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Translating the cancer genome: Going beyond p values

Description: Cancer cells are endowed with diverse biological capabilities driven by myriad inherited and somatic genetic and epigenetic aberrations that commandeer key cancer-relevant pathways. Efforts to elucidate these aberrations began with Boveri's hypothesis of aberrant mitoses causing cancer and continue today with a suite of powerful high-resolution technologies that enable detailed catalogues of genomic aberrations and epigenomic modifications. Tomorrow will likely bring the complete atlas of reversible and irreversible alteration in individual cancers. The challenge now is to discern causal molecular abnormalities from genomic and epigenomic 'noise', to understand how the ensemble of these aberrations collaborate to drive cancer pathophysiology. Here, we highlight lessons learned from now classical examples of successful translation of genomic discoveries into clinical practice, lessons that may be used to guide and accelerate translation of emerging genomic insights into practical clinical endpoints that can impact on practice of cancer medicine.
Date: April 3, 2008
Creator: Chin, Lynda; Chin, Lynda & Gray, Joe W.
Partner: UNT Libraries Government Documents Department

Seismicity Precursors of the M6.0 2004 Parkfield and M7.0 1989Loma Prieta Earthquakes

Description: The M6.0 2004 Parkfield and M7.0 1989 Loma Prietastrike-slip earthquakes on the San Andreas Fault (SAF) were preceded byseismicity peaks occurring several months prior to the main events.Earthquakes directly within the SAF zone were intentionally excluded fromthe analysis because they manifest stress-release processes rather thanstress accumulation. The observed increase in seismicity is interpretedas a signature of the increasing stress level in the surrounding crust,whereas the peaks and the subsequent decrease in seismicity areattributed to damage-induced softening processes. Furthermore, in bothcases there is a distinctive zone of low seismic activity that surroundsthe epicentral region in the pre-event period. The increase of seismicityin the crust surrounding a potential future event and the development ofa low-seismicity epicentral zone can be regarded as promising precursoryinformation that could help signal the arrival of large earthquakes. TheGutenberg-Richter relationship (GRR) should allow extrapolation ofseismicity changes down to seismic noise level magnitudes. Thishypothesis is verified by comparison of seismic noise at 80 Hz with theParkfield M4 1993-1994 series, where noise peaks 5 months before theseries to about twice the background level.
Date: March 9, 2006
Creator: Korneev, Valeri A.
Partner: UNT Libraries Government Documents Department

Diversity of Decline-Rate-Corrected Type 1a Supernova Rise times:One Mode or Two?

Description: B-band light-curve rise times for eight unusually well-observed nearby Type Ia supernova (SNe) are fitted by a newly developed template-building algorithm, using light-curve functions that are smooth, flexible, and free of potential bias from externally derived templates and other prior assumptions. From the available literature, photometric BVRI data collected over many months, including the earliest points, are reconciled, combined, and fitted to a unique time of explosion for each SN. On average, after they are corrected for light-curve decline rate, three SNe rise in 18.81 {+-} 0.36 days, while five SNe rise in 16.64 {+-} 0.21 days. If all eight SNe are sampled from a single parent population (a hypothesis not favored by statistical tests), the rms intrinsic scatter of the decline-rate-corrected SN rise time is 0.96{sub -0.25}{sup +0.52} days--a first measurement of this dispersion. The corresponding global mean rise time is 17.44 {+-} 0.39 days, where the uncertainty is dominated by intrinsic variance. This value is {approx}2 days shorter than two published averages that nominally are twice as precise, though also based on small samples. When comparing high-z to low-z SN luminosities for determining cosmological parameters, bias can be introduced by use of a light-curve template with an unrealistic rise time. If the period over which light curves are sampled depends on z in a manner typical of current search and measurement strategies, a two-day discrepancy in template rise time can bias the luminosity comparison by {approx}0.03 magnitudes.
Date: May 1, 2007
Creator: Strovink, Mark
Partner: UNT Libraries Government Documents Department

The complete mitochondrial sequence of the"living fossil" Tricholepidion gertschi: structure, phylogenetic implications, and the description of a novel A/T asymmetrical bias

Description: Traditionally, the 'Apterygota' has been thought to consist of five orders of wingless hexapods (Protura, Collembola, Diplura, Microcoryphia and Zygentoma) believed to be collectively basal to insects (i.e., the Pterygota). However, some studies have questioned this affinity with insects (Dallai, Abele, Spears, Nardi). Further, within these groups are hotly debated issues, including the monophyly of Entognata (Koch, 1997; Kukalova Peck, 1987), the monophyly of Diplura (Bilinski, 1993; Stys and Bilinski, 1990), the affinity between Collembola and Protura (Dallai, 1994; Kristensen, 1981) and the position of Lepidotrichidae (below). In fact, these relationships constitute one of the most debated issues in hexapod phylogeny. The family Lepidotrichidae was first described by (Silvestri, 1912) (1912: 'Lepidothricinae') from a Baltic Amber fossil (Lepidothrix pilifera Menge). The only living representative of this family is Tricholepidion gertschi Wygodzinski. Since this species was first described (Wygodzinsky, 1961) its phylogenetic position has been difficult to establish, due to an 'array of unique characters' that are difficult to interpret in a phylogenetic framework. Tricholepidion (and therefore the whole family Lepidotrichidae) has been considered either as belonging to the order Zygentoma (Kristensen, 1997; Wygodzinsky, 1961), or basal to the rest of the Zygentoma plus the Pterygota (Beutel, 2001; Bitsch and Bitsch, 2000; Staniczek, 2000), although the significance of some of the morphological characters on which these analyses are based have been questioned (Dallai et al., 2001; Kristensen, 1997). If the latter hypothesis proved to be true, the family Lepidotrichidae, would better deserve the ordinal rank. Since studies based on morphological characters have failed to give a satisfactory answer, a broad scale molecular study is under way ((Nardi et al., 2001), Frati et al, submitted, il Gomphiocephalus) in order to use mitochondrial genome sequences to study the evolution and differentiation of the most basal hexapod groups, including Tricholepidion. Mitochondrial genomics, that is ...
Date: June 23, 2002
Creator: Nardi, F.; Frati, F.; Carapelli, A.; Dallai, R. & Boore, J.
Partner: UNT Libraries Government Documents Department

A Monte Carlo Study of the Robustness and Power Associated with Selected Tests of Variance Equality when Distributions are Non-Normal and Dissimilar in Form

Description: When selecting a method for testing variance equality, a researcher should select a method which is robust to distribution non-normality and dissimilarity. The method should also possess sufficient power to ascertain departures from the equal variance hypothesis. This Monte Carlo study examined the robustness and power of five tests of variance equality under specific conditions. The tests examined included one procedure proposed by O'Brien (1978), two by O'Brien (1979), and two by Conover, Johnson, and Johnson (1981). Specific conditions included assorted combinations of the following factors: k=2 and k=3 groups, normal and non-normal distributional forms, similar and dissimilar distributional forms, and equal and unequal sample sizes. Under the k=2 group condition, a total of 180 combinations were examined. A total of 54 combinations were examined under the k=3 group condition. The Type I error rates and statistical power estimates were based upon 1000 replications in each combination examined. Results of this study suggest that when sample sizes are relatively large, all five procedures are robust to distribution non-normality and dissimilarity, as well as being sufficiently powerful.
Date: August 1990
Creator: Hardy, James C. (James Clifford)
Partner: UNT Libraries

Robustness of Parametric and Nonparametric Tests When Distances between Points Change on an Ordinal Measurement Scale

Description: The purpose of this research was to evaluate the effect on parametric and nonparametric tests using ordinal data when the distances between points changed on the measurement scale. The research examined the performance of Type I and Type II error rates using selected parametric and nonparametric tests.
Date: August 1994
Creator: Chen, Andrew H. (Andrew Hwa-Fen)
Partner: UNT Libraries

Operon Formation is Driven by Co-Regulation and Not by Horizontal Gene Transfer

Description: Although operons are often subject to horizontal gene transfer (HGT), non-HGT genes are particularly likely to be in operons. To resolve this apparent discrepancy and to determine whether HGT is involved in operon formation, we examined the evolutionary history of the genes and operons in Escherichia coli K12. We show that genes that have homologs in distantly related bacteria but not in close relatives of E. coli (indicating HGTi) form new operons at about the same rates as native genes. Furthermore, genes in new operons are no more likely than other genes to have phylogenetic trees that are inconsistent with the species tree. In contrast, essential genes and ubiquitous genes without paralogs (genes believed to undergo HGT rarely) often form new operons. We conclude that HGT is not associated with operon formation, but instead promotes the prevalence of pre-existing operons. To explain operon formation, we propose that new operons reduce the amount of regulatory information required to specify optimal expression patterns. Consistent with this hypothesis, operons have greater amounts of conserved regulatory sequences than do individually transcribed genes.
Date: April 12, 2005
Creator: Price, Morgan N.; Huang, Katherine H.; Arkin, Adam P. & Alm, Eric J.
Partner: UNT Libraries Government Documents Department

Scale dependency of the effective matrix diffusion coefficient

Description: It has been recognized that matrix diffusion is an important process for retarding solute transport in fractured rock. Based on analyses of tracer transport data from a number of field tests, we demonstrate for the first time that the effective matrix-diffusion coefficient may be scale dependent and generally increases with test scale. A preliminary theoretical explanation of this scale dependency is also presented, based on the hypothesis that solute travel paths within a fracture network are fractals.
Date: May 30, 2003
Creator: Liu, H.H.; Bodvarsson, G.S. & Zhang, G.
Partner: UNT Libraries Government Documents Department

Rostral horn evolution among agamid lizards of the genus ceratophora endemic to Sri Lanka

Description: The first phylogenetic hypothesis for the Sri Lankan agamid lizard genus Ceratophora is presented based on 1670 aligned base positions (472 parsimony informative) of mitochondrial DNA sequences, representing coding regions for eight tRNAs, ND2, and portions of ND1 and COI. Phylogenetic analysis reveals multiple origins and possibly losses of rostral horns in the evolutionary history of Ceratophora. Our data suggest a middle Miocene origin of Ceratophora with the most recent branching of recognized species occurring at the Pliocene/Pleistocene boundary. Haplotype divergence suggests that an outgroup species, Lyriocephalus scutatus, dates at least to the Pliocene. These phylogenetic results provide a framework for comparative studies of the behavioral ecological importance of horn evolution in this group.
Date: July 10, 2001
Creator: Schulte II, James A.; Macey, J. Robert; Pethiyagoda, Rohan & Larson, Allan
Partner: UNT Libraries Government Documents Department

Mechanism of constitution liquid film migration

Description: Liquid film migration (LFM) in liquid phase sintering classically involves a large metastable liquid volume adjacent to solid, and migration occurs at an isolated solid-liquid (S-L) interface. Constitutional liquid film migration (CLFM), discovered in alloy 718, has major characteristics similar to those of LFM, except that the metastable liquid is from the constitutional liquation of precipitates on the grain boundary. The similarity between LFM and CLFM has led to the theory that coherency lattice strain responsible for LFM is also responsible for CLFM. The coherency strain hypothesis was tested in this study by evaluating whether the Hillert model of LFM would also apply for CLFM. Experimental results of CLFM in alloy 718 showed that migration velocity followed the trend predicted by the Hillert model. This indicates that the coherency strain hypothesis of LFM also applies for CLFM and that the coherency lattice strain responsible for LFM is also the driving force for CLFM.
Date: June 1, 1999
Partner: UNT Libraries Government Documents Department

A Proposed Experimental Test of the Neutrino Theory

Description: The experiment outlined in this proposal has the possibility of giving an answer to the important question, 'Does the neutrino exist'? It is unfortunate that at the present time, there is no convincing experimental that neutrinos exist. Two recent articles review the status of various experiments which could give information about neutrinos. In general, these experiments give results in agreement with the predictions of beta decay theory. But actually, if even the most complete of the 'recoil type' experiments could be performed satisfactorily, all that could be concluded would be the following: the energy and momentum relationships in beta decay are consistent with the theory that the known energy deficit is carried away by a single particle. But to emphasize the fact that this would not constitute a proof of the real existence of that particle, the following quotations from the review articles should be noted. Crane says, 'All of the evidence about the neutrino is, as already pointed out, indirect in character since neutrinos have not yet been caught after leaving the nucleus. It can, of course, be argued on very general grounds that, if energy is not conserved between nucleus and electron, momentum should not be expected to be conserved either, and in consequence of this, it has often been remarked that the recoiled experiments add nothing that is really new to their knowledge'. Allen concludes his article by saying, 'Practically all the experimental evidence indicates that there is an apparent non-conservation of momentum in the beta decay process, and that the neutrino hypothesis is at least one explanation of the missing momentum'.
Date: April 18, 1949
Creator: Alvarez, Luis W.
Partner: UNT Libraries Government Documents Department

Mineral Surface Processes Responsible for the Decreased Retardation or Enhanced Mobilization of {sub 137}Cs from HLW Tank Discharges

Description: Experimental research will determine how the sorption chemistry of Cs on Hanford vadose zone sediments changes after contact with solutions characteristic of high-level tank wastes (HLW). Our central hypothesis is that the high ionic-strength of tank wastes (i.e., > 5 mol/L NaNO3) will suppress all surface-exchange reactions of Cs, except those to the highly selective frayed edge sites (FES) of the micaceous fraction. We further speculate that the concentrations, ion selectivity, and structural aspects of the FES will change after contact with the harsh chemical conditions of HLW and these changes will be manifest in the macroscopic sorption behavior of Cs. We believe that migration predictions of Cs can be improved substantially if such changes are understood and quantified.
Date: June 1, 2000
Creator: Zachara, John M.; Serne, R. Jeffrey; Ellis, Paul D. & Bertsch, Paul M.
Partner: UNT Libraries Government Documents Department

Genomic and Genetic Approaches to Solvent Tolerance

Description: The proposed research is to understand and exploit the molecular basis that determines tolerance of the industrially important anaerobic clostridia to solvents. Furthermore, we aim to develop general genomic and metabolic engineering strategies for understanding the molecular basis of tolerance to chemicals and for developing tolerant strains. Our hypothesis is that the molecular basis of what makes bacterial cells able to withstand high solvent concentrations can be used to metabolically engineer cells so that they can tolerate higher concentrations of solvents and related chemicals.
Date: June 10, 2005
Creator: Papoutsakis, Eleftherios T.
Partner: UNT Libraries Government Documents Department

ANNUAL REPORT FOR ENVIRONMENTAL MANAGEMENT SCIENCE PROGRAM PROJECT NUMBER 86598 COUPLED FLOW AND REACTIVITY IN VARIABLY SATURATED POROUS MEDIA

Description: Improved models of contaminant migration in heterogeneous, variably saturated porous media are required to better define the long-term stewardship requirements for U.S. Department of Energy (DOE) lands and to assist in the design of effective vadose zone barriers to contaminant migrations. The objective of our three-year project is to meet the DOE need by developing new experimental approaches to describe adsorption and transport of contaminants in heterogeneous, variably saturated media (i.e., the vadose zone). The research specifically addresses the behavior of strontium, a high priority DOE contaminant. However, the key benefit of this research is improved conceptual models of how all contaminants migrate through heterogeneous, variably-saturated, porous media. Research activities are driven by the hypothesis that the reactivity of variably saturated porous media is dependent on the moisture content of the medium and can be represented by a relatively simple function applicable over a range of scales, contaminants, and media. A key and novel aspect of our research is the use of the 2-meter radius geocentrifuge capabilities at the Idaho National Engineering and Environmental Laboratory (INEEL) to conduct unsaturated reactive transport experiments (Figure 1). The experimental approach using the geocentrifuge provides data in a much shorter time period than conventional methods allowing us to complete more experiments and explore a wider range of moisture contents. The vadose zone research being done in this project will demonstrate the utility of environmental geocentrifuge experimental approaches and their applicability to DOE's vadose research needs.
Date: June 13, 2003
Creator: Palmer, Carl D.; Mattson, Earl D. & Smith, Robert W.
Partner: UNT Libraries Government Documents Department

ANNUAL REPORT FOR ENVIRONMENTAL MANAGEMENT SCIENCE PROGRAM PROJECT NUMBER 86598 COUPLED FLOW AND REACTIVITY IN VARIABLY SATURATED POROUS MEDIA

Description: Improved models of contaminant migration in heterogeneous, variably saturated porous media are required to better define the long-term stewardship requirements for U.S. Department of Energy (DOE) lands and to assist in the design of effective vadose zone barriers to contaminant migrations. The objective of our three-year project is to meet the DOE need by developing new experimental approaches to describe adsorption and transport of contaminants in heterogeneous, variably saturated media (i.e., the vadose zone). The research specifically addresses the behavior of strontium, a high priority DOE contaminant. However, the key benefit of this research is improved conceptual models of how all contaminants migrate through heterogeneous, variably-saturated, porous media. Research activities are driven by the hypothesis that the reactivity of variably saturated porous media is dependent on the moisture content of the medium and can be represented by a relatively simple function applicable over a range of scales, contaminants, and media. A key and novel aspect of our research is the use of the 2-meter radius geocentrifuge capabilities at the Idaho National Engineering and Environmental Laboratory (INEEL) to conduct unsaturated reactive transport experiments (Figure 1). The experimental approach using the geocentrifuge provides data in a much shorter time period than conventional methods allowing us to complete more experiments and explore a wider range of moisture contents. The vadose zone research being done in this project will demonstrate the utility of environmental geocentrifuge experimental approaches and their applicability to DOE's vadose research needs. This report summarizes our progress as of June 2003 in the first year of a three-year project.
Date: June 1, 2003
Creator: Palmer, Carl D.; Mattson, Earl D. & Smith, Robert W.
Partner: UNT Libraries Government Documents Department

PECULIAR OPTICAL AND IR BEHAVIOUR IN TYPE I SUPERNOVAE, AND THE ORIGIN OF THE 1.2 ABSORPTION

Description: A small number of type I supernovae exhibit well defined peculiarities. In particular some type I supernovae do not have the characteristic 6150 {angstrom} feature and some do not have the 1.2 {micro}m absorption. It is noted that all SN which lack the infrared absorption also lack the 6150 {angstrom} feature which is attributed to Si II. It is proposed that these supernovae constitute a single sub-class and that Si could be responsible for the strong unidentified infrared absorption which is characteristic of classical SNI. Si I has a dense array of strong lines in the near infrared so this ion could be responsible for the dominant features of SNIa IR behaviour. If this hypothesis is vindicated by subsequent observations or by calculation of synthetic spectra then it is most likely that the difference between ordinary supernovae and these peculiar ones is the abundance of Si.
Date: November 1, 1985
Creator: Graham, J.R.
Partner: UNT Libraries Government Documents Department

A theoretical description of inhomogeneous turbulence

Description: This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). In this LDRD, we have developed a highly compact and descriptive formalism that allows us to broach the theoretically formidable morass of inhomogeneous turbulence. Our formalism has two novel aspects: (a) an adaptation of helicity basis functions to represent an arbitrary incompressible channel flow and (b) the invocation of a hypothesis of random phase. A result of this compact formalism is that the mathematical description of inhomogeneous turbulence looks much like that of homogeneous turbulence--at the moment, the most rigorously explored terrain in turbulence research. As a result, we can explore the effect of boundaries on such important quantities as the gradients of mean flow, mean pressure, triple-velocity correlations and pressure velocity correlations, all of which vanish under the conventional, but artificial, assumption that the turbulence is statistically spatially uniform. Under suitable conditions, we have predicted that a mean flow gradient can develop even when none is initially present.
Date: March 1, 2000
Creator: Turner, L.
Partner: UNT Libraries Government Documents Department

An Analysis of Thirty Border Standard Metropolitan Statistical Areas in Relation to E. W. Burgess' Concentric Zone Hypothesis

Description: This study is made to evaluate some of these forces for the thirty titled Standard Metropolitan Statistical Areas of the United States which are located on and overlap borders of two or more states. The attempt is made to determine if border SMSAs conform to the Burgess model despite state lines and other barriers imposed between SMSA parts, or whether such barriers restrict functional growth to the state side containing the central city.
Date: June 1970
Creator: Bonner, Austin
Partner: UNT Libraries

Discovery of Non-random Spatial Distribution of Impacts in the Stardust Cometary Collector

Description: We report the discovery that impacts in the Stardust cometary collector are not distributed randomly in the collecting media, but appear to be clustered on scales smaller than {approx} 10 cm. We also report the discovery of at least two populations of oblique tracks. We evaluated several hypotheses that could explain the observations. No hypothesis was consistent with all the observations, but the preponderance of evidence points toward at least one impact on the central Whipple shield of the spacecraft as the origin of both clustering and low-angle oblique tracks. High-angle oblique tracks unambiguously originate from a non-cometary impact on the spacecraft bus just forward of the collector.
Date: April 6, 2007
Creator: Westphal, A J; Bastien, R K; Borg, J; Bridges, J; Brownlee, D E; Burchell, M J et al.
Partner: UNT Libraries Government Documents Department