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Variation in conserved non-coding sequences on chromosome 5q andsusceptibility to asthma and atopy

Description: Background: Evolutionarily conserved sequences likely havebiological function. Methods: To determine whether variation in conservedsequences in non-coding DNA contributes to risk for human disease, westudied six conserved non-coding elements in the Th2 cytokine cluster onhuman chromosome 5q31 in a large Hutterite pedigree and in samples ofoutbred European American and African American asthma cases and controls.Results: Among six conserved non-coding elements (>100 bp,>70percent identity; human-mouse comparison), we identified one singlenucleotide polymorphism (SNP) in each of two conserved elements and sixSNPs in the flanking regions of three conserved elements. We genotypedour samples for four of these SNPs and an additional three SNPs each inthe IL13 and IL4 genes. While there was only modest evidence forassociation with single SNPs in the Hutterite and European Americansamples (P<0.05), there were highly significant associations inEuropean Americans between asthma and haplotypes comprised of SNPs in theIL4 gene (P<0.001), including a SNP in a conserved non-codingelement. Furthermore, variation in the IL13 gene was strongly associatedwith total IgE (P = 0.00022) and allergic sensitization to mold allergens(P = 0.00076) in the Hutterites, and more modestly associated withsensitization to molds in the European Americans and African Americans (P<0.01). Conclusion: These results indicate that there is overalllittle variation in the conserved non-coding elements on 5q31, butvariation in IL4 and IL13, including possibly one SNP in a conservedelement, influence asthma and atopic phenotypes in diversepopulations.
Date: September 10, 2005
Creator: Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng; Kurz,Thorsten; Dubchak, Inna; Frazer, Kelly A. et al.
Partner: UNT Libraries Government Documents Department

An Enhancer Near ISL1 and an Ultraconserved Exon of PCBP2 areDerived from a Retroposon

Description: Hundreds of highly conserved distal cis-regulatory elementshave been characterized to date in vertebrate genomes1. Many thousandsmore are predicted based on comparative genomics2,3. Yet, in starkcontrast to the genes they regulate, virtually none of these regions canbe traced using sequence similarity in invertebrates, leaving theirevolutionary origin obscure. Here we show that a class of conserved,primarily non-coding regions in tetrapods originated from a novel shortinterspersed repetitive element (SINE) retroposon family that was activein Sarcopterygii (lobe-finned fishes and terrestrial vertebrates) in theSilurian at least 410 Mya4, and, remarkably, appears to be recentlyactive in the "living fossil" Indonesian coelacanth, Latimeriamenadoensis. We show that one copy is a distal enhancer, located 500kbfrom the neuro-developmental gene ISL1. Several others represent new,possibly regulatory, alternatively spliced exons in the middle ofpre-existing Sarcopterygian genes. One of these is the>200bpultraconserved region5, 100 percent identical in mammals, and 80 percentidentical to the coelacanth SINE, that contains a 31aa alternativelyspliced exon of the mRNA processing gene PCBP26. These add to a growinglist of examples7 in which relics of transposable elements have acquireda function that serves their host, a process termed "exaptation"8, andprovide an origin for at least some of the highly-conservedvertebrate-specific genomic sequences recently discovered usingcomparative genomics.
Date: November 27, 2005
Creator: Bejerano, Gill; Lowe, Craig; Ahituv, Nadav; King, Bryan; Siepel,Adam; Salama, Sofie et al.
Partner: UNT Libraries Government Documents Department

The sequence and analysis of duplication rich human chromosome 16

Description: We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility.
Date: August 1, 2004
Creator: Martin, Joel; Han, Cliff; Gordon, Laurie A.; Terry, Astrid; Prabhakar, Shyam; She, Xinwei et al.
Partner: UNT Libraries Government Documents Department

CAGE100: Real-Time Multi-Port Packet Capture System for 100 Gigabit Ethernet Traffic

Description: Future large scale sciences are anticipated to use massive amount of data in their experiments. DOE’s ESnet (Energy Science Network) is developing a 100 Gbps backbone based on this state-of-the-art 100 Gigabit Ethernet standard. ESnet will serve thousands of DOE and non-DOE scientists with its high bandwidth backbone, and connect several national laboratories. Current Ethernet test and debug solutions, such as network traffic capturer/analyzer tools, support up to 10 Gbps speed, and the very few capable of handling 100 Gbps are extremely costly. Such tools are essential in the development of high speed devices and routers, and ultimately the success of 100 Gigabit Ethernet.
Date: June 14, 2012
Creator: Farrokhnia, Shahin; Namazi, Ali; Azimi-Sadjadi, Babak & Lin, Chujen
Partner: UNT Libraries Government Documents Department

Genome-wide analysis of promoter architecture in Drosophila melanogaster

Description: Core promoters are critical regions for gene regulation in higher eukaryotes. However, the boundaries of promoter regions, the relative rates of initiation at the transcription start sites (TSSs) distributed within them, and the functional significance of promoter architecture remain poorly understood. We produced a high-resolution map of promoters active in the Drosophila melanogaster embryo by integrating data from three independent and complementary methods: 21 million cap analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid amplification of cDNA ends (RLMRACE) reads, and 50,000 cap-trapped expressed sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis indicates that, due to non-promoter-associated RNA background signal, previous studies have likely overestimated the number of promoter-associated CAGE clusters by fivefold. We show that TSS distributions form a complex continuum of shapes, and that promoters active in the embryo and adult have highly similar shapes in 95% of cases. This suggests that these distributions are generally determined by static elements such as local DNA sequence and are not modulated by dynamic signals such as histone modifications. Transcription factor binding motifs are differentially enriched as a function of promoter shape, and peaked promoter shape is correlated with both temporal and spatial regulation of gene expression. Our results contribute to the emerging view that core promoters are functionally diverse and control patterning of gene expression in Drosophila and mammals.
Date: October 20, 2010
Creator: Hoskins, Roger A.; Landolin, Jane M.; Brown, James B.; Sandler, Jeremy E.; Takahashi, Hazuki; Lassmann, Timo et al.
Partner: UNT Libraries Government Documents Department


Description: The theory of tomographical imaging with limited-angular input is discussed , from which two reconstruction algorithms are derived. The existence of missing information due to incomplete angular coverage is demonstrated. and an iteration algorithm to recover this information from a priori knowledge on the finite extent of the object developed. Smoothing algorithms to stabilize reconstructions in the presence of noise are given. The effects of digitization and finite truncation of the reconstruction region in numerical computation are also analysed. It is shown that the limited-angle problem is governed by a set of eigenvalues whose spectrum is determined by the imaging angle and the finite extent of the object. The distortion on a point source caused by the missing information is calculated; from the results some properties of the iteration scheme, such as spatial uniformity, are derived.
Date: September 1, 1980
Creator: Tam, K. C. & Perez-Mendez, V.
Partner: UNT Libraries Government Documents Department

Oncology Center

Description: Efforts by the Hollings Cancer Center to earn a designation as a National Cancer Center are outlined.
Date: September 21, 2009
Creator: Kraft, Andrew S.
Partner: UNT Libraries Government Documents Department

SARC: Development and Support of a Sarcoma Research Consortium Infrastructure

Description: SARC is a non-for-profit organization whose mission and vision is to advocate for the collaboration on the design of clinical trials on sarcoma, to further the knowledge regarding the diagnosis and treatment of sarcoma and provide accurate and up to date information to physicians, patients and families. The objectives are to assist in the development of the infrastructure for the continued growth and spectrum of clinical research, to facilitate biannual meeting of investigators, and to develop a preclinical research base that would design and conduct research that would improve the process of drug treatments selected for clinical research trials.
Date: October 29, 2007
Creator: Arkison, Jim
Partner: UNT Libraries Government Documents Department

Regeneration of Tissues and Organs Using Autologous Cells

Description: The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute’s ongoing programs are aimed at developing regenerative medicine technologies that employ a patient’s own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body’s own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat conditions where other approaches have failed.
Date: October 11, 2012
Creator: Anthony Atala, M.D.
Partner: UNT Libraries Government Documents Department

Corn Storage Protein - A Molecular Genetic Model

Description: Corn is the highest yielding crop on earth and probably the most valuable agricultural product of the United States. Because it converts sun energy through photosynthesis into starch and proteins, we addressed energy savings by focusing on protein quality. People and animals require essential amino acids derived from the digestion of proteins. If proteins are relatively low in certain essential amino acids, the crop becomes nutritionally defective and has to be supplemented. Such deficiency affects meat and fish production and countries where corn is a staple. Because corn seed proteins have relatively low levels of lysine and methionine, a diet has to be supplemented with soybeans for the missing lysine and with chemically synthesized methionine. We therefore have studied genes expressed during maize seed development and their chromosomal organization. A critical technical requirement for the understanding of the molecular structure of genes and their positional information was DNA sequencing. Because of the length of sequences, DNA sequencing methods themselves were insufficient for this type of analysis. We therefore developed the so-called “DNA shotgun sequencing” strategy, where overlapping DNA fragments were sequenced in parallel and used to reconstruct large DNA molecules via overlaps. Our publications became the most frequently cited ones during the decade of 1981-1990 and former Associate Director of Science for the Office of Basic Energy Sciences Patricia M. Dehmer presented our work as one of the great successes of this program. A major component of the sequencing strategy was the development of bacterial strains and vectors, which were also used to develop the first biotechnology crops. These crops possessed new traits thanks to the expression of foreign genes in plants. To enable such expression, chimeric genes had to be constructed using our materials and methods by the industry. Because we made our materials and methods freely available to ...
Date: May 31, 2013
Creator: Messing, Joachim
Partner: UNT Libraries Government Documents Department

Development of a System for Rapid Detection of Contaminants in Water Supplies Using Magnetic Resonance and Nanoparticles

Description: To keep the water supply safe and to ensure a swift and accurate response to a water supply contamination event, rapid and robust methods for microbial testing are necessary. Current technologies are complex, lengthy and costly and there is a need for rapid, reliable, and precise approaches that can readily address this fundamental security and safety issue. T2 Biosystems is focused on providing solutions to this problem by making breakthroughs in nanotechnology and biosensor techniques that address the current technical restrictions facing rapid, molecular analysis in complex samples. In order to apply the T2 Biosystems nucleic acid detection procedure to the analysis of nucleic acid targets in unprocessed water samples, Bacillus thuringeinsis was selected as a model organism and local river water was selected as the sample matrix. The initial assay reagent formulation was conceived with a manual magnetic resonance reader, was optimized using a high throughput system, and transferred back to the MR reader for potential field use. The final assay employing the designed and manufactured instruments was capable of detecting 10 CFU/mL of B. thuringiensis directly within the environmental water sample within 90 minutes. Further, discrimination of two closely related species of Bacilli was accomplished using the methods of this project; greater than 3-fold discrimination between B. cereus and B. thuringiensis at a concentrations spanning 10 CFU/mL to 10{sup 5} CFU/mL was observed.
Date: September 14, 2010
Creator: Lowery, Thomas J; Neely, Lori; Chepin, James; Wellman, Parris; Toso, Ken; Murray, Paul et al.
Partner: UNT Libraries Government Documents Department

RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach

Description: RegPredict web server is designed to provide comparative genomics tools for reconstruction and analysis of microbial regulons using comparative genomics approach. The server allows the user to rapidly generate reference sets of regulons and regulatory motif profiles in a group of prokaryotic genomes. The new concept of a cluster of co-regulated orthologous operons allows the user to distribute the analysis of large regulons and to perform the comparative analysis of multiple clusters independently. Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several scenarios for the generation of starting gene sets. RegPredict provides a comprehensive collection of manually curated positional weight matrices of regulatory motifs. It is based on genomic sequences, ortholog and operon predictions from the MicrobesOnline. An interactive web interface of RegPredict integrates and presents diverse genomic and functional information about the candidate regulon members from several web resources. RegPredict is freely accessible at http://regpredict.lbl.gov.
Date: May 26, 2010
Creator: Novichkov, Pavel S.; Rodionov, Dmitry A.; Stavrovskaya, Elena D.; Novichkova, Elena S.; Kazakov, Alexey E.; Gelfand, Mikhail S. et al.
Partner: UNT Libraries Government Documents Department

Characterization of the effects of x-ray irradiation on the hierarchical structure and mechanical properties of human cortical bone

Description: Bone comprises a complex structure of primarily collagen, hydroxyapatite and water, where each hierarchical structural level contributes to its strength, ductility and toughness. These properties, however, are degraded by irradiation, arising from medical therapy or bone-allograft sterilization. We provide here a mechanistic framework for how irradiation affects the nature and properties of human cortical bone over a range of characteristic (nano to macro) length-scales, following x-­ray exposures up to 630 kGy. Macroscopically, bone strength, ductility and fracture resistance are seen to be progressively degraded with increasing irradiation levels. At the micron-­scale, fracture properties, evaluated using in-situ scanning electron microscopy and synchrotron x-ray computed micro-tomography, provide mechanistic information on how cracks interact with the bone-matrix structure. At sub-micron scales, strength properties are evaluated with in-situ tensile tests in the synchrotron using small-/wide-angle x-ray scattering/diffraction, where strains are simultaneously measured in the macroscopic tissue, collagen fibrils and mineral. Compared to healthy bone, results show that the fibrillar strain is decreased by ~40% following 70 kGy exposures, consistent with significant stiffening and degradation of the collagen. We attribute the irradiation-­induced deterioration in mechanical properties to mechanisms at multiple length-scales, including changes in crack paths at micron-­scales, loss of plasticity from suppressed fibrillar sliding at sub-­micron scales, and the loss and damage of collagen at the nano-­scales, the latter being assessed using Raman and Fourier-Transform-Infrared spectroscopy and a fluorometric assay.
Date: August 19, 2011
Creator: Barth, Holly; Zimmermann, Elizabeth; Schaible, Eric; Tang, Simon; Alliston, Tamara & Ritchie, Robert
Partner: UNT Libraries Government Documents Department

Targeting the tumor microenvironment

Description: Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.
Date: November 7, 2006
Creator: Kenny, P.A.; Lee, G.Y. & Bissell, M.J.
Partner: UNT Libraries Government Documents Department

CRADA No. BNL-C-97-10 between BNL and Cotton, Inc. Final abstract and final report [Final Report of Research carried out under DOE CRADA No. BNL-C-97-10 - "Prediction of Yield in Cotton"]

Description: The objectives of this work were to determine if the numbér of fiber cell initials varied genetically and to compare the number of initials with that of mature fibers obtained at harvest time. The method used to count the number of fiber cell initials is direct, simple, quick and done while the plant is growing. In contrast, the currently used commercial process is indirect and needs large amount mature fibers gathered at harvest time. However, all current work on cotton yield is based on fiber numbers obtained by the indirect commercial process. Consequently, it was necessary to compare results obtained from the two methods using the same plants as the source of material. The results show that the number of fiber initials per ovule differed significantly (P>0.05) for seven cultivars in 1995 and 1996. AIso, a 1997 study shows the number of fiber initials varied by 15% over boll positions and environments, with rankings among cultivars generally consistent across boll positions and sampling times. Finally, although there were differences among cultivars for initial fiber cell number, all cultivars had nearly the same number of mature lint fibers per seed. This last finding is significant. It indicates that the rate of fiber cell initiation varies among cultivars; the lower the rate, the greater the difference between the number of initials and the number of mature fiber cells. If the rate of fiber initiation is relatively high, the number of initials and mature fibers differs by about 11%; if it is low, the difference is as high as 31%. Cotton breeders may be able to use genetic differences for the number of fiber initials and/or the rate of fiber cell initiation in crop improvement programs.
Date: January 3, 2000
Partner: UNT Libraries Government Documents Department

Wind-Tunnel Development of Ailerons for the Curtiss XP-60 Airplane, Special Report

Description: An investigation was made in the LWAL 7- by 10-foot tunnel of internally balanced, sealed ailerons for the Curtiss XP-60 airplane. Ailerons with tabs and. with various amounts of balance were tested. Stick forces were estimated for several aileron arrangements including an arrangement recommended for the airplane. Flight tests of the recommended arrangement are discussed briefly in an appendix, The results of the wind-tunnel and flight tests indicate that the ailerons of large or fast airplanes may be satisfactorily balanced by the method developed.
Date: September 1942
Creator: Rogallo, F. M. & Lowry, John G.
Partner: UNT Libraries Government Documents Department