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Data Acquisition and Analysis at the Structural Biology Center
The Structural Biology Center (SBC), a national user facility for macromolecular crystallography located at Argonne National Laboratory`s Advanced Photon Source, is currently being built and commissioned. SBC facilities include a bending-magnet beamline, an insertion-device beamline, laboratory and office space adjacent to the beamlines, and associated instrumentation, experimental apparatus, and facilities. SBC technical facilities will support anomalous dispersion phasing experiments, data collection from microcrystals, data collection from crystals with large molecular structures and rapid data collection from multiple related crystal structures for protein engineering and drug design. The SBC Computing Systems and Software Engineering Group is tasked with developing the SBC Control System, which includes computing systems, network, and software. The emphasis of SBC Control System development has been to provide efficient and convenient beamline control, data acquisition, and data analysis for maximal facility and experimenter productivity. This paper describes the SBC Control System development, specifically data acquisition and analysis at the SBC, and the development methods used to meet this goal.
The extracellular matrix of plants: Molecular, cellular and developmental biology
A symposium entitled ``The Extracellular Matrix of Plants: Molecular, Cellular and Developmental Biology was held in Tamarron, Colorado, March 15--21, 1996. The following topics were explored in addresses by 43 speakers: structure and biochemistry of cell walls; biochemistry, molecular biology and biosynthesis of lignin; secretory pathway and synthesis of glycoproteins; biosynthesis of matrix polysaccharides, callose and cellulose; role of the extracellular matrix in plant growth and development; plant cell walls in symbiosis and pathogenesis.
Construction of a genome-wide human BAC-Unigene resource. Final progress report, 1989--1996
Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes (non-redundant, unigene sets of cDNA representing EST clusters) are available for human alone. A total of 44,000 Unigene cDNA clones have been supplied by Research Genetics. Unigenes, or cDNAs are excellent resource for map building for two reasons. Firstly, they exist in two alternative forms -- as both sequence information for PCR primer pairs, and cDNA clones -- thus making library screening by colony hybridization as well as pooled library PCR possible. The authors have developed an efficient and robust procedure to screen genomic libraries with large number of DNA probes. Secondly, the linkage and order of expressed sequences, or genes are highly conserved among human, mouse and other mammalian species. Therefore, mapping with cDNA markers rather than random anonymous STSs will greatly facilitate comparative, evolutionary studies as well as physical map building. They have currently deconvoluted over 10,000 Unigene probes against a 4X coverage human BAC clones from the approved library D by high density colony hybridization method. 10,000 batches of Unigenes are arrayed in an imaginary 100 X 100 matrix from which 100 row pools and 100 column pools are obtained. Library filters are hybridized with pooled probes, thus reducing the number of hybridization required for addressing the positives for each Unigene from 10,000 to 200. Details on the experimental scheme as well as daily progress report is posted on the Web site (http://www.tree.caltech.edu).
The tomography beamline at the National Synchrotron Light Source
We compared the image contrast of a monochromatic CT, Multiple Energy Computed Tomography (MECT), and conventional CT scanner using phantoms. The experimental results indicate that monochromatic CT, with beam energy tuned just above the iodine K-edge, has about a 3 fold advantage in iodine contrast over conventional CT with a 120 kVp beam. Modeling using the same beams at a 3 rad dose and 3 mm slice height on an 18 cm diameter acrylic phantom, the simulations show a noise of 1.2 HU for MECT and 1.9 HU for CCT. Furthermore, despite the Cupping-effect corrections the bone contrast is lower in CCT and varies by 24 HU moving from the phantom`s center to the edge; this indicates an advantage for MECT in detecting and quantifying lesions differing from surrounding tissue by their mean atomic number.
On the computational complexity of sequence design problems
Inverse protein folding concerns the identification of an amino acid sequence that folds to a given structure. Sequence design problems attempt to avoid the apparent difficulty of inverse protein folding by defining an energy that can be minimized to find protein-like sequences. The authors evaluate the practical relevance of two sequence design problems by analyzing their computation complexity. They show that the canonical method of sequence design is intractable, and describe approximation algorithms for this problem. The authors also describe an efficient algorithm that exactly solves the grand canonical method. The analysis shows how sequence design problems can fail to reduce the difficulty of the inverse protein folding problem, and highlights the need to analyze these problems to evaluate their practical relevance.
The Human Genome Project: Information access, management, and regulation. Final report
The Human Genome Project is a large, internationally coordinated effort in biological research directed at creating a detailed map of human DNA. This report describes the access of information, management, and regulation of the project. The project led to the development of an instructional module titled The Human Genome Project: Biology, Computers, and Privacy, designed for use in high school biology classes. The module consists of print materials and both Macintosh and Windows versions of related computer software-Appendix A contains a copy of the print materials and discs containing the two versions of the software.
How do plants enlarge? A balancing act. Workship on plant growth: Final report
There are signals that coordinate the development of various plant parts and thus the rates of enlargement of various plant parts and these were explored during the workshop. The participants tried to systematize their knowledge and identify over-arching concepts that need more investigation. It was generally agreed that the cell wall cannot be viewed as a passive plastic material. Synthesis and deposition take place and cause changes in the molecular architecture of the wall. Questions arise from the fact that the wall is not a constant or uniform structure but undergoes highly organized changes during enlargement while bearing a considerable load. Recent advances in signaling, biochemical analysis and ultrastructure visualization are beginning to relate to the molecular load-bearing and enzymatic activities in the wall. The participants agreed that there probably is enough information to begin developing a comprehensive model that would balance wall effects with the limitation of growth by transport, especially for water, and this could help clarify events occurring at different time scales and places. Beyond that, there seems to be a need to resolve problems of solute transport and wall behavior that are poorly understood in growing regions, leaving many promising areas for future experiments. Understanding each balancing act seems to be just the beginning.
How do plants enlarge? A balancing act; Final report
Cells of plants are surrounded by strong walls that prevent rupture from internal pressures that can be two or three times that of an automobile tire. In this way, the walls protect the cytoplasm. However, at the same time, the cells can enlarge as they grow. How this balancing act works and how it enlarges the plant were the subject of a recent conference at the University of Delaware in Lewes. The aim was to identify areas for future research that could explain the enlargement of whole plants. There is a large practical need to predict and modify plant enlargement but the additional processes that overlie the molecular ones need to be integrated with the molecular information before a picture will emerge. How best to accomplish this involved input from cross-disciplinary areas in biomechanics, physics and engineering as well as molecular biology, biochemistry and ultrastructure.
Doses delivered to normal brain under different treatment protocols at Brookhaven National Laboratory
As of October 31, 1996, 23 glioblastoma multiforme patients underwent BNCT under several treatment protocols at the Brookhaven Medical Research Reactor. For treatment planning and dosimetry purposes, these protocols may be divided into four groups. The first group comprises protocols that used an 8-cm collimator and allowed a peak normal brain dose of 10.5 Gy-Eq to avolume of 1 cm{sup 3} were the thermal neutron flux was maximal (even if it happened to be in the tumor volume). The second group differs from the first in that it allowed a peak normal brain dose of 12.6 Gy-Eq. The protocols of the third and fourth groups allowed the prescribed peak normal brain dose of 12.6 Gy-Eq to be outside of the tumor volume, used a 12-cm collimator and, respectively, uni- or bilateral irradiations. We describe the treatment planning procedures and report the doses delivered to various structures of the brain.
Correlation of clinical outcome to the estimated radiation dose from Boron Neutron Capture Therapy (BNCT)
A phase I/II trial delivering a single fraction of BNCT using p-Boronophenylalanine-Fructose and epithermal neutrons at the the Brookhaven Medical Research Reactor was initiated in September 1994. The primary endpiont of the study was to evaluate the feasibility and safety of a given BNCT dose. The clinical outcome of the disease was a secondary endpoint of the study. The objective of this paper is to evaluate the correlation of the clinical outcome of patients to the estimated radiation dose from BNCT.
Environmental stress-mediated changes in transcriptional and translational regulation of protein synthesis in crop plants. Final report
The research described in this final report focused on the influence of stress agents on protein synthesis in crop plants (primarily soybean). Investigations into the `heat shock` (HS) stress mediated changes in transcriptional and translocational regulation of protein synthesis coupled with studies on anaerobic water deficit and other stress mediated alterations in protein synthesis in plants provided the basis of the research. Understanding of the HS gene expression and function(s) of the HSPs may clarify regulatory mechanisms operative in development. Since the reproductive systems of plants if often very temperature sensitive, it may be that the system could be manipulated to provide greater thermotolerance.
A treatment planning comparison of BPA- or BSH-based BNCT of malignant gliomas
Accurate delivery of the prescribed dose during clinical BNCT requires knowledge (or reasonably valid assumptions) about the boron concentrations in tumor and normal tissues. For conversion of physical dose (Gy) into photon-equivalent dose (Gy-Eq), relative biological effectiveness (RBE) and/or compound-adjusted biological effectiveness (CBE) factors are required for each tissue. The BNCT treatment planning software requires input of the following values: the boron concentration in blood and tumor, RBEs in brain, tumor and skin for the high-LET beam components, the CBE factors for brain, tumor, and skin, and the RBE for the gamma component.
Protocols for BNCT of glioblastoma multiforme at Brookhaven: Practical considerations
In this report we discuss some issues considered in selecting initial protocols for boron neutron capture therapy (BNCT) of human glioblastoma multiforme. First the tolerance of normal tissues, especially the brain, to the radiation field. Radiation doses limits were based on results with human and animal exposures. Estimates of tumor control doses were based on the results of single-fraction photon therapy and single fraction BNCT both in humans and experimental animals. Of the two boron compounds (BSH and BPA), BPA was chosen since a FDA-sanctioned protocol for distribution in humans was in effect at the time the first BNCT protocols were written and therapy studies in experimental animals had shown it to be more effective than BSH.
A fast look-up algorithm for detecting repetitive DNA sequences
We have presented a fast linear time algorithm for recognizing tandem repeats. Our algorithm is a one pass algorithm. No information about the periodicity of tandem repeats is needed. The use of the indices calculated from non-continuous and overlapping {kappa}-tuples allow tandem repeats with insertions and deletions to be recognized.
The linear, no-threshold hypothesis linking health effects to tissue absorbed dose appears principally inapplicable at low doses
A discussion of the theoretical aspects of low dose radiobiology.
Preparation of oligonucleotide arrays for hybridization studies: Final report, 2/15/92-5/4/96
We have developed several novel ways to prepare DNA. In each, the deprotection step in each synthesis cycle is accomplished with light. The group we developed for this process is dimethoxybenzoin (DMB) which, when attached to acidic functionalities, is readily removed with long wavelength (350nm) UV irradiation that will not damage the DNA bases.
Immunological memory is associative
The purpose of this paper is to show that immunological memory is an associative and robust memory that belongs to the class of sparse distributed memories. This class of memories derives its associative and robust nature by sparsely sampling the input space and distributing the data among many independent agents. Other members of this class include a model of the cerebellar cortex and Sparse Distributed Memory (SDM). First we present a simplified account of the immune response and immunological memory. Next we present SDM, and then we show the correlations between immunological memory and SDM. Finally, we show how associative recall in the immune response can be both beneficial and detrimental to the fitness of an individual.
Regulation of terpene metabolism. Final technical report, March 15, 1988--March 14, 1996
This research focuses on the following topics: the biosynthesis and catabolism of monoterpenes; the organization of monoterpene metabolism; the developmental regulation of monoterpene metabolism; the flux control of precursor supply; and the integration of monoterpene and higher terpenoid metabolism.
Considerations for patient positioning in static beams for BNCT
The objective of this short communication is to provide a guideline for patient positioning, verification, and immobilization for boron neutron capture therapy.
FASEB summer research conference on signal transduction in plants. Final report, June 16, 1996--June 21, 1996
This is the program from the second FASEB conference on Signal Transduction in Plants. Topic areas included the following: environmental signaling; perception and transduction of light signals; signaling in plant microbe interactions; signaling in plant pathogen interactions; cell, cell communication; cytoskeleton, plasma membrane, and cellwall continuum; signaling molecules in plant growth and development I and II. A list of participants is included.
The ROVCO2 surface decontamination system
DOE needs to decontaminated over one million square feet of nuclear contaminated concrete surfaces. The 1000 lb ROVCO2 system, which automates blasting functions and eliminates secondary blasting waste, integrates a remotely operated vehicle and an enhanced commercial CO{sub 2} blasting system with an Oceaneering-developed work arm and control system. The remote operation protects the operation from contamination and supports functional automation of tedious tasks. The blasting system shoots pellets of dry ice propelled by pressurized gas at the surface to be cleaned. Impact of the pellets fractures and scales off a layer of the contaminated surface. At impact, the pellets return to a gaseous state which is vacuumed up with the debris. The CO{sub 2} gas and debris are passed through the vacuum filter, leaving only the removed material for waste disposal. Phase 2 testing achieved nearly all of the success criteria, with the exception of the commercial workhead`s performance.
Alpha-emitters for medical therapy workshop
A workshop on ``Alpha-Emitters for Medical Therapy`` was held May 30-31, 1996 in Denver Colorado to identify research goals and potential clinical needs for applying alpha-particle emitters and to provide DOE with sufficient information for future planning. The workshop was attended by 36 participants representing radiooncology, nuclear medicine, immunotherapy, radiobiology, molecular biology, biochemistry, radiopharmaceutical chemistry, dosimetry, and physics. This report provides a summary of the key points and recommendations arrived at during the conference.
Disability rights in dialogue with clinical genetics conference, May 31 to June 2, 1996
The issue of prenatal diagnosis and selective abortion has been hotly debated in the medical, genetic counselling, feminist, parents, disability rights and bio-ethics literature, each of the various positions critiquing each other. People from the disability rights community in particular have began to articulate a critical view of the practice of widespread prenatal diagnosis with intent to abort because the pregnancy might result in a child with a disability. Unfortunately, people from the various disciplines and perspectives, such as bioethics, disability rights, feminism and so forth, by and large, have tended only to write for themselves and their colleagues. Few people have crossed disciplines to try to talk to people with other views. The rapid advances of genome research have continued to produce new prenatal tests, raising many complex ethical questions regarding the applications of prenatal testing. But the widely disparate positions of the various factions has made it difficult to move toward formulation of public policy change necessary to encompass these new genetic technologies. Genetic counselling is in the front lines of the controversial social and ethical issues arising from prenatal diagnosis, in its interface between medical science and the consumer of services. The primary intent of the conference was to invite and facilitate productive dialogue between individuals and groups of people who have traditionally not interacted as a result of their disparate views on these issues and to learn from this process, emphasizing the involvement of people with disabilities and people who work in clinical genetics.
DNA sequencing technology, walking with modular primers. Final report
The success of the Human Genome Project depends on the development of adequate technology for rapid and inexpensive DNA sequencing, which will also benefit biomedical research in general. The authors are working on DNA technologies that eliminate primer synthesis, the main bottleneck in sequencing by primer walking. They have developed modular primers that are assembled from three 5-mer, 6-mer or 7-mer modules selected from a presynthesized library of as few as 1,000 oligonucleotides ({double_bond}4, {double_bond}5, {double_bond}7). The three modules anneal contiguously at the selected template site and prime there uniquely, even though each is not unique for the most part when used alone. This technique is expected to speed up primer walking 30 to 50 fold, and reduce the sequencing cost by a factor of 5 to 15. Time and expensive will be saved on primer synthesis itself and even more so due to closed-loop automation of primer walking, made possible by the instant availability of primers. Apart from saving time and cost, closed-loop automation would also minimize the errors and complications associated with human intervention between the walks. The author has also developed two additional approaches to primer-library based sequencing. One involves a branched structure of modular primers which has a distinctly different mechanism of achieving priming specificity. The other introduces the concept of ``Differential Extension with Nucleotide Subsets`` as an approach increasing priming specificity, priming strength and allowing cycle sequencing. These approaches are expected to be more robust than the original version of the modular primer technique.
Hemispheric Center for Environmental Technology: Research and Development Capabilities
Contains vugraphs: decontamination and decommissioning, Latin America`s D&D needs, metal decontamination, concrete decontamination, structural demolition and dust suppression, melting/solidification/remelting/separation of glass and metals, demonstrations, decision making, information systems, waste processing, tank waste treatment, characterization/monitoring/sensor technology, metal recycling, etc.
Plant, cell, and molecular mechanisms of abscisic-acid regulation of stomatal apertures. A new mechanism for the regulation of stomatal-aperture size in intact leaves: Accumulation of mesophyll-derived sucrose in the guard-cell wall of Vicia faba L.
At various times after pulse labeling Vicia faba L. leaflets with {sup 14}CO{sub 2}, whole-leaf pieces and rinsed epidermal peels were harvested and subsequently processed for histochemical analysis. Cells dissected from whole leaf retained apoplastic contents whereas those from rinsed peels contained only cytoplastic contents. Sucrose specific radioactivity peaked in palisade cells, 111 GBq{center_dot}mol{sup {minus}1}, at 20 min. In contrast, the {sup 14}C content and sucrose specific radioactivity were very low in guard cells for 20 min, implying little CO{sub 2} incorporation; both then peaked at 40 min. The guard-cell apoplast had a high maximum sucrose specific radioactivity and a high sucrose influx rate. These and other comparisons implied the presence of (a) multiple sucrose pools in mesophyll cells, (b) a localized mesophyll-apoplast region that exchanges with phloem and stomata, and (c) mesophyll-derived sucrose in guard-cell walls sufficient to diminish stomatal opening by {approximately} 4 {micro}m. Factors expected to enhance sucrose accumulation in guard-cell walls are (a) high transpiration rate, which closes stomata, and (b) high apoplastic sucrose concentration, which is elevated when mesophyll-sucrose efflux exceeds translocation. Therefore, multiple physiological factors are integrated in the attenuation of stomatal-aperture size by this previously unrecognized mechanism.
Comparisons of TORT and MCNP dose calculations for BNCT treatment planning
The relative merit of using a deterministic code to calculate dose distributions for BNCT applications were examined. The TORT discrete deterministic ordinated code was used in comparison to MCNP4A to calculate dose distributions for BNCT applications
Electrokinetic decontamination of concrete
ELECTROSORB Electrokinetic Extraction Technology, developed by ISOTRON Corp., offers a cost-effective approach to treating contaminated concrete. Heavy metals/radionuclides trapped in concrete can be extracted using this process if they are chemically solubilized; solubilizers used are citric acid alone and a mixture of citric and nitric acids. A DC electric field is applied across the contaminated concrete to electrokinetically transport the solubilized contaminants from the concrete pores to a collector on the concrete surface. The collector is an extraction pad laid on the surface. The pad provides confinement for a planar electrode and solubilizer solution; it is operated under a vacuum to hold the pad against the concrete surface. Operation requires little attendance, reducing the workers` health hazards. The process incorporates a mechanism for recycling the solubilizer solution. A field demonstration of the process took place in Building 21 of DOE`s Mound facility in Miamisburg, OH, over 12 days in June 1996. The thorium species present in this building`s concrete floors included ThO{sub 2} and thorium oxalate. The nitric acid was found to facilitate Th extraction.
Human genome education model project. Ethical, legal, and social implications of the human genome project: Education of interdisciplinary professionals
This meeting was held June 10, 1996 at Georgetown University. The purpose of this meeting was to provide a multidisciplinary forum for exchange of state-of-the-art information on the human genome education model. Topics of discussion include the following: psychosocial issues; ethical issues for professionals; legislative issues and update; and education issues.
Carbon and Hydrogen Matabolism of Green Algae in Light and Dark: Final Report
This report provides an overview of the progress made during this study. Progress is reported in chloroplast respiration, photoregulation of chloroplast respiration, reductive carboxylic acid cycle, and in oxy-hydrogen reaction all in Chlamydomonas.
Technical basis for dose reconstruction
The purpose of this paper is to consider two general topics: technical considerations of why dose-reconstruction studies should or should not be performed and methods of dose reconstruction. The first topic is of general and growing interest as the number of dose-reconstruction studies increases, and one asks the question whether it is necessary to perform a dose reconstruction for virtually every site at which, for example, the Department of Energy (DOE) has operated a nuclear-related facility. And there is the broader question of how one might logically draw the line at performing or not performing dose-reconstruction (radiological and chemical) studies for virtually every industrial complex in the entire country. The second question is also of general interest. There is no single correct way to perform a dose-reconstruction study, and it is important not to follow blindly a single method to the point that cheaper, faster, more accurate, and more transparent methods might not be developed and applied.
Some recent developments in treatment planning software and methodology for BNCT
Over the past several years/the Idaho National Engineering Laboratory (INEL) has led the development of a unique, internationally-recognized set of software modules (BNCT rtpe) for computational dosimetry and treatment planning for Boron Neutron Capture Therapy (BNCT). The computational capability represented by this software is essential to the proper administration of all forms of radiotherapy for cancer. Such software addresses the need to perform pretreatment computation and optimization of the radiation dose distribution in the target volume. This permits the achievement of the optimal therapeutic ratio (tumor dose relative to critical normal tissue dose) for each individual patient via a systematic procedure for specifying the appropriate irradiation parameters to be employed for a given treatment. These parameters include angle of therapy beam incidence, beam aperture and shape,and beam intensity as a function of position across the beam front. The INEL software is used for treatment planning in the current series of human glioma trials at Brookhaven National Laboratory (BNL) and has also been licensed for research and developmental purposes to several other BNCT research centers in the US and in Europe.
[Final report of research carried out under DOE CRADA Number BNL-C-95-07]
No Description Available.
Laser surface cleaning
Decontamination of contaminated metal and material recycle, two of 31 priority needs identified by the D&D focus group, are the most promising applications for laser ablation within the DOE complex. F2 Associates has developed a robotic laser ablation system that is capable of high contamination rates, waste volume reduction, surface pore cleaning, and real-time characterization of materials. It is being demonstrated that this system will be the most cost-effective technology for metal decontamination and material recycle.
Single-cell bioluminescence and GFP in biofilm research
Using flow cells and a combination of microscopy techniques, we can unequivocally identify single bacterial cells that express bioluminescent and fluorescent bioreporters. We have shown that, for attached cells, bioluminescence output within a bacterial strain can vary greatly from cell to cell.
DOE occupational radiation exposure 1996 report
The goal of the US Department of Energy (DOE) is to conduct its radiological operations to ensure the health and safety of all DOE employees including contractors and subcontractors. The DOE strives to maintain radiation exposures to its workers below administrative control levels and DOE limits and to further reduce these exposures and releases to levels that are ``As Low As Reasonably Achievable`` (ALARA). The DOE Occupational Radiation Exposure Report, 1996 provides summary and analysis of the occupational radiation exposure received by individuals associated with DOE activities. The DOE mission includes stewardship of the nuclear weapons stockpile and the associated facilities, environmental restoration of DOE and precursor agency sites, and energy research. Collective exposure at DOE has declined by 80% over the past decade due to a cessation in opportunities for exposure during the transition in DOE mission from weapons production to cleanup, deactivation and decommissioning, and changes in reporting requirements and dose calculation methodology. In 1996, the collective dose decreased by 10% from the 1995 value due to decreased doses at five of the seven highest-dose DOE sites. For 1996, these sites attributed the reduction in collective dose to the completion of several decontamination and decommissioning projects, reduced spent fuel storage activities, and effective ALARA practices. This report is intended to be a valuable tool for managers in their management of radiological safety programs and commitment of resources.
Fourth international workshop on human chromosome 5. Final progress report
The Fourth International Workshop on Human Chromosome 5 was held in Manchester, UK on November 9--10, 1996 and was hosted by the University of Manchester. The major goals of the workshop were: (1) to collate the various genetic, cytogenetic and physical maps of human chromosome 5; (2) to integrate these maps and identify/correct discrepancies between them wherever possible; (3) to catalogue the sequence-ready contigs of the chromosome; (4) to co-ordinate the various sequencing efforts to avoid future duplication; (5) to establish the first (to the author`s knowledge) web site for the human chromosome 5 community which contains the above information in a readily accessible form.
Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor
Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope {sup 10}B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/{sup 10}B reactions ({sup 10}B(n,{alpha}){sup 7}Li) resulting in the production of localized high LET radiation from alpha and {sup 7}Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released is microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams.
Evaluation of boronated EGF as a potential delivery agent for BNCT of brain tumors
The epidermal growth factor receptor (EGFR) gene is often amplified in human glioblastomas, but, reflecting the cellular heterogeneity of these tumors, the frequency of amplification is variable. Since the number of EGFR has been considered as a potential target for the specific delivery of diagnostic and therapeutic agents to brain tumors. Initially, the focus was on using anti-EGFR monoclonal antibodies or their fragments, but within the past few years there has been increasing interest in using EGF based bioconjugates as targeting agents. Recently, we have described a method for the boronation of EGF and have characterized the resulting bioconjugates in vitro. In the present study, we have investigated the potential usefulness of boronated EGF as a delivery agent for neutron capture therapy in rats bearing intracerebral implants of the C6 glioma, which has been transfected with the gene encoding EGFR. Our results indicate that following intratumoral injection, boronated EGF selectivity targeted the transfected EGFR positive C6 glioma, and that the amount of delivered to the tumor exceeded by 3-4 orders of magnitude that which could be delivered by intravenous injection.
Rational enhancement of enzyme performance in organic solvents. Final technical report, 1992--1996
This research focused on the following: the dependence of enzymatic activity of several model hydrolases in nonaqueous solvents; control of substrate selectivity of the protease subtilisin Carlsberg by the solvent; control of catalytic activity and enantioselectivity of this enzyme in organic solvents by immobilization support; lipase-catalyzed acylation of sugars in anhydrous hydrophobic media; the possibility of accelerating enzymatic processes in organic solvents by certain cosolvents; whether lipase catalysis in organic solvents can be enhanced by introducing interfaces in the in the reaction medium; the structure of proteins suspended in organic solvents; improving enzymatic enantioselectivity in organic solvents; analyzing the plunge in enzymatic activity upon replacing water with organic solvents; and the structural basis for the phenomenon of molecular memory of imprinted proteins in organic solvents.
Large scale solubilization of coal and bioconversion to utilizable energy. Quarterly report, July 1, 1996--September 30 1996
A purification of the Neurospora protein with coal solubilization activity (CSA) using DEAE cellulose chromatography is described. The protein is heavily glycosylated suggesting that it is different than tyrosinase or common phenol oxidases even though it resembles these proteins in enzyme activity and molecular weight.
Fiber optic coherent laser radar 3D vision system
This CLVS will provide a substantial advance in high speed computer vision performance to support robotic Environmental Management (EM) operations. This 3D system employs a compact fiber optic based scanner and operator at a 128 x 128 pixel frame at one frame per second with a range resolution of 1 mm over its 1.5 meter working range. Using acousto-optic deflectors, the scanner is completely randomly addressable. This can provide live 3D monitoring for situations where it is necessary to update once per second. This can be used for decontamination and decommissioning operations in which robotic systems are altering the scene such as in waste removal, surface scarafacing, or equipment disassembly and removal. The fiber- optic coherent laser radar based system is immune to variations in lighting, color, or surface shading, which have plagued the reliability of existing 3D vision systems, while providing substantially superior range resolution.
Yield effects on bale density and time required for commercial harvesting and baling of switchgrass
The objective of this study was to obtain mowing, raking and baling data for switchgrass yields to determine whether economic projections for harvesting and baling are valid for switchgrass as an energy crop. The study demonstrated that data for haymaking cannot be extrapolated to switchgrass.
Interfacial properties of hydrosoluble polymers. Final report, June 15, 1993--June 15, 1996
During this period, the authors treated a myriad of problems associated with the interfacial properties of macromolecules. Many of them concerned indirect interactions between surfaces engendered by intervening species. The issues ranged from colloidal forces to membrane induced coupling between embedded macromolecules (membrane-bound proteins). This report presents summaries of the following papers published as a result of this study: membrane interactions with polymers and colloids; escape transitions and force laws for compressed polymer mushrooms; interaction between finite-sized particles and end grafted polymers; one long chain among shorter chains--the Flory approach revisited; conformation of star polymers in high molecular weight solvents; membrane-induced interactions between inclusions; filled polymer brushes--a hydrodynamic analogy; polymer adsorption at liquid/air interfaces under lateral pressure; flow induced instability of the interface between a fluid and a gel at low Reynolds number; and fluctuation-induced forces in stacked fluid membranes.
A method for the assessment of specific energy distribution in a model tumor system
Due to the short range of alpha particles in tissue, the calculation of dose from internally deposited alpha emitters requires a detailed analysis of the microscopic distribution of the radionuclide in order to determine the spatial distribution of energy emission events and, from this, the spatial distribution of dose. In the present study, the authors used quantitative autoradiography (QAR) to assess the microdistribution of a radiolabeled monoclonal antibody (MAb) fragment in human glioma xenografts in mice.
10. international mouse genome conference
Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.
EPR techniques for space biodosimetry
Retrospective dosimetry of tooth enamel has become an increasingly complex and difficult discipline to undertake while still attaining accuracy. The paper provides a review of the major obstacles, advances and pertinent phenomenon associated with low level retrospective dosimetry of human tooth enamel. Also covered is the many sources of error in EPR dosimetry, their potential solutions, as well as the different analysis and scanning techniques in use with their prospective pros and cons. Prospective directions for new approaches, methods, and instruments are also reviewed.
Uptake of the BPA into glioblastoma multiforme correlates with tumor cellularity
Fourteen patients scheduled to undergo craniotomy for glioblastoma multiforme were infused with p-boronophenylalanine fructose intravenously for 2 hours prior to surgery. Tissues removed during the procedure and blood obtained at its conclusion were analyzed for boron by direct current plasma-atomic emission spectroscopy. The results are presented herein.
An 800-MeV proton beam spill calculation
Using LAHET, the Los Alamos High-Energy Transport code, the authors calculated the radiation hazard from an 800-MeV proton beam spill at the bending magnet. Neutron doses were calculated at an area above the 84.0-cm-thick concrete roof, where there existed a gap with only 30.48-cm concrete shielding. The authors also studied the effect of the gap and proposed a corrective action.
Application of MCNP{trademark} to storage facility dose rate assessment
The MCNP code is widely used in the determination of neutral particle dose rate analyses. In this paper we examine the application of MCNP to several storage facilities containing special nuclear material, SNM, wherein the neutron dose rate is the primary quantity of interest. In particular, we describe the special geometry, modeling assumptions, and physics considerations encountered in each of three applications.
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