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
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
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
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
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
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
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
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
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 ...
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 transcriptionaltarget 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 ...
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.
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
Sterol regulatory element-binding protein (SREBP)-1 is a keytranscription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic...Full Text Available
Hepatocyte nuclear factor (HNF) 4α is a keytranscription factor regulating endo/xenobiotic-metabolizing enzymes and transporters. We investigated whether microRNAs are involved in the regulation...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 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
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...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 ...
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
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 ...
SummarySoluble epoxide hydrolase (sEH) is a key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). Genetic variations...Full Text Available
Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation....Full Text Available
Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis....Full Text Available
Given the high prevalence of overweight and low levels of physical activity among children, a better understanding of physical activity behaviour is an important step in intervention planning. This...Full Text Available
Recently, we demonstrated that the central ghrelin signalling system, involving the ghrelin receptor (GHS-R1A), is important for alcohol reinforcement. Ghrelin targets a key mesolimbic circuit involved...Full Text Available
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 ...
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 ...
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 NREL Sensitized Solar Cell (SSC) Core Program supports the Solar America Initiative by: (1) targeting new devices and processes for commercialization by 2015 that are less expensive, more efficient, highly reliable, and environmentally benign; (2) collaborating with DOE OS/BES to conduct basic research targeting breakthroughs in key areas, such as ultra-high efficiency and/or ultra-low cost materials and devices.
The UK government's economy-wide 60% carbon dioxide reduction target by 2050 requires a paradigm shift in the whole energy system. Numerous analytical studies have concluded that the power sector is a critical contributor to a low carbon energy system, and electricity generation has dominated the policy discussion on UK decarbonisation scenarios. However, range of technical, social and market challenges, combined with alternate market investment strategies mean that large scale deployment of key classes of low carbon electricity technologies is fraught with uncertainty. The UK MARKAL energy systems model has been used to investigate these long-term uncertainties in key electricity generation options. A range of power sector specific parametric sensitivities have been performed under a 'what-if' framework to provide a systematic exploration of least-cost energy system configurations under a broad, ...
The UK government's economy-wide 60% carbon dioxide reduction target by 2050 requires a paradigm shift in the whole energy system. Numerous analytical studies have concluded that the power sector is a critical contributor to a low carbon energy system, and electricity generation has dominated the policy discussion on UK decarbonisation scenarios. However, range of technical, social and market challenges, combined with alternate market investment strategies mean that large scale deployment of key classes of low carbon electricity technologies is fraught with uncertainty. The UK MARKAL energy systems model has been used to investigate these long-term uncertainties in key electricity generation options. A range of power sector specific parametric sensitivities have been performed under a 'what-if' framework to provide a systematic exploration of least-cost energy system configurations under a broad, integrated set of input ...
The thymus is a key organ of the immune system in most vertebrates and, for this reason, it has been used in this paper for the generation of a normalized cDNA library from sea bass (Dicentrarchus labrax), one of the most extensively cultured species in South Mediterranean aquaculture. A total of 1632 ESTs from this library were initially analysed for sequence quality and vector sequences and, after this control, 1264 (77% of total clones sequenced) high-quality ESTs were further processed. The total collection of D. labrax thymus ESTs has been deposited in the EBI-GenBank-DBJ database (GenBank accession numbers from FN565576 to FN566839). The functional classification of ESTs was performed by Gene Ontology and KEGG annotation and, successively, the sequences were analysed using the Immuno...
Abstract Plant pathogenic bacteria of the genus Xanthomonas cause a variety of diseases in economically important monocotyledonous and dicotyledonous crop plants worldwide. Successful infection and bacterial multiplication in the host tissue often depend on the virulence factors secreted including adhesins, polysaccharides, LPS and degradative enzymes. One of the key pathogenicity factors is the type III secretion system, which injects effector proteins into the host cell cytosol to manipulate plant cellular processes such as basal defense to the benefit of the pathogen. The coordinated expression of bacterial virulence factors is orchestrated by quorum-sensing pathways, multiple two-component systems and transcriptional regulators such as Clp, Zur, FhrR, HrpX and HpaR. Furthermore, virule...
Recently, we cloned purpurin cDNA as an upregulated gene in the axotomized fish retina. The retina-specific protein was secreted from photoreceptors to ganglion cell layer during an early stage of optic nerve regeneration in zebrafish retina. The purpurin worked as a trigger molecule for axonal regrowth in adult injured fish retina. During zebrafish development, purpurin mRNA first appeared in ventral retina at 2 days post-fertilization (dpf) and spread out to the outer nuclear layer at 3 dpf. Here, we investigated the role of purpurin for zebrafish retinal development using morpholino gene knockdown technique. Injection of purpurin morpholino into the 1-2 cell stage of embryos significantly inhibited the transcriptional and translational expression of purpurin at 3 dpf. In the purpurin mo...
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...
The molecular environment of the key subdomain IIId of the internal ribosome entry site (IRES) element of hepatitis C virus (HCV) RNA in the binary complex with the human 40S ribosomal subunit was studied. To this end, HCV IRES derivatives bearing perfluorophenylazido groups activatable by mild UV at nucleotides G263 or A275 in the subdomain IIId stem were used. They were prepared by the complementary addressed modification of the corresponding RNA transcript with alkylating oligodeoxyribonucleotide derivatives. None of the RNA derivatives were shown to be crosslinked to the 18S rRNA. It was found that the photoreactive groups of the IRES G263 and A275 nucleotides are crosslinked to ribosomal proteins S3a, S14, and S16. For the IRES derivative with the photoreactive group in nucleotide G26...
A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...
... Targeted fields of research Continuation of ongoing research - Finalising detailed design work on the ITER project; getting JET operational at full power; Improvement of the basic concepts of fusion devices - Fusion plasmas; theoretical studies; technology watch on research into inertial confinement; new experimental concepts and systems; etc.; Long-term technology - Preparations for building a demonstration reactor (development of tritium breeding blankets; prospective ...
BackgroundMicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as...Full Text Available
Smooth muscle cell (SMC) proliferation and migration are key processes that occur in the pathogenesis of atherosclerosis and post-angioplasty restenosis. In the present study, we designed locked nucleic...Full Text Available
Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of lysine and arginine ...
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 ...
In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone ...
This paper outlines an approach to develop estimates of individual customer contestability using a combined statistical and engineering analysis. The approach is targeted for use for mid-size commercial and industrial customers who are not being considered for individual flexible pricing contracts. Contestability is defined as the potential lost revenue associated with customers leaving the utility or significantly reducing electricity purchases. Contestability is modeled from the customer`s perspective using a two-stage decision process. In the first stage, the customer decides if he will continue to purchase electricity from the utility (referred to as customer retention), and in the second stage, the customer determines the amount of electricity purchased (referred to as load retention). Measures of individual customer contestability will be key factors in developing market segments and new rate offerings in future energy markets.
Aims A depressed cGMP-dependent protein kinase (PKG) activity is implicated in nitrate tolerance. The present study determines whether the leucine zipper-positive (LZ+) isoform of myosin phosphatase target subunit 1 (MYPT1), a keytarget protein for PKG actions, is involved in the development of nitrate tolerance. Methods and results Nitrate tolerance in in vitro preparations was obtained by a 24 h incubation with nitroglycerin (NTG). Nitrate tolerance in in vivo preparations was obtained by subcutaneous injection of mice with NTG, and the aortas were used. Protein levels of total MYPT1, MYPT1 (LZ+), PP1Cd, myosin light chain (MLC), and phosphorylated MLC were determined by Western blot analysis. Isometric vessel tension was determined by an organ chamber technique. Protein levels of MYPT1...
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
The purpose of this study is to extend the knowledge base for wetland treatment to include processes and substances of particular importance to small, on-site systems receiving oil and gas well waste water. Collection of data on the sorption of heavy metals and the degradation of toxic organics is one of the key tasks. The toxic organics phenolics and anthracene, and chromium and copper have been selected as target adsorbates. An information search was performed on oil refinery waste treatment wetland systems.
Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...
In June 2009, the State of Hawaii enacted an Energy Efficiency Portfolio Standard (EEPS) with a target of 4,300 gigawatt hours (GWh) by 2030 (Hawaii 2009). Upon setting this goal, the Hawaii Clean Energy Initiative, Booz Allen Hamilton (BAH), and the National Renewable Energy Laboratory (NREL), working with select local stakeholders, partnered to execute the first key step toward attaining the EEPS goal: the creation of a high-resolution roadmap outlining key areas of potential electricity savings. This roadmap was divided into two core elements: savings from new construction and savings from existing buildings. BAH focused primarily on the existing building analysis, while NREL focused on new construction forecasting. This report presents the results of the Booz Allen Hamilton study on the existing building stock of Hawaii, along with conclusions on the key drivers of potential energy efficiency ...
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
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 ...
Measurements using radioactive targets are important for the determination of key reaction path ways associated with the synthesis of the elements in nuclear astrophysics (sprocess), advanced fuel cycle initiative (transmutation of radioactive waste), and stockpile stewardship. High precision capture cross-section measurements are needed to interpret observations, predict elemental or isotopical ratios, and unobserved abundances. There are two new detector systems that are presently being commissioned at Los Alamos National Laboratory for very precise measurements of (n,{gamma}) and (n,f) cross-sections using small quantities of radioactive samples. DANCE (Detector for Advanced Neutron-Capture Experiments), a 4 {pi} gamma array made up of 160 BaF{sub 2} detectors, is designed to measure neutron capture cross-sections of unstable nuclei in the low-energy range (thermal to {approx}500 keV). The high granularity and high detection efficiency of ...
We report a search for small RNAs (sRNAs) in the low-GC, gram-positive human pathogen Streptococcus pneumoniae. Based on bioinformatic analyses by Livny et al. (J. Livny, A. Brencic, S. Lory, and M. K. Waldor, Nucleic Acids Res. 34:3484-3493, 2006), we tested 40 candidates by Northern blotting and confirmed the expression of nine new and one previously reported (CcnA) sRNAs in strain D39. CcnA is one of five redundant sRNAs reported by Halfmann et al. (A. Halfmann, M. Kovacs, R. Hakenbeck, and R. Bruckner, Mol. Microbiol. 66:110-126, 2007) that are positively controlled by the CiaR response regulator. We characterized 3 of these 14 sRNAs: Spd-sr17 (144 nucleotides [nt]; decreased in stationary phase), Spd-sr37 (80 nt; strongly expressed in all growth phases), and CcnA (93 nt; induced by competence stimulatory peptide). Spd-sr17 and CcnA likely fold into structures containing single-stranded regions between hairpin structures, whereas Spd-sr37 forms a base-paired structure. Primer ...
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
Two candidate small interfering RNAs (siRNAs) corresponding to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene. The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing reporter, was transfected with siRNAs into HEK 293T cells. At various time points of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA transcript were detected by fluorescence microscopy, flow cytometry, Western blot, and real-time quantitative PCR, respectively. The results showed that the cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher level compared with those transfected with pEGFP-S, which contains wildtype SARS-CoV spike gene sequence. The green fluorescence, mean fluorescence intensity, and ...
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 uncoupling protein (UCP) is a proton/anion transporter found in the inner mitochondrial membrane of brown adipocyte. Although UCP has nor been detected in mitochondria from any other tissue, it shares structural and catalytic properties with several other mitochondrial carrier proteins. Although UCP was discovered only recently it is one of the most extensively studied mitochondrial carrier proteins.More recently, the mouse, rat, and human genes encoding for UCP have been isolated and sequenced. The availability of these various tools has led to several significant observations. UCP gene expression is strongly controlled at the level of transcription by signals that are activated after the stimulation of brown adipocytes by norepinephrine. The comparison of UCP gene with the genes encoding the adenine nucleotide translocator revealed the existence of structural and evolutionary homologies. Moreover, in humans the UCP gene and one form of adenine nucleotide ...
RNA interference (RNAi) plays an important role in regulating gene expression in eukaryotes. Previously, we generated Arabidopsis and tobacco plants expressing double-stranded RNA (dsRNA) targeting a cotton bollworm (Helicoverpa armigera) P450 gene, CYP6AE14. Bollworms fed on transgenic dsCYP6AE14 plants showed suppressed CYP6AE14 expression and reduced growth on gossypol-containing diet (Mao et?al., in Nat Biotechnol 25: 1307?1313, 2007). Here we report generation and analysis of dsRNA-expressing cotton (Gossypium hirsutum) plants. Bollworm larvae reared on T2 plants of the ds6-3 line exhibited drastically retarded growth, and the transgenic plants were less damaged by bollworms than the control. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that the CYP6AE1...
Regulation of transcription initiation by RNA polymerase II requires TFIID, a multisubunit complex composed of the TATA binding protein (TBP) and at least seven tightly associated factors (TAFs). Some TAFs act as direct targets or coactivators for promoter-specific activators while others serve as interfaces for TAF-TAF interactions. Here, we report the molecular cloning, expression and characterization of Drosophila dTAFII60 and its human homolog, hTAFII70. Recombinant TAFII60/70 binds weakly to TBP and tightly to the largest subunit of TFIID, TAFII250. In the presence of TAFII60/70, TBP and TAFII250, a stable ternary complex is formed. Both the human and Drosophila proteins directly interact with another TFIID subunit, dTAFII40. Our findings reveal that Drosophila TAFII60 and human TAFII70 share a high degree of structural similarity and that their interactions with other subunits of TFIID are conserved.Images
The National Food and Nutrient Analysis Program (NFNAP) was designed to expand the quantity and improve the quality of data in the United States Department of Agriculture (USDA) food composition databases through the collection and analysis of nationally representative samples of foods and beverages. This paper describes some of the findings from the NFNAP and its impact on the food composition databases produced by USDA. The NFNAP employs statistically valid sampling plans, comprehensive quality control, and USDA analytical oversight to generate new and updated analytical data for food components. USDA food consumption and composition data were used to target those foods that are major contributors of nutrients of public health significance to the U.S. diet (454 Key Foods). Foods were ran...
An enantiocontrolled route to aziridinomitosenes had been developed from l-serine methyl ester hydrochloride. The tetracyclic target ring system was assembled by an internal azomethine ylide cycloaddition reaction based on silver ion-assisted intramolecular oxazole alkylation and cyanide-induced ylide generation via a labile oxazoline intermediate (62 to 66). Other key steps include reductive detritylation of 26, methylation of the N-H aziridine 56, oxidation of the sensitive cyclohexenedione 68 to quinone 70, and carbamoylation using Fmoc-NCO. Although the aziridinomitosene tetracycle is sensitive, a range of protecting group manipulations and redox chemistry can be performed if suitable precautions are taken. A study of DNA alkylation by the first C-6,C-7-unsubstituted aziridinomitosene 11a has been carried out, and evidence for DNA cross-link formation involving nucleophilic addition to the quinone subunit is described. PMID:14677970
Gas nitridation has shown excellent promise to form dense, electrically conductive and corrosion-resistant Cr-nitride surface layers on Ni-Cr base alloys for use as proton exchange membrane fuel cell (PEMFC) bipolar plates. Due to the high cost of nickel, Fe-base bipolar plate alloys are needed to meet the cost targets for many PEMFC applications. Unfortunately, nitridation of Fe-base stainless steel alloys typically leads to internal Cr-nitride precipitation rather than the desired protective surface nitride layer formation, due to the high permeability of nitrogen in these alloys. This paper reports the finding that it is possible to form a continuous, protective Cr-nitride (CrN and Cr2N) surface layer through nitridation of Fe-base stainless steel alloys. The key to form a protective Cr...
In Europe, the use of anti-EGFR monoclonal antibodies is restricted to Kirsten RAS (KRAS) wild-type colorectal tumors. Information on the KRAS status of the patients tumor is thus key for clinical practice; however, there is little guidance or definition on which KRAS mutations to assess and how to assess them. To ensure the consistency and the quality of KRAS test results in Europe, an interlaboratory control network needs to be set up. This pilot study aimed to identify the variables that need to be assessed in a quality control scheme and to provide a first assessment in a selected set of laboratories. Fourteen different tumor cases were circulated between 13 laboratories by a central laboratory acting as the referent for the mutation status determination. This study illustrated that of...
This self-evaluation report offers a summary of results from FY2000 actions to achieve Pacific Northwest National Laboratory's strategy and provides an analysis of the state of their self-assessment process. The result of their integrated planning and assessment process identifies Laboratory strengths and opportunities for improvement. Critical elements of that process are included in this report; namely, a high-level summary of external oversight activities, progress against Operations Improvement Initiatives, and a summary of Laboratory strengths and areas for improvement developed by management from across the laboratory. Some key areas targeted for improvement in FY2001 are: systems approach to resource management; information protection; integrated safety management flow-down to the benchtop; cost management; integrated assessment; Price Anderson Amendments Act (PAAA) Program; and travel risk mitigation.
One proposed solution to the problem of ballast-mediated aquatic invasions involves chemically treating ballast water to kill keytarget organisms. Here, we examine the efficacy of three commercially available ballast water biocides using vegetative microalgae, dinoflagellate resting cysts and bacteria as test organisms. Chemicals tested were the ballast water biocides SeaKleen and Peraclean Ocean, and the chlorine dioxide biocide Vibrex. Results demonstrate that the applicability of each of the three chemical biocides as a routine ballast water treatment is limited by factors such as cost, biological effectiveness and possible residual toxicity of the discharged ballast water (assessed on the basis of impact on motility of vegetative marine microalgae). Of the three biocides tested, Perac...
The entire Electric Power Research Institute (EPRI) cofiring program has been in existence of some 9 years. This report presents a summary of the major elements of that program, focusing upon the following questions: (1) In pursuit of increased use of renewable energy in the US economy, why was electricity generation considered the most promising target, and why was cofiring pursued as the most effective near-term technology to use in broadening the use of biomass within the electricity generating arena? (2) What were the unique accomplishments of EPRI before the development of the Cooperative Agreement, which made developing the partnership with EPRI a highly cost-effective approach for USDOE? (3) What were the key accomplishments of the Cooperative Agreement in the development and execution of test and demonstration programs-accomplishments which significantly furthered the process of commercializing cofiring?
For early-stage firms, successful commercialization of each new product is critically important, given the shortage of financial resources, the limited product portfolio, and small staffs typical of such firms. This paper investigates two key contributing factors for new product success in entrepreneurial firms: designing products that are appealing to target users in both form and function and designing products that can be manufactured at an attractive margin so that the new enterprise can generate much needed positive cash flow. These two practices-industrial design and cost engineering-are well studied in the context of larger, established corporations but have not been explored in the context of new ventures. This study focuses on the intensity of individual and combined adoption of d...
Daylight responsive dimming systems have been used in few buildings to date because they require improvements to improve reliability. The key underlying factor contributing to poor performance is the variability of the ratio of the photosensor signal to daylight workplane illuminance in accordance with sun position, sky condition, and fenestration condition. Therefore, this paper describes the integrated systems between automated roller shade systems and daylight responsive dimming systems with an improved closed-loop proportional control algorithm, and the relative performance of the integrated systems and single systems. The concept of the improved closed-loop proportional control algorithm for the integrated systems is to predict the varying correlation of photosensor signal to daylight workplane illuminance according to roller shade height and sky conditions for improvement of the system accuracy. In this study, the performance of the integrated systems with ...
The feasibility study on conceptual design methodology for accelerator-driven sodium-cooled sub-critical transmutation reactors has been conducted to optimize the design parameters from the scale laws and validates the reactor performance with the integrated code system. A 1000 MWth sodium-cooled sub-critical transmutation reactor has been scaled and verified through the methodology in this paper, which is referred to Advanced Liquid Metal Reactor (ALMR). A Pb-Bi target material and a partitioned fuel are the liquid phases, and they are cooled by the circulation of secondary Pb-Bi coolant and by primary sodium coolant, respectively. Overall key design parameters are generated from the scale laws and they are improved and validated by the integrated code system. Integrated Code System (ICS) consists of LAHET, HMCNP, ORIGEN2, and COMMIX codes and some files. Through ICS the target region, the core region, and ...
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
Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity...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
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 ...
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
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
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
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
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
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
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
A guidance document on the instrumentation for monitoring and control of cycle chemistry for the steam-water circuits of fossil-fired and combined-cycle power plants was developed within the IAPWS Power Cycle Chemistry Working Group. This technical guidance document has been authorized by the International Association for the Properties of Water and Steam (IAPWS) at its meeting in Doorwerth, The Netherlands, 6-11 September, 2009, for issue by its Secretariat. The members of the IAPWS are: Britain and Ireland, Canada, the Czech Republic, Denmark, France, Germany, Greece, Japan, Russia, and the United States of America, and the associate members Argentina and Brazil, Italy, and Switzerland. In order to achieve suitable chemical conditions in steam-water circuits it is essential to establish reliable monitoring of key parameters on every plant. This enables the demonstration of operation within cycle chemistry targets, and alerts the operators to ...
The report presents a long-range plan for a broad-based, coordinated research, development and market transformation program for reducing the lighting energy intensities in commercial and residential buildings in California without compromising lighting quality. An effective program to advance lighting energy efficiency in California must be based on an understanding that lighting is a mature field and the lighting industry has developed many specialized products that meet a wide variety of light needs for different building types. Above all else, the lighting field is diverse and there are applications for a wide range of lighting products, systems, and strategies. Given the range of existing lighting solutions, an effective energy efficient lighting research portfolio must be broad-based and diverse to match the diversity of the lighting market itself. The belief that there is one solution--a magic bullet, such as a better lamp, for example--that will propel lighting efficiency ...
Antisense- or RNAi-mediated suppression of the biosynthesis of nutritionally inferior storage proteins is a promising strategy for improving the amino acid profile of seeds. However, the potential pleiotropic effects of this on interconnected pathways and the agronomic quality traits need to be addressed. In the current study, a transcriptomic analysis of an antisense C-hordein line of barley was performed, using a grain-specific cDNA array. The C-hordein antisense line is characterized by marked changes in storage protein and amino acid profiles, while the seed weight is within the normal range and no external morphological irregularities were observed. The results of the transcriptome analysis showed excellent correlation with data on changes in the relative proportions of storage proteins and amino acid composition. The antisense line had a lower C-hordein level and down-regulated transcript encoding C-hordein. The production of the S-rich B/gamma- and ...
Antisense- or RNAi-mediated suppression of the biosynthesis of nutritionally inferior storage proteins is a promising strategy for improving the amino acid profile of seeds. However, the potential pleiotropic effects of this on interconnected pathways and the agronomic quality traits need to be addressed. In the current study, a transcriptomic analysis of an antisense C-hordein line of barley was performed, using a grain-specific cDNA array. The C-hordein antisense line is characterized by marked changes in storage protein and amino acid profiles, while the seed weight is within the normal range and no external morphological irregularities were observed. The results of the transcriptome analysis showed excellent correlation with data on changes in the relative proportions of storage proteins and amino acid composition. The antisense line had a lower C-hordein level and down-regulated transcript encoding C-hordein. The production of the S-rich B/ - and D-hordeins ...
The most serious challenges in the design of chambers for inertial fusion energy (IFE) are 1) protecting the first wall from fusion energy pulses on the order of several hundred megajoules released in the form of x rays, target debris, and high energy neutrons, and 2) operating the chamber at a pulse repetition rate of 5-10 Hz (i.e., re-establishing, the wall protection and chamber conditions needed for beam propagation to the target between pulses). In meeting these challenges, designers have capitalized on the ability to separate the fusion burn physics from the geometry and environment of the fusion chamber. Most recent conceptual designs use gases or flowing liquids inside the chamber. Thin liquid layers of molten salt or metal and low pressure, high-Z gases can protect the first wall from x rays and target debris, while thick liquid layers have the added benefit of protecting structures from fusion neutrons thereby ...
Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, primitive neuroectodermal ...
This Progress Report describes the operation of the Los Alamos Meson Physics Facility (LAMPF) and the research programs carried out there for the years 1992 and 1993. The accelerator operated for over 100 days in 1992, providing beams of H{sup +}, H{sup {minus}}, and polarized H{sup {minus}} for a rich and varied research program in nuclear physics. The accelerator had only fair beam availability in 1992 (for example, the average H{sup +} beam availability was 72%), caused largely by problems in the 201-MHz rf system. A major effort was expended to address these problems before the 1993 run. These efforts were rewarded by good beam availability in 1993 and few problems with the 201-MHz system. LAMPF operated remarkably smoothly during 1993, in the midst of a period of great uncertainty in the future of the facility and the downsizing of MP Division, which led to the loss of a large number of key people to positions elsewhere in the Laboratory. The H{sup +} ...
The concept of nanocrystal conversion chemistry, which involves the use of pre-formed nanoparticles as templates for chemical transformation into derivative solids, has emerged as a powerful approach for designing the synthesis of complex nanocrystalline solids. The general strategy exploits established synthetic capabilities in simple nanocrystal systems and uses these nanocrystals as templates that help to define the composition, crystal structure, and morphology of product nanocrystals. This article highlights key examples of 'conversion chemistry' approaches to the synthesis of nanocrystalline solids using a variety of techniques, including galvanic replacement, diffusion, oxidation, and ion exchange. The discussion is organized according to classes of solids, highlighting the diverse target systems that are accessible using similar chemical concepts: metals, oxides, chalcogenides, phosphides, alloys, intermetallic compounds, sulfides, and ...
The purpose of this project is to demonstrate targeted infill and extension drilling opportunities, better determinations of oil-in-place, methods for improved completion efficiency and the suitability of waterflooding in certain shallow-shelf carbonate reservoirs in the Williston Basin, Montana, North Dakota and South Dakota. Cores from five Red River wells in the Bowman-Harding study area have been examined and described in detail; contracts have been awarded for a 3-D survey in Bowman Co., ND and a 2D, multi-component survey in Richland Co.; extended-time pressure buildup data have been analyzed from two wells which are candidates for jetting-lance completion workovers; a 20-day injectivity test has been completed in the Red River (upper member); a jetting-lance completion program has commenced with one job completed and three more scheduled during April; and reservoir data from three key Red River fields in the Bowman-Harding study area has ...
Anti-proton and positron Galactic cosmic ray (GCR) spectra are among the keytargets for indirect detection of dark matter (DM). The boost factors, corresponding to an enhancement of the signal|linked to the clumpiness properties of the dark matter distribution|, have been taken as high as thousands in the past. The dramatic impact of these boost factors for indirect detection of antiparticles, for instance with the PAMELA satellite or the coming AMS-02 experiment, asks for their detailed calculation. We take into account the state-of-the-art results of high resolution N-body dark matter simulations to calculate the most likely energy dependent boost factors|linked to the GCR propagation properties|, for anti-protons and positrons. The results from extreme, but still possible, configurations of the clumpy dark matter component is also discussed. Starting from the mass and space distributions of sub-halos, the anti-proton and positron ...
Elevated nuclear factor kappa B (NF-@kB) activity and interleukin-6 (IL-6) secretion participates in the pathology of several age and inflammatory-related diseases, including age-related macular degeneration (AMD), in which retinal pigment epithelial cells are the keytarget. Recent findings reveal that heat shock protein 70 (Hsp70) may affect regulation of NF-@kB. In the current study, effects of Hsp70 expression on NF-@kB RelA/p65 activity were evaluated in human retinal pigment epithelial cells (ARPE-19) by using celastrol, a novel anti-inflammatory compound. Anti-inflammatory properties of celastrol were determined by measuring expression levels of IL-6 and endogenous NF-@kB levels during lipopolysaccharide (LPS) exposure by using enzyme-linked immunosorbent assays (ELISA). Cell viabil...
As part of efforts to develop improved methods for NMR protein sample preparation and structure determination, the Northeast Structural Genomics Consortium (NESG) has implemented an NMR screening pipeline for protein target selection, construct optimization, and buffer optimization, incorporating efficient microscale NMR screening of proteins using a micro-cryoprobe. The process is feasible because the newest generation probe requires only small amounts of protein, typically 30-200 ?g in 8-35 ?l volume. Extensive automation has been made possible by the combination of database tools, mechanization of key process steps, and the use of a micro-cryoprobe that gives excellent data while requiring little optimization and manual setup. In this perspective, we describe the overall process used by the NESG for screening NMR samples as part of a sample optimization process, assessing optimal construct design and solution conditions, as well as for ...
This dissertation describes a measurement of the rate ofnuclear muon capture by the proton, performed by the MuCap Collaborationusing a new technique based on a time projection chamber operating inultraclean, deuterium-depleted hydrogen gas at room temperature and 1 MPapressure. The hydrogen target's low gas density of 1 percent compared toliquid hydrogen is key to avoiding uncertainties that arise from theformation of muonic molecules. The capture rate was obtained from thedifference between the mu- disappearance rate in hydrogen--as determinedfrom data collected in the experiment's first physics run in fall2004--and the world averagefor the mu+ decay rate. After combining theresults of my analysis with the results from another independent analysisof the 2004 data, the muon capture rate from the hyperfine singlet groundstate of the mu-p atom is found to be Lambda_S = 725.0 +- 17.4 1/s, fromwhich the induced pseudoscalar ...
An uncertainty decrease is an very important issue for enhancing risk-informed (RI) activities worldwide. Especially, a relatively large uncertainty in a level-2 (L2) PSA risk compared with level-1 internal PSA risk has been a bottleneck problem in the RI application to the extent of a severe accident management. According to the ASME PRA standard in which sources of an uncertainty to capture a category-II RI (= Option 2) capability are listed, an uncertainty analysis which identifies the key sources of an uncertainty and includes sensitivity studies for dominant contributors to LERF (Large Early Release Frequency) needs to be provided. To solve these problems, USNRC have developed the 'SPAR-LERF' model related to the L2 RI application and 'L2 uncertainty assessment and improvement' work is being taken as a main PSA2 topic of the SARNET (Severe Accident Research Network of Excellence) program in Europe by OECD/NEA. Domestically, a mid/long-term R and D is being ...
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
Based on the IAPWS technical guidance on ''Instrumentation for Monitoring and Control of Cycle Chemistry for Steam-Water Circuits of Fossil-Fired and Combined Cycle Power Plants,'' the latest situation regarding instrumentation for nuclear power plants is discussed. As a result of the discussion, it is concluded that: (1) Reliable and safe operation of plants is established by the application of suitable chemical conditions in plant cooling systems, which should be supported by the selection of suitable control targets for monitoring and by the application of reliable instruments. (2) The minimum level of key instrumentation consists of on-line as well as off-line instruments for monitoring the key parameters: - on-line: pH, conductivity, cation conductivity, O{sub 2} and H{sub 2} concentrations, electrochemical corrosion potential; - off-line: radioactive nuclides ({sup 60}Co, {sup ...
Economics may one day dictate that it makes sense to replace oil or natural gas with coal in boilers that were originally designed to burn oil or gas. In recognition of this future possibility, Pittsburgh Energy Technical Center (PETC) has supported a program led by ABB Power Plant Laboratories in cooperation with the Energy and Fuels Research Center of Penn State University to develop the High Efficiency Advanced Coal Combustor (HEACC). The objective of the program is to demonstrate the technical and economic feasibility of retrofitting a gas/oil designed boiler to burn micronized coal. In support of the overall objective the following specific areas were targeted: a coal handling/preparation system that can meet the technical requirements for retrofitting microfine coal on a boiler designed for burning oil or natural gas; maintaining boiler thermal performance in accordance with specifications when burning oil or natural gas; maintaining NOx emissions at or below ...
The performance of a convolution/superposition based treatment planning system depends on the ability of the dose calculation algorithm to accurately account for physical interactions taking place in the tissue, key components of the linac head and on the accuracy of the photon beam model. Generally the user has little or no control over the performance of the dose calculation algorithm but is responsible for the accuracy of the beam model within the constraints imposed by the system. This study explores the dosimetric impact of limitations in photon beam modeling accuracy on complex 3D clinical treatment plans. A total of 70 photon beam models was created in the Pinnacle(TM) treatment planning system. Two of the models served as references for 6 MV and 15 MV beams, while the rest were created by perturbing the reference models in order to produce specific deviations in specific regions of the calculated dose profiles (central axis and transverse). The beam models ...
BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, ...
This paper introduces the JNM Special Issue on the development of a first wall for the reaction chamber in a laser fusion power plant. In this approach to fusion energy a spherical target is injected into a large chamber and heated to fusion burn by an array of lasers. The target emissions are absorbed by the wall and encapsulating blanket, and the resulting heat converted into electricity. The bulk of the energy deposited in the first wall is in the form of X-rays (1.0-100 keV) and ions (0.1-4 MeV). In order to have a practical power plant, the first wall must be resistant to these emissions and suffer virtually no erosion on each shot. A wall candidate based on tungsten armor bonded to a low activation ferritic steel substrate has been chosen as the initial system to be studied. The choice was based on the vast experience with these materials in a nuclear environment and the ability to address most of the key remaining ...
This paper reviews three key initiatives undertaken in the historical city of Oxford to bring about reductions in energy-related CO_2 emissions on a city-wide scale. The author has been part of all the three initiatives. In 2002, a collaborative partnership between academia, industry and city council started the Oxford Solar Initiative (OSI) which uses a community-based approach to help households and organisations in Oxford, financially and technically, to install solar energy systems and energy efficiency measures in buildings. So far OSI has facilitated the installation of 80 active solar systems, over 450 energy efficiency measures and 3,000 low energy bulbs. The scientific basis of OSI is a GIS-based DECoRuM model which estimates and maps baseline energy use and CO_2 emissions on a house-by house level, identifies 'pollution' hotspots, predicts the potential for reductions in CO_2 emissions and monitors reductions achieved as a result of deploying energy ...
Introduction Uchide and Ide [SSA Spring Meeting, 2009] proposed a new framework for studying the scaling and overall nature of earthquake rupture growth in terms of cumulative moment functions. For better understanding of rupture growth processes, spatiotemporally local processes are also important. The nature of high-frequency (HF) radiation has been investigated for some time, but its role in the earthquake rupture process is still unclear. A wavelet analysis reveals that the HF radiation (e.g., 4 - 32 Hz) of the 2004 Parkfield earthquake is peaky, which implies that the sources of the HF radiation are isolated in space and time. We experiment with applying a matched filter analysis using small template events occurring near the target event rupture area to test whether it can reveal the HF radiation sources for a regular large earthquake. Method We design a matched filter for multiple components and stations. Shelly et al. [2007] attempted identifying ...
All microRNA (miRNA) target—finder algorithms return lists of candidate target genes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach...Full Text Available
The cell cycle-regulatory transcription 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
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
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
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
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
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
Sewage waste disposal facilities in the Florida Keys include septic tanks and individual package plants in place of municipal collection facilities in most locations. In Key Largo, both facilities discharge...Full Text Available
In key management schemes that realize secure multicast communications encrypted by group keys on a public network, tree structures are often used to update the group keys efficiently. Selcuk and Sidhu have proposed an efficient scheme which updates dynamically the tree structures based on the withdrawal probabilities of members. In this paper, it is shown that Selcuk-Sidhu scheme is asymptotically optimal for the cost of withdrawal. Furthermore, a new key management scheme, which takes account of key update costs of joining in addition to withdrawal, is proposed. It is proved that the proposed scheme is also asymptotically optimal, and it is shown by simulation that it can attain good performance for nonasymptotic cases.
IntroductionBreast cancer is the most diagnosed and second leading cause of cancer deaths in the U.S. female population. An estimated 5 to 10 percent of all breast cancers are inherited, caused by mutations in the breast cancer susceptibility genes (BRCA1/2). As many as 90% of all mutations are nonsense mutations, causing a truncated polypeptide product. A popular and low cost method of mutation detection has been the protein truncation test (PTT), where target regions of BRCA1/2 are PCR amplified, transcribed/translated in a cell-free protein synthesis system and analyzed for truncated polypeptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. We previously reported a novel High Throughput Solid-Phase PTT (HTS-PTT) based on an enzyme-linked immunosorbent assay (ELISA) format that eliminates the need for radioactivity, SDS-PAGE and subjective interpretation of the results. Here, we report the next generation HTS-PTT ...
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 T539fsdelC)/wt-HNF-1#beta# impaired SI ...
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...
Strategic management of key accounts has become an important component of many companies' sales efforts. This research introduces a strategic framework of key account performance that integrates theory from relationship marketing, key account management, and customer equity. Using the three drivers of customer equity - value equity, brand equity, and relationship equity - the framework captures both the relational outcomes (relationship commitment and trust) and financial performance outcomes (profitability and share of spend) of strategic decisions made in key account programs. Implications and future research are then discussed.
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
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
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
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
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
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
BackgroundMalignant catarrhal fever (MCF) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes...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 ...
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
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
Zebrafish transgenesis is a powerful and increasingly common strategy to assay vertebrate transcriptional regulatory control. Several challenges remain, however, to the broader application of...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
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
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
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
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
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 ...
Human antibodies targeting prostate cancer cell surface epitopes may be useful for imaging and therapy. The objective of this study was to evaluate the tumor targeting of an internalizing human...Full Text Available
Computational prediction of microRNA targets remains a challenging problem. The existing rule-based, data-driven and expression profiling approaches to target prediction are mostly approached from the...Full Text Available
In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly...Full Text Available
The U.S. Department of Energy (DOE) and the U.S. Council for Automotive Research (composed of automakers Ford, General Motors, and Chrysler) announced in January 2002 a new cooperative research effort. Known as 'FreedomCAR' (derived from 'Freedom' and 'Cooperative Automotive Research'), it represents DOE's commitment to developing public/private partnerships to fund high-risk, high-payoff research into advanced automotive technologies. Efficient fuel cell technology, which uses hydrogen to power automobiles without air pollution, is a very promising pathway to achieving the ultimate vision. The new partnership replaces and builds upon the Partnership for a New Generation of Vehicles initiative that ran from 1993 through 2001. The Advanced Power Electronics and Electric Machines (APEEM) subprogram within the FreedomCAR and Vehicle Technologies Program provides support and guidance for many cutting-edge automotive ...
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 ...
Computational fluid dynamics(CFD) code FLUENT was used to simulate the thermal hydraulic processes occurring in conceptual design of the accelerator-driven subcritical reactor(ADSR) liquid lead target. The purpose of the analysis is to investigate the thermal hydraulic characteristics of liquid lead as ADSR target material with various target geometries and injection locations of proton beam. In the calculation analysis, the local temperature of the liquid lead target rises to the boiling temperature very rapidly. When the proton beam is injected from the bottom of the target system, the duration time to reach the boiling temperature is longer and the temperature distribution is flatter than other cases.
On-orbit spectral calibration of hyperspectral imaging data is a key step for quantitatively analyzing them. Like the atmospheric correction, accurate spectral calibration is very necessary for improved studies of land or ocean surface properties. Based on the previous literatures, a new method which coupled an optimization algorithm was developed to simultaneously retrieve the central wavelength and the full width at half maximum (FWHM) of the hyperspectral sensor without needing the in situ reflectance spectra. Firstly, the Hyperion data set simulated using MODTRAN4 with the Hyperion spectral specification was used to test the new method, and the results indicated that the maximum error was less than 0.1 and 0.7 nm for central wavelength and FWHM respectively when the spectral shift is 5 nm. Then the algorithm was applied to the Hyperion data acquired on May 20, 2008 over Heihe River Basin and it was iteratively performed for each detector of the two ...
The minimization of the environmental footprint is the underlying principle of companies involved in sustainable development. At the same time, those companies seek to contribute to the economic and social development of the communities in which they have a presence. The evidence linking sustainable development and value creation are examined in this report targeted to the investment community, which is part of an overall leadership initiative undertaken by the Conference Board of Canada. The benchmarks of companies committed to sustainable development have, on the whole, been matched or exceeded, as shown by recent evidence based on the performance of seven prominent funds and indices managed in Canada, the United States, and western Europe. They are: the Domini Social Equity Fund (American focus), the EcoValue 21{sup TM} (American focus), the Dow Jones Sustainability Group Index (international focus), Storebrand Scudder Environmental Value Fund (European focus), ...
In the Savannah River Site's (SRS') Solid Waste Management Program, a key to success is the Public Involvement Program. The Solid Waste Division at SRS manages the site's transuranic, low-level, mixed, and hazardous wastes. All decisions associated with management of this waste are of interest to the public and successful program implementation would be impossible without a vigorous public involvement program. The SRS Solid Waste Division (SWD) and its Department of Energy (DOE) customer developed, implemented, and maintain a comprehensive public participation and communications program. It is staffed by public participation and technical specialists to ensure information is presented in a manner that is technically accurate while being tailored for understanding by people without a technical background. The program provides the public with accurate, complete, timely information and early meaningful participation opportunities. It also ...
A real-time neutron radiography imaging system has been installed at the Texas A and M University Nuclear Science Center. The system employs a scintillating screen viewed by a low-light TV camera with a front surface mirror placed at 45deg to the neutron beam. The key components of the system are the neutron camera and the image capture and processing unit. The neutron camera uses an NE 426 scintillating screen (ZnS), front surface mirror, remote focus and zoom lens, intensified relay optics (IRO) and monochrome CCD television camera. The image capture and processing unit consists of an IBM PC AT-compatible computer, arithmetic frame grabber, frame processor and high-resolution color monitor. The neutron camera is similar to others using a silicon intensified target (SIT) television camera to provide a TV image of the low-level light from a NE 426 screen. The IRO and CCD camera are used in place of the SIT camera. The computer digitizes the TV ...
A real-time neutron radiography imaging system has been installed at the Texas A and M University Nuclear Science Center. The system employs a scintillating screen viewed by a low-light TV camera with a front surface mirror placed at 45deg to the neutron beam. The key components of the system are the neutron camera and the image capture and processing unit. The neutron camera uses an NE 426 scintillating screen (ZnS), front surface mirror, remote focus and zoom lens, intensified relay optics (IRO) and monochrome CCD television camera. The image capture and processing unit consists of an IBM PC AT-compatible computer, arithmetic frame grabber, frame processor and high-resolution color monitor. The neutron camera is similar to others using a silicon intensified target (SIT) television camera to provide a TV image of the low-level light from a NE 426 screen. The IRO and CCD camera are used in place of the SIT camera. The computer digitizes the TV ...
Gas nitridation has shown excellent promise to form dense, electrically conductive and corrosion-resistant Cr-nitride surface layers on Ni-Cr base alloys for use as proton exchange membrane fuel cell (PEMFC) bipolar plates. Due to the high cost of nickel, Fe-base bipolar plate alloys are needed to meet the cost targets for many PEMFC applications. Unfortunately, nitridation of Fe-base stainless steel alloys typically leads to internal Cr-nitride precipitation rather than the desired protective surface nitride layer formation, due to the high permeability of nitrogen in these alloys. This paper reports the finding that it is possible to form a continuous, protective Cr-nitride (CrN and Cr{sub 2}N) surface layer through nitridation of Fe-base stainless steel alloys. The key to form a protective Cr-nitride surface layer was found to be the initial formation of oxide during nitridation, which prevented the internal nitridation typically observed ...
Gas nitridation has shown excellent promise to form dense, electrically conductive and corrosion-resistant Cr-nitride surface layers on Ni-Cr base alloys for use as proton exchange membrane fuel cell (PEMFC) bipolar plates. Due to the high cost of nickel, Fe-base bipolar plate alloys are needed to meet the cost targets for many PEMFC applications. Unfortunately, nitridation of Fe-base stainless steel alloys typically leads to internal Cr-nitride precipitation rather than the desired protective surface nitride layer formation, due to the high permeability of nitrogen in these alloys. This paper reports the finding that it is possible to form a continuous, protective Cr-nitride (CrN and Cr{sub 2}N) surface layer through nitridation of Fe-base stainless steel alloys. The key to form a protective Cr-nitride surface layer was found to be the initial formation of oxide during nitridation, which prevented the internal nitridation typically observed ...
One of the challenges facing Clean Development Mechanism (CDM) projects today is their limited ability to secure financing for the underlying greenhouse gas emission reduction activities, particularly in the least developed countries. Among the key reasons for this is the fact that most financial intermediaries in the CDM host countries have limited or no knowledge of the CDM Modalities and Procedures. Moreover, approaches, tools and skills for CDM project appraisal are lacking or are asymmetrical to the skills in comparable institutions in developed countries. Consequently, developing country financial institutions are unable to properly evaluate the risks and rewards associated with investing or lending to developers undertaking CDM projects, and therefore have, by-and-large, refrained from financing these projects. In addition, some potential project proponents lack experience in structuring arrangements for financing a project. This Guidebook - commissioned by ...
If geothermal heat pumps (GHPs) are to make a significant mark in the market, we believe that it will be through energy service pricing contracts offered by retailcos. The benefits of GHPs are ideally suited to energy service pricing (ESP) contractual arrangements; however, few retailcos are thoroughly familiar with the benefits of GHPs. Many of the same barriers that have prevented GHPs from reaching their full potential in the current market environment remain in place for retailcos. A lack of awareness, concerns over the actual efficiencies of GHPs, perceptions of extremely high first costs, unknown records for maintenance costs, etc. have all contributed to limited adoption of GHP technology. These same factors are of concern to retailcos as they contemplate long term customer contracts. The central focus of this project was the creation of models, using actual GHP operating data and the experience of seasoned professionals, to simulate the financial performance of GHPs in ...
Geologic sequestration represents a promising strategy for isolating CO{sub 2} waste streams from the atmosphere. Successful implementation of this approach hinges on our ability to predict the relative effectiveness of subsurface CO{sub 2} migration and sequestration as a function of keytarget-formation and cap-rock properties, which will enable us to identify optimal sites and evaluate their long-term isolation performance. Quantifying this functional relationship requires a modeling capability that explicitly couples multiphase flow and kinetically controlled geochemical processes. We have developed a unique computational package that meets these criteria, and used it to model CO{sub 2} injection at Statoil's North-Sea Sleipner facility, the world's first saline-aquifer storage site. The package integrates a state-of-the-art reactive transport simulator (NUFT) with supporting geochemical software and databases (SUPCRT92). ...
Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes ...
The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in the blood of mice, ...
Threat characterization is a key component in evaluating the threat faced by control systems. Without a thorough understanding of the threat faced by critical infrastructure networks, adequate resources cannot be allocated or directed effectively to the defense of these systems. Traditional methods of threat analysis focus on identifying the capabilities and motivations of a specific attacker, assessing the value the adversary would place on targeted systems, and deploying defenses according to the threat posed by the potential adversary. Too many effective exploits and tools exist and are easily accessible to anyone with access to an Internet connection, minimal technical skills, and a significantly reduced motivational threshold to be able to narrow the field of potential adversaries effectively. Understanding how hackers evaluate new IT security research and incorporate significant new ideas into their own tools provides a means of ...
An uncertainty decrease is an very important issue for enhancing risk-informed (RI) activities worldwide. Especially, a relatively large uncertainty in a level-2 (L2) PSA risk compared with level-1 internal PSA risk has been a bottleneck problem in the RI application to the extent of a severe accident management. According to the ASME PRA standard in which sources of an uncertainty to capture a category-II RI (= Option 2) capability are listed, an uncertainty analysis which identifies the key sources of an uncertainty and includes sensitivity studies for dominant contributors to LERF (Large Early Release Frequency) needs to be provided. To solve these problems, USNRC have developed the 'SPAR-LERF' model related to the L2 RI application and 'L2 uncertainty assessment and improvement' work is being taken as a main PSA2 topic of the SARNET (Severe Accident Research Network of Excellence) program in Europe by OECD/NEA. Domestically, ...
Experimental and computational investigations were performed in order to better understand the mechanical response of rigid targets with various geometries to the detonation of shallow buried explosives. The motion of the targets was measured by use of high-speed digital video photography. This work involved flat targets, targets that were downwardly convex, and targets that were downwardly concave with explosive charges located at various positions beneath the targets. It was observed that, in general, angled hulls - whether downwardly concave or convex - tended to reduce the amount of momentum imparted to the center of mass of the targets. Computations were performed by use of an arbitrary Langrangian-Eulerian treatment in a nonlinear finite element code. A model based on quasi-static te...
In an effort to develop octahedral metal complexes as chemotherapeutic and diagnostic agents targeted to DNA, it is critical to optimize the properties of their cellular uptake. Appending d-octaarginine...Full Text Available
The design of the absorber blocks for internal and external dumping of the SPS proton beam is discussed. In addition, the external target stations for slow and fast extracted proton beams are described.
... L. Sutton. 2000. Is the aquatic weed hygrophila, Hygrophila polysperma (Polemoniales: Acanthaceae), a suitable target for classical biological ... ...
Nato SCI-12 on Camouflage Evaluation Workshop on Search and Target Acquisition The Netherlands, June 1999. Image Discrimination Models for Object Detection ...
By W. Wayne Scott. Langley Research Center. SUMMARY. Thin- and thick-target bremsstrahlung spectra are presented for electron energies up to 7.0 MeV. ...
For companies, relationships with external actors may constitute intangible assets. Many firms have put in place key account management programs in order to pay sufficient attention to strategically important customers and the marketing literature has studied such programs. However, a company's relationship portfolio also comprises relationships with other types of actors. The objective of this paper is to show that ? across the different types of external relationships a company may develop ? some relationships have more importance than others and, hence, are key. The authors argue that, as a consequence, the keyness of certain relationships has led to the emergence of approaches which can be referred to as key relationship management. For this purpose, the authors first present empirical...
The National Ignition Facility (NIF) is a proposed Department of Energy facility which will contribute to the resolution of important Defense Program and inertial fusion energy issues for energy production in the future. The NIF will consist of a laser system with 192 independent beamlets transported to a target chamber. The target chamber is a multi-purpose structure that provides the interface between the target and the laser optics. The chamber must be capable of achieving moderate vacuum levels in reasonable times; it must remain dimensionally stable within micron tolerances, provide support for the optics, diagnostics, and target positioner; it must minimize the debris from the x-ray and laser light environments; and it must be capable of supporting external neutron shielding. The chamber must also be fabricated from a low neutron activation material. The fusion reaction in the ...
AbstractIndividual informed consent is a key ethical obligation for clinical studies, but empirical studies show that key requirements are often not met. Common recommendations to strengthen...Full Text Available
AMP-activated-protein-kinase (AMPK) is a key sensor and regulator of cellular and whole-body energy metabolism and plays a key role in regulation of lipid metabolism. Since lipid metabolism...Full Text Available
Food-deprived pigeons were presented with a row of four response keys situated above a grain hopper aperture. At the start of a trial, three of four keys were randomly selected and illuminated white...Full Text Available
We proposed a solid and a mercury target concepts through the preliminary conceptual design. To feasible these concepts, analysis and experimental works are being carried out. This paper introduces an outline of present status of target R and D such as heat transfer augmentation experiments for the solid target, mercury flow tests with a loop of maximum flow rate of 15L/min, flow pattern measurements for a cold source moderator etc. as well as preliminary conceptual design works. (author)
... Uninterrupted access to and use of critical infrastructure in the Arabian Gulf region are key to the successful prosecution of the Global War on Terror ...
We present a protocol for quantum key distribution using discrete modulation of coherent states of light. Information is encoded in the variable phase of coherent states which can be chosen from a regular discrete set ranging from binary to continuous modulation similar to phase-shift keying in classical communication. Information is decoded by simultaneous homodyne measurement of both quadratures and requires no active choice of basis. The protocol utilizes either direct or reverse reconciliation both with and without postselection. We analyze the security of the protocol and show how to enhance it by the optimal choice of all variable parameters of the quantum signal.
In the CERN approach to the design of a neutrino factory, the repetition frequency of the proton beam is high enough to consider stationary solid targets as a viable solution for multi-MW beams. The target consists of high density tantalum spheres of 2 mm diameter which can efficiently be cooled by passing a high mass flow He-gas stream through the voids between the Ta-granules. Very small thermal shocks and stresses will arise in this fine grained structure due to the relatively long burst of 3.3 ms from the SPL-proton linac. In a quadruple target system where each target receives only one quarter of the total beam power of 4 MW, conservative temperature levels and adequate lifetimes of the target are estimated in its very high radiation environment. A conceptual design of the integration of the target into the magnetic horn-pion-collector is presented.
In 1998, EU legislation initiated a liberalisation process among European energy markets. The process of market opening has significantly changed the functioning of the markets and the competition conditions of the energy sector. At the same time, the industry witnessed a surge of mergers and far-reaching changes in the structure of German electricity and natural gas markets occurred. Against this background, the doctoral thesis at hand surveys the merger activities in the energy sector as well as the merger control policy of the German Federal Cartel Office during the first years of liberalisation. The study starts with a portrayal of the institutional framework of the German merger control regime and a survey of the relevant economic literature on horizontal and vertical mergers. Subsequent to the legal and theoretical considerations, the merger activities and the merger control policy of the German Federal Cartel Office are investigated empirically. The data set is based on ...
The project is devoted to the development of novel insoluble anodes for copper electrowinning and electrolytic manganese dioxide (EMD) production. The anodes are made of titanium-lead composite material produced by techniques of powder metallurgy, compaction of titanium powder, sintering and subsequent lead infiltration. The titanium-lead anode combines beneficial electrochemical behavior of a lead anode with high mechanical properties and corrosion resistance of a titanium anode. In the titanium-lead anode, the titanium stabilizes the lead, preventing it from spalling, and the lead sheathes the titanium, protecting it from passivation. Interconnections between manufacturing process, structure, composition and properties of the titanium-lead composite material were investigated. The material containing 20-30 vol.% of lead had optimal combination of mechanical and electrochemical properties. Optimal process parameters to manufacture the anodes were identified. Prototypes having ...
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 ...
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 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 proper development of ...
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.
The White Rose Oil Project, located in the Jeanne d'Arc Basin 350 km east of St. John's, is reported to continue paying benefits for the oil and gas industry in eastern Canada. The operator, Husky Energy, is said to be on target and expects first oil from the project in late 2005 or early 2006. Peak production for the White Rose Field is projected at 100,000 bbl/d. The project has a total capital cost of $2.35 billion. The first phase of the project, comprised of four wells, including an oil producer, was completed in July. The estimated productive capacity of this well is between 25,000 and 35,000 bbl/d. Other major milestones achieved at the White Rose project include movement of the topside modules onto the Sea Rose floating production, storage and offloading (FPSO) vessel, consisting of 17 lifts during the seven-week program. Individual lifts up to 1,250 tons were carried by the Lampson 2600 Trans-lift crane at the Cow Head Fabrication ...
Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal ...
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 ...
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.
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 ...
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...
PurposeWe conducted a comparative study of Clinical Target Volume (CTV) definition of pelvic lymph nodes by multiple GU radiation oncologists looking at the levels...Full Text Available
To capitalize on the response of tumor cells to ionizing radiation, we developed a controlled-release nanoparticle drug delivery system using a targeting peptide that recognizes a radiation-induced...Full Text Available
The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I...Full Text Available
The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large...Full Text Available
The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles...Full Text Available
... detected (and reported) as a by-product of MRM screening (MS/MS) targeted by Law or Rule ... detected (and reported) as a by-product of MRM screening (MS/MS) targeted by Law or Rule ...
The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with non-classical cellular targets. Unfortunately, target-based drug discovery against...Full Text Available
Many genetic processes depend on proteins interacting with specific sequences on DNA. Despite the large excess of nonspecific DNA in the cell, proteins can locate their targets rapidly. After initial...Full Text Available
Peroxisomes, glyoxysomes, glycosomes, and hydrogenosomes have each been classified as microbodies, i.e., subcellular organelles with an electron-dense matrix that is bound by a single membrane. We investigated...Full Text Available
Considering accessibility of the 3′UTR is believed to increase the precision of microRNA target predictions. We show that, contrary to common belief, ranking by the hybridization energy or by...Full Text Available
Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53 target genes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates...Full Text Available
Operant conditioning techniques were applied to the study of how target fixations are controlled by the probability of signal occurrence. In a standard vigilance setting, gaze at three illuminable...Full Text Available
Cytokinesis in animal and fungal cells utilizes a contractile actomyosin ring (AMR). However, how myosin II is targeted to the division site and promotes AMR assembly, and how the AMR coordinates with...Full Text Available
Purposes1. To determine the optimal pelvic nodal clinical target volume for post-operative treatment of endometrial cancer. 2. To compare the DVH of different treatment planning...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 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
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
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
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
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
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
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
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 in patterns unrelated to those of ...
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
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 important for gradual ...
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 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
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
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
... they assisted in the 2000 attack on the USS Cole? ... List the types of targets that ETA has attacked. ... was at least partially responsible for the attack. ...
... Tanzania, and the attack on the USS COLE. ... vis another has no bearing on the legality of the attack. If the person attacked is a combatant, the use of ...
The production of polarized negative ion beams by collisional pumping is described. Collisional pumping utilizes repeated charge changing collisions in a thick electron-spin-polarized gas or vapor target to form a polarized fast atom beam. The polarized fast atom beam is then partially converted into a polarized negative ion beam in a vapor target. Analysis is presented for a hydrogen beam passing through either a thick polarized H atom target or a thick polarized alkali target. Large polarizations and large currents may be possible.
The production of polarized negative ion beams by ''collisional pumping'' is described. Collisional pumping utilizes repeated charge changing collisions in a thick electron-spin-polarized gas or vapor target to form a polarized fast atom beam. The polarized fast atom beam is then partially converted into a polarized negative ion beam in a vapor target. Analysis is presented for a hydrogen beam passing through either a thick polarized H atom target or a thick polarized alkali target. Large polarizations and large currents may be possible.
While there is growing interest in Real Time Pricing as a competitive tool, its adoption to date has been constrained by wariness on the part of many utilities and many of their customers. That wariness is not misplaced, for Real Time Pricing is not for everyone. In order for both utilities and their customers to benefit, the pricing system must be properly tailored for, and offered to, the appropriate audience. This paper discusses needs for identifying targets, implications of targeting of Real Time Pricing to various types of customers, and implications for design and marketing of such pricing systems. Examples from utility experiences are provided, and recommendations are offered for development of improved targeting of Real Time Pricing.
This paper present the results of a series of calculations made to determine the "2"3"8Pu production potential of several advanced target assembly designs in the Fast Flux Test Facility (FFTF). These calculations show that by using advanced target designs the intimately mix the "2"3"7Np target material with an yttrium hydride moderator, the FFTF has the potential of producing up to 30 kg of high-quality "2"3"8Pu per year.
We apply the framework developed in Target space duality I: general theory. We show that both nonabelian duality and Poisson-Lie duality are examples of the general theory. We propose how the formalism leads to a systematic study of duality by studying few scenarios that lead to open questions in the theory of Lie algebras. We present evidence that there are probably new examples of irreducible target space duality.
The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.
This paper illustrates how the techniques developed by the authors for capital cost targeting of mass exchange networks can be applied to determination of capital investment targets for reduction in effluent for existing systems involving mass exchange. The results is an impact diagram which shows the relationship between effluent reduction and capital investment, indicating a region of limiting return on investment as well as the maximum possible reduction in effluent. (au)
In order to facilitate observations of low energy nuclear reactions, a new type recoil mass-separator together with a new gas-jet target system is being developed at the tandem accelerator facility in Kyushu University. The expected mass-resolving power of the separator is 220 for a solid angle of 10 msr and the practical thickness of the gas-jet target will exceed 0.1 atm#centre dot#cm for the light elements of H and He. (author).
A portable fiber optic detector that senses the presence of specific target chemicals by electrostatically attracting the target chemical to an aromatic compound coating on an optical fiber. Attaching the target chemical to the coated fiber reduces the fluorescence so that a photon sensing detector records the reduced light level and activates an appropriate alarm or indicator.
A 16 l liquid parahydrogen target has been developed for a measurement of the parity-violating {gamma}-asymmetry in the capture of polarized cold neutrons on protons in the {rvec n} + p {yields} d + {gamma} reaction by the NPDGamma collaboration. The target system was carefully designed to meet the stringent requirements on systematic effects for the experiment and also to satisfy hydrogen safety requirements. The target was designed to preserve the neutron polarization during neutron scattering on liquid hydrogen (LH{sub 2}), optimize the statistical sensitivity to the {rvec n} + p {yields} d + {gamma} reaction, minimize backgrounds coming from neutron interaction with the beam windows of the target cryostat, minimize LH{sub 2} density fluctuations which can introduce extra noise in the gamma asymmetry signal, and control systematic effects. The target incorporates two mechanical ...
...2010-10-01 2010-10-01 false Energy Policy Act target group certification...Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION...Provisions and Clauses 952.226-73 Energy Policy Act target group...
We prove that the 1984 protocol of Bennett and Brassard (BB84) for quantum key distribution is secure. We first give a key distribution protocol based on entanglement purification, which can be proven secure using methods from Lo and Chau's proof of security for a similar protocol. We then show that the security of this protocol implies the security of BB84. The entanglement purification based protocol uses Calderbank-Shor-Steane codes, and properties of these codes are used to remove the use of quantum computation from the Lo-Chau protocol. (c) 2000 The American Physical Society.
Customer knowledge has become an important topic for both academicians and practitioners in recent years. However, there has been little academic research on the utilization of customer-specific knowledge. This study adds to our understanding in focusing on the relationships between various intra-organizational factors and customer knowledge utilization in the context of key account management. The results of the study show, that the use of teams, top management involvement, KAM formalization and CRM technology enhance the utilization of customer knowledge in the management of large industrial key account customers.
This paper discusses key methods for sustaining quality engineering data, the fundamental principles that these methods are based on, and the methods for supporting the performance of nuclear power plants by the provision of quality engineering data at all times. The concept of an 'engineering data foundation', and a Configuration Management data model are developed. The concepts and methods for managing the integrity of engineering data across many different databases and document systems are developed, including the key concepts of data-positions and data-values, Master Data and Copy Data, and the concept of a 'partnership between people and technology'. (author). 7 refs., 1 tab., 2 figs.
A key comparison has been made between the air-kerma standards of the ARPANSA and the BIPM in the low-energy X-ray range. The results show the standards to be in agreement at the level of the combined standard uncertainty of 7.0 parts in 10"3 for the 10 kV radiation quality and 3.7 parts in 10"3 for all other beam qualities. The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database. (authors)
This work describes the development of a synchronous key based on micro controller to the switching of three-phase power transformers, which makes possible the achievement of tests to register the inrush current, and the previous establishment of the instantaneous values of the voltage firstly applied to different phases of the energy process. This key is a value tool to the development electric power system projects and to the teaching and researching activities at the laboratory related to transitory phenomena and electric system protection.
although additional research is needed to corroborate such findings. Key words: Avicennia germinans; disturbance; downed wood; Everglades National Park; Hurricane Andrew;...
Background and PurposeHemodynamic insults at arterial bifurcations are hypothesized to play a key role in intracranial aneurysm formation. This study investigates...Full Text Available
Medical Science Liaison (MSL) teams are a well-recognized function within the pharmaceutical and medical products industries. While in most organizations, MSLs have focused on the development of relationships with individual Key Opinion Leaders, progressive companies have realized the value that MSLs can also bring to Key Account Management (KAM). This article discusses the five steps that should be followed in order to successfully integrate the support of Key Accounts into an MSL function. These include understanding the business approach to KAM, identifying what MSL resources are available, developing a comprehensive strategic plan, implementing the plan, and evaluating and making any necessary adjustments. Finally, a case example outlining the experience of a small pharmaceutical compa...
... elevated blood sugar levels, but not full-blown diabetes. What are the keys to preventing the disease? ... been well studied, in a study called The Diabetes Prevention Program, in several thousand people with this ...
Summary brochure of GeoPowering the West (GPW) activities, and areas of technology transfer and market transformation. It also provides current contact information for key DOE and national laboratory staff representing the GPW program.
The purpose of this report is to provide management with performance data on key performance indicators selected from the FFTF Early Warning System performance indicators.
... Uninterrupted access to and use of critical infrastructure in the Arabian Gulf region are key to the successful prosecution of the Global War on Terror ...
Citrate and lactose fermentation are subject to the same metabolic regulation. In both processes, pyruvate is the key intermediate. Lactococcus lactis subsp. lactis...Full Text Available
... very difficult to help get better and to rehabilitate and sometimes even need surgery. 00:04:21 ... step of treatment, from our standpoint, is to rehabilitate, to strengthen the shoulder. And the real key ...
The existence of thresholds for toxicants is a matter of debate in chemical risk assessment and regulation. Current risk assessment methods are based on the assumption that, in the absence of sufficient...Full Text Available
BackgroundFunction exertion of specific proteins are key factors in disease progression, thus the systematical identification of those specific proteins is a prerequisite to understand...Full Text Available
Target materials for inertial fusion energy (IFE) power plant designs might be selected for a wide variety of reasons including wall absorption of driver energy, material opacity, cost and ease of fabrication. While each of these issues are of great importance, target materials should also be selected based upon their safety and environmental (S and E) characteristics. The present work focuses on the recycling, waste management and accident dose characteristics of potential target materials. If target materials are recycled so that the quantity is small, isotopic separation may be economically viable. Therefore, calculations have been completed for all stable isotopes for all elements from lithium to polonium. The results of these calculations are used to identify specific isotopes and elements that are most likely to be offensive as well as those most likely to be acceptable in terms of their S and E ...
Certain allelochemicals of the marine dinoflagellate Alexandrium tamarense cause lysis of a broad spectrum of target protist cells but the lytic mechanism is poorly defined. We first hypothesized that membrane sterols serve as molecular targets of these lytic compounds, and that differences in sterol composition among donor and target cells may cause insensitivity of Alexandrium and sensitivity of targets to lytic compounds. We investigated Ca^2^+ influx after application of lytic fractions to a model cell line PC12 derived from a pheochromocytoma of the rat adrenal medulla to establish how the lytic compounds affect ion flux associated with lysis of target membranes. The lytic compounds increased permeability of the cell membrane for Ca^2^+ ions even during blockade of Ca^2^+ channels wit...
A simple electromagnetic transport system was constructed to identify very rare positrons produced in a powerful laser beam interaction with a target. Testing experiments were carried out with CO[sub 2]-laser (10[sup 12] W/cm[sup 2]) beam pulses ([tau] = 50 ns, f = 0.01 Hz) focused on the copper target, as well as with a 96 MeV alpha-particle beam irradiated carbon target. The results showed that the developed system could be effectively used for positron identification and evaluation of their energy by means of a time-of-flight method. The computerized system to deal with this problem, together with others related to the power laser beam interaction with targets, has been constructed. (orig.).
The modeling methods used to compute the neutron-induced activation of target and near-target materials in the NIF facility are presented. A detailed space and energy description of the neutron environment in the different materials is provided. A new capability has been developed to treat in a general way the activation of debris produced in an operational regime of yield and no-yield experiments. First calculations are addressed to analyze the activity of the debris into the target chamber. The contribution of the different components to activity, interior dose rates, and waste disposal rating (WDR) is determined. The importance of the activation coming from primary irradiation in the target, and from secondary irradiation in debris deposited onto the first wall is assessed. Finally, waste hazards of the activated debris when removed out of the chamber and stored are analyzed. (authors)
Using static Michelson interferometer to get the spectrum information of measurement targets for spectrum identification, under the condition that the interference length is constant, the system can be optimized by BP neural network algorithm for the mixed spectral separation process. Thereby it can realize improving the recognition probability of camouflage target. Collecting the spectrum information in field of view (FOV) by the interferometer and linear array CCD detector, composing the set of mixed spectrum data, with known absorption spectrum of the material as a hidden layer of rules, it used BP neural network to separate the mixed spectrum data. Experiment with different distances, different combinations of mixed background spectrum as the initial data, using steel target (size: 1.5 m x 1.5 m) made of four kinds, the recognition probability of non-camouflage target is about 90% by BP neural ...
In the Fourth Dutch National Environmental Outlook (NMP, abbreviated in Dutch) of the National Institute of Public Health and the Environment (VROM), published in July 1997, possible future developments in the traffic and transport sector in the Netherlands are described for the period 1995-2020 and also evaluates present Dutch policies. NMP-4 also offers possible solutions for expected environmental problems. This report serves as a background document for the traffic and transport sector. With a view to present Dutch policies, the main conclusions drawn from the Outlook are that: (1) the policy targets for car and lorry use for 2010 will not be met, (2) the target for CO2 emissions from road transport for 2010 will not be met, (3) the NOx emission target for 2010 will be met for cars, but not for trucks, (4) the VOC emission target for 2010 will be met for cars, but not for trucks, and (5) the noise ...
A measuring-basis encrypted quantum key distribution scheme is proposed by using twelve nonorthogonal states in a four-state system and the measuring-basis encryption technique. In this scheme, two bits of classical information can be encoded on one four-state particle and the transmitted particles can be fully used.
...Keeping chickens: a beginner's guide : Directgov - Environment and greener living chickens, feeding chickens, egg marking, registering a ...flock, battery hens Chickens; Department for Environment, Food and Rural Affairs; Registrations; Animals; Livestock; Local government; Local ...authorities A guide for people keeping chickens on the laws for registering and feeding them, and how to spot key diseases. A ...guide for people keeping chickens on the laws for registering and feeding them, and how to spot key diseases. Keeping chickens: ...
Since 1998, The Pennsylvania State University successfully managed the Consortium for Premium Carbon Products from Coal (CPCPC), which was a vehicle for industry-driven research on the promotion, development, and transfer of innovative technologies on premium carbon products from coal to the U.S. industry. The CPCPC was an initiative led by Penn State, its cocharter member West Virginia University (WVU), and the U.S. Department of Energy's (DOE) National Energy Technology Laboratory (NETL), who also provided the base funding for the program, with Penn State responsible for consortium management. CPCPC began in 1998 under DOE Cooperative Agreement No. DE-FC26-98FT40350. This agreement ended November 2004 but the CPCPC activity continued under cooperative agreement No. DE-FC26-03NT41874, which started October 1, 2003 and ended December 31, 2010. The objective of the second agreement was to continue the successful operation of the CPCPC. The CPCPC enjoyed tremendous success with ...
On 7 May 2009, the Ministry of the Environment set up a working group to evaluate the possible use of biodegradable waste and other biodegradable material flows for energy production and obstacles to promoting their use in the whole production cycle. The deadline for the working group was 31 January 2010. According to its mandate, the working group had to make proposals for the measures needed to promote the energy use of biodegradable waste in order to fulfil the targets of the Government Foresight Report on Long-term Climate and Energy Policy. The working group proposes thirteen measures to be put into operation so that the investments aimed at the energy use of biodegradable waste would grow significantly from the present level. The most important measure is a full ban on depositing biodegradable waste in landfills. The working group sees that the reduction of greenhouse gas emissions from landfills should, in any case, be made more effective and that the ...
Purpose: Various published reports involving intensity-modulated radiotherapy (IMRT) plans developed using automated optimization (inverse planning) have demonstrated highly conformal plans. These reported conformal IMRT plans involve significant target dose inhomogeneity, including both overdosage and underdosage within the target volume. In this study, we demonstrate the development of optimized beamlet IMRT plans that satisfy rigorous dose homogeneity requirements for all target volumes (e.g., #+-#5%), while also sparing the parotids and other normal structures. Methods and Materials: The treatment plans of 15 patients with oropharyngeal cancer who were previously treated with forward-planned multisegmental IMRT were planned again using an automated optimization system developed in-house. The optimization system allows for variable sized beamlets computed using a three-dimensional convolution/superposition dose ...
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 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.
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.
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).
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 identifying transcriptional regulatory 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.
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 ...
The production methods for seven radioisotopes, Ga-67, Sr-85, Pd-103, In-111, Tu-167, Hg-197 and Pb-203, by using a classical 1.5m cyclotron in the Institute of Physics and Power Engineering, Obninsk, USSR, are described. At present, more than 50 cyclotrons in different countries are used for the production of radioisotopes applied to medicine. Radioisotopes are produced with the cyclotron in the I.Ph.P.E. in the form of irradiated targets, which are delivered to Moscow radiopharmaceutical factory, where radiopharmaceuticals are produced on the base of these targets. The cyclotron is operated in two regimes providing the acceleration of protons, deuterons and alpha -particles. Two types of target assemblies are used for irradiation, the one is intended for the internal beam, and the other is for the external beam. The reactions used for the production of seven radioisotopes described above, the types of ...
The production methods for seven radioisotopes, Ga-67, Sr-85, Pd-103, In-111, Tm-167, Hg-197 and Pb-203, by using a classical 1.5m cyclotron in the Institute of Physics and Power Engineering, Obninsk, USSR, are described. At present, more than 50 cyclotrons in different countries are used for the production of radioisotopes applied to medicine. Radioisotopes are produced with the cyclotron in the I.Ph.P.E. in the form of irradiated targets, which are delivered to Moscow radiopharmaceutical factory, where radiopharmaceuticals are produced on the base of these targets. The cyclotron is operated in two regimes providing the acceleration of protons, deuterons and alpha -particles. Two types of target assemblies are used for irradiation, the one is intended for the internal beam, and the other is for the external beam. The reactions used for the production of seven radioisotopes described above, the types of ...
This paper proposes a new pattern recognition system employing optical joint transform correlation (JTC) technique which offers a great number of advantages over similar digital techniques, including very fast operation, simple architecture and capability of updating the reference image in real time. The proposed JTC technique incorporates a synthetic discriminant function (SDF) of the target image estimated from different training images to make the pattern recognition performance invariant to noise and distortion. It then involves four different phase-shifted versions of the same target SDF reference image, which are individually joint transform correlated with the given input scene. When the correlation signals are combined, it produces a single cross-correlation peak corresponding to each potential target present in the given input scene. The proposed technique also includes a fringe-adjusted filter to generate a ...
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 ...
Laser optical pumping can be used to produce polarized alkali atom beams or polarized alkali vapor targets. Polarized alkali atom beams can be converted into polarized alkali ion beams, and polarized alkali vapor targets can be used to produce polarized H/sup -/ or /sup 3/He/sup -/ ion beams. In this paper the authors discuss how the polarized alkali atom beams and polarized alkali vapor targets are used to produce polarized ion beams with emphasis on the production of polarized negative ion beams.
The HARP experiment at CERN is performing extensive measurements of hadron production cross sections and secondary particle yields, in the momentum range 1.5-15 GeV/c, over the full solid angle and using a large set of cryogenic and solid targets. First measurements of hadron production cross-sections in the forward region are reported using an aluminium target 5% of an interaction length thick and a proton beam of 12.9 GeV/c. A preliminary analysis in the large angle region of elastic scattering events produced with the cryogenic hydrogen target at 3 GeV/c beam momentum is also presented.
Carrier-free radionuclides of tungsten and tantalum, "1"7"6","1"7"7W and "1"7"6","1"7"7Ta have been produced by heavy ion activation of holmium target with 97 MeV "1"6O"5"+ beam. Radiochemical separation scheme has been developed to isolate tungsten and tantalum radionuclides from the holmium target matrix. (author)
Carrier-free radioisotopes of tungsten, "1"7"6","1"7"7W, and their corresponding daughter radionuclides "1"7"6","1"7"7Ta, have been produced in holmium target by heavy ion activation with "1"6O"5"+ beam. An attempt has been made to separate these carrier-free radionuclides from bulk holmium target through LLX using cation exchanger HDEHP. (author)
A simple highly efficient procedure has been developed for recovery of thallium radioisotopes from lead and bismuth targets irradiated by 1-GeV protons. The procedure is based on the use of extraction chromatography. The cross-sections have been determined for formation of {sup 200}Pb, {sup 201}Pb, {sup 202m}Pb, and {sup 203}Pb radioisotopes in targets from lead with natural isotopic composition, irradiated by 1-GeV protons.
A simple highly efficient procedure has been developed for recovery of thallium radioisotopes from lead and bismuth targets irradiated by 1-GeV protons. The procedure is based on the use of extraction chromatography. The cross-sections have been determined for formation of "2"0"0Pb, "2"0"1Pb, "2"0"2"mPb, and "2"0"3Pb radioisotopes in targets from lead with natural isotopic composition, irradiated by 1-GeV protons.
The paper presents results of experimental research on the interaction of a pulsed plasma-ion stream with a tungsten (W) target. The pulsed hydrogen plasma was produced within the RPI-IBIS (Multi-Rod Plasma Injector) facility at IPJ in Swierk. Measurements were carried out by means of optical spectroscopy and corpuscular diagnostic techniques. For experiments with the W-target the operational conditions (so-called PID mode) were chosen when a clean hydrogen plasma stream was generated. Attention was paid to the identification of WI and WII spectral lines.
A modified variable structure interacting multiple model (M-VSIMM) estimator for complex hybrid maneuver target tracking is presented. The M-VSIMM could potentially be applied to fire control systems (FCS) used on warships. Target model groups were designed using 3D dimensional dynamic target models. Optimal model group selection logic was proposed, contrary to the activation and termination logic in the original VSIMM. The system will respond faster with optimal model group selection logic. After performing simulations, the tracking performances of the Kalman, ?-?(-?), VDIE, IMM and M-VSIMM filters were compared under various maneuvering conditions.
Preliminary experiments have been performed to investigate the effects of radiative cooling on plasma jets. Thin (3 um - 5 um) conical shells were irradiated with an intense laser, driving jets with velocities > 100 km/s. Through use of different target materials - aluminium, copper and gold - the degree of radiative losses was altered, and their importance for jet collimation investigated. A number of temporally resoved optical diagnostics was used, providing information about the jet evolution. Gold jets were seen to be narrower than those from copper targets, while aluminium targets produced the least collimated flows.
The velocity distribution of electrons ejected close to the forward direction by 0.8-2 MeV/A ions traversing various solid targets, including a Au monocrystal, is measured in coincidence with emerging charge-selected ions. The velocity spectrum is observed to be independent of outgoing projectile velocity and charge state for polycrystalline targets. Measurements on the Au crystal under channeling conditions show dependences on final charge state, and are tentatively explained by assuming that the main contribution to the production yield comes from the non-channeled fraction of the ions. A simple model for the creation of the forward-ejected electrons is proposed, which accounts for most of the experimental findings.
A computer-assisted rotation and stationary conformation radiotherapy system with overrunning multileaf collimators has been developed. This system can produce any shape of target volume, including a number of target areas outside the axis of the rotation, regardless of the location of the axis at 360"0 rotation irradiation. In addition, by changing the dose rate and deleting a partial region within a field, multiple stationary irradiation can produce more homogeneous target volumes - thus avoiding excessive irradiation to critical organs - than the rotation technique. (orig.).
The centroid and envelope dynamics of a high-intensity charged particle beam are investigated as a beam smoothing technique to achieve uniform illumination over a suitably chosen region of the target for applications to ion-beam-driven high energy density physics and heavy ion fusion. The motion of the beam centroid projected onto the target follows a smooth pattern to achieve the desired illumination, for improved stability properties during the beam-target interaction. The centroid dynamics is controlled by an oscillating "wobbler", a set of electrically-biased plates driven by RF voltage. __________________________________________________
Understanding the physical characteristics of the local microenvironment in which Mycobacterium tuberculosis resides is an important goal that may allow the targeting of metabolic processes...Full Text Available
Several different aspects of the influence of the target backing on in-beam electron spectra following compound nuclear reactions induced by accelerated ions at tandem energies irradiating backed targets are discussed in detail. This discussion is illustrated by a few typical examples, such as "1"2C"5"+ and "3"1P"1"0"+ beams at 4 MeV/u bombarding Sn(+Be), Sn(+Au), Pb(+C) backed targets. Moreover, the relative influence of electron backscattering, electron Doppler shift and Doppler broadening as well as #delta#-electron emission on the low energy electron spectra (E_e#<=#100 keV) obtained under such conditions are investigated in the frame of the available experimental data. (orig.).
Using the complex Kohn method, we have calculated variational values of phase shifts and the annihilation parameter, Z_{eff}, for the elastic scattering of positrons by molecular hydrogen. Our results are sensitive to small changes in the accuracy of the wave function representing the target hydrogen molecule. We have developed a systematic approach to demonstrate that, at low positron energies, there are particular forms of the Kohn trial wave function for which the results of variational calculations are not reliable, even when the target wave function accounts for as much as 96.8% of the correlation energy of H_{2}. We find that reliable results can be recovered if our calculations are extended to admit more sophisticated target wave functions accounting for 99.7% of the correlation energy. Remaining discrepancies between theory and experiment are briefly discussed.
Axon outgrowth and guidance to the proper target requires the coordination of filamentous (F)-actin and microtubules (MTs), the dynamic cytoskeletal polymers that promote shape change and locomotion....Full Text Available
We develop a systematic framework for studying target space duality at the classical level. We show that target space duality between manifolds M and M-tilde arises because of the existence of a very special symplectic manifold. This manifold locally looks like MxM-tilde and admits a double fibration. We analyze the local geometric requirements necessary for target space duality and prove that both manifolds must admit flat orthogonal connections. We show how abelian duality, nonabelian duality and Poisson-Lie duality are all special cases of a more general framework. As an example we exhibit new (nonlinear) dualities in the case M=M-tilde=R{sup n}.
This report discusses the experimental setup of experiment 814 at Brookhaven AGS. This experiment involves the collision of silicon ions with target nuclei. The detector systems are discussed primarily. (LSP)
The oviduct is an exquisitely designed organ that functions in picking-up ovulated oocytes, transporting gametes in opposite directions to the site of fertilization, providing a suitable environment...Full Text Available
Motivation: Automatic recognition of cell identities is critical for quantitative measurement, targeting and manipulation of cells of model animals at single-cell resolution. It has been...Full Text Available
The success of monoclonal antibodies in clinical practice is dependent on good design. Finding a suitable target is the most important part as other properties of the antibody can be altered by genetic...Full Text Available
Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...
Nov 21, 2003... for the European Space Agency's Automated Transport Vehicle, a new, uncrewed station cargo vehicle targeted for launch late next year. ...
Congestive heart failure (CHF) is a leading cause of morbidity and mortality. CHF is marked by atrial and ventricular enlargement and reduced cardiac contractility, as well as an association...Full Text Available
PurposeClinical trials have commenced to evaluate the feasibility of targeting malignant gliomas with genetically engineered cytolytic T-cells (CTLs) delivered directly...Full Text Available
Chaperones (stress proteins) are essential proteins to help the formation and maintenance of the proper conformation of other proteins and to promote cell survival after a large variety of environmental...Full Text Available
In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences...Full Text Available
The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding...Full Text Available
An application that provides a flexible and easy to use interface to the GAMMA spectral simulation package is described that is targeted at investigations using in vivo MR spectroscopic methods....Full Text Available
The potential of radiolabelled phenylpiperazines as agents for the detection and therapy of tumours of neural crest origin was evaluated by in vitro pharmacological studies with human neuroblastoma...Full Text Available
This letter reports a study designed to measure the benefits of voicing in the recognition of concurrent syllables. The target and distracter syllables were either voiced or whispered, producing...Full Text Available
Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based...Full Text Available
... defense's weapons are Space-based kinetic-kill vehicles ... I ti I obtained by dividing the weapons as ... of the optimal weapon-arge assigntments and ...
... In the Proceedings of INTC 2003, we studied charging effects on target coverage during electrospinning (16). ... of Fibers from Electrospinning of ...
The biosynthesis of insect juvenile hormone (JH) and its neuroendocrine control are attractive targets for chemical control of insect pests and vectors of disease. To facilitate the molecular...Full Text Available
The pleiotropic actions of neuromodulators on pre- and postsynaptic targets present challenges to disentangling the mechanisms underlying regulation of synaptic transmission. Within the striatum,...Full Text Available
BackgroundThe metagenomic analysis of microbial communities holds the potential to improve our understanding of the role of microbes in clinical conditions. Recent, dramatic improvements...Full Text Available
The immune system plays a crucial role in maintaining health; however, accumulating evidence indicates that this system can be the target for immunotoxic effects caused by a variety of chemicals including...Full Text Available
BackgroundAmino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved...Full Text Available
Objective: Given the increasing popularity of motorcycle riding and heightened risk of injury or death associated with being a rider, this study explored rider behavior as a determinant of rider safety and, in particular, key beliefs and motivations that influence such behavior. To enhance the effectiveness of future education and training interventions, it is important to understand riders' own views about what influences how they ride. Specifically, this study sought to identify key determinants of riders' behaviors in relation to the social context of riding, including social and identity-related influences relating to the group (group norms and group identity) as well as the self (moral/personal norm and self-identity). Method: Qualitative research was undertaken via group discussions ...
Purpose - This paper aims to explore the links between revenue management and business-to-business (B2B) relationships and explains how revenue management can both support and damage B2B relationships. Design/methodology/approach - A single case study method was employed to conduct qualitative research into a company and its key accounts. In-depth data were collected from three divergent sources (company revenue managers, company account managers and nine of the company's key accounts) through semi-structured interviews, observations and document studies. Findings - The research findings reveal that from the company's perspective, managers acknowledge that revenue management has positively influenced the process of identifying and analysing key account activities and conducting contractual...
Purpose - Key account management (KAM) programmes are a way for companies to develop existing relationships and increase sales, thus being proactive and searching for opportunities (which is often expected of KAM). It is also a way to meet changing customer demands arising from changes in purchasing strategy, buyers' mergers and acquisitions and the search for synergies in order to reduce costs. The purpose of this article is to analyse different key account management programmes on how they manage the sales process complexity and customer expectations. Design/methodology/approach - The paper draws on qualitative data collected during a field study of ABB and six of their major customers, based on annual or biannual interviews with 50 individuals within ABB from 1996 to 2006 and three to t...
Customer relationships, product development, data integration and demand-driven supply chains are key concepts for companies that wish to remain competitive in today?s global economy. To address this important information management issue, the present study examines how, within a demand-driven network context, an eCRM can influence the interorganizational product development process between a manufacturer and its key customers. The theoretical model, built on research related to a technology assimilation model based on Fichman?s (2000) work, was tested on data from 104 manufacturers in the wireless equipment sector. The results show that the adoption of an eCRM does not moderate the relationship between collaborative e-product development involving a manufacturer and its key customers and ...
The phenomenon of key supply management (KSM) in business companies is far less investigated than the phenomenon of key account management (KAM) which beneficiates, both in practice and in an academic context, from a growing interest. This article is based on the empirical analysis of a sample of 10 international companies which have recently launched KSM programmes or are currently working on launching such programs. It examines the difficulties these companies come up against when implementing such programmes and proposes to organize these difficulties around three dimensions: 1) the difficulties in implementing real supplier portfolio approaches; 2) the narrow view of value co-creation with suppliers, and 3) the persistent lack of integration of the purchasing function with other intern...
SYNOPSISRhomboid proteases are a fascinating class of enzymes that combine a serine protease active site within the core of an integral membrane protein. Despite having key roles...Full Text Available
It has become increasing clear that alterations in cellular metabolism have a key role in the generation and maintenance of cancer. Some of the metabolic changes can be attributed to the activation...Full Text Available
The establishment of the primary meristems through proliferation after germination is essential for plant post-embryonic development. Cytokinins have long been considered a key regulator of...Full Text Available
Eukaryotic cells can massively transport their own cytoplasmic contents into a lytic compartment, the vacuole/lysosome, for recycling through a conserved system called autophagy. The key process in...Full Text Available
BackgroundDysregulation of the insulin-like growth factor (IGF) system, a common consequence of adiposity-induced insulin resistance, may be a key underlying mechanism...Full Text Available
For aerodynamic force measurement in the ISL shock tunnel, the authors have developed a novel measurement technique. Its key feature is a mounting support, which releases the test model and tightens it again after a free flight duration of 10 to 15 millis...
Despite the availability of dozens of animal genome sequences, two key questions remain unanswered: First, what fraction of any species' genome confers biological function, and second, are apparent...Full Text Available
KOREA-JAPAN NUCLEAR WEAPON FREE ZONE (KJNWFZ) CONCEPT PAPER ...A Korea-Japan2 Nuclear Weapon Free Zone (hereafter KJNWFZ) is a new concept.Once realized, ...Finally, we outline the key elements of the Korea-Japan NWFZ proposed in this paper, noting
Hundreds of genomes have been successfully sequenced to date, and the data are publicly available. At the same time, the advances in large-scale expression and purification of recombinant proteins have...Full Text Available
The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as ...Full Text Available
How learning and memory is achieved in the brain is a central question in neuroscience. Key to today’s research into information storage in the brain is the concept of synaptic plasticity, a...Full Text Available