Endoreduplication represents a cell cycle variant during which multiple rounds of DNA replication occur without subsequent chromosome separation and cytokinesis, resulting into a cellular increase of the DNA content. Although the DNA ploidy level of cells is controlled by external stimuli such as light, currently limited knowledge is available on how environmental signals regulate the endoreduplication cycle at the molecular level. Previously, we have demonstrated that the conversion from the mitotic cell cycle into an endoreduplication cycle is mediated by the atypical E2F transcription factor DEL1 that operates as a repressor of endocycle onset. Here, we identified DEL1 as a transcriptional target of the classical E2Fb and E2Fc transcription factors that antagonistically control DEL1 transcript levels through competition for a single E2F cis-acting binding site. Correspondingly ...
BackgroundA wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data...Full Text Available
Comparative sequence analysis of the human and the pufferfish Fugu rubripes (fugu) genomes has revealed several novel functional coding and noncoding regions in the human genome. In particular, the fugu genome has been extremely valuable for identifyingtranscriptionalregulatory elements in human loci harboring unusually high levels of evolutionary conservation to rodent genomes. In such regions, the large evolutionary distance between human and fishes provides an additional filter through which functional noncoding elements can be detected with high efficiency.
Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatorytranscription factor, have been implicated in synaptic plasticity...Full Text Available
The Far UpStream Element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream...Full Text Available
Background The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. Results We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression ...
How transcription factors interpret the cis-regulatory logic encoded within enhancers to mediate quantitative changes in spatiotemporally restricted expression patterns during animal...Full Text Available
Zebrafish transgenesis is a powerful and increasingly common strategy to assay vertebrate transcriptionalregulatory control. Several challenges remain, however, to the broader application of...Full Text Available
Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease,...Full Text Available
The Center for Nuclear Waste Regulatory Analyses organized and hosted a workshop on ``Rock Mechanics Issues in Repository Design and Performance Assessment`` on behalf its sponsor the U.S. Nuclear Regulatory Commission (NRC). This workshop was held on September 19- 20, 1994 at the Holiday Inn Crowne Plaza, Rockville, Maryland. The objectives of the workshop were to stimulate exchange of technical information among parties actively investigating rock mechanics issues relevant to the proposed high-level waste repository at Yucca Mountain and identify/confirm rock mechanics issues important to repository design and performance assessment The workshop contained three technical sessions and two panel discussions. The participants included technical and research staffs representing the NRC and the Department of Energy and their contractors, as well as researchers from the academic, commercial, and international technical ...
The DNA sequence motif ATTTGCAT (octamer) or its inverse complement has been identified as an evolutionarily conserved element in the promoter region of immunoglobulin genes. Two major DNA-binding proteins that bind in a sequence-specific manner to the octamer DNA sequence have been identified in mammalian species--a ubiquitously expressed protein (Oct-1) and a lymphoid-specific protein (Oct-2). During characterization of the promoter region of the chicken immunoglobulin light chain gene, the authors identified two homologous octamer-binding proteins in chicken B cells. when the cloning of the human gene for Oct-2 revealed it to be a member of a distinct family of homeobox genes, they sought to determine if the human Oct-2 cDNA could be used to identify homologous chicken homeobox genes. Using a human Oct-2 homeobox-specific DNA probe, they were able to identify 6-10 ...
Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic...Full Text Available
The ETS proteins are a family of transcription factors (TFs) that regulate a variety of biological processes. We made genome-wide analyses to explore the classification of the ETS gene family. We identified...Full Text Available
We have used a cell-free polymerase I transcription system derived from HeLa cells to study the regulation of human rRNA synthesis. Analysis of deletion mutants spanning the start site of transcription at nucleotide +1 indicates that the control region affecting initiation of human rRNA synthesis is contained within sequences from nucleotides -158 to +18. This promoter region can be subdivided into (i) a central segment of approximately 40 base pair that is required for transcription and (ii) flanking sequences that influence the efficiency of transcription in vitro. We have examined the in vitro transcriptional activity of the human extract under various conditions that are thought to modulate rRNA synthesis in vivo. Cell-free extracts prepared from HeLa cells infected with adenovirus 2 synthesize human rRNA at levels greatly decreased relative to uninfected cell extracts. By ...
Promoters are important regulatory elements that contain the necessary sequence features for cells to initiate transcription. To functionally characterize a large set of human promoters, we measured...Full Text Available
BackgroundNeuropeptide Y is a key neurotransmitter of the central nervous system which plays a vital role in the feed energy homeostasis in mammals. Mutations in the regulatory and...Full Text Available
The development of chromatin immunoprecipitation methods coupled with DNA microarray (ChIP-chip) technology has enabled genome-wide identification of cis-DNA regulatory elements to which transcription...Full Text Available
BackgroundGATA-2 is a transcription factor required for hematopoietic stem cell survival as well as for neuronal development in vertebrates. It has been shown that specific expression...Full Text Available
KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks...Full Text Available
BackgroundWe have recently introduced a predictive framework for studying gene transcriptional regulation in simpler organisms using a novel supervised learning algorithm called...Full Text Available
The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most ...
Motivation: The identification of gene regulatory modules is an important yet challenging problem in computational biology. While many computational methods have been proposed to identify...Full Text Available
The cell cycle-regulatorytranscription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance....Full Text Available
The products of trithorax group (trxG) genes maintain active transcription of many important developmental regulatory genes, including homeotic genes. Several trxG proteins have been shown to act in...Full Text Available
A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila....Full Text Available
Hox genes encode a family of transcriptional regulators that operate differential developmental programs along the anteroposterior axis of bilateral animals. Regulatory changes affecting Hox gene expression are believed to have been crucial for the evolution of animal body plans. In Drosophila melanogaster, Hox expression is post-transcriptionally regulated by microRNAs (miRNAs) acting on target sites located in the 3' untranslated regions (3'UTRs) of Hox mRNAs. Notably, recent work has shown that during D. melanogaster development Hox genes produce mRNAs with variable 3'UTRs (short and long forms) in different sets of tissues as a result of alternative polyadenylation; importantly, Hox short and long 3'UTRs contain very different target sites for miRNAs. Here, we use a computational approach to explore the evolution of Hox 3'UTRs treated with especial regard to miRNA regulation. Our work is focused on the 12 Drosophila ...
In Borrelia burgdorferi (Bb), the Lyme disease spirochete, the alternative σ factor σ54 (RpoN) directly activates transcription of another alternative σ...Full Text Available
The study concludes that while the diversification into nonutility activities by the Rural Electric Cooperatives and the Rural Telephone Cooperatives has been expanding, the regulatory activities by the Rural Electrification Administration and the state public utility commissions have been inadequate to guard against cross-subsidization. In fact, there generally exist no data to identify and investigate illegal cross-subsidization activities of cooperatives. Increasing the regulatory functions of state public utility commissions and the REA was recommended.
Innate immune responses are regulated by microorganisms and cell death, as well as by a third class of stress signal from the nervous and endocrine systems. The innate immune system also feeds back, through the production of cytokines, to regulate the function of the central nervous system (CNS), and this has effects on behaviour. These signals provide an extrinsic regulatory circuit that links physiological, social and environmental conditions, as perceived by the CNS, with transcriptional 'decision-making' in leukocytes. CNS-mediated regulation of innate immune responses optimizes total organism fitness and provides new opportunities for therapeutic control of chronic infectious, inflammatory and neuropsychiatric diseases.
Extending genome wide association analysis by the inclusion of gene expression data may assist in the dissection of complex traits. We examined piebald, a pigmentation phenotype in both human and Merino...Full Text Available
BackgroundGene regulation is a key mechanism in higher eukaryotic cellular processes. One of the major challenges in gene regulation studies is to identify regulators affecting the...Full Text Available
From Toki-shakuyaku-san, an herbal formulation for “cleansing stagnated blood,” a key gene regulatory compound was purified and identified through a screening based on DNA microarray...Full Text Available
When preadipocytes differentiate into adipocytes, several differentiation-linked genes are activated. Lipo-protein lipase (LPL) is one of the first genes induced during this process. To investigate early events in adipocyte development, we have focused on the transcriptional activation of the LPL gene. For this purpose, we have cloned and fused different parts of intragenic and flanking sequences with a chloramphenicol acetyltransferase reporter gene. Transient transfection experiments and DNase I hypersensitivity assays indicate that several positive as well as negative elements contribute to transcriptional regulation of the LPL gene. When reporter gene constructs were stably introduced into preadipocytes, we were able to monitor and compare the activation patterns of different promoter deletion mutants at selected time points representing the process of adipocyte development. We could delimit two cis-regulatory elements ...
Mutations in transcription factors hepatocyte nuclear factors (HNF)-1#alpha# and HNF-1#beta# cause maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. HNF-1#alpha# and HNF-1#beta# mutations are well studied in some tissues, but the mechanism by which HNF-1#alpha# and HNF-1#beta# mutations affect sucrase-isomaltase (SI) transcription in the small intestine is unclear. We studied the effects of 13 HNF-1#alpha# mutants and 2 HNF-1#beta# mutants on human SI gene transcription, which were identified in subjects with MODY3 and MODY5, respectively. Transactivation activity of 11 HNF-1#alpha# and 2 HNF-1#beta# mutants was significantly lower than that of wild (wt)-HNF-1#alpha# and wt-HNF-1#beta#. Furthermore, in co-expression studies with mutant (mu)-HNF-1#alpha#/ wt-HNF-1#beta# and wt-HNF-1#alpha#/mu-HNF-1#beta#, the combination of mu-HNF-1#alpha# (P379fsdelCT and ...
Abstract The Hippo pathway is an evolutionally conserved protein kinase cascade involved in regulating organ size in vivo and cell contact inhibition in vitro by governing cell proliferation and apoptosis. Deregulation of the Hippo pathway is linked to cancer development. Its first core kinase Warts was identified in Drosophila more than 15 years ago, but it gained much attention when other core components of the pathway were identified 8 years later. Major discoveries of the pathway were made during past several years. The core kinase components Hippo, Salvador, Warts, and Mats in the fly and Mst1/2, WW45, Lats1/2, and Mob1 in mammals phosphorylate and inactivate downstream transcriptional co-activators Yorkie in the fly, Yes-associated protein (YAP) and transcriptional co-activator with ...
The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc target genes have been identified, the molecular determinants of Myc’s transcriptional...Full Text Available
BackgroundUsing a transcriptional profiling approach, we recently identified myeloid-related protein-8/14 (MRP-8/14) to be expressed by platelets during acute MI....Full Text Available
We have identified another Drosophila GTP-binding protein (G protein) alpha subunit, dGq alpha-3. Transcripts encoding dGq alpha-3 are derived from alternative splicing of the dGq alpha locus previously...Full Text Available
Transcriptional silencing in Saccharomyces cerevisiae occurs at several genetic loci, including the ribosomal DNA (rDNA). Silencing at telomeres (telomere position effect [TPE])...Full Text Available
Objective: Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. Methods: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage,...
The cAMP response element-binding protein (CREB) is a highly conserved transcription factor that integrates signaling through the cAMP-dependent protein kinase A (PKA) in many eukaryotes. PKA plays a critical role in Dictyostelium development but no CREB homologue has been identified in this system. Here we show that Dictyostelium utilizes a CREB-like protein, BzpF, to integrate PKA signaling during late development. bzpF^- mutants produce compromised spores, which are extremely unstable and germination defective. Previously, we have found that BzpF binds the canonical CRE motif in vitro. In this paper, we determined the DNA binding specificity of BzpF using protein binding microarray (PBM) and showed that the motif with the highest specificity is a CRE-like sequence. BzpF is necessary to ...
This document defines the services the Waste Sampling and Characterization Facility (WSCF) shall provide Effluent Monitoring (EM) throughout the calendar year for analysis. The internal memo contained in Appendix A identifies the samples Em plans to submit for analysis in CY-1995. Analysis of effluent (liquid and air discharges) and environmental (air, liquid, animal, and vegetative) samples is required using standard laboratory procedures, in accordance with regulatory and control requirements. This report describes regulatory reporting requirements and WSCF services and data quality objectives.
Immune function is critical in health and disease. The control and regulation of immune reactions is an area of intense investigation that has important implications for allogeneic hematopoietic cell transplantation. Immune reactions are regulated in a number of important ways. Compartmentalization of immune responses and the production of both pro-inflammatory and anti-inflammatory cytokines play a major role. More recently several populations of T cells that regulate immune responses termed regulatory T cells have been identified. This manuscript will focus on CD4^+CD25^+FoxP3^+ natural regulatory T cells (T"r"e"g) and @a@bTCR^+CD4^+NK1.1^+ natural killer T (NK-T) cells which both suppress graft vs host disease but appear to function by distinct mechanisms.
The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to and activate transcription from the Dopa decarboxylase (Ddc) gene. A structure-function analysis of NTF-1 led to the identification of a discrete amino-terminal activation domain. Here, we report that an NTF-1 mutant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive heterodimers with the full-length protein. Ectopically expressing this dominant-negative protein or the full-length protein in developing Drosophila embryos leads to dire developmental consequences. Overexpressing the trans-dominant NTF-1 leads to lethality, while overexpressing full-length NTF-1 results in both lethality and morphogenetic defects. Our results suggest that both the activity and the regulation of NTF-1 are critical for viability and ...
Understanding of probiotic-induced regulatory gene expression and networking is critical to further explore their roles in controlling infection. Transcriptional profile of selected innate immune genes in primary bovine intestinal epithelial cells was assessed over a time course of incubation with the probiotic Lactobacillus plantarum 299v. Based on gene expression results, a time point was chosen to prime epithelial cells with the probiotic prior to infection with rotavirus. Plaque assays and genomic analysis provided the basis for establishing the efficacy of probiotics in preventing a rotaviral infection. Plaque assays revealed that the probiotic is capable of decreasing (at least by 100-fold) the levels of live virus when the cells were primed with the probiotic. Results from gene expr...
Over the decades, basic research in life sciences has profited greatly from the study of the small unicellular fungal species Saccharomyces cerevisiae. This yeast turned out to be key for the identification and understanding of molecular mechanisms that underlay the basic functions of all eukaryotic cells. These include, but are not limited to, the regulatory mechanisms behind cellular reproduction (cell cycle control), cellular morphogenesis (cell polarity, cytoskeleton and membrane trafficking) and the management of cellular information (chromosome biology, transcription and translation). Rapid access to genomic information of many yeast species, combined with bioinformatics analyses, provide information on the evolutionary history of yeasts and the molecular ancestry of their constituen...
This report describes the fiscal 1998 result on development of genome informatics technology. As comparative analysis technique of genes, the combination of electrophoresis and PCR was used. For improvement of the throughput and reproducibility of the technique, module- shuffling primers were used, and the multi(96)-arrayed capillary fragment analyzer was devised. The system detecting SNPs rapidly was also developed successfully. As analysis technology of DNA sequence by use of triple- stranded DNA formation, study was made on construction of long cDNA libraries, selective subtraction of specific sequences from libraries, and the basic technology of homologous cloning. Study was also made on each reaction step of IGCR technique for fast analysis, and specifications of a fluorescence transfer monitor. As modeling technique of genetic sequence information, the simulation model was developed for gene expression regulatory networks during muscle differentiation, and ...
A reliable source of specific criteria for recognizing a wetland, as defined for regulatory purposes would be valuable. In 1987 the Army Corps of Engineers developed a technical manual for identifying wetlands (1987 Wetlands Manual). An interagency manual (1989 Wetlands Manual) was later developed. This manual has been used to identify wetlands according to three evidentiary factors: vegetation, hydrology, and soil. This paper addresses the development of criteria to delineate wetlands, and describes some of the logic used by federal courts to uphold the limited constitutional use of the 1989 Wetlands Manual.
DescriptionThe recent sequencing of the complete genomes of several streptomycete species revealed the presence of a large number of cryptic' secondary metabolic gene clusters, and led to the realisation that these organisms have the ability to produce many more natural products than had previously been recognised. One of the aims of our work is to identify the physiological signals and regulatory mechanisms responsible for the activation of these 'cryptic' pathways, thus unleashing the full biosynthetic p [continued...
Due to the large number of chemicals in commerce without adequate toxicity characterization data, coupled with an ineffective federal policy for chemical management in the United States, many states are grappling with the challenge to identify toxic chemicals that may pose a risk to human health and the environment. Specific populations (e.g., children, elderly) are particularly sensitive to these toxic chemicals. In 2008, the Children's Safe Product Act (CSPA) was passed in Washington State. The CSPA included specific requirements to identify High Priority Chemicals (HPCs) and Chemicals of High Concern to Children (CHCCs). To implement this legislation, a methodology was developed to identify HPCs from authoritative scientific and regulatory sources on the basis of toxicity criteria. Another set of chemicals of concern was then identified from authoritative sources, based on their ...
Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in either expression or ...
Objectives1. To establish the present capacity and capability across all the sectors within the UK for - a) Undertaking research in the areas of toxicology and ecotoxicology and environmental hazard and risk assessment work on chemical subtances including emerging containments (e.g. enginerred nanomaterials); and b) Applying these skills in the policy and regulatory context. 2) The range of chemicals involved should include pharmaceutical and medical products, crop protection agents, biocides, vet [continued...]DescriptionThe aim of this project is to identify the current status of the scientific community, areas of expertise, and identify the gaps in skills, knowledge or recruitment. The project will use a questionnaire approach to obtain this information for all sectors of the business community. The analysis will identify the gaps in provision, and areas where investment is needed in future training ...
The analysis is submitted in support of the effluent limitations guidelines and standards for the Coastal Oil and Gas Industry. The report analyzes the cost-effectiveness of 10 regulatory options organized by three wastestreams. The document compares the total annualized cost incurred for each of the regulatory options within each wastestream to the corresponding effectiveness of that option in reducing the discharge of pollutants. Section Two discusses the cost-effectiveness methodology used and identifies the pollutants included in the analysis, presenting their toxic weighting factors and removal efficiencies. Section Three presents the results of the analysis. In Section Four, the cost-effectiveness values are compared to cost-effectiveness values for other promulgated rules. Appendix A presents data on pollutants, pollutant removals, annualized costs, and other, more detailed information.
The authors have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken {beta}-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in primary erythrocytes. Binding sites for the erythroid-specific factor (Eryf1) are found within regulatory regions for all chicken globin genes. A strong Eryf1 binding site is also present within the enhancer of at least one human globin gene, and proteins from human erythroid cells (but not HeLa cells) bind to both the chicken and the human sites.
The levels of General Transcription Factor (TF) IIA were examined during mammalian brain development and in rat embryo fibroblasts and transformed cell lines. The large TFIIA subunit paralogues ab and t are largely produced in unsynchronized cell lines, yet only TFIIA ab is observed in a number of differentiated tissue extracts. Steady-state protein levels of the TFIIA t, ab, and g subunits were significantly reduced when human embryonal (ec) and hepatic carcinoma cell lines were stimulated to differentiate with either all-trans-retinoic acid (ATRA) or sodium butyrate. ATRA-treated NT2-ec cells required replating to induce a neuronal phenotype and loss of detectable TFIIA t and g proteins. High levels of TFIIA t, ab, and g and Sp factors were identified in extracts from human fetal and rat...
The role of law in a federal regulatory agency is examined from an organizational perspective. While law is usually viewed in terms of its legal, political, and social value consequences, it is postulated that it also has significant organizational consequences. The impact of those consequences is examined in the case of a single agency, the US Nuclear Regulatory Commission. The legal process is shown to be a powerful organizational characteristic of the government administrative agency, beginning with statuatory definition of organization goals, structure, and procedures and ending with judicial review of actions. Agency lawyers are shown to represent a distinct professional subculture within this agency. Their values and orientations toward business, the role of regulation, and the role of nuclear utilities are different from the 95% of agency employees subculture based on a physical science/engineering background. It is concluded that agency ...
The Interstate Oil and Gas Compact Commission (IOGCC) engaged in numerous projects outlined under the scope of work discussed in the United States Department of Energy (DOE) grant number DE-FG26-01BC15336 awarded to the IOGCC. Numerous projects were completed that were extremely valuable to state oil and gas agencies as a result of work performed utilizing resources provided by the grant. There are numerous areas in which state agencies still need assistance. This additional assistance will need to be addressed under another grant because funding resources have been exhausted under The scope of work objectives for the eight projects covered under this grant is as follows: (1) Improve uniformity within state oil and gas data management efforts. (2) Conduct environmental compliance workshops and related educational projects on natural gas and oil exploration and production. (3) Improve regulatory efficiency through partnering opportunities provided by the Appalachian ...
The Nuclear Regulatory Commission (NRC) is conducting an enhanced participatory rulemaking to establish radiological criteria for site cleanup and decommissioning of NRC-licensed facilities. Open public meetings were held during 1993 in Chicago, IL, San Francisco, CA, Boston, MA, Dallas, TX, Philadelphia, PA, Atlanta, GA, and Washington, DC. Interested parties were invited to provide input on the rulemaking issues before the NRC staff develops a draft proposed rule. This report summarizes 3,635 comments categorized from transcripts of the seven workshops and 1,677 comments from 100 NRC docketed letters from individuals and organizations. No analysis or response to the comments is included. The comments reflect a broad spectrum of viewpoints on the issues related to radiological criteria for site cleanup and decommissioning. The NRC also held public meetings on the scope of the Generic Environmental Impact Statement (GEIS) during July 1993. The ...
Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT activation. Our findings ...
Abstract Sam68 (Src-associated protein in mitosis 68-kDa) is a multifunctional protein, known to govern cellular signal transduction, transcription, RNA metabolism, proliferation, apoptosis, and HIV-1 replication. Although intrinsic mechanisms that modulate Sam68 function are beginning to emerge, the regulatory events contributing to its expression remain elusive. We previously reported that heat shock protein-22 (Hsp22) antagonizes Sam68 function in rev-response element (RRE)-mediated gene expression. We now demonstrate that Sam68 levels correlate inversely with Hsp22 in a variety of cells, including U87, Jurkat, 293T, and U-937. In U87 glioblastoma cells, which contained high levels of Hsp22 than other cell lines tested, Hsp22 knockdown dramatically increased both Sam68 mRNA and protein,...
Full text: Korea Atomic Energy Research Institute (KAERI) has many R and D facilities in operation. including HANARO research reactor, radioactive waste treatment facility (RWTF), post-irradiation examination facility (PIEF) and irradiated material test facility (IMEF). Recently. nation-wide interest is focused on the safety and security of major industrial facilities. Safe operation of nuclear facilities is imperative because of the consequence of public disaster by radiological release/contamination, in case of an accident. Recently, Ministry of Science and Technology (MOST) of the Korean government announced amendments of Atomic Energy laws to enforce requirements of the physical protection and radiological emergency. All provisions on nuclear safety regulation and radiation protection are entrusted to the Atomic Energy Act(AEA). The Act is enacted as the main law concerning the safety regulation of nuclear installations, and is supplemented by the Enforcement Decree and Enforcement ...
This report presents the results of a systems failure analysis study of the CANDU 3 reactor design; the study was performed for the US Nuclear Regulatory Commission. As part of the study a review of the CANDU 3 design documentation was performed, a plant assessment methodology was developed, representative plant initiating events were identified for detailed analysis, and a plant assessment was performed. The results of the plant assessment included classification of the CANDU 3 event sequences that were analyzed, determination of CANDU 3 systems that are ''significant to safety,'' and identification of key operator actions for the analyzed events.
A case study of a small-scale hydroelectric plant to identify implementation problems is presented. The Montello hydroelectric plant is described including the background and history of the plant, the physical characteristics, the financial history and costs, operation, regulatory agencies, and the problems encountered in its operation. The analyses of the energy and capacity (demand) credits for the Montello hydroelectric plant when it is added to the Wisconsin Power and Light Company generating system is described. The WP and L base case and the results of the analyses are discussed. (WHK)
This safety design guide for pipe rupture protection identifies high-energy systems in which pipe ruptures must be postulated to occur, as well as systems that must be protected from the dynamic effects of such ruptures. Dynamic effects considered in this SDG consist of pipe whip (including missiles generated by pipe ruptures, if any) and jet impingement, Requirements for protection against the dynamic effects of a postulated pipe rupture and method of protection of essential structures, systems and components are specified for these effects. The change status for the regulatory requirements, code and standards should be traced and this safety design guide shall be updated accordingly. 2 tabs., 5 refs. (Author) .new.
The primary objective of this study was to identify, characterize, and map the wetlands in the Bear Creek watershed. A preliminary wetland categorization system based on the Cowardin classification system (Cowardin et al. 1979) with additional site-specific topographic, vegetation, and disturbance characteristic modifiers was developed to characterize the type of wetlands that exist in the Bear Creek watershed. An additional objective was to detect possible relationships among site soils, hydrology, and the occurrence of wetlands in the watershed through a comparison of existing data with the field survey. Research needs are discussed in the context of wetland functions and values and regulatory requirements for wetland impact assessment and compensatory mitigation.
The objective of project is to derive the policy recommendations to improve the efficiency of CANDU plants regulation. These policy recommendations will eventually contribute to the upgrading of Korean nuclear regulatory system and safety enhancement. During the second phase of this 2 years study, following research activities were done. Review the technical basis and framework of the new Canadian Regulation System and IAEA. Analysis on the interview of Wolsung operation staffs to identify important safety issues and regulation problems experienced at operation. Providing a plan of CANDU regulation system enhancement program.
DFNA5 was first identified as a gene causing autosomal dominant hearing loss (HL). Different mutations have been found, all exerting a highly specific gain-of-function effect, in which skipping of exon 8 causes the HL. Later reports revealed the involvement of the gene in different types of cancer. Epigenetic silencing of DFNA5 in a large percentage of gastric, colorectal and breast tumors and p53-dependent transcriptional activity have been reported, concluding that DFNA5 acts as a tumor suppressor gene in different frequent types of cancer. Despite these data, the molecular function of DFNA5 has not been investigated properly. Previous transfection studies with mutant DFNA5 in yeast and in mammalian cells showed a toxic effect of the mutant protein, which was not seen after transfection ...
AbstractBackground: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD). Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25). Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) with...
To gain insight into the changes in the transcriptome of soybean roots during soybean cyst nematode (SCN) infection, we conducted genome-wide gene expression profiling using serial analysis of gene expression (SAGE) combined with Solexa sequencing. More than 3 million tags were generated from the SCN-infected and uninfected roots, and 366941 and 314591 clean UniTags were obtained from SCN-infected and uninfected samples, respectively. In the SCN-infected sample, 48249 UniTags represented 18114 reference genes. In the uninfected control, 46290 UniTags represented 19323 reference genes. Comparison of tag frequencies identified 1405 genes that were expressed at greater levels in SCN-infected roots than in uninfected roots, and 1191 genes that were expressed at lower levels. Quantitative real-...
Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed...Full Text Available
Extensive gene expression during meiosis is a hallmark of spermatogenesis. Although it was generally accepted that RNA transcription ceases during meiosis, recent observations suggest that some transcription...Full Text Available
In response to stress, cells start transcriptional and transcription-independent programs that can lead to adaptation or death. Here, we show that multiple inducers of autophagy, including nutrient...Full Text Available
We explored transcriptional responses of the fission yeast Schizosaccharomyces pombe to various environmental stresses. DNA microarrays were used to characterize changes in expression...Full Text Available
Three transcription units are present in the adenovirus type 2 region EII. Transcription units EIIaE and EIIaL encode the mRNA for the 72,000-dalton DNA binding protein, early and late in the lytic...Full Text Available
The movement from traditional regulatory hearings to negotiated settlements represents both a departure from cost of service regulation and a relaxation of regulatory oversight. Under negotiation parties are able to renegotiate inclusions in their cost of service while simultaneously creating a profit margin for the regulated firm where none existed under the cost of service outcome of a traditional hearing. This paper constructs a model to illustrate the existence of positive gains to pipeline and shipper from the re-allocation of expenses through time in the regulated pipeline services market in Canada. Behaviour consistent with the model is observable in anecdotal and econometric evidence gathered from the library of the National Energy Board of Canada, responsible for pipeline toll regulation in Canada. Empirical investigation by into settlement procedures in the Florida electricity market reveals similar findings; however, this analysis ...
This is the first volume of a two-volume report. Volume 2 will be published at a later date. This report presents the results of a research project conducted by Brookhaven National Laboratory for the United States Nuclear Regulatory Commission, Office of Nuclear Regulatory Research. The purpose of the project was to develop a general methodology to be use in the assessment of the organizational factors which affect performance reliability (safety) in a nuclear power plant. The research described in this report includes the development of the Nuclear Organization and Management Analysis Concept (GNOMIC). This concept characterizes the organizational factors that impact safety performance in a nuclear power plant and identifies some methods for systematically measuring and analyzing the influence of these factors on safety performance. This report is divided into two parts; Part 1 presents an overview of the development of ...
Ageing of nuclear power plants means evolution of material or equipment properties on one side, and evolution of personnel skill and procedure adequacy on the other side, both of which, after a certain time, may not be compatible with the required safety provisions, or with an economic operation of the plant. Repair or replacement of components, as well as change in service conditions for a better compatibility with component reduced capabilities can be used to mitigate ageing effects. The paper summarises the results of a study conducted in this field with the support of the European Commission. It presents: the synthesis of the work done under international auspices, and in the European context; the comparison of ageing management approaches used in several European countries with international recommendations; the summary of the various potential phenomena and their governing parameters, the methods of in-service ageing identification and possible mitigation methods; illustrative ...
Purpose : To detect differentially expressed genes in the patients with uterine cervical cancer during the radiation therapy. Materials and Methods : In patients with biopsy proven uterine cervical cancer, we took a tumor tissue just before radiation therapy and at 40 minutes after external irradiation of 1.8 Gy. Total RNAs isolated from non-irradiated and irradiated tumor tissue samples were analyzed using the differential-display reverse transcription-polymerase chain reaction (DDRT-PCR). Complementary DNA (cDNA) fragments corresponding to differentially expressed messenger RNAs(mRNAs) were eluted, and cloned. The differential expression of the corresponding mRNAs was confirmed by reverse northern blot. Differentially expressed cDNA bands were sequenced. Nucleotide sequence data were analyzed in the Gene Bank and EMBL databases via the BLAST network server to identify homologies to known genes or cDNA fragments. Expression pattern of ...
The purpose of this hearing was to bring to the public`s attention a better understanding of both the shortcomings as well as the benefits of the existing wetlands regulations programs, policies and regulations. In addition an attempt was made to highlight those areas where there have been problems with restrictive or confusing regulations, time delays, and costs involved. Ultimately, the purpose is to identify areas in the federal regulations, and if necessary in the federal wetlands related laws, that can be amended, so these work better.
WIPS (Whip and Impact of Piping Systems) is a special purpose computer code for the structural analysis of pipe whip dynamic effects following a postulated pipe rupture. WIPS has been developed primarily to provide support for the pipe whip analysis procedures described in Section 3.6.2 of the US Nuclear Regulatory Commission Standard Review Plan. This report summarizes the purpose and scope of the WIPS development effort, identifying those clauses in the Standard Review Plan which refer to pipe whip analysis, and indicating how the WIPS code can be used to provide supporting data. Detailed information on use of the code is contained in accompanying reports which cover: (1) user instructions; (2) theory; (3) programming procedures; and (4) verification examples.
Nano- and microstructured surfaces are known to impact on the binding and differentiation of cells, but the detailed basic understanding of the underlying regulatory mechanisms is still scarce, which impedes the rational design of smart biomaterials. Towards a comprehensive analysis of the interplay between topographical parameters such as feature design and lateral and vertical dimensions we here report on a combinatorial screening approach, BioSurface Structure Array (BSSA) of test squares each with a distinct topography. Using such BSSA libraries of 504 topographically distinct surface structures, we have identified combinations of size, gap and height of structures which enhance mineralization as well as the expression of osteogenic markers of a preosteoblastic murine cell line. This g...
This sampling and analysis plan (SAP) identifies characterization objectives pertaining to sample collection, laboratory analytical evaluation, and reporting requirements for vapor samples obtained during the operation of mixer pumps in tank 241-AZ-101. The primary purpose of the mixer pump test (MPT) is to demonstrate that the two 300 horsepower mixer pumps installed in tank 241-AZ-101 can mobilize the settled sludge so that it can be retrieved for treatment and vitrification. Sampling will be performed in accordance with Tank 241-AZ-101 Mixer Pump Test Data Quality Objective (Banning 1999) and Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis (Mulkey 1999). The sampling will verify if current air emission estimates used in the permit application are correct and provide information for future air permit applications.
Most analyses of the alternative strategies used by utilities to comply with Title IV requirements have focused on factors directly related to controlling sulfur dioxide (SO{sub 2}) emissions. However, utilities must meet a number of additional environmental requirements at the same tune they comply with the acid rain program. To illuminate the potential synergies and conflicts that might exist between the other regulatory mandates and the acid rain program, a thorough examination of all the various programs and their interrelationships must be conducted. This paper reviews the environmental mandates that utilities will have to plan to meet in the next decade concurrently with the acid rain program, and it analyzes the interactions among the various programs to identify potential synergies and conflicts.
Korea Atomic Energy Research Institute (KAERI) has many R and D facilities in operation, including HANARO research reactor, radioactive waste treatment facility (RWTF), post-irradiation examination facility (PIEF) and irradiated material test facility (IMEF). Recently, nation-wide interest is focused on the safety and security of major industrial facilities. Safe operation of nuclear facilities is imperative because of the consequence of public disaster by radiological release/ contamination, in case of an accident. Recently, Ministry of Science and Technology (MOST) of the Korean government announced amendments of Atomic Energy laws to enforce requirements of the physical protection and radiological emergency. In this paper, the context of amended Atomic Energy laws were reviewed to confirm quality assurance measures and identify additional QA activities, if any, that is required by the amendment
The cost-effectiveness (CE) analysis presents an evaluation of the technical efficiency of pollutant control options for the proposed effluent limitations guidelines. The proposed BAT and PSES apply to six subcategories: Dissolving Kraft; Dissolving Sulfite; Bleached Papergrade Kraft; Papergrade Sulfite; Unbleached Kraft; and Semichemical. The document compares the total annualized cost incurred for each of the regulatory options within each subcategory to the corresponding effectiveness of that option in reducing the discharge of pollutants. Section Two discusses the cost-effectiveness methodology and identifies the pollutants included in the analysis and their toxic weighting factors. Section Three describes the options evaluated for each subcategory. Section Four presents the results of the CE analysis. Section Five presents a separate analysis of AOX (adsorbable organic halides).
The SCDAP computer code, which is being developed under the sponsorship of the United States Nuclear Regulatory Commission, models the progression of light water reactor core damage including core heatup, core disruption and debris formation, debris heatup, and debris melting. SCDAP is being used to help identify and understand the phenomena that control core behavior during a severe accident, to help quantify uncertainties in risk assessment analysis, and to support planning and interpretation of severe fuel damage experiments and data. Comparisons between SCDAP calculations and the experimental data showed good agreement. Calculated and measured bundle temperatures for SFD-ST were within 200 K for the entire bundle and within 20 K for maximum cladding temperatures. For ESSI-2, calculated and measured maximum cladding temperatures were within 50 K, and the extensive liquefaction and relocation that was calculated was in agreement with ...
The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. Whereas most of the members of this family have been extensively characterized, the therapeutic potential and pharmacology of SF-1 still remains elusive. Described here is the identification and characterization of selective inhibitory chemical probes of SF-1 by a rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908 compounds from the National Institute of Health's Molecular Libraries Small Molecule Repository was screened in a transactivation cell-based assay employing a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified as potent submicromolar ...
Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various target genes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction in TRAP220(MED1) recruitment during the T(3)-repressive phase. We also uncover direct ...
The Atomic Energy commission of Syria (AECS) is nominated by Syrian legislation as the regulatory authority in respect of radiation protection and safety and security of radioactive sources. In addition AECS is providing a wide range of Technical Services (TS) through its various departments. In this paper, the cooperation and coordination between the regulatory authority and the providers of technical services in Syria are described. The adjustment of the regulatory programme as to make maximal use of the available technical resources is presented. It was shown that this relationship does not jeopardize the effective independency of the regulatory authority which is maintained by keeping the regulatory decisions based on pure regulatory considerations. (author)
Mutations in the mouse formin (Fmn) gene, formerly known as the limb deformity (ld) gene, give rise to recessively inherited limb deformities and renal malformations or aplasia. The Fmn gene encodes many differentially processed transcripts that are expressed in both adult and embryonic tissues. To study the genomic organization of the Fmn locus, we have used Fmn probes to isolate and characterize genomic clones spanning 500 kb. Our analysis of these clones shows that the Fmn gene is composed of at least 24 exons and spans 400 kb. We have identified two novel exons that are expressed in the developing embryonic limb bud as well as adult tissues such as brain and kidney. We have also used a microsatellite polymorphism from within the Fmn gene to map it genetically to a 2.2-cM interval between D2Mit58 and D2Mit103. 36 refs., 6 figs., 1 tab.
A new method is being developed to quickly screen for the human exposure potential to polycyclic aromatic hydrocarbons (PAHs) and organochlorines (OCs). The development involves two key elements: identifying suitable signals that represent intracellular changes that are specific to PAH and OC exposure, and constructing a device to guide the biological cell growth so that signals from individual cells are consistent and reproducible. We are completing the identification of suitable signals by using synchrotron radiation-based (SR) Fourier-transform infrared (FTIR) spectromicroscopy in the mid-infrared region (4000-400 cm-1). Distinct changes have been observed in the IR spectra after treatment of human cells in culture medium with PAHs and OCs. The potential use of this method for detecting exposure to PAHs and OCs has been tested and compared to a reverse transcription polymerase chain reaction (RT-PCR) assay that quantifies increased ...
The recently described retinoid X receptors (RXRs) respond to the novel retinoid 9-cis-retinoic acid and also serve as heterodimeric partners for the vitamin D, thyroid hormone, and retinoic acid receptors (VDR, TR, and RAR, respectively). In this work, the authors report high-resolution localization of the human RXR genes within cytogenetic bands and also within a standard reference map of cosmid DNA markers on human chromosomes. They have determined the location of the human RXR genes by pairwise hybridization of the RXR cosmids and reference markers, using fluorescence in situ hybridization. They localized (i) RXR[alpha] (RXRA) to chromosome 9 band q34.3; (ii) RXR[beta] (RXRB) to chromosome 6 band 21.3; and (iii) RXR[gamma] (RXRG) to chromosome 1 band q22-q23. Six retinoid-responsive transcription factors have been identified so far, including three retinoic acid receptors in addition to the three RXRs. Interestingly, each of these receptors ...
Abstract in english The tegument surface of the adult schistosome, bounded by a normal plasma membrane overlain by a secreted membranocalyx, holds the key to understanding how schistosomes evade host immune responses. Recent advances in mass spectrometry (MS), and the sequencing of the Schistosoma mansoni transcriptome/genome, have facilitated schistosome proteomics. We detached the tegument from the worm body and enriched its surface membranes by differential extraction, before subjecting t (more) he preparation to liquid chromatography-based proteomics to identify its constituents. The most exposed proteins on live worms were labelled with impearmeant biotinylation reagents, and we also developed methods to isolate the membranocalyx for analysis. We identified transporters for sugars, amino acids, inorganic ions and water, which confirm the importance of the tegument plasma membrane in nutrient acquisition and solute balance. Enzymes, ...
The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. The authors have identified two additional genes, GRO#beta# and GRO#gamma#, that share 90% and 86% identity at the deduced amino acid level with the original GRO#alpha# isolate. One amino acid substitution of proline in GRO#alpha# by leucine in GRO#beta# and GRO#gamma# leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived ...
Many Pacific Basin countries rely on oil for electricity production. Alternative fuel sources such as coal, which is available in the Pacific Basin, can help mitigate adverse impacts of sudden price increases or supply disruptions. Coal combustion produces solid and potentially hazardous wastes of concern to environmental regulators and utility managers. This paper identifies issues associated with managing coal combustion wastes in the Pacific Basin, using the state of Hawaii as a case study. Hawaii is typical of many Pacific Basin locations in that it depends on oil, has limited sites, for waste management operations, and is subject to domestic and international waste management regulations. The paper discusses coal-fired utility wastes, environmental impacts of coal combustion waste disposal, and regulatory requirements that impact coal waste management. From this baseline, potential on- and off-island options for coal waste management are ...
The Creating Wetlands in the Oil Sands Reclamation workshop was held to solicit expert views from leading authorities in a number of disciplines related to the creation and study of wetlands, as well as to investigate challenges in the creation of wetlands in reclaimed oil sands landscapes. This document provided a detailed transcript of each presentation and all discussions that followed. The workshop was divided into 5 sessions: (1) wetlands background information; (2) groundwater conditions and boreal wetlands; (3) creating wetland types; (4) wildlife in boreal wetlands and traditional environmental knowledge; and (5) treatment wetlands. An expert panel overview provided presentations on post-mining restoration of boreal landscapes in oil sands regions; the creation of fens, marshes and shallow water wetlands at oil sands sites and the restoration of damaged peatlands. A outline of the physical scale of the oil sands mining disturbances was provided during the ...
BackgroundBiodiesel or ethanol derived from lipids or starch produced by microalgae may overcome many of the sustainability challenges previously ascribed to petroleum-based fuels and first generation plant-based biofuels. The paucity of microalgae genome sequences, however, limits gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for the non-model microalgae species, Dunaliella tertiolecta, and identify pathways and genes of importance related to biofuel production.ResultsNext generation DNA pyrosequencing technology applied to D. tertiolecta transcripts produced 1,363,336 high quality reads with an average length of 400 bases. Following quality and size trimming, ~ 45% of the high quality reads were assembled into 33,307 isotigs with a 31-fold coverage and 376,482 singletons. Assembled sequences and singletons were subjected to BLAST similarity searches and annotated with ...
In neurodegenerative conditions such as Alzheimer's and prion disease it has been shown that host genetic background can have a significant effect on susceptibility. Indeed, human genome-wide association studies (GWAS) have implicated several candidate genes. Understanding such genetic susceptibility is relevant to risks of developing variant CJD (vCJD) in populations exposed to bovine spongiform encephalopathy (BSE) and understanding mechanisms of neurodegeneration. In mice, aspects of prion disease susceptibility can be modelled by examining the incubation period following experimental inoculation. Quantitative trait linkage studies have already identified multiple candidate genes; however, it is also possible to take an individual candidate gene approach. Rarb and Stmn2 were selected as candidates based on the known association with vCJD. Because of the increasing overlap described between prion and Alzheimer's diseases we also chose Clu, Picalm and Cr1, which ...
Global acetylation of histone H4 is a mark of gene transcriptional activation. The c-Myc transcription factor binds to specific DNA sites in cellular chromatin and induces the acetylation of...Full Text Available
BackgroundIsoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response...Full Text Available
A detailed map of the transcriptional organization of the CELO virus genome was produced. Recent computer analysis of CELO virus has indicated the presence of 38 putative open reading frames (ORFs)....Full Text Available
A regional analysis of nucleotide substitution rates along human genes and their flanking regions allows us to quantify the effect of mutational mechanisms associated with transcription in germ line...Full Text Available
Mutations in SOX9, a gene essential for chondrocyte differentiation cause the human disease campomelic dysplasia (CD). To understand how SOX9 activates transcription, we characterized...Full Text Available
A continuous stream of activating and repressing signals is processed by the transcription complex paused at the promoter of the c-myc proto-oncogene. The general transcription factor...Full Text Available
SUMMARYReplication timing is frequently discussed superficially in terms of its relationship to transcriptional activity via chromatin structure. However, so little is known about...Full Text Available
A structurally conserved element, the trigger loop, has been suggested to play a key role in substrate selection and catalysis of RNA polymerase II (pol II) transcription elongation. Recently resolved...Full Text Available
We recently found that many RNA polymerase II transcription factors are modified with N-acetylglucosamine residues. These sugar moieties confer upon transcription factors an ability to bind the lectin wheat germ agglutinin. We have taken advantage of this interaction to devise a purification procedure for the "GC-box" binding transcription factor Sp1. Crude nuclear extracts are first subjected to wheat germ agglutinin affinity chromatography and then subjected to sequence-specific DNA affinity chromatography. The Sp1 protein purified by this procedure is at least 95% pure, and the overall recovery is greater than 80%. In addition to yielding larger quantities of Sp1 than conventional schemes, the new purification procedure is also simpler and more rapid. We show that wheat germ agglutinin affinity chromatography can also be used to purify the glycosylated forms of the CCAAT-binding transcription factor. ...
The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated...Full Text Available
BackgroundModeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in...Full Text Available
We describe an Ebolavirus minigenome-based system that is suitable for high-throughput screening of compounds able to impair Ebolavirus virus replication and/or transcription....Full Text Available
SummaryThe general transcription factor TFIID is a large multi-subunit complex required for the transcription of most protein-encoding genes by RNA polymerase II. Taking advantage...Full Text Available
Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) allows researchers to determine the genome-wide binding locations of individual transcription factors (TFs) at high resolution....Full Text Available
Auxin modulates diverse plant developmental pathways through direct transcriptional regulation and cooperative signaling with other plant hormones. Genetic and biochemical approaches have clarified...Full Text Available
BackgroundPolyadenylation of RNA has a decisive influence on RNA stability. Depending on the organisms or subcellular compartment, it either enhances transcript stability or targets...Full Text Available
BackgroundThe mammalian FoxO transcription factors function to regulate diverse physiological processes. Emerging evidence that both BDNF and lithium suppress FoxO...Full Text Available
The ternary complex factor (TCF) Elk-1 is a transcription factor that regulates immediate early gene (IEG) expression via the serum response element (SRE) DNA consensus site. Elk-1 is associated with...Full Text Available
The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB...Full Text Available
In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing...Full Text Available
Generation of replicative defective viruses is frequently observed during viral infections. We now report that encapsidation and reverse transcription of spliced viral RNA is an additional mechanism...Full Text Available
Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted...Full Text Available
As many as 59% of the transcription factors in Escherichia coli regulate the transcription rate of their own genes. This suggests that auto-regulation has one or more important...Full Text Available
The regulation of gene expression in the brain reward regions is known to contribute to the pathogenesis and persistence of drug addiction. Increasing evidence suggests that the regulation of gene transcription...Full Text Available
We have previously shown that a T to G transversion at the second T of the conalbumin "TATA" box drastically decreases specific initiation of transcription by RNA polymerase B (1). We now report that...Full Text Available
In the yeast Saccharomyces cerevisiae, a and α mating-type information is stored in transcriptionally silenced cassettes called HML and HMR....Full Text Available
BackgroundInferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance...Full Text Available
As the new entrants in the global nuclear construction market are increasing and the establishment of an effective and sustainable regulatory infrastructure becomes more important, they have requested international assistance from the international nuclear communities with mature nuclear regulatory programmes. It needs to optimize the use of limited resources from regulatory organization providing support to regulatory infrastructure of new comers. This paper suggests the resource portfolio concept like a GE/Mckinsey Matrix used in business management and tries to apply it to the current needs considered in the regulatory support program in Korea as the case study
Regulatory T cells are proposed to play a central role in the maintenance of immunological tolerance in the periphery, and studies in many animal models demonstrate their capacity to inhibit inflammatory...Full Text Available
Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant...Full Text Available
Cockayne syndrome (CS) is a rare autosomal recessive disease, which shows diverse clinical symptoms such as photosensitivity, severe mental retardation and developmental defects. CS cells are hypersensitive to killing by ultraviolet (UV)-irradiation and defective in transcription-coupled repair. Two genetic complementation groups in CS (CS-A and CS-B) have been identified. We analyzed mutations of the CSA gene in 5 CS-A patients and identified 3 types of mutations. Four unrelated CS-A patients (CS2OS, CS2AW, Nps2 and CS2SE) had a deletion including exon 4, suggesting that there is a founder effect on the CSA mutation in Japanese CS-A patients. Patient CS2SE was a compound heterozygote for this deletion and an amino acid substitution at the 106th glutamine to proline (Q106P) in the WD-40 repeat motif of the CSA protein, which resulted in a defective nucleotide excision repair. Patient Mps1 had a large deletion in the ...
The three mammalian transforming growth factor (TGF)-? isoforms (TGF-?1, TGF-?2, and TGF-?3) differ in their putative roles in radiation-induced fibrosis in intestine and other organs. Furthermore, tissue specificity of TGF-? action may result from temporal or spatial changes in production and/or activation. The present study examined shifts in the cell types expressing TGF-? mRNA relative to TGF-? immunoreactivity and histopathological injury during radiation enteropathy development. A 4-cm loop of rat small intestine was locally exposed to 0, 12, or 21-Gy single doses of x-irradiation. Sham-irradiated and irradiated intestine were procured 2 and 26 weeks after irradiation. Cells expressing the TGF-?1, TGF-?2, or TGF-?3 transcripts were identified by in situ hybridization with digoxigenin-labeled riboprobes. Intestinal wall TGF-? immunoreactivity was measured using computerized image analysis, and structural radiation injury was assessed by ...
Rice is a very important food staple that feeds more than half the world's population. Two major Asian cultivated rice (Oryza sativa L.) subspecies, japonica and indica, show significant phenotypic variation in their stress responses. However, the molecular mechanisms underlying this phenotypic variation are still largely unknown. A common link among different stresses is that they produce an oxidative burst and result in an increase of reactive oxygen species (ROS). In this study, methyl viologen (MV) as a ROS agent was applied to investigate the rice oxidative stress response. We observed that 93-11 (indica) seedlings exhibited leaf senescence with severe lesions under MV treatment compared to Nipponbare (japonica). Whole-genome microarray experiments were conducted, and 1,062 probe sets were identified with gene expression level polymorphisms between the two rice cultivars in addition to differential expression under MV treatment, which were assigned as Core ...
This report describes the basis, results, and related risk implications of an analysis performed by an ad hoc working group of the U.S. Nuclear Regulatory Commission (NRC) to assess the containment bypass potential attributable to steam generator tube rupture (SGTR) induced by severe accident conditions. The SGTR Severe Accident Working Group, comprised of staff members from the NRC`s Offices of Nuclear Reactor Regulation (NRR) and Nuclear Regulatory Research (RES), undertook the analysis beginning in December 1995 to support a proposed steam generator integrity rule. The work drew upon previous risk and thermal-hydraulic analyses of core damage sequences, with a focus on the Surry plant as a representative example. This analysis yielded new results, however, derived by predicting thermal-hydraulic conditions of selected severe accident scenarios using the SCDAP/RELAP5 computer code, flawed tube failure modeling, and tube failure probability ...
Over the past few years, the development of domestic oil shale resources has regained significant attention. High oil prices, emerging recovery technologies, increasing world demand for liquid hydrocarbons, and the continued decline in United States conventional oil production has contributed to this interest. Several initiatives have been undertaken by the United States federal government and the private sector to encourage the development of a domestic oil shale industry. The United States has nearly 2.0 trillion barrels of oil shale resources across the eastern and western states. However, the development of this massive resource is constrained by a number of key factors, such as resource access, technology, economics, infrastructure and environmental and regulatory issues. In order to review emerging oil shale technologies from 23 companies and identify options to accelerate the development of this resource, a comprehensive analysis has ...
An internal flooding (IF) risk assessment refers to the quantitative probabilistic safety assessment (PSA) treatment of flooding as a result of pipe and tank breaks inside the plants, as well as from other recognized flood sources. The industry consensus standard for Internal Events Probabilistic Risk Assessment (ASME-RA-Sb-2005) includes high-level and supporting technical requirements for developing internal flooding probabilistic risk assessment (IFPRA). This industry standard is endorsed in Regulatory Guide 1.200, Revision 1 as an acceptable approach for addressing the risk contribution from IF events for risk informed applications that require U.S. Nuclear Regulatory commission (NRC) approval. In 2006, EPRI published a draft report for IFPRA that addresses the requirements of the ASME PRA consensus standard and have made efforts to refine and update the final EPRI IFPRA guideline. Westinghouse has performed an IFPRA analysis for several ...
Drosophila melanogaster has long been at the forefront of studies of transcriptional regulation in animals. Many fundamental ideas--such as cis control elements that act over long distances, the regulation of development by hierarchical cascades of transcription factors, dosage compensation, and position effect variegation--originated from studies of the fruit fly. The recent completion of the euchromatic DNA sequence of Drosophila is another breakthrough. The sequence data highlight important unanswered questions. For example, only one-fifth of the 124 Mb of Drosophila euchromatic DNA codes for protein. The function of the remaining 100 Mb of mostly unique DNA is largely unknown. Some proportion of this non-reading frame DNA must encode the functional recognition sites targeted by the approximately 700 sequence-specific DNA binding proteins that regulate transcription in Drosophila, but what proportion? Most or very ...
A variety of special regulations exist in Costa Rica for registration and transport of hazardous substances; these set the requirements for entry into the country and the security of transport units. However, the regulations mentioned no specific rules for storing hazardous substances. Tax deposits have been the initial place where are stored the substances that enter the country.The creation of basic rules that would be regulating the storage of hazardous substances has taken place through the analysis of regulations and national and international laws governing hazardous substances. The regulatory domain that currently exists will be established with a field research in fiscal deposits in the metropolitan area. The storage and security measures that have been used by the personnel handling the substances will be identified to be putting the reality with that the hazardous substances have been handled in tax deposits. A rule base for the ...
Traditionally, probabilistic risk analyses [PRA] of severe accidents in nuclear power plants have limited themselves to consideration of the set of initiating events occurring during full power operation. However, some analyses of accident initiators during low power, shutdown, and other modes of plant operation other than full power have been performed. These studies as well as the Chernobyl accident and recent operating experience at U.S. pressurized water reactors suggested that risks during low power and shutdown could be significant. As such, the analysis of the frequencies, consequences, and risks of these accidents was identified as one task in the Nuclear Regulatory Commission staff's study of the implications of the Chernobyl accident to U.S. commercial nuclear power plants. The surry PRA project is an ongoing high priority effort at BNL [Brookhaven National Laboratory] that is expected to continue for the next several years. As the ...
A ground-breaking study was recently completed as part of the Seabrook Level 2 PRA update. This study updates the post-core damage phenomena to be consistent with the most recent information and includes accident management activities that should be modeled in the Level 2 PRA. Overall, the result is a Level 2 PRA that fully meets the requirements of the ASME PRA Standard with respect to modeling accident management in the LERF assessment and NRC requirements in Regulatory Guide 1.174 for considering late containment failures. This technical paper deals only with the incorporation of operator actions into the Level 2 PRA based on a comprehensive study of the Seabrook Station accident response procedures and guidance. The paper describes the process used to identify the key operator actions that can influence the Level 2 PRA results and the development of success criteria for these key operator actions. This addresses a key requirement of the ...
A ground-breaking study was recently completed as part of the Seabrook Level 2 PRA update. This study updates the post-core damage phenomena to be consistent with the most recent information and includes accident management activities that should be modeled in the Level 2 PRA. Overall, the result is a Level 2 PRA that fully meets the requirements of the ASME PRA Standard with respect to modeling accident management in the LERF assessment and NRC requirements in Regulatory Guide 1.174 for considering late containment failures. This technical paper deals only with the incorporation of operator actions into the Level 2 PRA based on a comprehensive study of the Seabrook Station accident response procedures and guidance. The paper describes the process used to identify the key operator actions that can influence the Level 2 PRA results and the development of success criteria for these key operator actions. This addresses a key requirement of the ...
The 3001 Storage Canal is located under portions of Buildings 3001 and 3019 at Oak Ridge National Laboratory (ORNL) and has a capacity of approximately 62,000 gallons of water. The term canal has historically been used to identify this structure, however, the canal is an in-ground reinforced concrete structure satisfying the regulatory definition of a tank. From 1943 through 1963, the canal in Building 3001 was designed to be an integral part of the system for handling irradiated fuel from the Oak Ridge Graphite Reactor. Because one of the main initial purposes of the reactor was to produce plutonium for the chemical processing pilot plant in Building 3019, the canal was designed to be the connecting link between the reactor and the pilot plant. During the war years, natural uranium slugs were irradiated in the reactor and then pushed out of the graphite matrix into the system of diversion plates and chutes which directed the fuel into the deep ...
The US Department of Energy (DOE) Defense Waste Management Plan has the objective of final disposal for high-level waste (HLW) generated from defense programs. The DOE sites that generate HLW are located at the Savannah River Operations Office in Aiken, South Carolina, the Hanford site in Richland, Washington, and the Idaho Operations Office in Idaho Falls, Idaho. The purpose in the development of a quality assurance (QA) specification for organizations involved in HLW production is to establish uniform requirements that ensure that radioactive waste is converted to a waste form and canistered in such a way that it is acceptable in a federal repository licensed by the US Nuclear Regulatory Commission (NRC). A QA specification has been developed that will be applied to those activities important to certification of the product. The basic requirements are defined in national consensus standards and DOE directives. The supplemental requirements ...
There are many sources of population exposures to power-frequency (50/60 Hz) electric and magnetic fields including household appliances and wiring, neighborhood distribution circuits, and high-voltage transmission lines. Bioeffects studies were unable to demonstrate that exposures to power-frequency fields can affect public health. Researcher have likewise been unable to show that the health effects of such exposures are negligible. State and federal regulatory agencies are, therefore, grappling with questions of whether and how to regulate the sitting or design of new extra high-voltage transmission lines so as to control the ground-level fields to which people are exposed. The purpose of this dissertation is to illuminate some of the exposure-related aspects of these question. A taxonomy of the relationship between field encounter and effect is developed to clarify the meaning of terms such as exposure and dose in the power-frequency context. The major inputs to ...
Over the past few years, NPCIL has performed comprehensive Level-1 Probabilistic Safety Assessment (PSA) for a 220 MWe Pressurised Heavy Water Reactor (PHWR) at Kakrapar Atomic Power Station (KAPS) and for the first 540 MWe PHWR at Tarapur Atomic Power Project (TAPP- 3 and 4). The major objective of these PSAs was to present an integrated picture of the safety of the plant to identify and understand key plant vulnerabilities. As a result of the availability of these PSAs, there is a desire to use them to operate the plants in the most efficient manner practicable. In recent years, the operation of Indian Nuclear Power Plants has been characterized by improved availability/capacity factors and reduced forced outages. Frequency of planned outages is also being reduced. In order to achieve this, the PSAs are now being used as an engineering tool for optimization of Technical Specifications with regard to Allowed Outage Time (AOT) and Surveillance Test Intervals ...
One of the issues identified in the US Nuclear Regulatory Commission`s Nuclear Plant Aging Research program plan is the need to understand the state of ``mothballed`` or other out-of-service equipment to ensure subsequent safe operation. Programs for proper storage and preservation of materials and components are required by NRC regulations (10 CFR 50, Appendix B). However, materials and components have been seriously degraded due to improper storage, protection, or layup, at facilities under construction as well as those with operating licenses. Pacific Northwest Laboratory has evaluated management of aging for unstarted or mothballed nuclear power plants. The investigations revealed that no uniform guidance in the industry addresses reactor layup. In each case investigated, layup was not initiated in a timely manner, primarily because of schedule uncertainty. Hence, it is reasonable to assume that this delay resulted in accelerated aging of ...
Managing public lands for maximum social benefit is becoming an increasingly complex task. The growing need for domestically produced mineral raw materials and energy, and the conflicting interests over the use of public lands, have added new dimensions to the management issues. This report covers the first phase of a long-term program initiated by the Division of State Lands to improve their capability to evaluate the tar-sand and oil-shale resources in Utah. The scope of this phase of the study was limited to examination and analysis of existing information and to development models for data processing and resource evaluation. The study was effective in identifying problem areas and demonstrating the potential value of the proposed systems for management of state lands. It is anticipated that effective evaluation of the oil-shale and tar-sand resources in Utah, supported by readily accessible physical data, will lead to improved management both in policy and in ...
This project aims at developing risk-informed application technologies to enhance the safety and economy of nuclear power plant altogether. For this, the Integrated Level 1 and 2 PSA model is developed. In addition, the fire and internal flooding PSA models are improved according to the PSA standard of U.S.A. To solve the issues of domestic PSA model, the best-estimate thermal hydraulic analyses are preformed for the ATWS and LSSB. In order to reduce the uncertainty of PSA, several new PSA technologies are developed: (1) more exact quantification of large fault tree, (2) importance measure including the effects of external PSA. As feasibility studies of Option 2 and 3, the class of 6 systems' SSC are re-classified based on the risk information and the sensitivity analyses is performed for the EDG starting time, respectively. It is also improved that the methodology to identify the vital area of NPP. The research results of this project can be used in the ...
This study effort was required as a preliminary step prior to initiation of field measurements of atmospheric dispersion in coastal regions. The Nuclear Regulatory Commission (NRC) is in the process of planning an extensive field measurement program to generate data which will serve as improved data bases for licensing decisions, confirmation of regulations, standards, and guides, and for site characterizations. The study being reported here is an effort directed to obtaining as much information as is possible from existing studies that is relevant toward NRC's objectives. For this study, reports covering research and meteorological measurements conducted for industrial purposes, utility needs, military objectives, and academic studies were obtained and critically reviewed in light of NRC's current data needs. This report provides an interpretation of the extent of existing usable information, an indication of the potential for tailoring existing ...
As part of the Nondestructive Evaluation Reliability Program sponsored by the US Nuclear Regulatory Commission, the Pacific Northwest Laboratory is developing a method that uses risk-based approaches to establish in-service inspection plans for nuclear power plant components. This method uses probabilistic risk assessment (PRA) results and Failure Modes and Effects Analysis (FEMA) techniques to identify and prioritize the most risk-important systems and components for inspection. The Surry Nuclear Power Station Unit 1 was selected for pilot applications of this method. The specific systems addressed in this report are the reactor pressure vessel, the reactor coolant, the low-pressure injection, and the auxiliary feedwater. The results provide a risk-based ranking of components within these systems and relate the target risk to target failure probability values for individual components. These results will be used to guide the development of ...
The purpose of this assessment is to develop a versatile process that will provide a mechanism for evaluating both present and future risks to this environment. Much of the regulatory and environmental interest in the port has centered around a Ballast Water Treatment facility that treats and discharges up to 30 mgd of oily ballast water brought in by crude oil tankers. However, six point discharges and other potential sources of pollution exist in the area. The authors have delineated eleven subareas in the port in order to identify the potential anthropogenic stressors, as well as the receptors that could be exposed to these stressors. Potential effects were then characterized for each exposure. Each component is ranked and integrated, resulting in a relative risk estimate in each subarea. Both the discernible risks, based on available data, and the data gaps are presented. Uncertainty is expressed as a range of high and low risk associated ...
The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across tree parts and seven annexes the activities developed by the organism during 2007. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the occupational surveillance; the environmental monitoring; improved organizational. Also, this publication have annexes with the following content: regulatory documents; inspections to medical, industrial and training installations; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.
We report the identification and characterization of a new Drosophila clock-regulated gene, takeout (to). to is a member of a novel...Full Text Available
The biophysical properties of membrane phospholipids are controlled by the composition of their constituent fatty acids and are tightly regulated in Escherichia...Full Text Available
Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to significant cell-to-cell variations in mRNA and protein levels. This variation...Full Text Available
The glass gene is required for proper photo-receptor differentiation during development of the Drosophila eye glass codes for a DNA-binding protein containing five zinc fingers that we show is a transcriptional activator. A comparison of the sequences of the glass genes from two species of Drosophila and a detailed functional domain analysis of the Drosophila melanogaster glass gene reveal that both the DNA-binding domain and the transcriptional-activation domain are highly conserved between the two species. Analysis of the DNA-binding domain of glass indicates that the three carboxyl-terminal zinc fingers alone are necessary and sufficient for DNA binding. We also show that a deletion mutant of glass containing only the DNA-binding domain can behave in a dominant-negative manner both in vivo and in a cell culture assay that measures transcriptional activation. PMID:7604032
Phosphorylation is one of the most frequent modifications in intracellular signaling and is implicated in many processes ranging from transcriptional control to signal transduction in innate immunity....Full Text Available
Although the p53 tumor suppressor is relatively well characterized, much less is known about the functions of other members of the p53 family, p73 and p63. Here, we present evidence that in specific pathological conditions caused by exposure of normal cells to bile acids in acidic conditions, p73 protein plays the predominant role in the DNA damage response. These pathological conditions frequently occur during gastric reflux in the human esophagus and are associated with progression to esophageal adenocarcinoma. We found that despite strong DNA damage induced by bile acid exposure, only p73 (but not p53 and p63) is selectively activated in a c-Abl kinase-dependent manner. The activated p73 protein induces DNA damage repair. Using a human DNA repair PCR array, we identified multiple DNA repair genes affected by p73. Two glycosylases involved in base excision repair, SMUG1 and MUTYH, were characterized and found to be transcriptionally regulated ...
After the transcription of the electricity directive in national legislations, the European electricity market appears to be a vast set of juxtaposed markets which are weakly connected at the level of their wholesale contracts compartment. Referring to the technological peculiarities of electricity as a commodity, the paper identifies the direct conditions of regional integration of the electricity markets, those which would favour cross-border trade and allow to be near the normal functioning of a regional commodity market. The infrastructure network dependence and the need of a stringent technical coordination necessitate to unify the operation of the different systems and the rules of access, or at the least to come near this unification by strong coordination. A second major condition, which is not fully debated, is the increasing connexion of short-term markets, via daily physical trade and emergence of a European financial market, which ...
A nucleoside triphosphate binding site on calf thymus RNA polymerase II was identified by using photoaffinity analogues of adenosine 5'-triphosphate and guanosine 5'-triphosphate. Both radiolabeled 8-azidoadenosine 5'-triphosphate (8-N3ATP) and radiolabeled 8-azidoguanosine 5'-triphosphate (8-N3GTP) bound to a single polypeptide of this enzyme. This polypeptide has a molecular mass of 37 kilodaltons and an isoelectric point of 5.4. Ultraviolet (UV) irradiation was necessary for photolabeling to occur. In addition, no labeling occurred when the probe was prephotolyzed or when the enzyme was inactivated. Furthermore, photolabeling of the enzyme could be decreased by preincubation with natural substrates. To provide evidence that the radiolabeled polypeptide forms a part of the domain of the nucleoside triphosphate binding site, experiments were performed using unlabeled 8-N3ATP. Although this unlabeled analogue was not a substrate ...
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; ...
We previously reported the identification of a new family of plant methyltransferases (MTs), named the SABATH family, that use S-adenosyl-l-methionine (SAM) to methylate a carboxyl moiety or a nitrogen-containing functional group on a diverse array of plant compounds. The Arabidopsis genome alone contains 24 distinct SABATH genes. To identify the catalytic specificities of members of this protein family in Arabidopsis, we screened recombinantly expressed and purified enzymes with a large number of potential substrates. Here, we report that the Arabidopsis thaliana gene At3g44860 encodes a protein with high catalytic specificity towards farnesoic acid (FA). Under steady-state conditions, this farnesoic acid carboxyl methyltransferase (FAMT) exhibits K{sub M} values of 41 and 71 {mu}M for FA and SAM, respectively. A three-dimensional model of FAMT constructed based upon similarity to the experimentally determined structure of Clarkia breweri salicylic acid ...
BackgroundThe presence of regulatory T (Treg) cells in human endometrium is crucial for maintaining immunological homeostasis within the uterus. For this study we decided to evaluate...Full Text Available
Main results of 15-year SSTC NRS activity in the field of technical support of regulatory authority are presented. The article also described management policy, quality assurance system, personnel training system and international co-operation of SSTC. (author)
Reverse engineering of gene regulatory networks has been an intensively studied topic in bioinformatics since it constitutes an intermediate step from explorative to causative gene expression...Full Text Available
That regulatory T cells (Tregs) have a crucial role in controlling allergic diseases such as asthma is now undisputed. The cytokines most commonly implicated in Treg-mediated suppression of...Full Text Available
Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we ...
The report analyzes the cost-effectiveness of two alternative regulatory options: A Treated Discharge Option and a Zero Discharge Option. The report compares the total annualized cost incurred for each of the two regulatory options to the corresponding ef...
Transcription for a hybrid SV40 promoter-beta globin coding sequence recombinant initiates from both early-early (EE) and late-early (LE) SV40 start sites (EES and LES) in the absence of DNA replication....Full Text Available
RNA was synthesized in vitro from a T3 DNA template by T3 RNA polymerase and subsequently separated into seven discrete size classes (molecular weights ranging between 0.21 x 10(6) and 6.2 x 10(6))...Full Text Available
The nucleotide sequence of the 5'-terminal oligonucleotides produced by pancreatic RNase digestion of bacteriophage T3 RNA polymerase (EC 2.7.7.6) transcripts of T3 DNA has been determined. The sequence...Full Text Available
Yeast arginyl-tRNA synthetase recognizes the non-modified wild-type transcripts derived from both yeast tRNA(Arg) and tRNA(Asp) with equal efficiency. It discriminates its cognate natural substrate,...Full Text Available
The transcriptional co-activator PGC-1α regulates functional plasticity in adipose tissue by linking sympathetic input to the transcriptional program of adaptive thermogenesis. We report here...Full Text Available
Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing...Full Text Available
α1-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation...Full Text Available
Loss-of-function mutations in the regulatory gene areA of Aspergillus nidulans prevent the utilization of a wide variety of nitrogen sources. The phenotypes of nit-2 mutants of Neurospora crassa suggest...Full Text Available
In August 1995, the Nuclear Regulatory Commission (NRC) issued a policy statement proposing improved regulatory decisionmaking by increasing the use of PRA [probabilistic risk assessment] in all regulatory matters to the extent supported by the state-of-the-art in PRA methods and data. A key aspect in using PRA in risk-informed regulatory activities is establishing the appropriate scope and attributes of the PRA. In this regard, ASME decided to develop a consensus PRA Standard. The objective is to develop a PRA Standard such that the technical quality of nuclear plant PRAs will be sufficient to support risk-informed regulatory applications. This paper presents examples recommendations for the systems analysis element of a PRA for incorporation into the ASME PRA Standard.
In August 1995, the US Nuclear Regulatory Commission (NRC) issued a policy statement proposing improved regulatory decision making by increasing the use of probabilistic risk assessment (PRA) in all regulatory matters to the extent supported by the state-of-the-art in PRA methods and data. A key aspect in using PRA in risk-informed regulatory activities is establishing the appropriate scope and attributes of the PRA. In this regard, the American Society of Mechanical Engineers (ASME) decided to develop a consensus PRA standard. The objective is to develop a PRA standard such that the technical quality of nuclear plant PRAs will be sufficient to support risk-informed regulatory applications. The authors present example recommendations for the systems analysis element of a PRA for incorporation into the ASME PRA standard.
This report, the eighth in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1992. A special emphasis on accomplishments in nuclear power plant aging research reflects recognition that a number of plants are entering the final portion of their original 40-year operating licenses and that, in addition to current aging effects, a focus on safety considerations for license renewal becomes timely. The primary purpose of performing regulatory research is to develop and provide the Commission and its staff with the technical bases for regulatory decisions on the safe operation of licensed nuclear reactors and facilities, to find unknown or unexpected safety problems, and to develop data and related information for the purpose of revising the ...
This report, the eighth in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1992. A special emphasis on accomplishments in nuclear power plant aging research reflects recognition that a number of plants are entering the final portion of their original 40-year operating licenses and that, in addition to current aging effects, a focus on safety considerations for license renewal becomes timely. The primary purpose of performing regulatory research is to develop and provide the Commission and its staff with the technical bases for regulatory decisions on the safe operation of licensed nuclear reactors and facilities, to find unknown or unexpected safety problems, and to develop data and related information for the purpose of revising the ...
Mimivirus is the prototype of a new family (the Mimiviridae) of nucleocytoplasmic large DNA viruses (NCLDVs), which already include the Poxviridae, Iridoviridae, Phycodnaviridae and Asfarviridae. Mimivirus specifically replicates in cells from the genus Acanthamoeba. Proteomic analysis of purified mimivirus particles revealed the presence of many subunits of the DNA-directed RNA polymerase II complex. A fully functional pre-transcriptional complex appears to be loaded in the virions, allowing mimivirus to initiate transcription within the host cytoplasm immediately upon infection independently of the host nuclear apparatus. To fully understand this process, a systematic study of mimivirus proteins that are predicted (by bioinformatics) or suspected (by proteomic analysis) to be involved in...
Quantitative Real-Time PCR (qRT-PCR) is a widely used tool to study host responses against parasites. A crucial step in the gene quantification process is the normalization of the expression data against stable housekeeping genes (HKGs). However, in recent years, several reports have showed that the transcriptional levels of such HKGs can change dramatically, especially when cellular changes appear in the tissues investigated. The aim of the current study was to assess the variability of 11 putative HKGs in bovine abomasal tissue during an infection with the parasitic nematode Ostertagia ostertagi. Gene transcription levels of selected potential HKGs were measured by qRT-PCR and the expression stabilities evaluated using geNorm, NormFinder, and The Mann-Whitney-U test. The analysis showed ...
Abstract This study reports the effects of varying concentrations of copper sulfate on the metabolic and gene transcriptional profile of a recombinant Chinese hamster ovary (CHO) cell line producing an immunoglobulin G (IgG)-fusion protein (B0). Addition of 50 M copper sulfate significantly decreased lactate accumulation in the cultures while increasing viable cell density and protein titer. These changes could be seen from day 6 and became increasingly evident with culture duration. Reducing the copper sulfate concentration to 5 M retained all the above beneficial effects, but with the added benefit of reduced levels of the aggregated form of the B0 protein. To profile the cellular changes due to copper sulfate addition at the transcriptional level, Affymetrix CHO microarrays were used to...
This presentation outlined the energy policy in the United States and its impact on frontier development in Alaska, deepwater offshore fields and in the western oil shale resources. The energy strategy focuses on technologies that increase domestic production from existing resources as well as technologies that create new sources of energy. In addition to emphasizing the cooperation between Canada and the United States in ensuring energy supply security and stability, this paper discussed the importance of overall bilateral trade between the 2 countries. It was noted that Canada is the United State's most secure and reliable energy partner and is the number 1 supplier of imported oil, natural gas, electricity and uranium. The Bush administration's energy policy is based on the mandate to supply stable, reliable, secure, affordable and environmentally sound energy for the country's growing economy. The energy strategy focuses on increasing energy supplies, ...
On 21 October 1994, three brothers entered a waste repository at Tammiku, Estonia, without authorization and removed a metal container enclosing a caesium-137 source. During the removal the source was dislodged and fell to the ground. One of the men picked up the source, placed it in his pocket and took it to his home in the nearby village of Kiisa. Very soon after entry into the repository he began to feel ill, and few hours later he began to vomit. The man was subsequently admitted to hospital with severe injuries to his leg and hip and died on 2 November 1994. The injury and subsequent death were not attributed to radiation exposure, and the source remained in the man's house with his wife and stepson and the boy's great-grandmother. The boy was hospitalized on 17 November with severe burns on his hands, and these were identified by a doctor as radiation induced. The authorities were alerted, and the Estonian Rescue Board recovered the source from the house. The ...
This report discusses the safety approach of the Advanced Liquid Metal reactor program, sponsored by the US Department of Energy, which relies upon passive reactor responses to off-normal condition to limit power and temperature excursions to levels that allow safety margins. Gas expansion modules (GEM) have included in the design to provide negative reactivity to enhance these margins in the extremely unlikely event that pumping power is lost and the highly reliable scram system fails to operate. The feasibility and beneficial features of these devices were first demonstrated in the core of the Fast Flux Test Facility (FFTF) in 1986. Preapplication safety evaluations by the US Nuclear Regulatory Commission have identified areas that must be addressed if these devices are to be relied on. One of these areas is the response of the reactor when it is critical and the pumps are turned on, resulting in positive reactivity being added to the core. ...
The safety approach of the Advanced Liquid Metal Reactor program, sponsored by the U.S. Department of Energy, relies upon passive reactor responses to off-normal conditions to limit power and temperature excursions to levels that allow large safety margins. Gas expansion modules (GEM) have been included in the design to provide negative reactivity to enhance these margins in the extremely unlikely event that pumping power is lost and the highly reliable scram system fails to operate. The feasibility and beneficial features of these devices were first demonstrated in the core of the Fast Flux Test Facility (FFTF) in 1986. Pre-application safety evaluations by the U.S. Nuclear Regulatory Commission have identified areas that must be addressed if these devices are to be relied on. One of these areas is the response of the reactor when it is critical and the pumps are turned on, resulting in positive reactivity being added to the core. Tests to ...
The Office of Civilian Radioactive Waste Management (OCRWM) must, among other things, be equipped to readily produce, file, store, access, retrieve, and transfer a wide variety of technical and institutional data and information. The data and information regularly produced by members of the OCRWM Program supports, and will continue to support, a wide range of program activities. Some of the more important of these information communication-related activities include: supporting the preparation, submittal, and review of a license application to the Nuclear Regulatory Commission (NRC) to authorize the construction of a geologic repository; responding to requests for information from parties affected by and/or interested in the program; and providing evidence of compliance with all relevant Federal, State, local, and Indian Tribe regulations, statutes, and/or treaties. The OCRWM Telecommunications Network Plan (TNP) is intended to identify, as ...
The Rocky Flats Plant, located approximately 26 km northwest of downtown Denver, Colorado, has developed an emergency response atmospheric dispersion model for complex terrain applications. Plant personnel would use the model, known as the Terrain-Responsive Atmospheric Code (TRAC) (Hodgin 1985) to project plume impacts and provide off-site protective action recommendations to the State of Colorado should a hazardous material release occur from the facility. The Colorado Department of Health (CDH) entered into an interagency agreement with the Rocky Flats Plant prime contractor, EG&G Rocky Flats, and the US Department of Energy to evaluate TRAC as an acceptable emergency response tool. After exhaustive research of similar evaluation processes from other emergency response and regulatory organizations, the interagency committee devised a formal acceptance process. The process contains an evaluation protocol (Hodgin and Smith 1992), descriptions of ...
This paper describes the unique challenges involved in achieving compliance with the Resource Conservation and Recovery Act (Public Law 94-580) Land Disposal Restrictions (LDR) treatment standards for four types of mixed wastes generated throughout the U.S. Department of Energy (DOE) complex: (1) radioactively contaminated lead acid batteries; (2) radioactively contaminated cadmium-, mercury-, and silver-containing batteries; (3) mercury-bearing mixed wastes; and (4) radioactive lead solids. For each of these mixed waste types, the paper identifies the strategy pursued by DOE's Office of Pollution Prevention and Resource Conservation Policy and Guidance (EH-43) in coordination with other DOE elements and the U.S. Environmental Protection Agency (EPA) to meet the compliance challenge. Specifically, a regulatory interpretation was obtained from EPA agreeing that the LDR treatment standard for wastes in the D008 'Radioactive Lead Solids' ...
The object of this paper is to identify the key elements that impact a radiation dose at EAB (Exclusion Area Boundary). This study is based on the AST (Alternative Source Terms) as defined in Regulatory Guide 1.183. The LOCA (Loss of Coolant Accident) and the LRA (Locked Rotor Accident) are selected as limiting cases. A sensitivity analysis of accidental behavior with respect to various parameters during LOCA and LRA at Kori Unit 1 is also undertaken for the following objectives: to determine the limiting parameters, to find the impact trend of the radiation dose, and to find the safety margin between AST and TID (Technical Information Document) methodologies. This work confirms that key parameters are particulate removal rate, decontamination factor, iodine chemical form, gap fraction, partitioning factor, and the impact of isotopes group. Comparing TID with AST, the radiation dose of TID is about 80% greater than that of AST under a LOCA, and ...
An initial review was conducted of the current treatment operations for remediation of groundwater contaminated with trichloroethene (TCE) at the Fort lewis Logistics Center. Results from this review indicate the two pump-and-treat systems are effectively containing the TCE plume within the upper unconfined aquifer (Vashon Drift). However, mass balance calculations show the existing treatment systems alone will not accomplish the remedial action objective of cleaning up the aquifer to drinking water standards within 30 years as specified in the Record of Decision (ROD). This conclusion is based on the estimated mass of TCE at the source term (51,000 kg), the calculated mass of TCE in the aquifer (4,900 kg), and the removal rate of the pump-and-treat systems that currently ranges from 324 to 667 kg of TCe per year. Four areas within the TCE plume have been identified where enhancements could be made to the existing treatment operations. These are, Area 1 -- the ...
The Nuclear Regulatory Commission (NRC) has sponsored several studies to identify and quantify, through the use of models, the potential health effects of accidental releases of radionuclides from nuclear power plants. The Reactor Safety Study provided the basis for most of the earlier estimates related to these health effects. Subsequent efforts by NRC-supported groups resulted in improved health effects models that were published in the report entitled {open_quotes}Health Effects Models for Nuclear Power Plant Consequence Analysis{close_quotes}, NUREG/CR-4214, 1985 and revised further in the 1989 report NUREG/CR-4214, Rev. 1, Part 2. The health effects models presented in the 1989 NUREG/CR-4214 report were developed for exposure to low-linear energy transfer (LET) (beta and gamma) radiation based on the best scientific information available at that time. Since the 1989 report was published, two addenda to that report have been prepared to (1) ...
The goal of this paper is to explore how compliance with the Clean Air Act Amendments of 1990 (CAAA), especially Title IV and emission trading under it, will affect the current relationship between state and federal regulation. It is difficult, with the limited experience we have had under Title IV, to be definitive about or to be a very strong advocate of too many policy positions. What may be most helpful at this point is to identify where the difficult issues in state/federal relations might arise; and then to explore ways in which tensions might be either avoided or resolved. One anticipated conclusion is that a traditional regulatory mindset could be very destructive if applied to this new area of oversight without due sensitivity to what Congress is trying to achieve in Title IV. That concern pervaded the early legislative debates; and it persists today. Title IV presents some unique challenges to state regulators and will require some ...
This is the second technical report, covering the period from April 1, 2003 through September 30, 2003. This project brings together three parts of the oil exploration, development, and permitting process to form the foundation for a more fully integrated information technology infrastructure for the State of Alaska. The geo-technical component is a shared effort between the State Department of Administration and the US Department of Energy. The Alaska Oil and Gas Conservation Commission is rapidly converting high volumes of paper documents and geo-technical information to formats suitable for search and retrieval over the Internet. The permitting component is under the lead of the DNR Office of Project Management and Permitting. A web-based system will enable the public and other review participants to track permit status, submit and view comments, and obtain important project information on-line. By automating several functions of the current manual process, permit applications will ...
Based on the occurrence of a number of plant incidents during low power and shutdown operating conditions, the Nuclear Regulatory Commission (NRC) has initiated several programs to better quantify risk during these periods. One specific issue of interest is the loss of residual heat removal (RHR) under reduced coolant inventory conditions. This issue is also of interest in the Federal Republic of Germany and an experiment was performed in the integral PKL-3 experimental facility at Siemens-KWU to supply applicable data. Recently, an effort has been undertaken at the Idaho National Engineering Laboratory (INEL) to identify and analyze the important thermal-hydraulic phenomena in pressurized water reactors following loss of vital AC power and consequent loss of the RHR system during reduced inventory operation. The thermal-hydraulic response of a nuclear steam supply system (NSSS) with a closed reactor coolant system (RCS) to loss of residual ...
BackgroundThe pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra-vascular host cell...Full Text Available
BackgroundHerbivore feeding elicits dramatic increases in defenses, most of which require jasmonate (JA) signaling, and against which specialist herbivores are thought to be better...Full Text Available
The structural phosphoprotein NS of vesicular stomatitis virus, in association with the virion-associated RNA polymerase L protein, transcribes the genome ribonucleoprotein template in vitro. It contains...Full Text Available
Borna disease virus (BDV) uses a unique strategy of replication and transcription which takes place in the nucleus, unlike other known, nonsegmented, negative-stranded RNA viruses of animal origin....Full Text Available
SummaryBrown fat is specialized in energy expenditure, a process that is principally controlled by the transcriptional co-activator PGC-1α. Here we describe a molecular...Full Text Available
Skeletal muscle and adipose tissue development often has a reciprocal relationship in vivo, particularly in myodystrophic states. We have investigated whether determined myoblasts with no inherent adipogenic...Full Text Available
Known vertebrate GATA proteins contain two zinc fingers and are required in development, whereas invertebrates express a class of essential proteins containing one GATA-type zinc finger. We isolated...Full Text Available
The bovine syncytial virus, a member of the retroviral subfamily Spumavirinae, causes a persistent, asymptomatic infection in cattle. Nucleotide sequence analysis of the viral genome revealed two overlapping...Full Text Available
Mitochondria and peroxisomes execute some analogous, nonredundant functions including fatty acid oxidation and detoxification of reactive oxygen species, and, in response to select metabolic cues, undergo...Full Text Available
Earlier we have shown that exogenous expression of HIPPI, a molecular partner of Huntingtin interacting protein HIP-1, induces apoptosis and increases expression of caspases-1, -8 and -10 in HeLa and...Full Text Available
Current genome-wide association studies (GWAS) are moving towards the use of large cohorts of primary cell lines to study a disease of interest and to assign biological relevance to the genetic signals...Full Text Available
Purpose of ReviewThe vertebrate cap’n’collar family transcription factor Nrf2 and its invertebrate homologs SKN-1 (in worms) and CncC (in flies) function...Full Text Available
The mini-chromosome maintenance proteins Mcm2–7 are essential for DNA replication. They are loaded onto replication origins during G1 phase of the cell cycle to form a pre-replication complex...Full Text Available
AbstractThe tick-borne protozoan parasite Theileria annulata causes a debilitating disease of cattle called Tropical Theileriosis. The parasite predominantly invades...Full Text Available
Post-transcriptional nucleoside modifications fine-tune the biophysical and biochemical properties of transfer RNA (tRNA) so that it is optimized for participation in cellular processes. Here we report...Full Text Available
BackgroundChromatin insulators or boundary elements are a class of functional elements in the eukaryotic genome. They regulate gene transcription by interfering with promoter-enhancer...Full Text Available
A series of deletion mutants extending from -250 toward the capsite has been constructed in the early promoter region of the adenovirus 2 EIIa gene and tested both in vitro, and in vivo after transfection...Full Text Available
The specific binding of transcription factors to cognate sequence elements is thought to be critical for the generation of specific gene expression programs. Members of the nuclear factor κB...Full Text Available
p53 plays a critical role in tumor suppression. As a transcription factor, in response to stress signals, p53 regulates its target genes and initiates stress responses, including cell cycle arrest,...Full Text Available
BackgroundActivation of the signal transducer and activator of transcription 3 (STAT3) within antigen presenting cells (APCs) is linked to abnormal APCs differentiation and function....Full Text Available
BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available
Dal82p binds to the UISALL sites of allophanate-induced genes of the allantoin-degradative pathway and functions synergistically with the GATA family Gln3p and Gat1p transcriptional...Full Text Available
BackgroundThe common liver fluke Fasciola hepatica is the agent of a zoonosis with significant economic consequences in livestock production worldwide, and increasing...Full Text Available
CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure...Full Text Available
Efficiency of translation termination relies on the specific recognition of the three stop codons by the eukaryotic translation termination factor eRF1. To date only a few proteins are known to be involved...Full Text Available
Recognition of acetylated chromatin by the bromodomains and extra-terminal domain (BET) family proteins is a hallmark for transcriptional activation and anchoring viral genomes to mitotic chromosomes...Full Text Available
The accepted model of retroviral reverse transcription includes a circular DNA intermediate which requires strand displacement synthesis for linearization and creation of an integration-competent, long...Full Text Available
Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN). Our recent study...Full Text Available
The Sleeping Beauty (SB) transposon system represents an important alternative to viral integrating vector systems but may, as its viral counterparts, be subject to transcriptional silencing. To investigate...Full Text Available
Although genetically identical for autosomal Chrs (Chr), male and female preimplantation embryos could display sex-specific transcriptional regulation. To illustrate sex-specific differences at the...Full Text Available
By pretreating simian virus 40-infected BSC-1 cells with glucosamine, [3H]uridine labeling of both cellular and viral RNA can be halted instantaneously by addition of cold uridine. We have...Full Text Available
Methylation of RNA by methyltransferases is a phylogenetically ubiquitous post-transcriptional modification that occurs most extensively in transfer RNA (tRNA) and ribosomal RNA (rRNA). Biochemical...Full Text Available
Adipocyte differentiation is a complex developmental process that involves the coordinated interplay of numerous transcription factors. PPARγ has emerged as a master regulator of adipogenesis...Full Text Available
Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes. Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia...Full Text Available
Brown fat is a specialized tissue that can dissipate energy and counteract obesity through a pattern of gene expression that greatly increases mitochondrial content and uncoupled respiration. PRDM16...Full Text Available
In mice and humans the circadian rhythm of many biochemical reactions, physiology, and behavior is generated by a transcriptional-translation feedback loop (TTFL) made up of the so-called core clock...Full Text Available
Polyploidy is an important force in the evolution of flowering plants. Genomic merger and doubling induce an extensive array of genomic effects, including immediate and long-term alterations in the...Full Text Available
BackgroundIdentification of urinary biomarkers for detection of bladder cancer recurrence would be beneficial to minimize the frequency of cystoscopy. Our objective was to determine...Full Text Available
Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null ...Full Text Available
Menin, which is encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor and transcriptional regulator. Menin controls proliferation and apoptosis of cells, especially pancreatic...Full Text Available
BackgroundNKX2-3 is associated with inflammatory bowel disease (IBD). NKX2-3 is expressed in microvascular endothelial cells and the muscularis...Full Text Available
NF-κB, a transcription factor first discovered in 1986, is now known to be closely connected to the process of tumorogenesis based on a multiplicity of evidence. (1)...Full Text Available
BackgroundIncreasing evidence demonstrates that stem cells maintain their identities by a unique transcription network and chromatin structure. Opposing epigenetic modifications...Full Text Available
The sequence-dependent structural variability and conformational dynamics of DNA play pivotal roles in many biological milieus, such as in the site-specific binding of transcription factors to target...Full Text Available
BackgroundMalignant catarrhal fever (MCF) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes...Full Text Available
We have characterized the kinetic response of gene targets throughout the murine genome to transcriptional modulation by the glucocorticoid receptor (GR). In contrast to a model in which multiple genes...Full Text Available
BackgroundSerine proteinase inhibitors (Serpins) are a large superfamily of structurally related, but functionally diverse proteins that control essential proteolytic pathways in...Full Text Available
The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic...Full Text Available
Juvenile hormone analog (JHA) insecticides are relatively nontoxic to vertebrates and offer effective control of certain insect pests. Recent reports of resistance in whiteflies and mosquitoes demonstrate...Full Text Available
The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ 3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activatin observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analyzed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found ...
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human...Full Text Available
The spliced alignment of expressed sequence data to genomic sequence has proven a key tool in the comprehensive annotation of genes in eukaryotic genomes. A novel algorithm was developed to assemble...Full Text Available
IntroductionThe murine air pouch is a bursa-like space that resembles the human synovial membrane. Injection of monosodium urate (MSU) crystals into the pouch elicits an acute inflammatory...Full Text Available
Exposure of animals to hyperoxia decreases lung VEGF mRNA expression concomitant with an acute increase in VEGF protein within the epithelial lining fluid (ELF). The VEGF concentration in ELF...Full Text Available
BACKGROUND: Mitochondrial changes have been described in muscle tissue in acquired hypothyroidism. Among the molecular mechanisms by which thyroid hormones regulate expression of nuclear genes encoding...Full Text Available
BackgroundThe zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In...Full Text Available
BackgroundPromoter region plays an important role in determining where the transcription of a particular gene should be initiated. Computational prediction of eukaryotic Pol II promoter...Full Text Available
BackgroundHIV-1 reverse transcriptase (RT) is a heterodimer composed of p66 and p51 subunits and is responsible for reverse transcription of the viral RNA genome into DNA. RT can...Full Text Available
BackgroundHuman Papillomavirus (HPV) E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the...Full Text Available
Gene arrays containing all currently known open reading frames of Bacillus subtilis were used to examine the general stress response of Bacillus. By proteomics, transcriptional...Full Text Available
Bovine embryos can be generated by in vitro fertilization or somatic nuclear transfer; however, these differ from their in vivo counterparts in many aspects and exhibit a higher proportion of developmental...Full Text Available
Zinc is an essential trace metal ion for growth, but an excess of Zn is toxic and microorganisms express diverse resistance mechanisms. To understand global bacterial responses to excess Zn, we conducted...Full Text Available
Transcription factors drive organogenesis, from the initiation of cell fate decisions to the maintenance and implementation of these decisions. The Drosophila embryonic salivary gland...Full Text Available
Hematopoietic stem cells replenish all the cells of the blood throughout the lifetime of an animal. Although thousands of stem cells reside in the bone marrow, only a few contribute to blood production...Full Text Available
Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the...Full Text Available
BackgroundNF-κB is a survival signaling transcription factor complex involved in the malignant phenotype of many cancers, including squamous cell carcinomas (SCC). The citrus...Full Text Available
Pseudomonas mandelii liquid cultures were studied to determine the effect of pH and temperature on denitrification gene expression, which was quantified by quantitative reverse transcription-PCR....Full Text Available
BackgroundThe transcription factor Pax6 is essential for the development of the central nervous system and it exerts its multiple functions by regulating the expression of downstream...Full Text Available
Exposure of Mycobacterium tuberculosis to hypoxia is known to alter the expression of many genes, including ones thought to be involved in latency, via the transcription factor DevR...Full Text Available
September 14, 2010 ADHD: Signs, Symptoms, Research NIMH researchers talk about the symptoms of ADHD as well as the latest research. Download this video. Watch on YouTube. Transcript Announcer: ADHD- Attention Deficit Hyperactivity Disorder- is one of the ...
BackgroundThere is an ever increasing rate of data made available on genetic variation, transcriptomes and proteomes. Similarly, a growing variety of bioinformatic programs are becoming...Full Text Available
IntroductionTyrosine phosphorylated signal transducer and activator of transcription 3 (pStat3) is expressed in numerous cancers and is required for mediating tumorigenesis. Autocrine...Full Text Available
Although skin is usually exposed during human exposures to ionizing radiation, there have been no thorough examinations of the transcriptional response of skin fibroblasts and keratinocytes...Full Text Available
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR...Full Text Available
Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently...Full Text Available
The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation...Full Text Available
BackgroundInterest in lycopene metabolism and regulation is growing rapidly because accumulative studies have suggested an important role for lycopene in human health promotion....Full Text Available
Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several...Full Text Available
A high-throughput assay for enzyme activity has been developed that is reaction independent. In this assay, a small-molecule yeast three-hybrid system is used to link enzyme catalysis to transcription...Full Text Available
SummarySpatial control of gene expression, at the level of both transcription and translation, is critical for cellular differentiation [1-Full Text Available
The genomic termini of RNA viruses contain essential cis-acting signals for such diverse functions as packaging, genome translation, mRNA transcription, and RNA replication, and thus...Full Text Available
During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates...Full Text Available
BackgroundThe successful interaction of bacterial pathogens with host tissues requires the sensing of specific chemical and physical cues. The human gut contains a huge number of...Full Text Available
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available
The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies—including...Full Text Available
The abnormal megakaryocytopoiesis associated with idiopathic myelofibrosis (IM) plays a role in its pathogenesis. Because mice with defective expression of transcription factor GATA-1 (GATA-1low...Full Text Available
SummaryActivating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines...Full Text Available
Siderophores are essential factors for iron (Fe) acquisition in bacteria during colonization and infection of eukaryotic hosts, which restrain iron access through iron-binding protein, such as lactoferrin...Full Text Available
During complementary chromatic adaptation (CCA), cyanobacterial light harvesting structures called phycobilisomes are restructured in response to ambient light quality shifts. Transcription of genes...Full Text Available
A search for homologs of the Bacillus subtilis PhoP response regulator in the group A streptococcus (GAS) genome revealed three good candidates. Inactivation of one of these, recently...Full Text Available
BackgroundThe MYC transcription factors are known to be involved in the biology of many human cancer types. But little is known about the Myc/microRNAs cooperation in the regulation...Full Text Available
In addition to inducing new transcriptional activities that lead within a few hours to the accumulation of heat shock proteins (Hsps), heat shock activates within minutes the major signaling transduction...Full Text Available
increased knowledge as result of about a year's work, has led us first to ...... James Webb: And the advanced technology on which military power is going to be ..... on the road and I've been with the real big dogs and I know the deal ...
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T{sub 3}) receptors. Promoters containing the palindromic T{sub 3} response element TCAGGTCA TGACCTGA are positively regulated by the T{sub 3} receptor after the administration of T{sub 3}, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T{sub 3} or estrogen receptors on the estrogen or T{sub 3} response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer inhibitory functions to other classes of ...
This report, the fifth in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1989. The goal of this office is to ensure that safety-related research provides the technical bases for rulemaking and for related decisions in support of NRC licensing and inspection activities. This research is necessary to make certain that the regulations that are imposed on licensees provide an adequate margin of safety so as to protect the health and safety of the public. This report describes both the direct contributions to scientific and technical knowledge with regard to nuclear safety and their regulatory applications.
This report, the seventh in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1991. The goal of this office is to ensure that safety-related research provides the technical bases for rulemaking and for related decisions in support of NRC licensing and inspection activities. This research is necessary to make certain that the regulations that are imposed on licensees provide an adequate margin of safety so as to protect the health and safety of the public. This report describes both the direct contributions to scientific and technical knowledge with regard to nuclear safety and their regulatory applications.
This report, the seventh in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1991. The goal of this office is to ensure that safety-related research provides the technical bases for rulemaking and for related decisions in support of NRC licensing and inspection activities. This research is necessary to make certain that the regulations that are imposed on licensees provide an adequate margin of safety so as to protect the health and safety of the public. This report describes both the direct contributions to scientific and technical knowledge with regard to nuclear safety and their regulatory applications.
This report, the sixth in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1990. The goal of this office is to ensure that safety-related research provides the technical bases for rulemaking and for related decisions in support of NRC licensing and inspection activities. This research is necessary to make certain that the regulations that are imposed on licensees provide an adequate margin of safety so as to protect the health and safety of the public. This report describes both the direct contributions to scientific and technical knowledge with regard to nuclear safety and their regulatory applications.
This report, the fourth in a series of annual reports, was prepared in response to Congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during 1988. The goal of this office is to ensure that safety-related research provides the technical bases for rulemaking and for related decisions in support of NRC licensing and inspection activities. This research is necessary to make certain that the regulations that are imposed on licensees provide an adequate margin of safety so as to protect the health and safety of the public. This report describes both the direct contributions to scientific and technical knowledge with regard to nuclear safety and their regulatory applications.
This report is the second in a series of annual reports responding to congressional inquiries as to the utilization of nuclear regulatory research. NUREG-1175, ''NRC Safety Research in Support of Regulation,'' published in May 1986, reported major research accomplishments between about FY 1980 and FY 1985. This report narrates the accomplishments of FY 1986 and does not restate earlier accomplishments. Earlier research results are mentioned in the context of current results in the interest of continuity. Both the direct contributions to scientific and technical knowledge and their regulatory applications, when there has been a definite regulatory outcome during FY 1986, have been described.
The authors trace the early history of nuclear power regulation in the US. Focusing on the Atomic Energy Commission, they describe the role of other groups that figured in the development of regulatory policies, including the Congressional Joint Committee on Atomic Energy, other federal agencies, state governments, the nuclear industry, and scientific organizations. They consider changes in public perceptions of and attitudes toward atomic energy and the dangers of radiation exposure. The basic purpose of the book is to provide the Nuclear Regulatory Commission and the general public with information on the historical antecedents and background of regulatory issues so that there will be continuity in policy decisions. The book concludes with an annotated bibliography of selected references. 19 figures.
Legionella pneumophila is a gram-negative bacterial species that is ubiquitous in almost any aqueous environment. It is the agent of Legionnaires’ disease, an acute and often...Full Text Available
Within the cardiac cell, the movements of calcium ions are tightly regulated by a number of regulatory proteins including pumps, and channels. The sarcoplasmic reticulum (SR) is in large part...Full Text Available
and used to reduce or replace petroleum-based transportation fuel, heating oil or jet fuel). In addition, this rule includes a new regulatory provision establishing a...
In the aftermath of the 9/11 terrorist attacks on the United States, there was heightened interest worldwide in protecting nuclear power plants against intentional aircraft attack by terrorists. This paper presents our perspective into regulatory requirements for intentional aircraft crash that were set forth in foreign countries, including the latest rulemaking by the U.S. Nuclear Regulatory Commission (NRC), i.e., 10 CFR 50.54(hh) and 10 CFR 50.150 that have been made effective in May and July of 2009, respectively. In light of these international efforts to further enhance safety of NPPs, a study is also underway at the Korea Institute of Nuclear Safety (KINS) to establish an effective and efficient regulatory approach in consideration of the state of the art in this area
The world's fleet of nuclear power plants is, on average, more than 20 years old. Even though the design life of a nuclear power plant is typically 30-40 years, it is quite feasible that many plants will be able to operate in excess of their design lives, provided that nuclear power plant engineers demonstrate by analysis, trending, equipment and system upgrades, increased vigilance, testing and ageing management that the plant will operate safely. In the operation of nuclear power plants, safety should be always the prime consideration. Plant operators and regulators must always ensure that plant safety is maintained, and where possible enhanced, during a plant's operating lifetime. Nuclear power plant life management (PLiM) has gained increased attention over the past decade, and effective ageing management of systems, structures and components (SSCs) is a key element in PLiM for the safe and reliable long term operation of nuclear power plants. A PLiM programme is an effective tool ...
In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published...Full Text Available
The rates of synthesis of a class of both secreted and intracellular degradative enzymes in Bacillus subtilis are controlled by a signal transduction pathway defined by at least four regulatory genes:...Full Text Available
Public Law 95-209 includes a requirement that the Advisory Committee on Reactor Safeguards submit an annual report to Congress on the safety research program of the Nuclear Regulatory Commission. This report presents the results of the ACRS review and evaluation of the NRC safety research program for Fiscal Year 1983. The report contains a number of comments and recommendations.
Public Law 95-209 includes a requirement that the Advisory Committee on Reactor Safeguards submit an annual report to Congress on the safety research program of the Nuclear Regulatory Commission. This report presents the results of the ACRS review and evaluation of the NRC safety research program for Fiscal Year 1982. The report contains a number of comments and recommendations.
This report presents information and analysis to assist BLM in clarifying oil shale research needs. It provides technical guidance on research needs in support of their regulatory responsibilities for onshore mineral activities involving oil shale. It provides an assessment of research needed to support the regulatory and managerial role of the BLM as well as others involved in the development of oil shale resources on public and Indian lands in the western United States.
Regulatory T (T reg) cells exert powerful down-modulatory effects on immune responses, but it is not known how they act in vivo. Using intravital two-photon laser scanning microscopy we determined that,...Full Text Available
This document contains eleven papers on various aspects of low-level radioactive waste regulation. Topics include: EPA environmental standards; international exemption principles; the concept of below regulatory concern; envirocare activities in Utah; mixed waste; FUSRAP and the Superfund; and a review of various incentive programs. Individual papers are processed separately for the data base. (TEM)
To be able to carry out review functions regulatory authorities must be able to make critical evaluations of proponent's safety cases. In Sweden the Swedish Radiation Safety Authority aims to have in place its own suite of performance assessment tools. This paper looks at the role and application of a regulator's models to important features of current modelling in a proponent's performance assessment. (authors)
BackgroundATRX is a tightly-regulated multifunctional protein with crucial roles in mammalian development. Mutations in the ATRX gene cause ATR-X syndrome, an X-linked...Full Text Available
Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR)...Full Text Available
The fourth in a series of international Leak-Before-Break (LBB) Seminars supported in part by the US Nuclear Regulatory Commission was held at the National Central Library in Taipei, Taiwan on May 11 and 12, 1989. The seminar updated the international polices and supporting research on LBB. Attendees included representatives from regulatory agencies, electric utilities, nuclear power plant fabricators, research organizations, and academic institutions. Regulatory policy was the subject of presentations by Mr. G. Arlotto (US NRC, USA) Dr. B. Jarman (AECB, Canada), Dr.P. Milella (ENEA-DISP, Italy), Dr. C. Faidy (EDF/Septen, France ), and Dr. K. Takumi (NUPEC, Japan). A paper by Mr. K. Wichman and Mr. A. Lee of the US NRC Office of Nuclear Reactor Regulation is included as background material to these proceedings; it discusses the history and status of LBB applications in US nuclear power plants. In addition, several papers on ...
The goal of this study is to estimate the relevance and Influence of the Existing Regulation and the RI-PBR to the institutionalization of the regulatory system. This study reviews the current regulatory system and the status of the RI-PBR implementation of the US NRC and Korea based upon SECY Papers, Risk Informed Regulation Implementation Plan (RIRIP) of the US NRC and other domestic studies. In order to investigate the perceptions, knowledge level, ground for the regulatory change, a survey was performed to Korean nuclear utilities, researchers and regulators on the perception on the RIR. The questionnaire was composed of 50 questions regarding personal details on work experience, level of education and specific field of work ; level of knowledge on the risk informed performance based regulation (RI-PBR); the perception of the current regulation, the effectiveness, level of procedure, flexibility, dependency on the ...
The Drosophila sequence-specific DNA binding protein, Adf-1, is capable of activating transcription of the alcohol dehydrogenase gene, Adh, and is implicated in the transcriptional control of other developmentally regulated genes. We have cloned the cDNA encoding Adf-1 by generating specific DNA probes deduced from partial amino acid sequence of the protein. Several cDNA clones encoding an extended open reading frame were isolated from a phage lambda library. The complete amino acid sequence of Adf-1 deduced from the longest cDNA reveals structural similarities to the putative helix-turn-helix DNA binding motif of Myb and Myb-related proteins. DNA sequence analysis of genomic clones and Northern blot analysis of mRNA suggest that Adf-1 is a single-copy gene encoding a 1.9-kb transcript. Purified recombinant Adf-1 expressed in Escherichia coli binds specifically to Adf-1 recognition sites and activates ...
The State Energy Conservation Office has executed its first Fuel Cell Project which was awarded under a Department of Energy competitive grant process. The Texas LPG Fuel Processor Development and Fuel Cell Demonstration Program is a broad-based public/private partnership led by the Texas State Energy Conservation Office (SECO). Partners include the Alternative Fuels Research and Education Division (AFRED) of the Railroad Commission of Texas; Plug Power, Inc., Latham, NY, UOP/HyRadix, Des Plaines, IL; Southwest Research Institute (SwRI), San Antonio, TX; the Texas Natural Resource Conservation Commission (TNRCC), and the Texas Department of Transportation (TxDOT). The team proposes to mount a development and demonstration program to field-test and evaluate markets for HyRadix?s LPG fuel processor system integrated into Plug Power?s residential-scale GenSys 5C (5 kW) PEM fuel cell system in a variety of building types and conditions of service. The program?s primary goal is ...
A probabilistic precursor study provides a complement to the 'root cause' analysis approach by focusing on how an event might have developed adversely, and implies the mapping of an operational event on a probabilistic risk model of the plant in order to obtain a quantitative assessment of the safety significance of the event. In order to benefit from state-of-the-art PSA features but also to assure repeatability of the analysis, a comprehensive set of PSAEA guidelines was developed. This PSAEA procedure was established in 1996-1998 by Enconet Consulting in the framework of an international project on behalf of - and involving - the nuclear regulatory bodies from 6 countries: AECB (Canada), AVN (Belgium), CSN (Spain), HSK (Switzerland), NII (United Kingdom) and SKI (Sweden). The PSAEA procedure defines preliminary requirements for the PSA model and code, and identifies input requirements such as information on plant status, event sequence ...
This assessment is a feasibility study according to ISO 14024. It deals with the question whether an ecolabel is suitable for wood pellet heating systems and how concrete criteria for an ecolabel for wood pellet heating plants could be specified. The study begins with a comprehensive market analysis in order to identify possible plants for which an ecolabel would make sense. In the main part of the study, the environmental relevance of the chosen plants is analysed. For this analysis, plant manufacturers were interviewed and a comparison between wood pellet heating systems and heating systems which use gas, oil or wood was carried out. On the basis of this analysis, it was possible to derive a number of criteria which were discussed with company representatives and other experts in this field. As a result of this dialogue and the investigation process as a whole, the introduction of an ecolabel for wood pellet heating plants can be recommended. Wood pellet heating ...
Poncirin, flavanone glycoside, isolated from the fruit of Poncirus trifoliata, has anti-bacterial and anti-inflammatory activities. In this study, the effects of poncirin on the differentiation of mesenchymal stem cells were investigated. The C3H10T1/2 mesenchymal stem cells and primary bone marrow mesenchymal stem cells were studied. In the C3H10T1/2 cells, poncirin prevented adipocyte differentiation, as demonstrated by inhibition of cytoplasm lipid droplet accumulation and peroxisome proliferator-activating receptor-? (PPAR-?) and CCAAT-enhancer-binding protein-? (C/EBP-?) mRNA expression. By contrast, poncirin enhanced the expression of the key osteogenic transcription factors, runt-related transcription factor 2 (Runx2) and transcriptional coactivator with PDZ-binding motif (TAZ). Poncirin also enhanced expression of the osteogenic marker genes including alkaline phosphatase (ALP) and osteocalcin (OC). Poncirin ...
Transcriptional regulation of the galactose-metabolizing genes in Saccharomyces cerevisiae depends on three core proteins: Gal4p, the transcriptional activator that binds to upstream activating DNA sequences (UASGAL); Gal80p, a repressor that binds to the carboxyl terminus of Gal4p and inhibits transcription; and Gal3p, a cytoplasmic transducer that, upon binding galactose and adenosine 5'-triphosphate, relieves Gal80p repression. The current model of induction relies on Gal3p sequestering Gal80p in the cytoplasm. However, the rapid induction of this system implies that there is a missing factor. Our structure of Gal80p in complex with a peptide from the carboxyl-terminal activation domain of Gal4p reveals the existence of a dinucleotide that mediates the interaction between the two. Biochemical and in vivo experiments suggests that nicotinamide adenine dinucleotide phosphate (NADP) plays a key role in the initial ...
Low expression of osmotically responsive genes 2 (LOS2) encodes an enolase (2-phospho-D-glycerate hydrolase, EC 4.2.1.11) that converts 2-phospho-D-glycerate (PGA) to phosphoenolpyruvate (PEP) in the glycolytic pathway in Arabidopsis. Meanwhile, it is a transcriptional activator of cold-responsive gene, negatively controlling the expression of STZ/ZAT10, a zinc finger transcriptional repressor of cold-responsive gene from Arabidopsis. A novel LOS2 gene, designated PtrLOS2 (GenBank accession number GQ144341), was isolated from trifoliate orange [Poncirus trifoliata (L.) Raf.]. The PtrLOS2 cDNA is 1 662 bp in length with a 1 338 bp open reading frame (ORF), encoding a deduced 445 amino acid residue protein with a predicted molecular mass of 47.79 kDa and an isoelectric point of 5.54. The ded...
The PMS2 gene encodes a protein that is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published PMS2 cDNA sequence lack an upstream in-frame stop codon preceding the presumptive initiating methionine. To evaluate the 5` terminus of the PMS2 coding region further, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5` genomic segment of the PMS2 locus. The PMS2 gene transcripts were found to have heterogeneous but colinear 5` termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5-kDa polypeptide was found to initiate transcriptionally within PMS2 from the opposite strand. 23 refs., 5 figs., 2 tabs.
Amyloid precursor protein (APP), a key protein in pathogenesis of Alzheimer's disease (AD), is a type I transmembrane protein which can be cleaved by b- and g-secretase to release the amyloidogenic b-amyloid peptides (Ab) and the APP intracellular domain (AICD). While Ab has been widely believed to initiate pathogenic cascades culminating AD, the physiological functions and regulations of AICD remain elusive. In present study, endogenous AICD was demonstrated to be increased by canonical Wnt signal. Instead of due to g-secretase activity, enhanced AICD expression was found due to the increased protein stability by Wnt/b-catenin. b-Catenin was demonstrated to be an associating partner of AICD, capable of promoting AICD mediated transcriptional activity. Investigation by AICD mutants proved ...
Purpose The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancer...
Retroelements constitute a large part of the human genome. These sequences are mostly silenced in normal cells, but genome-wide DNA hypomethylation in cancers might lead to their re-expression. Whether this re-expression really occurs in human cancers is largely unkown. We therefore investigated expression and DNA methylation of several classes of retroelements in human prostate cancer tissues and cell lines by quantitative reverse transcription-polymerase chain reaction and pyrosequencing, respectively. The most striking finding was strong and generalized increased expression of the HERV-K_22q11.23 provirus in cancers, including de novo expression of a spliced accessory Np9 transcript in some tumors. In parallel, DNA methylation in the long terminal repeat (LTR) decreased. Conversely, HER...
Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.
Mutations in sclerostin function or expression cause sclerosing bone dysplasias, involving decreased antagonism of Wnt/Lrp5 signaling. Conversely, deletion of the VHL tumor suppressor in osteoblasts, which stabilize HIF-a isoforms and thereby enables HIF-a/b-driven gene transcription, increases bone mineral content and cross-sectional area compared to wild-type controls. We examined the influence of cellular hypoxia (1% oxygen) upon sclerostin expression and canonical Wnt signaling. Osteoblasts and osteocytes cultured under hypoxia revealed decreased sclerostin transcript and protein, and increased expression and nuclear localization of activated b-catenin. Similarly, both hypoxia and the hypoxia mimetic DFO increased b-catenin gene reporter activity. Hypoxia and its mimetics increased exp...
Ozone has in recent years been increasingly investigated for its potential use in the control of insect pests of stored cereals. Ozone is a powerful oxidizing agent that can react directly, or via production of reactive oxygen species, with proteins, DNA and double bonds of polyunsaturated fatty acids (PUFA). The aim of the present study was to investigate the mode of action in ozone toxicity using the red flour beetle, Tribolium castaneum (Herbst), as a relevant model. Transcription of focal genes thought to be involved in protection against ozone, and repair of cellular damage caused by ozone exposure, was studied together with the composition of storage lipid fatty acids and membrane phospholipid fatty acids in order to detect lipid peroxidation. Contrary to expectations, transcription ...
Harvested plant organs such as heads of broccoli (Brassica oleracea L. var. italica) experience a range of stresses that can lead to premature reduction in quality and eventual senescence. Understanding plant responses to stress may open up novel opportunities to extend postharvest life. One of the first stresses experienced by harvested organs is likely to be water deficit stress since severance of the vascular system halts the normal flux of water into the tissue. For broccoli branchlets with their cut ends held in water, transcriptome analysis based on hybridization of broccoli floret mRNA to a heterologous Arabidopsis microarray revealed that the transcript abundance of 431 genes reliably changed within 48h of harvest. Of these, transcripts of 146 genes increased and 34 genes decreased...
Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. We have created a database of evolutionary conserved regions (ECRs) in vertebrate genomes entitled ECRbase that is constructed from a collection of pairwise vertebrate genome alignments produced by the ECR Browser database. ECRbase features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a collection of promoters in all vertebrate genomes presented in the database. The database also contains a collection of annotated transcription factor binding sites (TFBS) in all ECRs and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and two pufferfish genomes. It is freely accessible at http://ECRbase.dcode.org.
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17b-estradiol (E2), although glycyrrhizin di...
Industrial radiography accounts for approximately half of all the reported accidents for the nuclear related industry, in both developed and developing countries. This Safety Report is the result of a review made of a large selection of accidents in industrial radiography reported by regulatory authorities, professional associations and scientific journals. A small, representative selection of 43 accident descriptions has been used to illustrate the primary causes of radiography accidents, and a set of measures provided to prevent the recurrence of such accidents or to mitigate the consequences of those that do occur. These accident descriptions were categorized by primary causes as follows: inadequate regulatory control; failure to follow operational procedures; inadequate training; inadequate maintenance; human error; equipment malfunction or defect; design flaws; and wilful violation. The information in this Safety report is intended for use ...
With the introduction of competition and diversification into retail utility services, rate-making methods are being rethought. Rates that are strictly cost-based may be too slow in responding to changes within the utility industry. And the advent of independent power production as a significant source of energy calls for greater flexibility in pricing of wholesale utility services as well. Various deregulation or reregulation plans have been formulated, including both price cap and price floor proposals. Some regulatory authorities have embraced market-based pricing over cost-based methods as the best solution to pricing problems. This article addresses Federal Energy Regulatory Commission response to market-based rates.
Wiskott-Aldrich syndrome protein (WASp) is essential for optimal T cell activation. Patients with WAS exhibit both immunodeficiency and a marked susceptibility to systemic autoimmunity. We investigated...Full Text Available
In addition to the well documented role of cytokines in mediating tissue-level interactions, it is now clear that matrix macromolecules fulfil a complementary regulatory function. Data highlighted in...Full Text Available
DNA transposons are efficient tools in transgenesis and have therefore become popular in the analysis of the regulatory genome in vertebrates via enhancer trap screens. Here, I discuss recent progress...Full Text Available
Rhizobium leguminosarum, biovar viceae, strain RCC1001 contains two glutamine synthetase activities, GSI and GSII. We report here the identification of glnA, the structural gene for GSI. A 2 kb fragment...Full Text Available
The RNA-binding protein Hfq is recognized as an important regulatory factor in a variety of cellular processes, including stress resistance and pathogenesis. Hfq has been shown in several bacteria to...Full Text Available
SUMMARYThe biologic and clinical significance of KIT overexpression that associates with KIT gain-of- function mutations occurring in subsets...Full Text Available
Background/AimsHelicobacter pylori (H. pylori) infection appears to subvert the human iron regulatory mechanism and thus upregulates hepcidin, resulting...Full Text Available
A regulatory locus on the Staphylococcus aureus chromosome, designated sar, is involved in the expression of cell wall proteins, some of which are potentially important in the pathogenesis of endocarditis....Full Text Available
A positive, genetic selection against the activity of the nitrogen regulatory (NTR) system was used to isolate insertion mutations affecting nitrogen regulation in Klebsiella aerogenes. Two classes...Full Text Available
The level of bone morphogenetic protein 2 (BMP2) profoundly influences essential cell behaviors such as proliferation, differentiation, apoptosis, and migration. The spatial and temporal pattern...Full Text Available
...broad range of experience in designing and building research and development laboratories for products such as vaccines, blood and sera, biological products, medical devices, solid dosage forms , highly potent products and cytotoxic material. We also have experience in a range of modular laboratories for TSE research, ...
Phospho-beta-galactosidase (P-beta-gal), the enzyme which catalyzes the first step in the metabolism of intracellular lactose phosphate, occurred at high specific activity in the cytoplasm in 12 of...Full Text Available
Most genetic changes that promote tumorigenesis involve dysregulation of G1 cell cycle progression. A key regulatory site in G1 is a growth factor–dependent restriction point (R) where cells...Full Text Available
Regulatory agencies currently rely on rodent carcinogenicity bioassay data to predict whether or not a given chemical poses a carcinogenic threat to humans. We argue that it is always more useful to...Full Text Available
Protein post-translational modifications are an important biological regulatory mechanism, and the rate of their discovery using high throughput techniques is rapidly increasingly. To make use of this...Full Text Available
Medical treatment of heroin addiction with methadone and other pharmacotherapies has important benefits for individuals and society. However, regulatory policies have separated this treatment from the...Full Text Available
We examine how the structure and function of indirect flight muscle (IFM) and the entire flight system of Drosophila melanogaster are affected by phosphorylation of the myosin regulatory light chain...Full Text Available
Government agencies responsible for protecting the public from the adverse effects of toxic chemicals must set priorities for research, regulatory action, protocol testing, and monitoring due to the...Full Text Available
This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judges (AU), the Directors` Decisions (DD), and the Decisions on Petitions for Rulemaking (DPRM).
This report includes the issuances received during the specified period from the Commission, the Atomic Safety and Licensing Appeal Boards, the Atomic Safety and Licensing Boards, the Administrative Law Judge, the Directors' Decisions, and the Denials of Petitions for Rulemaking.
This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Appeal Boards (ALAB), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judge (ALJ), the Directors' Decisions (DD), and the Denials of Petitions for Rulemaking (DPRM).
This report includes the issuances received during the specified period from the Commission (CLl), the Atomic Safety and Licensing Appeal Boards (ALAB), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judge (ALJ), The Directors' Decisions (DD), and the Denials of Petitions For Rulemaking (DPRM).
This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judges (ALJ), the Directors Decisions (DD), and the Decisions on Petitions for Rulemaking (DPRM).
The Regulatory Agenda is a semiannual compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and of all petitions for rulemaking that the NRC has received that are pending disposition.
Choline (Cho)-containing phospholipids are the most abundant phospholipids in cellular membranes and play fundamental structural as well as regulatory roles in cell metabolism and signaling. Although...Full Text Available
Although the heart rapidly adapts cardiac output to match the body’s circulatory demands, the regulatory mechanisms ensuring that sufficient ATP is available to perform the required...Full Text Available
Electricity markets in the United States are undergoing unprecedented structural changes as a result of the confluence of regulatory, competitive, and technological forces. This paper introduces these structural changes and forces and discuss the implications, markets and commercialization scenarios for emerging fuel cells in evolving US electricity markets.
This manual provides information to assist in selection and designing control measures for reducing pollutant discharges from combined sewer overflows (CSOs). he manual will be useful for municipal public works staff, design engineers, and regulatory agency staff tasked with the ...
BackgroundRecent data show aberrant and altered expression of regulatory noncoding micro (mi) RNAs in prostate cancer (PCa). A large number of miRNAs are encoded in organized intronic...Full Text Available
BackgroundModern approaches to treating genetic disorders, cancers and even epidemics rely on a detailed understanding of the underlying gene signaling network. Previous work has...Full Text Available
BackgroundThe immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients...Full Text Available
Myosin phosphatase target subunit 1 (MYPT1) is the regulatory subunit of myosin light chain phosphatase (MLCP). It plays a critical role in vasodilatation induced by cGMP-elevating agents such as nitric...Full Text Available
Skeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in Growth and Differentiation Factor 6 (Gdf6) have numerous...Full Text Available
The genetic systems of bacteria that have the ability to use organic pollutants as carbon and energy sources can be adapted to create bacterial biosensors for the detection of industrial pollution....Full Text Available
Progress is reported in the following subject areas: (1) chemistry of the arogenate molecule; (2) plant enzymology at the organismal level; (3) isolation of regulatory mutants in tobacco; and (4) stability of the haploid state in Nicotiana sylvestris.
The programming of cellular networks to achieve new biological functions depends on the development of genetic tools that link the presence of a molecular signal to gene-regulatory activity. Recently,...Full Text Available
Bistability plays a central role in the gene regulatory networks (GRNs) controlling many essential biological functions, including cellular differentiation and cell cycle control. However, establishing...Full Text Available
FXYD1 (phospholemman) is a member of an evolutionarily conserved family of membrane proteins that regulate the function of the Na,K-ATPase enzyme complex in specific tissues and specific physiological...Full Text Available
The report details the economic impact of two alternative regulatory options; a Treated Discharge Option and a Zero Discharge Option on facilities that would have to comply with the regulations as part of the reproposal of effluent limitations and standar...
The report presents detailed technical information concerning application of flue gas desulfurization (FGD) systems to industrial boilers. The information was obtained by a survey of plant personnel, control system vendors, regulatory agencies, and consulting engineering firms. T...
The ability to adapt to adverse environmental conditions encountered in food and during host infection is a sine qua non for a successful Listeria monocytogenes infection. This ability...Full Text Available
This cost-effectiveness analysis supports the proposed effluent limitations guidelines and standards for the Metal Products and Machinery Industry (MP and M) Phase I Industry. The report assesses the cost-effectiveness of five regulatory options for indir...
This analysis, submitted in support of proposed effluent limitations guidelines and standards for the centralized waste treatment (CWT) industry, investigates the cost-effectiveness of 24 regulatory options, representing all possible combinations of nine ...
BackgroundSteroidogenic acute regulatory (StAR) protein related lipid transfer (START) domains are small globular modules that form a cavity where lipids and lipid hormones bind....Full Text Available
Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations,...Full Text Available
BackgroundAs the first pathway-specific enzyme in carotenoid biosynthesis, phytoene synthase (PSY) is a prime regulatory target. This includes a number of biotechnological approaches...Full Text Available
Zipper-interacting protein kinase (ZIPK) is a member of the death-associated protein kinase family associated with apoptosis in nonmuscle cells where it phosphorylates myosin regulatory light chain...Full Text Available
The licensing status and procedures, regulatory framework, and current safety issues of CANDU type reactors, Wolsong units 2, 3 and 4 are examined. Licensing difficulties and lessons learned during the safety review of Wolsong 2, 3 and 4 and future requirements are also summarized. The review was conducted, not only to confirm the design adequacy with respect to the domestic atomic laws and regulatory requirements of the vendor country, Canada, but also to reflect into the design the lessons learned from the regulatory experiences of operating Wolsong I to enhance the safety as high as practically possible. Safety issues observed during the licensing review, such as containment integrity, fuel channel integrity, etc., are summarized. Several efforts have been conducted to harmonize the Canadian regulations with the Korean ones by establishing domestic regulatory positions and guidelines. For example, ...
Biosynthesis and uptake of siderophores in Aspergillus nidulans are regulated not only by iron availability but also by ambient pH: expression of this high-affinity iron uptake system...Full Text Available
The carboxyl-terminal region of tubulin alpha and beta subunits plays a major role in regulating its assembly into microtubules and constitutes an essential domain for the selective interaction of microtubule-associated...Full Text Available
Oncolytic viruses (OVs) represent a relatively novel anti-cancer modality. Like other new cancer treatments, effective OV therapy will likely require combination with conventional treatments. In order...Full Text Available
The report gives an initial assessment of the feasibility of disposing of flue gas desulfurization wastes in mines and in the ocean. The purpose of the assessment was to evaluate environmental, technical, regulatory, and economic aspects of the use of such disposal sites. Availab...
The accumulation of α-1,4-polyglucans is an important strategy to cope with transient starvation conditions in the environment. In bacteria and plants, the synthesis of glycogen and starch occurs...Full Text Available
BackgroundSearching for approximate patterns in large promoter sequences frequently produces an exceedingly high numbers of results. Our aim was to exploit biological knowledge for...Full Text Available
Leaf senescence is a developmentally programmed degeneration process, which is fine tuned by a complex regulatory network for plant fitness. However, molecular regulation of leaf senescence is poorly...Full Text Available
c-Jun N-terminal kinase 2 (JNK2) isoforms are transcribed from the jnk2 gene and are highly homologous with jnk1 and jnk3 transcriptional products....Full Text Available
The biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect’s life. However, the molecular actions of these hormones are not well understood....Full Text Available
A conserved multi-subunit complex (MybMuvB, MMB), regulates transcriptional activity of many different target genes in Drosophila somatic cells. A paralogous complex, tMAC, controls...Full Text Available
The 5'-terminal structures of human adenovirus type 2 (Ad2) early region 2 (E2) mRNA were investigated. The E2 transcription unit has several interesting properties, including the presence of a TATA-like...Full Text Available
In order to study the intragenic profiles of active transcription, we determined the relative levels of active RNA polymerase II present at the 3′- and 5′-ends of 261 yeast genes by...Full Text Available
Simian virus 40 transcriptional complexes could be extracted from CV1 cells late in infection and separated from the bulk of inactive viral chromatin. Sucrose gradient sedimentation, cesium sulfate...Full Text Available
Histone H3 mRNAs were found in polyA(+) fractions of total RNA prepared from alfalfa plants, calli and somatic embryos. The sequence analysis of cDNAs revealed the presence of a polyA tail on independent...Full Text Available
LIMD1 is a tumour suppressor gene (TSG) down regulated in ∼80% of lung cancers with loss also demonstrated in breast and head and neck squamous cell carcinomas. LIMD1 is also a candidate TSG...Full Text Available
SummaryThe transcriptional co-repressor SMRT utilizes two major receptor interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification....Full Text Available
Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The...Full Text Available
BackgroundThe large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity...Full Text Available
Hepatocyte nuclear factor (HNF) 4α is a key transcription factor regulating endo/xenobiotic-metabolizing enzymes and transporters. We investigated whether microRNAs are involved in the regulation...Full Text Available
The CCAAT/enhancer-binding protein β (C/EBPβ) is required for adipocyte differentiation and maturation. We have studied the role of the transcription factor, C/EBPβ,...Full Text Available
BackgroundHerpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction...Full Text Available
Stem-boring insects and methyl jasmonate (MeJA) are thought to induce similar complex chemical and anatomical defenses in conifers. To compare insect- and MeJA-induced terpenoid responses, we analyzed...Full Text Available
Recombinant plasmids containing mutant or wild-type adenovirus serotype 2 EIa genes that produce the 12S mRNA alone, the 13S mRNA alone, or both mRNAs were cotransfected into HeLa cells with plasmids...Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
The development of leukemia and thyroid cancer is characterized by activation of the abl oncogene and ret oncogene, respectively. In order to clarify the relationship between these gene aberrations and radiation, the pro-myelogenous leukemia-derived cell line HL60 and the thyroid cancer-derived cell line 8505C, were irradiated in vitro with 100Gy of X-rays. RNA was then extracted from 10"8 cells of the respective cell lines and examined by the reverse transcription PCR method for rearrangements of abl and ret genes. Five kinds of positive bands were observed in the HL-60 cells irradiated with 100Gy of X-ray. Similarly, six positive bands were also observed in the 8505C cells irradiated with 100Gy. In vitro X-irradiation activation of oncogenes found in radiation induced cancers imply that gene rearrangement by X-rays is involved in the development of malignant tumors. Furthermore, in an experiment to detect radiation effects in A-bomb survivors, RNA was extracted ...
The expression status of the estrogen receptor alpha (ERα) and that of the epidermal growth factor receptor Her-2/neu frequently correlate inversely in breast cancers. While ERα-dependent...Full Text Available
Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction...Full Text Available
The proteins encoded by polar-localized mRNAs play an important role in cell fate specification along the anteroposterior axis of the Drosophila embryo. The only maternally synthesized mRNA known previously...Full Text Available
Several different approaches exist to generate expressed RNA interference (RNAi) precursors for multiple target inhibition, a strategy referred to as combinatorial (co)RNAi. One such approach makes...Full Text Available
The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and...Full Text Available
The retrovirus-like particles of Drosophila are intermediates of retrotransposition of the transposable element copia. In these particles, a 39-nucleotide-long fragment from the 5' region of Drosophila...Full Text Available
The Epstein-Barr virus nuclear antigen (EBNA I) present in latently infected cells is encoded in a 2-kilobase exon contained in the BamHI K viral genomic fragment. This exon is, however, found within...Full Text Available
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by E(2), whereas glycyrrhizin had no ...
AbstractT-box family transcription factors play many roles in Metazoan development. Here we characterise Tbx6r, a unique Tbx6 paralogue isolated from the amphibian Xenopus....Full Text Available
The methylation of lysine 4 of Histone H3 (H3K4me) is an important component of epigenetic regulation. H3K4 methylation is a consequence of transcriptional activity, but also has been shown to contribute...Full Text Available
Microarray is a powerful tool for genome-wide gene expression analysis. In microarray expression data, often mean and variance have certain relationships. We present a non-parametric mean-variance smoothing...Full Text Available
The goal of the present work was to determine the impact of N3-methyladenine (3-mA), an important lesion generated by many environmental agents and anticancer drugs, on in vivo DNA replication and in vitro RNA transcription. Due to 3-mA chemical instability, the stable isostere 3-methyl-3-deazaadenine (3-m-c(3)A) was site specifically positioned into an oligodeoxynucleotide. The oligomer was, then incorporated into a vector system that is rapidly converted to ssDNA inside yeast cells and requires DNA replication opposite the lesion for plasmid clonal selection. For control purposes, an adenine or a stable apurinic/apyrimidinic (AP)-lesion was placed at the same site. The presence of each lesion in the oligonucleotide was confirmed by MALDI-TOF analysis. Plasmids were then transfected into yeast cells. While the AP-site dramatically reduced plasmid replication in all strains, the 3-m-c(3)A had a slight effect in the rad30 background which significantly increased ...
Tea catechin is one of the compounds that are closely related to obesity and insulin sensitivity. In order to determine the effect of catechin on adipocyte differentiation, we treated 3T3-L1 preadipocytes...Full Text Available
Oil and gas industry is the largest user of radioactive materials in Nigeria. They make use of radiation generators, sealed and unsealed radioactive sources.Some of these are potentially dangerous to human health and environment if not properly controlled. here is also the need to maintain control over occupational exposures to radiation, as well as to protect the public and the environment through proper management of wastes that may be radiologically hazardous. To minimize these, effective regulatory infrastructure is being put in place.For a smooth take-off of the nuclear power program, the National Nuclear Regulatory Authority and other stake holders in the nuclear industry need to start to put together licensing procedure for these.
Abstract: The Hanford Tanks Initiative (HTI) is a five-year project resulting from the technical and financial partnership of the U.S. Department of Energy`s Office of Waste Management (EM-30) and Office of Science and Technology Development (EM-50). The HTI project accelerates activities to gain key technical, cost performance, and regulatory information on two high-level waste tanks. The HTI will provide a basis for design and regulatory decisions affecting the remainder of the Tank Waste Remediation System`s tank waste retrieval Program.
In this study, the state-of-the art for estimating LERF is considered for the regulatory risk-informed decisions. The consideration is mainly focused on (1) the relationship between Level 2 PSA and LERF evaluation methodology, (2) the standard requirements in terms of modeling preparation and the acceptance criteria based on the application capability II of ASME PRA standard, and (3) some pending issues for developing and proposing a simplified LERF model. This study is preliminarily presented and will be updated for establishing detailed evaluation scheme of extended MPAS (multi-purpose probabilistic analysis of safety) model and preparing the technical basis.
Different cases exist in various countries regarding the institutional status, the organization and the technical resources of the Nuclear Regulatory Authority (NRA): there are NRAs having extended internal technical capability and others relying mostly on external technical support. Considering the research and development activities and the very broad range of technical matters on which the regulatory and licensing activity are based, the NRA can not rely only on internal resources, and generally there is the need of technical and scientific support together with enhanced international cooperation. The international cooperation and networking among NRAs, and their Technical Support Organizations (TSO), represents a fundamental way to maintain competence, capability and knowledge. Within the EU member states this is becoming more and more an institutional duty. In providing technical support for regulatory activity, the ...
We present a technique for identifying the amino acids responsible for a loss of immunoreactivity in response to treating an antigen with a chemical modifier. This is of particular interest...Full Text Available
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that factor(s) in the mouse erythroleukemia cell can genetically complement ...
NFAT involvement in adipocyte physiological processes was examined by treatment with CsA and/or GSK3{beta} inhibitors (Li{sup +} or TZDZ-8), which prevent or increase NFAT nuclear translocation, respectively. CsA treatment reduced basal and TNF{alpha}-induced rates of lipolysis by 50%. Adipocytes preincubated with Li{sup +} or TZDZ-8 prior to CsA and/or TNF{alpha}, exhibited enhanced basal rates of lipolysis and complete inhibition of CsA-mediated decreased rates of lipolysis. CsA treatment dramatically reduced the mRNA levels of adipocyte-specific genes (aP2, HSL, PPAR{gamma}, ACS and Adn), compared with control or TNF{alpha}-treatment, whereas Li{sup +} pretreatment blocked the inhibitory effects of CsA, and mRNA levels of aP2, HSL, PPAR{gamma}, and ACS were found at or above control levels. NFAT nuclear localization, assessed by EMSA, confirmed that CsA or Li{sup +} treatments inhibited or increased NFAT nuclear translocation, respectively. These results show that NFAT proteins in ...
Metabolic engineering of photosynthetic organisms is required for utilization of light energy and for reducing carbon emissions.Control of transcriptional regulators is a powerful approach for changing cellular dynamics, because a set of genes is concomitantly regulated. Here, we show that overexpression of a group 2 ? factor, SigE, enhances the expressions of sugar catabolic genes in the unicellular cyanobacterium, Synechocystis sp. PCC 6803. Transcriptome analysis revealed that genes for the oxidative pentose phosphate pathway and glycogen catabolism are induced by overproduction of SigE. Immunoblotting showed that protein levels of sugar catabolic enzymes, such as glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glycogen phosphorylase, and isoamylase, are increased. Glycogen levels are reduced in the SigE-overexpressing strain grown under light. Metabolome analysis revealed that metabolite levels of the TCA cycle and acetyl-CoA are ...
Epidemiological studies have revealed that butyrate and 17?-estradiol (E2) may decrease the incidence of colorectal cancer (CRC). In peripheral tissue, E2 can be produced locally by 17?-hydroxysteroid dehydrogenase 1 (HSD17B1) estrone (E1) reduction. Using quantitative real-time polymerase chain reaction and western blotting analysis, we found that sodium butyrate significantly upregulates HSD17B1 long and short transcripts and protein levels in HT29 and SW707 CRC cells. Chromatin immunoprecipitation analysis showed that upregulation of these transcript levels correlated with an increase in binding of Polymerase II to proximal and distal promoters of HSD17B1. Moreover, we observed that upregulation of HSD17B1 protein levels was associated with increased conversion of E1 to E2 in HT29 and S...
Boron (B) is an essential plant micronutrient that is toxic at higher levels. NIP5;1 is a boric acid channel required for B uptake and growth under B deficiency. Accumulation of the NIP5;1 transcript is upregulated under B deficiency in Arabidopsis thaliana roots. To elucidate the mechanism of regulation, the 5' untranslated region (UTR) of NIP5;1 was tested for its ability to confer B-dependent regulation using ?-glucuronidase and green fluorescent protein as reporters. This analysis showed that the 5' UTR was involved in NIP5;1 transcript accumulation in response to B conditions. We also found that high-B conditions trigger NIP5;1 mRNA degradation and that the sequence from +182 to +200 bp in the 5' UTR is required for this mRNA destabilization. In the nip5;1-1 mutant background, a NIP5;1 complementation construct without the 5' UTR produced high levels of mRNA accumulation, increased B concentrations in tissues, and reduced growth under ...
We describe a method for affinity purification of sequence-specific DNA binding proteins that is fast and effective. Complementary chemically synthesized oligodeoxynucleotides that contain a recognition site for a sequence-specific DNA binding protein are annealed and ligated to give oligomers. This DNA is then covalently coupled to Sepharose CL-2B with cyanogen bromide to yield the affinity resin. A partially purified protein fraction is combined with competitor DNA and subsequently passed through the DNA-Sepharose resin. The desired sequence-specific DNA binding protein is purified because it preferentially binds to the recognition sites in the affinity resin rather than to the nonspecific competitor DNA in solution. For example, a protein fraction that is enriched for transcription factor Sp1 can be further purified 500- to 1000-fold by two sequential affinity chromatography steps to give Sp1 of an estimated 90% homogeneity with 30% yield. In addition, the use ...
The online communicative environment is expected to revolutionize political discourse as it expands to cover underrepresented groups and ideas. In this platform, marginalized groups such as indigenous communities from the developing world can articulate claims, strategically mobilize and participate in the forms of meaning-making that constitute them. However, there is skepticism on the actual value of online spaces in effecting agency in an internet-mediated environment. Using James Scott's notion of 'hidden transcripts' and Andrew Feenberg's 'democratic rationalization of technology', the paper explores strategic approaches and historical, social, and political conditions embedded in the construction, negotiation, and transformation of indigenous online activist media. In-depth interview...
Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.
Transdifferentiation of an individual's own cells into functional differentiated cells to replace an organ's lost function would be a personalized approach to therapeutics. In this two part series, we will describe the progress toward establishing functional transdifferentiated adrenal cortical cells. In this article (Part 1), we describe adrenal development and function, and discuss genes involved in these processess and selected for use in our pilot studies of transdifferentiation that are presented in the second article (Part 2).
Two aspects of the chromatin repeat length (r_l) are discussed: (i) Why is r_l longer for slowly dividing cells than in rapidly dividing cells?, and (ii) Why is the temporal evolution of r_l a decreasing function of time (t) in mammalian cortical neurons whereas it is an increasing function of t for granule cells around the time of birth? These questions are discussed in terms of a hypothesis which assumes a correlation between deoxyribonucleic acid (DNA) packaging, transcription, and replication. (author). 27 refs.
The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline ...
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus (JCV), a human papovavirus. PML is a relatively rare disease seen predominantly in immunocompromised individuals and is a frequent complication observed in AIDS patients. The significantly higher incidence of PML in AIDS patients than in other immunosuppressive disorders has suggested that the presence of human immunodeficiency virus type 1 (HIV-1) in the brain may directly or indirectly contribute to the pathogenesis of this disease. In the present study the authors have examined the expression of the JCV genome in both glial and non-glial cells in the presence of HIV-1 regulatory proteins. They find that the HIV-1-encoded trans-regulatory protein tat increases the basal activity of the JCV late promoter, JCV{sub L}, in glial cells. They conclude that the presence of the HIV-1-encoded tat protein may positively ...
Atomic Energy Regulatory Board carries out the regulatory review of the reactor physics design, commissioning and operational aspects through Project Design Safety Committee and Specialist Group of reactor physicists with wide experience in the design, commissioning and operational safety review of NPPs. TAPP-3 and 4 PHWRs, being the first indigenous design of 540 MWe Units, are quite different than the standard 220 MWe PHWRs. The safety review of reactor physics design was quite complex, as majority of the systems were new. The Reactor Physics Specialist Group carried out extensive safety review of 540 MWe PHWR reactor physics design and made significant contributions of design modifications and improvements in the operational procedures. Some salient contributions include: Monitoring the core during bulk addition of moderator without the availability of shutdown systems. Logics for providing safety cover in case of malfunction of SDS-1, Use ...
Regulatory genes called small RNAs (sRNAs) are known to play critical roles in cellular responses to changing environments. For several sRNAs, regulation is effected by coupled stoichiometric degradation with messenger RNAs (mRNAs). The nonlinearity inherent in this regulatory scheme indicates that exact analytical solutions for the corresponding stochastic models are intractable. Here, we present a variational approach to analyze a well-studied stochastic model for regulation by sRNAs via coupled degradation. The proposed approach is efficient and provides accurate estimates of mean mRNA levels as well as higher order terms. Results from the variational ansatz are in excellent agreement with data from stochastic simulations for a wide range of parameters, including regions of parameter space where mean-field approaches break down. The proposed approach can be applied to quantitatively model stochastic gene expression in complex ...
The Regulatory Agenda is a semiannual compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and of all petitions for rulemaking that the NRC has received that are pending disposition. The agenda consists of two sections that have been updated through June 30, 1997. Section 1, ``Rules,`` includes (A) rules on which final action has been taken since December 31, 1996, the closing date of the last NRC Regulatory Agenda; (B) rules published previously as proposed rules on which the Commission has not taken final action; (C) rules published as advance notices of proposed rulemaking for which neither a proposed nor final rule has been issued; and (D) unpublished rules on which the NRC expects to take action. Section 2, ``Petitions for Rulemaking,`` includes (A) petitions denied or incorporated into final rules since December 31, 1996; (B) petitions incorporated into proposed rules; ...
Vascular endothelial growth factor (VEGF) is a mitogen that is critically involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and how transcription factors participate in the regulation of vegf gene expression are not fully understood. Here we report the cloning and sequencing of the zebrafish vegf promoter which revealed that the promoter contains a number of bone morphogenetic protein (BMP)-activated Smad binding elements (SBE), implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf. Electrophoretic mobility shift assays of adding recombinant Smad proteins to the SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf promoter resulted in mobility shift of the oligonucleotides. These changes demonstrate potential interactions between Smad1/5 and the vegf promoter. Reporter activity assays using the wild-type or SBE-deleted vegf promoters to drive the luciferase reporter gene expression revealed ...
Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression level, BGH3 was induced by TGF-{beta}1, but calponin 3 was not significantly regulated by mechanical strain or TGF-{beta}1, ...
HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration into the Sfpi1 locus activates the myeloid ...
Neuronal transcription factors play vital roles in the specification and development of neurons, including dopaminergic (DA) neurons. Mutations in the gene encoding the purine biosynthetic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause the resulting intractable and largely untreatable neurological impairment of Lesch-Nyhan disease (LND). The disorder is associated with a defect in basal ganglia DA pathways. The mechanisms connecting the purine metabolic defect and the central nervous system (CNS) phenotype are poorly understood but have been presumed to reflect a developmental defect of DA neurons. We have examined the effect of HPRT deficiency on the differentiation of neurons in the well-established human (NT2) embryonic carcinoma neurogenesis model. We have used a retrovirus expressing a small hairpin RNA (shRNA) to knock down HPRT gene expression and have examined the expression of a number of transcription factors ...
In 1993 the Government of Armenia made a decision to restart Armenian Nuclear Power Plant (ANPP) which was shutdown in 1989. Shortly after that decision Armenian Nuclear Regulatory Authority (ANRA) was established. Absence of local technical support and limited international support created difficulties for new established ANAR during its activities on regulating ANPP modernization process and issuing authorization for restart. Necessity to establish TSO occurred at this stage. By initiative of ANRA a small TSO was established in 2002 with limited staff called Nuclear and Radiation Safety Centre (NRSC). This paper briefly describes the establishment, development and the current activities and problems of NRSC. (author)
This report summarizes a public workshop that was held on April 27, 1999, in Rockville, Maryland. The workshop was conducted as part of the US Nuclear Regulatory Commission's (NRC) efforts to further develop its understanding of the risks associated with low power and shutdown operations at US nuclear power plants. A sufficient understanding of such risks is required to support decision-making for risk-informed regulation, in particular Regulatory Guide 1.174, and the development of a consensus standard. During the workshop the NRC staff discussed and requested feedback from the public (including representatives of the nuclear industry, state governments, consultants, private industry, and the media) on the risk associated with low-power and shutdown operations.
This is the seventh report by the Advisory Committee on Reactor Safeguards (ACRS) in response to the Congressional requirement for an annual report on the Nuclear Regulatory Commission (NRC) Reactor Safety Research Program. As previously requested by the Congress, the timing of this report has been adjusted to enable the ACRS to address the proposed budget for FY 1985 that has been submitted to the Congress by the President. Part I is a compilation of our comments and recommendations regarding the NRC Safety Research Program budget for FY 1985. It is intended to serve as an Executive Summary. Part II is divided into eight chapters, each of which represents a Decision Unit of the NRC research program. In each chapter, specific comments are included on the research involved in the Decision Unit, an assessment of priorities, and recommendations regarding new directions and levels of funding.
This is the sixth report by the Advisory Committee on Reactor Safeguards (ACRS) that has been prepared in response to the Congressional requirement for an annual report on the Nuclear Regulatory Commission (NRC) Reactor Safety Research Program. Part I is a compilation of our general comments and recommendations regarding the NRC Safety Research Program, and includes budget recommendations and an identification of matters of special importance that deserve increased emphasis. It is intended to serve as an Executive Summary. Part II is divided into ten chapters, each of which represents a Decision Unit of the NRC research program. In each chapter, specific comments are included on the research involved in the Decision Unit, an assessment of priorities, and recommendations regarding new directions and levels of funding.
The author investigates whether the international law regime so far has developed any legal principles dealing with the problem of the dumping of radioactive waste in the sub-seabed, and whether any of such provisions available adequately tackle the problem in the light of the gravity of danger emanating from radioactive waste. The study covers over 30 different texts of international treaties and protocols. Points of main interest are the London Dumping Convention and the Montego Bay Convention on the Law of the Sea. The author concludes that the disposal of radioactive waste into the seabed belongs to the permissible, although not specially allowed activities within the framework of the freedom of the high seas, and therefore urgently calls for establishing an international regulatory system pertaining to the planning and accomplishment of such activities. An outline legal concept of a regulatory system is explained. (orig./HSCH).
Radioactive waste for legal and regulatory purposes may be defined as material that contains or is contaminated with radio-nuclides at concentrations or activities greater than clearance levels as established by the regulatory body, and for which no use is foreseen. Safe management of radioactive waste is essential to ensure protection of humans and environment. Radioactive waste management policy is a guideline for the safe management of radioactive waste. It expresses the commitment of the country towards the goal. Government should initiate investigation into best long-term option for management of spent nuclear fuels. Process of selecting option and eventual site should involve comprehensive public participation within set time frames (with deep geological disposal as preferred management option).
This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the complex, tissue-specific expression and regulation observed in vivo. The expression of the tissue renin-angiotensin systems, which may have important physiological functions, is also described. In addition, the pathway of renin biosynthesis and secretion is reviewed. This includes speculation on the fate of circulating prorenin and the physiological role of multiple renin forms and secretory pathways. The molecular approaches described in this paper have greatly advanced our knowledge of the biology of the renin-angiotensin system. Future studies using these and other approaches should provide further insight into this complex system.
The Seabed Disposal Project (SDP) was evaluating the technical feasibility of high-level nuclear waste disposal in deep ocean sediments. Working standards were needed for risk assessments, evaluation of alternative designs, sensitivity studies, and conceptual design guidelines. This report completes a three part program to develop radiological standards for the feasibility phase of the SDP. The characteristics of subseabed disposal and how they affect the selection of standards are discussed. General radiological protection standards are reviewed, along with some new methods, and a systematic approach to developing standards is presented. The selected interim radiological standards for the SDP and the reasons for their selection are given. These standards have no legal or regulatory status and will be replaced or modified by regulatory agencies if subseabed disposal is implemented. 56 refs., 29 figs., 15 tabs.
SMART (System-Integrated Modular Advanced Reactor) is a first-of-the-kind integral reactor with 330 MW thermal power under active development by Korea Atomic Energy Research Institute (KAERI) for power generation and seawater desalination. SMART employs various design features that are not typically found in other nuclear power plants. Examples include a unique passive residual heat removal system (PRHRS), and enclosure of a pressurizer, eight helical steam generators, and eight canned reactor coolant pumps inside the reactor pressure vessel. This paper presents risk insights on the SMART reactor gained during the development of a regulatory PSA model by Korea Institute of Nuclear Safety (KINS)
Introduction: Haploidentical transplantation, with extensive T cell depletion to prevent GvHD, is associated with a high incidence of infection-related deaths. The key challenge is to improve immune recovery with allogeneic donor T cells without triggering GvHD. As T regulatory cells (Tregs) controlled GvHD in pre-clinical studies, the present study evaluated the impact of an infusion of donor CD4/CD25 + Tregs, followed by an inoculum of donor mature T cells (Tcons) and positively immunoselected CD34 + cells in the setting of haploidentical stem cell transplantation. Patients and methods: Twenty-eight patients were enrolled in this study (22 AML; 5 ALL; 1 NHL). All received immunoselected Tregs (CliniMACS, Miltenyi Biotec) followed by positively immunoselected CD34 + cells together with Tc...
Internationally, on-line maintenance (OLM) of nuclear power plants under the operation is prevailed to enhance nuclear safety and economics. In recent years, Korea Hydro and Nuclear Power Co. Ltd. (KHNP) is eager to apply OLM. Ministry of Education, Science and Technology (MEST) has established the related technology development program as an item of 'Overall Planning on Nuclear Safety(2010-2014)' through acceptance to the request of KHNP in 2009. OLM is defined as maintenance that is performed with the main generator connected to the grid. In other words, it means a preventive maintenance to be implemented during the allowable outage time (AOT) with ignoring inoperability of safety-related equipment listed in the technical specifications. The Korea Institute of Nuclear Safety (KINS) is developing the assessment technology of safety concerns for OLM under the auspices of MEST. Draft regulatory rule-making for OLM is devised as a part of the development of the ...
The need for efficient management of industrial chemical wastes, especially those considered hazardous or radioactive, is receiving increased attention in the United States. During the past five years, several federal laws have addressed the establishment of stronger programs for the control of hazardous and residual wastes. At a facility such as Oak Ridge National Laboratory (ORNL), an efficient waste management program is an absolute necessity to ensure protection of human health and compliance with regulatory requirements addressing the treatment and disposal of hazardous, nonhazardous, and radioactive wastes. This report highlights the major regulatory requirements under which the Laboratory must operate and their impact on ORNL facilities. Individual waste streams, estimates of quantities of waste, and current waste management operations are discussed.
Research and bioethical policies are increasingly seen to facilitate, rather than to impede, scientific progress. Bioethical structures, nonetheless, often fail to account for or to shape the specific social surrounds in which scientific research is conducted. In Taiwan, a perceived shortage in human biological donations threatens to hamper stem cell research progress. This paper considers the stalled national biobank project and the lack of a reliable embryo supply for stem cell research, and suggests that one must look beyond regulatory structures in seeking explanations for such shortages. Specific aspects of Taiwan's democratization and social changes combine with problematic relations between patients and physicians to shape the terrain upon which human biologicals are given or withhe...
Abstract Objective. Anti-TNF-a antibodies has been suggested to modulate regulatory T cell (Treg) percentages in rheumatoid arthritis, but results from studies of Crohn's disease (CD) are conflicting. We investigated dynamic changes of circulating Tregs in CD during treatment with the anti-TNF-a-antibody adalimumab (Humira, Abbott Laboratories A/S, Emdrupvej 28C, DK-2100 Copenhagen). Material and methods. Blood samples from 26 CD patients were analysed using flow cytometry before and 1 and 26 weeks after initiation of adalimumab treatment to determine the percentage of Tregs among CD4++ T cells. Results. In spite of a significant decline in disease activity scores and biochemical markers of inflammation, during the first week of treatment, we did not observe early modulating effects of ada...
Various initiatives have been undertaken by the Federal Energy Regulatory Commission (FERC) to deregulate wholesale electric energy markets. These initiatives have focused on restructuring the transmission systems in the US and recently have culminated in a proposal requiring formation of and participation in regional transmission organizations. The overall form of regulation selected to determine rates for transmission entities as well as underlying regulatory decisions reached on key issues will have profound implications for transmission entities. For example, traditional cost-based regulation would require one set of accounting and reporting rules, while incentive-based regulation may not be subject to those same rules. An overview of some of the major accounting and financial reporting issues that will need to be considered is presented.
Previous studies have been conducted in gene expression profiling to identify groups of genes that characterize the colorectal carcinoma disease. Despite the success of previous attempts to identify...Full Text Available
This plan details the methods and procedures necessary to ensure a safe transition in the operation of the Light Duty Utility Arm (LDUA) System. The steps identified here outline the work scope and identify responsibilities to complete startup, and turnover of the LDUA to Characterization Project Operations (CPO).
While genomic alterations identified in human tumors using techniques such as comparative genomic hybridisation (CGH) may be recurrent, they frequently encompass large regions, in some cases...Full Text Available
The development of a computational intelligent tools based on neural network to identify commercial losses or fraud (theft energy), considering information from a database electric utility, is presented.
A method to identify hadronic molecules in the particle spectrum is reviewed and the conditions for its applicability discussed. Special emphasis is put on the discussion of molecule candidates in the baryon spectrum. (orig.)
Descriptive assessment methods have been used in applied settings to identify consequences for problem behavior, thereby aiding in the design of effective treatment programs. Consensus has not been...Full Text Available
Cancers are highly heterogeneous and contain many passenger and driver mutations. To functionally identify tumor suppressor genes relevant to human cancer, we compiled pools of short harpin...Full Text Available
Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified...Full Text Available
...dates of the implementation of the standard unique health identifier for health care providers. 162.404 Section 162.404 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA...
Protection of wetlands became a national issue in 1988 when President George Bush pledged no net loss of wetlands in the US under his [open quotes]environmental presidency.[close quotes] As wetlands became a national issue, the job of protecting them became an obligation for many groups, including hydro-power developers. Now, when a site selected for development includes an area that may be classified as a wetland, the developer quickly discovers the importance of recognizing and protecting these natural habitats. Federal legislation severely limits development of wetland, and most states increase the restrictions with their own wetlands regulations. The difficulty of defining wetlands complicates federal and state enforcement. Land that appears to be dry may in fact be classified as a wetland. So, even if a site appears dry, potential hydro developers must confirm whether or not any jurisdictional wetlands are present. Regulated lands include much more than marshes and swamps. Further ...
A series of questions and answers addresses issues related to developing synthetic fuels, including the potential supplies, regulatory road blocks, and development incentives to promote the role of the private sector. Chevron's efforts in the area of synfuels are aimed at shale oil tar sands and coal conversion. The status of these research and development projects and the projected recoverable reserves from each are summarized. (DCK)
In this study, for the institutionalization of risk informed and performance based regulation in Korea, the latest technical movements of overseas countries are examined and reviewed. And the issues that was found when license change petition using risk information was submitted in Korean regulatory body are reviewed. Based on these review, the applicable areas to domestic situation will be found and proposed. This study can contribute to setting up the proper direction for the institutionalization of risk informed and performance based regulation
In this study, for the institutionalization of risk informed and performance based regulation in Korea, the latest technical movements of overseas countries are examined and reviewed. And the issues that was found when license change petition using risk information was submitted in Korean regulatory body are reviewed. Based on these review, the applicable areas to domestic situation will be found and proposed. This study can contribute to setting up the proper direction for the institutionalization of risk informed and performance based regulation.
In 1991 the Federal Energy Regulatory Commission (FERC) continued it efforts to restructure the electric utility industry, emphasizing market-based pricing of wholesale power transactions and transmission access and pricing. Other issues covered in this report include pricing and policy initiatives, filing procedures, the generic rate of return on common equity, the price squeeze, contract interpretation, and legislative developments.
This report includes the issuances received during the specified period from the Commission (CLI), the Atomic Safety and Licensing Appeal Boards (ALAB), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judge (ALJ), the Directors' Decisions (DD), and the Denials of Petitions For Rulemaking (DPRM).
This report includes the issuances received during November, 1983, from the Commission (CLI), the Atomic Safety and Licensing Appeal Boards (ALAB), the Atomic Safety and Licensing Boards (LBP), the Administrative Law Judge (ALJ), the Directors' Decisions (DD), and the Denials of Petitions for Rulemaking (DPRM).
We have isolated a human thrombomodulin cDNA, and a human genomic clone containing the putative promoter domain, as well as the translated and untranslated regions of the endothelial cell receptor....Full Text Available
Backgroundβ2-Adrenergic receptors (β2AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic...Full Text Available
The Sacramento Municipal Utility District is developing a number of demonstration projects using geothermal heat pumps. This paper discusses some of the barriers and issues that have emerged over the past two years. The most important barriers are: regulatory impediments; high first cost; and a lack of local design and installation infrastructure.
The Department of Energy has used its seldom-used statutory authority and filed comments with the Federal Energy Regulatory Commission urging support for Public Service Company of Indiana's request that the FERC allow it to sell up to 450 megawatts of firm power to eligible wholesale purchasers at negotiated or market-based rates in exchange for open transmission access for other generators.
BackgroundAberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role...Full Text Available