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Behavior, a Balanced Network of Chemical Transformations(Biokinetics)

Description: While the concept of a biological system as a balanced network of chemical transformations is not a new one, experimental definition of specific systems has been lacking. This paper defines theoretically and experimentally a number of such networks and their behavior and response to some limited environmental changes.
Date: January 13, 1954
Creator: Bradley, D.F. & Calvin, M.
Partner: UNT Libraries Government Documents Department

A biological model for controlling interface growth and morphology.

Description: Biological systems create proteins that perform tasks more efficiently and precisely than conventional chemicals. For example, many plants and animals produce proteins to control the freezing of water. Biological antifreeze proteins (AFPs) inhibit the solidification process, even below the freezing point. These molecules bond to specific sites at the ice/water interface and are theorized to suppress solidification chemically or geometrically. In this project, we investigated the theoretical and experimental data on AFPs and performed analyses to understand the unique physics of AFPs. The experimental literature was analyzed to determine chemical mechanisms and effects of protein bonding at ice surfaces, specifically thermodynamic freezing point depression, suppression of ice nucleation, decrease in dendrite growth kinetics, solute drag on the moving solid/liquid interface, and stearic pinning of the ice interface. Stearic pinning was found to be the most likely candidate to explain experimental results, including freezing point depression, growth morphologies, and thermal hysteresis. A new stearic pinning model was developed and applied to AFPs, with excellent quantitative results. Understanding biological antifreeze mechanisms could enable important medical and engineering applications, but considerable future work will be necessary.
Date: January 1, 2004
Creator: Hoyt, Jeffrey John & Holm, Elizabeth Ann
Partner: UNT Libraries Government Documents Department

The mechanics of soft biological composites.

Description: Biological tissues are uniquely structured materials with technologically appealing properties. Soft tissues such as skin, are constructed from a composite of strong fibrils and fluid-like matrix components. This was the first coordinated experimental/modeling project at Sandia or in the open literature to consider the mechanics of micromechanically-based anisotropy and viscoelasticity of soft biological tissues. We have exploited and applied Sandia's expertise in experimentation and mechanics modeling to better elucidate the behavior of collagen fibril-reinforced soft tissues. The purpose of this project was to provide a detailed understanding of the deformation of ocular tissues, specifically the highly structured skin-like tissue in the cornea. This discovery improved our knowledge of soft/complex materials testing and modeling. It also provided insight into the way that cornea tissue is bio-engineered such that under physiologically-relevant conditions it has a unique set of properties which enhance functionality. These results also provide insight into how non-physiologic loading conditions, such as corrective surgeries, may push the cornea outside of its natural design window, resulting in unexpected non-linear responses. Furthermore, this project created a clearer understanding of the mechanics of soft tissues that could lead to bio-inspired materials, such as highly supple and impact resistant body armor, and improve our design of human-machine interfaces, such as micro-electrical-mechanical (MEMS) based prosthetics.
Date: October 1, 2007
Creator: Nguyen, Thao D. (Sandia National Laboratories, Livermore, CA); Grazier, John Mark; Boyce, Brad Lee & Jones, Reese E. (Sandia National Laboratories, Livermore, CA)
Partner: UNT Libraries Government Documents Department

An HSEF for murine myeloid leukemia

Description: In the past decade, a large amount of effort has gone into the development of hit size effectiveness functions (HSEFs), with the ultimate aim of replacing the present absorbed dose-RBE-Q system. However, the absorbed dose determined at the tissue level is incapable of providing information on single hits on (doses to) the single cell. As a result, it is necessary to resort to microdosimetry, which is capable of providing not only the number of hits on cells, but the distribution of hit sizes as well. From this information, an HSEF can be derived. However, to date there have been no sets of data available on animals exposed to radiations of several qualities, and for which microdosimetric data were available. The objective of the present set of experiments was to remedy this situation. Large numbers of mice were exposed to radiations of several different qualities, and were observed throughout their entire lifespan for the appearance of myeloid leukemia. The HSEF developed for this neoplasm is presented and discussed.
Date: October 1, 1996
Creator: Bond, V.P.; Cronkite, E.P.; Bullis, J.E.; Wuu, C.S.; Marino, S.A. & Zaider, M.
Partner: UNT Libraries Government Documents Department

5. international workshop on the identification of transcribed sequences

Description: This workshop was held November 5--8, 1995 in Les Embiez, France. The purpose of this conference was to provide a multidisciplinary forum for exchange of state-of-the-art information on mapping the human genome. Attention is focused on the following topics: transcriptional maps; functional analysis; techniques; model organisms; and tissue specific libraries and genes. Abstracts are included of the papers that were presented.
Date: December 31, 1995
Partner: UNT Libraries Government Documents Department

Anthropometry for WorldSID, a World-Harmonized Midsize Male Side Impact Crash Dummy

Description: The WorldSID project is a global effort to design a new generation side impact crash test dummy under the direction of the International Organization for Standardization (ISO). The first WorldSID crash dummy will represent a world-harmonized mid-size adult male. This paper discusses the research and rationale undertaken to define the anthropometry of a world standard midsize male in the typical automotive seated posture. Various anthropometry databases are compared region by region and in terms of the key dimensions needed for crash dummy design. The Anthropometry for Motor Vehicle Occupants (AMVO) dataset, as established by the University of Michigan Transportation Research Institute (UMTRI), is selected as the basis for the WorldSID mid-size male, updated to include revisions to the pelvis bone location. The proposed mass of the dummy is 77.3kg with full arms. The rationale for the selected mass is discussed. The joint location and surface landmark database is appended to this paper.
Date: June 19, 2000
Creator: Moss, S.; Wang, Z.; Salloum, M.; Reed, M.; Ratingen, M. Van; Cesari, D. et al.
Partner: UNT Libraries Government Documents Department

Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

Description: This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.
Date: August 1, 1997
Creator: Zhang, Y. & Woloschak, G.E.
Partner: UNT Libraries Government Documents Department

Dysregulation of temperature and liver cytokine gene expression in immunodeficient wasted mice

Description: Wasted mice bear the spontaneous autosomal recessive mutation wst/wst; this genotype is associated with weight loss beginning at 21 days of age, neurologic dysfunction, immunodeficiency at mucosal sites, and increased sensitivity to the killing effects of ionizing radiation. The pathology underlying the disease symptoms is unknown. Experiments reported here were designed to examine thermoregulation and liver expression of specific cytokines in wasted mice and in littermate and parental controls. Our experiments found that wasted mice begin to show a drop in body temperature at 21-23 days following birth, continuing until death at the age of 28 days. Concomitant with that, livers from wasted mice expressed increased amounts of mRNAs specific for cytokines IL,6 and IL-1, the acute phase reactant C-reactive protein, c-jun, and apoptosis-associated Rp-8 when compared to littermate and parental control animals. Levels of {beta}-transforming growth factor (TGF), c-fos, proliferating cell nuclear antigen (PCNA), and ornithine amino transferase (OAT) transcripts were the same in livers from wasted mice and controls. These results suggest a relationship between an acute phase reactant response in wasted mice and temperature dysregulation.
Date: April 25, 1995
Creator: Libertin, C. R.; Ling-Indeck, L.; Weaver, P.; Chang-Liu, Chin-Mei; Strezoska, V.; Heckert, B. et al.
Partner: UNT Libraries Government Documents Department

Interstellar colonization and the zoo hypothesis

Description: Michael Hart and others have pointed out that current estimates of the number of technological civilizations arisen in the Galaxy since its formation is in fundamental conflict with the expectation that such a civilization could colonize and utilize the entire Galaxy in 10 to 20 million years. This dilemma can be called Hart's paradox. Resolution of the paradox requires that one or more of the following are true: we are the Galaxy's first technical civilization; interstellar travel is immensely impractical or simply impossible; technological civilizations are very short-lived; or we inhabit a wildnerness preserve. The latter is the zoo hypothesis. (GHT)
Date: January 1, 1978
Creator: Jones, E.M.
Partner: UNT Libraries Government Documents Department

Model-building codes for membrane proteins.

Description: We have developed a novel approach to modeling the transmembrane spanning helical bundles of integral membrane proteins using only a sparse set of distance constraints, such as those derived from MS3-D, dipolar-EPR and FRET experiments. Algorithms have been written for searching the conformational space of membrane protein folds matching the set of distance constraints, which provides initial structures for local conformational searches. Local conformation search is achieved by optimizing these candidates against a custom penalty function that incorporates both measures derived from statistical analysis of solved membrane protein structures and distance constraints obtained from experiments. This results in refined helical bundles to which the interhelical loops and amino acid side-chains are added. Using a set of only 27 distance constraints extracted from the literature, our methods successfully recover the structure of dark-adapted rhodopsin to within 3.2 {angstrom} of the crystal structure.
Date: January 1, 2005
Creator: Shirley, David Noyes; Hunt, Thomas W.; Brown, W. Michael; Schoeniger, Joseph S. (Sandia National Laboratories, Livermore, CA); Slepoy, Alexander; Sale, Kenneth L. (Sandia National Laboratories, Livermore, CA) et al.
Partner: UNT Libraries Government Documents Department

Mice, myths, and men

Description: The author discusses some examples of how different experimental animal systems have helped to answer questions about the effects of radiation, in particular, carcinogenesis, and to indicate how the new experimental model systems promise an even more exciting future. Entwined in these themes will be observations about susceptibility and extrapolation across species. The hope of developing acceptable methods of extrapolation of estimates of the risk of radiogenic cancer increases as molecular biology reveals the trail of remarkable similarities in the genetic control of many functions common to many species. A major concern about even attempting to extrapolate estimates of risks of radiation-induced cancer across species has been that the mechanisms of carcinogenesis were so different among different species that it would negate the validity of extrapolation. The more that has become known about the genes involved in cancer, especially those related to the initial events in carcinogenesis, the more have the reasons for considering methods of extrapolation across species increased.
Date: December 31, 1994
Creator: Fry, R.J.M.
Partner: UNT Libraries Government Documents Department

International radiobiology archives of long-term animal studies. I. Descriptions of participating institutions and studies

Description: This document describes archived radiobiology animal studies. Information is presented on experimental details, pathology, radioactivity, results, dosimetry, status, and animal type employed.
Date: July 1, 1996
Creator: Gerber, G. B.; Watson, C. R.; Sugahara, T. & Okada, S.
Partner: UNT Libraries Government Documents Department

Environmental and health aspects of CIS-module production, use and disposal

Description: Copper indium diselenide (CIS) is one of the most promising compounds in thin film technology. Since there is scant information available about environmental and health hazards, a study was initiated to characterize risks associated with the production, use and disposal of thin film photovoltaic modules. Data available from literature and developers of this technology contribute to an assessment of potential risks during production. In laboratory experiments the release of hazardous materials during operation caused by accidents or false handling and after disposal are simulated. In biological experiments the possible impact on living matter is established. These experiments comprise toxicity tests with aquatic organisms and rats representing mammals.
Date: December 31, 1994
Creator: Thumm, W.; Finke, A.; Neumeier, B.; Beck, B.; Kettrup, A.; Steinberger, H. et al.
Partner: UNT Libraries Government Documents Department

Improved risk estimates for carbon tetrachloride. Project status report and technical progress report

Description: Carbon tetrachloride (CCl{sub 4}) has been used extensively within the Department of Energy (DOE) nuclear weapons facilities. High levels of CCl{sub 4} at these facilities represent a potential health hazard for workers conducting cleanup operations and for surrounding communities. The overall purpose of these studies is to improve the scientific basis for assessing the health risk associated with human exposure to CCl{sub 4}. Specifically, the authors will determine the toxicokinetics of inhaled and ingested CCl{sub 4} in F344/Crl rats. B6C3F{sub 1} mice, and Syrian hamsters. They will also evaluate species differences in the metabolism of CCl{sub 4} by rats, mice, hamsters, and man. Dose-response relationships will be determined in all these studies. This information will be used to improve the physiologically based pharmacokinetic (PBPK) model for CCl{sub 4} originally developed by Paustenbach et al. (1988) and more recently revised by Thrall and Kenny (1996). The authors will also provide scientific evidence that CCl{sub 4}, like chloroform, is a hepatocarcinogen only when exposure results in cell damage, cell killing, and regenerative cell proliferation.
Date: September 1, 1997
Creator: Benson, J.M.; Nikula, K.J.; Barr, E.B.; Springer, D.L. & Thrall, K.D.
Partner: UNT Libraries Government Documents Department

Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

Description: Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.
Date: September 4, 1997
Creator: Mendelsohn, M.L. & Pierce, P.A.
Partner: UNT Libraries Government Documents Department

The use of transgenic animals to study lipoprotein metabolism

Description: The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.
Date: December 1, 1993
Creator: Rubin, E.M. & Plump, A.S.
Partner: UNT Libraries Government Documents Department

Relevance of in vivo models in melanoma skin cancer

Description: A discussion of possible wavelength dependence of induction of cutaneous malignant melanoma (CMM) is provided. Strengths and weaknesses of various experimental approaches to better understanding of the prevalence of CMM in different human populations including latitude effects are compared. Further the advantages and limitations of the use of the laboratory opossum (Monodelphis domestic), transgenic mice containing SV40 ongogene sequences under tyrosinase promoter control, and a backcross hybrid fish of the genus Xenophorus are contrasted.
Date: December 31, 1995
Creator: Setlow, R.B.
Partner: UNT Libraries Government Documents Department

Modeling Multiple Causes of Carcinogenesis

Description: An array of epidemiological results and databases on test animal indicate that risk of cancer and atherosclerosis can be up- or down-regulated by diet through a range of 200%. Other factors contribute incrementally and include the natural terrestrial environment and various human activities that jointly produce complex exposures to endotoxin-producing microorganisms, ionizing radiations, and chemicals. Ordinary personal habits and simple physical irritants have been demonstrated to affect the immune response and risk of disease. There tends to be poor statistical correlation of long-term risk with single agent exposures incurred throughout working careers. However, Agency recommendations for control of hazardous exposures to humans has been substance-specific instead of contextually realistic even though there is consistent evidence for common mechanisms of toxicological and carcinogenic action. That behavior seems to be best explained by molecular stresses from cellular oxygen metabolism and phagocytosis of antigenic invasion as well as breakdown of normal metabolic compounds associated with homeostatic- and injury-related renewal of cells. There is continually mounting evidence that marrow stroma, comprised largely of monocyte-macrophages and fibroblasts, is important to phagocytic and cytokinetic response, but the complex action of the immune process is difficult to infer from first-principle logic or biomarkers of toxic injury. The many diverse database studies all seem to implicate two important processes, i.e., the univalent reduction of molecular oxygen and breakdown of aginuine, an amino acid, by hydrolysis or digestion of protein which is attendant to normal antigen-antibody action. This behavior indicates that protection guidelines and risk coefficients should be context dependent to include reference considerations of the composite action of parameters that mediate oxygen metabolism. A logic of this type permits the realistic common-scale modeling of multiple causes of carcinogenesis and shifts the risk-assessment logic to considerations of �what dose does?� in contrast to the current process of the substance-specific ...
Date: January 24, 1999
Creator: Jones, T.D.
Partner: UNT Libraries Government Documents Department