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The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

Description: Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis than those with low levels. Knock down of HJURP in human breast cancer cells using shRNA reduced the sensitivity ...
Date: June 25, 2010
Creator: Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody et al.
Partner: UNT Libraries Government Documents Department

Prediction of epigenetically regulated genes in breast cancer cell lines

Description: Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fxed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis. Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically signifcant negative correlation between methylation profles and gene expression in the panel of breast cancer cell lines. Subnetwork enrichment of these genes has identifed 35 common regulators with 6 or more predicted markers. In addition to identifying epigenetically regulated genes, we show evidence of differentially expressed ...
Date: May 4, 2010
Creator: Loss, Leandro A; Sadanandam, Anguraj; Durinck, Steffen; Nautiyal, Shivani; Flaucher, Diane; Carlton, Victoria EH et al.
Partner: UNT Libraries Government Documents Department

Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

Description: Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also reveal the molecular differences between cancer and normal that ...
Date: June 18, 2009
Creator: Spellman, Paul T.; Heiser, Laura & Gray, Joe W.
Partner: UNT Libraries Government Documents Department

Medically relevant ElectroNeedle technology development.

Description: ElectroNeedles technology was developed as part of an earlier Grand Challenge effort on Bio-Micro Fuel Cell project. During this earlier work, the fabrication of the ElectroNeedles was accomplished along with proof-of-concept work on several electrochemically active analytes such as glucose, quinone and ferricyanide. Additionally, earlier work demonstrated technology potential in the field of immunosensors by specifically detecting Troponin, a cardiac biomarker. The current work focused upon fabrication process reproducibility of the ElectroNeedles and then using the devices to sensitively detect p-cresol, a biomarker for kidney failure or nephrotoxicity. Valuable lessons were learned regarding fabrication assurance and quality. The detection of p-cresol was accomplished by electrochemistry as well as using fluorescence to benchmark ElectroNeedles performance. Results from these studies will serve as a guide for the future fabrication processes involving ElectroNeedles as well as provide the groundwork necessary to expand technology applications. One paper has been accepted for publication acknowledging LDRD funding (K. E. Achyuthan et al, Comb. Chem. & HTS, 2008). We are exploring the scope for a second paper describing the applications potential of this technology.
Date: November 1, 2008
Creator: Schmidt, Carrie Frances; Thomas, Michael Loren; McClain, Jaime L.; Harper, Jason C.; Achyuthan, Komandoor E. & Ten Eyck, Gregory A.
Partner: UNT Libraries Government Documents Department

Microanalytical Methods for Bio-Forensics Investigations

Description: Forensics investigations of bio-crime or bio-terrorism incidents require careful analysis of collected evidentiary material. Although the biological markers in the evidentiary material are important (e.g. genomic signatures, protein markers), the elemental make-up of the organisms themselves and the surrounding non-biological material is extremely useful for attributing a specific process and, perhaps, specific persons to the production of the biological agent. This talk will describe the coordinated use of microanalytical techniques such as SEM-EDX, STEM-EDX, and NanoSIMS for generating compositional signatures for bio-forensics investigations. These analytical techniques span length scales from the 50 {micro}m range to the 5nm range. The range of analytical sensitivities spans from {approx}.5wt% for EDX down to parts per billion for SIMS techniques. In addition, we will discuss the use of spectrum imaging techniques for rapidly extracting the key elemental signatures from large scale data sets. Spectrum imaging techniques combined with multivariate statistical analysis allow for the collection and interrogation or enormous quantities of data without pre-biasing the answer.[1] Spectrum imaging has been used successfully in EDX microanalysis[1] (both in the SEM and TEM) and TOF-SIMS[2]. In this study, a set of test biological agents, ?-irradiated Bacillus thuringiensis (Bt), were examined using the aforementioned microanalytical techniques. The sample set included a number of processing conditions to gauge the ability of these techniques to identify the production methods of these simulated agents. Complementary but distinct forensic signatures were obtained by all three analytical techniques. Figure 1 shows two types of silicate particles observed among the spore material itself. At this length scale, the spores themselves cannot be resolved, but the presence of these silicates is key marker for distinguishing this production route. A STEM-EDX spectrum image from the same material does not show these large silicates but instead shows the segregation of elements such as sulfur and silicon ...
Date: February 10, 2006
Creator: Brewer, L N; Weber, P K; Grant, R P; Ghosal, S & Michael, J R
Partner: UNT Libraries Government Documents Department

Aequorin as a bioluminescent indicator for use in the determination of biomolecules in single cells. Final technical report

Description: During this funding period, the laboratories of Drs. Anderson and Daunert have performed a considerable amount of work toward addressing the issues associated with small volume analysis necessary for single cell studies. In that respect, their research has been focused on (1) developing new assays that can be miniaturized and are suitable for small volume and single cell analysis; (2) fabricating pL-vials that simulate the volume of single cells and setting up instrumentation capable of low-volume detection; (3) developing reproducible and reliable microinjection techniques; (4) developing methods of analysis for biomolecules in the pL-vials and employing these assays in the detection of biomolecules in single cells. The accomplishments attained in all these areas are described below. A total of 24 publications and 35 presentations have resulted from this work.
Date: February 17, 2000
Creator: Daunert, Sylvia
Partner: UNT Libraries Government Documents Department

Application of spectral hole burning to the study of in vitro cellular systems

Description: Chapter 1 of this thesis describes the various stages of tumor development and a multitude of diagnostic techniques used to detect cancer. Chapter 2 gives an overview of the aspects of hole burning spectroscopy important for its application to the study of cellular systems. Chapter 3 gives general descriptions of cellular organelles, structures, and physical properties that can serve as possible markers for the differentiation of normal and cancerous cells. Also described in Chapter 3 are the principles of cryobiology important for low temperature spectroscopy of cells, characterization of MCF-10F (normal) and MCF-7 (cancer) cells lines which will serve as model systems, and cellular characteristics of aluminum phthalocyanine tetrasulfonate (APT), which was used as the test probe. Chapters 4 and 5 are previously published papers by the author pertaining to the results obtained from the application of hole burning to the study of cellular systems. Chapter 4 presents the first results obtained by spectral hole burning of cellular systems and Chapter 5 gives results for the differentiation of MCF-10F and MCF-7 cells stained with APT by an external applied electric (Stark) field. A general conclusion is presented in Chapter 6. Appendices A and B provide additional characterization of the cell/probe model systems. Appendix A describes the uptake and subcellular distribution of APT in MCF-10F and MCF-7 cells and Appendix B compares the hole burning characteristics of APT in cells when the cells are in suspension and when they are examined while adhering to a glass coverslip. Appendix C presents preliminary results for a novel probe molecule, referred to as a molecular thumbtack, designed by the authors for use in future hole burning applications to cellular systems.
Date: November 8, 1999
Creator: Milanovich, Nebojsa
Partner: UNT Libraries Government Documents Department

Early lung cancer detection project: Evaluation of 5, 10, 15, 20 tetrakis (4-carboxyphenyl) porphine (H{sub 2}TCPP). Final report

Description: The author evaluated a synthetic porphyrin, 5, 10, 15, 20 tetrakis (4-carboxyphenyl) porphene (H{sub 2}TCPP) as a marker of carcinogenesis. H{sub 2}TCPP was compared with two other carcinogenesis markers evaluated in the laboratory for their ability to detect exfoliated sputum cells undergoing transformation to lung cancer. In the present project the authors first established optimal conditions for cultured neoplastic and non-neoplastic (sputum) cells to take up H{sub 2}TCPP. This was accomplished using spectrofluorimetry and video-enhanced fluorescent microscopy to maximize H{sub 2}TCPP auto-fluorescence across a matrix of substrate conditions, including; reagent concentration, incubation time, temperature, and pH. The second aim was to validate H{sub 2}TCPP on clinical material obtained from subjects monitored in advance of clinical cancer and link those marker results with subsequent histologic confirmation of disease. This was accomplished by applying H{sub 2}TCPP to sputum specimens archived by the Frost Center at Johns Hopkins which maintains a record of the clinical course and long-term follow-up for the patients from whom the specimens were obtained. The authors have used fluorescent immunostaining and flow cytometry to compare uptake of these cytoplasmic Mabs to that of a potential new marker of carcinogenesis, 5, 10, 15, 20 tetrakis (4 carboxyphenyl) porphene (H{sub 2}TCPP). The nuclear uptake of H{sub 2}TCPP was compared to a standard quantitative fluorescent DNA marker (7-AAD).
Date: October 1, 1998
Creator: Tockman, M.S.
Partner: UNT Libraries Government Documents Department

[A comprehensive signature biomarker analysis of the in-situ viable biomass, community composition, and nutritional status attributes of deep subsurface microbiota]. Final report

Description: The TAN sites contains subsurface sediment contaminated with trichloroethylene (TC). A suite of microbiological analyses, including ester-linked phospholipid fatty acid (PLFA) analysis, were performed to ascertain the microbial ecology associated with TCE degradation processes. The objective of the PLFA analyses were: (1) to determine the distribution of viable microbes throughout a vertical depth profile through the TCE plume, (2) determine the community composition of the viable extant microbiota and (3) relate the data derived from the PLFA analyses to other measures of the in situ microbiota as well as to the presence of TCE degradative products.
Date: September 1, 1998
Partner: UNT Libraries Government Documents Department

The dynamics of carbon exchange in vertically stratified coastal bacterioplankton communities

Description: This research focuses on the development and application of novel molecular methods to measure bacterioplankton growth state in situ. These methods included bulk or population-based studies and single cell studies. Due to the limited duration of support and subsequent termination of the molecular-focused PIs, only the former bulk method was applied to marine samples. In addition, basic laboratory studies were completed which addressed why the selected biomarkers were regulated by bacterial growth state.
Date: July 1, 1998
Creator: Blum, P.
Partner: UNT Libraries Government Documents Department

Signature lipid biomarkers for in situ microbial biomass, community structure and nutritional status of deep subsurface microbiota in relation to geochemical gradients. Final technical report

Description: To obtain a better understanding of the microbial ecology of the deep subsurface, it was necessary to employ alternate techniques for the identification of microorganisms in situ. Classical microbiological techniques assay only those organisms which are culturable with bias occurring towards the media selected. Since culturable microorganisms typically represents only 0.1 to 10% of the extant microbiota, techniques for the direct assay of microorganisms in situ were needed. The analysis of cellular lipid biomarkers is a technique whereby microbial communities can be assayed directly in a variety of environmental matrices. Through the quantitative recovery of lipid biomarkers, estimations of cell biomass, community composition and community nutritional and/or physiological status can be obtained.
Date: February 1, 1998
Creator: White, D. C. & Ringelberg, D. B.
Partner: UNT Libraries Government Documents Department

Construction of genome-wide physical BAC contigs using mapped cDNA as probes: Toward an integrated BAC library resource for genome sequencing and analysis. Annual report, July 1995--January 1997

Description: The goal of human genome project is to characterize and sequence entire genomes of human and several model organisms, thus providing complete sets of information on the entire structure of transcribed, regulatory and other functional regions for these organisms. In the past years, a number of useful genetic and physical markers on human and mouse genomes have been made available along with the advent of BAC library resources for these organisms. The advances in technology and resource development made it feasible to efficiently construct genome-wide physical BAC contigs for human and other genomes. Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes are available for human genome mapping. ESTs and cDNAs are excellent resources for building contig maps for two reasons. Firstly, they exist in two alternative forms--as both sequence information for PCR primer pairs, and cDoreen genomic libraries efficiently for large number of DNA probes by combining over 100 cDNA probes in each hybridization. Second, the linkage and order of genes are rather conserved among human, mouse and other model organisms. Therefore, gene markers have advantages over random anonymous STSs in building maps for comparative genomic studies.
Date: December 31, 1997
Creator: Mitchell, S.C.; Bocskai, D. & Cao, Y.
Partner: UNT Libraries Government Documents Department

[One-step PCR sequencing]. Final report, July 1, 1994--August 31, 1997

Description: The author explored the use of a novel class of boronated nucleic acids, the boranophosphates, as an alternative, but complementary method to dideoxysequencing. Boranophosphates can be used to directly amplify and sequence single- or double-stranded DNA. Fragments are derived not from truncations during polymerase synthesis, but from insertion and digestion back to a boronated marker or delimiter that was incorporated during exponential amplification. The method, which the author calls Boronated One-Step PCR Sequencing, is unique in that it employs a new class of {alpha}-P-boronated 2{prime}-deoxynucleoside 5{prime}-triphosphates first synthesized in the laboratory. These boronated triphosphates exhibit useful properties: (a) they are heat stable, (b) they can be base-specifically incorporated into DNA during the polymerase chain reaction, and (c) once incorporated, the boranophosphate nucleotide (marker) blocks the action of exonuclease. Thus, the positions of the stably-incorporated boronated markers can be revealed by a simple exonuclease digestion, producing a series of fragments--each of which is terminated base-specifically at the boronated markers--and thereby defining the sequence of the PCR product.
Date: December 31, 1997
Creator: Shaw, B.R.
Partner: UNT Libraries Government Documents Department

Rapid, potentially automatable, method extract biomarkers for HPLC/ESI/MS/MS to detect and identify BW agents

Description: The program proposes to concentrate on the rapid recovery of signature biomarkers based on automated high-pressure, high-temperature solvent extraction (ASE) and/or supercritical fluid extraction (SFE) to produce lipids, nucleic acids and proteins sequentially concentrated and purified in minutes with yields especially from microeukaryotes, Gram-positive bacteria and spores. Lipids are extracted in higher proportions greater than classical one-phase, room temperature solvent extraction without major changes in lipid composition. High performance liquid chromatography (HPLC) with or without derivatization, electrospray ionization (ESI) and highly specific detection by mass spectrometry (MS) particularly with (MS){sup n} provides the detection, identification and because the signature lipid biomarkers are both phenotypic as well as genotypic biomarkers, insights into potential infectivity of BW agents. Feasibility has been demonstrated with detection, identification, and determination of infectious potential of Cryptosporidium parvum at the sensitivity of a single oocyst (which is unculturable in vitro) and accurate identification and prediction, pathogenicity, and drug-resistance of Mycobacteria spp.
Date: December 1997
Creator: White, D. C.; Burkhalter, R. S.; Smith, C. & Whitaker, K. W.
Partner: UNT Libraries Government Documents Department

Molecular epidemiology of severe ambient air pollution on women and the developing fetus. Final report, September 15, 1993--September 14, 1996

Description: This research goal was validation of a number of biomarkers in two groups of Polish women and their newborn infants: 70 mother/child pairs from Krakow, a city with elevated air pollution and 90 pairs from Limanowa, a less polluted area.
Date: November 1, 1997
Creator: Perera, F.P.
Partner: UNT Libraries Government Documents Department

Inflammatory bowel disease gene discovery. CRADA final report

Description: The ultimate goal of this project is to identify the human gene(s) responsible for the disorder known as IBD. The work was planned in two phases. The desired products resulting from Phase 1 were BAC clone(s) containing the genetic marker(s) identified by gene/Networks, Inc. as potentially linked to IBD, plasmid subclones of those BAC(s), and new genetic markers developed from these plasmid subclones. The newly developed markers would be genotyped by gene/Networks, Inc. to ascertain evidence for linkage or non-linkage of IBD to this region. If non-linkage was indicated, the project would move to investigation of other candidate chromosomal regions. Where linkage was indicated, the project would move to Phase 2, in which a physical map of the candidate region(s) would be developed. The products of this phase would be contig(s) of BAC clones in the region exhibiting linkage to IBD, as well as plasmic subclones of the BACs and further genetic marker development. There would also be continued genotyping with new polymorphic markers during this phase. It was anticipated that clones identified and developed during these two phases would provide the physical resources for eventual disease gene discovery.
Date: September 9, 1997
Partner: UNT Libraries Government Documents Department

Modeling human risk: Cell & molecular biology in context

Description: It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.
Date: June 1, 1997
Partner: UNT Libraries Government Documents Department

Use of chromosome translocations for measuring prior environment exposures in humans

Description: Recent advances in cytogenetic methodology are beginning to have a major impact upon our ability to provide assessments of environmental exposure in humans. The advent of fluorescent-based techniques for `painting` whole chromosomes has made the analysis of chromosome translocations rapid, specific, sensitive and routine. Chromosome painting has been used to address a wide variety of scientific questions, resulting in an increased understanding of the biological consequences of adverse environmental exposure. This paper describes the use of chromosome translocations as a biological marker of exposure and effect in humans. The relevance of translocations is discussed, as are the advantages and disadvantages of painting compared to classical cytogenetic methods for translocation evaluation. The factors to consider in the use of translocations as a retrospective indicator of exposure are then described. Several theoretical parameters that are important to the use of translocations are provided, and the paper concludes with a vision for the future of cytogenetic methodology.
Date: May 1, 1997
Creator: Tucker, J. D.
Partner: UNT Libraries Government Documents Department

Tulane/Xavier Center for Bioenvironmental Research; project: hazardous materials in aquatic environments; subproject: biomarkers and risk assessment in Bayou Trepagnier, LA

Description: Tulane and Xavier Universities have singled out the environment as a major strategic focus for research and training for now and beyond the year 2000. the Tulane/Xavier Center for Bioenvironmental Research (CBR) was established in 1989 as the umbrella organization to coordinate environmental research at both universities. CBR projects funded by the DOE under the Hazardous Materials in Aquatic Environments grant are defining the following: (1) the complex interactions that occur during the transport of contaminants through wetlands environments, (2) the actual and potential impact of contaminants on ecological systems and health, (3) the mechanisms and new technologies through which these impacts might be remediated, and (4) new programs aimed at educating and training environmental workers of the future. The subproject described in this report, `Biomarkers and Risk Assessment in Bayou Trepagnier, LN`, is particularly relevant to the US Department of Energy`s Environmental Restoration and Waste Management program aimed at solving problems related to hazard monitoring and clean-up prioritization at sites with aquatic pollution problems in the DOE complex.
Date: December 31, 1996
Creator: Ide, C.
Partner: UNT Libraries Government Documents Department

Chromosome translocations measured by fluorescence in-situ hybridization: A promising biomarker

Description: A biomarker for exposure and risk assessment would be most useful if it employs an endpoint that is highly quantitative, is stable with time, and is relevant to human risk. Recent advances in chromosome staining using fluorescence in situ hybridization (FISH) facilitate fast and reliable measurement of reciprocal translocations, a kind of DNA damage linked to both prior exposure and risk. In contrast to other biomarkers available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time post exposure, has a rather small inter-individual variability, and can be measured accurately at the low levels. Here, the authors discuss results from their studies demonstrating that chromosome painting can be used to reconstruct radiation dose for workers exposed within the dose limits, for individuals exposed a long time ago, and even for those who have been diagnosed with leukemia but not yet undergone therapy.
Date: October 1, 1995
Creator: Lucas, J.N. & Straume, T.
Partner: UNT Libraries Government Documents Department

National Biomedical Tracer Facility: Project definition study

Description: The Los Alamos National Laboratory is an ideal institution and New Mexico is an ideal location for siting the National Biomedical Tracer Facility (NBTF). The essence of the Los Alamos proposal is the development of two complementary irradiation facilities that combined with our existing radiochemical processing hot cell facilities and waste handling and disposal facilities provide a low cost alternative to other proposals that seek to satisfy the objectives of the NBTF. We propose the construction of a 30 MeV cyclotron facility at the site of the radiochemical facilities, and the construction of a 100 MeV target station at LAMPF to satisfy the requirements and objectives of the NBTF. We do not require any modifications to our existing radiochemical processing hot cell facilities or our waste treatment and disposal facilities to accomplish the objectives of the NBTF. The total capital cost for the facility defined by the project definition study is $15.2 M. This cost estimate includes $9.9 M for the cyclotron and associated facility, $2.0 M for the 100 MeV target station at LAMPF, and $3.3 M for design.
Date: May 31, 1995
Creator: Heaton, R.; Peterson, E. & Smith, P.
Partner: UNT Libraries Government Documents Department

Paleohydrologic investigations in the vicinity of Yucca Mountain: Late Quaternary paleobotanical and polynological records

Description: The primary objective of this research in the vicinity of the proposed Yucca Mountain Nuclear Waste Repository is the detection of episodes of increased runoff and groundwater discharge in this presently arid area. Ancient, inactive spring deposits in nearby valley bottoms (Haynes, 1967; Quade, 1986; Quade and Pratt, 1989), evidence for perennial water in presently dry canyons (Spaulding, 1992), and recent claims for extraordinary increases in precipitation during the last glacial age (Forester, 1994), provide good reason to further investigate both lowland spring-discharge habitats, and upland drainages. The ultimate purpose is to assess the long-term variability of the hydrologic system in the vicinity of Yucca Mountain in response to naturally occurring climatic changes. The data generated in the course of this study are derived from radiocarbon dated packrat (Neotoma) middens. This report presents the results of an initial assessment of the hydrologic stability of the candidate area based on a limited suite of middens from localities that, on geomorphic and hydrologic grounds, could have been close to ancient stream-side or spring environments. Paleoclimatic reconstructions are another means of studying the long-term climatic hydrologic stability of the Candidate Area include, and are also generated from packrat midden data. A different flora characterized the Candidate Area during the last glacial age in response to a cooler and wetter climate, and the plant species that comprised this flora can be used to reconstruct specific components of past climatic regimes. Thus, a secondary objective of this study is to compare the plant macrofossil data generated in this study to other records from the Candidate Area (Spaulding, 1985; Wigand, 1990) to determine if these new data are consistent with prior reconstructions. 66 refs., 4 figs., 13 tabs.
Date: October 5, 1994
Creator: Spaulding, W.G.
Partner: UNT Libraries Government Documents Department

Flow cytometry: A powerful technology for measuring biomarkers

Description: A broad definition of a biomarker is that it is a measurable characteristic of a biological system that changes upon exposure to a physical or chemical insult. While the definition can be further refined, it is sufficient for the purposes of demonstrating the advantages of flow cytometry for making quantitative measurements of biomarkers. Flow cytometry and cell sorting technologies have emerged during the past 25 years to take their place alongside other essential tools used in biology such as optical and electron microscopy. This paper describes the basics of flow cytometry technology, provides illustrative examples of applications of the technology in the field of biomarkers, describes recent developments in flow cytometry that have not yet been applied to biomarker measurements, and projects future developments of the technology. The examples of uses of flow cytometry for biomarker quantification cited in this paper are meant to be illustrative and not exhaustive in the sense of providing a review of the field.
Date: September 1, 1994
Creator: Jett, J. H.
Partner: UNT Libraries Government Documents Department

Monochromosomal hybrids for the analysis of the human genome. Final technical report

Description: The objective of this research project is to produce panels of mouse/human and/or Chinese hamster/human hybrid cell lines each harboring a single different human chromosome. The human chromosome present in rodent cell will be marked with a dominant selectable marker and maintained by selection. In these experiments human chromosomes first ``tagged`` with a selectable marker in human cells are subsequently transferred to rodent cells by microcell fusion method. Several different experimental schemes have been developed to ``tag`` human chromosomes with a selectable marker. Amphotropic retroviral vectors provide a highly efficient system to introduce selectable markers into normal diploid human cells. The integration of retroviral vector into the cell genome occurs at random by recombination at a defined nucleotide sequence in the LTRs and only a single copy of the vector integrates in a cell. This property of retroviral vectors allows to isolate a segment of the chromosomal DNA flanking the vector integration site by PCR amplification. In these studies the amphotropic retroviral vector pZIPgpt that carries a dominant selectable marker gpt, is used to tag the human chromosomes in normal diploid cells. Human DNA flanking the integrated vector is rescued by PCR amplification and cloned into a plasmid vector. Cloned human DNA is then used to probe Southern blots of DNAs from a panel of hybrid cell lines to identify the chromosome of its origin. This allows them to identify clonal human cell lines, each carrying the marker integrated into a different chromosome. Marked chromosomes are then transferred to rodent cells by MMCT.
Date: September 1, 1994
Creator: Athwal, R. S.
Partner: UNT Libraries Government Documents Department