements in factories
- Author
-
Daichi, Kubo, Takeru, Naiki, Hiroshi, Yokomizo, Tadashi, Nishide, Masaharu, Yamamoto, Graduate School of Engineering, Okayama University of Science, Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science, and Okayama Occupational Health Promotion center
- Published
- 2018
7. Blood Compatibility of Plasticizers for a Blood Circulation Tube : Studies on human blood
- Author
-
Hiroshi, Shibata, Takuya, Daiou, Yu, Kosaka, Yuta, Imamura, Daiki, Suzuki, Shingo, Okamoto, Hironobu, Sugiyama, Takeru, Naiki, Graduate School of Engineering, Okayama University of Science, Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science, and Biomedical Engineering Center, Nikkiso Corporation
- Published
- 2018
8. Studying the Elution Kinetics of Components in the Priming-Rinse Dialyzer Solution Using a Two-Compartmental Model
- Author
-
Koji, Matsuura, Midori, Futami, Yoshie, Asahara, Kazunori, Takemoto, Shuhei, Nakaji, Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science, and Department of Biomedical Science Educational Center, Kake Gakuen
- Published
- 2018
9. Physical Aspects of Cell Culture Substrates: Topography, Roughness, and Elasticity
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA., Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Macromolecular Sciences and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Center for Functional Nanostructures (CFN), Karlsruhe Institute of Technology (KIT), Wolfgang???Gaede???Str. 1a, 76131 Karlsruhe, Germany, Zoologisches Institut, Zell??? und Neurobiologie, Karlsruhe Institute of Technology (KIT), Haid???und???Neu???Stra??e 9, 76131 Karlsruhe, Germany, Ross, Aftin M., Jiang, Zhongxiang, Bastmeyer, Martin, Lahann, Joerg, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA., Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Macromolecular Sciences and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Center for Functional Nanostructures (CFN), Karlsruhe Institute of Technology (KIT), Wolfgang???Gaede???Str. 1a, 76131 Karlsruhe, Germany, Zoologisches Institut, Zell??? und Neurobiologie, Karlsruhe Institute of Technology (KIT), Haid???und???Neu???Stra??e 9, 76131 Karlsruhe, Germany, Ross, Aftin M., Jiang, Zhongxiang, Bastmeyer, Martin, and Lahann, Joerg
- Abstract
The cellular environment impacts a myriad of cellular functions by providing signals that can modulate cell phenotype and function. Physical cues such as topography, roughness, gradients, and elasticity are of particular importance. Thus, synthetic substrates can be potentially useful tools for exploring the influence of the aforementioned physical properties on cellular function. Many micro??? and nanofabrication processes have been employed to control substrate characteristics in both 2D and 3D environments. This review highlights strategies for modulating the physical properties of surfaces, the influence of these changes on cell responses, and the promise and limitations of these surfaces in in???vitro settings. While both hard and soft materials are discussed, emphasis is placed on soft substrates. Moreover, methods for creating synthetic substrates for cell studies, substrate properties, and impact of substrate properties on cell behavior are the main focus of this review. The cellular environment plays a significant role in cell phenotype and function. As such, physical properties of cell culture substrates including topography, roughness, and elasticity may be utilized to investigate the influence of these physical cues on the cellular response. In this review, strategies for modulating the physical properties of surfaces, the influence of these changes on cell responses, and the promise and limitations of these surfaces in in???vitro settings are highlighted, with a particular emphasis on elastic substrates.
- Published
- 2012
10. Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA ; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI 48109, USA, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA, Department of Pathology, University of Michigan, Ann Arbor, MI, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA, Kim, Y., Gelehrter, S. K., Fifer, C. G., Lu, J. C., Owens, G. E., Berman, D. R., Williams, J., Wilkinson, J. E., Ives, K. A., Xu, Z., Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA ; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI 48109, USA, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA, Department of Pathology, University of Michigan, Ann Arbor, MI, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA, Kim, Y., Gelehrter, S. K., Fifer, C. G., Lu, J. C., Owens, G. E., Berman, D. R., Williams, J., Wilkinson, J. E., Ives, K. A., and Xu, Z.
- Abstract
Objectives Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. Methods The experiments involved 11 gravid sheep at 102???129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 ??s) delivered by an external 1-MHz focused ultrasound transducer at a 0.2???1-kHz pulse-repetition rate and 10???16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury. Results Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Conclusion Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright ?? 2011 ISUOG. Published by John Wiley & Sons, Ltd.
- Published
- 2011
11. Primary rat hepatocyte culture on 3D nanofibrous polymer scaffolds for toxicology and pharmaceutical research
- Author
-
University of Michigan, Macromolecular Science and Engineering Center, Ann Arbor, Michigan, Department of Biologic and Materials Sciences, Department of Biomedical Engineering, University of Michigan, Macromolecular Science and Engineering Center, 1011 North University Ave, Room 2211, Ann Arbor, Michigan 48109-1078; telephone: +1-734-764-2209; fax: +1-734-647-2110 ; Department of Biologic and Materials Sciences, Department of Biomedical Engineering, University of Michigan, Macromolecular Science and Engineering Center, 1011 North University Ave, Room 2211, Ann Arbor, Michigan 48109-1078; telephone: +1-734-764-2209; fax: +1-734-647-2110., Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; telephone: +49-40-7410-58572; fax: +49-40-7410-45311, Department of Internal Medicine and Department of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; telephone: +49-40-7410-58572; fax: +49-40-7410-45311 ; Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; telephone: +49-40-7410-58572; fax: +49-40-7410-45311., Bierwolf, Jeanette, Lutgehetmann, Marc, Feng, Kai, Erbes, Johannes, Deichmann, Steffen, Toronyi, Eva, Stieglitz, Christina, Nashan, Bjoern, Ma, Peter X., Pollok, Joerg M., University of Michigan, Macromolecular Science and Engineering Center, Ann Arbor, Michigan, Department of Biologic and Materials Sciences, Department of Biomedical Engineering, University of Michigan, Macromolecular Science and Engineering Center, 1011 North University Ave, Room 2211, Ann Arbor, Michigan 48109-1078; telephone: +1-734-764-2209; fax: +1-734-647-2110 ; Department of Biologic and Materials Sciences, Department of Biomedical Engineering, University of Michigan, Macromolecular Science and Engineering Center, 1011 North University Ave, Room 2211, Ann Arbor, Michigan 48109-1078; telephone: +1-734-764-2209; fax: +1-734-647-2110., Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; telephone: +49-40-7410-58572; fax: +49-40-7410-45311, Department of Internal Medicine and Department of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; telephone: +49-40-7410-58572; fax: +49-40-7410-45311 ; Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; telephone: +49-40-7410-58572; fax: +49-40-7410-45311., Bierwolf, Jeanette, Lutgehetmann, Marc, Feng, Kai, Erbes, Johannes, Deichmann, Steffen, Toronyi, Eva, Stieglitz, Christina, Nashan, Bjoern, Ma, Peter X., and Pollok, Joerg M.
- Abstract
Primary rat hepatocytes are a widely used experimental model to estimate drug metabolism and toxicity. In currently used two-dimensional (2D) cell culture systems, typical problems like morphological changes and the loss of liver cell-specific functions occur. We hypothesize that the use of polymer scaffolds could overcome these problems and support the establishment of three-dimensional (3D) culture systems in pharmaceutical research. Isolated primary rat hepatocytes were cultured on collagen-coated nanofibrous scaffolds for 7 days. Cell loading efficiency was quantified via DNA content measurement. Cell viability and presence of liver-cell-specific functions (albumin secretion, glycogen storage capacity) were evaluated. The activity of liver-specific factors was analyzed by immunofluorescent staining. RNA was isolated to establish quantitative real-time PCR. Our results indicate that primary rat hepatocytes cultured on nanofibrous scaffolds revealed high viability and well-preserved glycogen storage. Albumin secretion was existent during the entire culture period. Hepatocytes remain HNF-4 positive, indicating highly preserved cell differentiation. Aggregated hepatocytes re-established positive signaling for Connexin 32, a marker for differentiated hepatocyte interaction. ZO-1-positive hepatocytes were detected indicating formation of tight junctions. Expression of cytochrome isoenzymes was inducible. Altogether the data suggest that nanofibrous scaffolds provide a good in vitro microenvironment for neo tissue regeneration of primary rat hepatocytes. Biotechnol. Bioeng. 2011; 108:141???150. ?? 2010 Wiley Periodicals, Inc.
- Published
- 2011
12. Recreating the perivascular niche ex vivo using a microfluidic approach
- Author
-
Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California ; Department of Biomedical Engineering, University of California-Irvine, Irvine, California ; Department of Biomedical Engineering, University of Michigan, 2154 Lurie Biomedical Engineering Building, 1101 Beal Ave, Ann Arbor, Michigan 48109; telephone: 734-615-1398; fax: 734-647-4834 ; Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California, Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California, Department of Biomedical Engineering, University of California-Irvine, Irvine, California, Department of Biomedical Engineering, University of California-Irvine, Irvine, California ; Life Sciences Division, Department of Cancer & DNA Damage Responses, Lawrence Berkeley National Laboratory, Berkeley, California, Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California ; Department of Biomedical Engineering, University of California-Irvine, Irvine, California ; School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea, Carrion, Bita, Huang, Carlos P., Ghajar, Cyrus M., Kachgal, Suraj, Kniazeva, Ekaterina, Jeon, Noo Li, Putnam, Andrew J., Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California ; Department of Biomedical Engineering, University of California-Irvine, Irvine, California ; Department of Biomedical Engineering, University of Michigan, 2154 Lurie Biomedical Engineering Building, 1101 Beal Ave, Ann Arbor, Michigan 48109; telephone: 734-615-1398; fax: 734-647-4834 ; Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California, Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California, Department of Biomedical Engineering, University of California-Irvine, Irvine, California, Department of Biomedical Engineering, University of California-Irvine, Irvine, California ; Life Sciences Division, Department of Cancer & DNA Damage Responses, Lawrence Berkeley National Laboratory, Berkeley, California, Department of Chemical Engineering and Materials Science, University of California-Irvine, Irvine, California ; Department of Biomedical Engineering, University of California-Irvine, Irvine, California ; School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea, Carrion, Bita, Huang, Carlos P., Ghajar, Cyrus M., Kachgal, Suraj, Kniazeva, Ekaterina, Jeon, Noo Li, and Putnam, Andrew J.
- Abstract
Stem cell niches are composed of numerous microenvironmental features, including soluble and insoluble factors, cues from other cells, and the extracellular matrix (ECM), which collectively serve to maintain stem cell quiescence and promote their ability to support tissue homeostasis. A hallmark of many adult stem cell niches is their proximity to the vasculature in vivo, a feature common to neural stem cells, mesenchymal stem cells (MSCs) from bone marrow and adipose tissue, hematopoietic stem cells, and many tumor stem cells. In this study, we describe a novel 3D microfluidic device (MFD) as a model system in which to study the molecular regulation of perivascular stem cell niches. Endothelial cells (ECs) suspended within 3D fibrin gels patterned in the device adjacent to stromal cells (either fibroblasts or bone marrow-derived MSCs) executed a morphogenetic process akin to vasculogenesis, forming a primitive vascular plexus and maturing into a robust capillary network with hollow well-defined lumens. Both MSCs and fibroblasts formed pericytic associations with the ECs but promoted capillary morphogenesis with distinct kinetics. Biochemical assays within the niche revealed that the perivascular association of MSCs required interaction between their Α6Β1 integrin receptor and EC-deposited laminin. These studies demonstrate the potential of this physiologically relevant ex vivo model system to study how proximity to blood vessels may influence stem cell multipotency. Biotechnol. Bioeng. 2010;107: 1024–1032. © 2010 Wiley Periodicals, Inc.
- Published
- 2010
13. Definition and classification of hyperkinetic movements in childhood
- Author
-
Nursing, School of Health Professions and Studies, University of Michigan, Flint, Michigan, USA, Deptartments of Biomedical Engineering, Biokinesiology, and Neurology, University of Southern California, Los Angeles, California, USA ; Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089-1111, Extramural Research Program, NIH/NINDS, Bethesda, Maryland, USA, Division of Developmental Paediatrics, University of Toronto, Toronto, Ontario, Canada, Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA, Movement Disorders Center, Toronto Western Hospital and Department of Medicine, University of Toronto, Toronto, Ontario, Canada, Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA, Pediatrics and Neurology, Child Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, Functional and Applied Biomechanics Section, NIH, Bethesda, Maryland, USA, Movement Disorders Clinic, Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel, Department of Bioengineering, Stanford University, Stanford, California, USA, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, Pediatrics and Neurology, Pediatric Movement Disorders, The Children's Hospital, University of Colorado, Aurora, Colorado, USA, Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California, USA, Neuropediatric Unit, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm, Sweden, Orthopaedic Hospital Center for Cerebral Palsy, Tarjan Center, University of California - Los Angeles, Los Angeles, California, USA, Movement Disorder and Tourette Syndrome Clinics, Child Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA, Department of Physical Therapy, Samuel Merritt University, Oakland, California, USA, Pediatric Rehabilitation Medicine, Gillette Children's Specialty Healthcare, St. Paul, Minnesota, USA, Departments of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA, Northwestern University Physical Therapy and Human Movement Sciences, Chicago, Illinois, USA, Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA, Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, Pediatrics, Developmental Pediatrics, McMaster University, Hamilton, Ontario, Canada, School of Physical Therapy, Slippery Rock University, Slippery Rock, Pennsylvania, USA, Department of Neurology, Columbia University Medical Center, New York, New York, USA, Department of Orthopedic Surgery, Stanford University Medical Center, Stanford, California, USA, Pediatric Neurology, Shriners Hospital for Children, Oregon Health & Science University, Portland, Oregon, USA, Biology, Electrical and Computer Engineering, and Physics, Northeastern University, Boston, Massachusettes, USA, Neurology and Pediatrics, Pediatric Motor Disorders Research Program, University of Utah School of Medicine, Salt Lake City, Utah, USA, Department of Biomedical Engineering and Division of Biokinesiology & Physical Therapy, The University of Southern California, Los Angeles, California, Sanger, Terence D., Chen, Daofen, Fehlings, Darcy L., Hallett, Mark, Lang, Anthony E., Mink, Jonathan W., Singer, Harvey S., Alter, Katharine, Ben-Pazi, Hilla, Butler, Erin E., Chen, Robert, Collins, Abigail, Dayanidhi, Sudarshan, Forssberg, Hans, Fowler, Eileen, Gilbert, Donald L., Gorman, Sharon L., Gormley, Mark E., Jinnah, H. A., Kornblau, Barbara, Krosschell, Kristin J., Lehman, Rebecca K., MacKinnon, Colum, Malanga, C. J., Mesterman, Ronit, Michaels, Margaret Barry, Pearson, Toni S., Rose, Jessica, Russman, Barry S., Sternad, Dagmar, Swoboda, Kathy J., Valero-Cuevas, Francisco, Nursing, School of Health Professions and Studies, University of Michigan, Flint, Michigan, USA, Deptartments of Biomedical Engineering, Biokinesiology, and Neurology, University of Southern California, Los Angeles, California, USA ; Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089-1111, Extramural Research Program, NIH/NINDS, Bethesda, Maryland, USA, Division of Developmental Paediatrics, University of Toronto, Toronto, Ontario, Canada, Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA, Movement Disorders Center, Toronto Western Hospital and Department of Medicine, University of Toronto, Toronto, Ontario, Canada, Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA, Pediatrics and Neurology, Child Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, Functional and Applied Biomechanics Section, NIH, Bethesda, Maryland, USA, Movement Disorders Clinic, Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel, Department of Bioengineering, Stanford University, Stanford, California, USA, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, Pediatrics and Neurology, Pediatric Movement Disorders, The Children's Hospital, University of Colorado, Aurora, Colorado, USA, Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California, USA, Neuropediatric Unit, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm, Sweden, Orthopaedic Hospital Center for Cerebral Palsy, Tarjan Center, University of California - Los Angeles, Los Angeles, California, USA, Movement Disorder and Tourette Syndrome Clinics, Child Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA, Department of Physical Therapy, Samuel Merritt University, Oakland, California, USA, Pediatric Rehabilitation Medicine, Gillette Children's Specialty Healthcare, St. Paul, Minnesota, USA, Departments of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA, Northwestern University Physical Therapy and Human Movement Sciences, Chicago, Illinois, USA, Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA, Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, Pediatrics, Developmental Pediatrics, McMaster University, Hamilton, Ontario, Canada, School of Physical Therapy, Slippery Rock University, Slippery Rock, Pennsylvania, USA, Department of Neurology, Columbia University Medical Center, New York, New York, USA, Department of Orthopedic Surgery, Stanford University Medical Center, Stanford, California, USA, Pediatric Neurology, Shriners Hospital for Children, Oregon Health & Science University, Portland, Oregon, USA, Biology, Electrical and Computer Engineering, and Physics, Northeastern University, Boston, Massachusettes, USA, Neurology and Pediatrics, Pediatric Motor Disorders Research Program, University of Utah School of Medicine, Salt Lake City, Utah, USA, Department of Biomedical Engineering and Division of Biokinesiology & Physical Therapy, The University of Southern California, Los Angeles, California, Sanger, Terence D., Chen, Daofen, Fehlings, Darcy L., Hallett, Mark, Lang, Anthony E., Mink, Jonathan W., Singer, Harvey S., Alter, Katharine, Ben-Pazi, Hilla, Butler, Erin E., Chen, Robert, Collins, Abigail, Dayanidhi, Sudarshan, Forssberg, Hans, Fowler, Eileen, Gilbert, Donald L., Gorman, Sharon L., Gormley, Mark E., Jinnah, H. A., Kornblau, Barbara, Krosschell, Kristin J., Lehman, Rebecca K., MacKinnon, Colum, Malanga, C. J., Mesterman, Ronit, Michaels, Margaret Barry, Pearson, Toni S., Rose, Jessica, Russman, Barry S., Sternad, Dagmar, Swoboda, Kathy J., and Valero-Cuevas, Francisco
- Abstract
Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back-and-forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials. ?? 2010 Movement Disorder Society
- Published
- 2010
14. Kinetic properties of ASC protein aggregation in epithelial cells
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, Michigan, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan ; Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, Michigan ; Associate Professor, Department of Biomedical Engineering, University of Michigan College of Engineering, 1101 Beal Avenue, Box 2170, Ann Arbor, MI 48109-2099., Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan ; Professor, Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Box 2200, Ann Arbor, MI 48109-2200., Cheng, Jun, Waite, Andrea L., Tkaczyk, Eric R., Ke, Kevin, Richards, Neil, Hunt, Alan J., Gumucio, Deborah L., Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, Michigan, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan ; Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, Michigan ; Associate Professor, Department of Biomedical Engineering, University of Michigan College of Engineering, 1101 Beal Avenue, Box 2170, Ann Arbor, MI 48109-2099., Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan ; Professor, Department of Cell and Developmental Biology, University of Michigan Medical School, 109 Zina Pitcher Place, Box 2200, Ann Arbor, MI 48109-2200., Cheng, Jun, Waite, Andrea L., Tkaczyk, Eric R., Ke, Kevin, Richards, Neil, Hunt, Alan J., and Gumucio, Deborah L.
- Abstract
A poptosis-associated s peck-like protein with C ARD domain (ASC), an adaptor protein composed of caspase recruitment and pyrin domains, can efficiently self-associate to form a large spherical structure, called a speck. Although ASC aggregation is generally involved with both inflammatory processes and apoptosis, the detailed dynamics of speck formation have not been characterized. In this report, speck formation in HeLa cells transfected with ASC is examined by time-lapse live-imaging by confocal laser scanning microscopy. The results show that ASC aggregation is a very rapid and tightly regulated process. Prior to speck formation, soluble ASC aggregation is a low probability event, and the affinity of ASC subunits for one another is very low. Following a speck nucleation event, the affinity for further addition of ASC subunits increases dramatically, and aggregation is a highly energetically favorable reaction (Gibbs free energy????????????40???kJ/mol). This leads to a rapid depletion of soluble ASC, making it highly unlikely that a second speck will form inside the same cell and assuring that speck formation is ???all or none,??? with a well-defined end point. Comparison with kinetic models of the aggregation process indicates diffusion, instead of active transport, is the dominant process for speck growth. Though speck formation and aggresome formation share some properties, we show that the two processes are distinct. J. Cell. Physiol. 222: 738???747, 2010. ?? 2009 Wiley-Liss, Inc.
- Published
- 2010
15. The pore size of polycaprolactone scaffolds has limited influence on bone regeneration in an in vivo model
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2099, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2099 ; Department of Biologic and Material Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2099 ; Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2125 ; Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109-0329 ; 1109 Gerstacker Bldg., 2200 Bonisteel Blvd., Ann Arbor, Michigan 48109-2099, Roosa, Sara M. Mantila, Kemppainen, Jessica M., Moffitt, Erin N., Krebsbach, Paul H., Hollister, Scott J., Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2099, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2099 ; Department of Biologic and Material Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2099 ; Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109-2125 ; Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109-0329 ; 1109 Gerstacker Bldg., 2200 Bonisteel Blvd., Ann Arbor, Michigan 48109-2099, Roosa, Sara M. Mantila, Kemppainen, Jessica M., Moffitt, Erin N., Krebsbach, Paul H., and Hollister, Scott J.
- Abstract
Bone tissue engineering scaffolds should be designed to optimize mass transport, cell migration, and mechanical integrity to facilitate and enhance new bone growth. Although many scaffold parameters could be modified to fulfill these requirements, pore size is an important scaffold characteristic that can be rigorously controlled with indirect solid freeform fabrication. We explored the effect of pore size on bone regeneration and scaffold mechanical properties using polycaprolactone (PCL) scaffolds designed with interconnected, cylindrical orthogonal pores. Three scaffold designs with unique microarchitectures were fabricated, having pore sizes of 350, 550, or 800 ??m. Bone morphogenetic protein-7 transduced human gingival fibroblasts were suspended in fibrin gel, seeded into scaffolds, and implanted subcutaneously in immuno-compromised mice for 4 or 8 weeks. We found that (1) modulus and peak stress of the scaffold/bone constructs depended on pore size and porosity at 4 weeks but not at 8 weeks, (2) bone growth inside pores depended on pore size at 4 weeks but not at 8 weeks, and (3) the length of implantation time had a limited effect on scaffold/bone construct properties. In conclusion, pore sizes between 350 and 800 ??m play a limited role in bone regeneration in this tissue engineering model. Therefore, it may be advantageous to explore the effects of other scaffold structural properties, such as pore shape, pore interconnectivity, or scaffold permeability, on bone regeneration when designing PCL scaffolds for bone tissue engineering. ?? 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
- Published
- 2010
16. Quantitative inference of cellular parameters from microfluidic cell culture systems
- Author
-
Department of Chemical Engineering, University of Michigan, 3328 G.G. Brown, 2300 Hayward, Ann Arbor, Michigan 48109; telephone: 734-763-0679; fax: 734-764-7453, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Chemical Engineering, University of Michigan, 3328 G.G. Brown, 2300 Hayward, Ann Arbor, Michigan 48109; telephone: 734-763-0679; fax: 734-764-7453 ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan ; Department of Chemical Engineering, University of Michigan, 3328 G.G. Brown, 2300 Hayward, Ann Arbor, Michigan 48109; telephone: 734-763-0679; fax: 734-764-7453., Mehta, Khamir, Mehta, Geeta, Takayama, Shuichi, Linderman, Jennifer, Department of Chemical Engineering, University of Michigan, 3328 G.G. Brown, 2300 Hayward, Ann Arbor, Michigan 48109; telephone: 734-763-0679; fax: 734-764-7453, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Chemical Engineering, University of Michigan, 3328 G.G. Brown, 2300 Hayward, Ann Arbor, Michigan 48109; telephone: 734-763-0679; fax: 734-764-7453 ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan ; Department of Chemical Engineering, University of Michigan, 3328 G.G. Brown, 2300 Hayward, Ann Arbor, Michigan 48109; telephone: 734-763-0679; fax: 734-764-7453., Mehta, Khamir, Mehta, Geeta, Takayama, Shuichi, and Linderman, Jennifer
- Abstract
Microfluidic cell culture systems offer a convenient way to measure cell biophysical parameters in conditions close to the physiological environment. We demonstrate the application of a mathematical model describing the spatial distribution of nutrient and growth factor concentrations in inferring cellular oxygen uptake rates from experimental measurements. We use experimental measurements of oxygen concentrations in a poly(dimethylsiloxane) (PDMS) microreactor culturing human hepatocellular liver carcinoma cells (HepG2) to infer quantitative information on cellular oxygen uptake rates. We use a novel microchannel design to avoid the parameter correlation problem associated with simultaneous cellular uptake and diffusion of oxygen through the PDMS surface. We find that the cellular uptake of oxygen is dependent on the cell density and can be modeled using a logistic term in the Michaelis???Menten equation. Our results are significant not only for the development of novel assays to quantitatively infer cell response to stimuli, but also for the development, design, and optimization of novel in vitro systems for drug discovery and tissue engineering. Biotechnol. Bioeng. 2009;103: 966???974. ?? 2009 Wiley Periodicals, Inc.
- Published
- 2009
17. In vitro Toxicity Testing of Nanoparticles in 3D Cell Culture
- Author
-
Department of Biomedical Engineering, Chemical Engineering, Material Science and Engineering University of Michigan 3074 H. H. Dow Building 2300 Hayward Street Ann Arbor, MI 48109 (USA), Department of Biomedical Engineering, Chemical Engineering, Material Science and Engineering University of Michigan 3074 H. H. Dow Building 2300 Hayward Street Ann Arbor, MI 48109 (USA) ; Department of Biomedical Engineering, Chemical Engineering, Material Science and Engineering University of Michigan 3074 H. H. Dow Building 2300 Hayward Street Ann Arbor, MI 48109 (USA)., Nico Technologies Co. Ypsilanti, MI 48198 (USA), Lee, Jungwoo, Lilly, G. Daniel, Doty, R. Christopher, Podsiadlo, Paul, Kotov, Nicholas A., Department of Biomedical Engineering, Chemical Engineering, Material Science and Engineering University of Michigan 3074 H. H. Dow Building 2300 Hayward Street Ann Arbor, MI 48109 (USA), Department of Biomedical Engineering, Chemical Engineering, Material Science and Engineering University of Michigan 3074 H. H. Dow Building 2300 Hayward Street Ann Arbor, MI 48109 (USA) ; Department of Biomedical Engineering, Chemical Engineering, Material Science and Engineering University of Michigan 3074 H. H. Dow Building 2300 Hayward Street Ann Arbor, MI 48109 (USA)., Nico Technologies Co. Ypsilanti, MI 48198 (USA), Lee, Jungwoo, Lilly, G. Daniel, Doty, R. Christopher, Podsiadlo, Paul, and Kotov, Nicholas A.
- Abstract
Common 2D cell cultures do not adequately represent the functions of 3D tissues that have extensive cell–cell and cell–matrix interactions, as well as markedly different diffusion/transport conditions. Hence, testing cytotoxicity in 2D cultures may not accurately reflect the actual toxicity of nanoparticles (NPs) and other nanostructures in the body. To obtain more adequate and detailed information about NP–tissue interactions, we here introduce a 3D-spheroid-culture-based NP toxicology testing system. Hydrogel inverted colloidal crystal (ICC) scaffolds are used to create a physiologically relevant and standardized 3D liver tissue spheroid model for in vitro assay application. Toxicity of CdTe and Au NPs are tested in both 2D and 3D spheroid cultures. The results reveal that NP toxic effects are significantly reduced in the spheroid culture when compared to the 2D culture data. Tissue-like morphology and phenotypic change are identified to be the major factors in diminishing toxicity. Acting as an intermediate stage bridging in vitro 2D and in vivo, our in vitro 3D cell-culture model would extend current cellular level cytotoxicity to the tissue level, thereby improving the predictive power of in vitro NP toxicology.
- Published
- 2009
18. Spectral-spatial pulse design for through-plane phase precompensatory slice selection in T 2 * -weighted functional MRI
- Author
-
Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Athinoula A. Martinos Center for Biomedical Imaging, 149 13th Street, Suite 2301, Charlestown, MA 02129, USA, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, GE Healthcare, Waukesha, WI, Yip, Chun-Yu, Yoon, Daehyun, Olafsson, Valur, Lee, Sangwoo, Grissom, William A., Fessler, Jeffrey A., Noll, Douglas C., Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Athinoula A. Martinos Center for Biomedical Imaging, 149 13th Street, Suite 2301, Charlestown, MA 02129, USA, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, GE Healthcare, Waukesha, WI, Yip, Chun-Yu, Yoon, Daehyun, Olafsson, Valur, Lee, Sangwoo, Grissom, William A., Fessler, Jeffrey A., and Noll, Douglas C.
- Abstract
T 2 * -weighted functional MR images suffer from signal loss artifacts caused by the magnetic susceptibility differences between air cavities and brain tissues. We propose a novel spectral-spatial pulse design that is slice-selective and capable of mitigating the signal loss. The two-dimensional spectral???spatial pulses create precompensatory phase variations that counteract through-plane dephasing, relying on the assumption that resonance frequency offset and through-plane field gradient are spatially correlated. The pulses can be precomputed before functional MRI experiments and used repeatedly for different slices in different subjects. Experiments with human subjects showed that the pulses were effective in slice selection and loss mitigation at different brain regions. Magn Reson Med 61:1137???1147, 2009. ?? 2009 Wiley-Liss, Inc.
- Published
- 2009
19. Influence of hormones and hormone metabolites on the growth of schwann cells derived from embryonic stem cells and on tumor cell lines expressing variable levels of neurofibromin This article was accepted for inclusion in the Special Focus on Stem Cells??? Developmental Dynamics 236 #12 .
- Author
-
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Internal Medicine-Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan ; Department of Cell and Developmental Biology, University of Michigan Medical School, 3053 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, Department of Pediatrics, Neurology Division, University of Florida College of Medicine, Gainesville, Florida, Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, Roth, Therese M., Ramamurthy, Poornapriya, Muir, David, Wallace, Margaret R., Zhu, Yuan, Chang, Lou, Barald, Kate F., Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Internal Medicine-Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan ; Department of Cell and Developmental Biology, University of Michigan Medical School, 3053 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, Department of Pediatrics, Neurology Division, University of Florida College of Medicine, Gainesville, Florida, Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, Roth, Therese M., Ramamurthy, Poornapriya, Muir, David, Wallace, Margaret R., Zhu, Yuan, Chang, Lou, and Barald, Kate F.
- Abstract
Loss of neurofibromin, the protein product of the tumor suppressor gene neurofibromatosis type 1 (NF1), is associated with neurofibromas, composed largely of Schwann cells. The number and size of neurofibromas in NF1 patients have been shown to increase during pregnancy. A mouse embryonic stem cell (mESC) model was used, in which mESCs with varying levels of neurofibromin were differentiated into Schwann-like cells. NF1 cell lines derived from a malignant and a benign human tumor were used to study proliferation in response to hormones. Estrogen and androgen receptors were not expressed or expressed at very low levels in the NF1+/+ cells, at low levels in NF1+/???cells, and robust levels in NF1???/???cells. A 17??-estradiol (E2) metabolite, 2-methoxy estradiol (2ME2) is cytotoxic to the NF1???/??? malignant tumor cell line, and inhibits proliferation in the other cell lines. 2ME2 or its derivatives could provide new treatment avenues for NF1 hormone-sensitive tumors at times of greatet hormonal influence. Developmental Dynamics 237:513???524, 2008.?? 2008 Wiley-Liss, Inc.
- Published
- 2008
20. Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants
- Author
-
Department of Biomedical Engineering, University of Michigan, MI, USA, Department of Biomedical Engineering, University of Wisconsin-Madison, WI, USA, Wadsworth Center, Albany, New York, USA, Williams, Justin C., Hippensteel, Joseph A., Dilgen, John, Shain, William, Kipke, Daryl R., Department of Biomedical Engineering, University of Michigan, MI, USA, Department of Biomedical Engineering, University of Wisconsin-Madison, WI, USA, Wadsworth Center, Albany, New York, USA, Williams, Justin C., Hippensteel, Joseph A., Dilgen, John, Shain, William, and Kipke, Daryl R.
- Abstract
A series of animal experiments was conducted to characterize changes in the complex impedance of chronically implanted electrodes in neural tissue. Consistent trends in impedance changes were observed across all animals, characterized as a general increase in the measured impedance magnitude at 1 kHz. Impedance changes reach a peak approximately 7 days post-implant. Reactive responses around individual electrodes were described using immuno- and histo-chemistry and confocal microscopy. These observations were compared to measured impedance changes. Several features of impedance changes were able to differentiate between confined and extensive histological reactions. In general, impedance magnitude at 1 kHz was significantly increased in extensive reactions, starting about 4 days post-implant. Electrodes with extensive reactions also displayed impedance spectra with a characteristic change at high frequencies. This change was manifested in the formation of a semi-circular arc in the Nyquist space, suggestive of increased cellular density in close proximity to the electrode site. These results suggest that changes in impedance spectra are directly influenced by cellular distributions around implanted electrodes over time and that impedance measurements may provide an online assessment of cellular reactions to implanted devices.
- Published
- 2008
21. Biomolecular motor-driven microtubule translocation in the presence of shear flow: analysis of redirection behaviours
- Author
-
Department of Mechanical Engineering, University of Michigan, 2350 Hayward Street, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109, USA, Department of Mechanical Engineering, University of Michigan, 2350 Hayward Street, Ann Arbor, MI 48109, USA ; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109, USA, Ann Arbor, Kim, Taesung, Kao, Ming-Tse, Meyhöfer, Edgar, Hasselbrink, Ernest F., Department of Mechanical Engineering, University of Michigan, 2350 Hayward Street, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109, USA, Department of Mechanical Engineering, University of Michigan, 2350 Hayward Street, Ann Arbor, MI 48109, USA ; Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109, USA, Ann Arbor, Kim, Taesung, Kao, Ming-Tse, Meyhöfer, Edgar, and Hasselbrink, Ernest F.
- Abstract
We suggest a concept for powering microfluidic devices with biomolecular motors and microtubules to meet the demands for highly efficient microfluidic devices. However, to successfully implement such devices, we require methods for active control over the direction of microtubule translocation. While most previous work has employed largely microfabricated passive mechanical patterns designed to guide the direction of microtubules, in this paper we demonstrate that hydrodynamic shear flow can be used to align microtubules translocating on a kinesin-coated surface in a direction parallel to the fluid flow. Our evidence supports the hypothesis that the mechanism of microtubule redirection is simply that drag force induced by viscous shear bends the leading end of a microtubule, which may be cantilevered beyond its kinesin supports. This cantilevered end deflects towards the flow direction, until it is subsequently bound to additional kinesins; as translocation continues, the process repeats until the microtubule is largely aligned with the flow, to a limit determined by random fluctuations created by thermal energy. We present statistics on the rate of microtubule alignment versus various strengths of shear flow as well as concentrations of kinesin, and also investigate the effects of shear flow on the motility.
- Published
- 2008
22. Magnetic field perturbation of neural recording and stimulating microelectrodes
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA, Ann Arbor, Martinez-Santiesteban, Francisco M., Swanson, Scott D., Noll, Douglas C., Anderson, David J., Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA, Ann Arbor, Martinez-Santiesteban, Francisco M., Swanson, Scott D., Noll, Douglas C., and Anderson, David J.
- Abstract
To improve the overall temporal and spatial resolution of brain mapping techniques, in animal models, some attempts have been reported to join electrophysiological methods with functional magnetic resonance imaging (fMRI). However, little attention has been paid to the image artefacts produced by the microelectrodes that compromise the anatomical or functional information of those studies. This work presents a group of simulations and MR images that show the limitations of wire microelectrodes and the potential advantages of silicon technology, in terms of image quality, in MRI environments. Magnetic field perturbations are calculated using a Fourier-based method for platinum (Pt) and tungsten (W) microwires as well as two different silicon technologies. We conclude that image artefacts produced by microelectrodes are highly dependent not only on the magnetic susceptibility of the materials used but also on the size, shape and orientation of the electrodes with respect to the main magnetic field. In addition silicon microelectrodes present better MRI characteristics than metallic microelectrodes. However, metallization layers added to silicon materials can adversely affect the quality of MR images. Therefore only those silicon microelectrodes that minimize the amount of metallic material can be considered MR-compatible and therefore suitable for possible simultaneous fMRI and electrophysiological studies. High resolution gradient echo images acquired at 2 T (TR/TE = 100/15 ms, voxel size = 100 × 100 × 100 µm3) of platinum–iridium (Pt–Ir, 90%–10%) and tungsten microwires show a complete signal loss that covers a volume significantly larger than the actual volume occupied by the microelectrodes: roughly 400 times larger for Pt–Ir and 180 for W, at the tip of the microelectrodes. Similar MR images of a single-shank silicon microelectrode only produce a partial volume effect on the voxels occupied by the probe with less than 50% of signal loss.
- Published
- 2008
23. Image registration methods in high-dimensional space
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 ; Department of Radiology, University of Michigan, Ann Arbor, MI 48109-0533, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 ; Department of EECS, University of Michigan, Ann Arbor, MI 48109-2122 ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, Department of Radiology, University of Michigan, Ann Arbor, MI 48109-0533 ; Department of EECS, University of Michigan, Ann Arbor, MI 48109-2122, Neemuchwala, Huzefa, Hero, Alfred, Zabuawala, Sakina, Carson, Paul, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 ; Department of Radiology, University of Michigan, Ann Arbor, MI 48109-0533, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 ; Department of EECS, University of Michigan, Ann Arbor, MI 48109-2122 ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, Department of Radiology, University of Michigan, Ann Arbor, MI 48109-0533 ; Department of EECS, University of Michigan, Ann Arbor, MI 48109-2122, Neemuchwala, Huzefa, Hero, Alfred, Zabuawala, Sakina, and Carson, Paul
- Published
- 2007
24. A mouse embryonic stem cell model of Schwann cell differentiation for studies of the role of neurofibromatosis type 1 in Schwann cell development and tumor formation
- Author
-
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; The Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Program in Neuroscience, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; The Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan ; Program in Neuroscience, University of Michigan, Ann Arbor, Michigan ; Department of Cell and Developmental Biology, University of Michigan Medical School, 3053 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA, Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, Roth, Therese M., Ramamurthy, Poornapriya, Ebisu, Fumi, Lisak, Robert P., Bealmear, Beverly M., Barald, Kate F., Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; The Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; Program in Neuroscience, University of Michigan, Ann Arbor, Michigan, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan ; The Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan ; Program in Neuroscience, University of Michigan, Ann Arbor, Michigan ; Department of Cell and Developmental Biology, University of Michigan Medical School, 3053 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA, Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, Roth, Therese M., Ramamurthy, Poornapriya, Ebisu, Fumi, Lisak, Robert P., Bealmear, Beverly M., and Barald, Kate F.
- Abstract
The neurofibromatosis Type 1 (NF1) gene functions as a tumor suppressor gene. One known function of neurofibromin, the NF1 protein product, is to accelerate the slow intrinsic GTPase activity of Ras to increase the production of inactive rasGDP, with wide-ranging effects on p21ras pathways. Loss of neurofibromin in the autosomal dominant disorder NF1 is associated with tumors of the peripheral nervous system, particularly neurofibromas, benign lesions in which the major affected cell type is the Schwann cell (SC). NF1 is the most common cancer predisposition syndrome affecting the nervous system. We have developed an in vitro system for differentiating mouse embryonic stem cells (mESC) that are NF1 wild type (+/+), heterozygous (+/−), or null (−/−) into SC-like cells to study the role of NF1 in SC development and tumor formation. These mES-generated SC-like cells, regardless of their NF1 status, express SC markers correlated with their stage of maturation, including myelin proteins. They also support and preferentially direct neurite outgrowth from primary neurons. NF1 null and heterozygous SC-like cells proliferate at an accelerated rate compared to NF1 wild type; this growth advantage can be reverted to wild type levels using an inhibitor of MAP kinase kinase (Mek). The mESC of all NF1 types can also be differentiated into neuron-like cells. This novel model system provides an ideal paradigm for studies of the role of NF1 in cell growth and differentiation of the different cell types affected by NF1 in cells with differing levels of neurofibromin that are neither transformed nor malignant. © 2007 Wiley-Liss, Inc.
- Published
- 2007
25. Joint design of trajectory and RF pulses for parallel excitation
- Author
-
Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Functional MRI Laboratory, University of Michigan, 2360 Bonisteel Ave., Ann Arbor, MI 48109-2108, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Yip, Chun-Yu, Grissom, William A., Fessler, Jeffrey A., Noll, Douglas C., Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Functional MRI Laboratory, University of Michigan, 2360 Bonisteel Ave., Ann Arbor, MI 48109-2108, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, Yip, Chun-Yu, Grissom, William A., Fessler, Jeffrey A., and Noll, Douglas C.
- Abstract
We propose an alternating optimization framework for the joint design of excitation k-space trajectory and RF pulses for small-tip-angle parallel excitation. Using Bloch simulations, we show that compared with conventional designs with predetermined trajectories, joint designs can often excite target patterns with improved accuracy and reduced total integrated pulse power, particularly at high reduction factors. These benefits come at a modest increase in computational time. Magn Reson Med 58:598–604, 2007. © 2007 Wiley-Liss, Inc.
- Published
- 2007
26. Label-Free Affinity Assays by Rapid Detection of Immune Complexes in Submicrometer Pores This work was supported by an NSF CAREER award (M.M.) and by a research grant from IMRA America and AISIN USA as well as seed funds from the College of Engineering, University of Michigan. The authors thank Daniel J. Estes, Amy P. Wong, Irina Gitlin, and Paul Bina for valuable discussions.
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2099, USA, Department of Biomedical Engineering and Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, MI 48109-2099, USA, Departments of Biomedical Engineering and Chemical Engineering, University of Michigan, Engineering Research Building (ERB), Room 4107, 2200 Bonisteel Blvd., Ann Arbor, MI 48109-2099, USA, Fax: (+1)???734-763-4371, Uram, Jeffrey D., Ke, Kevin, Hunt, Alan J., Mayer, Michael, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2099, USA, Department of Biomedical Engineering and Center for Ultrafast Optical Science, University of Michigan, Ann Arbor, MI 48109-2099, USA, Departments of Biomedical Engineering and Chemical Engineering, University of Michigan, Engineering Research Building (ERB), Room 4107, 2200 Bonisteel Blvd., Ann Arbor, MI 48109-2099, USA, Fax: (+1)???734-763-4371, Uram, Jeffrey D., Ke, Kevin, Hunt, Alan J., and Mayer, Michael
- Abstract
No Abstract
- Published
- 2007
27. Use of Air-Liquid Two-Phase Flow in Hydrophobic Microfluidic Channels for Disposable Flow Cytometers
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, 3304; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Department of Mechanical Engineering, University of Michigan, Ann Arbor, 2272; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Department of Mechanical Engineering, University of Michigan, Ann Arbor, 2272; Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Ann Arbor, MI, 48109-2125; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Department of Biomedical Engineering, University of Michigan, Ann Arbor, 3304; Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Ann Arbor, MI, 48109-2125; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Ann Arbor, Huh, Dongeun, Tung, Yi-Chung, Wei, Hsien-Hung, Grotberg, James B., Skerlos, Steven J., Kurabayashi, Katsuo, Takayama, Shuichi, Department of Biomedical Engineering, University of Michigan, Ann Arbor, 3304; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Department of Mechanical Engineering, University of Michigan, Ann Arbor, 2272; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Department of Mechanical Engineering, University of Michigan, Ann Arbor, 2272; Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Ann Arbor, MI, 48109-2125; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Department of Biomedical Engineering, University of Michigan, Ann Arbor, 3304; Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Ann Arbor, MI, 48109-2125; GG Brown, 2350 Hayward, Ann Arbor, MI, 48109-2125, Ann Arbor, Huh, Dongeun, Tung, Yi-Chung, Wei, Hsien-Hung, Grotberg, James B., Skerlos, Steven J., Kurabayashi, Katsuo, and Takayama, Shuichi
- Abstract
This paper describes a disposable flow cytometer that uses an air-liquid two-phase microfluidic system to produce a focused high-speed liquid sample stream of particles and cells. The susceptibility of thin liquid columns to instabilities may suggest that focusing of sample liquids with streams of air would be difficult. The design of channel geometry, control of flow rates, and use of appropriate surface chemistries on the channel walls, however, enabled the generation of thin (15???100??m) and partially bounded sample streams that were stable and suitable for rapid cell analysis. Using an inverted epi-fluorescence microscope with a photo-multiplier tube, we demonstrated that the system is capable of counting the number of beads and C 2 C 12 myoblast cells. The effects of different flow rates and surface chemistries of the channel walls on the air-liquid two-phase flows were characterized using optical and confocal microscopy. Use of air instead of liquids as a sheath fluid eliminates the need for large sheath liquid reservoirs, and reduces the volume and weight requirements. The low manufacturing cost and high volumetric efficiency make the air-sheath flow cytometer attractive for use as a stand-alone device or as an integrated component of bio-artificial hybrid microsystems.
- Published
- 2006
28. Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) filmThis work was supported by the Center for Wireless Integrated Microsystems NSF EEC-9986866 and the Whitaker Foundation.
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA, Dow Chemical Co., Freeport, TX 77541, USA, Ann Arbor, Ludwig, Kip A., Uram, Jeffrey D., Yang, Junyan, Martin, David C., Kipke, Daryl R., Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA, Dow Chemical Co., Freeport, TX 77541, USA, Ann Arbor, Ludwig, Kip A., Uram, Jeffrey D., Yang, Junyan, Martin, David C., and Kipke, Daryl R.
- Abstract
Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward the recording sites or minimizing the inherent immune response. The end goal of these efforts is to generate an ideal long-term interface between the recording electrode and surrounding tissue. The goal of this study was to refine a method to electrochemically deposit surfactant-templated ordered poly(3,4-ethylenedioxythiophene) (PEDOT) films on the recording sites of standard ‘Michigan’ probes and to evaluate the efficacy of these modified sites in recording chronic neural activity. PEDOT-coated site performance was compared to control sites over a six-week evaluation period in terms of impedance spectroscopy, signal-to-noise ratio, number of viable unit potentials recorded and local field potential recordings. PEDOT sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. The benefit of reduced initial impedance, however, was mitigated by the impedance contribution of typical silicon electrode encapsulation. Coating sites with PEDOT also reduced the amount of low-frequency drift evident in local field potential recordings. These findings indicate that electrode sites electrochemically deposited with PEDOT films are suitable for recording neural activity in vivo for extended periods. This study also provided a unique opportunity to monitor how neural recording characteristics develop over the six weeks following implantation.
- Published
- 2006
29. Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects
- Author
-
fMRI Laboratory, University of Michigan, Ann Arbor, Michigan, USA ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA ; UM fMRI Laboratory, 2360 Bonisteel Ave., Ann Arbor, MI 48109-2108, fMRI Laboratory, University of Michigan, Ann Arbor, Michigan, USA ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA, Hernandez-Garcia, Luis, Lee, Gregory R., Vazquez, Alberto L., Yip, Chun-Yu, Noll, Douglas C., fMRI Laboratory, University of Michigan, Ann Arbor, Michigan, USA ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA ; UM fMRI Laboratory, 2360 Bonisteel Ave., Ann Arbor, MI 48109-2108, fMRI Laboratory, University of Michigan, Ann Arbor, Michigan, USA ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA, Hernandez-Garcia, Luis, Lee, Gregory R., Vazquez, Alberto L., Yip, Chun-Yu, and Noll, Douglas C.
- Abstract
A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes. Magn Reson Med, 2005. © 2005 Wiley-Liss, Inc.
- Published
- 2006
30. Method of organic carcinogenic substances control in different physical nature objects
- Author
-
Сушко, Ольга Анатоліївна; Kharkiv National University of Radio Electronics 14, Lenin ave., Kharkiv, Ukraine, 61166, Рожицький, Микола Миколайович; Department of Biomedical Engineering 14, Lenin ave., Kharkiv, Ukraine, 61166, Сушко, Ольга Анатоліївна; Kharkiv National University of Radio Electronics 14, Lenin ave., Kharkiv, Ukraine, 61166, and Рожицький, Микола Миколайович; Department of Biomedical Engineering 14, Lenin ave., Kharkiv, Ukraine, 61166
- Abstract
Chemical carcinogenesis caused by intake of exogenous carcinogenic organic compounds is the most widespread reason for initiation and progress of cancer. So the analytical methods for such compounds detection should have low detection limits and high selectivity. Known analytical methods for the carcinogenic substances detection have a number of disadvantages and limitations. Therefore, we have proposed a new optical nanophotonic method for carcinogenic substances detection such as polynuclear aromatic hydrocarbons (PAH) in objects of different physical nature liquids in the first place. This method is based on main physical peculiarities of a new optical science called nanophotonics which, in short, describes size dependent optical transitions in quantum confined space. The article considers main principals of using nanophotonics for the purpose of chemical organic carcinogens detection with the help of so called nanophotonic analytical instruments – sensors. The latter main detection element constitutes nanophotonic material such as semiconductor quantum dots. The specific interactions of the organic carcinogens with the detection elements bringing to the emission of optical analytical signal represent the essence of nanophotonic analytical method revealing its advantages over known approaches. Proposed method and its instrumental realization for certain PAH detection was experimentally tested. As the detection elements semiconductor CdSe/ZnS/TOPO quantum dots were used. On the basis of the obtained results nanophotonic method of analytical control of exogenous carcinogenic substance was developed and its main characteristics were defined showing good perspective for its utilization in ecology, biomedicine and other fields., Работа посвящена обоснованию нового аналитического метода контроля органических канцерогенных веществ в объектах разной физической природы, что использует подходы и достижения современной нанофотоники. Сформулированы основные принципы данного метода, его преимущества и использования в соответствующих аналитических устройствах – сенсорах. Проведено тестирование метода с использованием модельных объектов, содержащих канцерогенный полициклический ароматический углеводород., Робота присвячена обґрунтуванню нового аналітичного методу контролю органічних канцерогенних речовин в об’єктах різної фізичної природи, що використовує підходи та досягнення сучасної нанофотоніки. Сформульовано основні принципи даного методу, його позитивні якості та застосування у відповідних аналітичних пристроях – сенсорах. Проведено тестування методу з використанням модельних об’єктів, що містять канцерогенний поліциклічний ароматичний вуглеводень.
- Published
- 2014
31. Chemically Orthogonal Three???Patch Microparticles
- Author
-
Department of Biomedical Engineering, Chemical Engineering, Macromolecular Science and Engineering, Material Science and Engineering, University of Michigan, Ann Arbor, 48109 (USA) http://www.umich.edu/???lahannj/index.htm, Institute of Functional Interfaces, Karlsruhe Institute of Technology, Hermann???von???Helmholtz???Platz 1, 76344 Eggenstein???Leopoldshafen (Germany), Rahmani, Sahar, Saha, Sampa, Durmaz, Hakan, Donini, Alessandro, Misra, Asish C, Yoon, Jaewon, Lahann, Joerg, Department of Biomedical Engineering, Chemical Engineering, Macromolecular Science and Engineering, Material Science and Engineering, University of Michigan, Ann Arbor, 48109 (USA) http://www.umich.edu/???lahannj/index.htm, Institute of Functional Interfaces, Karlsruhe Institute of Technology, Hermann???von???Helmholtz???Platz 1, 76344 Eggenstein???Leopoldshafen (Germany), Rahmani, Sahar, Saha, Sampa, Durmaz, Hakan, Donini, Alessandro, Misra, Asish C, Yoon, Jaewon, and Lahann, Joerg
- Abstract
Compared to two???dimensional substrates, only a few methodologies exist for the spatially controlled decoration of three???dimensional objects, such as microparticles. Combining electrohydrodynamic co???jetting with synthetic polymer chemistry, we were able to create two??? and three???patch microparticles displaying chemically orthogonal anchor groups on three distinct surface patches of the same particle. This approach takes advantage of a combination of novel chemically orthogonal polylactide???based polymers and their processing by electrohydrodynamic co???jetting to yield unprecedented multifunctional microparticles. Several micropatterned particles were fabricated displaying orthogonal click functionalities. Specifically, we demonstrate novel two??? and three???patch particles. Multi???patch particles are highly sought after for their potential to present multiple distinct ligands in a directional manner. This work clearly establishes a viable route towards orthogonal reaction strategies on multivalent micropatterned particles. Patchwork???Familie : Mikropartikel aus drei Patches (siehe Schema) mit funktionalisierten Poly(lactid)???Derivaten in ausgew??hlten Kompartimenten wurden durch elektrohydrodynamisches (EHD) Co???Spr??hen hergestellt. Die Mikropartikel wurden durch konfokale Raman???Mikrospektroskopie charakterisiert, und die bioorthogonale Oberfl??chenmodifikation eines jedes Patches wurde belegt.
- Published
- 2014
32. Large thin overlapping coils, a novel approach for multichannel transcranial magnetic stimulation
- Author
-
Nieminen, Jaakko O., Perustieteiden korkeakoulu, School of Science, Neurotieteen ja lääketieteellisen tekniikan laitos, Department of Neuroscience and Biomedical Engineering, Ilmoniemi, Risto, Department of Biomedical Engineering and Computational Science (BECS), Lääketieteellisen tekniikan ja laskennallisen tieteen laitos, Koponen, Lari, Nieminen, Jaakko O., Perustieteiden korkeakoulu, School of Science, Neurotieteen ja lääketieteellisen tekniikan laitos, Department of Neuroscience and Biomedical Engineering, Ilmoniemi, Risto, Department of Biomedical Engineering and Computational Science (BECS), Lääketieteellisen tekniikan ja laskennallisen tieteen laitos, and Koponen, Lari
- Abstract
Transcranial magnetic stimulation (TMS) allows for studying the functionality of the brain. Present TMS devices have one or two separate stimulation coils. More stimulation coils would allow new types of stimulation sequences, and thus they could be used to reveal more about brain functionality. However, due to the dimensions of the existing TMS coils, having multiple separate coils is a very limited approach. Rather, the coils should be combined into a single multichannel (mTMS) device. The purpose of this Thesis is to make mTMS more feasible. In order to realize this purpose, a new coil design paradigm is introduced which employs large thin overlapping coils. This paradigm requires a new coil design method and a new coil-former design method, which are developed and tested in this Thesis. This Thesis solves two problems that appear with existing mTMS designs and is a significant step towards successful mTMS., Transkraniaalinen magneettistimulaatio (TMS) mahdollistaa aivotoiminnan tutkimisen. Nykyisissä TMS-laitteissa on yleensä yksi tai joissain tapauksissa kaksi erillistä stimulaatiokelaa. Suurempi kelamäärä mahdollistaisi uudentyyppisiä stimulaatiosekvenssejä, jotka mahdollistaisivat monipuolisemman aivotoiminnan tutkimisen. Koska TMS-kelat ovat verrattain suurikokoisia, ei tätä tavoitetta kuitenkaan pystytä saavuttamaan yhdistämällä monta erillistä TMS-kelaa. Sen sijaan tarvittaisiin yksi monikanavainen (mTMS) laite, jossa eri kanavien kelat on yhdistetty yhdeksi suuremmaksi kokonaisuudeksi. Tämän diplomityön tarkoitus on edistää osaltaan mTMS-laitteen suunnittelua. Tätä varten esitellään uusi mTMS-rakenne, jossa mTMS-kela koostuu suurikokoisista ohuista päällekkäisistä keloista. Tässä diplomityössä kehitetään ja testataan yksittäisten kelojen suunnittelumenetelmä tämäntyyppistä mTMS-kelaa varten. Diplomityössä esiteltävä rakenne ratkaisee kaksi nykyisissä mTMS-kelarakennesuunnitelmissa esiintyvää ongelmaa.
- Published
- 2013
33. Katsaus Coxin selviytymismalleihin Gaussisia prosesseja käyttäen
- Author
-
Vehtari, Aki, Sähkötekniikan korkeakoulu, Department of Biomedical Engineering and Computational Science, Lääketieteellisen tekniikan ja laskennallisen tieteen laitos, Lampinen, Jouko, Suikkanen, Saara, Vehtari, Aki, Sähkötekniikan korkeakoulu, Department of Biomedical Engineering and Computational Science, Lääketieteellisen tekniikan ja laskennallisen tieteen laitos, Lampinen, Jouko, and Suikkanen, Saara
- Abstract
Selvitytymismallit ovat paljon käytettyjä mallinnusmenetelmiä lääketieteen parissa. Näiden mallien avulla pyritän mallintamaan elinajan odotetta sekundaaripreventiotapauksessa tapahtuman jälkeistä selviytymistä tutkittaessa tai primaaripreventiotapauksessa tutkittaessa ajan jaksoa ensimmäisen tapahtuman ilmentymiseen. Perinteisesti tähän tarkoitukseen ollaan käytetty Cox:in selviytymismalleja ja Kaplan-Meier estimaatteja. Näiden mallien puutteena on kuitenkin selittävien muuttujien aikariippuvuuden mallintaminen puuttuminen. Yleisessä tiedossa on, että aikariippuvuuksia on olemassa, näiden mallintaminen on vain hyvin hankalaa. Tässä työssä kertaan perinteisen Coxin selviytymis-mallin sekä Kaplan-Maierin estimaatin sekä tavan rakentaa selviytymismalli Coxin mallin pohjalta, joka on toteutettu Bayesilaisen laskennan ja Gaussisten prosessien avulla. Näiden menetelmien avulla malli aikariippuvuudelle saadaan mukaan survival-malliin ja mallin tarkkuus paranee verrattuna perinteiseen Coxin selviytymismalliin jonkin verran validointikriteeristä riippuen., Survival-models are widely used modeling tools among medical science. The aim of using these models is to model the life time of observed item after some procedure in secondary prevention and the first onset of the event in primary prevention. The models used for survival modeling are usually Cox survival model an Kaplan-Meier estimate. The onset of these models is that they lack the time dependency model which obviously do exist between covariates and observed items. The reason for this is that it has been really hard to interpret the time dependency model in to these models. In this thesis I review the original Cox survival model and Kaplan-Meier estimate and review a new way to construct a survival model based on Cox survival model, Bayesian data analysis, and Gaussian processes. In this way the time dependency model can be added to the survival model and the modeling accuracy improves at least on some level depending on what modeling accuracy measures we are using.
- Published
- 2013
34. Changes in corticospinal excitability during reach adaptation in force fields
- Author
-
UCL - SSS/IONS/COSY - Systems & cognitive Neuroscience, UCL - SST/ICTM/INMA - Pôle en ingénierie mathématique, Johns Hopkins School of Medicine - Department of Biomedical Engineering, Orban de Xivry, Jean-Jacques, Ahmadi-Pajouh, Mohammad Ali, Harran, Michelle D., Salimpour, Yousef, Shadmehr, Reza, UCL - SSS/IONS/COSY - Systems & cognitive Neuroscience, UCL - SST/ICTM/INMA - Pôle en ingénierie mathématique, Johns Hopkins School of Medicine - Department of Biomedical Engineering, Orban de Xivry, Jean-Jacques, Ahmadi-Pajouh, Mohammad Ali, Harran, Michelle D., Salimpour, Yousef, and Shadmehr, Reza
- Abstract
Both abrupt and gradually imposed perturbations produce adaptive changes in motor output, but the neural basis of adaptation may be distinct. Here, we measured the state of the motor cortex (M1) and the corticospinal network during adaptation by measuring motor evoked potentials(MEPs) before reach onset using transcranial magnetic stimulation of M1. Subjects reached in a force field in a schedule in which the field was introduced either abruptly or gradually over many trials. In both groups by end of training muscles that countered the perturbation in a given direction increased their activity during the reach (labeled as on-direction for each muscle). In the abrupt group, in the period before the reach toward the on-direction, MEPs in these muscles also increased, suggesting a direction-specific increase in the excitability of corticospinal network. However, in the gradual group these MEP changes were missing. Following training there was a period of washout. The MEPs did not return to baseline. Rather, in the abrupt group the off-direction MEPs increased to match the on-direction MEPs. Therefore, we observed changes in corticospinal excitability in the abrupt but not gradual condition. Abrupt training includes repetition of motor commands, and repetition may be the key factor that produces this plasticity. Furthermore, washout did not return MEPs to baseline, suggesting that washout engaged a new network that masked but did not erase the effects of previous adaptation. Abrupt but not gradual training appears to induce changes in M1 and/or corticospinal networks.
- Published
- 2013
35. Winner for outstanding research in the Ph.D. category for the 2013 society for biomaterials meeting and exposition, April 10???13, 2013, Boston, Massachusetts
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Rao, Rameshwar R., Peterson, Alexis W., Stegemann, Jan P., Department of Biomedical Engineering, University of Michigan, Ann Arbor, Rao, Rameshwar R., Peterson, Alexis W., and Stegemann, Jan P.
- Abstract
Modular tissue engineering applies biomaterials???based approaches to create discrete cell???seeded microenvironments, which can be further assembled into larger constructs for the repair of injured tissues. In the current study, we embedded human bone marrow???derived mesenchymal stem cells (MSC) and human adipose???derived stem cells (ASC) in collagen/fibrin (COL/FIB) and collagen/fibrin/hydroxyapatite (COL/FIB/HA) microbeads, and evaluated their suitability for bone tissue engineering applications. Microbeads were fabricated using a water???in???oil emulsification process, resulting in an average microbead diameter of approximately 130 ?? 25 ??m. Microbeads supported both cell viability and cell spreading of MSC and ASC over 7 days in culture. The embedded cells also began to remodel and compact the microbead matrix as demonstrated by confocal reflectance microscopy imaging. After two weeks of culture in media containing osteogenic supplements, both MSC and ASC deposited calcium mineral in COL/FIB microbeads, but not in COL/FIB/HA microbeads. There were no significant differences between MSC and ASC in any of the assays examined, suggesting that either cell type may be an appropriate cell source for orthopedic applications. This study has implications in the creation of defined microenvironments for bone repair, and in developing a modular approach for delivery of pre???differentiated cells. ?? 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
- Published
- 2013
36. Effects of BMI on the risk and frequency of AIS 3+ injuries in motor???vehicle crashes
- Author
-
Department of Emergency Medicine, University of Michigan Injury Center, Ann Arbor, MI 48109, USA, Department of Statistics, University of Michigan, Ann Arbor, MI 48109???1107, USA, Department of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, MI 48109???2029, USA, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA, University of Michigan Transportation Research Institute, Ann Arbor, MI 48109???2150, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109???2099, USA, Rupp, Jonathan D., Flannagan, Carol A.C., Leslie, Andrew J., Hoff, Carrie N., Reed, Matthew P., Cunningham, Rebecca M., Department of Emergency Medicine, University of Michigan Injury Center, Ann Arbor, MI 48109, USA, Department of Statistics, University of Michigan, Ann Arbor, MI 48109???1107, USA, Department of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, MI 48109???2029, USA, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA, University of Michigan Transportation Research Institute, Ann Arbor, MI 48109???2150, USA, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109???2099, USA, Rupp, Jonathan D., Flannagan, Carol A.C., Leslie, Andrew J., Hoff, Carrie N., Reed, Matthew P., and Cunningham, Rebecca M.
- Abstract
Objective: Determine the effects of BMI on the risk of serious???to???fatal injury (Abbreviated Injury Scale ??? 3 or AIS 3+) to different body regions for adults in frontal, nearside, farside, and rollover crashes. Design and Methods: Multivariate logistic regression analysis was applied to a probability sample of adult occupants involved in crashes generated by combining the National Automotive Sampling System (NASS???CDS) with a pseudoweighted version of the Crash Injury Research and Engineering Network database. Logistic regression models were applied to weighted data to estimate the change in the number of occupants with AIS 3+ injuries if no occupants were obese. Results: Increasing BMI increased risk of lower???extremity injury in frontal crashes, decreased risk of lower???extremity injury in nearside impacts, increased risk of upper???extremity injury in frontal and nearside crashes, and increased risk of spine injury in frontal crashes. Several of these findings were affected by interactions with gender and vehicle type. If no occupants in frontal crashes were obese, 7% fewer occupants would sustain AIS 3+ upper???extremity injuries, 8% fewer occupants would sustain AIS 3+ lower???extremity injuries, and 28% fewer occupants would sustain AIS 3+ spine injuries. Conclusions: Results of this study have implications on the design and evaluation of vehicle safety systems.
- Published
- 2013
37. Wrapping and dispersion of multiwalled carbon nanotubes improves electrical conductivity of protein???nanotube composite biomaterials
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, 1101 Beal Ave., Ann Arbor, Michigan 48109, Department of Chemistry, University of Michigan, Ann Arbor, 930 N. University Ave., Ann Arbor, Michigan 48108, Voge, Christopher M., Johns, Jeremy, Raghavan, Mekhala, Morris, Michael D., Stegemann, Jan P., Department of Biomedical Engineering, University of Michigan, Ann Arbor, 1101 Beal Ave., Ann Arbor, Michigan 48109, Department of Chemistry, University of Michigan, Ann Arbor, 930 N. University Ave., Ann Arbor, Michigan 48108, Voge, Christopher M., Johns, Jeremy, Raghavan, Mekhala, Morris, Michael D., and Stegemann, Jan P.
- Abstract
Composites of extracellular matrix proteins reinforced with carbon nanotubes have the potential to be used as conductive biopolymers in a variety of biomaterial applications. In this study, the effect of functionalization and polymer wrapping on the dispersion of multiwalled carbon nanotubes (MWCNT) in aqueous media was examined. Carboxylated MWCNT were wrapped in either Pluronic ?? F127 or gelatin. Raman spectroscopy and X???ray photoelectron spectroscopy showed that covalent functionalization of the pristine nanotubes disrupted the carbon lattice and added carboxyl groups. Polymer and gelatin wrapping resulted in increased surface adsorbed oxygen and nitrogen, respectively. Wrapping also markedly increased the stability of MWCNT suspensions in water as measured by settling time and zeta potential, with Pluronic ?? ???wrapped nanotubes showing the greatest effect. Treated MWCNT were used to make 3D collagen???fibrin???MWCNT composite materials. Carboxylated MWCNT resulted in a decrease in construct impedance by an order of magnitude, and wrapping with Pluronic ?? resulted in a further order of magnitude decrease. Functionalization and wrapping also were associated with maintenance of fibroblast function within protein???MWCNT materials. These data show that increased dispersion of nanotubes in protein???MWCNT composites leads to higher conductivity and improved cytocompatibility. Understanding how nanotubes interact with biological systems is important in enabling the development of new biomedical technologies. ?? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:231???238, 2013.
- Published
- 2012
38. Nano???/microfiber scaffold for tissue engineering: Physical and biological properties
- Author
-
Department of Cardiology, Restorative Sciences, and Endodontics, of the University of Michigan School of Dentistry and the Department of Biomedical Engineering, University of Michigan College of Engineering in Ann Arbor, Michigan, Department of Operative Dentistry School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil, Department of Operative Dentistry School of Dentistry, University of Paran??, Paran??, PR, Brazil, Technology Development Center, Federal University of Pelotas, Pelotas, RS, Brazil, Santana, Bianca Palma, dos Reis Paganotto, Gian Francesco, Nedel, Fernanda, Piva, Evandro, de Carvalho, Rodrigo Varella, N??r, Jacques Eduardo, Demarco, Fl??vio Fernando, Villarreal Carre??o, Neftali Lenin, Department of Cardiology, Restorative Sciences, and Endodontics, of the University of Michigan School of Dentistry and the Department of Biomedical Engineering, University of Michigan College of Engineering in Ann Arbor, Michigan, Department of Operative Dentistry School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil, Department of Operative Dentistry School of Dentistry, University of Paran??, Paran??, PR, Brazil, Technology Development Center, Federal University of Pelotas, Pelotas, RS, Brazil, Santana, Bianca Palma, dos Reis Paganotto, Gian Francesco, Nedel, Fernanda, Piva, Evandro, de Carvalho, Rodrigo Varella, N??r, Jacques Eduardo, Demarco, Fl??vio Fernando, and Villarreal Carre??o, Neftali Lenin
- Abstract
Alginate hydrogel (AH) has intrinsic physical and biological limitations that hinder its broader application in tissue engineering. We hypothesized that the inclusion of nanofibers in the hydrogel and the use of a biotemplate that mimics nature would enhance the translational potential of alginate hydrogels. In this study, we have shown a method to obtain nano???/microfibers of titanium (nfTD) and hydroxyapatite (nfHY) using cotton as a biotemplate. These fibers were incorporated in the alginate hydrogel and the mechanical characteristics and biological response to these reinforced materials were evaluated. We observed that these nanofibers resembled the structure of natural collagen and did not mediate cell toxicity. The incorporation of nfTD or nfHY to the AH has not increased the viscosity of the hydrogel. Therefore, this is a feasible method to produce a scaffold with improved physical characteristics, while at the same time generating an enhanced environment for cell adhesion and proliferation. ?? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3051???3058, 2012.
- Published
- 2012
39. Lab???on???a???chip biophotonics: its application to assisted reproductive technologies
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA, Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA, Department of Molecular and Integrated Physiology, University of Michigan, Ann Arbor, MI 48109, USA, Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Division of Nano???Bio and Chemical Engineering WCU Project, UNIST, Ulsan, Republic of Korea, Mappes, Timo, Schmidt, Holger, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA, Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA, Department of Molecular and Integrated Physiology, University of Michigan, Ann Arbor, MI 48109, USA, Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Division of Nano???Bio and Chemical Engineering WCU Project, UNIST, Ulsan, Republic of Korea, Mappes, Timo, and Schmidt, Holger
- Abstract
With the benefits of automation, sensitivity and precision, microfluidics has enabled complex and otherwise tedious experiments. Lately, lab???on???a???chip (LOC) has proven to be a useful tool for enhancing non???invasive assisted reproductive technology (ART). Non???invasive gamete and embryo assessment has largely been through periodic morpohological assessment using optical microscopy and early LOC ART was the same. As we realize that morphological assessment is a poor indication of gamete or embryo health, more advanced biophotonics has emerged in LOC ART to assay for metabolites or gamete separation via optoelectrical tweezers. Off???chip, even more advanced biophotonics with broad spectrum analysis of metabolites and secretomes has been developed that show even higher accuracy to predicting reproductive potential. The integration of broad spectrum metabolite analysis into LOC ART is an exciting future that merges automation and sensitivity with the already highly accurate and strong predictive power of biophotonics. (?? 2012 WILEY???VCH Verlag GmbH & Co. KGaA, Weinheim)
- Published
- 2012
40. Using polymeric materials to control stem cell behavior for tissue regeneration
- Author
-
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109???2099, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan 48109???1078, Zhang, Nianli, Kohn, David H., Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109???2099, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan 48109???1078, Zhang, Nianli, and Kohn, David H.
- Abstract
Patients with organ failure often suffer from increased morbidity and decreased quality of life. Current strategies of treating organ failure have limitations, including shortage of donor organs, low efficiency of grafts, and immunological problems. Tissue engineering emerged about two decades ago as a strategy to restore organ function with a living, functional engineered substitute. However, the ability to engineer a functional organ is limited by a limited understanding of the interactions between materials and cells that are required to yield functional tissue equivalents. Polymeric materials are one of the most promising classes of materials for use in tissue engineering, due to their biodegradability, flexibility in processing and property design, and the potential to use polymer properties to control cell function. Stem cells offer potential in tissue engineering because of their unique capacity to self???renew and differentiate into neurogenic, osteogenic, chondrogenic, and myogenic lineages under appropriate stimuli from extracellular components. This review examines recent advances in stem cell???polymer interactions for tissue regeneration, specifically highlighting control of polymer properties to direct adhesion, proliferation, and differentiation of stem cells, and how biomaterials can be designed to provide some of the stimuli to cells that the natural extracellular matrix does. (Part C) 96:63???81, 2012. ?? 2012 Wiley Periodicals, Inc.
- Published
- 2012
41. Functional Properties of Visual Pigments using A1 and A2 Chromophore: From Molecules to Ecology
- Author
-
Helsingin yliopisto, bio- ja ympäristötieteellinen tiedekunta, biotieteiden laitos, Helsingfors universitet, bio- och miljövetenskapliga fakulteten, biovetenskapliga institutionen, University of Helsinki, Faculty of Biological and Environmental Sciences, Department of Biosciences, Division of Physiology and Neuroscience, Department of Biomedical Engineering and Computational Science, Aalto University, Saarinen, Pia, Helsingin yliopisto, bio- ja ympäristötieteellinen tiedekunta, biotieteiden laitos, Helsingfors universitet, bio- och miljövetenskapliga fakulteten, biovetenskapliga institutionen, University of Helsinki, Faculty of Biological and Environmental Sciences, Department of Biosciences, Division of Physiology and Neuroscience, Department of Biomedical Engineering and Computational Science, Aalto University, and Saarinen, Pia
- Abstract
The first event in vision is the absorption of a photon by a visual pigment molecule in a retinal photoreceptor cell. Activation of the molecule triggers a chemical amplification cascade, which finally leads to a change in the membrane potential of the cell. However, a visual pigment molecule may also be spontaneously activated by thermal energy. The resulting electrical response is identical to that caused by a photon. Such false light signals form a background noise limiting the detection of dim light. The absorption spectrum of a visual pigment (its ability to use different wavelengths of light) and its propensity for thermal activation both depend on the minimum amount of energy required for activation (the activation energy Ea). These properties of the pigment can be tuned on an evolutionary time scale by changes in the amino acid sequence of the protein part (the opsin) or on a physiological time scale by changing the light-sensitive cofactor bound to the opsin, the chromophore. The latter option is accessible only to poikilothermic vertebrates having two alternative chromophores (retinal A1 and A2). In this thesis, functional consequences of the A1-A2 exchange were investigated. In the first part, the relation between the changes of the absorption spectrum and the activation energy was quantitatively measured in several species of amphibians and fishes using both chromophores. The A2-induced shift of the absorption spectrum towards longer wavelengths was found always to correlate with a decrease in Ea. Later investigations have confirmed that decreasing Ea increases the rate of thermal activations. Thus the switch from A1 to A2 in the same opsin gives a more red-sensitive but noisier pigment. Against this background, the second part of the thesis investigates chromophore usage in eight populations of nine-spined sticklebacks (Pungitius pungitius) from different light environments. The amino acid sequence of the rods was found to be identical in all population, Näkötapahtuma alkaa, kun verkkokalvon fotoreseptorisoluissa sijaitseva näköpigmenttimolekyyli absorboi fotonin. Molekyylin aktivoituminen käynnistää kemiallisen vahvistusketjun, jonka lopputuloksena solun kalvojännite muuttuu. Näköpigmenttimolekyyli voi kuitenkin aktivoitua myös spontaanisti lämpöenergian vaikutuksesta (termisesti), synnyttäen sähköisen vasteen joka on täysin samanlainen kuin fotonin aiheuttama. Tällaiset väärät valosignaalit muodostavat taustakohinan, joka rajoittaa heikkojen valojen havaitsemista. Näköpigmentin absorptiospektri (sen kyky käyttää valon eri aallonpituuksia) ja sen taipumus aktivoitua termisesti riippuvat molemmat aktivaation vaatimasta minimienergiamäärästä (ns. aktivaatioenergiasta Ea). Pigmentin ominaisuuksia voidaan säätää joko evolutiivisella aikaskaalalla proteiiniosan (opsiinin) aminohapposekvenssiä muuttamalla tai fysiologisella aikaskaalalla opsiiniin sidotun valoherkän kofaktorin, ns. kromoforin, vaihdolla. Jälkimmäinen optio on vain vaihtolämpöisillä selkärankaisilla, joilla on käytössään kaksi vaihtoehtoista kromoforia (retinaali A1 ja A2). Tässä väitöskirjassa tutkittiin A1-A2-vaihdon funktionaalisia seurauksia. Ensimmäisessä osassa mitattiin kvantitatiivisesti absorptiospektrin ja aktivaatioenergian muutosten suhdetta useilla sammakko- ja kalalajeilla. Todettiin että A2:een liittyvä absorptiospektrin siirtyminen pitempiin aallonpituuksiin korreloi aina Ea:n laskun kanssa. Myöhemmät tutkimukset ovat vahvistaneet, että Ea:n alentaminen lisää termisten aktivaatioiden määrää. A1-kromoforin vaihtaminen A2:een samassa opsiinissa antaa siis punaherkemmän mutta kohinaisemman pigmentin. Tätä taustaa vasten väitöskirjan toisessa osassa tutkittiin kromoforin käyttöä kahdeksassa, eri valoympäristöissä elävässä kymmenpiikkipopulaatiossa (Pungitius pungitius). Sauvasolujen opsiinien aminohapposekvenssi todettiin identtiseksi kaikissa populaatioissa, joten spektraaliherkkyyden vaihtelu johtui yksinomaan vaihtelevista A1:A2 suhteista.
- Published
- 2012
42. Modification of ventricular repolarization in silent long QT syndrome mutation carriers
- Author
-
Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Aalto University, Department of Biomedical Engineering and Computational Science, Hekkala, Anna-Mari, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Aalto University, Department of Biomedical Engineering and Computational Science, and Hekkala, Anna-Mari
- Abstract
Congenital long QT syndrome (LQTS) is a familial disorder characterized by ventricular repolarization that makes carriers vulnerable to malignant ventricular tachycardia and sudden cardiac death. The three main subtypes (LQT1, LQT2 and LQT3) constitute 95% of cases. The disorder is characterized by a prolonged QT interval in electrocardiograms (ECG), but a considerable portion are silent carriers presenting normal (QTc < 440 ms) or borderline (QTc < 470 ms) QT interval. Genetic testing is available only for 60-70% of patients. A number of pharmaceutical compounds also affect ventricular repolarization, causing a clinically similar disorder called acquired long QT syndrome. LQTS carriers - who already have impaired ventricular repolarization - are especially vulnerable. In this thesis, asymptomatic genotyped LQTS mutation carriers with non-diagnostic resting ECG were studied. The body surface potential mapping (BSPM) system was utilized for ECG recording, and signals were analyzed with an automated analysis program. QT interval length, and the end part of the T wave, the Tpe interval, was studied during exercise stress testing and an epinephrine bolus test. In the latter, T wave morphology was also analyzed. The effect of cetirizine was studied in LQTS carriers and also with supra- therapeutic dose in healthy volunteers. At rest, LQTS mutation carriers had a slightly longer heart rate adjusted QTc interval than healthy subjects (427 ± 31 ms and 379 ± 26 ms; p<0.001), but significant overlapping existed. LQT2 mutation carriers had a conspicuously long Tpe-interval (113 ± 24 ms; compared to 79 ± 11 ms in LQT1, 81 ± 17 ms in LQT3 and 78 ± 10 ms in controls; p<0.001). In exercise stress tests, LQT1 mutation carriers exhibit a long QT interval at high heart rates and during recovery, whereas LQT2 mutation carriers have a long Tpe interval at the beginning of exercise and at the end of recovery at low heart rates. LQT3 mutation carriers exhibit prominent shortening of both, Periytyvän pitkä QT -oireyhtymän (LQTS) geenimutaation kantajat altistuvat kammioperäiselle rytmihäiriölle, joka aiheuttaa joskus äkkikuoleman. Geenimutaation seurauksena sydänlihassolun ionikanavan toiminta muuttuu heikentäen sydänlihaksen sähköistä palautumista eli repolarisaatiota. Kolme yleisintä alatyyppiä (LQT1, LQT2 ja LQT3) kattavat noin 95 % tapauksista. Oireyhtymän voi tunnistaa sydänsähkökäyrästä (EKG) luettavasta pidentyneestä QT-ajasta. Noin neljänneksellä mutaatioiden kantajista QT-aika voi kuitenkin olla normaali, eikä geenitestinkään avulla voida tunnistaa kuin 60-70 % potilaista. Useat lääkeaineet vaikuttavat samoihin sydänlihassolun ionikanaviin aiheuttaen ns. hankitun pitkä QT -oireyhtymän. Periytyvää pitkä QT -oireyhtymää sairastavat ovat erityisessä riskiryhmässä, koska repolarisaatio on jo valmiiksi heikentynyt. Tämän tutkimuksen tarkoitus oli parantaa LQTS-diagnostiikkaa potilailla, joiden ilmiasu EKG:ssä on normaali. Tutkimukseen osallistui oireettomia LQTS-geenimutaatioiden kantajia, joilla oli normaali QT-aika. EKG rekisteröitiin monikanavaisella laitteistolla ja sähkösignaalit analysoitiin tietokoneohjelmalla. Kammiorepolarisaatiota tutkittiin mittaamalla QT-aikaa ja Tpe-aikaa (intervalli T aallon huipusta T-aallon loppuun) rasituskokeen aikana ja adrenaliini-injektion jälkeen. Jälkimmäisessä kokeessa tarkasteltiin myös T-aallon muotoa. Tutkimussarjassa todettiin, että käytetty analyysimenetelmä oli tarkka ja hyvin toistettava. LQTS-geenimutaatioiden kantajilla oli hivenen pidempi QT-aika kuin terveillä verrokeilla, mutta oli huomattavan vaihteleva. LQT2-kantajat saattoi tunnistaa pitkästä Tpe ajasta. Rasituskokeen aikana QT aika ja Tpe-aika käyttäytyivät eri tavoin eri LQTS-alatyypeillä. Pieni adrenaliiniannos aiheutti LQT2-kantajilla Tpe-ajan pitenemän. Suurempi adrenaliiniannos aiheutti T-aallon muutoksia, joita esiintyi enemmän LQTS-kantajilla kuin verrokeilla. Näitä muutoksia nähtiin myös LQT3-kantajilla, jotka eivät yleensä paljastu
- Published
- 2011
43. Polymer Scaffolds for Small-Diameter Vascular Tissue Engineering
- Author
-
Department of Biologic and Materials Sciences, 1011 North University Ave., Room 2211, The University of Michigan, Ann Arbor, MI 48109-1078 (USA), Department of Biologic and Materials Sciences, 1011 North University Ave., Room 2211, The University of Michigan, Ann Arbor, MI 48109-1078 (USA) ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109 (USA) ; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109 (USA) ; Department of Biologic and Materials Sciences, 1011 North University Ave., Room 2211, The University of Michigan, Ann Arbor, MI 48109-1078 (USA)., Ma, Haiyun, Hu, Jiang, Ma, Peter X., Department of Biologic and Materials Sciences, 1011 North University Ave., Room 2211, The University of Michigan, Ann Arbor, MI 48109-1078 (USA), Department of Biologic and Materials Sciences, 1011 North University Ave., Room 2211, The University of Michigan, Ann Arbor, MI 48109-1078 (USA) ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109 (USA) ; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109 (USA) ; Department of Biologic and Materials Sciences, 1011 North University Ave., Room 2211, The University of Michigan, Ann Arbor, MI 48109-1078 (USA)., Ma, Haiyun, Hu, Jiang, and Ma, Peter X.
- Abstract
To better engineer small-diameter blood vessels, a few types of novel scaffolds are fabricated from biodegradable poly( L -lactic acid) (PLLA) by means of thermally induced phase-separation (TIPS) techniques. By utilizing the differences in thermal conductivities of the mold materials and using benzene as the solvent scaffolds with oriented gradient microtubular structures in the axial or radial direction can be created. The porosity, tubular size, and the orientational direction of the microtubules can be controlled by the polymer concentration, the TIPS temperature, and by utilizing materials of different thermal conductivities. These gradient microtubular structures facilitate cell seeding and mass transfer for cell growth and function. Nanofibrous scaffolds with an oriented and interconnected microtubular pore network are also developed by a one-step TIPS method using a benzene/tetrahydrofuran mixture as the solvent without the need for porogen materials. The structural features of such scaffolds can be conveniently adjusted by varying the solvent ratio, phase-separation temperature, and polymer concentration to mimic the nanofibrous features of an extracellular matrix. These scaffolds were fabricated for the tissue engineering of small-diameter blood vessels by utilizing their advantageous structural features to facilitate blood-vessel regeneration.
- Published
- 2010
44. Electrodeposition on Nanofibrous Polymer Scaffolds: Rapid Mineralization, Tunable Calcium Phosphate Composition and Topography
- Author
-
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA ; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry and Chemical Engineering and Biological Engineering, Donghua University, Shanghai, 201620, P. R. China, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA ; Department of Biomedical Engineering, Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA ; Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA., He, Chuanglong, Xiao, Guiyong, Jin, Xiaobing, Sun, Chenghui, Ma, Peter X., Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA ; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry and Chemical Engineering and Biological Engineering, Donghua University, Shanghai, 201620, P. R. China, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA ; Department of Biomedical Engineering, Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA ; Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA., He, Chuanglong, Xiao, Guiyong, Jin, Xiaobing, Sun, Chenghui, and Ma, Peter X.
- Abstract
A straightforward, fast and versatile technique to fabricate mineralized nanofibrous polymer scaffolds for bone regeneration is developed. Nanofibrous poly( L -lactic acid) scaffolds are fabricated using both electrospinning and phase separation techniques. An electrodeposition process is designed to deposit calcium phosphate on the nanofibrous scaffolds. Such scaffolds contain a high quality mineral coating on the fiber surface and have surface topography and chemical composition that are tunable by varying the processing parameters. These scaffolds can mimic the composition and structure of the natural bone extracellular matrix and provide a more biocompatible interface for bone regeneration.
- Published
- 2010
45. What Best Protects the Inverted Weightbearing Ankle Against Further Inversion?
- Author
-
Med Sport, Section of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, Biomechanics Research Laboratory, Department of Mechanical Engineering and Applied Mechanics, Department of Biomedical Engineering, and Institute of Gerontology, Ashton-Miller, James, Ottaviani, Robert, Hutchinson, Christopher, Wojtys, Edward, Med Sport, Section of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, Biomechanics Research Laboratory, Department of Mechanical Engineering and Applied Mechanics, Department of Biomedical Engineering, and Institute of Gerontology, Ashton-Miller, James, Ottaviani, Robert, Hutchinson, Christopher, and Wojtys, Edward
- Abstract
We measured the maximal isometric eversion moment developed under full weightbearing in 20 healthy adult men (age, 24.4 ?? 3.4 years; mean ?? SD) with their ankles in 15?? of inversion. Tests were performed at both 0?? and 32?? of ankle plantar flexion in low- and in three-quarter-top shoes with and without adhesive ath letic tape or one of three proprietary ankle orthoses. At 0?? of ankle plantar flexion, the mean maximal voluntary resistance of the unprotected ankle to an inversion moment was 50 ?? 8 N-m; this increased by an average of 12% (or 6 N-m) when the subject wore a three- quarter-top basketball shoe. The maximal voluntary resistances to inversion moments developed with the ankles further protected by athletic tape or any of three orthoses were not significantly different. Biomechani cal calculations suggest that at 15?? of inversion the fully active ankle evertor muscles isometrically developed a moment up to six times larger than that developed when an athlete wears a three-quarter-top shoe alone and more than three times larger than that developed passively when the athlete has tape or an orthosis worn inside a three-quarter-top shoe. We conclude that fully activated and strong ankle evertor muscles are the best protection for a near-maximally inverted ankle at footstrike.
- Published
- 2010
46. The Effect of Exercise, Prewrap, and Athletic Tape on the Maximal Active and Passive Ankle Resistance to Ankle Inversion
- Author
-
Medsport, Section of Orthopaedic Surgery at the University of Michigan, Ann Arbor, Michigan, Department of Mechanical Engineering and Applied Mechanics, Department of Biomedical Engineering, and Institute of Gerontology at the University of Michigan, Ann Arbor, Michigan, Manfroy, Pierre, Ashton-Miller, James, Wojtys, Edward, Medsport, Section of Orthopaedic Surgery at the University of Michigan, Ann Arbor, Michigan, Department of Mechanical Engineering and Applied Mechanics, Department of Biomedical Engineering, and Institute of Gerontology at the University of Michigan, Ann Arbor, Michigan, Manfroy, Pierre, Ashton-Miller, James, and Wojtys, Edward
- Abstract
This investigation explored alternatives to the null hy potheses that maximal active and passive resistance to inversion developed by a near-maximally inverted and weightbearing ankle is not altered by 1) the use of prophylactic adhesive athletic tape, 2) the use of non- adhesive prewrap (underwrap), or 3) 40 minutes of vigorous exercise. Ten healthy men and 10 healthy women (mean age, 25 ?? 3 years) with no recent ankle injuries underwent testing to determine maximal ankle resistance to inversion under unipedal, weightbearing conditions. Tests were performed with and without the support of athletic tape, and before and after 40 min utes of exercise. Half the testing sessions were per formed with prewrap under the tape. At 15?? of inver sion, without any external ankle support, healthy young men and women could maximally resist a mean (SD) inversion moment of 52.9 (6.4) N-m and 28.3 (5.8) N-m, respectively. Although use of ankle tape provided a 10% increase in maximal resistance to inversion moments, this increase diminished to insignificant lev els after 40 minutes of vigorous exercise. Use of pre wrap improved maximal resistance to inversion by more than 10%.
- Published
- 2010
47. In situ Dynamic Rheological Study of Polyacrylamide during Gelation Coupled with Mathematical Models of Viscosity Advancement
- Author
-
Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA ; Department of Biologic and Materials Sciences (Dentistry), University of Michigan, Ann Arbor, MI 48109, USA ; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Fax: +1 734 763 2013, Savart, Thibaut, Dove, Caroline, Love, Brian J., Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA, Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA ; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA ; Department of Biologic and Materials Sciences (Dentistry), University of Michigan, Ann Arbor, MI 48109, USA ; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Fax: +1 734 763 2013, Savart, Thibaut, Dove, Caroline, and Love, Brian J.
- Abstract
Acrylamide dynamic viscosity has been measured in aqueous solutions. Separate rheological measurements were performed on neat resins devoid of the curing agent over a range of shear rates to yield the initial resin viscosity. The gels were also characterized by sub-ambient DSC to determine the phase structure as a function of formulation. The dynamic viscosity shows a marked sigmoidal behavior with a plateau viscosity. Mathematical interpretations of the gel time both by sigmoidal and power law models were comparable. The power law model allowed a direct determination of the gel time while the sigmoidal model yielded parameters associated with the initial viscosity, one associated with the plateau viscosity of the gel, and two time constants controlling the sharpness of the transition.
- Published
- 2010
48. Conjugated Polymers Combined with a Molecular Beacon for Label-Free and Self-Signal-Amplifying DNA Microarrays
- Author
-
Department of Materials Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA), Department of Chemical Engineering University of Michigan Ann Arbor, MI 48109 (USA), Macromolecular Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA), Department of Materials Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Department of Chemical Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Macromolecular Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Department of Biomedical Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Department of Materials Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA)., Lee, Kangwon, Rouillard, Jean-Marie, Kim, Bong-Gi, Gulari, Erdogan, Kim, Jinsang, Department of Materials Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA), Department of Chemical Engineering University of Michigan Ann Arbor, MI 48109 (USA), Macromolecular Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA), Department of Materials Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Department of Chemical Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Macromolecular Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Department of Biomedical Engineering University of Michigan Ann Arbor, MI 48109 (USA) ; Department of Materials Science and Engineering University of Michigan Ann Arbor, MI 48109 (USA)., Lee, Kangwon, Rouillard, Jean-Marie, Kim, Bong-Gi, Gulari, Erdogan, and Kim, Jinsang
- Abstract
A conjugated polymer (CP) and molecular-beacon-based solid-state DNA sensing system is developed to achieve sensitive, label-free detection. A novel conjugated poly(oxadiazole) derivative exhibiting amine and thiol functional groups ( POX-SH ) is developed for unique chemical and photochemical stability and convenient solid-state on-chip DNA synthesis. POX-SH is soluble in most nonpolar organic solvents and exhibits intense blue fluorescence. POX-SH is covalently immobilized onto a maleimido-functionalized glass slide by means of its thiol group. Molecular beacons having a fluorescent dye or quencher molecule as the fluorescence resonance energy transfer (FRET) acceptor are synthesized on the immobilized POX-SH layer through direct on-chip oligonucleotide synthesis using the amine side chain of POX-SH . Selective hybridization of the molecular beacon probes with the target DNA sequence opens up the molecular beacon probes and affects the FRET between POX-SH and the dye or quencher, producing a sensitive and label-free fluorescence sensory signal. Various molecular design parameters, such as the size of the stem and loop of the molecular beacon, the choice of dye, and the number of quencher molecules are systematically controlled, and their effects on the sensitivity and selectivity are investigated.
- Published
- 2009
49. Diffusional Self-Organization in Exponential Layer-By-Layer Films with Micro- and Nanoscale Periodicity
- Author
-
Department of Chemical Engineering, University of Michigan, Department of Biomedical Engineering, University of Michigan, Department of Mechanical Engineering, University of Michigan, Department of Materials Science and Engineering and Electron Microbeam Analysis Laboratory, University of Michigan, Departments of Chemical Engineering, Materials Science and Engineering, and Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (USA), Fax: (+1)???734-764-7453, Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA), Podsiadlo, Paul, Michel, Marc, Critchley, Kevin, Srivastava, Sudhanshu, Qin, Ming, Lee, Jung Woo, Verploegen, Eric, Hart, A. John, Qi, Ying, Kotov, Nicholas A., Department of Chemical Engineering, University of Michigan, Department of Biomedical Engineering, University of Michigan, Department of Mechanical Engineering, University of Michigan, Department of Materials Science and Engineering and Electron Microbeam Analysis Laboratory, University of Michigan, Departments of Chemical Engineering, Materials Science and Engineering, and Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (USA), Fax: (+1)???734-764-7453, Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA), Podsiadlo, Paul, Michel, Marc, Critchley, Kevin, Srivastava, Sudhanshu, Qin, Ming, Lee, Jung Woo, Verploegen, Eric, Hart, A. John, Qi, Ying, and Kotov, Nicholas A.
- Abstract
No Abstract
- Published
- 2009
50. Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model
- Author
-
Departments of Radiology and Radiation Oncology, Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan 48109-2200, Departments of Internal Medicine and Urology, University of Michigan Comprehensive Cancer Center, Michigan Center for Translational Pathology, Ann Arbor, Michigan 48109, Departments of Internal Medicine and Urology, University of Michigan Comprehensive Cancer Center, Michigan Center for Translational Pathology, Ann Arbor, Michigan 48109 ; 7308 CCC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5946., Biomedical NMR, Department of Biomedical Engineering, Eindhoven, University of Technology, Eindhoven, The Netherlands, Ortho Biotech Oncology Research and Development, Centocor, 145 King of Prussia Road, Radnor, Pennsylvania 19087, Rozel, Stefan, Galb??n, Craig J., Nicolay, Klaas, Lee, Kuei C., Sud, Sudha, Neeley, Chris, Snyder, Linda A., Chenevert, Thomas L., Rehemtulla, Alnawaz, Ross, Brian D., Pienta, Kenneth J., Departments of Radiology and Radiation Oncology, Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan 48109-2200, Departments of Internal Medicine and Urology, University of Michigan Comprehensive Cancer Center, Michigan Center for Translational Pathology, Ann Arbor, Michigan 48109, Departments of Internal Medicine and Urology, University of Michigan Comprehensive Cancer Center, Michigan Center for Translational Pathology, Ann Arbor, Michigan 48109 ; 7308 CCC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5946., Biomedical NMR, Department of Biomedical Engineering, Eindhoven, University of Technology, Eindhoven, The Netherlands, Ortho Biotech Oncology Research and Development, Centocor, 145 King of Prussia Road, Radnor, Pennsylvania 19087, Rozel, Stefan, Galb??n, Craig J., Nicolay, Klaas, Lee, Kuei C., Sud, Sudha, Neeley, Chris, Snyder, Linda A., Chenevert, Thomas L., Rehemtulla, Alnawaz, Ross, Brian D., and Pienta, Kenneth J.
- Abstract
Metastatic prostate cancer continues to be the second leading cause of cancer death in American men with an estimated 28,660 deaths in 2008. Recently, monocyte chemoattractant protein-1 (MCP-1, CCL2) has been identified as an important factor in the regulation of prostate metastasis. CCL2, shown to attract macrophages to the tumor site, has a direct promotional effect on tumor cell proliferation, migration, and survival. Previous studies have shown that anti-CCL2 antibodies given in combination with docetaxel were able to induce tumor regression in a pre-clinical prostate cancer model. A limitation for evaluating new treatments for metastatic prostate cancer to bone is the inability of imaging to objectively assess response to treatment. Diffusion-weighted MRI (DW-MRI) assesses response to anticancer therapies by quantifying the random (i.e., Brownian) motion of water molecules within the tumor mass, thus identifying cells undergoing apoptosis. We sought to measure the treatment response of prostate cancer in an osseous site to docetaxel, an anti-CCL2 agent, and combination treatments using DW-MRI. Measurements of tumor apparent diffusion coefficient (ADC) values were accomplished over time during a 14-day treatment period and compared to response as measured by bioluminescence imaging and survival studies. The diffusion data provided early predictive evidence of the most effective therapy, with survival data results correlating with the DW-MRI findings. DW-MRI is under active investigation in the pre-clinical and clinical settings to provide a sensitive and quantifiable means for early assessment of cancer treatment outcome. J. Cell. Biochem. 107: 58???64, 2009. ?? 2009 Wiley-Liss, Inc.
- Published
- 2009
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.