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Sample records for normal clrn1 protein

  1. CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development.

    Directory of Open Access Journals (Sweden)

    Scott F Geller

    2009-08-01

    Full Text Available Mutations in the CLRN1 gene cause Usher syndrome type 3 (USH3, a human disease characterized by progressive blindness and deafness. Clarin 1, the protein product of CLRN1, is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells, and recently demonstrated to be associated with the cytoskeleton. To study Clrn1, we created a Clrn1 knockout (KO mouse and characterized the histological and functional consequences of Clrn1 deletion in the retina and cochlea. Clrn1 KO mice do not develop a retinal degeneration phenotype, but exhibit progressive loss of sensory hair cells in the cochlea and deterioration of the organ of Corti by 4 months. Hair cell stereocilia in KO animals were longer and disorganized by 4 months, and some Clrn1 KO mice exhibited circling behavior by 5-6 months of age. Clrn1 mRNA expression was localized in the retina using in situ hybridization (ISH, laser capture microdissection (LCM, and RT-PCR. Retinal Clrn1 transcripts were found throughout development and adulthood by RT-PCR, although expression peaked at P7 and declined to undetectable levels in adult retina by ISH. LCM localized Clrn1 transcripts to the retinas inner nuclear layer, and WT levels of retinal Clrn1 expression were observed in photoreceptor-less retinas. Examination of Clrn1 KO mice suggests that CLRN1 is unnecessary in the murine retina but essential for normal cochlear development and function. This may reflect a redundancy in the mouse retina not present in human retina. In contrast to mouse KO models of USH1 and USH2, our data indicate that Clrn1 expression in the retina is restricted to the Müller glia. This is a novel finding, as most retinal degeneration associated proteins are expressed in photoreceptors, not in glia. If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal

  2. CLRN1 mutations cause nonsyndromic retinitis pigmentosa

    NARCIS (Netherlands)

    Khan, M.I.; Kersten, F.F.J.; Azam, M.; Collin, R.W.J.; Hussain, A.; Shah, S.T.; Keunen, J.E.E.; Kremer, J.M.J.; Cremers, F.P.M.; Qamar, R.; Hollander, A.I. den

    2011-01-01

    OBJECTIVE: To describe the mutations in the CLRN1 gene in patients from 2 consanguineous Pakistani families diagnosed with autosomal recessive retinitis pigmentosa (arRP). DESIGN: Case-series study. PARTICIPANTS: Affected and unaffected individuals of 2 consanguineous Pakistani families and 90

  3. The cone-dominant retina and the inner ear of zebrafish express the ortholog of CLRN1, the causative gene of human Usher syndrome type 3A.

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    Phillips, Jennifer B; Västinsalo, Hanna; Wegner, Jeremy; Clément, Aurélie; Sankila, Eeva-Marja; Westerfield, Monte

    2013-12-01

    Clarin-1 (CLRN1) is the causative gene in Usher syndrome type 3A, an autosomal recessive disorder characterized by progressive vision and hearing loss. CLRN1 encodes Clarin-1, a glycoprotein with homology to the tetraspanin family of proteins. Previous cell culture studies suggest that Clarin-1 localizes to the plasma membrane and interacts with the cytoskeleton. Mouse models demonstrate a role for the protein in mechanosensory hair bundle integrity, but the function of Clarin-1 in hearing remains unclear. Even less is known of its role in vision, because the Clrn1 knockout mouse does not exhibit a retinal phenotype and expression studies in murine retinas have provided conflicting results. Here, we describe cloning and expression analysis of the zebrafish clrn1 gene, and report protein localization of Clarin-1 in auditory and visual cells from embryonic through adult stages. We detect clrn1 transcripts as early as 24h post-fertilization, and expression is maintained through adulthood. In situ hybridization experiments show clrn1 transcripts enriched in mechanosensory hair cells and supporting cells of the inner ear and lateral line organ, photoreceptors, and cells of the inner retina. In mechanosensory hair cells, Clarin-1 is polarized to the apical cell body and the synapses. In the retina, Clarin-1 localizes to lateral cell contacts between photoreceptors and is associated with the outer limiting membrane and subapical processes emanating from Müller glial cells. We also find Clarin-1 protein in the outer plexiform, inner nuclear and ganglion cell layers of the retina. Given the importance of Clarin-1 function in the human retina, it is imperative to find an animal model with a comparable requirement. Our data provide a foundation for exploring the role of Clarin-1 in retinal cell function and survival in a diurnal, cone-dominant species. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Identification of a novel CLRN1 gene mutation in Usher syndrome type 3: two case reports.

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    Yoshimura, Hidekane; Oshikawa, Chie; Nakayama, Jun; Moteki, Hideaki; Usami, Shin-Ichi

    2015-05-01

    This study examines the CLRN1 gene mutation analysis in Japanese patients who were diagnosed with Usher syndrome type 3 (USH3) on the basis of clinical findings. Genetic analysis using massively parallel DNA sequencing (MPS) was conducted to search for 9 causative USH genes in 2 USH3 patients. We identified the novel pathogenic mutation in the CLRN1 gene in 2 patients. The missense mutation was confirmed by functional prediction software and segregation analysis. Both patients were diagnosed as having USH3 caused by the CLRN1 gene mutation. This is the first report of USH3 with a CLRN1 gene mutation in Asian populations. Validating the presence of clinical findings is imperative for properly differentiating among USH subtypes. In addition, mutation screening using MPS enables the identification of causative mutations in USH. The clinical diagnosis of this phenotypically variable disease can then be confirmed. © The Author(s) 2015.

  5. Localization and expression of clarin-1, the Clrn1 gene product, in auditory hair cells and photoreceptors

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    Zallocchi, Marisa; Meehan, Daniel T.; Delimont, Duane; Askew, Charles; Garrige, Suneetha; Gratton, Michael Anne; Rothermund-Franklin, Christie A.; Cosgrove, Dominic

    2009-01-01

    The Usher syndrome 3A (CLRN1) gene encodes clarin-1, which is a member of the tetraspanin family of transmembrane proteins. Although identified more than 6 years ago, little is known about its localization or function in the eye and ear. We developed a polyclonal antibody that react with all clarin-1 isoforms and used it to characterize protein expression in cochlea and retina. In the cochlea, we observe clarin-1expression in the stereocilia of P0 mice, and in synaptic terminals present at the base of the auditory hair cells from E18 to P6. In the retina, clarin-1 localizes to the connecting cilia, inner segment of photoreceptors and to the ribbon synapses. RT-PCR from P0 cochlea and P28 retina show mRNAs encoding only isoforms 2 and 3. Western-blots show that only isoform 2 is present in protein extracts from these same tissues. We examined clarin-1 expression in the immortomouse-derived hair cell line UB/OC-1. Only isoform 2 is expressed in UB/OC-1 at both mRNA and protein levels, suggesting this isoform is biologically relevant to hair cell function. The protein co-localizes with microtubules and post-transgolgi vesicles. The sub-cellular localization of clarin-1 in hair cells and photoreceptors suggests it functions at both the basal and apical poles of neurosensoriepithelia. PMID:19539019

  6. Unilateral retinitis pigmentosa occurring in an individual with a mutation in the CLRN1 gene.

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    Sim, Peng Yong; Jeganathan, V Swetha E; Wright, Alan F; Cackett, Peter

    2018-03-15

    This case report depicts the clinical course of a female patient with unilateral retinitis pigmentosa, who first presented at the age of 12 years. Fundus photography at the time revealed unilateral pigmentary retinopathy, which was associated with extinguished electroretinogram (ERG) signal. At 35 years of age, fundus examination revealed deterioration of pre-existing unilateral pigmentary retinopathy with progressive visual field defect detected on Goldmann visual field testing. ERG findings remained unchanged and multifocal ERG showed unilateral decrease in amplitude in the affected eye. The patient was referred for genetic counselling. Next-generation sequencing identified a deleterious heterozygous c.118T>G (p.Cys40Gly) mutation in the CLRN1 gene. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Zebrafish Models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal That Clarin-1 Is an Essential Hair Bundle Protein.

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    Gopal, Suhasini R; Chen, Daniel H-C; Chou, Shih-Wei; Zang, Jingjing; Neuhauss, Stephan C F; Stepanyan, Ruben; McDermott, Brian M; Alagramam, Kumar N

    2015-07-15

    Usher syndrome type III (USH3) is characterized by progressive loss of hearing and vision, and varying degrees of vestibular dysfunction. It is caused by mutations that affect the human clarin-1 protein (hCLRN1), a member of the tetraspanin protein family. The missense mutation CLRN1(N48K), which affects a conserved N-glycosylation site in hCLRN1, is a common causative USH3 mutation among Ashkenazi Jews. The affected individuals hear at birth but lose that function over time. Here, we developed an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype. Immunolabeling demonstrated that Clrn1 localized to the hair cell bundles (hair bundles). The clrn1 mutants generated by zinc finger nucleases displayed aberrant hair bundle morphology with diminished function. Two transgenic zebrafish that express either hCLRN1 or hCLRN1(N48K) in hair cells were produced to examine the subcellular localization patterns of wild-type and mutant human proteins. hCLRN1 localized to the hair bundles similarly to zebrafish Clrn1; in contrast, hCLRN1(N48K) largely mislocalized to the cell body with a small amount reaching the hair bundle. We propose that this small amount of hCLRN1(N48K) in the hair bundle provides clarin-1-mediated function during the early stages of life; however, the presence of hCLRN1(N48K) in the hair bundle diminishes over time because of intracellular degradation of the mutant protein, leading to progressive loss of hair bundle integrity and hair cell function. These findings and genetic tools provide an understanding and path forward to identify therapies to mitigate hearing loss linked to the CLRN1 mutation. Mutations in the clarin-1 gene affect eye and ear function in humans. Individuals with the CLRN1(N48K) mutation are born able to hear but lose that function over time. Here, we develop an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype

  8. A deep intronic CLRN1 (USH3A) founder mutation generates an aberrant exon and underlies severe Usher syndrome on the Arabian Peninsula.

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    Khan, Arif O; Becirovic, Elvir; Betz, Christian; Neuhaus, Christine; Altmüller, Janine; Maria Riedmayr, Lisa; Motameny, Susanne; Nürnberg, Gudrun; Nürnberg, Peter; Bolz, Hanno J

    2017-05-03

    Deafblindness is mostly due to Usher syndrome caused by recessive mutations in the known genes. Mutation-negative patients therefore either have distinct diseases, mutations in yet unknown Usher genes or in extra-exonic parts of the known genes - to date a largely unexplored possibility. In a consanguineous Saudi family segregating Usher syndrome type 1 (USH1), NGS of genes for Usher syndrome, deafness and retinal dystrophy and subsequent whole-exome sequencing each failed to identify a mutation. Genome-wide linkage analysis revealed two small candidate regions on chromosome 3, one containing the USH3A gene CLRN1, which has never been associated with Usher syndrome in Saudi Arabia. Whole-genome sequencing (WGS) identified a homozygous deep intronic mutation, c.254-649T > G, predicted to generate a novel donor splice site. CLRN1 minigene-based analysis confirmed the splicing of an aberrant exon due to usage of this novel motif, resulting in a frameshift and a premature termination codon. We identified this mutation in an additional two of seven unrelated mutation-negative Saudi USH1 patients. Locus-specific markers indicated that c.254-649T > G CLRN1 represents a founder allele that may significantly contribute to deafblindness in this population. Our finding underlines the potential of WGS to uncover atypically localized, hidden mutations in patients who lack exonic mutations in the known disease genes.

  9. The mechanosensory structure of the hair cell requires clarin-1, a protein encoded by Usher syndrome III causative gene.

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    Geng, Ruishuang; Melki, Sami; Chen, Daniel H-C; Tian, Guilian; Furness, David N; Oshima-Takago, Tomoko; Neef, Jakob; Moser, Tobias; Askew, Charles; Horwitz, Geoff; Holt, Jeffrey R; Imanishi, Yoshikazu; Alagramam, Kumar N

    2012-07-11

    Mutation in the clarin-1 gene (Clrn1) results in loss of hearing and vision in humans (Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 gene (Clrn1(-/-)) show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca(2+) currents and membrane capacitance from inner hair cells that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] loading, and transduction currents pointed to diminished cochlear hair bundle function in Clrn1(-/-) mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip links and staircase arrangement of stereocilia were not primarily affected by Clrn1(-/-) mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant p.N48K failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p.N48K in clarin-1 (Clrn1(N48K)) supports our in vitro and Clrn1(-/-) mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Furthermore, the ear phenotype in the Clrn1(N48K) mouse suggests that it is a valuable model for ear disease in CLRN1(N48K), the most prevalent Usher syndrome III mutation in North America.

  10. The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene

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    Geng, Ruishuang; Melki, Sami; Chen, Daniel H.-C.; Tian, Guilian; Furness, David; Oshima-Takago, Tomoko; Neef, Jakob; Moser, Tobias; Askew, Charles; Horwitz, Geoff; Holt, Jeffrey; Imanishi, Yoshikazu; Alagramam, Kumar N.

    2012-01-01

    Mutation in the clarin-1 gene results in loss of hearing and vision in humans (Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 (Clrn1−/−) gene show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca2+ currents and membrane capacitance from IHCs that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 loading and transduction currents pointed to diminished cochlear hair bundle function in Clrn1−/− mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip-links and staircase arrangement of stereocilia were not primarily affected by Clrn1−/− mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant, p.N48K, failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p. N48K in clarin-1 (Clrn1N48K) supports our in vitro and Clrn1−/− mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Further, the ear phenotype in the Clrn1N48K mouse suggests that it is a valuable model for ear disease in CLRN1N48K, the most prevalent Usher III mutation in North America. PMID:22787034

  11. A modified gelatin zymography technique incorporating total protein normalization.

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    Raykin, Julia; Snider, Eric; Bheri, Sruti; Mulvihill, John; Ethier, C Ross

    2017-03-15

    Gelatinase zymography is a commonly used laboratory procedure; however, variability in sample loading and concentration reduce the accuracy of quantitative results obtained from this technique. To facilitate normalization of gelatinase activity by loaded protein amount, we developed a protocol using the trihalocompound 2,2,2-trichloroethanol to allow for gelatin zymography and total protein labeling within the same gel. We showed that detected protein levels increased linearly with loading, and describe a loading concentration range over which normalized gelatinase activity was constant. We conclude that in-gel total protein detection is feasible in gelatin zymography and greatly improves comparison of gelatinase activity between samples. Published by Elsevier Inc.

  12. RPE cell surface proteins in normal and dystrophic rats

    International Nuclear Information System (INIS)

    Clark, V.M.; Hall, M.O.

    1986-01-01

    Membrane-bound proteins in plasma membrane enriched fractions from cultured rat RPE were analyzed by two-dimensional gel electrophoresis. Membrane proteins were characterized on three increasingly specific levels. Total protein was visualized by silver staining. A maximum of 102 separate proteins were counted in silver-stained gels. Glycoproteins were labeled with 3H-glucosamine or 3H-fucose and detected by autoradiography. Thirty-eight fucose-labeled and 61-71 glucosamine-labeled proteins were identified. All of the fucose-labeled proteins were labeled with glucosamine-derived radioactivity. Proteins exposed at the cell surface were labeled by lactoperoxidase-catalyzed radioiodination prior to preparation of membranes for two-dimensional analysis. Forty separate 125I-labeled surface proteins were resolved by two-dimensional electrophoresis/autoradiography. Comparison with the glycoprotein map showed that a number of these surface labeled proteins were glycoproteins. Two-dimensional maps of total protein, fucose-labeled, and glucosamine-labeled glycoproteins, and 125I-labeled surface proteins of membranes from dystrophic (RCS rdy-p+) and normal (Long Evans or RCS rdy+p+) RPE were compared. No differences in the total protein or surface-labeled proteins were observed. However, the results suggest that a 183K glycoprotein is more heavily glycosylated with glucosamine and fucose in normal RPE membranes as compared to membranes from dystrophic RPE

  13. Cy5 total protein normalization in Western blot analysis.

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    Hagner-McWhirter, Åsa; Laurin, Ylva; Larsson, Anita; Bjerneld, Erik J; Rönn, Ola

    2015-10-01

    Western blotting is a widely used method for analyzing specific target proteins in complex protein samples. Housekeeping proteins are often used for normalization to correct for uneven sample loads, but these require careful validation since expression levels may vary with cell type and treatment. We present a new, more reliable method for normalization using Cy5-prelabeled total protein as a loading control. We used a prelabeling protocol based on Cy5 N-hydroxysuccinimide ester labeling that produces a linear signal response. We obtained a low coefficient of variation (CV) of 7% between the ratio of extracellular signal-regulated kinase (ERK1/2) target to Cy5 total protein control signals over the whole loading range from 2.5 to 20.0μg of Chinese hamster ovary cell lysate protein. Corresponding experiments using actin or tubulin as controls for normalization resulted in CVs of 13 and 18%, respectively. Glyceraldehyde-3-phosphate dehydrogenase did not produce a proportional signal and was not suitable for normalization in these cells. A comparison of ERK1/2 signals from labeled and unlabeled samples showed that Cy5 prelabeling did not affect antibody binding. By using total protein normalization we analyzed PP2A and Smad2/3 levels with high confidence. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. WEBnm@: a web application for normal mode analyses of proteins

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    Reuter Nathalie

    2005-03-01

    Full Text Available Abstract Background Normal mode analysis (NMA has become the method of choice to investigate the slowest motions in macromolecular systems. NMA is especially useful for large biomolecular assemblies, such as transmembrane channels or virus capsids. NMA relies on the hypothesis that the vibrational normal modes having the lowest frequencies (also named soft modes describe the largest movements in a protein and are the ones that are functionally relevant. Results We developed a web-based server to perform normal modes calculations and different types of analyses. Starting from a structure file provided by the user in the PDB format, the server calculates the normal modes and subsequently offers the user a series of automated calculations; normalized squared atomic displacements, vector field representation and animation of the first six vibrational modes. Each analysis is performed independently from the others and results can be visualized using only a web browser. No additional plug-in or software is required. For users who would like to analyze the results with their favorite software, raw results can also be downloaded. The application is available on http://www.bioinfo.no/tools/normalmodes. We present here the underlying theory, the application architecture and an illustration of its features using a large transmembrane protein as an example. Conclusion We built an efficient and modular web application for normal mode analysis of proteins. Non specialists can easily and rapidly evaluate the degree of flexibility of multi-domain protein assemblies and characterize the large amplitude movements of their domains.

  15. Normal mode-guided transition pathway generation in proteins.

    Directory of Open Access Journals (Sweden)

    Byung Ho Lee

    Full Text Available The biological function of proteins is closely related to its structural motion. For instance, structurally misfolded proteins do not function properly. Although we are able to experimentally obtain structural information on proteins, it is still challenging to capture their dynamics, such as transition processes. Therefore, we need a simulation method to predict the transition pathways of a protein in order to understand and study large functional deformations. Here, we present a new simulation method called normal mode-guided elastic network interpolation (NGENI that performs normal modes analysis iteratively to predict transition pathways of proteins. To be more specific, NGENI obtains displacement vectors that determine intermediate structures by interpolating the distance between two end-point conformations, similar to a morphing method called elastic network interpolation. However, the displacement vector is regarded as a linear combination of the normal mode vectors of each intermediate structure, in order to enhance the physical sense of the proposed pathways. As a result, we can generate more reasonable transition pathways geometrically and thermodynamically. By using not only all normal modes, but also in part using only the lowest normal modes, NGENI can still generate reasonable pathways for large deformations in proteins. This study shows that global protein transitions are dominated by collective motion, which means that a few lowest normal modes play an important role in this process. NGENI has considerable merit in terms of computational cost because it is possible to generate transition pathways by partial degrees of freedom, while conventional methods are not capable of this.

  16. SwarmDock and the Use of Normal Modes in Protein-Protein Docking

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    Paul A. Bates

    2010-09-01

    Full Text Available Here is presented an investigation of the use of normal modes in protein-protein docking, both in theory and in practice. Upper limits of the ability of normal modes to capture the unbound to bound conformational change are calculated on a large test set, with particular focus on the binding interface, the subset of residues from which the binding energy is calculated. Further, the SwarmDock algorithm is presented, to demonstrate that the modelling of conformational change as a linear combination of normal modes is an effective method of modelling flexibility in protein-protein docking.

  17. Protein Degradation in Normal and Beige (Chediak-Higashi) Mice

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    Lyons, Robert T.; Pitot, Henry C.

    1978-01-01

    The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [14C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal. The rates of uptake and degradation of an exogenous protein were determined in normal and beige mice by intravenously injecting 125I-bovine serum albumin and following, in peripheral blood, the loss with time of phosphotungstic acid-insoluble bovine serum albumin and the parallel appearance of phosphotungstic acid-soluble (degraded) material. No significant differences were observed between beige and normal mice in the uptake by liver lysosomes of 125I-bovine serum albumin (t½ = 3.9 and 2.8 h, respectively). However, it was found that lysosomes from livers of beige mice released phosphotungstic acid-soluble radioactivity at a rate significantly slower than normal (t½ = 6.8 and 3.1 h, respectively). This defect in beige mice could be corrected by chronic administration of carbamyl choline (t½ = 3.5 h), a cholinergic agonist which raises intracellular cyclic GMP levels. However, no significant differences between normal and beige mice were observed either in the ability of soluble extracts of liver and kidney to bind [3H]cyclic GMP in vitro or in the basal levels of cyclic AMP in both tissues. The relevance of these observations to the presumed biochemical defect underlying the Chediak-Higashi syndrome is discussed. PMID:202611

  18. ProNormz--an integrated approach for human proteins and protein kinases normalization.

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    Subramani, Suresh; Raja, Kalpana; Natarajan, Jeyakumar

    2014-02-01

    The task of recognizing and normalizing protein name mentions in biomedical literature is a challenging task and important for text mining applications such as protein-protein interactions, pathway reconstruction and many more. In this paper, we present ProNormz, an integrated approach for human proteins (HPs) tagging and normalization. In Homo sapiens, a greater number of biological processes are regulated by a large human gene family called protein kinases by post translational phosphorylation. Recognition and normalization of human protein kinases (HPKs) is considered to be important for the extraction of the underlying information on its regulatory mechanism from biomedical literature. ProNormz distinguishes HPKs from other HPs besides tagging and normalization. To our knowledge, ProNormz is the first normalization system available to distinguish HPKs from other HPs in addition to gene normalization task. ProNormz incorporates a specialized synonyms dictionary for human proteins and protein kinases, a set of 15 string matching rules and a disambiguation module to achieve the normalization. Experimental results on benchmark BioCreative II training and test datasets show that our integrated approach achieve a fairly good performance and outperforms more sophisticated semantic similarity and disambiguation systems presented in BioCreative II GN task. As a freely available web tool, ProNormz is useful to developers as extensible gene normalization implementation, to researchers as a standard for comparing their innovative techniques, and to biologists for normalization and categorization of HPs and HPKs mentions in biomedical literature. URL: http://www.biominingbu.org/pronormz. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Serum Copper and Plasma Protein Status in Normal Pregnancy

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    Nushrat Noor, Nasim Jahan, Nayma Sultana

    2012-12-01

    Full Text Available AbstractBackground: Gradual alteration of serum copper and some plasma protein levels may occur with advancement of pregnancy, which is associated with increased maternal and infant morbidity and mortality.Objective: To observe serum copper and plasma protein levels in normal pregnant women of different trimesters in order to find out their nutritional status.Methods: This cross sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC, Dhaka, between 1st January 2010 and December 2010. Ninety normal pregnant women of different trimesters with age 20-30 years were included in the study group. They were selected from Out Patient Department of Obstetrics and Gynaecology, SSMC. Age matched 30 non-pregnant women were taken as control. Serum copper level was measured by Spectrophotometric method, serum total protein and albumin levels were estimated by standard method. Statistical analysis was done by one way ANOVA, Bonferroni and Pearson’s correlation coefficient test as applicable.Results: Serum Cu levels were significantly higher in all trimesters of pregnant women compared to control. Again, this value was significantly higher in 3rd trimester than that of in 1st and 2nd trimester and also in 2nd trimester than that of in 1st trimester. In addition, mean serum total protein level was significantly lower in 3rd trimester than control but no statistically significant difference was observed among different trimesters. Again, mean serum albumin level was significantly lower in 2nd and 3rd trimester than 1st trimester and control. In addition, serum Cu concentration showed significant positive correlation with different trimesters of gestation.Conclusion: This study reveals that hypercupremia along with hypoproteinemia occur in pregnant women from 1st to 3rd trimester of gestation. This gradual alteration of micro and macronutrients become more profound with advancement of pregnancy.

  20. Rap G protein signal in normal and disordered lymphohematopoiesis.

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    Minato, Nagahiro

    2013-09-10

    Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the development and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy. © 2013 Elsevier Inc. All rights reserved.

  1. STAT proteins: from normal control of cellular events to tumorigenesis.

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    Calò, Valentina; Migliavacca, Manuela; Bazan, Viviana; Macaluso, Marcella; Buscemi, Maria; Gebbia, Nicola; Russo, Antonio

    2003-11-01

    Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is made up of STAT2, STAT4, and STAT6, which are activated by a small number of cytokines and play a distinct role in the development of T-cells and in IFNgamma signaling. The other group includes STAT1, STAT3, and STAT5, activated in different tissues by means of a series of ligands and involved in IFN signaling, development of the mammary gland, response to GH, and embriogenesis. This latter group of STATS plays an important role in controlling cell-cycle progression and apoptosis and thus contributes to oncogenesis. Although an increased expression of STAT1 has been observed in many human neoplasias, this molecule can be considered a potential tumor suppressor, since it plays an important role in growth arrest and in promoting apoptosis. On the other hand, STAT3 and 5 are considered as oncogenes, since they bring about the activation of cyclin D1, c-Myc, and bcl-xl expression, and are involved in promoting cell-cycle progression, cellular transformation, and in preventing apoptosis.

  2. Kinome signaling through regulated protein-protein interactions in normal and cancer cells.

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    Pawson, Tony; Kofler, Michael

    2009-04-01

    The flow of molecular information through normal and oncogenic signaling pathways frequently depends on protein phosphorylation, mediated by specific kinases, and the selective binding of the resulting phosphorylation sites to interaction domains present on downstream targets. This physical and functional interplay of catalytic and interaction domains can be clearly seen in cytoplasmic tyrosine kinases such as Src, Abl, Fes, and ZAP-70. Although the kinase and SH2 domains of these proteins possess similar intrinsic properties of phosphorylating tyrosine residues or binding phosphotyrosine sites, they also undergo intramolecular interactions when linked together, in a fashion that varies from protein to protein. These cooperative interactions can have diverse effects on substrate recognition and kinase activity, and provide a variety of mechanisms to link the stimulation of catalytic activity to substrate recognition. Taken together, these data have suggested how protein kinases, and the signaling pathways in which they are embedded, can evolve complex properties through the stepwise linkage of domains within single polypeptides or multi-protein assemblies.

  3. Normal mode analysis as a method to derive protein dynamics information from the Protein Data Bank.

    Science.gov (United States)

    Wako, Hiroshi; Endo, Shigeru

    2017-12-01

    Normal mode analysis (NMA) can facilitate quick and systematic investigation of protein dynamics using data from the Protein Data Bank (PDB). We developed an elastic network model-based NMA program using dihedral angles as independent variables. Compared to the NMA programs that use Cartesian coordinates as independent variables, key attributes of the proposed program are as follows: (1) chain connectivity related to the folding pattern of a polypeptide chain is naturally embedded in the model; (2) the full-atom system is acceptable, and owing to a considerably smaller number of independent variables, the PDB data can be used without further manipulation; (3) the number of variables can be easily reduced by some of the rotatable dihedral angles; (4) the PDB data for any molecule besides proteins can be considered without coarse-graining; and (5) individual motions of constituent subunits and ligand molecules can be easily decomposed into external and internal motions to examine their mutual and intrinsic motions. Its performance is illustrated with an example of a DNA-binding allosteric protein, a catabolite activator protein. In particular, the focus is on the conformational change upon cAMP and DNA binding, and on the communication between their binding sites remotely located from each other. In this illustration, NMA creates a vivid picture of the protein dynamics at various levels of the structures, i.e., atoms, residues, secondary structures, domains, subunits, and the complete system, including DNA and cAMP. Comparative studies of the specific protein in different states, e.g., apo- and holo-conformations, and free and complexed configurations, provide useful information for studying structurally and functionally important aspects of the protein.

  4. Dendritic protein synthesis in the normal and diseased brain

    Science.gov (United States)

    Swanger, Sharon A.; Bassell, Gary J.

    2015-01-01

    Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases. PMID:23262237

  5. Myb proteins: angels and demons in normal and transformed cells.

    Science.gov (United States)

    Zhou, Ye; Ness, Scott A

    2011-01-01

    A key regulator of proliferation, differentiation and cell fate, the c-Myb transcription factor regulates the expression of hundreds of genes and is in turn regulated by numerous pathways and protein interactions. However, the most unique feature of c-Myb is that it can be converted into an oncogenic transforming protein through a few mutations that completely change its activity and specificity. The c-Myb protein is a myriad of interactions and activities rolled up in a protein that controls proliferation and differentiation in many different cell types. Here we discuss the background and recent progress that have led to a better understanding of this complex protein, and outline the questions that have yet to be answered.

  6. Molecular analysis of quality protein (QPM) and normal maize ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... genetic variation among QPM and normal maize varieties is important for an efficient selection and .... olymerase chain reaction (PCR) amplifications of RAPD and ISSR ..... Genetic characterization of Malawian cowpea.

  7. Trichohyalin-like 1 protein, a member of fused S100 proteins, is expressed in normal and pathologic human skin

    Energy Technology Data Exchange (ETDEWEB)

    Yamakoshi, Takako [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Makino, Teruhiko, E-mail: tmakino@med.u-toyama.ac.jp [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Ur Rehman, Mati; Yoshihisa, Yoko [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Sugimori, Michiya [Department of Integrative Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Shimizu, Tadamichi, E-mail: shimizut@med.u-toyama.ac.jp [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan)

    2013-03-01

    Highlights: ► Trichohyalin-like 1 protein is a member of the fused-type S100 protein gene family. ► Specific antibodies against the C-terminus of the TCHHL1 protein were generated. ► TCHHL1 proteins were expressed in the basal layer of the normal epidermis. ► TCHHL1 proteins were strongly expressed in tumor nests of BCC and SCC. ► The expression of TCHHL1 proteins increased in epidermis of psoriasis vulgaris. - Abstract: Trichohyalin-like 1 (TCHHL1) protein is a novel member of the fused-type S100 protein gene family. The deduced amino acid sequence of TCHHL1 contains an EF-hand domain in the N-terminus, one trans-membrane domain and a nuclear localization signal. We generated specific antibodies against the C-terminus of the TCHHL1 protein and examined the expression of TCHHL1 proteins in normal and pathological human skin. An immunohistochemical study showed that TCHHL1 proteins were expressed in the basal layer of the normal epidermis. In addition, signals of TCHHL1 proteins were observed around the nuclei of cultured growing keratinocytes. Accordingly, TCHHL1 mRNA has been detected in normal skin and cultured growing keratinocytes. Furthermore, TCHHL1 proteins were strongly expressed in the peripheral areas of tumor nests in basal cell carcinomas and squamous cell carcinomas. A dramatic increase in the number of Ki67 positive cells was observed in TCHHL1-expressing areas. The expression of TCHHL1 proteins also increased in non-cancerous hyperproliferative epidermal tissues such as those of psoriasis vulgaris and lichen planus. These findings highlight the possibility that TCHHL1 proteins are expressed in growing keratinocytes of the epidermis and might be associated with the proliferation of keratinocytes.

  8. Trichohyalin-like 1 protein, a member of fused S100 proteins, is expressed in normal and pathologic human skin

    International Nuclear Information System (INIS)

    Yamakoshi, Takako; Makino, Teruhiko; Ur Rehman, Mati; Yoshihisa, Yoko; Sugimori, Michiya; Shimizu, Tadamichi

    2013-01-01

    Highlights: ► Trichohyalin-like 1 protein is a member of the fused-type S100 protein gene family. ► Specific antibodies against the C-terminus of the TCHHL1 protein were generated. ► TCHHL1 proteins were expressed in the basal layer of the normal epidermis. ► TCHHL1 proteins were strongly expressed in tumor nests of BCC and SCC. ► The expression of TCHHL1 proteins increased in epidermis of psoriasis vulgaris. - Abstract: Trichohyalin-like 1 (TCHHL1) protein is a novel member of the fused-type S100 protein gene family. The deduced amino acid sequence of TCHHL1 contains an EF-hand domain in the N-terminus, one trans-membrane domain and a nuclear localization signal. We generated specific antibodies against the C-terminus of the TCHHL1 protein and examined the expression of TCHHL1 proteins in normal and pathological human skin. An immunohistochemical study showed that TCHHL1 proteins were expressed in the basal layer of the normal epidermis. In addition, signals of TCHHL1 proteins were observed around the nuclei of cultured growing keratinocytes. Accordingly, TCHHL1 mRNA has been detected in normal skin and cultured growing keratinocytes. Furthermore, TCHHL1 proteins were strongly expressed in the peripheral areas of tumor nests in basal cell carcinomas and squamous cell carcinomas. A dramatic increase in the number of Ki67 positive cells was observed in TCHHL1-expressing areas. The expression of TCHHL1 proteins also increased in non-cancerous hyperproliferative epidermal tissues such as those of psoriasis vulgaris and lichen planus. These findings highlight the possibility that TCHHL1 proteins are expressed in growing keratinocytes of the epidermis and might be associated with the proliferation of keratinocytes

  9. Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

    International Nuclear Information System (INIS)

    Asafi, M S; Tekpinar, M; Yildirim, A

    2016-01-01

    Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated. (paper)

  10. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    International Nuclear Information System (INIS)

    Curtis, Carol D; Thorngren, Daniel L; Nardulli, Ann M

    2010-01-01

    During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

  11. Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models.

    Science.gov (United States)

    Khan, Sehrish Haider; Javed, Muhammad Rizwan; Qasim, Muhammad; Shahzadi, Samar; Jalil, Asma; Rehman, Shahid Ur

    2014-01-01

    Usher syndrome is an autosomal recessive disorder that causes hearing loss, Retinitis Pigmentosa (RP) and vestibular dysfunction. It is clinically and genetically heterogeneous disorder which is clinically divided into three types i.e. type I, type II and type III. To date, there are about twelve loci and ten identified genes which are associated with Usher syndrome. A mutation in any of these genes e.g. CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, USH2A and DFNB31 can result in Usher syndrome or non-syndromic deafness. These genes provide instructions for making proteins that play important roles in normal hearing, balance and vision. Studies have shown that protein structures of only seven genes have been determined experimentally and there are still three genes whose structures are unavailable. These genes are Clarin-1, GPR98 and Usherin. In the absence of an experimentally determined structure, homology modeling and threading often provide a useful 3D model of a protein. Therefore in the current study Clarin-1 and GPR98 proteins have been analyzed for signal peptide, domains and motifs. Clarin-1 protein was found to be without any signal peptide and consists of prokar lipoprotein domain. Clarin-1 is classified within claudin 2 super family and consists of twelve motifs. Whereas, GPR98 has a 29 amino acids long signal peptide and classified within GPCR family 2 having Concanavalin A-like lectin/glucanase superfamily. It was found to be consists of GPS and G protein receptor F2 domains and twenty nine motifs. Their 3D structures have been predicted using I-TASSER server. The model of Clarin-1 showed only α-helix but no beta sheets while model of GPR98 showed both α-helix and β sheets. The predicted structures were then evaluated and validated by MolProbity and Ramachandran plot. The evaluation of the predicted structures showed 78.9% residues of Clarin-1 and 78.9% residues of GPR98 within favored regions. The findings of present study has resulted in the

  12. Relation between Protein Intrinsic Normal Mode Weights and Pre-Existing Conformer Populations.

    Science.gov (United States)

    Ozgur, Beytullah; Ozdemir, E Sila; Gursoy, Attila; Keskin, Ozlem

    2017-04-20

    Intrinsic fluctuations of a protein enable it to sample a large repertoire of conformers including the open and closed forms. These distinct forms of the protein called conformational substates pre-exist together in equilibrium as an ensemble independent from its ligands. The role of ligand might be simply to alter the equilibrium toward the most appropriate form for binding. Normal mode analysis is proved to be useful in identifying the directions of conformational changes between substates. In this study, we demonstrate that the ratios of normalized weights of a few normal modes driving the protein between its substates can give insights about the ratios of kinetic conversion rates of the substates, although a direct relation between the eigenvalues and kinetic conversion rates or populations of each substate could not be observed. The correlation between the normalized mode weight ratios and the kinetic rate ratios is around 83% on a set of 11 non-enzyme proteins and around 59% on a set of 17 enzymes. The results are suggestive that mode motions carry intrinsic relations with thermodynamics and kinetics of the proteins.

  13. Effect of 60Co-irradiation on normal and low protein diet fed rat brain

    International Nuclear Information System (INIS)

    Hasan, S.S.; Habibullah, M.

    1980-01-01

    The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain. (orig.) [de

  14. Effect of /sup 60/Co-irradiation on normal and low protein diet fed rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, S S [Garhwal Univ., Srinagar, Uttar Pradesh (India). Dept. of Zoology; Habibullah, M [Jawaharlal Nehru Univ., New Delhi (India). Neurobiology Lab.

    1980-06-01

    The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain.

  15. Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

    1980-07-01

    High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

  16. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    Science.gov (United States)

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

  17. Effects of whey protein and its two major protein components on satiety and food intake in normal-weight women.

    Science.gov (United States)

    Chungchunlam, Sylvia M S; Henare, Sharon J; Ganesh, Siva; Moughan, Paul J

    2017-06-01

    Protein is the most satiating macronutrient and is source dependent, with whey protein thought to be particularly satiating. The purported satiating effect of whey protein may be due to the unique mixture of proteins in whey or to the major constituent individual proteins (β-lactoglobulin and α-lactalbumin). The objective of the study was to compare the effects of isoenergetic (~2100kJ, ~500kcal) preload meals enriched (~50g protein) with either whey protein isolate (WP), β-lactoglobulin (BL) isolate or α-lactalbumin (AL) isolate, on food intake at an ad libitum test meal 120min later and subjective ratings of appetite (hunger, desire to eat, prospective food consumption and fullness) using visual analogue scales (VAS). Twenty adult normal-weight women (mean age 24.2±0.8years; mean BMI 22.7±0.4kg/m 2 ) participated in the study which used a single-blind completely randomised block design, where each subject consumed each of the three preload meals. Energy intake at the ad libitum test meal and total energy intakes (preload+test meal) did not differ between the three preload meals (p>0.05). There were no significant differences observed for the VAS scores and net incremental area under the curve (net iAUC) during the 120min following consumption of the three preload meals for subjective ratings of appetite (p>0.05). The findings show that the satiating effect of whey protein was similar to that of BL or AL individually and suggest that the major whey protein components BL and AL do not mediate the satiating effect of whey protein. The present human trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12615000344594. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Complete topology inversion can be part of normal membrane protein biogenesis.

    Science.gov (United States)

    Woodall, Nicholas B; Hadley, Sarah; Yin, Ying; Bowie, James U

    2017-04-01

    The topology of helical membrane proteins is generally defined during insertion of the transmembrane helices, yet it is now clear that it is possible for topology to change under unusual circumstances. It remains unclear, however, if topology reorientation is part of normal biogenesis. For dual topology dimer proteins such as the multidrug transporter EmrE, there may be evolutionary pressure to allow topology flipping so that the populations of both orientations can be equalized. We previously demonstrated that when EmrE is forced to insert in a distorted topology, topology flipping of the first transmembrane helix can occur during translation. Here, we show that topological malleability also extends to the C-terminal helix and that even complete topology inversion of the entire EmrE protein can occur after the full protein is translated and inserted. Thus, topology rearrangements are possible during normal biogenesis. Wholesale topology flipping is remarkable given the physical constraints of the membrane and expands the range of possible membrane protein folding pathways, both productive and detrimental. © 2017 The Protein Society.

  19. Serum protein concentration in low-dose total body irradiation of normal and malnourished rats

    International Nuclear Information System (INIS)

    Viana, W.C.M.; Lambertz, D.; Borges, E.S.; Neto, A.M.O.; Lambertz, K.M.F.T.; Amaral, A.

    2016-01-01

    Among the radiotherapeutics' modalities, total body irradiation (TBI) is used as treatment for certain hematological, oncological and immunological diseases. The aim of this study was to evaluate the long-term effects of low-dose TBI on plasma concentration of total protein and albumin using prematurely and undernourished rats as animal model. For this, four groups with 9 animals each were formed: Normal nourished (N); Malnourished (M); Irradiated Normal nourished (IN); Irradiated Malnourished (IM). At the age of 28 days, rats of the IN and IM groups underwent total body gamma irradiation with a source of cobalt-60. Total protein and Albumin in the blood serum was quantified by colorimetry. This research indicates that procedures involving low-dose total body irradiation in children have repercussions in the reduction in body-mass as well as in the plasma levels of total protein and albumin. Our findings reinforce the periodic monitoring of total serum protein and albumin levels as an important tool in long-term follow-up of pediatric patients in treatments associated to total body irradiation. - Highlights: • Low-dose total body irradiation (TBI) in children have repercussions in their body-mass. • Long-term total protein and albumin levels are affected by TBI. • The monitoring of total protein and albumin levels are useful in the follow-up of TBI pediatric patients.

  20. Cytoskeletal proteins in the follicular wall of normal andcystic ovaries of sows

    Directory of Open Access Journals (Sweden)

    Fabiano J.F. de Sant'Ana

    2015-02-01

    Full Text Available The expression of cytoskeletal proteins was evaluated immunohistochemically in 36 normal ovaries sampled from 18 sows and 44 cystic ovaries sampled from of 22 sows, was evaluated. All sows had history of reproductive problems, such as infertility or subfertility. The immunohistochemically stained area (IHCSA was quantified through image analysis to evaluate the expression of these proteins in the follicular wall of secondary, tertiary, and cystic follicles. Cytokeratins (CK immunoreactivity was strong in the granulosa cell layer (GC and mild in the theca interna (TI and externa (TE of the normal follicles. There was severe reduction of the reaction to CK in the GC in the cystic follicles, mainly in the luteinized cysts. The immunoreactivity for vimentin was higher in the GC from normal and cystic follicles in contrast with the other follicular structures. In the luteinized cysts, the IHCSA for vimentin was significantly higher in TI and in both observed cysts, the labeling was more accentuated in TE. Immunohistochemical detection of desmin and α-SMA was restricted to the TE, without differences between the normal and cystic follicles. The results of the current study show that the development of ovarian cysts in sows is associated to changes in the expression of the cytoskeletal proteins CK and vimentin.

  1. Endogenous protein "barcode" for data validation and normalization in quantitative MS analysis.

    Science.gov (United States)

    Lee, Wooram; Lazar, Iulia M

    2014-07-01

    Quantitative proteomic experiments with mass spectrometry detection are typically conducted by using stable isotope labeling and label-free quantitation approaches. Proteins with housekeeping functions and stable expression level such actin, tubulin, and glyceraldehyde-3-phosphate dehydrogenase are frequently used as endogenous controls. Recent studies have shown that the expression level of such common housekeeping proteins is, in fact, dependent on various factors such as cell type, cell cycle, or disease status and can change in response to a biochemical stimulation. The interference of such phenomena can, therefore, substantially compromise their use for data validation, alter the interpretation of results, and lead to erroneous conclusions. In this work, we advance the concept of a protein "barcode" for data normalization and validation in quantitative proteomic experiments. The barcode comprises a novel set of proteins that was generated from cell cycle experiments performed with MCF7, an estrogen receptor positive breast cancer cell line, and MCF10A, a nontumorigenic immortalized breast cell line. The protein set was selected from a list of ~3700 proteins identified in different cellular subfractions and cell cycle stages of MCF7/MCF10A cells, based on the stability of spectral count data generated with an LTQ ion trap mass spectrometer. A total of 11 proteins qualified as endogenous standards for the nuclear and 62 for the cytoplasmic barcode, respectively. The validation of the protein sets was performed with a complementary SKBR3/Her2+ cell line.

  2. Effect of cobratoxin binding on the normal mode vibration within acetylcholine binding protein.

    Science.gov (United States)

    Bertaccini, Edward J; Lindahl, Erik; Sixma, Titia; Trudell, James R

    2008-04-01

    Recent crystal structures of the acetylcholine binding protein (AChBP) have revealed surprisingly small structural alterations upon ligand binding. Here we investigate the extent to which ligand binding may affect receptor dynamics. AChBP is a homologue of the extracellular component of ligand-gated ion channels (LGICs). We have previously used an elastic network normal-mode analysis to propose a gating mechanism for the LGICs and to suggest the effects of various ligands on such motions. However, the difficulties with elastic network methods lie in their inability to account for the modest effects of a small ligand or mutation on ion channel motion. Here, we report the successful application of an elastic network normal mode technique to measure the effects of large ligand binding on receptor dynamics. The present calculations demonstrate a clear alteration in the native symmetric motions of a protein due to the presence of large protein cobratoxin ligands. In particular, normal-mode analysis revealed that cobratoxin binding to this protein significantly dampened the axially symmetric motion of the AChBP that may be associated with channel gating in the full nAChR. The results suggest that alterations in receptor dynamics could be a general feature of ligand binding.

  3. Normal values of urine total protein- and albumin-to-creatinine ratios in term newborns.

    Science.gov (United States)

    El Hamel, Chahrazed; Chianea, Thierry; Thon, Séverine; Lepichoux, Anne; Yardin, Catherine; Guigonis, Vincent

    2017-01-01

    It is important to have an accurate assessment of urinary protein when glomerulopathy or kidney injury is suspected. Currently available normal values for the neonate population have limited value, in part because they are based on small populations and obsolete creatinine assays. We have performed a prospective study with the aim to update the normal upper values of the urinary total protein-to-creatinine and albumin-to-creatinine ratios in term newborns. Urine samples were collected from 277 healthy, full-term newborns within the first 48 hours (D0-1) and between 72 and 120 h of life (D3-4). Total protein, albumin, creatinine and osmolality were measured and the upper limit of normal (upper-limit) values determined. At D0-1 and D3-4, the upper-limit values for the total protein-to-creatinine ratio were 1431 and 1205 mg/g (162 and 136 g/mol) and those for the albumin-to-creatinine ratio were 746 and 301 mg/g (84 and 34 g/mol), respectively. The upper-limit values were significantly higher at D0-1 than at D3-4 only for the albumin-to-creatinine ratio. This study determined the upper limit of normal values for urinary total protein-to-creatinine and albumin-to-creatinine ratios in the largest population of newborns studied to date. These values can therefore be considered as the most clinically relevant data currently available for the detection and diagnosis of glomerular injury in daily clinical practice in this population.

  4. Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis.

    Science.gov (United States)

    Oldereid, N B; Angelis, P D; Wiger, R; Clausen, O P

    2001-05-01

    We investigated the frequency of spontaneous apoptosis and expression of the Bcl-2 family of proteins during normal spermatogenesis in man. Testicular tissue with both normal morphology and DNA content was obtained from necro-donors and fixed in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2 family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry. Germ cell apoptosis was detected in all testes and was mainly seen in primary spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were preferentially expressed in the compartments of spermatocytes and differentiating spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed a preferential expression in nuclei of round spermatids, whereas Bad was only seen in the acrosome region of various stages of spermatids. Mcl-1 staining was weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1) proteins was not detected by immunohistochemistry. The results show that spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2 family proteins are distributed preferentially within distinct germ cell compartments suggesting a specific role for these proteins in the processes of differentiation and maturation during human spermatogenesis.

  5. Study of nuclear proteins in normal and xeroderma pigmentosum lymphoblastoid cells

    International Nuclear Information System (INIS)

    Amari, N.M.B.

    1985-01-01

    Nuclear histone and nonhistone (NHP) proteins from normal human and xeroderma pigmentosum, complementation group A (XP-A) lymphoblastoid cells were compared both qualitatively, quantitatively and for binding affinity for DNA. Histones and four NHP fractions (NHP/sub 1-4/) were isolated from purified cell nuclei. Binding affinity to [ 3 H] melanoma DNA of histones and each NHP fraction was then determined using gradient dialysis followed by a filter assay. Histones and each NHP fraction were then sub-fractionated by polyacrylamide gel electrophoresis. Densitometric scans of the separation of these proteins on the gels were qualitatively, and quantitatively analyzed and compared between the two cell lines. No qualitative or quantitative differences were observed between histones from XP-A or normal cells

  6. pGenN, a Gene Normalization Tool for Plant Genes and Proteins in Scientific Literature

    Science.gov (United States)

    Ding, Ruoyao; Arighi, Cecilia N.; Lee, Jung-Youn; Wu, Cathy H.; Vijay-Shanker, K.

    2015-01-01

    Background Automatically detecting gene/protein names in the literature and connecting them to databases records, also known as gene normalization, provides a means to structure the information buried in free-text literature. Gene normalization is critical for improving the coverage of annotation in the databases, and is an essential component of many text mining systems and database curation pipelines. Methods In this manuscript, we describe a gene normalization system specifically tailored for plant species, called pGenN (pivot-based Gene Normalization). The system consists of three steps: dictionary-based gene mention detection, species assignment, and intra species normalization. We have developed new heuristics to improve each of these phases. Results We evaluated the performance of pGenN on an in-house expertly annotated corpus consisting of 104 plant relevant abstracts. Our system achieved an F-value of 88.9% (Precision 90.9% and Recall 87.2%) on this corpus, outperforming state-of-art systems presented in BioCreative III. We have processed over 440,000 plant-related Medline abstracts using pGenN. The gene normalization results are stored in a local database for direct query from the pGenN web interface (proteininformationresource.org/pgenn/). The annotated literature corpus is also publicly available through the PIR text mining portal (proteininformationresource.org/iprolink/). PMID:26258475

  7. Radioimmunoassay of alpha-foeto protein in the amniotic fluid in normal and pathological pregnancies

    International Nuclear Information System (INIS)

    Degueldre, M.; Golstein, J.; Rodesch, F.; L'Hermite, M.

    1975-01-01

    A radioimmunoassay of AFP was developed and the normal amniotic concentrations of this protein were measured as a function of the gestation age. The specific reagents used included a rabbit anti-AFP serum and a highly purified preparation of AFP labelled with 125 I, which also served as a standard. Amniotic fluid was drawn off by amniocentesis between the 11th and 40th week following the last menstrual period. Samples of amniotic fluid were also obtained in 2 cases of foetal death in utero and 3 cases of anencephaly. The normal amniotic AFP concentration limits were particularly well established between the 14th and 18th weeks, an ideal period to perform an amniocentesis both from a technical viewpoint and with regard to the bulk of information obtainable for the antenatal diagnosis of many congenital diseases. The concentrations observed in pathological cases were distinctly higher than the upper 95% confidence limit of normal values for the gestation age considered [fr

  8. On the variability of the salting-out curves of proteins of normal human plasma and serum

    NARCIS (Netherlands)

    Steyn-Parvé, Elizabeth P.; Hout, A.J. van den

    1953-01-01

    Salting-out curves of proteins of normal human plasma reflect the influence of a number of other factors besides the protein composition: the manner of obtaining the blood, the nature of the anti-coagulant used, the non-protein components of the plasma. Diagrams of serum and plasma obtained from

  9. Protein and Carbohydrate Accumulation in Normal and High-Lysine Barley in Spike Culture

    DEFF Research Database (Denmark)

    Mather, D.E; Giese, Nanna Henriette

    1984-01-01

    Spikes of barley cv. Bomi and high-lysine mutants Riso 1508 and Riso 56 were cultured on liquid media at varying N and sucrose levels. Bomi accumulated N in response to increasing N levels in the medium and a higher level was reached than in spikes of intact plants. The distribution of N in salt......-soluble, hordein, and non-protein N fractions appeared to be normal. Endosperm dry weight and starch were lower than in intact plants and declined at higher N levels. A linear relationship was observed between starch content and the concentration of sucrose in the endosperm water. Uptake of culture medium...

  10. The acyl-CoA binding protein is required for normal epidermal barrier function in mice

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Bek, Signe; Marcher, Ann-Britt

    2012-01-01

    (+/+) and ACBP(-/-) mice showed very similar composition, except for a significant and specific decrease in the very long chain free fatty acids (VLC-FFA) in stratum corneum of ACBP(-/-) mice. This finding indicates that ACBP is critically involved in the processes that lead to production of stratum corneum VLC......The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP(-/-) mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling...... with age. Morphology and development of skin and appendages are normal in ACBP(-/-) mice; however, the stratum corneum display altered biophysical properties with reduced proton activity and decreased water content. Mass spectrometry analyses of lipids from epidermis and stratum corneum of ACBP...

  11. Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

    Directory of Open Access Journals (Sweden)

    Elisabeth Warnke

    2017-08-01

    Full Text Available Background/Aims: Spaceflight impacts on the function of the thyroid gland in vivo. In vitro normal and malignant thyrocytes assemble in part to multicellular spheroids (MCS after exposure to the random positioning machine (RPM, while a number of cells remain adherent (AD. We aim to elucidate possible differences between AD and MCS cells compared to 1g-controls of normal human thyroid cells. Methods: Cells of the human follicular epithelial thyroid cell line Nthy-ori 3-1 were incubated for up to 72 h on the RPM. Afterwards, they were investigated by phase-contrast microscopy, quantitative real-time PCR and by determination of cytokines released in their supernatants. Results: A significant up-regulation of IL6, IL8 and CCL2 gene expression was found after a 4h RPM-exposure, when the whole population was still growing adherently. MCS and AD cells were detected after 24 h on the RPM. At this time, a significantly reduced gene expression in MCS compared to 1g-controls was visible for IL6, IL8, FN1, ITGB1, LAMA1, CCL2, and TLN1. After a 72 h RPM-exposure, IL-6, IL-8, and TIMP-1 secretion rates were increased significantly. Conclusion: Normal thyrocytes form MCS within 24 h. Cytokines seem to be involved in the initiation of MCS formation via focal adhesion proteins.

  12. Spatial Expression of Otolith Matrix Protein-1 and Otolin-1 in Normally and Kinetotically Swimming Fish.

    Science.gov (United States)

    Weigele, Jochen; Franz-Odendaal, Tamara A; Hilbig, Reinhard

    2015-10-01

    Kinetosis (motion sickness) has been repeatedly shown to affect some fish of a given clutch following the transition from 1g to microgravity or from hypergravity to 1g. This susceptibility to kinetosis may be correlated with irregular inner ear otolith growth. Otoliths are mainly composed of calcium carbonate and matrix proteins, which play an important role in the process of otolith mineralization. Here, we examine the morphology of otoliths and the expression pattern of the major otolith proteins OMP-1 and otolin-1 in a series of hypergravity experiments. In the utricle, OMP-1 is present in centripetal (medial) and centrifugal (lateral) regions of the meshwork area. In the saccule, OMP-1 was expressed within a dorsal and a ventral narrow band of the meshwork area opposite to the periphery of the sulcus acusticus. In normal animals, the spatial expression pattern of OMP-1 reaches more posteriorly in the centrifugal aspect and is considerably broader in the centripetal portion of the utricle compared to kinetotic animals. However, otolin-1 was not expressed in the utricule. In the saccule, no differences were observed for either gene when comparing normal and kinetotically behaving fish. The difference in the utricular OMP-1 expression pattern between normally and kinetotically swimming fish indicates a different otolith morphology and thus a different geometry of the otoliths resting on the corresponding sensory maculae. As the utricle is the endorgan responsible for sensing gravity, the aberrant morphology of the utricular otoliths, based on OMP-1 expression, likely leads to the observed kinetotic behavior. © 2015 Wiley Periodicals, Inc.

  13. On the sensitivity of protein data bank normal mode analysis: an application to GH10 xylanases

    Science.gov (United States)

    Tirion, Monique M.

    2015-12-01

    Protein data bank entries obtain distinct, reproducible flexibility characteristics determined by normal mode analyses of their three dimensional coordinate files. We study the effectiveness and sensitivity of this technique by analyzing the results on one class of glycosidases: family 10 xylanases. A conserved tryptophan that appears to affect access to the active site can be in one of two conformations according to x-ray crystallographic electron density data. The two alternate orientations of this active site tryptophan lead to distinct flexibility spectra, with one orientation thwarting the oscillations seen in the other. The particular orientation of this sidechain furthermore affects the appearance of the motility of a distant, C terminal region we term the mallet. The mallet region is known to separate members of this family of enzymes into two classes.

  14. On the sensitivity of protein data bank normal mode analysis: an application to GH10 xylanases

    International Nuclear Information System (INIS)

    Tirion, Monique M

    2015-01-01

    Protein data bank entries obtain distinct, reproducible flexibility characteristics determined by normal mode analyses of their three dimensional coordinate files. We study the effectiveness and sensitivity of this technique by analyzing the results on one class of glycosidases: family 10 xylanases. A conserved tryptophan that appears to affect access to the active site can be in one of two conformations according to x-ray crystallographic electron density data. The two alternate orientations of this active site tryptophan lead to distinct flexibility spectra, with one orientation thwarting the oscillations seen in the other. The particular orientation of this sidechain furthermore affects the appearance of the motility of a distant, C terminal region we term the mallet. The mallet region is known to separate members of this family of enzymes into two classes. (paper)

  15. Calmodulin and calmodulin-binding proteins in cystic fibrosis and normal human fibroblasts

    International Nuclear Information System (INIS)

    Tallant, E.A.; Wallace, R.W.

    1986-01-01

    The authors have investigated the possibility that a lesion in a calmodulin (CaM)-dependent regulatory mechanism may be involved in cystic fibrosis (CF). The level of CaM, CaM-binding proteins (CaM-BP) and a CaM-dependent phosphatase (CaM-Ptase) have been compared in cultured fibroblasts from CF patients versus age- and sex-matched control subjects. The CaM concentration, measured by radioimmunoassay, ranged from 0.20 to 0.76 μg/mg protein (n=8); there was no significant difference in the average CaM concentration from CF patients vs controls. Using Western blotting techniques with 125 I-CaM, they detected at least ten distinct CaM-BPs in fibroblasts with molecular weights ranging from 230K to 37K; the only consistent difference between control and CF cell lines was in a 46.5K CaM-BP, which was depressed in all three CF samples. The 46.5 K CaM-BP was found only in the particulate fraction. A 59K CaM-BP was identified as a CaM-Ptase by its crossreactivity with an antibody against a brain CaM-Ptase. There was no significant difference in CaM-Ptase activity or in the amount of the phosphatase as determined by radioimmunoassay in CF vs. normal samples (n=8). Thus, the level of CaM as well as its various enzymes and proteins do not appear to be altered in CF fibroblasts except for a CaM-BP of 46.5K, the identity of which is currently being investigated

  16. Addition of arginine and leucine to low or normal protein diets: performance, carcass characteristics and intramuscular fat of finishing pigs

    Directory of Open Access Journals (Sweden)

    Núria Tous

    2016-12-01

    Full Text Available The effect of dietary crude protein (CP reduction, supplementation with arginine or leucine on intramuscular fat (IMF content was evaluated in (Landrace × Duroc × Pietrain pigs. One-hundred and eight barrows (67 ± 4 kg were assigned to six diets (n=6 pens of 3 pigs each: four normal CP diets containing 16% CP from 60 to 90 kg and 13% CP from 90 to 115 kg live weight (normal protein; normal protein high Arg, normal protein high Leu or normal protein high Arg and Leu and two low CP diets containing 14% CP from 60 to 90 kg and 11.8% CP from 90 to 115 kg live weight (with or without supplementation of both amino acids. The high Leu and Arg diets were supplemented to obtain ratios of standard ileal digestible Leu/Lys and Arg/Lys of 4 and 2, respectively. While feed to gain ratio tended to increase (p<0.05, final weight (p<0.01, average daily feed intake (ADFI (p<0.05 and average daily gain (ADG (p<0.01 were reduced in animals fed low-protein diets supplemented with Arg and Leu compared to the ones fed low-protein diet unsupplemented. Marbling and IMF content in loin were reduced when Arg was supplemented (p<0.05 in normal protein diets. Supplementing these diets with Arg also reduced belly weight (p<0.01 and increased lean meat percentage (p<0.05. Contrary to the initial hypothesis, reduction of CP or dietary supplementation with Leu had no effect on IMF content and supplementation with Arg reduced it.

  17. Addition of arginine and leucine to low or normal protein diets: performance, carcass characteristics and intramuscular fat of finishing pigs

    Energy Technology Data Exchange (ETDEWEB)

    Tous, N.; Lizardo, R.; Vilà, B.; Gispert, M.; Font-i-Furnols, M.; Esteve-Garcia, E.

    2016-07-01

    The effect of dietary crude protein (CP) reduction, supplementation with arginine or leucine on intramuscular fat (IMF) content was evaluated in (Landrace × Duroc) × Pietrain pigs. One-hundred and eight barrows (67 ± 4 kg) were assigned to six diets (n=6 pens of 3 pigs each): four normal CP diets containing 16% CP from 60 to 90 kg and 13% CP from 90 to 115 kg live weight (normal protein; normal protein high Arg, normal protein high Leu or normal protein high Arg and Leu) and two low CP diets containing 14% CP from 60 to 90 kg and 11.8% CP from 90 to 115 kg live weight (with or without supplementation of both amino acids). The high Leu and Arg diets were supplemented to obtain ratios of standard ileal digestible Leu/Lys and Arg/Lys of 4 and 2, respectively. While feed to gain ratio tended to increase (p<0.05), final weight (p<0.01), average daily feed intake (ADFI) (p<0.05) and average daily gain (ADG) (p<0.01) were reduced in animals fed low-protein diets supplemented with Arg and Leu compared to the ones fed low-protein diet unsupplemented. Marbling and IMF content in loin were reduced when Arg was supplemented (p<0.05) in normal protein diets. Supplementing these diets with Arg also reduced belly weight (p<0.01) and increased lean meat percentage (p<0.05). Contrary to the initial hypothesis, reduction of CP or dietary supplementation with Leu had no effect on IMF content and supplementation with Arg reduced it.

  18. Addition of arginine and leucine to low or normal protein diets: performance, carcass characteristics and intramuscular fat of finishing pigs

    International Nuclear Information System (INIS)

    Tous, N.; Lizardo, R.; Vilà, B.; Gispert, M.; Font-i-Furnols, M.; Esteve-Garcia, E.

    2016-01-01

    The effect of dietary crude protein (CP) reduction, supplementation with arginine or leucine on intramuscular fat (IMF) content was evaluated in (Landrace × Duroc) × Pietrain pigs. One-hundred and eight barrows (67 ± 4 kg) were assigned to six diets (n=6 pens of 3 pigs each): four normal CP diets containing 16% CP from 60 to 90 kg and 13% CP from 90 to 115 kg live weight (normal protein; normal protein high Arg, normal protein high Leu or normal protein high Arg and Leu) and two low CP diets containing 14% CP from 60 to 90 kg and 11.8% CP from 90 to 115 kg live weight (with or without supplementation of both amino acids). The high Leu and Arg diets were supplemented to obtain ratios of standard ileal digestible Leu/Lys and Arg/Lys of 4 and 2, respectively. While feed to gain ratio tended to increase (p<0.05), final weight (p<0.01), average daily feed intake (ADFI) (p<0.05) and average daily gain (ADG) (p<0.01) were reduced in animals fed low-protein diets supplemented with Arg and Leu compared to the ones fed low-protein diet unsupplemented. Marbling and IMF content in loin were reduced when Arg was supplemented (p<0.05) in normal protein diets. Supplementing these diets with Arg also reduced belly weight (p<0.01) and increased lean meat percentage (p<0.05). Contrary to the initial hypothesis, reduction of CP or dietary supplementation with Leu had no effect on IMF content and supplementation with Arg reduced it.

  19. [Morphology of basement membrane and associated matrix proteins in normal and pathological tissues].

    Science.gov (United States)

    Nerlich, A

    1995-01-01

    Basement membranes (BM) are specialized structures of the extracellular matrix. Their composition is of particular importance for the maintenance of normal morphological and functional properties of a multitude of organs and tissue systems and it is thus required for regular homeostasis of body function. Generally, they possess three main functions, i.e. participation in the maintenance of tissue structure, control of fluid and substrate exchange, and regulation of cell growth and differentiation. BMs are made up by various components which are in part specifically localized within the BM zone, or which represent ubiquitous matrix constituents with specific quantitative and/or qualitative differences in their localization. On the basis of a thorough immunohistochemical analysis of normal and diseased tissues, we provide here a concept of "functional morphology/pathomorphology" of the different BM components analyzed: 1.) The ubiquitous BM-constituent collagen IV primarily stabilizes the BM-zone and thus represents the "backbone" of the BM providing mechanical strength. Its loss leads to cystic tissue transformation as it is evidenced from the analysis of polycystic nephropathies. Thus, in other cystic tissue transformations a similar formal pathogenesis may be present. 2.) The specific localization of collagen VII as the main structural component of anchoring fibrils underlines the mechanical anchoring function of this collagenous protein. Defects in this protein lead to hereditary epidermolysis. The rapid re-occurrence of epidermal collagen VII during normal human wound healing indicates a quick reconstitution of the mechanical tensile strength of healing wounds. 3.) The BM-specific heparan sulfate proteoglycan (HSPG, Perlecan) with its highly negative anionic charge can be assumed to exert filter control. This assumption is corroborated by the localizatory findings of a preferential deposition of HSPG in endothelial and particularly in glomerular BM. Similarly

  20. NormaCurve: a SuperCurve-based method that simultaneously quantifies and normalizes reverse phase protein array data.

    Directory of Open Access Journals (Sweden)

    Sylvie Troncale

    Full Text Available MOTIVATION: Reverse phase protein array (RPPA is a powerful dot-blot technology that allows studying protein expression levels as well as post-translational modifications in a large number of samples simultaneously. Yet, correct interpretation of RPPA data has remained a major challenge for its broad-scale application and its translation into clinical research. Satisfying quantification tools are available to assess a relative protein expression level from a serial dilution curve. However, appropriate tools allowing the normalization of the data for external sources of variation are currently missing. RESULTS: Here we propose a new method, called NormaCurve, that allows simultaneous quantification and normalization of RPPA data. For this, we modified the quantification method SuperCurve in order to include normalization for (i background fluorescence, (ii variation in the total amount of spotted protein and (iii spatial bias on the arrays. Using a spike-in design with a purified protein, we test the capacity of different models to properly estimate normalized relative expression levels. The best performing model, NormaCurve, takes into account a negative control array without primary antibody, an array stained with a total protein stain and spatial covariates. We show that this normalization is reproducible and we discuss the number of serial dilutions and the number of replicates that are required to obtain robust data. We thus provide a ready-to-use method for reliable and reproducible normalization of RPPA data, which should facilitate the interpretation and the development of this promising technology. AVAILABILITY: The raw data, the scripts and the normacurve package are available at the following web site: http://microarrays.curie.fr.

  1. Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles (Terrapene carolina carolina).

    Science.gov (United States)

    Royal, Lillian W; Lascelles, B Duncan X; Lewbart, Gregory A; Correa, Maria T; Jones, Samuel L

    2012-06-01

    This pilot study was designed to determine whether cyclooxygenase (COX)-1, COX-2, or both are expressed in normal turtle tissues and whether level of expression changes when tissue becomes inflamed. Five eastern box turtles, Terrapene carolina carolina, that either died or were euthanatized due to disease or injuries were used for this work. Tissues were obtained from the five turtles. Western blot analysis was used to evaluate tissues for COX-1 and COX-2 proteins. Densiometric analysis was used to compare Western blot bands within each turtle. COX-1 and COX-2 were found in the liver, kidney, grossly normal muscle, and grossly traumatized (inflamed) muscle of all study turtles. In all cases, COX-1 and COX-2 proteins were increased in traumatized muscle over grossly normal nontraumatized muscle. The highest levels of COX-1 and COX-2 proteins were found in kidney and liver. There was no statistical difference between the amount of COX-1 protein in liver and kidney, but traumatized muscle compared with grossly normal muscle had significantly greater COX-1 but not COX 2 protein concentrations. There was no statistical difference between the amount of COX-2 protein in liver and kidney. Traumatized muscle expressed nonstatistically significant greater amounts of COX-2 compared with grossly normal muscle. COX-1 and COX-2 proteins are expressed in turtle tissues, and both isoforms are upregulated during inflammation of muscle tissue. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) that block both COX isoforms might be more efficacious than COX-2-selective drugs. This work suggests that NSAIDs should be evaluated for potential liver and kidney toxicity in turtles.

  2. Expression and function of the protein tyrosine phosphatase receptor J (PTPRJ in normal mammary epithelial cells and breast tumors.

    Directory of Open Access Journals (Sweden)

    Chanel E Smart

    Full Text Available The protein tyrosine phosphatase receptor J, PTPRJ, is a tumor suppressor gene that has been implicated in a range of cancers, including breast cancer, yet little is known about its role in normal breast physiology or in mammary gland tumorigenesis. In this paper we show that PTPRJ mRNA is expressed in normal breast tissue and reduced in corresponding tumors. Meta-analysis revealed that the gene encoding PTPRJ is frequently lost in breast tumors and that low expression of the transcript associated with poorer overall survival at 20 years. Immunohistochemistry of PTPRJ protein in normal human breast tissue revealed a distinctive apical localisation in the luminal cells of alveoli and ducts. Qualitative analysis of a cohort of invasive ductal carcinomas revealed retention of normal apical PTPRJ localization where tubule formation was maintained but that tumors mostly exhibited diffuse cytoplasmic staining, indicating that dysregulation of localisation associated with loss of tissue architecture in tumorigenesis. The murine ortholog, Ptprj, exhibited a similar localisation in normal mammary gland, and was differentially regulated throughout lactational development, and in an in vitro model of mammary epithelial differentiation. Furthermore, ectopic expression of human PTPRJ in HC11 murine mammary epithelial cells inhibited dome formation. These data indicate that PTPRJ may regulate differentiation of normal mammary epithelia and that dysregulation of protein localisation may be associated with tumorigenesis.

  3. Serum levels of growth hormone binding protein in children with normal and precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Fisker, Sidse; Scheike, Thomas Harder

    2000-01-01

    To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty.......To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty....

  4. Differential metabolism and leakage of protein in an inherited cataract and a normal lens cultured with ouabain

    International Nuclear Information System (INIS)

    Piatigorsky, J.; Fukui, H.N.; Kinoshita, J.H.

    1978-01-01

    Ocular lenses in Nakano mice showed marked changes in synthesis, degradation and leakage of protein during cataractogenesis. The cataract-associated changes included the differential lowering of crystalline synthesis, the cleavage of crystallin polypeptides to lower molecular weight forms and the leakage of crystallins from cultured lenses. Ouabain treatment of normal lenses induced these alterations, suggesting that changes in the intracellular levels of Na + and K + affect the anabolism and catabolism of protein during cataract formation. 35 S-methionine was used during the course of the experiments as a method of protein identification. (author)

  5. Absence of penicillin-binding protein 4 from an apparently normal strain of Bacillus subtilis.

    OpenAIRE

    Buchanan, C E

    1987-01-01

    The phenotype of a Bacillus subtilis 168 strain with no detectable penicillin-binding protein 4 was examined. Despite the fact that penicillin-binding protein 4 is one of the most penicillin-sensitive proteins in the species, its apparent loss had no obvious effect on the organism or its susceptibility to various beta-lactam antibiotics.

  6. The effect of tranilast on fibroblast activation protein α (FAP-α expression in normal and keloid fibroblasts in vitro

    Directory of Open Access Journals (Sweden)

    Paweł P. Antończak

    2017-07-01

    Full Text Available Introduction . Tranilast (N-(3’,4’-demethoxycinnamoyl-anthranilic acid is an anti-allergic drug. Its mechanism of action is based on the inhibition of antigen-induced release of chemical mediators from mast cells and basophils. It also reveals antifibroproliferative activities. These properties of tranilast are used in the treatment of hypertrophic scars and keloids. Keloids are characterized by incorrect extracellular matrix components turnover. Fibroblasts derived from keloids reveal overproduction of collagen type I and decreased degradation of extracellular matrix in comparison with normal fibroblasts. Fibroblast activation protein α (FAP-α may play an important role in remodeling of extracellular matrix and the invasive properties of keloids. Objective . In the present study, the effect of tranilast on expression of FAP-α gene and its protein was evaluated in normal human dermal fibroblasts and fibroblasts derived from keloids cultured in vitro . Materials and methods. In the first stage of the study, the influence of tranilast on cell viability was estimated. The second stage of the study included the quantitative evaluation of FAP-α mRNA expression in normal and keloid fibroblasts treated with tranilast. The third stage of the study comprised fibroblast activation protein α expression analysis in the examined cells treated with tranilast. Results and conclusions . The expression of FAP-α gene and fibroblast activation protein α is higher in keloid fibroblasts. Tranilast at concentrations of 3 μM and 30 μM up-regulated mRNA FAP-α expression in normal fibroblasts but did not influence keloid fibroblasts. The drug, at concentrations of 30 μM and 300 μM up-regulated fibroblast activation protein α expression in normal fibroblasts and did not influence keloid fibroblasts. Tranilast antiproliferative effect is not associated with FAP-α expression in keloid fibroblasts.

  7. Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach

    Directory of Open Access Journals (Sweden)

    De Marco Federico

    2010-03-01

    Full Text Available Abstract Background The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS, which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. Results The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. Conclusions Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

  8. Association between uncoupling protein 2, adiponectin and resting energy expenditure in obese women with normal and low resting energy expenditure.

    Science.gov (United States)

    Taghadomi Masoumi, Zahra; Eshraghian, Mohammad Reza; Hedayati, Mahdi; Pishva, Hamideh

    2018-02-01

    Obesity is recognized as the most prevalent metabolic disease worldwide. Decreases in energy expenditure may increase risk of obesity. One of the key regulators of energy balance is uncoupling protein2 (UCP2), a transporter protein presents in mitochondrial inner membrane. Moreover, adiponectin is the most abundant adipocytokine, it may play a role in energy metabolism and gene expression of UCP2. The aim of this study was to investigate potential associations between the level of uncoupling protein 2 and adiponectin and their relationship with REE (Resting Energy Expenditure) in obese women with normal and low resting energy expenditure. A total of 49 subjects (women, 25-50 years old), were included in current study, 16 subjects with BMI > 30 and low resting energy expenditure, 17 subjects with BMI > 30 and normal resting energy expenditure and 16 non-obese subjects as a control group. Anthropometric, body composition parameters and resting energy expenditure were measured. Plasma adiponectin, UCP2 protein and total protein in PBMC were determined. Measured resting energy expenditure in obese subjects with low REE was significantly lower than other groups. Plasma adiponectin in the obese subjects with low REE was significantly lower compared to normal weight group. There was a significant relationship between 'UCP2 protein/Total protein' ratio and plasma adiponectin in obese group with low REE and in three groups when we pooled. There was a significant association between REE and plasma adiponectin in three groups when we pooled. There was a significant association between plasma adiponectin and REE. Moreover, there was a significant relationship between UCP2 and REE.

  9. Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells

    Czech Academy of Sciences Publication Activity Database

    Hubáčková, Soňa; Krejčíková, Kateřina; Bartek, Jiří; Hodný, Zdeněk

    2012-01-01

    Roč. 287, č. 32 (2012), s. 26702-26714 ISSN 0021-9258 R&D Projects: GA ČR GA204/08/1418 Grant - others:Novo Nordisk(DK) R153-A12997; EK(XE) 223575 Institutional support: RVO:68378050 Keywords : cancer tumor promoter * DNA-binding protein * protein phosphorylation * tyrosine protein kinase * interleukin-6 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.651, year: 2012

  10. Comparative proteomic analysis of plasma membrane proteins between human osteosarcoma and normal osteoblastic cell lines

    International Nuclear Information System (INIS)

    Zhang, Zhiyu; Ma, Fang; Cai, Zhengdong; Zhang, Lijun; Hua, Yingqi; Jia, Xiaofang; Li, Jian; Hu, Shuo; Peng, Xia; Yang, Pengyuan; Sun, Mengxiong

    2010-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone in children and adolescents. However, the knowledge in diagnostic modalities has progressed less. To identify new biomarkers for the early diagnosis of OS as well as for potential novel therapeutic candidates, we performed a sub-cellular comparative proteomic research. An osteosarcoma cell line (MG-63) and human osteoblastic cells (hFOB1.19) were used as our comparative model. Plasma membrane (PM) was obtained by aqueous two-phase partition. Proteins were analyzed through iTRAQ-based quantitative differential LC/MS/MS. The location and function of differential proteins were analyzed through GO database. Protein-protein interaction was examined through String software. One of differentially expressed proteins was verified by immunohistochemistry. 342 non-redundant proteins were identified, 68 of which were differentially expressed with 1.5-fold difference, with 25 up-regulated and 43 down-regulated. Among those differential proteins, 69% ware plasma membrane, which are related to the biological processes of binding, cell structure, signal transduction, cell adhesion, etc., and interaction with each other. One protein--CD151 located in net nodes was verified to be over-expressed in osteosarcoma tissue by immunohistochemistry. It is the first time to use plasma membrane proteomics for studying the OS membrane proteins according to our knowledge. We generated preliminary but comprehensive data about membrane protein of osteosarcoma. Among these, CD151 was further validated in patient samples, and this small molecule membrane might be a new target for OS research. The plasma membrane proteins identified in this study may provide new insight into osteosarcoma biology and potential diagnostic and therapeutic biomarkers

  11. Structural and metabolic studies of O-linked fucose-containing proteins of normal and virally-transformed rat fibroblasts

    International Nuclear Information System (INIS)

    Morton, P.A.

    1985-01-01

    Previous studies in this laboratory have demonstrated that cultured human and rodent cells contain a series of low molecular weight glycosylated amino acids of unusual structure, designated amino acid fucosides. The incorporation of radiolabelled-fucose into one of these components, designated FL4a (glucosylfucosylthreonine), is markedly-reduced in transformed epithelial and fibroblastic cells. The authors have examined fucose-labelled normal and virally-transformed rat fibroblast cell lines for glycoproteins which might be precursors to amino acid fucosides. Using milk alkaline/borohydride treatment (the beta-elimination reaction) to release O-linked oligosaccharides from proteins, they have isolated and partially characterized two low M/sub r/ reaction products (designated DS-ol and TS-ol) released from macromolecular cell material. The identity of one of these components (DS-ol, glucosylfucitol) suggested the existence in these cells of a direct protein precursor to FL4a. They examined fucose-labelled macromolecular cell material for proteins which release DS-ol (DS-proteins.). Using gel filtration chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with subsequent autoradiography, they have observed DS-proteins which appear to exhibit a broad molecular weight size range, and are also present in culture medium from normal and transformed cells. The findings suggest that mammalian cells contain DS-proteins and TS-proteins with a novel carbohydrate-peptide linkage wherein L-fucose is O-linked to a polypeptide backbone. Metabolic studies were undertaken to examine both the relationship between DS-protein and FL4a and the biochemical basis for the decreased level of FL4a and the biochemical basis for the decreased level of FL4a observed in transformed cells

  12. The course of protein synthesis during grain filling in normal and high lysine barley

    International Nuclear Information System (INIS)

    Giese, H.; Andersen, B.

    1984-01-01

    A study of the course of protein synthesis during grain filling in Bomi and the high lysine barleys Hily 82/3 and Risoe 56 showed that the four salt-soluble proteins, protein Z, β-amylase and the chymotrypsin inhibitors CI-1 and CI-2, are synthesized in greater amounts earlier in the high lysine lines than in Bomi. On the other hand, the hordeins are synthesized in greater amounts earlier during grain filling in Bomi than in Hily 82/3 and Risoe 56. There is no indication of a significant reduction of total protein synthesis in the high lysine lines compared with the standard lines Bomi and Pirrka. Hily 82/3 and Risoe 56 are very similar in protein composition in that they have a lower hordein content and higher levels, particularly of β-amylase and the chymotrypsin inhibitors, than Bomi. (author)

  13. The Colonic Microbiome and Epithelial Transcriptome Are Altered in Rats Fed a High-Protein Diet Compared with a Normal-Protein Diet.

    Science.gov (United States)

    Mu, Chunlong; Yang, Yuxiang; Luo, Zhen; Guan, Leluo; Zhu, Weiyun

    2016-03-01

    A high-protein diet (HPD) can produce hazardous compounds and reduce butyrate-producing bacteria in feces, which may be detrimental to gut health. However, information on whether HPD affects intestinal function is limited. The aim of this study was to determine the impact of an HPD on the microbiota, microbial metabolites, and epithelial transcriptome in the colons of rats. Adult male Wistar rats were fed either a normal-protein diet (20% protein, 56% carbohydrate) or an HPD (45% protein, 30% carbohydrate) for 6 wk (n = 10 rats per group, individually fed). After 6 wk, the colonic microbiome, microbial metabolites, and epithelial transcriptome were determined. Compared with the normal-protein diet, the HPD adversely altered the colonic microbiota by increasing (P 0.7, P < 0.05) with genes and metabolites generally regarded as being involved in disease pathogenesis, suggesting these bacteria may mediate the detrimental effects of HPDs on colonic health. Our findings suggest that the HPD altered the colonic microbial community, shifted the metabolic profile, and affected the host response in the colons of rats toward an increased risk of colonic disease. © 2016 American Society for Nutrition.

  14. Synthesis of a posterior indicator protein in normal embryos and double abdomens of Smittia sp. (Chironomidae, Diptera).

    Science.gov (United States)

    Jäckle, H; Kalthoff, K

    1980-01-01

    In embryos of the chironomid midge Smittia, synthesis of a posterior indicator protein designated PI1 (Mr approximately 50,000; pI approximately 5.5) forecasts development of an abdomen as opposed to head and thorax. The protein is synthesized several hours before germ anlage formation. In normal embryos at early blastoderm stages, synthesis of PI1 is restricted to posterior embryonic fragments but not to pole cells. In "double-abdomen" embryos, a mirror-image duplication of the abdomen is formed by cells that would otherwise develop into head and thorax. Embryos were programmed for double-abdomen development by UV irradiation of the anterior pole, and half of them were reprogrammed for normal development by subsequent exposure to visible light (photoreversal). Correspondingly, PI1 was synthesized in anterior fragments of UV-irradiated embryos but not after photoreversal. In a control experiment, UV irradiation of the posterior pole caused neither double-abdomen formation nor PI1 synthesis in anterior fragments. The identity of PI1 formed in anterior fragments of prospective double abdomens with the protein found in posterior fragments was revealed by two-dimensional gel electrophoresis and limited proteolysis. Suppression of PI1 synthesis in anterior fragments of normal embryos is ascribed to the activity of cytoplasmic ribonucleoprotein particles thought to act as anterior determinants. Images PMID:6935679

  15. Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes.

    Science.gov (United States)

    Clark, David J; Fondrie, William E; Yang, Austin; Mao, Li

    2016-02-05

    Exosomes are 30-100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals

  16. High proportions of older people with normal nutritional status have poor protein intake and low diet quality.

    Science.gov (United States)

    Jyväkorpi, S K; Pitkälä, K H; Puranen, T M; Björkman, M P; Kautiainen, H; Strandberg, T E; Soini, H H; Suominen, M H

    2016-01-01

    The Mini Nutritional Assessment (MNA) is a well-validated instrument examining the nutritional status of older people. The aim of this study was to examine how older people's energy and nutrient intakes are associated with the MNA and to determine how sensitive and specific MNA is in identifying those having low energy and protein intakes. This cross-sectional study combined data from five nutritional studies (N=900): both home-dwelling and institutionalized older people without and with disabilities. Their nutritional status was assessed with MNA, and nutrient intakes were retrieved from 1 to 3day food diaries. Nutrient intakes were divided according to MNA status (normal nutritional status, at-risk of malnutrition, malnourished). Sensitivity, specificity, and likelihood ratios of MNA of various cut-off points were tested with recommended protein and energy intakes. ROC curves was constructed. Energy, protein and most nutrient intakes showed logical linear trends according to MNA classes. However, more than three-fourths of the participants with MNA>23.5 had lower than recommended protein intakes. Sensitivity of MNA ranged from 0.32 to 0.82 for recommended energy (F:1570kcal/d/M:2070kcal/d) and protein intakes (1.0g/kg BW or 1.2g/kgBW) cut-off points, and specificity from 0.75 to 0.25, respectively. AUC values were low (0.52-0.53). MNA status was consistently associated with nutrient intakes and diet quality. However, a high proportion of older people even with normal nutritional status had poor energy and protein intakes. Thus, MNA does not identify all those with poor nutrient intakes who may be at risk of developing malnutrition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Olfactory marker protein: turnover and transport in normal and regenerating neurons

    International Nuclear Information System (INIS)

    Kream, R.M.; Margolis, F.L.

    1984-01-01

    A 19,000-dalton acidic protein designated olfactory marker protein (OMP) is a cell-specific marker of mature olfactory chemosensory neurons. Intranasal irrigation of mouse olfactory epithelium with [ 35 S]methionine labeled OMP to high specific activity. Turnover and transport characteristics of 35 S-labeled OMP were compared to those of 35 S-labeled global cytosol protein in groups of young, adult, and Triton-treated adult mice. The latter contained primarily large numbers of regenerating olfactory neurons. In olfactory epithelium of young and Triton-treated mice, the specific activity of OMP was three times that of global cytosol protein, whereas in adults the two measures were equal. In all three groups, however, the rate of degradation of OMP was roughly equal to that of cytosol protein (T1/2 . 5 to 6 days). By contrast, differences in T1/2 for OMP decline in the bulb of adult, young, and Triton-treated adult mice were highly significant (T1/2's of 9.3, 6.1, and 4 to 5 days, respectively; p . 0.001). The specific activity of [35S]methionine incorporated in OMP exceeded that of the free amino acid 5-fold, indicating minimal precursor reutilization during the course of our experiments. Turnover data indicate that increased isotope incorporation into OMP in the epithelium is matched by an accelerated rate of degradation in the bulb. This may be correlated with the physiological state or developmental age of the primary neurons since in young and Triton-treated adult mice, rapidly maturing ''young'' olfactory neurons represent a larger proportion of the total population than in adults. Thus, OMP behaves as a typical, relatively slowly transported soluble protein (v . 2 to 4 mm/day, slow component b)

  18. Effect of whey protein and a free amino acid mixture simulating whey protein on measures of satiety in normal-weight women.

    Science.gov (United States)

    Chungchunlam, Sylvia M S; Henare, Sharon J; Ganesh, Siva; Moughan, Paul J

    2016-11-01

    Dietary protein is considered more satiating than carbohydrate, and whey protein is more satiating than other protein sources. The purported satiating effect of whey protein may be due to direct effects of the unique mixture of proteins in whey, due to the effects of peptides released upon digestion and/or its amino acid composition. The objective of the present study was to compare the satiating effects of intact whey protein isolate (WPI) or a free amino acid mixture (AAM) simulating the amino acid composition of the WPI. A single-blind completely randomised block design included twenty, healthy, adult women (age 24·2 (sem 0·8) years) of normal weight (BMI 22·7 (sem 0·4) kg/m2). Following consumption of isoenergetic (approximately 1800 kJ) preload meals enriched (52 g amino acid equivalent) with WPI or AAM, consumption of an ad libitum test meal 120 min later and subjective feelings of appetite using visual analogue scales (VAS) were determined. There were no significant differences (P=0·24) in the ad libitum test meal intakes between the WPI (268·5 (sem 27·3) g) and the AAM (238·4 (sem 22·7) g) preload meals. Subjective VAS ratings of appetite did not differ significantly between the WPI and the AAM preload meals (P>0·05). Intact whey protein and a free AAM simulating the whey protein showed similar effects on satiety. This suggests that the satiating effect of whey protein may be related to its specific amino acid composition.

  19. Normal protein intake is required for body weight loss and weight maintenance, and elevated protein intake for additional preservation of resting energy expenditure and fat free mass.

    Science.gov (United States)

    Soenen, Stijn; Martens, Eveline A P; Hochstenbach-Waelen, Ananda; Lemmens, Sofie G T; Westerterp-Plantenga, Margriet S

    2013-05-01

    Energy-restricted high-protein diets (HPDs) have shown favorable results for body weight (BW) management, yet studies differ in their outcomes depending on the dietary protein content. Our objective was to determine the effects of dietary protein content on BW loss-related variables during a 6-mo energy restriction with the use of diets containing protein at the level of requirement [normal-protein diet (NPD), 0.8 g · kg BW(-1) (.) d(-1)] and above (HPD, 1.2 g · kg BW(-1) (.) d(-1)). In overweight and obese participants (24 men and 48 women), BW, body composition, and metabolic responses were assessed before and after subsequent energy intakes of 100, 33, and 67% of the original individual daily energy requirements. Protein intake was consistent in the NPD (0.8 ± 0.3 g · kg BW(-1) (.) d(-1)) and HPD (1.2 ± 0.3 g · kg BW(-1) (.) d(-1)) groups throughout the study (P body fat mass similarly decreased in the NPD and HPD groups (P initial sparing effect of FFM and lowering of DBP.

  20. LSM Proteins Provide Accurate Splicing and Decay of Selected Transcripts to Ensure Normal Arabidopsis Development[W

    Science.gov (United States)

    Perea-Resa, Carlos; Hernández-Verdeja, Tamara; López-Cobollo, Rosa; Castellano, María del Mar; Salinas, Julio

    2012-01-01

    In yeast and animals, SM-like (LSM) proteins typically exist as heptameric complexes and are involved in different aspects of RNA metabolism. Eight LSM proteins, LSM1 to 8, are highly conserved and form two distinct heteroheptameric complexes, LSM1-7 and LSM2-8,that function in mRNA decay and splicing, respectively. A search of the Arabidopsis thaliana genome identifies 11 genes encoding proteins related to the eight conserved LSMs, the genes encoding the putative LSM1, LSM3, and LSM6 proteins being duplicated. Here, we report the molecular and functional characterization of the Arabidopsis LSM gene family. Our results show that the 11 LSM genes are active and encode proteins that are also organized in two different heptameric complexes. The LSM1-7 complex is cytoplasmic and is involved in P-body formation and mRNA decay by promoting decapping. The LSM2-8 complex is nuclear and is required for precursor mRNA splicing through U6 small nuclear RNA stabilization. More importantly, our results also reveal that these complexes are essential for the correct turnover and splicing of selected development-related mRNAs and for the normal development of Arabidopsis. We propose that LSMs play a critical role in Arabidopsis development by ensuring the appropriate development-related gene expression through the regulation of mRNA splicing and decay. PMID:23221597

  1. PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice

    Science.gov (United States)

    Zinker, Bradley A.; Rondinone, Cristina M.; Trevillyan, James M.; Gum, Rebecca J.; Clampit, Jill E.; Waring, Jeffrey F.; Xie, Nancy; Wilcox, Denise; Jacobson, Peer; Frost, Leigh; Kroeger, Paul E.; Reilly, Regina M.; Koterski, Sandra; Opgenorth, Terry J.; Ulrich, Roger G.; Crosby, Seth; Butler, Madeline; Murray, Susan F.; McKay, Robert A.; Bhanot, Sanjay; Monia, Brett P.; Jirousek, Michael R.

    2002-01-01

    The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA1C. Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, were increased and PI3-kinase p85α expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes. PMID:12169659

  2. Estimation of low-dose radiation-responsive proteins in the absence of genomic instability in normal human fibroblast cells.

    Science.gov (United States)

    Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Nam, Seon Young; Kim, Cha Soon

    2017-11-01

    Low-dose radiation has various biological effects such as adaptive responses, low-dose hypersensitivity, as well as beneficial effects. However, little is known about the particular proteins involved in these effects. Here, we sought to identify low-dose radiation-responsive phosphoproteins in normal fibroblast cells. We assessed genomic instability and proliferation of fibroblast cells after γ-irradiation by γ-H2AX foci and micronucleus formation analyses and BrdU incorporation assay, respectively. We screened fibroblast cells 8 h after low-dose (0.05 Gy) γ-irradiation using Phospho Explorer Antibody Microarray and validated two differentially expressed phosphoproteins using Western blotting. Cell proliferation proceeded normally in the absence of genomic instability after low-dose γ-irradiation. Phospho antibody microarray analysis and Western blotting revealed increased expression of two phosphoproteins, phospho-NFκB (Ser536) and phospho-P70S6K (Ser418), 8 h after low-dose radiation. Our findings suggest that low-dose radiation of normal fibroblast cells activates the expression of phospho-NFκB (Ser536) and phospho-P70S6K (Ser418) in the absence of genomic instability. Therefore, these proteins may be involved in DNA damage repair processes.

  3. Correlation Between Placental Matrix Metalloproteinase 9 and Tumor Necrosis Factor-α Protein Expression Throughout Gestation in Normal Human Pregnancy.

    Science.gov (United States)

    Basu, Jayasri; Agamasu, Enyonam; Bendek, Bolek; Salafia, Carolyn M; Mishra, Aruna; Lopez, Julia Vasquez; Kroes, Jessica; Dragich, Sharon Claire; Thakur, Ashley; Mikhail, Magdy

    2018-04-01

    Matrix metalloproteinases (MMPs), specifically MMP-9 plays a role in human placentation. The enzyme confers an invasive ability to cytotrophoblasts and degrades the endometrial matrix as the cells infiltrate the decidua to keep up with placental growth. Since tumor necrosis factor-α (TNF-α) can induce the synthesis of MMP-9, we investigated the patterns of changes in and correlation between placental villous MMP-9 and TNF-α expressions throughout normal human gestation. Placentas were obtained from 179 normal pregnant women who underwent elective abortion or term delivery. Chorionic villi isolated from placental samples were grouped as first, second, and third trimester (7 0/7 -13 0/7 , 13 1/7 -23 6/7 , and 37 0/7 -42 4/7 weeks, respectively). Chorionic villous TNF-α and MMP-9 proteins were assayed using enzyme immunoassay kits. There were significant differences in MMP-9 and TNF-α protein expressions among the trimester groups ( P = .001). The MMP-9 protein increased progressively with an increase in gestational age (GA), but TNF-α peaked in the second trimester. Within each trimester group, we searched for the effects of variation of GA in days on the 2 variables. A significant positive correlation between MMP-9 and GA was noted in the first trimester ( r = 0.364, P = .005). No other comparisons were significant. When GA was controlled for, partial correlation revealed a significant positive correlation between TNF-α and MMP-9 only in the second trimester ( r = 0.300, P = .018). We hypothesize that the TNF-α peak and the positive correlation between TNF-α and MMP-9 in the second trimester of normal human gestation could contribute toward a successful pregnancy outcome.

  4. Effect of passive smoking on the levels of pregnancy associated plasma protein-A in normal rats

    International Nuclear Information System (INIS)

    Naveed, A.K.; Rahim, A.; Malik, M.S.

    2010-01-01

    To measure the levels of pregnancy associated plasma protein- A (PAPPA-A) in normal rats exposed to cigarette smoke. Sixty albino rats of Sprague- Dawley strain weighing 200-250 gm, divided into two groups. Both the groups were kept in identical chambers. One group of 30 rats was further exposed to passive cigarette smoke for 4 weeks. No increase was observed in the levels of serum PAPP-A of both the groups: Passive smokers and not exposed to passive smoking i.e. P > 0.05. Smoking does not increase the levels of PAPP-A. (author)

  5. All-atom normal-mode analysis reveals an RNA-induced allostery in a bacteriophage coat protein.

    Science.gov (United States)

    Dykeman, Eric C; Twarock, Reidun

    2010-03-01

    Assembly of the T=3 bacteriophage MS2 is initiated by the binding of a 19 nucleotide RNA stem loop from within the phage genome to a symmetric coat protein dimer. This binding event effects a folding of the FG loop in one of the protein subunits of the dimer and results in the formation of an asymmetric dimer. Since both the symmetric and asymmetric forms of the dimer are needed for the assembly of the protein container, this allosteric switch plays an important role in the life cycle of the phage. We provide here details of an all-atom normal-mode analysis of this allosteric effect. The results suggest that asymmetric contacts between the A -duplex RNA phosphodiester backbone of the stem loop with the EF loop in one coat protein subunit results in an increased dynamic behavior of its FG loop. The four lowest-frequency modes, which encompass motions predominantly on the FG loops, account for over 90% of the increased dynamic behavior due to a localization of the vibrational pattern on a single FG loop. Finally, we show that an analysis of the allosteric effect using an elastic network model fails to predict this localization effect, highlighting the importance of using an all-atom full force field method for this problem.

  6. Retinol-Binding Protein 4 in Young Men With Low Versus Normal Birth Weight

    DEFF Research Database (Denmark)

    Ribel-Madsen, Rasmus; Brøns, Charlotte; Friedrichsen, Martin

    2011-01-01

    = 15.4 µg/ml (9.5; 21.3), P index (D(i)) (ß = -2.4% (-4.5%; -0.2%), P = 0.04) and increased basal hepatic glucose production rate (HGP) (ß = 0.02 mg kg(-1) min(-1) (0.002; 0.04), P = 0.03), but not associated...... with peripheral glucose disposal rate or hepatic insulin resistance index. RBP4 levels were not influenced by overfeeding or related to peripheral and hepatic insulin resistance provoked by the dietary intervention. In conclusion, plasma RBP4 in young men associates with components of the metabolic syndrome...... = 20) or normal (n = 26) birth weight underwent a 5-day high-fat high-calorie (HFHC) dietary intervention. In vivo glucose metabolism was assessed by euglycemic-hyperinsulinemic clamp, glucose tracer and intravenous glucose tolerance test techniques. Body composition was measured by a dual-energy x...

  7. Changes in energy expenditure associated with ingestion of high protein, high fat versus high protein, low fat meals among underweight, normal weight, and overweight females

    Directory of Open Access Journals (Sweden)

    White Barry D

    2007-11-01

    Full Text Available Abstract Background Metabolic rate is known to rise above basal levels after eating, especially following protein consumption. Yet, this postprandial rise in metabolism appears to vary among individuals. This study examined changes in energy expenditure in response to ingestion of a high protein, high fat (HPHF meal versus an isocaloric high protein, low fat (HPLF meal in underweight, normal weight, or overweight females (n = 21 aged 19–28 years. Methods Energy expenditure, measured using indirect calorimetry, was assessed before and every 30 minutes for 3.5 hours following consumption of the meals on two separate occasions. Height and weight were measured using standard techniques. Body composition was measured using bioelectrical impedance analysis. Results Significant positive correlations were found between body mass index (BMI and baseline metabolic rate (MR (r = 0.539; p = 0.017, between body weight and baseline MR (r = 0.567; p = 0.011, between BMI and average total change in MR (r = 0.591; p = 0.008, and between body weight and average total change in MR (r = 0.464; p = 0.045. Metabolic rate (kcal/min was significantly higher in the overweight group than the normal weight group, which was significantly higher than the underweight group across all times and treatments. However, when metabolic rate was expressed per kg fat free mass (ffm, no significant difference was found in postprandial energy expenditure between the overweight and normal groups. Changes in MR (kcal/min and kcal/min/kg ffm from the baseline rate did not significantly differ in the underweight (n = 3 or in the overweight subjects (n = 5 following consumption of either meal at any time. Changes in MR (kcal/min and kcal/min/kg ffm from baseline were significantly higher in normal weight subjects (n = 11 across all times following consumption of the HPHF meal versus the HPLF meal. Conclusion There is no diet-induced thermogenic advantage between the HPHF and HPLF meals in

  8. Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation

    Science.gov (United States)

    Zallocchi, Marisa; Meehan, Daniel T.; Delimont, Duane; Rutledge, Joseph; Gratton, Michael Anne; Flannery, John; Cosgrove, Dominic

    2012-01-01

    The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G-protein coupled receptor 1 (VLGR1) have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause Usher syndrome, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa. Here we show developmental expression of these Usher proteins in afferent spiral ganglion neurons and hair cell synapses. We identify a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we performed morphological and quantitative analysis of the neuronal fibers and their synapses in the Clrn1−/− mouse, which was generated by incomplete deletion of the gene. These mice showed a delay in neuronal/synaptic maturation by both immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames waltzerav3J mice also suggests a delay in hair cell synaptogenesis. Collectively, these results show that, in addition to the well documented role for Usher proteins in stereocilia development, Usher protein complexes comprised of specific protein isoforms likely function in synaptic maturation as well. PMID:22363448

  9. Role for a novel Usher protein complex in hair cell synaptic maturation.

    Directory of Open Access Journals (Sweden)

    Marisa Zallocchi

    Full Text Available The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23, protocadherin-15 (PCDH15 and the very large G-protein coupled receptor 1 (VLGR1 have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause Usher syndrome, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa. Here we show developmental expression of these Usher proteins in afferent spiral ganglion neurons and hair cell synapses. We identify a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we performed morphological and quantitative analysis of the neuronal fibers and their synapses in the Clrn1-/- mouse, which was generated by incomplete deletion of the gene. These mice showed a delay in neuronal/synaptic maturation by both immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames waltzer(av3J mice also suggests a delay in hair cell synaptogenesis. Collectively, these results show that, in addition to the well documented role for Usher proteins in stereocilia development, Usher protein complexes comprised of specific protein isoforms likely function in synaptic maturation as well.

  10. Phosphorylation of intracellular proteins related to the multihormonal regulation of prolactin: comparison of normal anterior pituitary cells in culture with the tumor-derived GH cell lines

    International Nuclear Information System (INIS)

    Beretta, L.; Boutterin, M.C.; Sobel, A.

    1988-01-01

    We have previously identified a group of cytoplasmic phosphoproteins (proteins 1-11) whose phosphorylation could be related, on a pharmacological basis, to the multihormonal regulation of PRL synthesis and release in the anterior pituitary tumor-derived GH cell lines. Phosphoproteins with identical migration properties on two-dimensional electrophoresis gels were also detectable in normal rat anterior pituitary cells in culture. We designed appropriate culture and [ 32 P] phosphate-labeling conditions allowing to analyze the regulation of the phosphorylation of these proteins in normal pituitary cells. TRH, 12-O-tetradecanoylphorbol-13-acetate, and vasoactive intestinal peptide induced the same qualitative changes in phosphorylation of proteins 1-11 in normal as in GH cells. Quantitative differences observed are most likely due to the heterogeneity of primary pituitary cultures. Phosphorylation changes affecting proteins 14-16, not previously detected in GH cells, were also observed with normal anterior pituitary cells. GH cell lines have lost the sensitivity of pituitary lactotrophs for dopamine, an important physiological inhibitor of PRL synthesis and release. In normal anterior pituitary cells in culture, dopamine inhibited also the TRH-stimulated phosphorylation of proteins 1-10, thus strengthening the correlation between phosphorylation of these proteins and multihormonal regulation of pituitary cell functions. Our results indicate: 1) that the same phosphoproteins as in GH cells are related to the multihormonal regulation of nontumoral, normal anterior pituitary cells in culture; 2) that dopamine acts by interfering with the phosphorylation of these proteins

  11. Fat storage-inducing transmembrane protein 2 is required for normal fat storage in adipose tissue.

    Science.gov (United States)

    Miranda, Diego A; Kim, Ji-Hyun; Nguyen, Long N; Cheng, Wang; Tan, Bryan C; Goh, Vera J; Tan, Jolene S Y; Yaligar, Jadegoud; Kn, Bhanu Prakash; Velan, S Sendhil; Wang, Hongyan; Silver, David L

    2014-04-04

    Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo.

  12. Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

    Science.gov (United States)

    West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

    2010-11-01

    Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

  13. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein.

    Science.gov (United States)

    Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M; Monick, Martha M; Lin, Yong; Carter, A Brent; Klingelhutz, Aloysius J; Nyunoya, Toru

    2014-09-01

    Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner's syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.

  14. Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis.

    Science.gov (United States)

    Eriguchi, Rieko; Obi, Yoshitsugu; Streja, Elani; Tortorici, Amanda R; Rhee, Connie M; Soohoo, Melissa; Kim, Taehee; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

    2017-07-07

    There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients. Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011). Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model ( P trend urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality ( P trend urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk. Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality. Copyright © 2017 by the American Society of Nephrology.

  15. Protein Profiling of Isolated Leukocytes, Myofibroblasts, Epithelial, Basal, and Endothelial Cells from Normal, Hyperplastic, Cancerous, and Inflammatory Human Prostate Tissues

    Directory of Open Access Journals (Sweden)

    Zahraa I. Khamis, Kenneth A. Iczkowski, Ziad J. Sahab, Qing-Xiang Amy Sang

    2010-01-01

    Full Text Available In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prsotate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

  16. Model-free methods of analyzing domain motions in proteins from simulation : A comparison of normal mode analysis and molecular dynamics simulation of lysozyme

    NARCIS (Netherlands)

    Hayward, S.; Kitao, A.; Berendsen, H.J.C.

    Model-free methods are introduced to determine quantities pertaining to protein domain motions from normal mode analyses and molecular dynamics simulations, For the normal mode analysis, the methods are based on the assumption that in low frequency modes, domain motions can be well approximated by

  17. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    DEFF Research Database (Denmark)

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

    2008-01-01

    in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

  18. Nuclear location of tumor suppressor protein maspin inhibits proliferation of breast cancer cells without affecting proliferation of normal epithelial cells

    International Nuclear Information System (INIS)

    Machowska, Magdalena; Wachowicz, Katarzyna; Sopel, Mirosław; Rzepecki, Ryszard

    2014-01-01

    Maspin, which is classified as a tumor suppressor protein, is downregulated in many types of cancer. Several studies have suggested potential anti-proliferative activity of maspin as well as sensitizing activity of maspin for therapeutic cytotoxic agents in breast cancer tissue culture and animal models. All of the experimental data gathered so far have been based on studies with maspin localized cytoplasmically, while maspin in breast cancer tumor cells may be located in the cytoplasm, nucleus or both. In this study, the effect of maspin cytoplasmic and nuclear location and expression level on breast cancer proliferation and patient survival was studied. Tissue sections from 166 patients with invasive ductal breast cancer were stained by immunohistochemistry for maspin and Ki-67 protein. The localization and expression level of maspin were correlated with estimated patient overall survival and percent of Ki-67-positive cells. In further studies, we created constructs for transient transfection of maspin into breast cancer cells with targeted cytoplasmic and nuclear location. We analyzed the effect of maspin location in normal epithelial cell line MCF10A and three breast cancer cell lines - MCF-7, MDA-MB-231 and SKBR-3 - by immunofluorescence and proliferation assay. We observed a strong positive correlation between moderate and high nuclear maspin level and survival of patients. Moreover, a statistically significant negative relationship was observed between nuclear maspin and Ki-67 expression in patients with invasive ductal breast cancer. Spearman’s correlation analysis showed a negative correlation between level of maspin localized in nucleus and percentage of Ki-67 positive cells. No such differences were observed in cells with cytoplasmic maspin. We found a strong correlation between nuclear maspin and loss of Ki-67 protein in breast cancer cell lines, while there was no effect in normal epithelial cells from breast. The anti-proliferative effect of nuclear

  19. Nuclear location of tumor suppressor protein maspin inhibits proliferation of breast cancer cells without affecting proliferation of normal epithelial cells

    Science.gov (United States)

    2014-01-01

    Background Maspin, which is classified as a tumor suppressor protein, is downregulated in many types of cancer. Several studies have suggested potential anti-proliferative activity of maspin as well as sensitizing activity of maspin for therapeutic cytotoxic agents in breast cancer tissue culture and animal models. All of the experimental data gathered so far have been based on studies with maspin localized cytoplasmically, while maspin in breast cancer tumor cells may be located in the cytoplasm, nucleus or both. In this study, the effect of maspin cytoplasmic and nuclear location and expression level on breast cancer proliferation and patient survival was studied. Methods Tissue sections from 166 patients with invasive ductal breast cancer were stained by immunohistochemistry for maspin and Ki-67 protein. The localization and expression level of maspin were correlated with estimated patient overall survival and percent of Ki-67-positive cells. In further studies, we created constructs for transient transfection of maspin into breast cancer cells with targeted cytoplasmic and nuclear location. We analyzed the effect of maspin location in normal epithelial cell line MCF10A and three breast cancer cell lines - MCF-7, MDA-MB-231 and SKBR-3 - by immunofluorescence and proliferation assay. Results We observed a strong positive correlation between moderate and high nuclear maspin level and survival of patients. Moreover, a statistically significant negative relationship was observed between nuclear maspin and Ki-67 expression in patients with invasive ductal breast cancer. Spearman’s correlation analysis showed a negative correlation between level of maspin localized in nucleus and percentage of Ki-67 positive cells. No such differences were observed in cells with cytoplasmic maspin. We found a strong correlation between nuclear maspin and loss of Ki-67 protein in breast cancer cell lines, while there was no effect in normal epithelial cells from breast. The anti

  20. Analysis of drug-protein binding using on-line immunoextraction and high-performance affinity microcolumns: Studies with normal and glycated human serum albumin.

    Science.gov (United States)

    Matsuda, Ryan; Jobe, Donald; Beyersdorf, Jared; Hage, David S

    2015-10-16

    A method combining on-line immunoextraction microcolumns with high-performance affinity chromatography (HPAC) was developed and tested for use in examining drug-protein interactions with normal or modified proteins. Normal human serum albumin (HSA) and glycated HSA were used as model proteins for this work. High-performance immunoextraction microcolumns with sizes of 1.0-2.0 cm × 2.1mm i.d. and containing anti-HSA polyclonal antibodies were developed and tested for their ability to bind normal HSA or glycated HSA. These microcolumns were able to extract up to 82-93% for either type of protein at 0.05-0.10 mL/min and had a binding capacity of 0.34-0.42 nmol HSA for a 1.0 cm × 2.1mm i.d. microcolumn. The immunoextraction microcolumns and their adsorbed proteins were tested for use in various approaches for drug binding studies. Frontal analysis was used with the adsorbed HSA/glycated HSA to measure the overall affinities of these proteins for the drugs warfarin and gliclazide, giving comparable values to those obtained previously using similar protein preparations that had been covalently immobilized within HPAC columns. Zonal elution competition studies with gliclazide were next performed to examine the specific interactions of this drug at Sudlow sites I and II of the adsorbed proteins. These results were also comparable to those noted in prior work with covalently immobilized samples of normal HSA or glycated HSA. These experiments indicated that drug-protein binding studies can be carried out by using on-line immunoextraction microcolumns with HPAC. The same method could be used in the future with clinical samples and other drugs or proteins of interest in pharmaceutical studies or biomedical research. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Effect of irradiation on cell cycle, cell death and expression of its related proteins in normal human oral keratinocytes

    International Nuclear Information System (INIS)

    Kang, Mi Ae; Heo, Min Suk; Lee, Sam Sun; Oh, Sung Ook; Choi, Soon Chul; Park, Tae Won; Lee, Sul Mi; Jeon, In Seong

    2003-01-01

    To investigate the radiosensitivity of the normal human oral keratinocytes (NHOK), and the effect of irradiation on cell cycle and protein expression. To evaluate the radiosensitivity of NHOK, the number of colonies and cells were counted after irradiation and the SF2 (survival fraction as 2 Gy) value, and the cell survival curve fitted on a linear-quadratic model were obtained. LDH analysis was carried out to evaluate the necrosis of NHOK at 1, 2,3, and 4 days after 2, 10, and 20 Gy irradiation. Cell cycle arrest and the induction of apoptosis were analyzed using flow cytometry at 1, 2, 3, and 4 days after 2, 10, and 20 Gy irradiation. Finally, proteins related cell cycle arrest and apoptosis were analysed by Western blot. The number of survival cell was significantly decreased in a dose-dependent manner. The cell survival curve showed SF2, α, and β values to be 0.568, 0.209, and 0.020 respectively. At 20 Gy irradiated cells showed higher optical density than the control group. After irradiation, apoptosis was not observed but G2 arrest was observed in the NHOK cells. 1 day after 10 Gy irradiation, the expression of p53 remained unchanged, the p21 WAF1/Cip1 increased and the mdm2 decreased. The expression of bax, bcl-2, cyclin B1, and cyclin D remained unchanged. These results indicate that NHOK responds to irradiation by G2 arrest, which is possibly mediated by the expression of p21 WAF1/Cip1 , and that cell necrosis occurs by high dose irradiation.

  2. Comparison of true metabolisable energy and true amino acid availability between normal maize and quality protein maize (Shandan 17

    Directory of Open Access Journals (Sweden)

    Mei Li Zhang

    2010-01-01

    Full Text Available A precision-fed assay was conducted to determine true metabolisable energy and true amino acid digestibility in Chinese quality protein maize (QPM compared with normal maize (NM. Thirty adult roosters, kept in individual cages, were made to fast for 48h and then tub-fed 50g QPM or NM per bird and their excreta was colleted for the subsequent 48h. Additional fifteen roosters were made to fast in order to estimate endogenous losses of energy and amino acids (AA in excreta. Gross energy of the two types of maize were similar; the lysine content in NM and QPM were 0.27% and 0.41% (DM basis, respectively. True metabolisable energy (TME and true metabolisable energy nitrogen corrected (TMEn values of QPM and NM were not significantly different (P>0.05. Digestibility of some AA, including lysine and methionine, in QPM were higher than those in NM (P<0.05. The results of this study indicated that the nutritive value of QPM might be higher than that of NM.

  3. Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Tracy Ho

    Full Text Available Amyloid precursor protein (APP is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.

  4. Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts

    International Nuclear Information System (INIS)

    Keyse, S.M.; Tyrrell, R.M.

    1987-01-01

    We have analyzed the pattern of protein synthesis in solar near ultraviolet (334 nm, 365 nm) and near visible (405 nm) irradiated normal human skin fibroblasts. Two hours after irradiation we find that one major stress protein of approximately 32 kDa is induced in irradiated cells. This protein is not induced by ultraviolet radiation at wavelengths shorter than 334 nm and is not inducible by heat shock treatment of these cells. Although sodium arsenite, diamide, and menadione all induced a 32-kDa protein, they also induced the major heat shock proteins. In contrast, the oxidizing agent, hydrogen peroxide, induced the low molecular weight stress protein without causing induction of the major heat shock proteins. A comparison of the 32-kDa proteins induced by sodium arsenite, H 2 O 2 , and solar near ultraviolet radiation using chemical peptide mapping shows that they are closely related. These results imply that the pathways for induction of the heat shock response and the 32-kDa protein are not identical and suggest that, at least in the case of radiation and treatment with H 2 O 2 , the 32-kDa protein might be induced in response to cellular oxidative stress. This conclusion is supported by the observation that depletion of endogenous cellular glutathione prior to solar near ultraviolet irradiation lowers the fluence threshold for induction of the 32-kDa stress protein

  5. Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes

    International Nuclear Information System (INIS)

    Villano, C.M.; White, L.A.

    2006-01-01

    The ID (inhibitor of differentiation or DNA binding) helix-loop-helix proteins are important mediators of cellular differentiation and proliferation in a variety of cell types through regulation of gene expression. Overexpression of the ID proteins in normal human keratinocytes results in extension of culture lifespan, indicating that these proteins are important for epidermal differentiation. Our hypothesis is that the ID proteins are targets of the retinoic acid signaling pathway in keratinocytes. Retinoids, vitamin A analogues, are powerful regulators of cell growth and differentiation and are widely used in the prevention and treatment of a variety of cancers in humans. Furthermore, retinoic acid is necessary for the maintenance of epithelial differentiation and demonstrates an inhibitory action on skin carcinogenesis. We examined the effect of all-trans retinoic acid on expression of ID-1, -2, -3, and -4 in normal human keratinocytes and found that exposure of these cells to all-trans retinoic acid causes an increase in both ID-1 and ID-3 gene expression. Furthermore, our data show that this increase is mediated by increased transcription involving several cis-acting elements in the distal portion of the promoter, including a CREB-binding site, an Egr1 element, and an YY1 site. These data demonstrate that the ID proteins are direct targets of the retinoic acid signaling pathway. Given the importance of the ID proteins to epidermal differentiation, these results suggest that IDs may be mediating some of the effects of all-trans retinoic acid in normal human keratinocytes

  6. Protonation states of histidine and other key residues in deoxy normal human adult hemoglobin by neutron protein crystallography

    International Nuclear Information System (INIS)

    Kovalevsky, Andrey; Chatake, Toshiyuki; Shibayama, Naoya; Park, Sam-Yong; Ishikawa, Takuya; Mustyakimov, Marat; Fisher, S. Zoe; Langan, Paul; Morimoto, Yukio

    2010-01-01

    Using neutron diffraction analysis, the protonation states of 35 of 38 histidine residues were determined for the deoxy form of normal human adult hemoglobin. Distal and buried histidines may contribute to the increased affinity of the deoxy state for hydrogen ions and its decreased affinity for oxygen compared with the oxygenated form. The protonation states of the histidine residues key to the function of deoxy (T-state) human hemoglobin have been investigated using neutron protein crystallography. These residues can reversibly bind protons, thereby regulating the oxygen affinity of hemoglobin. By examining the OMIT F o − F c and 2F o − F c neutron scattering maps, the protonation states of 35 of the 38 His residues were directly determined. The remaining three residues were found to be disordered. Surprisingly, seven pairs of His residues from equivalent α or β chains, αHis20, αHis50, αHis58, αHis89, βHis63, βHis143 and βHis146, have different protonation states. The protonation of distal His residues in the α 1 β 1 heterodimer and the protonation of αHis103 in both subunits demonstrates that these residues may participate in buffering hydrogen ions and may influence the oxygen binding. The observed protonation states of His residues are compared with their ΔpK a between the deoxy and oxy states. Examination of inter-subunit interfaces provided evidence for interactions that are essential for the stability of the deoxy tertiary structure

  7. The Differential Expression of Aqueous Soluble Proteins in Breast Normal and Cancerous Tissues in Relation to Ethnicity of the Patients; Chinese, Malay and Indian

    Directory of Open Access Journals (Sweden)

    Seng Liang

    2010-01-01

    Full Text Available Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC. A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.

  8. Marked differences in immunocytological localization of [3H]estradiol-binding protein in rat pancreatic acinar tumor cells compared to normal acinar cells

    International Nuclear Information System (INIS)

    Beaudoin, A.R.; Grondin, G.; St Jean, P.; Pettengill, O.; Longnecker, D.S.; Grossman, A.

    1991-01-01

    [ 3 H]Estradiol can bind to a specific protein in normal rat pancreatic acinar cells. Electron microscopic immunocytochemical analysis has shown this protein to be localized primarily in the rough endoplasmic reticulum and mitochondria. Rat exocrine pancreatic tumor cell lines, whether grown in tissue culture (AR42J) or as a tumor mass after sc injection into rats (DSL-2), lacked detectable amounts of this [ 3 H]estradiol-binding protein (EBP), as determined by the dextran-coated charcoal assay. Furthermore, primary exocrine pancreatic neoplasms induced with the carcinogen azaserine contained little or no detectable [ 3 H]estradiol-binding activity. However, electron immunocytochemical studies of transformed cells indicated the presence of material that cross-reacted with antibodies prepared against the [ 3 H]EBP. The immunopositive reaction in transformed cells was localized almost exclusively in lipid granules. Such lipid organelles in normal acinar cells, although present less frequently than in transformed cells, have never been observed to contain EBP-like immunopositive material. Presumably, the aberrant localization of EBP in these acinar tumor cells results in loss of function of this protein, which in normal pancreatic acinar cells appears to exert a modulating influence on zymogen granule formation and the process of secretion

  9. Multi-scaled normal mode analysis method for dynamics simulation of protein-membrane complexes: A case study of potassium channel gating motion correlations

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiaokun; Han, Min; Ming, Dengming, E-mail: dming@fudan.edu.cn [Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai (China)

    2015-10-07

    Membrane proteins play critically important roles in many cellular activities such as ions and small molecule transportation, signal recognition, and transduction. In order to fulfill their functions, these proteins must be placed in different membrane environments and a variety of protein-lipid interactions may affect the behavior of these proteins. One of the key effects of protein-lipid interactions is their ability to change the dynamics status of membrane proteins, thus adjusting their functions. Here, we present a multi-scaled normal mode analysis (mNMA) method to study the dynamics perturbation to the membrane proteins imposed by lipid bi-layer membrane fluctuations. In mNMA, channel proteins are simulated at all-atom level while the membrane is described with a coarse-grained model. mNMA calculations clearly show that channel gating motion can tightly couple with a variety of membrane deformations, including bending and twisting. We then examined bi-channel systems where two channels were separated with different distances. From mNMA calculations, we observed both positive and negative gating correlations between two neighboring channels, and the correlation has a maximum as the channel center-to-center distance is close to 2.5 times of their diameter. This distance is larger than recently found maximum attraction distance between two proteins embedded in membrane which is 1.5 times of the protein size, indicating that membrane fluctuation might impose collective motions among proteins within a larger area. The hybrid resolution feature in mNMA provides atomic dynamics information for key components in the system without costing much computer resource. We expect it to be a conventional simulation tool for ordinary laboratories to study the dynamics of very complicated biological assemblies. The source code is available upon request to the authors.

  10. Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Anthony, F; Masson, G M; Wood, P J [Southampton Univ. (UK)

    1983-01-01

    An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.4-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific ..beta../sub 1/ glycoprotein (SP/sub 1/) was also measured in these samples and normal ranges for PAPP-P and SP/sub 1/ were constructed from the results obtained.

  11. Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Anthony, F; Masson, G M; Wood, P J [Southampton Univ. (UK)

    1983-01-01

    An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.04-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific ..beta../sub 1/ glycoprotein (SP/sub 1/) was also measured in these samples and normal ranges for PAPP-A and SP/sub 1/ were constructed from the results obtained.

  12. Development of a radioimmunoassay for pregnancy-associated plasma protein A and establishment of normal levels in the first trimester of pregnancy

    International Nuclear Information System (INIS)

    Anthony, F.; Masson, G.M.; Wood, P.J.

    1983-01-01

    An accelerated double antibody method has been developed for the radioimmunoassay of pregnancy-associated plasma protein A (PAPP-A) in serum. The workable range for the assay was 0.4-1.8 mg/l of serum. PAPP-A levels were determined in single serum samples from 110 women with prospective normal pregnancies of between 7 and 14 weeks' gestation. The level of pregnancy specific #betta# 1 glycoprotein (SP 1 ) was also measured in these samples and normal ranges for PAPP-P and SP 1 were constructed from the results obtained. (author)

  13. Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training.

    Science.gov (United States)

    Bradley, Scott J; Kingwell, Bronwyn A; Canny, Benedict J; McConell, Glenn K

    2007-10-01

    Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.

  14. Differential expression and processing of transforming growth factor beta induced protein (TGFBIp) in the normal human cornea during postnatal development and aging

    DEFF Research Database (Denmark)

    Karring, Henrik; Runager, Kasper; Valnickova, Zuzana

    2010-01-01

    Transforming growth factor beta induced protein (TGFBIp, also named keratoepithelin) is an extracellular matrix protein abundant in the cornea. The purpose of this study was to determine the expression and processing of TGFBIp in the normal human cornea during postnatal development and aging...... trimming events from the N-terminus of mature TGFBIp generate TGFBIp isoforms which form a similar "zig-zag" pattern when separated by 2-D polyacrylamide gel electrophoresis (PAGE). This study shows that in humans TGFBIp is more abundant in mature corneas than in the developing cornea...... and that the processing of TGFBIp changes during postnatal development of the cornea. In addition, TGFBIp appears to be degraded in a highly orchestrated manner in the normal human cornea with the resulting C-terminal fragments being retained in the cornea. The age-related changes in the expression and processing...

  15. [Behavior of circadian rhythm of ACTH and cortisol in 16 normal subjects after a balanced normocaloric diet and after a high protein diet (Cosinor mean method)].

    Science.gov (United States)

    Sellini, M; Giovannini, C; Manzo, G; Barletta, C; Borboni, P

    1983-01-31

    In 16 normal subjects the circadian rhythm of ACTH has been studied during normal calories diet and after a 15 days period of high protein content diet (2 g/Kg body weight). The statistical study, according Cosinor method, has shown a significant increase of the mesor and of the amplitude, but has not shown any change of the ACTH and Cortisol rhythm, after hyperproteic diet. Data advise the increase of the tonic and fasic secretion of both hormones and shown the mantained acrophase. The action of the protein on the ACTH and Cortisol secretion does not seem related to mechanism like stress, neither to the probable mediation of intestinal like-ACTH messengers. On the contrary it seems related to a direct stimulus on the diencephalo-pituitary axis; it is possible that some amino-acids (tryptophan, arginine) act as a mediator, even if data concern just the effect of the over mentioned amino-acid in large doses.

  16. Brain protein synthesis in normal and demented patients. A study by P.E.T. with 11C-L methionine

    International Nuclear Information System (INIS)

    Bustany, P.; Soussaline, F.; Comar, D.; Henry, J.F.

    1982-09-01

    A compartmental model representing protein synthesis in the brain was validated experimentally in 9 baboons. After sequential injections of 11 C, 3 H and 14 C methionines on the same animal, followed by P.E.T. recording of the γ activity in a chosen brain section with time, the distribution of methionine injected into the different compartments of the model after a bolus was measured by crushing and precipitation with T.C.A. The agreement between direct in vitro findings and computed results is excellent. This method of studying brain protein synthesis in vivo was applied to 28 Alzheimer dementia cases and 20 normal subjects of the same age. The correlation between the results of clinical and psychometric tests and the brain protein synthesis activity confirms an anomaly in this biochemical synthesis process during the illness. A 65% fall in activity may be found in the frontal lobes of certain patients

  17. Angiotensin-converting enzyme-inhibitory activity in protein hydrolysates from normal and anthracnose disease-damaged Phaseolus vulgaris seeds.

    Science.gov (United States)

    Hernández-Álvarez, Alan Javier; Carrasco-Castilla, Janet; Dávila-Ortiz, Gloria; Alaiz, Manuel; Girón-Calle, Julio; Vioque-Peña, Javier; Jacinto-Hernández, Carmen; Jiménez-Martínez, Cristian

    2013-03-15

    Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity. Protein concentrates from beans spoiled by anthracnose disease and from regular beans as controls were prepared by alkaline extraction and precipitation at isolelectric pH and hydrolysed using Alcalase 2.4 L. The hydrolysates from spoiled beans had ACE-I-inhibitory activity (IC(50) 0.0191 mg protein mL(-1)) and were very similar to those from control beans in terms of ACE-I inhibition, peptide electrophoretic profile and kinetics of hydrolysis. Thus preparation of hydrolysates using beans affected by anthracnose disease would allow for revalorisation of this otherwise wasted product. The present results suggest the use of spoiled bean seeds, e.g. anthracnose-damaged beans, as an alternative for the isolation of ACE-I-inhibitory peptides to be further introduced as active ingredients in functional foods. © 2012 Society of Chemical Industry.

  18. An early function of the adenoviral E1B 55 kDa protein is required for the nuclear relocalization of the cellular p53 protein in adenovirus-infected normal human cells

    International Nuclear Information System (INIS)

    Cardoso, F.M.; Kato, Sayuri E.M.; Huang Wenying; Flint, S. Jane; Gonzalez, Ramon A.

    2008-01-01

    It is well established that the human subgroup C adenovirus type 5 (Ad5) E1B 55 kDa protein can regulate the activity and concentration of the cellular tumor suppressor, p53. However, the contribution(s) of these functions of the E1B protein to viral reproduction remains unclear. To investigate this issue, we examined properties of p53 in normal human cells infected by E1B mutant viruses that display defective entry into the late phase or viral late mRNA export. The steady-state concentrations of p53 were significantly higher in cells infected by the E1B 55 kDa null mutant Hr6 or three mutants carrying small insertions in the E1B 55 kDa protein coding sequence than in Ad5-infected cells. Nevertheless, none of the mutants induced apoptosis in infected cells. Rather, the localization of p53 to E1B containing nuclear sites observed during infection by Ad5 was prevented by mutations that impair interaction of the E1B protein with p53 and/or with the E4 Orf6 protein. These results indicate that the E1B protein fulfills an early function that correlates efficient entry into the late phase with the localization of E1B and p53 in the nucleus of Ad5-infected normal human cells

  19. Hematopoietic properties of granulocyte colony-stimulating factor/immunoglobulin (G-CSF/IgG-Fc fusion proteins in normal and neutropenic rodents.

    Directory of Open Access Journals (Sweden)

    George N Cox

    Full Text Available Previously we showed that granulocyte colony-stimulating factor (G-CSF in vitro bioactivity is preserved when the protein is joined via a flexible 7 amino acid linker to an immunoglobulin-1 (IgG1-Fc domain and that the G-CSF/IgG1-Fc fusion protein possessed a longer circulating half-life and improved hematopoietic properties compared to G-CSF in normal rats. We have extended this analysis by comparing the relative hematopoietic potencies of G-CSF/IgG1-Fc to G-CSF in normal mice and to G-CSF and polyethylene glycol (PEG -modified G-CSF in neutropenic rats. Mice were treated for 5 days using different doses and dosing regimens of G-CSF/IgG1-Fc or G-CSF and circulating neutrophil levels in the animals measured on Day 6. G-CSF/IgG1-Fc stimulated greater increases in blood neutrophils than comparable doses of G-CSF when administered using daily, every other day or every third day dosing regimens. In rats made neutropenic with cyclophosphamide, G-CSF/IgG1-Fc accelerated recovery of blood neutrophils to normal levels (from Day 9 to Day 5 when administered as 5 daily injections or as a single injection on Day 1. By contrast, G-CSF accelerated neutrophil recovery when administered as 5 daily injections, but not when administered as a single injection. G-CSF/IgG1-Fc was as effective as PEG-G-CSF at accelerating neutrophil recovery following a single injection in neutropenic rats. G-CSF/IgG1-Fc and G-CSF/IgG4-Fc fusion proteins in which the 7 amino acid linker was deleted also were effective at accelerating neutrophil recovery following a single injection in neutropenic rats. These studies confirm the enhanced in vivo hematopoietic properties of G-CSF/IgG-Fc fusion proteins.

  20. Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue

    NARCIS (Netherlands)

    Parmentier, H. K.; van Wichen, D. F.; Meyling, F. H.; Goudsmit, J.; Schuurman, H. J.

    1992-01-01

    The expression of regulatory proteins tat, rev, and nef of human immunodeficiency virus type-1 (HIV-1) and tat of HIV-2 was studied in frozen sections of lymph nodes from HIV-1-infected individuals, and various tissues from uninfected persons. In HIV-1-positive lymph nodes, monoclonal antibodies to

  1. Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

    Directory of Open Access Journals (Sweden)

    Yang Jin

    2008-08-01

    Full Text Available Abstract Background Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke, a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER functioning, our data highlighted a defensive role for the unfolded protein response (UPR program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer. Methods Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry. Results We show that: 1 CS induces ER stress and activates components of the UPR; 2 reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3 CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4 several major UPR regulators are increased either in expression (i.e., BiP and eIF2α or phosphorylation (i.e., phospho-eIF2α in a majority of human lung cancers. Conclusion These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have

  2. Tau protein degradation is catalyzed by the ATP/ubiquitin-independent 20S proteasome under normal cell conditions

    OpenAIRE

    Grune, Tilman; Botzen, Diana; Engels, Martina; Voss, Peter; Kaiser, Barbara; Jung, Tobias; Grimm, Stefanie; Ermak, Gennady; Davies, Kelvin J. A.

    2010-01-01

    Tau is the major protein exhibiting intracellular accumulation in Alzheimer disease. The mechanisms leading to its accumulation are not fully understood. It has been proposed that the proteasome is responsible for degrading tau but, since proteasomal inhibitors block both the ubiquitin-dependent 26S proteasome and the ubiqutin-independent 20S proteasome pathways, it is not clear which of these pathways is involved in tau degradation. Some involvement of the ubiquitin ligase, CHIP in tau degra...

  3. Expressão da proteína Bax no tecido mamário normal de mulheres no menacme tratadas com raloxifeno Expression of Bax protein in normal tissue of premenopausal women treated with raloxifene

    Directory of Open Access Journals (Sweden)

    Ana Maria Furtado-Veloso

    2008-04-01

    Full Text Available OBJETIVO: avaliar a expressão do antígeno Bax no epitélio mamário normal de mulheres na pré-menopausa tratadas com raloxifeno. MÉTODOS: estudo randomizado duplo-cego, envolvendo 33 mulheres pré-menopáusicas com fibroadenoma. As pacientes foram divididas em dois grupos: Placebo, (n=18 e Raloxifeno 60 mg, (n=15. A medicação foi usada durante 22 dias, começando no primeiro dia do ciclo menstrual. Uma biópsia foi realizada no 23º dia do ciclo menstrual, durante a qual uma amostra do tecido mamário normal adjacente ao fibroadenoma foi coletada e submetida a estudo imuno-histoquímico utilizando o anticorpo policlonal anti-Bax para avaliar a expressão da proteína Bax. A imunorreação para a proteína Bax foi avaliada, levando-se em consideração a intensidade e a fração de células coradas, cuja combinação resultou em um escore final de 0 a 6. Os casos com escore final >3 foram classificados como positivos para proteína Bax. O teste do c2 foi usado para análise estatística dos dados (pPURPOSE: to evaluate the expression of Bax antigen in the normal mammary epithelium of premenopausal women treated with raloxifene. METHODS: a randomized double-blind study was conducted in 33 ovulatory premenopausal women with fibroadenoma. Patients were divided into two groups: Placebo, (n=18 and Raloxifene 60 mg, (n=15. The medication was used for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day of the menstrual cycle and a sample of normal breast tissue adjacent to the fibroadenoma was collected and submitted to immunohistochemical study using anti-Bax polyclonal antibody to evaluate the expression of Bax protein. Immunoreaction for Bax was evaluated taking into consideration intensity and fraction of stained cells, whose combination resulted in a final score ranging from 0 to 6. Cases with a final score >3 were classified as positive for Bax. The c2 test was used for statistical

  4. Neural responses to visual food stimuli after a normal vs. higher protein breakfast in breakfast-skipping teens: a pilot fMRI study.

    Science.gov (United States)

    Leidy, Heather J; Lepping, Rebecca J; Savage, Cary R; Harris, Corey T

    2011-10-01

    This functional magnetic resonance imaging (fMRI) pilot study identified whether breakfast consumption would alter the neural activity in brain regions associated with food motivation and reward in overweight "breakfast skipping" (BS) adolescent girls and examined whether increased protein at breakfast would lead to additional alterations. Ten girls (Age: 15 ± 1 years; BMI percentile 93 ± 1%; BS 5 ± 1×/week) completed 3 testing days. Following the BS day, the participants were provided with, in randomized order, normal protein (NP; 18 ± 1 g protein) or higher protein (HP; 50 ± 1 g protein) breakfast meals to consume at home for 6 days. On day 7 of each pattern, the participants came to the laboratory to consume their respective breakfast followed by appetite questionnaires and an fMRI brain scan to identify brain activation responses to viewing food vs. nonfood images prior to lunch. Breakfast consumption led to enduring (i.e., 3-h post breakfast) reductions in neural activation in the hippocampus, amygdala, cingulate, and parahippocampus vs. BS. HP led to enduring reductions in insula and middle prefrontal cortex activation vs. NP. Hippocampal, amygdala, cingulate, and insular activations were correlated with appetite and inversely correlated with satiety. In summary, the addition of breakfast led to alterations in brain activation in regions previously associated with food motivation and reward with additional alterations following the higher-protein breakfast. These data suggest that increased dietary protein at breakfast might be a beneficial strategy to reduce reward-driven eating behavior in overweight teen girls. Due to the small sample size, caution is warranted when interpreting these preliminary findings.

  5. AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy.

    Directory of Open Access Journals (Sweden)

    Astra Dinculescu

    Full Text Available Usher syndrome type III (USH3A is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1 gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken β-actin promoter, which has important implications for the design of future USH3 gene therapy studies. Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins. Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells. Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder.

  6. AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy.

    Science.gov (United States)

    Dinculescu, Astra; Stupay, Rachel M; Deng, Wen-Tao; Dyka, Frank M; Min, Seok-Hong; Boye, Sanford L; Chiodo, Vince A; Abrahan, Carolina E; Zhu, Ping; Li, Qiuhong; Strettoi, Enrica; Novelli, Elena; Nagel-Wolfrum, Kerstin; Wolfrum, Uwe; Smith, W Clay; Hauswirth, William W

    2016-01-01

    Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken β-actin promoter, which has important implications for the design of future USH3 gene therapy studies. Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins. Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells. Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder.

  7. Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

    Science.gov (United States)

    Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

    2017-10-01

    Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Comparison of GLUT1, GLUT3, and GLUT4 mRNA and the subcellular distribution of their proteins in normal human muscle

    Science.gov (United States)

    Stuart, C. A.; Wen, G.; Gustafson, W. C.; Thompson, E. A.

    2000-01-01

    Basal, "insulin-independent" glucose uptake into skeletal muscle is provided by glucose transporters positioned at the plasma membrane. The relative amount of the three glucose transporters expressed in muscle has not been previously quantified. Using a combination of qualitative and quantitative ribonuclease protection assay (RPA) methods, we found in normal human muscle that GLUT1, GLUT3, and GLUT4 mRNA were expressed at 90 +/- 10, 46 +/- 4, and 156 +/- 12 copies/ng RNA, respectively. Muscle was fractionated by DNase digestion and differential sedimentation into membrane fractions enriched in plasma membranes (PM) or low-density microsomes (LDM). GLUT1 and GLUT4 proteins were distributed 57% to 67% in LDM, whereas GLUT3 protein was at least 88% in the PM-enriched fractions. These data suggest that basal glucose uptake into resting human muscle could be provided in part by each of these three isoforms.

  9. Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein

    Science.gov (United States)

    Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M.; Monick, Martha M.; Lin, Yong; Carter, A. Brent; Klingelhutz, Aloysius J.

    2014-01-01

    Background: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. Objectives: We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). Methods: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. Results: We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation. Citation: Jang JH, Bruse S, Huneidi S, Schrader RM, Monick MM, Lin Y, Carter AB, Klingelhutz AJ, Nyunoya T. 2014. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner’s syndrome protein. Environ Health Perspect 122:955–962; http://dx.doi.org/10.1289/ehp.1306911 PMID:24747221

  10. Normal mode analysis based on an elastic network model for biomolecules in the Protein Data Bank, which uses dihedral angles as independent variables.

    Science.gov (United States)

    Wako, Hiroshi; Endo, Shigeru

    2013-06-01

    We have developed a computer program, named PDBETA, that performs normal mode analysis (NMA) based on an elastic network model that uses dihedral angles as independent variables. Taking advantage of the relatively small number of degrees of freedom required to describe a molecular structure in dihedral angle space and a simple potential-energy function independent of atom types, we aimed to develop a program applicable to a full-atom system of any molecule in the Protein Data Bank (PDB). The algorithm for NMA used in PDBETA is the same as the computer program FEDER/2, developed previously. Therefore, the main challenge in developing PDBETA was to find a method that can automatically convert PDB data into molecular structure information in dihedral angle space. Here, we illustrate the performance of PDBETA with a protein-DNA complex, a protein-tRNA complex, and some non-protein small molecules, and show that the atomic fluctuations calculated by PDBETA reproduce the temperature factor data of these molecules in the PDB. A comparison was also made with elastic-network-model based NMA in a Cartesian-coordinate system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Fibrillarin, a nucleolar protein, is required for normal nuclear morphology and cellular growth in HeLa cells

    International Nuclear Information System (INIS)

    Amin, Mohammed Abdullahel; Matsunaga, Sachihiro; Ma, Nan; Takata, Hideaki; Yokoyama, Masami; Uchiyama, Susumu; Fukui, Kiichi

    2007-01-01

    Fibrillarin is a key small nucleolar protein in eukaryotes, which has an important role in pre-rRNA processing during ribosomal biogenesis. Though several functions of fibrillarin are known, its function during the cell cycle is still unknown. In this study, we confirmed the dynamic localization of fibrillarin during the cell cycle of HeLa cells and also performed functional studies by using a combination of immunofluorescence microscopy and RNAi technique. We observed that depletion of fibrillarin has almost no effect on the nucleolar structure. However, fibrillarin-depleted cells showed abnormal nuclear morphology. Moreover, fibrillarin depletion resulted in the reduction of the cellular growth and modest accumulation of cells with 4n DNA content. Our data suggest that fibrillarin would play a critical role in the maintenance of nuclear shape and cellular growth

  12. Comparison of malnutrition inflammation score, anthropometry and biochemical parameters in assessing the difference in protein-energy wasting between normal weight and obese patients undergoing haemodialysis.

    Science.gov (United States)

    Alipoor, Elham; Hosseinzadeh-Attar, Mohammad Javad; Mahdavi-Mazdeh, Mitra; Yaseri, Mehdi; Zahed, Narges S

    2017-07-01

    Protein-energy wasting (PEW) is prevalent in haemodialysis. Obesity is an independent risk factor of kidney insufficiency, but it is proposed to have beneficial roles in better outcomes in the final stage of disease. Better nutritional status and body reserves are among probable mechanisms, but direct examinations are limited. The present study aimed to investigate whether obese patients have preferable nutritional status compared to normal weight patients based on malnutrition inflammation score (MIS) and other PEW parameters in haemodialysis. This case-control study investigated 52 normal weight (18.5 < body mass index (BMI) < 25 kg/m 2 ) and 48 obese (BMI≥30 kg/m 2 ) patients on regular haemodialysis. PEW was assessed based on anthropometric and biochemical factors, recent weight changes, appetite, anorexia, dietary intake and MIS. Obese patients had better MIS compared with the normal weight group (P < 0.001), although varying degrees of wasting were prevalent among this group too (75% mild and 25% moderate wasting). The obese group had less significant weight loss (4.2 vs 8%) and anorexia and better appetite. However, a considerable percentage of patients in both groups showed muscle (94.6% of normal weight and 19.5% of obese) and peripheral fat tissue (89.2% of normal weight and 31.7% of obese) losses compared to the 50th percentile. Biochemical parameters were not significantly different between groups except for triglyceride (P = 0.001), transferrin and total iron-binding capacity (P = 0.028). MIS was significantly better in obese patients; however, both groups showed degrees of wasting based on MIS and other PEW parameters. Nutritional status of obese haemodialysis patients should be monitored regularly because of high risk of PEW like other BMI categories. © 2017 Dietitians Association of Australia.

  13. Evidence of non-coincidence of normalized sigmoidal curves of two different structural properties for two-state protein folding/unfolding

    International Nuclear Information System (INIS)

    Rahaman, Hamidur; Khan, Md. Khurshid Alam; Hassan, Md. Imtaiyaz; Islam, Asimul; Moosavi-Movahedi, Ali Akbar; Ahmad, Faizan

    2013-01-01

    Highlights: ► Non-coincidence of normalized sigmoidal curves of two different structural properties is consistence with the two-state protein folding/unfolding. ► DSC measurements of denaturation show a two-state behavior of g-cyt-c at pH 6.0. ► Urea-induced denaturation of g-cyt-c is a variable two- state process at pH 6.0. ► GdmCl-induced denaturation of g-cyt-c is a fixed two- state process at pH 6.0. -- Abstract: In practice, the observation of non-coincidence of normalized sigmoidal transition curves measured by two different structural properties constitutes a proof of existence of thermodynamically stable intermediate(s) on the folding ↔ unfolding pathway of a protein. Here we give first experimental evidence that this non-coincidence is also observed for a two-state protein denaturation. Proof of this evidence comes from our studies of denaturation of goat cytochrome-c (g-cyt-c) at pH 6.0. These studies involve differential scanning calorimetry (DSC) measurements in the absence of urea and measurements of urea-induced denaturation curves monitored by observing changes in absorbance at 405, 530, and 695 nm and circular dichroism (CD) at 222, 405, and 416 nm. DSC measurements showed that denaturation of the protein is a two-state process, for calorimetric and van’t Hoff enthalpy changes are, within experimental errors, identical. Normalization of urea-induced denaturation curves monitored by optical properties leads to noncoincident sigmoidal curves. Heat-induced transition of g-cyt-c in the presence of different urea concentrations was monitored by CD at 222 nm and absorption at 405 nm. It was observed that these two different structural probes gave not only identical values of T m (transition temperature), ΔH m (change in enthalpy at T m ) and ΔC p (constant-pressure heat capacity change), but these thermodynamic parameters in the absence of urea are also in agreement with those obtained from DSC measurements

  14. Connexin 39.9 Protein Is Necessary for Coordinated Activation of Slow-twitch Muscle and Normal Behavior in Zebrafish*

    Science.gov (United States)

    Hirata, Hiromi; Wen, Hua; Kawakami, Yu; Naganawa, Yuriko; Ogino, Kazutoyo; Yamada, Kenta; Saint-Amant, Louis; Low, Sean E.; Cui, Wilson W.; Zhou, Weibin; Sprague, Shawn M.; Asakawa, Kazuhide; Muto, Akira; Kawakami, Koichi; Kuwada, John Y.

    2012-01-01

    In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca2+ transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers. PMID:22075003

  15. Effect of high-protein or normal-protein diet on weight loss, body composition, hormone, and metabolic profile in southern Brazilian women with polycystic ovary syndrome: a randomized study.

    Science.gov (United States)

    Toscani, Mariana K; Mario, Fernanda M; Radavelli-Bagatini, Simone; Wiltgen, Denusa; Matos, Maria Cristina; Spritzer, Poli Maria

    2011-11-01

    The aim of the present study was to assess the effects of a high protein (HP) and a normal protein (NP) diet on patients with polycystic ovary syndrome (PCOS) and body mass index-matched controls in a sample of southern Brazilian women. This 8-week randomized trial was carried out at a university gynecological endocrinology clinic and included 18 patients with PCOS and 22 controls. Changes in weight, body composition, hormone, and metabolic profile were analyzed in women randomized to receive HP (30% protein, 40% carbohydrate, and 30% lipid) or NP (15% protein, 55% carbohydrate, and 30% lipid). The energy content was estimated for each participant at 20-25 kcal/kg current weight/day. Physical activity, blood pressure, homeostasis model assessment (HOMA) index, and fasting and 2-h glucose and insulin remained stable during the intervention in PCOS and controls, even in the presence of weight loss. There were no changes in lipid profile in either group. In contrast, body weight, body mass index (BMI), waist circumference, percent of body fat, and sum of trunk skinfolds decreased significantly after both diets in both groups. Total testosterone also decreased in PCOS and controls regardless of diet. In conclusion, calorie reduction, rather than protein content, seemed to affect body composition and hormonal profile in this short-term study. These findings emphasize the role of non-pharmacological interventions to reduce weight and ameliorate the anthropometric and clinical phenotype in PCOS.

  16. The human adenovirus type 5 E1B 55 kDa protein obstructs inhibition of viral replication by type I interferon in normal human cells.

    Directory of Open Access Journals (Sweden)

    Jasdave S Chahal

    Full Text Available Vectors derived from human adenovirus type 5, which typically lack the E1A and E1B genes, induce robust innate immune responses that limit their therapeutic efficacy. We reported previously that the E1B 55 kDa protein inhibits expression of a set of cellular genes that is highly enriched for those associated with anti-viral defense and immune responses, and includes many interferon-sensitive genes. The sensitivity of replication of E1B 55 kDa null-mutants to exogenous interferon (IFN was therefore examined in normal human fibroblasts and respiratory epithelial cells. Yields of the mutants were reduced at least 500-fold, compared to only 5-fold, for wild-type (WT virus replication. To investigate the mechanistic basis of such inhibition, the accumulation of viral early proteins and genomes was compared by immunoblotting and qPCR, respectively, in WT- and mutant-infected cells in the absence or presence of exogenous IFN. Both the concentration of viral genomes detected during the late phase and the numbers of viral replication centers formed were strongly reduced in IFN-treated cells in the absence of the E1B protein, despite production of similar quantities of viral replication proteins. These defects could not be attributed to degradation of entering viral genomes, induction of apoptosis, or failure to reorganize components of PML nuclear bodies. Nor was assembly of the E1B- and E4 Orf6 protein- E3 ubiquitin ligase required to prevent inhibition of viral replication by IFN. However, by using RT-PCR, the E1B 55 kDa protein was demonstrated to be a potent repressor of expression of IFN-inducible genes in IFN-treated cells. We propose that a primary function of the previously described transcriptional repression activity of the E1B 55 kDa protein is to block expression of IFN- inducible genes, and hence to facilitate formation of viral replication centers and genome replication.

  17. Characteristics of Febrile Patients with Normal White Blood Cell Counts and High C-Reactive Protein Levels in an Emergency Department

    Directory of Open Access Journals (Sweden)

    Kuan-Ting Liu

    2008-05-01

    Full Text Available Fever is one of the more common chief complaints of patients who visit emergency departments (ED. Many febrile patients have markedly elevated C-reactive protein (CRP levels and normal white blood cell (WBC counts. Most of these patients have bacterial infection and no previous underlying disease of impaired WBC functioning. We reviewed patients who visited our ED between November 2003 and July 2004. The WBC count and CRP level of patients over 18 years of age who visited the ED because of or with fever were recorded. Patients who had normal WBC count (4,000–10,000/mL and high CRP level (> 100 mg/L were included. The data, including gender, age and length of hospital stay, were reviewed. Underlying diseases, diagnosis of the febrile disease and final condition were recorded according to the chart. Within the study period, 54,078 patients visited our ED. Of 5,628 febrile adults, 214 (3.8% had elevated CRP level and normal WBC count. The major cause of febrility was infection (82.24%. Most of these patients were admitted (92.99%. There were 32 patients with malignant neoplasm, nine with liver cirrhosis, 66 with diabetes mellitus and 11 with uremia. There were no significant differences in age and gender between patients with and those without neoplasm. However, a higher inhospital mortality rate and other causes of febrility were noted in patients with neoplasm. It was not rare in febrile patients who visited the ED to have a high CRP level but normal WBC count. These patients did not necessarily have an underlying malignant neoplasm or hematologic illness. Factors other than malignant neoplasm or hematologic illness may be associated with the WBC response, and CRP may be a better indicator of infection under such conditions.

  18. A comprehensive two-dimensional gel protein database of noncultured unfractionated normal human epidermal keratinocytes: towards an integrated approach to the study of cell proliferation, differentiation and skin diseases

    DEFF Research Database (Denmark)

    Celis, J E; Madsen, Peder; Rasmussen, H H

    1991-01-01

    A two-dimensional (2-D) gel database of cellular proteins from noncultured, unfractionated normal human epidermal keratinocytes has been established. A total of 2651 [35S]methionine-labeled cellular proteins (1868 isoelectric focusing, 783 nonequilibrium pH gradient electrophoresis) were resolved...

  19. Expression of cellular prion protein in the frontal and occipital lobe in Alzheimer's disease, diffuse Lewy body disease, and in normal brain: an immunohistochemical study.

    Science.gov (United States)

    Rezaie, Payam; Pontikis, Charlie C; Hudson, Lance; Cairns, Nigel J; Lantos, Peter L

    2005-08-01

    Cellular prion protein (PrP(c)) is a glycoprotein expressed at low to moderate levels within the nervous system. Recent studies suggest that PrP(c) may possess neuroprotective functions and that its expression is upregulated in certain neurodegenerative disorders. We investigated whether PrP(c) expression is altered in the frontal and occipital cortex in two well-characterized neurodegenerative disorders--Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD)--compared with that in normal human brain using immunohistochemistry and computerized image analysis. The distribution of PrP(c) was further tested for correlation with glial reactivity. We found that PrP(c) was localized mainly in the gray matter (predominantly in neurons) and expressed at higher levels within the occipital cortex in the normal human brain. Image analysis revealed no significant variability in PrP(c) expression between DLBD and control cases. However, blood vessels within the white matter of DLBD cases showed immunoreactivity to PrP(c). By contrast, this protein was differentially expressed in the frontal and occipital cortex of AD cases; it was markedly overexpressed in the former and significantly reduced in the latter. Epitope specificity of antibodies appeared important when detecting PrP(c). The distribution of PrP(c) did not correlate with glial immunoreactivity. In conclusion, this study supports the proposal that regional changes in expression of PrP(c) may occur in certain neurodegenerative disorders such as AD, but not in other disorders such as DLBD.

  20. Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

    Science.gov (United States)

    Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

    2017-09-01

    Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (Pbreast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

  1. Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

    International Nuclear Information System (INIS)

    Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

    1988-01-01

    Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

  2. Low levels of Survival Motor Neuron protein are sufficient for normal muscle function in the SMNΔ7 mouse model of SMA.

    Science.gov (United States)

    Iyer, Chitra C; McGovern, Vicki L; Murray, Jason D; Gombash, Sara E; Zaworski, Phillip G; Foust, Kevin D; Janssen, Paul M L; Burghes, Arthur H M

    2015-11-01

    Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons. SMA is caused by deletion or mutation of the Survival Motor Neuron 1 (SMN1) gene and retention of the SMN2 gene. The loss of SMN1 results in reduced levels of the SMN protein. SMN levels appear to be particularly important in motor neurons; however SMN levels above that produced by two copies of SMN2 have been suggested to be important in muscle. Studying the spatial requirement of SMN is important in both understanding how SMN deficiency causes SMA and in the development of effective therapies. Using Myf5-Cre, a muscle-specific Cre driver, and the Cre-loxP recombination system, we deleted mouse Smn in the muscle of mice with SMN2 and SMNΔ7 transgenes in the background, thus providing low level of SMN in the muscle. As a reciprocal experiment, we restored normal levels of SMN in the muscle with low SMN levels in all other tissues. We observed that decreasing SMN in the muscle has no phenotypic effect. This was corroborated by muscle physiology studies with twitch force, tetanic and eccentric contraction all being normal. In addition, electrocardiogram and muscle fiber size distribution were also normal. Replacement of Smn in muscle did not rescue SMA mice. Thus the muscle does not appear to require high levels of SMN above what is produced by two copies of SMN2 (and SMNΔ7). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Mutation of the protein kinase C site in borna disease virus phosphoprotein abrogates viral interference with neuronal signaling and restores normal synaptic activity.

    Directory of Open Access Journals (Sweden)

    Christine M A Prat

    2009-05-01

    Full Text Available Understanding the pathogenesis of infection by neurotropic viruses represents a major challenge and may improve our knowledge of many human neurological diseases for which viruses are thought to play a role. Borna disease virus (BDV represents an attractive model system to analyze the molecular mechanisms whereby a virus can persist in the central nervous system (CNS and lead to altered brain function, in the absence of overt cytolysis or inflammation. Recently, we showed that BDV selectively impairs neuronal plasticity through interfering with protein kinase C (PKC-dependent signaling in neurons. Here, we tested the hypothesis that BDV phosphoprotein (P may serve as a PKC decoy substrate when expressed in neurons, resulting in an interference with PKC-dependent signaling and impaired neuronal activity. By using a recombinant BDV with mutated PKC phosphorylation site on P, we demonstrate the central role of this protein in BDV pathogenesis. We first showed that the kinetics of dissemination of this recombinant virus was strongly delayed, suggesting that phosphorylation of P by PKC is required for optimal viral spread in neurons. Moreover, neurons infected with this mutant virus exhibited a normal pattern of phosphorylation of the PKC endogenous substrates MARCKS and SNAP-25. Finally, activity-dependent modulation of synaptic activity was restored, as assessed by measuring calcium dynamics in response to depolarization and the electrical properties of neuronal networks grown on microelectrode arrays. Therefore, preventing P phosphorylation by PKC abolishes viral interference with neuronal activity in response to stimulation. Our findings illustrate a novel example of viral interference with a differentiated neuronal function, mainly through competition with the PKC signaling pathway. In addition, we provide the first evidence that a viral protein can specifically interfere with stimulus-induced synaptic plasticity in neurons.

  4. Bone Morphogenetic Protein (BMP-4 and BMP-7 regulate differentially Transforming Growth Factor (TGF-β1 in normal human lung fibroblasts (NHLF

    Directory of Open Access Journals (Sweden)

    Lloyd Clare M

    2010-06-01

    Full Text Available Abstract Background Airway remodelling is thought to be under the control of a complex group of molecules belonging to the Transforming Growth Factor (TGF-superfamily. The Bone Morphogenetic Proteins (BMPs belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-β-induced profibrotic functions in lung fibroblasts. Methods Cell cultures were exposed to TGF-β1 alone or in the presence of BMP-4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of α-smooth muscle actin (α-SMA by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP activity was assessed by zymography. Results We have demonstrated TGF-β1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-β1-induced extracellular matrix protein production. TGF-β1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-β1-induced MMP-13 release compared to untreated and TGF-β1-treated cells. TGF-β1 also induced a myofibroblast-like transformation which was partially inhibited by BMP-7 but not BMP-4. Conclusions Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for

  5. Postprandial glucose-lowering effect of premeal consumption of protein-enriched, dietary fiber-fortified bar in individuals with type 2 diabetes mellitus or normal glucose tolerance.

    Science.gov (United States)

    Bae, Jae Hyun; Kim, Lee Kyung; Min, Se Hee; Ahn, Chang Ho; Cho, Young Min

    2018-03-04

    Protein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. The present study was carried out to investigate the postprandial glucose-lowering effect of a premeal protein-enriched, dietary fiber-fortified bar (PFB), which contains moderate amounts of protein, in individuals with type 2 diabetes mellitus or normal glucose tolerance (NGT). The participants (15 type 2 diabetes mellitus and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests, 1 week apart in reverse order. Plasma levels of glucose, insulin, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide were measured. During the mixed meal tolerance tests, the incremental area under the curve from 0 to 180 min of plasma glucose levels was lower with premeal PFB than with postmeal PFB in the type 2 diabetes mellitus (14,723 ± 1,310 mg min/dL vs 19,642 ± 1,367 mg min/dL; P = 0.0002) and NGT participants (3,943 ± 416 mg min/dL vs 4,827 ± 520 mg min/dL, P = 0.0296). In the type 2 diabetes mellitus participants, insulinogenic index and the incremental area under the curve from 0 to 180 min of plasma total glucagon-like peptide-1 levels were higher with premeal PFB than with postmeal PFB, but not in the NGT participants. There was no difference in postprandial glucose-dependent insulinotropic polypeptide levels between premeal and postmeal PFB in both groups. Acute administration of premeal PFB decreased postprandial glucose excursion in both type 2 diabetes mellitus and NGT participants. In the type 2 diabetes mellitus participants, premeal PFB augmented the early-phase insulin secretion, possibly through enhancing glucagon-like peptide-1 secretion. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons

  6. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  7. Errors in Computing the Normalized Protein Catabolic Rate due to Use of Single-pool Urea Kinetic Modeling or to Omission of the Residual Kidney Urea Clearance.

    Science.gov (United States)

    Daugirdas, John T

    2017-07-01

    The protein catabolic rate normalized to body size (PCRn) often is computed in dialysis units to obtain information about protein ingestion. However, errors can manifest when inappropriate modeling methods are used. We used a variable volume 2-pool urea kinetic model to examine the percent errors in PCRn due to use of a 1-pool urea kinetic model or after omission of residual urea clearance (Kru). When a single-pool model was used, 2 sources of errors were identified. The first, dependent on the ratio of dialyzer urea clearance to urea distribution volume (K/V), resulted in a 7% inflation of the PCRn when K/V was in the range of 6 mL/min per L. A second, larger error appeared when Kt/V values were below 1.0 and was related to underestimation of urea distribution volume (due to overestimation of effective clearance) by the single-pool model. A previously reported prediction equation for PCRn was valid, but data suggest that it should be modified using 2-pool eKt/V and V coefficients instead of single-pool values. A third source of error, this one unrelated to use of a single-pool model, namely omission of Kru, was shown to result in an underestimation of PCRn, such that each ml/minute Kru per 35 L of V caused a 5.6% underestimate in PCRn. Marked overestimation of PCRn can result due to inappropriate use of a single-pool urea kinetic model, particularly when Kt/V <1.0 (as in short daily dialysis), or after omission of residual native kidney clearance. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. Presence or absence of carbohydrates and the proportion of fat in a high-protein diet affect appetite suppression but not energy expenditure in normal-weight human subjects fed in energy balance.

    Science.gov (United States)

    Veldhorst, Margriet A B; Westerterp, Klaas R; van Vught, Anneke J A H; Westerterp-Plantenga, Margriet S

    2010-11-01

    Two types of relatively high-protein diets, with a normal or low proportion of carbohydrates, have been shown effective for weight loss. The objective was to assess the significance of the presence or absence of carbohydrates and the proportion of fat in high-protein diets for affecting appetite suppression, energy expenditure, and fat oxidation in normal-weight subjects in energy balance. Subjects (aged 23 (sd 3) years and BMI 22·0 (sd 1·9) kg/m2) were stratified in two groups. Each was offered two diets in a randomised cross-over design: group 1 (n 22) - normal protein (NP; 10, 60 and 30 % energy (En%) from protein, carbohydrate and fat), high protein (HP; 30, 40 and 30 En%); group 2 (n 23) - normal protein (NP-g; 10, 60 and 30 En%), high protein, carbohydrate-free (HP-0C; 30, 0 and 70 En%) for 2 d; NP-g and HP-0C were preceded by glycogen-lowering exercise (day 1). Appetite was measured throughout day 2 using visual analogue scales (VAS). Energy expenditure (EE) and substrate oxidation (respiratory quotient; RQ) were measured in a respiration chamber (08.00 hours on day 2 until 07.30 hours on day 3). Fasting plasma β-hydroxybutyrate (BHB) concentration was measured (day 3). NP-g and NP did not differ in hunger, EE, RQ and BHB. HP-0C and HP v. NP-g and NP, respectively, were lower in hunger (P fat oxidation were higher on a high-protein diet without than with carbohydrates exchanged for fat. Energy expenditure was not affected by the carbohydrate content of a high-protein diet.

  9. Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells

    International Nuclear Information System (INIS)

    Dassé, E; Volpe, G; Walton, D S; Wilson, N; Del Pozzo, W; O'Neill, L P; Slany, R K; Frampton, J; Dumon, S

    2012-01-01

    The proto-oncogenic protein c-Myb is an essential regulator of hematopoiesis and is frequently deregulated in hematological diseases such as lymphoma and leukemia. To gain insight into the mechanisms underlying the aberrant expression of c-Myb in myeloid leukemia, we analyzed and compared c-myb gene transcriptional regulation using two cell lines modeling normal hematopoietic progenitor cells (HPCs) and transformed myelomonocytic blasts. We report that the transcription factors HoxA9, Meis1, Pbx1 and Pbx2 bind in vivo to the c-myb locus and maintain its expression through different mechanisms in HPCs and leukemic cells. Our analysis also points to a critical role for Pbx2 in deregulating c-myb expression in murine myeloid cells cotransformed by the cooperative activity of HoxA9 and Meis1. This effect is associated with an intronic positioning of epigenetic marks and RNA polymerase II binding in the orthologous region of a previously described alternative promoter for c-myb. Taken together, our results could provide a first hint to explain the abnormal expression of c-myb in leukemic cells

  10. The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles.

    Science.gov (United States)

    McGee, Joann; Goodyear, Richard J; McMillan, D Randy; Stauffer, Eric A; Holt, Jeffrey R; Locke, Kirsten G; Birch, David G; Legan, P Kevin; White, Perrin C; Walsh, Edward J; Richardson, Guy P

    2006-06-14

    Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles.

  11. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for

  12. Characteristics of six small heat shock protein genes from Bactrocera dorsalis: Diverse expression under conditions of thermal stress and normal growth.

    Science.gov (United States)

    Dou, Wei; Tian, Yi; Liu, Hong; Shi, Yan; Smagghe, Guy; Wang, Jin-Jun

    2017-11-01

    To explore the functions of small heat shock proteins (sHsps) in relation to thermal stress and development in Bactrocera dorsalis (Hendel), one of the most economically important pest species attacking a wide range of fruits and vegetables, six full-length cDNAs of sHsp genes (BdHsp17.7, 18.4, 20.4, 20.6, 21.6 and 23.8) were cloned, and the expression patterns in different developmental stages and tissues, as well as in response to both thermal and 20-hydroxyecdysone (20E) exposures, were examined using real time quantitative PCR. The open reading frames (ORFs) of six sHsps are 453, 489, 537, 543, 567 and 630bp in length, encoding proteins with molecular weights of 17.7, 18.4, 20.4, 20.6, 21.6 and 23.8kDa, respectively. BdHsp18.4 and BdHsp20.4 maintained lower expression levels in both eggs and larvae, whereas remarkably up-regulated after the larval-pupal transformation, suggesting that these two sHsps may be involved in metamorphosis. Significant tissue specificity exists among sHsps: the highest expression of BdHsp20.6 and BdHsp23.8 in the Malpighian tubules and ovary, respectively, versus a peak in the fat body for others. BdHsp20.4 and BdHsp20.6 were significantly up-regulated by thermal stress. In contrast, BdHsp18.4 and BdHsp23.8 reacted only to heat stress. BdHsp17.7 and BdHsp21.6 were insensitive to both heat and cold stresses. The degree of sHsps response depends on intensity of 20E treatment, i.e., dose and time. These results strongly suggest functional differentiation within the sHsp subfamily in B. dorsalis. The physiological function of sHsp members under thermal stress and normal growth remains the subjects of further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Changes in serum cystatin C, creatinine, and C-reactive protein after cardiopulmonary bypass in patients with normal preoperative kidney function.

    Science.gov (United States)

    Svensson, Anders S; Kvitting, John-Peder Escobar; Kovesdy, Csaba P; Cederholm, Ingemar; Szabó, Zoltán

    2016-06-01

    The use of cardiopulmonary bypass (CPB) can cause changes in serum creatinine and cystatin C independent of glomerular filtration rate. We aimed to quantify the temporal changes of these biomarkers and C-reactive protein (CRP) after CPB. This was a prospective study at an academic medical centre between April and October 2013. We compared postoperative changes in serum creatinine and cystatin C in 38 patients with normal preoperative kidney function who underwent cardiac surgery using CPB and did not develop perioperative acute kidney injury (AKI). The effect of inflammation on intra-individual changes was examined in mixed effects regressions, using measurements of pre- and postoperative CRP. Both serum creatinine (79.9 ± 22.7 vs. 92.6 ± 21.4 µmol/L, P = 0.001) and cystatin C (1.16 ± 0.39 vs. 1.33 ± 0.37 mg/L, P = 0.012) decreased significantly in the first 8 h postoperatively compared to preoperatively, as a result of haemodilution. Thereafter serum creatinine returned to preoperative levels, whereas serum cystatin C continued to rise and was significantly elevated at 72 h post-CPB compared to preoperative levels (1.53 ± 0.48 vs. 1.33 ± 0.37 mg/L, P = 0.003). CRP levels increased significantly post-CPB and were significantly associated with increases in both serum creatinine and cystatin C. Serum creatinine and cystatin C appear not to be interchangeable biomarkers during and immediately after CPB. Processes unrelated to kidney function such as acute inflammation have a significant effect on post-CPB changes in these biomarkers, and may result in significant increases in serum cystatin C that could erroneously be interpreted as AKI. © 2015 Asian Pacific Society of Nephrology.

  14. Radiation-induced DNA damage in tumors and normal tissues. III. Oxygen dependence of the formation of strand breaks and DNA-protein crosslinks

    International Nuclear Information System (INIS)

    Zhang, H.; Wallen, C.A.; Wheeler, K.T.; Joch, C.J.

    1995-01-01

    Results from several laboratories, including ours, have suggested that measurements of radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) may be used to estimate the hypoxic fraction or fractional hypoxic volume of tumors and normal tissues. This suggestion has been predicated on both published and nonpublished information that (1) the oxygen dependence of the formation of strand breaks in irradiated mammalian cells is similar to the oxygen dependence of radiation-produced cell killing, and (2) the oxygen dependence of the formation of DPCs in irradiated mammalian cells is the mirror image of the oxygen dependence of radiation-induced cell killing. However, the published studies that attempted to determine the relationship between the oxygen dependence of the formation of strand breaks and the radiation sensitivity of mammalian cells were not performed at 37 degrees C, the exact oxygen concentrations were not always known, and the results were conflicting. In addition, most of the data on the oxygen dependence of the formation of DPCs are unpublished. Consequently, we have undertaken a comprehensive investigation of one cell line, 9L/Ro rat brain tumor cells, to determine if the shape of the oxygen dependence curve and the K m value for radiation-induced strand breaks and DPCs were similar when 9L cells were irradiated under both ideal gas-liquid equilibrium conditions at 4 degrees C and nonideal gas-liquid equilibrium conditions at 37 degrees C. At 4 degrees C under ideal gas-liquid equilibrium conditions, the K m for the formation of strand breaks was approximately 0.0045 mM, and Km for radiation sensitivity was approximately 0.005mM. A similar comparison for the formation of DPCs at 4 degrees C could not be made, because the efficiency of the formation of DPC was much lower at 4 degrees C than at 37 degrees C. 30 refs., 3 figs

  15. The Effect of Serum 25-Hydroxyvitamin D Concentrations on Elevated Serum C-Reactive Protein Concentrations in Normal Weight, Overweight and Obese Participants of a Preventive Health Program.

    Science.gov (United States)

    Mastroeni, Silmara S B S; Munasinghe, Lalani L; Pham, Truong-Minh; Loehr, Sarah A; Ekwaru, John Paul; Mastroeni, Marco F; Veugelers, Paul J

    2016-11-04

    The hypothesized effect of vitamin D on C-reactive protein (CRP) has received substantial attention as a potential means to alleviate the risk for cardiovascular disease. However, observational studies have been inconsistent in their reporting of associations between serum 25-hydroxyvitamin D (25(OH)D) and CRP concentrations, and trials and meta analyses have been inconsistent in their conclusions regarding the effect of vitamin D supplementation on CRP concentrations. These supplementation trials were mostly conducted among patients with more or less inflammatory complications and did not consider potential distinctive effects by weight status. To further our understanding of the potential influences of vitamin D on CRP, we analyzed longitudinal observations of 6755 participants of a preventative health program. On average, serum 25(OH)D concentrations increased from 88.3 to 121.0 nmol/L and those of CRP decreased from 1.7 to 1.6 mg/L between baseline and follow up. Relative to obese participants without temporal increases in 25(OH)D, those who showed improvements of <25, 25-50, 50-75, and more than 75 nmol/L at follow up were 0.57 (95% confidence interval: 0.37-0.88), 0.54 (0.34-0.85), 0.49 (0.30-0.80), and 0.48 (0.29-0.78) times as likely to have elevated CRP concentrations (≥1 mg/L), respectively. These associations were less pronounced and not statistically significant for normal weight and overweight participants. Herewith, the findings suggest that promotion of adequate serum 25(OH)D concentrations among obese individuals along with healthy lifestyles may alleviate the public health burden associated with cardiovascular disease.

  16. Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivo

    DEFF Research Database (Denmark)

    Henriksen, Kim; Gram, Jeppe; Høegh-Andersen, Pernille

    2005-01-01

    of osteoclast markers, morphology, and localization of proteins involved in bone resorption, such as ClC-7 and cathepsin K. The ability to resorb bone was also normal. In vivo, we compared the bone resorption and bone formation response to T3 in ADOI patients and age- and sex-matched controls. We found...

  17. Major proteins in normal human lymphocyte subpopulations separated by fluorescence-activated cell sorting and analyzed by two-dimensional gel electrophoresis

    DEFF Research Database (Denmark)

    Madsen, P S; Hokland, M; Ellegaard, J

    1988-01-01

    markers were observed in all cell types. All the putative protein markers have been identified in the protein database of human peripheral blood mononuclear cells (PBMCs) (see accompanying article by Celis et al.). Comparison of the overall patterns of protein synthesis of the unsorted PBMCs with those...... of the four subpopulations showed that the synthesis of some major PBMC proteins decreased substantially in the sorted subsets. These proteins are most likely not of monocyte origin, as these cells constituted only about 15% of the total PBMCs. Also, the inhibition does not seem to be due to the addition...

  18. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-01-01

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57 Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the 57 Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues

  19. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Science.gov (United States)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-04-01

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

  20. The {sup 57}Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@gmail.com; Alenkina, I. V. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation); Vinogradov, A. V.; Konstantinova, T. S. [Ural State Medical University (Russian Federation); Semionkin, V. A. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation)

    2015-04-15

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the {sup 57}Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the {sup 57}Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues.

  1. Association between intake of dietary protein and 3-year-change in body growth among normal and overweight 6-year-old boys and girls (CoSCIS)

    DEFF Research Database (Denmark)

    van Vught, Anneke J A H; Heitmann, Berit L; Nieuwenhuizen, Arie G

    2010-01-01

    OBJECTIVE: Growth hormone (GH) affects linear growth and body composition, by increasing the secretion of insulin-like growth factor-I (IGF-I), muscle protein synthesis and lipolysis. The intake of protein (PROT) as well as the specific amino acids arginine (ARG) and lysine (LYS) stimulates GH/IG...

  2. Effects of 2 weeks lower limb immobilization and two separate rehabilitation regimens on gastrocnemius muscle protein turnover signaling and normalization genes

    DEFF Research Database (Denmark)

    Nedergaard, Anders; Jespersen, Jakob G; Pingel, Jessica

    2012-01-01

    of resistance training and continued protein/carbohydrate supplementation (Study 2). We obtained muscle biopsies from the medial gastrocnemius prior to immobilization (PRE), post-immobilization (IMMO) and post-rehabilitation (REHAB) and measured protein expression and phosphorylation of Akt, mTOR, S6k, 4E-BP1...

  3. Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN). Detection by enzyme-linked immunosorbent assay and purification from normal human urine

    DEFF Research Database (Denmark)

    Reimert, C M; Minuva, U; Kharazmi, A

    1991-01-01

    Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) is one of the cationic proteins found in the granules of the human eosinophilic granulocytes. EPX was purified from extracts of granules isolated from blood buffy coat cells of healthy donors. Polyclonal anti-EPX antibodies were...

  4. Malware Normalization

    OpenAIRE

    Christodorescu, Mihai; Kinder, Johannes; Jha, Somesh; Katzenbeisser, Stefan; Veith, Helmut

    2005-01-01

    Malware is code designed for a malicious purpose, such as obtaining root privilege on a host. A malware detector identifies malware and thus prevents it from adversely affecting a host. In order to evade detection by malware detectors, malware writers use various obfuscation techniques to transform their malware. There is strong evidence that commercial malware detectors are susceptible to these evasion tactics. In this paper, we describe the design and implementation of a malware normalizer ...

  5. Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study.

    Science.gov (United States)

    Lee, Do-Hun; Phi, Ji Hoon; Chung, You-Nam; Lee, Yun-Jin; Kim, Seung-Ki; Cho, Byung-Kyu; Kim, Dong Won; Park, Moon-Sik; Wang, Kyu-Chang

    2010-05-01

    The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes. Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group. There were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.

  6. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Igor Sterle

    2014-01-01

    Full Text Available Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5 and transient receptor potential vanilloid channels (TRPV1, and TRPV4. Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  7. Effect of insulin on albumin production and incorporation of 14C-leucine into proteins in isolated parenchymal liver cells from normal rats

    DEFF Research Database (Denmark)

    Dich, J; Gluud, C N

    1975-01-01

    the immunologically determined increment in the incubation medium was 1.7 +/- 0.2 mug albumin/min per g liver wet wt. This is about 30% of the rate of production in the perfused liver. Addition of insulin (10(-6)-10(-10) M) enhanced albumin production (50-17%), and incorporation of 14C-leucine both into albumin (50......Parenchymal rat liver cells were isolated by a modification of the collagenase method of Quistorff, Bondesen and Grunnet. The cells secreted albumin into the medium and incorporated 14C-leucine both into cell proteins and proteins secreted into the medium. Albumin production measured from......-8%), secreted proteins (40-9%) and cell proteins (20-8%). Insulin does not increase the production of albumin by depleting the cells. The effect of insulin on albumin production is compatible with an effect on the rate of synthesis as the specific activity of albumin is unaffected by addition of insulin....

  8. Alpha-feto protein radioimmunoassay and its values for the diagnosis of hepatoma among normal Japanese population and those with chronic schistosomiasis

    International Nuclear Information System (INIS)

    Lio, Masahiro; Yamada, Hideo; Luchi, Masahiko

    1972-01-01

    Since its first report made by Ablevet al., α-feto protein which appears both in fetal serum and serum in the cases with hepatoma drew attention of hepatologist in order to establish an qualitative method to diagnose the presence of hepatoma. Since conventional liver scintigraphy is not able to make the diagnosis of the nature of lesion which appears as space occupying lesion need for the more qualitative method facilitated the establishment of the method to detect the presence of α-feto protein in serum. α-feto protein in the serum of hepatoma cases was reported to be identical to fetal α-feto protein by the immunological method. At first, assay of the α-feto protein was performed using the precipitation reaction in agar gel and became quite popular among clinical hepatologist. Detection sensitivity of this conventional method, however, is approximately 10 μgr/ml and α-feto protein was detected in 80% of hepatoma patient. However detection percentage of the hepatoma cases associated with chronic schistosomiasis was found to be as poor as 30% which was measured by our group at Kofu municipal Hospital. Because of the frequent incidences of deformed and small liver by scintigraphy among cases with chronic schistosomiasis and these abnormal liver scintigraphy easily lead one to middiagnose the presence of hepatoma, establishment of more sensitive assay method is needed. After the success of purification and crystallization of the α-feto protein by the group of Univ. of Hokkaido, the radioimmunoassay technique was developed in Japan and α-feto-125 Kit is now became available commercially. Initial trial of this new promising and this double antibody technique enabled us to measure 2 mμgr/ml of α-feto protein which was almost 500-1,000 times more sensitive than those of the conventional method.

  9. Conformational variability of the stationary phase survival protein E from Xylella fastidiosa revealed by X-ray crystallography, small-angle X-ray scattering studies, and normal mode analysis.

    Science.gov (United States)

    Machado, Agnes Thiane Pereira; Fonseca, Emanuella Maria Barreto; Reis, Marcelo Augusto Dos; Saraiva, Antonio Marcos; Santos, Clelton Aparecido Dos; de Toledo, Marcelo Augusto Szymanski; Polikarpov, Igor; de Souza, Anete Pereira; Aparicio, Ricardo; Iulek, Jorge

    2017-10-01

    Xylella fastidiosa is a xylem-limited bacterium that infects a wide variety of plants. Stationary phase survival protein E is classified as a nucleotidase, which is expressed when bacterial cells are in the stationary growth phase and subjected to environmental stresses. Here, we report four refined X-ray structures of this protein from X. fastidiosa in four different crystal forms in the presence and/or absence of the substrate 3'-AMP. In all chains, the conserved loop verified in family members assumes a closed conformation in either condition. Therefore, the enzymatic mechanism for the target protein might be different of its homologs. Two crystal forms exhibit two monomers whereas the other two show four monomers in the asymmetric unit. While the biological unit has been characterized as a tetramer, differences of their sizes and symmetry are remarkable. Four conformers identified by Small-Angle X-ray Scattering (SAXS) in a ligand-free solution are related to the low frequency normal modes of the crystallographic structures associated with rigid body-like protomer arrangements responsible for the longitudinal and symmetric adjustments between tetramers. When the substrate is present in solution, only two conformers are selected. The most prominent conformer for each case is associated to a normal mode able to elongate the protein by moving apart two dimers. To our knowledge, this work was the first investigation based on the normal modes that analyzed the quaternary structure variability for an enzyme of the SurE family followed by crystallography and SAXS validation. The combined results raise new directions to study allosteric features of XfSurE protein. © 2017 Wiley Periodicals, Inc.

  10. Normal accidents

    International Nuclear Information System (INIS)

    Perrow, C.

    1989-01-01

    The author has chosen numerous concrete examples to illustrate the hazardousness inherent in high-risk technologies. Starting with the TMI reactor accident in 1979, he shows that it is not only the nuclear energy sector that bears the risk of 'normal accidents', but also quite a number of other technologies and industrial sectors, or research fields. The author refers to the petrochemical industry, shipping, air traffic, large dams, mining activities, and genetic engineering, showing that due to the complexity of the systems and their manifold, rapidly interacting processes, accidents happen that cannot be thoroughly calculated, and hence are unavoidable. (orig./HP) [de

  11. A novel 5-bp deletion in Clarin 1 in a family with Usher syndrome.

    Science.gov (United States)

    Akoury, Elie; El Zir, Elie; Mansour, Ahmad; Mégarbané, André; Majewski, Jacek; Slim, Rima

    2011-11-01

    To identify the genetic defect in a Lebanese family with two sibs diagnosed with Usher Syndrome. Exome capture and sequencing were performed on DNA from one affected member using Agilent in solution bead capture, followed by Illumina sequencing. This analysis revealed the presence of a novel homozygous 5-bp deletion, in Clarin 1 (CLRN1), a known gene responsible for Usher syndrome type III. The deletion is inherited from both parents and segregates with the disease phenotype in the family. The 5-bp deletion, c.301_305delGTCAT, p.Val101SerfsX27, is predicted to result in a frameshift and protein truncation after 27 amino acids. Sequencing all the coding regions of the CLRN1 gene in the proband did not reveal any other mutation or variant. Here we describe a novel deletion in CLRN1. Our data support previously reported intra familial variability in the clinical features of Usher syndrome type I and III.

  12. Salivary protein concentration, flow rate, buffer capacity and pH estimation: A comparative study among young and elderly subjects, both normal and with gingivitis and periodontitis.

    Science.gov (United States)

    Shaila, Mulki; Pai, G Prakash; Shetty, Pushparaj

    2013-01-01

    To evaluate the salivary protein concentration in gingivitis and periodontitis patients and compare the parameters like salivary total protein, salivary albumin, salivary flow rate, pH, buffer capacity and flow rate in both young and elderly patients with simple methods. One hundred and twenty subjects were grouped based on their age as young and elderly. Each group was subgrouped (20 subjects) as controls, gingivitis and periodontitis. Unstimulated whole saliva was collected from patients and flow rate was noted down during collection of the sample. Salivary protein estimation was done using the Biuret method and salivary albumin was assessed using the Bromocresol green method. pH was estimated with a pHmeter and buffering capacity was analyzed with the titration method. Student's t-test, Fisher's test (ANOVA) and Tukey HSD (ANOVA) tests were used for statistical analysis. A very highly significant rise in the salivary total protein and albumin concentration was noted in gingivitis and periodontitis subjects of both young and elderly. An overall decrease in salivary flow rate was observed among the elderly, and also the salivary flow rate of women was significantly lower than that of men. Significant associations between salivary total protein and albumin in gingivitis and periodontitis were found with simple biochemical tests. A decrease in salivary flow rate among elderly and among women was noted.

  13. Downregulation of miRNA-30c and miR-203a is associated with hepatitis C virus core protein-induced epithelial–mesenchymal transition in normal hepatocytes and hepatocellular carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dongjing [Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha 410008 (China); Wu, Jilin, E-mail: 6296082@qq.com [Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha 410008 (China); Liu, Meizhou [Department of Medical Service, Shenzhen Second People' s Hospital, Shenzhen, Guangdong 518035 (China); Yin, Hui [Staff' s Hospital, Central South University, Changsha, Hunan 410078 (China); He, Jiantai [Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha 410008 (China); Zhang, Bo, E-mail: zhangbo8095@126.com [Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China)

    2015-09-04

    Hepatitis C virus (HCV) Core protein has been demonstrated to induce epithelial–mesenchymal transition (EMT) and is associated with cancer progression of hepatocellular carcinoma (HCC). However, how the Core protein regulates EMT is still unclear. In this study, HCV Core protein was overexpressed by an adenovirus. The protein levels of EMT markers were measured by Western blot. The xenograft animal model was established by inoculation of HepG2 cells. Results showed that ectopic expression of HCV core protein induced EMT in L02 hepatocytes and HepG2 tumor cells by upregulating vimentin, Sanl1, and Snal2 expression and downregulating E-cadherin expression. Moreover, Core protein downregulated miR-30c and miR-203a levels in L02 and HepG2 cells, but artificial expression of miR-30c and miR-203a reversed Core protein-induced EMT. Further analysis showed that ectopic expression of HCV core protein stimulated cell proliferation, inhibited apoptosis, and increased cell migration, whereas artificial expression of miR-30c and miR-203a significantly reversed the role of Core protein in these cell functions in L02 and HepG2 cells. In the HepG2 xenograft tumor models, artificial expression of miR-30c and miR-203a inhibited EMT and tumor growth. Moreover, L02 cells overexpressing Core protein can form tumors in nude mice. In HCC patients, HCV infection significantly shortened patients' survival time, and loss of miR-30c and miR-203 expression correlated with poor survival. In conclusion, HCV core protein downregulates miR-30c and miR-203a expression, which results in activation of EMT in normal hepatocytes and HCC tumor cells. The Core protein-activated-EMT is involved in the carcinogenesis and progression of HCC. Loss of miR-30c and miR-203a expression is a marker for the poor prognosis of HCC. - Highlights: • HCV core protein downregulates miR-30c and miR-203a expression. • Downregulation of miR-30c and miR-203a activates EMT. • Activated-EMT is involved in the

  14. Ehlers-Danlos syndrome type IV : unusual congenital anomalies in a mother and son with a COL3A1 mutation and a normal collagen III protein profile

    NARCIS (Netherlands)

    Kroes, HY; Pals, G; van Essen, AJ

    A mother and son with Ehlers-Danlos syndrome (EDS) type IV and unusual congenital anomalies are described. The congenital anomalies include, in the mother, amniotic band-like constrictions on one hand, a unilateral clubfoot, and macrocephaly owing to normal-pressure hydrocephaly and, in the son, an

  15. Epidermal growth factor receptor-induced activato protein 1 activity controls density-dependent growht inhibition in normal rat kidney fibroblasts.

    NARCIS (Netherlands)

    Hornberg, J.J.; Dekker, H.; Peters, P.H.J.; Langerak, P.; Westerhoff, H.V.; Lankelma, J.; Zoelen, E.J.J.

    2006-01-01

    Density-dependent growth inhibition secures tissue homeostasis. Dysfunction of the mechanisms, which regulate this type of growth control is a major cause of neoplasia. In confluent normal rat kidney (NRK) fibroblasts, epidermal growth factor (EGF) receptor levels decline, ultimately rendering these

  16. Cone structure in patients with usher syndrome type III and mutations in the Clarin 1 gene.

    Science.gov (United States)

    Ratnam, Kavitha; Västinsalo, Hanna; Roorda, Austin; Sankila, Eeva-Marja K; Duncan, Jacque L

    2013-01-01

    To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost. Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations. These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3. clinicaltrials.gov Identifier: NCT00254605.

  17. Cone Structure in Patients With Usher Syndrome Type III and Mutations in the Clarin 1 Gene

    Science.gov (United States)

    Ratnam, Kavitha; Västinsalo, Hanna; Roorda, Austin; Sankila, Eeva-Marja K.; Duncan, Jacque L.

    2015-01-01

    Objective To study macular structure and function in patients with Usher syndrome type III (USH3) caused by mutations in the Clarin 1 gene (CLRN1). Methods High-resolution macular images were obtained by adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in 3 patients with USH3 and were compared with those of age-similar control subjects. Vision function measures included best-corrected visual acuity, kinetic and static perimetry, and full-field electroretinography. Coding regions of the CLRN1 gene were sequenced. Results CLRN1 mutations were present in all the patients; a 20-year-old man showed compound heterozygous mutations (p.N48K and p.S188X), and 2 unrelated women aged 25 and 32 years had homozygous mutations (p.N48K). Best-corrected visual acuity ranged from 20/16 to 20/40, with scotomas beginning at 3° eccentricity. The inner segment-outer segment junction or the inner segment ellipsoid band was disrupted within 1° to 4° of the fovea, and the foveal inner and outer segment layers were significantly thinner than normal. Cones near the fovea in patients 1 and 2 showed normal spacing, and the preserved region ended abruptly. Retinal pigment epithelial cells were visible in patient 3 where cones were lost. Conclusions Cones were observed centrally but not in regions with scotomas, and retinal pigment epithelial cells were visible in regions without cones in patients with CLRN1 mutations. High-resolution measures of retinal structure demonstrate patterns of cone loss associated with CLRN1 mutations. Clinical Relevance These findings provide insight into the effect of CLRN1 mutations on macular cone structure, which has implications for the development of treatments for USH3. Trial Registration clinicaltrials.gov Identifier: NCT00254605 PMID:22964989

  18. PROTEIN TARGETING TO STARCH is required for localising GRANULE-BOUND STARCH SYNTHASE to starch granules and for normal amylose synthesis in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    David Seung

    2015-02-01

    Full Text Available The domestication of starch crops underpinned the development of human civilisation, yet we still do not fully understand how plants make starch. Starch is composed of glucose polymers that are branched (amylopectin or linear (amylose. The amount of amylose strongly influences the physico-chemical behaviour of starchy foods during cooking and of starch mixtures in non-food manufacturing processes. The GRANULE-BOUND STARCH SYNTHASE (GBSS is the glucosyltransferase specifically responsible for elongating amylose polymers and was the only protein known to be required for its biosynthesis. Here, we demonstrate that PROTEIN TARGETING TO STARCH (PTST is also specifically required for amylose synthesis in Arabidopsis. PTST is a plastidial protein possessing an N-terminal coiled coil domain and a C-terminal carbohydrate binding module (CBM. We discovered that Arabidopsis ptst mutants synthesise amylose-free starch and are phenotypically similar to mutants lacking GBSS. Analysis of granule-bound proteins showed a dramatic reduction of GBSS protein in ptst mutant starch granules. Pull-down assays with recombinant proteins in vitro, as well as immunoprecipitation assays in planta, revealed that GBSS physically interacts with PTST via a coiled coil. Furthermore, we show that the CBM domain of PTST, which mediates its interaction with starch granules, is also required for correct GBSS localisation. Fluorescently tagged Arabidopsis GBSS, expressed either in tobacco or Arabidopsis leaves, required the presence of Arabidopsis PTST to localise to starch granules. Mutation of the CBM of PTST caused GBSS to remain in the plastid stroma. PTST fulfils a previously unknown function in targeting GBSS to starch. This sheds new light on the importance of targeting biosynthetic enzymes to sub-cellular sites where their action is required. Importantly, PTST represents a promising new gene target for the biotechnological modification of starch composition, as it is

  19. Reconstructing Normality

    DEFF Research Database (Denmark)

    Gildberg, Frederik Alkier; Bradley, Stephen K.; Fristed, Peter Billeskov

    2012-01-01

    Forensic psychiatry is an area of priority for the Danish Government. As the field expands, this calls for increased knowledge about mental health nursing practice, as this is part of the forensic psychiatry treatment offered. However, only sparse research exists in this area. The aim of this study...... was to investigate the characteristics of forensic mental health nursing staff interaction with forensic mental health inpatients and to explore how staff give meaning to these interactions. The project included 32 forensic mental health staff members, with over 307 hours of participant observations, 48 informal....... The intention is to establish a trusting relationship to form behaviour and perceptual-corrective care, which is characterized by staff's endeavours to change, halt, or support the patient's behaviour or perception in relation to staff's perception of normality. The intention is to support and teach the patient...

  20. Pursuing Normality

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Handberg, Charlotte

    2018-01-01

    implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease......BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study...... was to understand the reflections on cancer survivorship care of lymphoma survivors to aid the future planning of cancer survivorship care and overcome barriers to participation. METHODS: Data were generated in a hematological ward during 4 months of ethnographic fieldwork, including participant observation and 46...

  1. Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Liat Medina

    2014-01-01

    Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

  2. Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection.

    Science.gov (United States)

    da Silva, Vanessa Kappel; de Freitas, Betânia Souza; da Silva Dornelles, Arethuza; Nery, Laura Roesler; Falavigna, Lucio; Ferreira, Rafael Dal Ponte; Bogo, Maurício Reis; Hallak, Jaime Eduardo Cecílio; Zuardi, Antônio Waldo; Crippa, José Alexandre S; Schröder, Nadja

    2014-02-01

    We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats. Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's, and has been related to cognitive deficits in animals and human subjects. Deficits in synaptic energy supply have been linked to neurodegenerative diseases, evidencing the key role played by mitochondria in maintaining viable neural cells and functional circuits. It has also been shown that brains of patients suffering from neurodegenerative diseases have increased expression of apoptosisrelated proteins and specific DNA fragmentation. Here, we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats. We found that CBD rescued iron-induced effects, bringing hippocampal DNM1L, caspase 3, and synaptophysin levels back to values comparable to the control group. Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.

  3. Expression of HSP27, HSP72 and MRP proteins in in vitro co-culture of colon tumour cell spheroids with normal cells after incubation with rhTGF- beta1 and/or CPT-11.

    Science.gov (United States)

    Paduch, Roman; Jakubowicz-Gil, Joanna; Kandefer-Szerszen, Martyna

    2009-12-01

    We studied the expression of inducible heat shock protein (HSP27, HSP72) and multidrug-resistance protein (MRP) in co-cultures of human colon carcinoma cell spheroids obtained from different grades of tumour with normal human colon epithelium, myofibroblast and endothelial cell monolayers. We also measured the influence of recombinant human transforming growth factor beta1 (rhTGF-beta1) and camptothecin (CPT-11), added as single agents or in combination, on the levels of the HSPs, MRP, interleukin (IL)-6 and nitric oxide (NO). An immunoblotting analysis with densitometry showed that rhTGF-beta1 and/or CPT-11 increased HSP27, HSP72 and MRP expression in tumour cells and myofibroblasts, as well as in co-cultures compared with appropriate controls. By contrast, in colonic epithelium, inhibition of HSPs and MRP was comparable with that of the control. In endothelial cells, HSP72 was undetectable. Direct interaction of colon tumour spheroids with normal myofibroblasts caused a significant, tumour-grade dependent increase in IL-6 production. Production of IL-6 was significantly lowered by rhTGF-beta1 and/or CPT-11. Tumour cell spheroids cultivated alone produced larger amounts of NO than normal cells. In co-culture, the level of the radical decreased compared with the sum of NO produced by the monocultures of the two types of cells. rhTGF-beta1 and/or CPT-11 decreased NO production both in tumour and normal cell monocultures and their co-cultures. In conclusion, direct interactions between tumour and normal cells influence the expression of HSP27, HSP72 and MRP, and alter IL-6 and NO production. rhTGF-beta1 and/or CPT-11 may potentate resistance to chemotherapy by increasing HSP and MRP expression but, on the other hand, they may limit tumour cell spread by decreasing the level of some soluble mediators of inflammation (IL-6 and NO).

  4. Mutational analysis of the glycosylphosphatidylinositol (GPI) anchor pathway demonstrates that GPI-anchored proteins are required for cell wall biogenesis and normal hyphal growth in Neurospora crassa.

    Science.gov (United States)

    Bowman, Shaun M; Piwowar, Amy; Al Dabbous, Mash'el; Vierula, John; Free, Stephen J

    2006-03-01

    Using mutational and proteomic approaches, we have demonstrated the importance of the glycosylphosphatidylinositol (GPI) anchor pathway for cell wall synthesis and integrity and for the overall morphology of the filamentous fungus Neurospora crassa. Mutants affected in the gpig-1, gpip-1, gpip-2, gpip-3, and gpit-1 genes, which encode components of the N. crassa GPI anchor biosynthetic pathway, have been characterized. GPI anchor mutants exhibit colonial morphologies, significantly reduced rates of growth, altered hyphal growth patterns, considerable cellular lysis, and an abnormal "cell-within-a-cell" phenotype. The mutants are deficient in the production of GPI-anchored proteins, verifying the requirement of each altered gene for the process of GPI-anchoring. The mutant cell walls are abnormally weak, contain reduced amounts of protein, and have an altered carbohydrate composition. The mutant cell walls lack a number of GPI-anchored proteins, putatively involved in cell wall biogenesis and remodeling. From these studies, we conclude that the GPI anchor pathway is critical for proper cell wall structure and function in N. crassa.

  5. Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin: potential role of protein Z as a powerful determinant of coagulation assays.

    Science.gov (United States)

    Choi, Qute; Kim, Ji-Eun; Hyun, Jungwon; Han, Kyou-Sup; Kim, Hyun Kyung

    2013-07-01

    The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them. The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured. The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0-3.0 was 290.1-494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro. The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle.

    Science.gov (United States)

    Lefort, Natalie; Glancy, Brian; Bowen, Benjamin; Willis, Wayne T; Bailowitz, Zachary; De Filippis, Elena A; Brophy, Colleen; Meyer, Christian; Højlund, Kurt; Yi, Zhengping; Mandarino, Lawrence J

    2010-10-01

    The contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle. Mitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-resistant individuals who were otherwise healthy. Respiration and reactive oxygen species (ROS) production rates were measured in vitro. Relative abundances of proteins detected by mass spectrometry were determined using a normalized spectral abundance factor method. NADH- and FADH(2)-linked maximal respiration rates were similar between lean and obese individuals. Rates of pyruvate and palmitoyl-DL-carnitine (both including malate) ROS production were significantly higher in obesity. Mitochondria from obese individuals maintained higher (more negative) extramitochondrial ATP free energy at low metabolic flux, suggesting that stronger mitochondrial thermodynamic driving forces may underlie the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransferase 1B). We provide data suggesting normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in parallel with high rates of ROS production. Furthermore, we show specific abundance differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insulin resistance.

  7. Hepatitis B virus (HBV)-specific T-cell responses to recombinant HBV core protein in patients with normal liver function and co-infected with chronic HBV and human immunodeficiency virus 1 (HIV-1)

    Science.gov (United States)

    2013-01-01

    Background Little is known about HBV-specific T-cell responses in chronic Hepatitis B patients (HBV) that are co-infected with Human immunodeficiency virus type 1 (HIV-1), especially those with normal alanine aminotransferase (ALT) levels. Methods Twenty-five patients with chronic HBV (11 hepatitis B e antigen [HBeAg]-positive, 14 HBeAg-negative) were enrolled in a cross-sectional study. A longitudinal study as also conducted in which follow-up was done at 3, 12, and 24 months, after acute HIV-1 infection, in 11 individuals who also had chronic HBV. Peripheral blood mononuclear cells were stimulated with recombinant HBV surface protein (S protein), core protein (C protein) or gag peptide. IFN-γ-secreting T cells were identified by ELISPOT assay. Results In the cross-sectional study, co-infected chronic HBV patients had lower C protein-specific T-cell responses compared with mono-infected individuals, though the difference was not significant. In co-infected, chronic HBV patients, the magnitude of C protein-specific T-cell responses was significantly greater in HBeAg-positive subjects compared to HBeAg-negative subjects (p = 0.011). C protein-specific T-cell responses were positively correlated with HBV viral load (rs = 0.40, p = 0.046). However, gag-specific T-cell responses were negatively correlated with HIV viral load (rs = −0.44, p = 0.026) and positively correlated with CD4+ count (rs = 0.46, p = 0.021). The results were different in mono-infected individuals. PBMCs from co-infected HBeAg-positive patients secreted more specific-IFN-γ in cultured supernatants compared with PBMCs from co-infected HBeAg-negative patients (p = 0.019). In the longitudinal study, S protein- and C protein-specific T-cell responses were decreased as the length of follow-up increased (p = 0.034, for S protein; p = 0.105, for C protein). Additionally, the S protein- and C protein-specific T-cell responses were significantly higher in HBe

  8. Variations au cours de la journée de l'incorporation in vivo de la leucine tritiée dans les protéines du cervelet et du cerveau du jeune rat normal et hypothyroïdien. Daily variations of the in vivo [3H] leucine incorporation into the cerebellar and cerebral proteins of the normal and hypothyroid young rat [(author's transl)].

    Science.gov (United States)

    Dainat, J; Rebière, A

    1978-02-15

    In the normal and hypothyroid 6-day-old rat, the specific radioactivity (RSA) and the relative RSA (ratio of the RSA to the [3H] lecine concentration of the acido soluble phase) of the cerebral and cerebellar proteins, changes during the day synchronally. They show a maximum at 15.00 h and a minimum at 0.300 h. At all stages studied, these values are significantly lower in the hyothyroid animals than in normal ones.

  9. Insulin-like growth factor binding protein-2, 28 kDa an 24 kDa insulin-like growth factor binding protein levels are decreased in fluid of dominant follicles, obtained from normal and polycystic ovaries

    NARCIS (Netherlands)

    A.G.P. Schuller (Alwin); D.J. Lindenbergh-Kortleve (Dicky); T.D. Pache; E.C. Zwarthoff (Ellen); B.C.J.M. Fauser (Bart); S.L.S. Drop (Stenvert)

    1993-01-01

    textabstractIn order to investigate potential changes in insulin-like growth factor binding proteins (IGFBPs) during human follicle maturation, we examined the IGFBP profiles in follicular fluid from follicles in different stages of maturation. Samples were obtained from ovaries of women with

  10. A Ketone Ester Diet Increases Brain Malonyl-CoA and Uncoupling Proteins 4 and 5 while Decreasing Food Intake in the Normal Wistar Rat*

    Science.gov (United States)

    Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M. Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L.

    2010-01-01

    Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD+]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain l-glutamate by 15–20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain. PMID:20529850

  11. A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat.

    Science.gov (United States)

    Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L

    2010-08-20

    Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.

  12. TSA and BIX-01294 Induced Normal DNA and Histone Methylation and Increased Protein Expression in Porcine Somatic Cell Nuclear Transfer Embryos.

    Science.gov (United States)

    Cao, Zubing; Hong, Renyun; Ding, Biao; Zuo, Xiaoyuan; Li, Hui; Ding, Jianping; Li, Yunsheng; Huang, Weiping; Zhang, Yunhai

    2017-01-01

    The poor efficiency of animal cloning is mainly attributed to the defects in epigenetic reprogramming of donor cells' chromatins during early embryonic development. Previous studies indicated that inhibition of histone deacetylases or methyltransferase, such as G9A, using Trichostatin A (TSA) or BIX-01294 significantly enhanced the developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. However, potential mechanisms underlying the improved early developmental competence of SCNT embryos exposed to TSA and BIX-01294 are largely unclear. Here we found that 50 nM TSA or 1.0 μM BIX-01294 treatment alone for 24 h significantly elevated the blastocyst rate (P TSA treatment alone significantly reduced H3K9me2 level at the 4-cell stage, which is comparable with that in in vivo and in vitro fertilized counterparts. However, only co-treatment significantly decreased the levels of 5mC and H3K9me2 in trophectoderm lineage and subsequently increased the expression of OCT4 and CDX2 associated with ICM and TE lineage differentiation. Altogether, these results demonstrate that co-treatment of TSA and BIX-01294 enhances the early developmental competence of porcine SCNT embryos via improvements in epigenetic status and protein expression.

  13. Human Calmodulin-Like Protein CALML3: A Novel Marker for Normal Oral Squamous Mucosa That Is Downregulated in Malignant Transformation

    Directory of Open Access Journals (Sweden)

    Michael D. Brooks

    2013-01-01

    Full Text Available Oral cancer is often diagnosed only at advanced stages due to a lack of reliable disease markers. The purpose of this study was to determine if the epithelial-specific human calmodulin-like protein (CALML3 could be used as marker for the various phases of oral tumor progression. Immunohistochemical analysis using an affinity-purified CALML3 antibody was performed on biopsy-confirmed oral tissue samples representing these phases. A total of 90 tissue specimens were derived from 52 patients. Each specimen was analyzed in the superficial and basal mucosal cell layers for overall staining and staining of cellular subcompartments. CALML3 was strongly expressed in benign oral mucosal cells with downregulation of expression as squamous cells progress to invasive carcinoma. Based on the Cochran-Armitage test for trend, expression in the nucleus and at the cytoplasmic membrane significantly decreased with increasing disease severity. Chi-square test showed that benign tissue specimens had significantly more expression compared to dysplasia/CIS and invasive specimens. Dysplasia/CIS tissue had significantly more expression than invasive tissue. We conclude that CALML3 is expressed in benign oral mucosal cells with a statistically significant trend in downregulation as tumorigenesis occurs. CALML3 may thus be a sensitive new marker for oral cancer screening.

  14. [{sup 18}F]DPA-714 PET imaging of translocator protein TSPO (18 kDa) in the normal and excitotoxically-lesioned nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Lavisse, S.; Inoue, K.; Jan, C.; Petit, F.; Dauguet, J.; Guillermier, M.; Rbah-Vidal, L.; Van Camp, N.; Aron-Badin, R.; Hantraye, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Peyronneau, M.A.; Goutal, S.; Dolle, F. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Remy, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Service de Neurologie, CHU Henri Mondor, Creteil (France)

    2014-12-09

    We aimed to characterize pharmacologically the TSPO- radioligand [{sup 18}F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA). [{sup 18}F]DPA-714 PET images were acquired before and at 2, 7, 14, 21, 49, 70, 91 days after putaminal lesioning. Blocking and displacement studies were carried out (PK11195). Different modelling approaches estimated rate constants and V{sub T} (total distribution volume) which was used to measure longitudinal changes in the lesioned putamen. Sections for immunohistochemical labelling were prepared at the same time-points to evaluate correlations between in vivo [{sup 18}F]DPA-714 binding and microglial/astrocytic activation. [{sup 18}F]DPA-714 showed a widespread distribution with a higher signal in the thalamus and occipital cortex and lower binding in the cerebellum. TSPO was expressed throughout the whole brain and about 73 % of [{sup 18}F]DPA-714 binding was specific for TSPO in vivo. The one-tissue compartment model (1-TCM) provided good and reproducible estimates of V{sub T} and rate constants, and V{sub T} values from the 1-TCM and the Logan approach were highly correlated (r {sup 2} = 0.85). QA lesioning induced an increase in V{sub T}, which was +17 %, +54 %, +157 % and +39 % higher than baseline on days 7, 14, 21 and 91 after QA injection, respectively. Immunohistochemistry revealed an early microglial and a delayed astrocytic activation after QA injection. [{sup 18}F]DPA-714 binding matched TSPO immunopositive areas and showed a stronger colocalization with CD68 microglia than with GFAP-activated astrocytes. [{sup 18}F]DPA-714 binds to TSPO with high specificity in the primate brain under normal conditions and in the QA model. This tracer provides a sensitive tool for assessing neuroinflammation in the human brain. (orig.)

  15. The effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls: a prospective cohort study.

    Science.gov (United States)

    Kirkeskov, Bente; Christensen, Robin; Bügel, Susanne; Bliddal, Henning; Danneskiold-Samsøe, Bente; Christensen, Lars Porskjær; Andersen, Jens Rikardt

    2011-08-15

    Rose hip (Rosa canina) has been used as an herbal remedy against a wide range of ailments including inflammatory disorders. The anti-inflammatory and antioxidant properties of rose hips have been evaluated in vitro and active constituents have been isolated. Rose hip contains antioxidant nutrients and an anti-inflammatory galactolipid. Rheumatoid arthritis (RA) is an inflammatory disease where activated cells release reactive oxygen substances. Thus it could be relevant to investigate if rose hip had an anti-inflammatory and/or antioxidant effect in this situation. In this open case-control study 20 female patients with RA and 10 female controls were given 10.5 g rose hip powder daily (Litozin®) for 28 days. Blood samples were analysed at baseline and follow-up for the capacity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase and the inflammatory marker C-reactive protein (CRP). The participants kept a food diary for the first 3 days and the last 3 days of the intervention period. The RA-patients completed The Stanford Health Assessment Questionnaire at baseline and follow-up. CRP-concentrations of both patients and healthy controls did not change. Nor was any effect found on the activity of antioxidant enzymes. There was no difference in food intake at baseline, but in the last week the RA-group reduced their energy intake. 10.5 g Litozin® in 28 days had neither effect on clinical symptoms or laboratory measurements in patients with RA or healthy controls. This is in contrast to previous intervention studies with rose hip powder that found a reduction in the concentration of CRP. The results of the present study indicate that a daily amount of approximately 10 g rose hip powder for one month has no anti-inflammatory and/or antioxidant effect. Copyright © 2011 Elsevier GmbH. All rights reserved.

  16. Mean Platelet Volume, Vitamin D and C Reactive Protein Levels in Normal Weight Children with Primary Snoring and Obstructive Sleep Apnea Syndrome.

    Science.gov (United States)

    Zicari, Anna Maria; Occasi, Francesca; Di Mauro, Federica; Lollobrigida, Valeria; Di Fraia, Marco; Savastano, Vincenzo; Loffredo, Lorenzo; Nicita, Francesco; Spalice, Alberto; Duse, Marzia

    2016-01-01

    Studies on Mean Platelet Volume (MPV) in children with Sleep Disordered Breathing (SDB) report conflicting results and the hypothesis of an intermittent hypoxemia leading to a systemic inflammation is reaching consensus. Vitamin D exerts anti-inflammatory properties and its deficiency has been supposed to play a role in sleep disorders. Emerging interest is rising about Primary Snoring (PS) since it is reasonable that also undetectable alteration of hypoxia might predispose to an increased production of inflammatory mediators. In this perspective, in a group of children affected by SDB, our aim was to investigate MPV, vitamin D and C Reactive Protein (CRP) levels, which had been previously evaluated separately in different studies focused only on Obstructive Sleep Apnea Syndrome (OSAS). We enrolled 137 children: 70 healthy controls (HC), 67 affected by SDB undergoing a polysomnographic evaluation, 22 with a diagnosis of PS and 45 with a diagnosis of OSAS. All patients underwent routine biochemical evaluations including blood cell counts, CRP and vitamin D. Children affected by SDB had a mean age of 8.49±2.19 and were prevalently males (23 females, 34%; 44 males, 66%). MPV levels were higher in OSAS and PS when compared to HC; platelet count (PLT) and CRP levels were higher while Vitamin D levels were lower in children with SDB when compared to HC. MPV levels were correlated with PLT (r = -0.54; pchildren with PS as well as in children with OSAS, and supports the underlying inflammation, hence, highlighting the importance of an early diagnosis of this previously considered benign form of SDB.

  17. Serum Levels Of Free And Total Insulin-Like Growth Factor (IGF)-1 And IGF Binding Protein-3 In Normal And Growth Hormone Deficient Children

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.E.T.; Hafez, M.H.

    2006-01-01

    Serum levels of total insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening growth hormone deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 pre-pubertal GH deficient (GHD) children to study the correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97-1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the pre-pubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD were decreased significantly with increasing the degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

  18. Serum levels of free and total insulin-link growth factor (IGF)-1 and (IGF) binding protein-3 in normal and growth hormone deficient children

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.E.T.; Hafez, H.M.

    2008-01-01

    Serum levels of total insulin-like growth factor- 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 prepubertal GH. deficient (GHD) children to study correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97. 1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD decreased significantly with increasing degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

  19. Mean Platelet Volume, Vitamin D and C Reactive Protein Levels in Normal Weight Children with Primary Snoring and Obstructive Sleep Apnea Syndrome.

    Directory of Open Access Journals (Sweden)

    Anna Maria Zicari

    Full Text Available Studies on Mean Platelet Volume (MPV in children with Sleep Disordered Breathing (SDB report conflicting results and the hypothesis of an intermittent hypoxemia leading to a systemic inflammation is reaching consensus. Vitamin D exerts anti-inflammatory properties and its deficiency has been supposed to play a role in sleep disorders. Emerging interest is rising about Primary Snoring (PS since it is reasonable that also undetectable alteration of hypoxia might predispose to an increased production of inflammatory mediators. In this perspective, in a group of children affected by SDB, our aim was to investigate MPV, vitamin D and C Reactive Protein (CRP levels, which had been previously evaluated separately in different studies focused only on Obstructive Sleep Apnea Syndrome (OSAS.We enrolled 137 children: 70 healthy controls (HC, 67 affected by SDB undergoing a polysomnographic evaluation, 22 with a diagnosis of PS and 45 with a diagnosis of OSAS. All patients underwent routine biochemical evaluations including blood cell counts, CRP and vitamin D.Children affected by SDB had a mean age of 8.49±2.19 and were prevalently males (23 females, 34%; 44 males, 66%. MPV levels were higher in OSAS and PS when compared to HC; platelet count (PLT and CRP levels were higher while Vitamin D levels were lower in children with SDB when compared to HC. MPV levels were correlated with PLT (r = -0.54; p<0.001, vitamin D (r = -0.39; p<0.001 and CRP (r = 0.21; p<0.01. A multiple regression was run to predict MPV levels from vitamin D, CRP and PLT and these variables significantly predicted MPV (F = 17.42, p<0.0001; adjusted R2 = 0.37. Only platelet count and vitamin D added statistically significantly to the prediction (p<0.05.The present study provides evidence of higher MPV and lower vitamin D levels in children with PS as well as in children with OSAS, and supports the underlying inflammation, hence, highlighting the importance of an early diagnosis of this

  20. Proteínas totais do liquido cefalorraqueano obtido por punção da cisterna magna: valores normais. Variações ligadas ao sexo Total protein content of normal cisternal cerebrospinal fluid: Variations related to sex

    Directory of Open Access Journals (Sweden)

    L. M. Singer Vermes

    1976-12-01

    Full Text Available Aplicando o método de Lowry, determinamos as proteínas totais do LCR considerado normal de 98 pessoas: 58 do sexo masculino e 40 do feminino. Todas as amostras de LCR foram obtidas por punção da cisterna magna (LCR-SO. Mediante tratamento estatístico dos valores obtidos, estabelecemos as taxas normais de proteinorraquia cisternal para a população mista: limite superior de 40,36 mg/100 ml, valor médio de 26,78 mg/100 e limite inferior de 13,20 mg/100 ml. Estes valores são superiores àqueles referidos na literatura. Foi verificado que a proteinorraquia total é, em média, significantemente maior nos indivíduos do sexo masculino, que nos de feminino. Consequentemente estabelecemos em separado os níveis normais de proteínas totais do LCR-SO para pessoas do sexo masculino e feminino. As taxas médias de proteínas totais do LCR-SO de pessoas do sexo masculino e feminino são de 28,76 e 23,91 mg/100 ml, respectivamente; os limites normais vão de 16,96 a 47,13 mg/100 ml para o sexo masculino e de 14,76 a 42,76 mg/100 ml para o sexo feminino.The total protein content of CSF collected from the cisterna magna (cisternal fluid of 98 patients (58 males and 40 females with no neurological diseases was determined by the colorimetric method devised by Lowry and co-workers. This method has been previously chosen based mainly on it's sensitivity, accuracy and low fluid consumption. The CSF samples were normal with regard to pressure, color, citology and it's content in glucose, chloride and urea. Complement fixation tests for syphilis and cisticercosis, as well as the globulin tests (Pandy, Nonne — Appelt and Takata-Ara were negative. The average value and the normal range of cisternal fluid total protein was calculated for the mixed population (males and females. The mean protein value was 26.78 mg/100 ml, the lower and upper limits were respectively 13.20 and 40.36 mg/100 ml. These data are higher than those stated in some publications, and

  1. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  2. Endometrial Polyps and Benign Endometrial Hyperplasia Present Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria.

    Science.gov (United States)

    Banas, Tomasz; Pitynski, Kazimierz; Mikos, Marcin; Cielecka-Kuszyk, Joanna

    2017-09-13

    DNA fragmentation factor 40 (DFF40) is a key executor of apoptosis. It localizes to the nucleus together with DNA fragmentation factor 45 (DFF45), which acts as a DFF40 inhibitor and chaperone. B-cell lymphoma (Bcl-2) protein is a proven antiapoptotic factor present in the cytoplasm. In this study, we aimed to investigate DFF40, DFF45, and Bcl-2 immunoexpression in endometrial polyps (EPs) and benign endometrial hyperplasia (BEH) tissue compared with that in normal proliferative endometrium (NPE) and normal secretory endometrium (NSE) as well as normal post menopausal endometrium (NAE). This study used archived samples from 65 and 62 cases of EPs and BEH, respectively. The control group consisted of 52 NPE, 54 NSE, and 54 NAE specimens. Immunohistochemistry was used to detect DFF40, DFF45, and Bcl-2. DFF40, DFF45, and Bcl-2 were more highly expressed in the glandular layer of EPs and BEH compared with the stroma, and this was not influenced by menopausal status. Both glandular and stromal expression of DFF40, DFF45, and Bcl-2 were significantly higher in EPs compared with NPE, NSE, and NAE. Glandular BEH tissue showed significantly higher DFF40, DFF45, and Bcl-2 expression than in NPE, NSE, and NAE. No differences in the glandular expression of DFF40, DFF45, and Bcl-2 were observed between EP and BEH tissues, while Bcl-2 stromal expression in BEH was significantly lower than in EPs. Glandular, menopause-independent DFF40, DFF45, and Bcl-2 overexpression may play an important role in the pathogenesis of EPs and BEH.

  3. Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to terminal duct lobular unit involution of the normal breast in Caucasian and African American women: The Susan G. Komen Tissue Bank.

    Science.gov (United States)

    Oh, Hannah; Pfeiffer, Ruth M; Falk, Roni T; Horne, Hisani N; Xiang, Jackie; Pollak, Michael; Brinton, Louise A; Storniolo, Anna Maria V; Sherman, Mark E; Gierach, Gretchen L; Figueroa, Jonine D

    2018-02-22

    Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin-like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 and 2012 (75% premenopausal), serum concentrations of IGF-I and binding protein (IGFBP)-3 were quantified using enzyme-linked immunosorbent assay. Hematoxilyn and eosin-stained tissue sections were assessed for numbers of TDLUs ("TDLU count"). Zero-inflated Poisson regression models with a robust variance estimator were used to estimate relative risks (RRs) for association of IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p = 0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p IGF-I:IGFBP-3 ratios were associated with higher TDLU count in Caucasian (RR T3vs.T1 =1.33, 95% CI = 1.02-1.75, p-trend = 0.04), but not in AA (RR T3vs.T1 =0.65, 95% CI = 0.42-1.00, p-trend = 0.05), women. Our data suggest a role of the IGF system, particularly IGFBP-3, in TDLU involution of the normal breast, a breast cancer risk factor, among Caucasian and AA women. © 2018 UICC.

  4. A small molecule mitigates hearing loss in a mouse model of Usher syndrome III.

    Science.gov (United States)

    Alagramam, Kumar N; Gopal, Suhasini R; Geng, Ruishuang; Chen, Daniel H-C; Nemet, Ina; Lee, Richard; Tian, Guilian; Miyagi, Masaru; Malagu, Karine F; Lock, Christopher J; Esmieu, William R K; Owens, Andrew P; Lindsay, Nicola A; Ouwehand, Krista; Albertus, Faywell; Fischer, David F; Bürli, Roland W; MacLeod, Angus M; Harte, William E; Palczewski, Krzysztof; Imanishi, Yoshikazu

    2016-06-01

    Usher syndrome type III (USH3), characterized by progressive deafness, variable balance disorder and blindness, is caused by destabilizing mutations in the gene encoding the clarin-1 (CLRN1) protein. Here we report a new strategy to mitigate hearing loss associated with a common USH3 mutation CLRN1(N48K) that involves cell-based high-throughput screening of small molecules capable of stabilizing CLRN1(N48K), followed by a secondary screening to eliminate general proteasome inhibitors, and finally an iterative process to optimize structure-activity relationships. This resulted in the identification of BioFocus 844 (BF844). To test the efficacy of BF844, we developed a mouse model that mimicked the progressive hearing loss associated with USH3. BF844 effectively attenuated progressive hearing loss and prevented deafness in this model. Because the CLRN1(N48K) mutation causes both hearing and vision loss, BF844 could in principle prevent both sensory deficiencies in patients with USH3. Moreover, the strategy described here could help identify drugs for other protein-destabilizing monogenic disorders.

  5. Normalization: A Preprocessing Stage

    OpenAIRE

    Patro, S. Gopal Krishna; Sahu, Kishore Kumar

    2015-01-01

    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  6. Comparative evaluation of the sperm characteristics and morphology of adult Wistar rats fed either low or normal protein-energy diets and orally dosed with aqueous Cuscuta australis extracts.

    Science.gov (United States)

    Omirinde, J O; Ozegbe, P C; Oyeyemi, M O

    2014-06-19

    Cuscuta australis (C. australis) seed and stem are commonly used as dietary supplements in a maize-meal, "Ogi", by the local population for the management of male and female reproductive dysfunctions. This study, as a part of on-going efforts, therefore, evaluated and compared the effects of Low Protein-energy (LP) and Normal Protein-energy (NP) diets on the sperm morphology and characteristics of adult Wistar rats orally dosed aqueous extracts of C. australis seed (LPSE and NPSE) and stem (LPST and NPST), 300 mg of extract/kg body weight of rat/day, for seven days. The control groups (LPWA and NPWA) received vehicle, water. Live-dead ratio and percentage of sperms with curved tail were significantly decreased (p<0.01) in the NPST relative to the NPWA, LPWA, LPST, NPSE and LPSE. Total abnormal sperm counts, acephalic sperms and tailless head sperms were significantly decreased (p<0.001, p<0.05 and p<0.001, respectively) in the LPST and NPST relative to LPSE, NPSE, LPWA and NPWA. The LPSE, LPST and NPST showed significantly decreased (p<0.05) percentages of sperms with either bent mid-piece or curved mid-piece relative to the LPWA. Significantly decreased (p<0.05) percentage of sperms with curved mid-piece was also observed in the NPSE relative to LPWA. Protein-energy diet significantly influenced (at least p<0.05) the effect of each extract on sperm motility and percentage of sperms with curved tail. Stem extract significantly decreased (p<0.01) the percentages of acephalic sperms and tailless head sperms. Diet-stem extract interaction significantly influenced (p<0.05) live-dead ratio. Our data suggest that orally administered aqueous extracts of C. australis generally enhanced the sperm morphology and characteristics of the male Wistar rat and that the stem extract maintained sperm morphology better than the seed extract. It also showed that the stem extract decreased live-dead ratio and that the efficacy of orally administered aqueous C. australis stem extract

  7. Mid-trimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, TNF-α, and lipopolysaccharide binding protein in normal pregnancies: a prospective evaluation according to parity, gestational age, and fetal gender.

    Science.gov (United States)

    Bamberg, Christian; Fotopoulou, Christina; Linder, Mattea; Roehr, Charles Christoph; Dudenhausen, Joachim W; Henrich, Wolfgang; Kalache, Karim

    2011-07-01

    To assess mid-trimester amniotic fluid concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender. Cytokine concentrations were measured within a week of amniocentesis during GW 15+0 to 20+6 and correlated with GW at birth, parity, and fetal gender. After exclusion of women with an adverse pregnancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0-5). Ranges for IL-6, IL-8, TNF-α, and LBP were 4.9-2620 pg/mL, 36.2-5843 pg/mL, 8.0-28.2 pg/mL, and 0.06-1.9 μg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-α values did between the 15(th) and 16(th) and the 15(th) and 18(th) weeks of gestation (Pparity or fetal gender were identified. Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-α concentrations. Further analyses are warranted to establish the role of cytokines in predicting adverse pregnancy outcomes.

  8. C-Reactive Protein Concentrations and Level of Physical Activity in Men and Women With Normal and Impaired Glucose Tolerance. A Cross-Sectional Population-Based Study in Sweden.

    Science.gov (United States)

    Hellgren, Margareta I; Larsson, Charlotte A; Daka, Bledar; Petzold, Max; Jansson, Per-Anders; Lindblad, Ulf

    2016-06-01

    We aimed to explore the association between self-reported leisure time physical activity (LTPA) and C-reactive protein (CRP) concentrations in men and women with and without impaired glucose tolerance (IGT). In a cross-sectional study, a random sample (n = 2,816) was examined with an oral glucose tolerance test, CRP and information about LTPA. Those with IGT or normal glucose tolerance (NGT) and CRP value ≤10 mg/L were selected (n = 2,367) for the study. An inverse association between LTPA and CRP concentrations was observed in the population (P men with IGT (P = .023) and in women with NGT. Men with IGT, reporting slight physical activity up to 4 hours a week presented significantly higher CRP concentrations than normoglycemic men (Δ0.6 mg/L, P = .004). However, this difference could not be found in men with IGT reporting more intense physical activity (Δ0.01 mg/L, P = .944). Physical inactivity seems to have greater inflammatory consequences for men (vs. women) with IGT. More importantly, although 4 hours of physical activity per week is more than the usual minimum recommendation, an even greater intensity of LTPA appears to be required to limit subclinical inflammation in men with IGT.

  9. Normalized modes at selected points without normalization

    Science.gov (United States)

    Kausel, Eduardo

    2018-04-01

    As every textbook on linear algebra demonstrates, the eigenvectors for the general eigenvalue problem | K - λM | = 0 involving two real, symmetric, positive definite matrices K , M satisfy some well-defined orthogonality conditions. Equally well-known is the fact that those eigenvectors can be normalized so that their modal mass μ =ϕT Mϕ is unity: it suffices to divide each unscaled mode by the square root of the modal mass. Thus, the normalization is the result of an explicit calculation applied to the modes after they were obtained by some means. However, we show herein that the normalized modes are not merely convenient forms of scaling, but that they are actually intrinsic properties of the pair of matrices K , M, that is, the matrices already "know" about normalization even before the modes have been obtained. This means that we can obtain individual components of the normalized modes directly from the eigenvalue problem, and without needing to obtain either all of the modes or for that matter, any one complete mode. These results are achieved by means of the residue theorem of operational calculus, a finding that is rather remarkable inasmuch as the residues themselves do not make use of any orthogonality conditions or normalization in the first place. It appears that this obscure property connecting the general eigenvalue problem of modal analysis with the residue theorem of operational calculus may have been overlooked up until now, but which has in turn interesting theoretical implications.Á

  10. Normal foot and ankle

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    The foot may be thought of as a bag of bones tied tightly together and functioning as a unit. The bones re expected to maintain their alignment without causing symptomatology to the patient. The author discusses a normal radiograph. The bones must have normal shape and normal alignment. The density of the soft tissues should be normal and there should be no fractures, tumors, or foreign bodies

  11. Neuronal protein gene product 9.5 (IEF SSP 6104) is expressed in cultured human MRC-5 fibroblasts of normal origin and is strongly down-regulated in their SV40 transformed counterparts

    DEFF Research Database (Denmark)

    Honoré, B; Rasmussen, H H; Vandekerckhove, J

    1991-01-01

    of proteins recovered from 2D gels we have identified PGP 9.5 UCH-L1 as polypeptide IEF SSP 6104 (Mr = 27,000, pI = 5.49) in the comprehensive 2D gel cellular protein database of human embryonal lung MRC-5 fibroblasts [(1989) Electrophoresis 10, 76 115; (1990) Electrophoresis 11, 1072 1113]. This protein...

  12. Baby Poop: What's Normal?

    Science.gov (United States)

    ... I'm breast-feeding my newborn and her bowel movements are yellow and mushy. Is this normal for baby poop? Answers from Jay L. Hoecker, M.D. Yellow, mushy bowel movements are perfectly normal for breast-fed babies. Still, ...

  13. Visual Memories Bypass Normalization.

    Science.gov (United States)

    Bloem, Ilona M; Watanabe, Yurika L; Kibbe, Melissa M; Ling, Sam

    2018-05-01

    How distinct are visual memory representations from visual perception? Although evidence suggests that briefly remembered stimuli are represented within early visual cortices, the degree to which these memory traces resemble true visual representations remains something of a mystery. Here, we tested whether both visual memory and perception succumb to a seemingly ubiquitous neural computation: normalization. Observers were asked to remember the contrast of visual stimuli, which were pitted against each other to promote normalization either in perception or in visual memory. Our results revealed robust normalization between visual representations in perception, yet no signature of normalization occurring between working memory stores-neither between representations in memory nor between memory representations and visual inputs. These results provide unique insight into the nature of visual memory representations, illustrating that visual memory representations follow a different set of computational rules, bypassing normalization, a canonical visual computation.

  14. Making nuclear 'normal'

    International Nuclear Information System (INIS)

    Haehlen, Peter; Elmiger, Bruno

    2000-01-01

    The mechanics of the Swiss NPPs' 'come and see' programme 1995-1999 were illustrated in our contributions to all PIME workshops since 1996. Now, after four annual 'waves', all the country has been covered by the NPPs' invitation to dialogue. This makes PIME 2000 the right time to shed some light on one particular objective of this initiative: making nuclear 'normal'. The principal aim of the 'come and see' programme, namely to give the Swiss NPPs 'a voice of their own' by the end of the nuclear moratorium 1990-2000, has clearly been attained and was commented on during earlier PIMEs. It is, however, equally important that Swiss nuclear energy not only made progress in terms of public 'presence', but also in terms of being perceived as a normal part of industry, as a normal branch of the economy. The message that Swiss nuclear energy is nothing but a normal business involving normal people, was stressed by several components of the multi-prong campaign: - The speakers in the TV ads were real - 'normal' - visitors' guides and not actors; - The testimonials in the print ads were all real NPP visitors - 'normal' people - and not models; - The mailings inviting a very large number of associations to 'come and see' activated a typical channel of 'normal' Swiss social life; - Spending money on ads (a new activity for Swiss NPPs) appears to have resulted in being perceived by the media as a normal branch of the economy. Today we feel that the 'normality' message has well been received by the media. In the controversy dealing with antinuclear arguments brought forward by environmental organisations journalists nowadays as a rule give nuclear energy a voice - a normal right to be heard. As in a 'normal' controversy, the media again actively ask themselves questions about specific antinuclear claims, much more than before 1990 when the moratorium started. The result is that in many cases such arguments are discarded by journalists, because they are, e.g., found to be

  15. Normal Levels of Urinary CC16 Protein. Comments on Beamer et al. Association of Children’s Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media. Int. J. Environ. Res. Public Health 2016, 13, 521.

    Directory of Open Access Journals (Sweden)

    Víctor García-Nieto

    2016-10-01

    Full Text Available In 1937, Max Clara described a new type of cell in the human lung, which was later determined to be an exocrine secretory cell type containing granules composed of proteins [1].[...

  16. "Normal" thrombin generation

    NARCIS (Netherlands)

    Butenas, S.; van't Veer, C.; Mann, K. G.

    1999-01-01

    We have investigated the influence of alterations in plasma coagulation factor levels between 50% and 150% of their mean values for prothrombin, factor X, factor XI, factor IX, factor VII, factor VIII, factor V, protein C, protein S, antithrombin III (AT-III), and tissue factor pathway inhibitor

  17. Normal Pressure Hydrocephalus

    Science.gov (United States)

    ... improves the chance of a good recovery. Without treatment, symptoms may worsen and cause death. What research is being done? The NINDS conducts and supports research on neurological disorders, including normal pressure hydrocephalus. Research on disorders such ...

  18. Normality in Analytical Psychology

    Science.gov (United States)

    Myers, Steve

    2013-01-01

    Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity. PMID:25379262

  19. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  20. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  1. Normal growth and development

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002456.htm Normal growth and development To use the sharing features on this page, please enable JavaScript. A child's growth and development can be divided into four periods: ...

  2. Smooth quantile normalization.

    Science.gov (United States)

    Hicks, Stephanie C; Okrah, Kwame; Paulson, Joseph N; Quackenbush, John; Irizarry, Rafael A; Bravo, Héctor Corrada

    2018-04-01

    Between-sample normalization is a critical step in genomic data analysis to remove systematic bias and unwanted technical variation in high-throughput data. Global normalization methods are based on the assumption that observed variability in global properties is due to technical reasons and are unrelated to the biology of interest. For example, some methods correct for differences in sequencing read counts by scaling features to have similar median values across samples, but these fail to reduce other forms of unwanted technical variation. Methods such as quantile normalization transform the statistical distributions across samples to be the same and assume global differences in the distribution are induced by only technical variation. However, it remains unclear how to proceed with normalization if these assumptions are violated, for example, if there are global differences in the statistical distributions between biological conditions or groups, and external information, such as negative or control features, is not available. Here, we introduce a generalization of quantile normalization, referred to as smooth quantile normalization (qsmooth), which is based on the assumption that the statistical distribution of each sample should be the same (or have the same distributional shape) within biological groups or conditions, but allowing that they may differ between groups. We illustrate the advantages of our method on several high-throughput datasets with global differences in distributions corresponding to different biological conditions. We also perform a Monte Carlo simulation study to illustrate the bias-variance tradeoff and root mean squared error of qsmooth compared to other global normalization methods. A software implementation is available from https://github.com/stephaniehicks/qsmooth.

  3. The normal bacterial flora prevents GI disease

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. The normal bacterial flora prevents GI disease. Inhibits pathogenic enteric bacteria. Decrease luminal pH; Secrete bacteriocidal proteins; Colonization resistance; Block epithelial binding – induce MUC2. Improves epithelial and mucosal barrier integrity. Produce ...

  4. CSF total protein

    Science.gov (United States)

    CSF total protein is a test to determine the amount of protein in your spinal fluid, also called cerebrospinal fluid (CSF). ... The normal protein range varies from lab to lab, but is typically about 15 to 60 milligrams per deciliter (mg/dL) ...

  5. Monitoring the normal body

    DEFF Research Database (Denmark)

    Nissen, Nina Konstantin; Holm, Lotte; Baarts, Charlotte

    2015-01-01

    of practices for monitoring their bodies based on different kinds of calculations of weight and body size, observations of body shape, and measurements of bodily firmness. Biometric measurements are familiar to them as are health authorities' recommendations. Despite not belonging to an extreme BMI category...... provides us with knowledge about how to prevent future overweight or obesity. This paper investigates body size ideals and monitoring practices among normal-weight and moderately overweight people. Methods : The study is based on in-depth interviews combined with observations. 24 participants were...... recruited by strategic sampling based on self-reported BMI 18.5-29.9 kg/m2 and socio-demographic factors. Inductive analysis was conducted. Results : Normal-weight and moderately overweight people have clear ideals for their body size. Despite being normal weight or close to this, they construct a variety...

  6. Increased reactive oxygen species production and lower abundance of complex I subunits and carnitine palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Lefort, Natalie; Glancy, Brian; Bowen, Benjamin

    2010-01-01

    the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine...

  7. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process......This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...

  8. Normalization of satellite imagery

    Science.gov (United States)

    Kim, Hongsuk H.; Elman, Gregory C.

    1990-01-01

    Sets of Thematic Mapper (TM) imagery taken over the Washington, DC metropolitan area during the months of November, March and May were converted into a form of ground reflectance imagery. This conversion was accomplished by adjusting the incident sunlight and view angles and by applying a pixel-by-pixel correction for atmospheric effects. Seasonal color changes of the area can be better observed when such normalization is applied to space imagery taken in time series. In normalized imagery, the grey scale depicts variations in surface reflectance and tonal signature of multi-band color imagery can be directly interpreted for quantitative information of the target.

  9. The normal holonomy group

    International Nuclear Information System (INIS)

    Olmos, C.

    1990-05-01

    The restricted holonomy group of a Riemannian manifold is a compact Lie group and its representation on the tangent space is a product of irreducible representations and a trivial one. Each one of the non-trivial factors is either an orthogonal representation of a connected compact Lie group which acts transitively on the unit sphere or it is the isotropy representation of a single Riemannian symmetric space of rank ≥ 2. We prove that, all these properties are also true for the representation on the normal space of the restricted normal holonomy group of any submanifold of a space of constant curvature. 4 refs

  10. Normality in Analytical Psychology

    Directory of Open Access Journals (Sweden)

    Steve Myers

    2013-11-01

    Full Text Available Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity.

  11. Medically-enhanced normality

    DEFF Research Database (Denmark)

    Møldrup, Claus; Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2003-01-01

    Objective: To consider public perspectives on the use of medicines for non-medical purposes, a usage called medically-enhanced normality (MEN). Method: Examples from the literature were combined with empirical data derived from two Danish research projects: a Delphi internet study and a Telebus...

  12. The Normal Fetal Pancreas.

    Science.gov (United States)

    Kivilevitch, Zvi; Achiron, Reuven; Perlman, Sharon; Gilboa, Yinon

    2017-10-01

    The aim of the study was to assess the sonographic feasibility of measuring the fetal pancreas and its normal development throughout pregnancy. We conducted a cross-sectional prospective study between 19 and 36 weeks' gestation. The study included singleton pregnancies with normal pregnancy follow-up. The pancreas circumference was measured. The first 90 cases were tested to assess feasibility. Two hundred ninety-seven fetuses of nondiabetic mothers were recruited during a 3-year period. The overall satisfactory visualization rate was 61.6%. The intraobserver and interobserver variability had high interclass correlation coefficients of of 0.964 and 0.967, respectively. A cubic polynomial regression described best the correlation of pancreas circumference with gestational age (r = 0.744; P pancreas circumference percentiles for each week of gestation were calculated. During the study period, we detected 2 cases with overgrowth syndrome and 1 case with an annular pancreas. In this study, we assessed the feasibility of sonography for measuring the fetal pancreas and established a normal reference range for the fetal pancreas circumference throughout pregnancy. This database can be helpful when investigating fetomaternal disorders that can involve its normal development. © 2017 by the American Institute of Ultrasound in Medicine.

  13. Parietal podocytes in normal human glomeruli.

    Science.gov (United States)

    Bariety, Jean; Mandet, Chantal; Hill, Gary S; Bruneval, Patrick

    2006-10-01

    Although parietal podocytes along the Bowman's capsule have been described by electron microscopy in the normal human kidney, their molecular composition remains unknown. Ten human normal kidneys that were removed for cancer were assessed for the presence and the extent of parietal podocytes along the Bowman's capsule. The expression of podocyte-specific proteins (podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and alpha-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2), cyclin-dependent kinase inhibitor p57, and intermediate filaments (cytokeratins and vimentin) was tested. In addition, six normal fetal kidneys were studied to track the ontogeny of parietal podocytes. The podocyte protein labeling detected parietal podocytes in all of the kidneys, was found in 76.6% on average of Bowman's capsule sections, and was prominent at the vascular pole. WT1 and p57 were expressed in some parietal cells, whereas PAX2 was present in all or most of them, so some parietal cells coexpressed WT1 and PAX2. Furthermore, parietal podocytes coexpressed WT1 and podocyte proteins. Cytokeratin-positive cells covered a variable part of the capsule and did not express podocyte proteins. Tuft-capsular podocyte bridges were present in 15.5 +/- 3.7% of the glomerular sections. Parietal podocytes often covered the juxtaglomerular arterioles and were present within the extraglomerular mesangium. Parietal podocytes were present in fetal kidneys. Parietal podocytes that express the same epitopes as visceral podocytes do exist along Bowman's capsule in the normal adult kidney. They are a constitutive cell type of the Bowman's capsule. Therefore, their role in physiology and pathology should be investigated.

  14. Establishing the proteome of normal human cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Steven E Schutzer

    2010-06-01

    Full Text Available Knowledge of the entire protein content, the proteome, of normal human cerebrospinal fluid (CSF would enable insights into neurologic and psychiatric disorders. Until now technologic hurdles and access to true normal samples hindered attaining this goal.We applied immunoaffinity separation and high sensitivity and resolution liquid chromatography-mass spectrometry to examine CSF from healthy normal individuals. 2630 proteins in CSF from normal subjects were identified, of which 56% were CSF-specific, not found in the much larger set of 3654 proteins we have identified in plasma. We also examined CSF from groups of subjects previously examined by others as surrogates for normals where neurologic symptoms warranted a lumbar puncture but where clinical laboratory were reported as normal. We found statistically significant differences between their CSF proteins and our non-neurological normals. We also examined CSF from 10 volunteer subjects who had lumbar punctures at least 4 weeks apart and found that there was little variability in CSF proteins in an individual as compared to subject to subject.Our results represent the most comprehensive characterization of true normal CSF to date. This normal CSF proteome establishes a comparative standard and basis for investigations into a variety of diseases with neurological and psychiatric features.

  15. Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Flyvbjerg, Allan; Frystyk, Jan

    1996-01-01

    Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF......-I. However, the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in puberty has not previously been studied....

  16. Idiopathic Normal Pressure Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Basant R. Nassar BS

    2016-04-01

    Full Text Available Idiopathic normal pressure hydrocephalus (iNPH is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” “gait disturbances,” “cognitive function,” “neuropsychology,” “imaging,” and “pathogenesis,” articles were obtained for this review. The majority of the articles were retrieved from the past 10 years. The purpose of this review article is to aid general practitioners in further understanding current findings on the pathogenesis, diagnosis, and treatment of iNPH.

  17. Normal Weight Dyslipidemia

    DEFF Research Database (Denmark)

    Ipsen, David Hojland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-01-01

    Objective: The liver coordinates lipid metabolism and may play a vital role in the development of dyslipidemia, even in the absence of obesity. Normal weight dyslipidemia (NWD) and patients with nonalcoholic fatty liver disease (NAFLD) who do not have obesity constitute a unique subset...... of individuals characterized by dyslipidemia and metabolic deterioration. This review examined the available literature on the role of the liver in dyslipidemia and the metabolic characteristics of patients with NAFLD who do not have obesity. Methods: PubMed was searched using the following keywords: nonobese......, dyslipidemia, NAFLD, NWD, liver, and metabolically obese/unhealthy normal weight. Additionally, article bibliographies were screened, and relevant citations were retrieved. Studies were excluded if they had not measured relevant biomarkers of dyslipidemia. Results: NWD and NAFLD without obesity share a similar...

  18. Ethics and "normal birth".

    Science.gov (United States)

    Lyerly, Anne Drapkin

    2012-12-01

    The concept of "normal birth" has been promoted as ideal by several international organizations, although debate about its meaning is ongoing. In this article, I examine the concept of normalcy to explore its ethical implications and raise a trio of concerns. First, in its emphasis on nonuse of technology as a goal, the concept of normalcy may marginalize women for whom medical intervention is necessary or beneficial. Second, in its emphasis on birth as a socially meaningful event, the mantra of normalcy may unintentionally avert attention to meaning in medically complicated births. Third, the emphasis on birth as a normal and healthy event may be a contributor to the long-standing tolerance for the dearth of evidence guiding the treatment of illness during pregnancy and the failure to responsibly and productively engage pregnant women in health research. Given these concerns, it is worth debating not just what "normal birth" means, but whether the term as an ideal earns its keep. © 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.

  19. Protein Linked to Atopic Dermatitis

    Science.gov (United States)

    ... Research Matters NIH Research Matters January 14, 2013 Protein Linked to Atopic Dermatitis Normal skin from a ... in mice suggests that lack of a certain protein may trigger atopic dermatitis, the most common type ...

  20. The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

    International Nuclear Information System (INIS)

    Ganzenmueller, Tina; Matthaei, Markus; Muench, Peter; Scheible, Michael; Iftner, Angelika; Hiller, Thomas; Leiprecht, Natalie; Probst, Sonja; Stubenrauch, Frank; Iftner, Thomas

    2008-01-01

    Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19 ARF induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53

  1. Normal Growth of Healthy Infants Born from HIV+ Mothers Fed a Reduced Protein Infant Formula Containing the Prebiotics Galacto-Oligosaccharides and Fructo-Oligosaccharides: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hugo Da Costa Ribeiro Júnior

    2015-01-01

    Full Text Available Objective The aim of the current study was to evaluate the safety of a new reduced protein (2.1 g/100 kcal infant formula containing 4 g/L of 90% galacto-oligosaccharides (GOS and 10% fructo-oligosaccharides (FOS. Methods Healthy term infants from Brazil were enrolled. Those born to human immunodeficiency virus (HIV-positive mothers were randomized to a test ( n = 65 or control ( n = 63 formula group. Infants born to HIV-negative mothers were either exclusively breast-fed ( n = 79 or received a mixed diet (breast milk and test formula, n = 65. Between 2 weeks and 4 months of age, infants were exclusively fed according to their assigned group. Anthropometric measurements were taken at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 months. Digestive tolerance was evaluated during the first 4 months. The primary outcome was mean daily weight gain between 2 weeks and 4 months in the test formula and breast-fed groups. Results Data from all infants ( N = 272 were used in the intention-to-treat (ITT analysis and data from 230 infants were used in the per-protocol (PP analysis. The difference in mean daily weight gain between 2 weeks and 4 months in the test formula and breast-fed groups was 1.257 g/day (onesided 95% confidence interval [CI]: -0.705 to inf, P < 0.001 in the PP analysis, showing that the lower bound of the 95% CI was above the -3.0 g/day non-inferiority margin. Results were similar in the ITT analysis. Symptoms of digestive tolerance and frequency of adverse events were similar in the two groups. Conclusions The formula containing 2.1 g/100 kcal protein and GOS and FOS was safe and tolerated well.

  2. Normal mode analysis and applications in biological physics.

    Science.gov (United States)

    Dykeman, Eric C; Sankey, Otto F

    2010-10-27

    Normal mode analysis has become a popular and often used theoretical tool in the study of functional motions in enzymes, viruses, and large protein assemblies. The use of normal modes in the study of these motions is often extremely fruitful since many of the functional motions of large proteins can be described using just a few normal modes which are intimately related to the overall structure of the protein. In this review, we present a broad overview of several popular methods used in the study of normal modes in biological physics including continuum elastic theory, the elastic network model, and a new all-atom method, recently developed, which is capable of computing a subset of the low frequency vibrational modes exactly. After a review of the various methods, we present several examples of applications of normal modes in the study of functional motions, with an emphasis on viral capsids.

  3. Theory of normal metals

    International Nuclear Information System (INIS)

    Mahan, G.D.

    1992-01-01

    The organizers requested that I give eight lectures on the theory of normal metals, ''with an eye on superconductivity.'' My job was to cover the general properties of metals. The topics were selected according to what the students would need to known for the following lectures on superconductivity. My role was to prepare the ground work for the later lectures. The problem is that there is not yet a widely accepted theory for the mechanism which pairs the electrons. Many mechanisms have been proposed, with those of phonons and spin fluctuations having the most followers. So I tried to discuss both topics. I also introduced the tight-binding model for metals, which forms the basis for most of the work on the cuprate superconductors

  4. 24-hour urine protein

    Science.gov (United States)

    ... your provider may be able to order a test that is done on just one urine sample (protein-to-creatinine ratio). Normal Results The normal ... Some labs use different measurements or test different samples. Talk to your provider about the meaning of your specific test ... Abnormal results may be due to: A group ...

  5. Ascorbate/menadione-induced oxidative stress kills cancer cells that express normal or mutated forms of the oncogenic protein Bcr-Abl. An in vitro and in vivo mechanistic study.

    Science.gov (United States)

    Beck, Raphaël; Pedrosa, Rozangela Curi; Dejeans, Nicolas; Glorieux, Christophe; Levêque, Philippe; Gallez, Bernard; Taper, Henryk; Eeckhoudt, Stéphane; Knoops, Laurent; Calderon, Pedro Buc; Verrax, Julien

    2011-10-01

    Numerous studies suggest that generation of oxidative stress could be useful in cancer treatment. In this study, we evaluated, in vitro and in vivo, the antitumor potential of oxidative stress induced by ascorbate/menadione (asc/men). This combination of a reducing agent (ascorbate) and a redox active quinone (menadione) generates redox cycling leading to formation of reactive oxygen species (ROS). Asc/men was tested in several cell types including K562 cells (a stable human-derived leukemia cell line), freshly isolated leukocytes from patients with chronic myeloid leukemia, BaF3 cells (a murine pro-B cell line) transfected with Bcr-Abl and peripheral blood leukocytes derived from healthy donors. Although these latter cells were resistant to asc/men, survival of all the other cell lines was markedly reduced, including the BaF3 cells expressing either wild-type or mutated Bcr-Abl. In a standard in vivo model of subcutaneous tumor transplantation, asc/men provoked a significant delay in the proliferation of K562 and BaF3 cells expressing the T315I mutated form of Bcr-Abl. No effect of asc/men was observed when these latter cells were injected into blood of mice most probably because of the high antioxidant potential of red blood cells, as shown by in vitro experiments. We postulate that cancer cells are more sensitive to asc/men than healthy cells because of their lack of antioxidant enzymes, mainly catalase. The mechanism underlying this cytotoxicity involves the oxidative cleavage of Hsp90 with a subsequent loss of its chaperone function thus leading to degradation of wild-type and mutated Bcr-Abl protein.

  6. Quantitation of mRNAs for α1-acid glycoprotein and for serum albumin in livers of normal, stressed, fasted, and refed rats. [125I or 131I radioimmunoassay for protein products of specific mRNA activity

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Linda Jean [Univ. of Rochester, NY (United States)

    1978-01-01

    A new procedure for determining the relative levels of a specific mRNA species was developed and applied to mRNA for rat serum albumin (RSA) and α1-AGP) in rat liver. The method is a radioimmunoassay (125In or 131I) for the completed protein, but which also detects antigenic determinants in nascent polypeptide chains on plysomes synthesizing the specific protein. Results show that 24 hs after stressing the rat by turpentine injection the total number of polysomes per mg DNA has increased by 20 to 25%; however, the number of RSA synthesizing polysomes per mg DNA has decreased slightly. In rats fasted for 6 days, the number of RSA synthesizing polysomes per mg polysomal RNA is only slightly below normal, but the total number of RSA synthesizing polysomes per mg DNA has decreased by 40%. Again, it is seen that RSA mRNA levels do not decrease as sharply as the rate of RSA synthesis. Twelve hours after refeeding the rats, the number of RSA synthesizing polysomes begins to increase, reaching a peak two to three times normal levels 24 to 48 hours after commencement of refeeding. During the first 24 hs after turpentine injection, there is a linear increase in the number of α1-AGP synthesizing polysomes. The increase is smaller during the next 24 hs and there is a small decrease between 48 and 72 hs. The serum concentrations of α1-AGP following turpentine treatment reflect these changes in polysome levels. It was not possible to compare the number of α1-AGP synthesizing polysomes in livers of normal, fasted, and refed rats because the levels detected were only slightly higher than those seen in rat and rat kidney polysome controls. This background activity must be eliminated before the technique can be applied to quantitating mRNA for proteins synthesized in very small quantities. This technique offers several advantages over other procedures commonly used to quantitate mRNA. (ERB)

  7. Quantitative proteome profiling of normal human circulating microparticles

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer T; Iversen, Line V

    2012-01-01

    Circulating microparticles (MPs) are produced as part of normal physiology. Their numbers, origin, and composition change in pathology. Despite this, the normal MP proteome has not yet been characterized with standardized high-resolution methods. We here quantitatively profile the normal MP...... proteome using nano-LC-MS/MS on an LTQ-Orbitrap with optimized sample collection, preparation, and analysis of 12 different normal samples. Analytical and procedural variation were estimated in triply processed samples analyzed in triplicate from two different donors. Label-free quantitation was validated...... by the correlation of cytoskeletal protein intensities with MP numbers obtained by flow cytometry. Finally, the validity of using pooled samples was evaluated using overlap protein identification numbers and multivariate data analysis. Using conservative parameters, 536 different unique proteins were quantitated...

  8. Short proofs of strong normalization

    OpenAIRE

    Wojdyga, Aleksander

    2008-01-01

    This paper presents simple, syntactic strong normalization proofs for the simply-typed lambda-calculus and the polymorphic lambda-calculus (system F) with the full set of logical connectives, and all the permutative reductions. The normalization proofs use translations of terms and types to systems, for which strong normalization property is known.

  9. Do vegetarians have a normal bone mass?

    Science.gov (United States)

    New, Susan A

    2004-09-01

    Public health strategies targeting the prevention of poor bone health on a population-wide basis are urgently required, with particular emphasis being placed on modifiable factors such as nutrition. The aim of this review was to assess the impact of a vegetarian diet on indices of skeletal integrity to address specifically whether vegetarians have a normal bone mass. Analysis of existing literature, through a combination of observational, clinical and intervention studies were assessed in relation to bone health for the following: lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets, consumption of animal versus vegetable protein, and fruit and vegetable consumption. Mechanisms of action for a dietary "component" effect were examined and other potential dietary differences between vegetarians and non-vegetarians were also explored. Key findings included: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone with high protein consumption (particularly without supporting calcium/alkali intakes) and low protein intake (particularly with respect to vegan diets) being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. The impact of a "vegetarian" diet on bone health is a hugely complex area since: 1) components of the diet (such as calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key lifestyle factors which are important to bone (such as physical activity) may be different; 3) the tools available for assessing consumption of food are relatively weak. However, from data available and given the limitations stipulated above, "vegetarians" do certainly appear to have "normal" bone mass. What remains our challenge is to determine what components of a vegetarian diet are of particular benefit to bone, at what levels and under

  10. Fatty acid uptake in normal human myocardium

    International Nuclear Information System (INIS)

    Vyska, K.; Meyer, W.; Stremmel, W.; Notohamiprodjo, G.; Minami, K.; Machulla, H.J.; Gleichmann, U.; Meyer, H.; Koerfer, R.

    1991-01-01

    Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an unstirred layer were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 ± 0.024 mumol/g and 0.37 ± 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells

  11. Chronic Treatment with Ang-(1-7 Reverses Abnormal Reactivity in the Corpus Cavernosum and Normalizes Diabetes-Induced Changes in the Protein Levels of ACE, ACE2, ROCK1, ROCK2 and Omega-Hydroxylase in a Rat Model of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Mariam H. M. Yousif

    2014-01-01

    Full Text Available Angiotensin-(1-7 [Ang-(1-7] may have beneficial effects in diabetes mellitus-induced erectile dysfunction (DMIED but its molecular actions in the diabetic corpus cavernosum (CC are not known. We characterized the effects of diabetes and/or chronic in vivo administration of Ang-(1-7 on vascular reactivity in the rat corpus cavernosum (CC and on protein expression levels of potential downstream effectors of the renin-angiotensin-aldosterone system (RAAS such as angiotensin-converting enzyme (ACE, ACE2, Rho kinases 1 and 2 (ROCK1 and ROCK2, and omega-hydroxylase, the cytochrome-P450 enzyme that metabolizes arachidonic acid to form the vasoconstrictor, 20-hydroxyeicosatetraenoic acid. Streptozotocin-treated rats were chronicically administered Ang-(1-7 with or without A779, a Mas receptor antagonist, during weeks 4 to 6 of diabetes. Ang-(1-7 reversed diabetes-induced abnormal reactivity to vasoactive agents (endothelin-1, phenylepherine, and carbachol in the CC without correcting hyperglycemia. Six weeks of diabetes led to elevated ACE, ROCK1, ROCK 2, and omega-hydroxylase and a concomitant decrease in ACE2 protein expression levels that were normalized by Ang-(1-7 treatment but not upon coadministration of A779. These data are supportive of the notion that the beneficial effects of Ang-(1-7 in DMIED involve counterregulation of diabetes-induced changes in ACE, ACE2, Rho kinases, and omega-hydroxylase proteins in the diabetic CC via a Mas receptor-dependent mechanism.

  12. Proteoglycans in Leiomyoma and Normal Myometrium

    Science.gov (United States)

    Barker, Nichole M.; Carrino, David A.; Caplan, Arnold I.; Hurd, William W.; Liu, James H.; Tan, Huiqing; Mesiano, Sam

    2015-01-01

    Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression. PMID:26423601

  13. Protein Structure-sensitive Analysis by Normal Pulse Voltammetry

    Czech Academy of Sciences Publication Activity Database

    Černocká, Hana; Paleček, Emil

    2016-01-01

    Roč. 28, č. 11 (2016), s. 2884-2889 ISSN 1040-0397 R&D Projects: GA ČR(CZ) GA15-15479S Institutional support: RVO:68081707 Keywords : mercury -electrodes * deoxyribonucleic-acid * hydrogen evolution Subject RIV: BO - Biophysics Impact factor: 2.851, year: 2016

  14. Bicervical normal uterus with normal vagina | Okeke | Annals of ...

    African Journals Online (AJOL)

    To the best of our knowledge, only few cases of bicervical normal uterus with normal vagina exist in the literature; one of the cases had an anterior‑posterior disposition. This form of uterine abnormality is not explicable by the existing classical theory of mullerian anomalies and suggests that a complex interplay of events ...

  15. Group normalization for genomic data.

    Science.gov (United States)

    Ghandi, Mahmoud; Beer, Michael A

    2012-01-01

    Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN), to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

  16. Group normalization for genomic data.

    Directory of Open Access Journals (Sweden)

    Mahmoud Ghandi

    Full Text Available Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN, to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

  17. Comparison of spectrum normalization techniques for univariate ...

    Indian Academy of Sciences (India)

    Laser-induced breakdown spectroscopy; univariate study; normalization models; stainless steel; standard error of prediction. Abstract. Analytical performance of six different spectrum normalization techniques, namelyinternal normalization, normalization with total light, normalization with background along with their ...

  18. Normal matter storage of antiprotons

    International Nuclear Information System (INIS)

    Campbell, L.J.

    1987-01-01

    Various simple issues connected with the possible storage of anti p in relative proximity to normal matter are discussed. Although equilibrium storage looks to be impossible, condensed matter systems are sufficiently rich and controllable that nonequilibrium storage is well worth pursuing. Experiments to elucidate the anti p interactions with normal matter are suggested. 32 refs

  19. The N'ormal Distribution

    Indian Academy of Sciences (India)

    An optimal way of choosing sample size in an opinion poll is indicated using the normal distribution. Introduction. In this article, the ubiquitous normal distribution is intro- duced as a convenient approximation for computing bino- mial probabilities for large values of n. Stirling's formula. • and DeMoivre-Laplace theorem ...

  20. Tumor cell surface proteins

    International Nuclear Information System (INIS)

    Kennel, S.J.; Braslawsky, G.R.; Flynn, K.; Foote, L.J.; Friedman, E.; Hotchkiss, J.A.; Huang, A.H.L.; Lankford, P.K.

    1982-01-01

    Cell surface proteins mediate interaction between cells and their environment. Unique tumor cell surface proteins are being identified and quantified in several tumor systems to address the following questions: (i) how do tumor-specific proteins arise during cell transformation; (ii) can these proteins be used as markers of tumor cell distribution in vivo; (iii) can cytotoxic drugs be targeted specifically to tumor cells using antibody; and (iv) can solid state radioimmunoassay of these proteins provide a means to quantify transformation frequencies. A tumor surface protein of 180,000 M/sub r/ (TSP-180) has been identified on cells of several lung carcinomas of BALB/c mice. TSP-180 was not detected on normal lung tissue, embryonic tissue, or other epithelial or sarcoma tumors, but it was found on lung carcinomas of other strains of mice. Considerable amino acid sequence homology exists among TSP-180's from several cell sources, indicating that TSP-180 synthesis is directed by normal cellular genes although it is not expressed in normal cells. The regulation of synthesis of TSP-180 and its relationship to normal cell surface proteins are being studied. Monoclonal antibodies (MoAb) to TSP-180 have been developed. The antibodies have been used in immunoaffinity chromatography to isolate TSP-180 from tumor cell sources. This purified tumor antigen was used to immunize rats. Antibody produced by these animals reacted at different sites (epitopes) on the TSP-180 molecule than did the original MoAb. These sera and MoAb from these animals are being used to identify normal cell components related to the TSP-180 molecule

  1. Complete Normal Ordering 1: Foundations

    CERN Document Server

    Ellis, John; Skliros, Dimitri P.

    2016-01-01

    We introduce a new prescription for quantising scalar field theories perturbatively around a true minimum of the full quantum effective action, which is to `complete normal order' the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all `cephalopod' Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of `complete normal ordering' (which is an extension of the standard field theory definition of normal ordering) reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative i...

  2. Is this the right normalization? A diagnostic tool for ChIP-seq normalization.

    Science.gov (United States)

    Angelini, Claudia; Heller, Ruth; Volkinshtein, Rita; Yekutieli, Daniel

    2015-05-09

    Chip-seq experiments are becoming a standard approach for genome-wide profiling protein-DNA interactions, such as detecting transcription factor binding sites, histone modification marks and RNA Polymerase II occupancy. However, when comparing a ChIP sample versus a control sample, such as Input DNA, normalization procedures have to be applied in order to remove experimental source of biases. Despite the substantial impact that the choice of the normalization method can have on the results of a ChIP-seq data analysis, their assessment is not fully explored in the literature. In particular, there are no diagnostic tools that show whether the applied normalization is indeed appropriate for the data being analyzed. In this work we propose a novel diagnostic tool to examine the appropriateness of the estimated normalization procedure. By plotting the empirical densities of log relative risks in bins of equal read count, along with the estimated normalization constant, after logarithmic transformation, the researcher is able to assess the appropriateness of the estimated normalization constant. We use the diagnostic plot to evaluate the appropriateness of the estimates obtained by CisGenome, NCIS and CCAT on several real data examples. Moreover, we show the impact that the choice of the normalization constant can have on standard tools for peak calling such as MACS or SICER. Finally, we propose a novel procedure for controlling the FDR using sample swapping. This procedure makes use of the estimated normalization constant in order to gain power over the naive choice of constant (used in MACS and SICER), which is the ratio of the total number of reads in the ChIP and Input samples. Linear normalization approaches aim to estimate a scale factor, r, to adjust for different sequencing depths when comparing ChIP versus Input samples. The estimated scaling factor can easily be incorporated in many peak caller algorithms to improve the accuracy of the peak identification. The

  3. The normal and pathological language

    OpenAIRE

    Espejo, Luis D.

    2014-01-01

    The extraordinary development of normal and pathological psychology has achieved in recent decades, thanks to the dual method of objective observation and oral survey enabled the researcher spirit of neuro-psychiatrist penetrate the intimate mechanism of the nervous system whose supreme manifestation is thought. It is normal psychology explaining the complicated game of perceptions: their methods of transmission, their centers of projection, its transformations and its synthesis to construct ...

  4. Is normal science good science?

    Directory of Open Access Journals (Sweden)

    Adrianna Kępińska

    2015-09-01

    Full Text Available “Normal science” is a concept introduced by Thomas Kuhn in The Structure of Scientific Revolutions (1962. In Kuhn’s view, normal science means “puzzle solving”, solving problems within the paradigm—framework most successful in solving current major scientific problems—rather than producing major novelties. This paper examines Kuhnian and Popperian accounts of normal science and their criticisms to assess if normal science is good. The advantage of normal science according to Kuhn was “psychological”: subjective satisfaction from successful “puzzle solving”. Popper argues for an “intellectual” science, one that consistently refutes conjectures (hypotheses and offers new ideas rather than focus on personal advantages. His account is criticized as too impersonal and idealistic. Feyerabend’s perspective seems more balanced; he argues for a community that would introduce new ideas, defend old ones, and enable scientists to develop in line with their subjective preferences. The paper concludes that normal science has no one clear-cut set of criteria encompassing its meaning and enabling clear assessment.

  5. nth roots of normal contractions

    International Nuclear Information System (INIS)

    Duggal, B.P.

    1992-07-01

    Given a complex separable Hilbert space H and a contraction A on H such that A n , n≥2 some integer, is normal it is shown that if the defect operator D A = (1 - A * A) 1/2 is of the Hilbert-Schmidt class, then A is similar to a normal contraction, either A or A 2 is normal, and if A 2 is normal (but A is not) then there is a normal contraction N and a positive definite contraction P of trace class such that parallel to A - N parallel to 1 = 1/2 parallel to P + P parallel to 1 (where parallel to · parallel to 1 denotes the trace norm). If T is a compact contraction such that its characteristics function admits a scalar factor, if T = A n for some integer n≥2 and contraction A with simple eigen-values, and if both T and A satisfy a ''reductive property'', then A is a compact normal contraction. (author). 16 refs

  6. Protein S

    Science.gov (United States)

    ... Normal Results Normal values are 60% to 150% inhibition. Normal value ranges may vary slightly among different ... Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us ...

  7. Protein C

    Science.gov (United States)

    ... Normal Results Normal values are 60% to 150% inhibition. Normal value ranges may vary slightly among different ... Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow us ...

  8. Alexander's disease in a neurologically normal child: a case report

    International Nuclear Information System (INIS)

    Guthrie, Scott O.; Knowles, Paul; Marshall, Robert; Burton, Edward M.

    2003-01-01

    We report the clinical and MRI findings of symmetric hyperintensity involving the deep and subcortical white matter of the frontal lobes in a neurologically normal child with macrocephaly. In this patient, a serum test for mutations in glial fibrillary acidic protein, used to diagnose Alexander's disease (AD), was positive. This case indicates an extraordinarily mild or early form of juvenile-onset AD. (orig.)

  9. Precaval retropancreatic space: Normal anatomy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeon Hee; Kim, Ki Whang; Kim, Myung Jin; Yoo, Hyung Sik; Lee, Jong Tae [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1992-07-15

    The authors defined precaval retropancreatic space as the space between pancreatic head with portal vein and IVC and analyzed the CT findings of this space to know the normal structures and size in this space. We evaluated 100 cases of normal abdominal CT scan to find out normal anatomic structures of precaval retropancreatic space retrospectively. We also measured the distance between these structures and calculated the minimum, maximum and mean values. At the splenoportal confluence level, normal structures between portal vein and IVC were vessel (21%), lymph node (19%), and caudate lobe of liver (2%) in order of frequency. The maximum AP diameter of portocaval lymph node was 4 mm. Common bile duct (CBD) was seen in 44% and the diameter was mean 3 mm and maximum 11 mm. CBD was located in extrapancreatic (75%) and lateral (60.6%) to pancreatic head. At IVC-left renal vein level, the maximum distance between CBD and IVC was 5 mm and the structure between posterior pancreatic surface and IVC was only fat tissue. Knowledge of these normal structures and measurement will be helpful in differentiating pancreatic mass with retropancreatic mass such as lymphadenopathy.

  10. Normal probability plots with confidence.

    Science.gov (United States)

    Chantarangsi, Wanpen; Liu, Wei; Bretz, Frank; Kiatsupaibul, Seksan; Hayter, Anthony J; Wan, Fang

    2015-01-01

    Normal probability plots are widely used as a statistical tool for assessing whether an observed simple random sample is drawn from a normally distributed population. The users, however, have to judge subjectively, if no objective rule is provided, whether the plotted points fall close to a straight line. In this paper, we focus on how a normal probability plot can be augmented by intervals for all the points so that, if the population distribution is normal, then all the points should fall into the corresponding intervals simultaneously with probability 1-α. These simultaneous 1-α probability intervals provide therefore an objective mean to judge whether the plotted points fall close to the straight line: the plotted points fall close to the straight line if and only if all the points fall into the corresponding intervals. The powers of several normal probability plot based (graphical) tests and the most popular nongraphical Anderson-Darling and Shapiro-Wilk tests are compared by simulation. Based on this comparison, recommendations are given in Section 3 on which graphical tests should be used in what circumstances. An example is provided to illustrate the methods. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 3j Symbols: To Normalize or Not to Normalize?

    Science.gov (United States)

    van Veenendaal, Michel

    2011-01-01

    The systematic use of alternative normalization constants for 3j symbols can lead to a more natural expression of quantities, such as vector products and spherical tensor operators. The redefined coupling constants directly equate tensor products to the inner and outer products without any additional square roots. The approach is extended to…

  12. CT and MRI normal findings

    International Nuclear Information System (INIS)

    Moeller, T.B.; Reif, E.

    1998-01-01

    This book gives answers to questions frequently heard especially from trainees and doctors not specialising in the field of radiology: Is that a normal finding? How do I decide? What are the objective criteria? The information presented is three-fold. The normal findings of the usual CT and MRI examinations are shown with high-quality pictures serving as a reference, with inscribed important additional information on measures, angles and other criteria describing the normal conditions. These criteria are further explained and evaluated in accompanying texts which also teach the systematic approach for individual picture analysis, and include a check list of major aspects, as a didactic guide for learning. The book is primarily intended for students, radiographers, radiology trainees and doctors from other medical fields, but radiology specialists will also find useful details of help in special cases. (orig./CB) [de

  13. Marrow transfusions into normal recipients

    International Nuclear Information System (INIS)

    Brecher, G.

    1983-01-01

    During the past several years we have explored the transfusion of bone marrow into normal nonirradiated mice. While transfused marrow proliferates readily in irradiated animals, only minimal proliferation takes place in nonirradiated recipients. It has generally been assumed that this was due to the lack of available proliferative sites in recipients with normal marrow. Last year we were able to report that the transfusion of 200 million bone marrow cells (about 2/3 of the total complement of marrow cells of a normal mouse) resulted in 20% to 25% of the recipient's marrow being replaced by donor marrow. Thus we can now study the behavior of animals that have been transfused (donor) and endogenous (recipient) marrow cells, although none of the tissues of either donor or recipient have been irradiated. With these animals we hope to investigate the nature of the peculiar phenomenon of serial exhaustion of marrow, also referred to as the limited self-replicability of stem cells

  14. The construction of normal expectations

    DEFF Research Database (Denmark)

    Quitzau, Maj-Britt; Røpke, Inge

    2008-01-01

    The gradual upward changes of standards in normal everyday life have significant environmental implications, and it is therefore important to study how these changes come about. The intention of the article is to analyze the social construction of normal expectations through a case study. The case...... concerns the present boom in bathroom renovations in Denmark, which offers an excellent opportunity to study the interplay between a wide variety of consumption drivers and social changes pointing toward long-term changes of normal expectations regarding bathroom standards. The study is problemoriented...... and transdisciplinary and draws on a wide range of sociological, anthropological, and economic theories. The empirical basis comprises a combination of statistics, a review of magazine and media coverage, visits to exhibitions, and qualitative interviews. A variety of consumption drivers are identified. Among...

  15. Recombinant Collagenlike Proteins

    Science.gov (United States)

    Fertala, Andzej

    2007-01-01

    A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, "Synthesis of human procollagens and collagens in recombinant DNA systems." Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications. Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.

  16. Normalized cDNA libraries

    Science.gov (United States)

    Soares, Marcelo B.; Efstratiadis, Argiris

    1997-01-01

    This invention provides a method to normalize a directional cDNA library constructed in a vector that allows propagation in single-stranded circle form comprising: (a) propagating the directional cDNA library in single-stranded circles; (b) generating fragments complementary to the 3' noncoding sequence of the single-stranded circles in the library to produce partial duplexes; (c) purifying the partial duplexes; (d) melting and reassociating the purified partial duplexes to moderate Cot; and (e) purifying the unassociated single-stranded circles, thereby generating a normalized cDNA library.

  17. Random Generators and Normal Numbers

    OpenAIRE

    Bailey, David H.; Crandall, Richard E.

    2002-01-01

    Pursuant to the authors' previous chaotic-dynamical model for random digits of fundamental constants, we investigate a complementary, statistical picture in which pseudorandom number generators (PRNGs) are central. Some rigorous results are achieved: We establish b-normality for constants of the form $\\sum_i 1/(b^{m_i} c^{n_i})$ for certain sequences $(m_i), (n_i)$ of integers. This work unifies and extends previously known classes of explicit normals. We prove that for coprime $b,c>1$ the...

  18. Complete normal ordering 1: Foundations

    Directory of Open Access Journals (Sweden)

    John Ellis

    2016-08-01

    Full Text Available We introduce a new prescription for quantising scalar field theories (in generic spacetime dimension and background perturbatively around a true minimum of the full quantum effective action, which is to ‘complete normal order’ the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all ‘cephalopod’ Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of ‘complete normal ordering’ (which is an extension of the standard field theory definition of normal ordering reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative interactions, and by using a point splitting ‘trick’ we extend this result to theories with derivative interactions, such as those appearing as non-linear σ-models in the world-sheet formulation of string theory. We focus here on theories with trivial vacua, generalising the discussion to non-trivial vacua in a follow-up paper.

  19. Normal forms in Poisson geometry

    NARCIS (Netherlands)

    Marcut, I.T.

    2013-01-01

    The structure of Poisson manifolds is highly nontrivial even locally. The first important result in this direction is Conn's linearization theorem around fixed points. One of the main results of this thesis (Theorem 2) is a normal form theorem in Poisson geometry, which is the Poisson-geometric

  20. Mixed normal inference on multicointegration

    NARCIS (Netherlands)

    Boswijk, H.P.

    2009-01-01

    Asymptotic likelihood analysis of cointegration in I(2) models, see Johansen (1997, 2006), Boswijk (2000) and Paruolo (2000), has shown that inference on most parameters is mixed normal, implying hypothesis test statistics with an asymptotic 2 null distribution. The asymptotic distribution of the

  1. Is My Child's Appetite Normal?

    Science.gov (United States)

    Is My Child’s Appetite Normal? Cayla, who is 4 years old, did not finish her lunch. But she is ready to play. Her ... snack for later. That is okay! Your child’s appetite changes. Children do not grow as fast in ...

  2. Transforming Normal Programs by Replacement

    NARCIS (Netherlands)

    Bossi, Annalisa; Pettorossi, A.; Cocco, Nicoletta; Etalle, Sandro

    1992-01-01

    The replacement transformation operation, already defined in [28], is studied wrt normal programs. We give applicability conditions able to ensure the correctness of the operation wrt Fitting's and Kunen's semantics. We show how replacement can mimic other transformation operations such as thinning,

  3. Semigroups of data normalization functions

    NARCIS (Netherlands)

    Warrens, Matthijs J.

    2016-01-01

    Variable centering and scaling are functions that are typically used in data normalization. Various properties of centering and scaling functions are presented. It is shown that if we use two centering functions (or scaling functions) successively, the result depends on the order in which the

  4. Normalizing Catastrophe: Sustainability and Scientism

    Science.gov (United States)

    Bonnett, Michael

    2013-01-01

    Making an adequate response to our deteriorating environmental situation is a matter of ever increasing urgency. It is argued that a central obstacle to achieving this is the way that scientism has become normalized in our thinking about environmental issues. This is taken to reflect on an underlying "metaphysics of mastery" that vitiates proper…

  5. Neutron RBE for normal tissues

    International Nuclear Information System (INIS)

    Field, S.B.; Hornsey, S.

    1979-01-01

    RBE for various normal tissues is considered as a function of neutron dose per fraction. Results from a variety of centres are reviewed. It is shown that RBE is dependent on neutron energy and is tissue dependent, but is not specially high for the more critical tissues or for damage occurring late after irradiation. (author)

  6. Normal and abnormal growth plate

    International Nuclear Information System (INIS)

    Kumar, R.; Madewell, J.E.; Swischuk, L.E.

    1987-01-01

    Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities

  7. Superconducting versus normal conducting cavities

    CERN Document Server

    Podlech, Holger

    2013-01-01

    One of the most important issues of high-power hadron linacs is the choice of technology with respect to superconducting or room-temperature operation. The favour for a specific technology depends on several parameters such as the beam energy, beam current, beam power and duty factor. This contribution gives an overview of the comparison between superconducting and normal conducting cavities. This includes basic radiofrequency (RF) parameters, design criteria, limitations, required RF and plug power as well as case studies.

  8. Normal Movement Selectivity in Autism

    OpenAIRE

    Dinstein, Ilan; Thomas, Cibu; Humphreys, Kate; Minshew, Nancy; Behrmann, Marlene; Heeger, David J.

    2010-01-01

    It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements, but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Moveme...

  9. Lithium control during normal operation

    International Nuclear Information System (INIS)

    Suryanarayan, S.; Jain, D.

    2010-01-01

    Periodic increases in lithium (Li) concentrations in the primary heat transport (PHT) system during normal operation are a generic problem at CANDU® stations. Lithiated mixed bed ion exchange resins are used at stations for pH control in the PHT system. Typically tight chemistry controls including Li concentrations are maintained in the PHT water. The reason for the Li increases during normal operation at CANDU stations such as Pickering was not fully understood. In order to address this issue a two pronged approach was employed. Firstly, PNGS-A data and information from other available sources was reviewed in an effort to identify possible factors that may contribute to the observed Li variations. Secondly, experimental studies were carried out to assess the importance of these factors in order to establish reasons for Li increases during normal operation. Based on the results of these studies, plausible mechanisms/reasons for Li increases have been identified and recommendations made for proactive control of Li concentrations in the PHT system. (author)

  10. Normalization of Gravitational Acceleration Models

    Science.gov (United States)

    Eckman, Randy A.; Brown, Aaron J.; Adamo, Daniel R.

    2011-01-01

    Unlike the uniform density spherical shell approximations of Newton, the con- sequence of spaceflight in the real universe is that gravitational fields are sensitive to the nonsphericity of their generating central bodies. The gravitational potential of a nonspherical central body is typically resolved using spherical harmonic approximations. However, attempting to directly calculate the spherical harmonic approximations results in at least two singularities which must be removed in order to generalize the method and solve for any possible orbit, including polar orbits. Three unique algorithms have been developed to eliminate these singularities by Samuel Pines [1], Bill Lear [2], and Robert Gottlieb [3]. This paper documents the methodical normalization of two1 of the three known formulations for singularity-free gravitational acceleration (namely, the Lear [2] and Gottlieb [3] algorithms) and formulates a general method for defining normalization parameters used to generate normalized Legendre Polynomials and ALFs for any algorithm. A treatment of the conventional formulation of the gravitational potential and acceleration is also provided, in addition to a brief overview of the philosophical differences between the three known singularity-free algorithms.

  11. "Ser diferente é normal?"/"Being different: is it normal?"

    Directory of Open Access Journals (Sweden)

    Viviane Veras

    2007-01-01

    Full Text Available A pergunta título deste trabalho retoma o slogan “Ser diferente é normal”, que é parte da campanha criada para uma organização não-governamental que atende portadores de Síndrome de Down. O objetivo é a inclusão social da pessoa com deficiência e o primeiro passo foi propor a inclusão de um grupo de diferentes no grupo dito normal. No vídeo de lançamento da campanha, o diferente, identificado como normal, é mostrado por meio de exemplos – um negro com cabelo black-power, um skin-head, um corpo tatuado, um corpo feminino halterofílico, uma família hippie, uma garota com síndrome de Down. A visão da adolescente dançando reduz, de certo modo, o efeito imaginário que vai além da síndrome, uma vez que apenas o corpo com seus olhinhos puxados se destacam, e não se interrogam questões cognitivas. Minha proposta é refletir sobre o estatuto paradoxal do exemplo, tal como é trabalhado nesse vídeo: se, por definição, um exemplo mostra de fato seu pertencimento a uma classe, pode-se concluir que é exatamente por ser exemplar que ele se encontra fora dela, no exato momento em que a exibe e define. The question in the title of this paper refers to the slogan "ser diferente é normal" ("It´s normal to be different", which is part of a campaign created for a NGO that supports people with Down syndrome. The objective of the campaign is to promote the social inclusion of individuals with Down syndrome, and the first step was to propose the inclusion of a group of "differents" in the so-called normal group. The film launching the campaign shows the different identified as normal by means of examples: a black man exhibiting blackpower haircut, a skin-head, a tattooed body, an over-athletic female body, a hippie family and a girl with Down syndrome. The vision of the dancing teenager lessens the imaginary effect that surpasses the syndrome, since only her body and her little oriental eyes stand out and no cognitive issues are

  12. Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

    Directory of Open Access Journals (Sweden)

    Marsha eMailick

    2014-09-01

    Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

  13. Understanding a Normal Distribution of Data.

    Science.gov (United States)

    Maltenfort, Mitchell G

    2015-12-01

    Assuming data follow a normal distribution is essential for many common statistical tests. However, what are normal data and when can we assume that a data set follows this distribution? What can be done to analyze non-normal data?

  14. Quantiles for Finite Mixtures of Normal Distributions

    Science.gov (United States)

    Rahman, Mezbahur; Rahman, Rumanur; Pearson, Larry M.

    2006-01-01

    Quantiles for finite mixtures of normal distributions are computed. The difference between a linear combination of independent normal random variables and a linear combination of independent normal densities is emphasized. (Contains 3 tables and 1 figure.)

  15. A locally adaptive normal distribution

    DEFF Research Database (Denmark)

    Arvanitidis, Georgios; Hansen, Lars Kai; Hauberg, Søren

    2016-01-01

    entropy distribution under the given metric. The underlying metric is, however, non-parametric. We develop a maximum likelihood algorithm to infer the distribution parameters that relies on a combination of gradient descent and Monte Carlo integration. We further extend the LAND to mixture models......The multivariate normal density is a monotonic function of the distance to the mean, and its ellipsoidal shape is due to the underlying Euclidean metric. We suggest to replace this metric with a locally adaptive, smoothly changing (Riemannian) metric that favors regions of high local density...

  16. Normal pediatric postmortem CT appearances

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Willemijn M.; Bosboom, Dennis G.H.; Koopmanschap, Desiree H.J.L.M. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Nievelstein, Rutger A.J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Nikkels, Peter G.J. [University Medical Center Utrecht, Department of Pathology, Utrecht (Netherlands); Rijn, Rick R. van [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands)

    2015-04-01

    Postmortem radiology is a rapidly developing specialty that is increasingly used as an adjunct to or substitute for conventional autopsy. The goal is to find patterns of disease and possibly the cause of death. Postmortem CT images bring to light processes of decomposition most radiologists are unfamiliar with. These postmortem changes, such as the formation of gas and edema, should not be mistaken for pathological processes that occur in living persons. In this review we discuss the normal postmortem thoraco-abdominal changes and how these appear on CT images, as well as how to differentiate these findings from those of pathological processes. (orig.)

  17. Multispectral histogram normalization contrast enhancement

    Science.gov (United States)

    Soha, J. M.; Schwartz, A. A.

    1979-01-01

    A multispectral histogram normalization or decorrelation enhancement which achieves effective color composites by removing interband correlation is described. The enhancement procedure employs either linear or nonlinear transformations to equalize principal component variances. An additional rotation to any set of orthogonal coordinates is thus possible, while full histogram utilization is maintained by avoiding the reintroduction of correlation. For the three-dimensional case, the enhancement procedure may be implemented with a lookup table. An application of the enhancement to Landsat multispectral scanning imagery is presented.

  18. Normal modes and continuous spectra

    International Nuclear Information System (INIS)

    Balmforth, N.J.; Morrison, P.J.

    1994-12-01

    The authors consider stability problems arising in fluids, plasmas and stellar systems that contain singularities resulting from wave-mean flow or wave-particle resonances. Such resonances lead to singularities in the differential equations determining the normal modes at the so-called critical points or layers. The locations of the singularities are determined by the eigenvalue of the problem, and as a result, the spectrum of eigenvalues forms a continuum. They outline a method to construct the singular eigenfunctions comprising the continuum for a variety of problems

  19. Normal movement selectivity in autism.

    Science.gov (United States)

    Dinstein, Ilan; Thomas, Cibu; Humphreys, Kate; Minshew, Nancy; Behrmann, Marlene; Heeger, David J

    2010-05-13

    It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Movement selectivity is a defining characteristic of neurons involved in movement perception, including mirror neurons, and, as such, these findings argue against a mirror system dysfunction in autism. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Update on normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Jyotiranjan Mallick

    2016-01-01

    Full Text Available Normal tension glaucoma (NTG is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases, systemic calcium channel blockers (such as nifedipine and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG.

  1. Normal variation of hepatic artery

    International Nuclear Information System (INIS)

    Kim, Inn; Nam, Myung Hyun; Rhim, Hyun Chul; Koh, Byung Hee; Seo, Heung Suk; Kim, Soon Yong

    1987-01-01

    This study was an analyses of blood supply of the liver in 125 patients who received hepatic arteriography and abdominal aortography from Jan. 1984 to Dec. 1986 at the Department of Radiology of Hanyang University Hospital. A. Variations in extrahepatic arteries: 1. The normal extrahepatic artery pattern occurred in 106 of 125 cases (84.8%) ; Right hepatic and left hepatic arteries arising from the hepatic artery proper and hepatic artery proper arising from the common hepatic artery. 2. The most common type of variation of extrahepatic artery was replaced right hepatic artery from superior mesenteric artery: 6 of 125 cases (4.8%). B. Variations in intrahepatic arteries: 1. The normal intrahepatic artery pattern occurred in 83 of 125 cases (66.4%). Right hepatic and left hepatic arteries arising from the hepatic artery proper and middle hepatic artery arising from lower portion of the umbilical point of left hepatic artery. 2. The most common variation of intrahepatic arteries was middle hepatic artery. 3. Among the variation of middle hepatic artery; Right, middle and left hepatic arteries arising from the same location at the hepatic artery proper was the most common type; 17 of 125 cases (13.6%)

  2. Is My Penis Normal? (For Teens)

    Science.gov (United States)

    ... Videos for Educators Search English Español Is My Penis Normal? KidsHealth / For Teens / Is My Penis Normal? Print en español ¿Es normal mi pene? ... any guy who's ever worried about whether his penis is a normal size. There's a fairly wide ...

  3. Normal vibrations in gallium arsenide

    International Nuclear Information System (INIS)

    Dolling, G.; Waugh, J.L.T.

    1964-01-01

    The triple axis crystal spectrometer at Chalk River has been used to observe coherent slow neutron scattering from a single crystal of pure gallium arsenide at 296 o K. The frequencies of normal modes of vibration propagating in the [ζ00], (ζζζ], and (0ζζ] crystal directions have been determined with a precision of between 1 and 2·5 per cent. A limited number of normal modes have also been studied at 95 and 184 o K. Considerable difficulty was experienced in obtaining welt resolved neutron peaks corresponding to the two non-degenerate optic modes for very small wave-vector, particularly at 296 o K. However, from a comparison of results obtained under various experimental conditions at several different points in reciprocal space, frequencies (units 10 12 c/s) for these modes (at 296 o K) have been assigned: T 8·02±0·08 and L 8·55±02. Other specific normal modes, with their measured frequencies are (a) (1,0,0): TO 7·56 ± 008, TA 2·36 ± 0·015, LO 7·22 ± 0·15, LA 6·80 ± 0·06; (b) (0·5, 0·5, 0·5): TO 7·84 ± 0·12, TA 1·86 ± 0·02, LO 7·15 ± 0·07, LA 6·26 ± 0·10; (c) (0, 0·65, 0·65): optic 8·08 ±0·13, 7·54 ± 0·12 and 6·57 ± 0·11, acoustic 5·58 ± 0·08, 3·42 · 0·06 and 2·36 ± 004. These results are generally slightly lower than the corresponding frequencies for germanium. An analysis in terms of various modifications of the dipole approximation model has been carried out. A feature of this analysis is that the charge on the gallium atom appears to be very small, about +0·04 e. The frequency distribution function has been derived from one of the force models. (author)

  4. Normal vibrations in gallium arsenide

    Energy Technology Data Exchange (ETDEWEB)

    Dolling, G; Waugh, J L T

    1964-07-01

    The triple axis crystal spectrometer at Chalk River has been used to observe coherent slow neutron scattering from a single crystal of pure gallium arsenide at 296{sup o}K. The frequencies of normal modes of vibration propagating in the [{zeta}00], ({zeta}{zeta}{zeta}], and (0{zeta}{zeta}] crystal directions have been determined with a precision of between 1 and 2{center_dot}5 per cent. A limited number of normal modes have also been studied at 95 and 184{sup o}K. Considerable difficulty was experienced in obtaining welt resolved neutron peaks corresponding to the two non-degenerate optic modes for very small wave-vector, particularly at 296{sup o}K. However, from a comparison of results obtained under various experimental conditions at several different points in reciprocal space, frequencies (units 10{sup 12} c/s) for these modes (at 296{sup o}K) have been assigned: T 8{center_dot}02{+-}0{center_dot}08 and L 8{center_dot}55{+-}02. Other specific normal modes, with their measured frequencies are (a) (1,0,0): TO 7{center_dot}56 {+-} 008, TA 2{center_dot}36 {+-} 0{center_dot}015, LO 7{center_dot}22 {+-} 0{center_dot}15, LA 6{center_dot}80 {+-} 0{center_dot}06; (b) (0{center_dot}5, 0{center_dot}5, 0{center_dot}5): TO 7{center_dot}84 {+-} 0{center_dot}12, TA 1{center_dot}86 {+-} 0{center_dot}02, LO 7{center_dot}15 {+-} 0{center_dot}07, LA 6{center_dot}26 {+-} 0{center_dot}10; (c) (0, 0{center_dot}65, 0{center_dot}65): optic 8{center_dot}08 {+-}0{center_dot}13, 7{center_dot}54 {+-} 0{center_dot}12 and 6{center_dot}57 {+-} 0{center_dot}11, acoustic 5{center_dot}58 {+-} 0{center_dot}08, 3{center_dot}42 {center_dot} 0{center_dot}06 and 2{center_dot}36 {+-} 004. These results are generally slightly lower than the corresponding frequencies for germanium. An analysis in terms of various modifications of the dipole approximation model has been carried out. A feature of this analysis is that the charge on the gallium atom appears to be very small, about +0{center_dot}04 e. The

  5. Striving for the unknown normal

    DEFF Research Database (Denmark)

    Nielsen, Mikka

    During the last decade, more and more people have received prescriptions for ADHD drug treatment, and simultaneously the legitimacy of the ADHD diagnosis has been heavily debated among both professionals and laymen. Based on an anthropological fieldwork among adults with ADHD, I illustrate how...... the ADHD diagnosis both answers and produces existential questions on what counts as normal behaviour and emotions. The diagnosis helps the diagnosed to identify, accept and handle problems by offering concrete explanations and solutions to diffuse experienced problems. But the diagnostic process...... is not only a clarifying procedure with a straight plan for treatment and direct effects. It is also a messy affair. In a process of experimenting with drugs and attempting to determine how or whether the medication eliminates the correct symptoms the diagnosed is put in an introspective, self...

  6. IIH with normal CSF pressures?

    Directory of Open Access Journals (Sweden)

    Soh Youn Suh

    2013-01-01

    Full Text Available Idiopathic intracranial hypertension (IIH is a condition of raised intracranial pressure (ICP in the absence of space occupying lesions. ICP is usually measured by lumbar puncture and a cerebrospinal fluid (CSF pressure above 250 mm H 2 O is one of the diagnostic criteria of IIH. Recently, we have encountered two patients who complained of headaches and exhibited disc swelling without an increased ICP. We prescribed acetazolamide and followed both patients frequently; because of the definite disc swelling with IIH related symptoms. Symptoms and signs resolved in both patients after they started taking acetazolamide. It is generally known that an elevated ICP, as measured by lumbar puncture, is the most important diagnostic sign of IIH. However, these cases caution even when CSF pressure is within the normal range, that suspicion should be raised when a patient has papilledema with related symptoms, since untreated papilledema may cause progressive and irreversible visual loss.

  7. CT in normal pressure hydrocephalus

    International Nuclear Information System (INIS)

    Fujita, Katsuzo; Nogaki, Hidekazu; Noda, Masaya; Kusunoki, Tadaki; Tamaki, Norihiko

    1981-01-01

    CT scans were obtained on 33 patients (age 73y. to 31y.) with the diagnosis of normal pressure hydrocephalus. In each case, the diagnosis was made on the basis of the symptoms, CT and cisternographic findings. Underlying diseases of normal pressure hydrocephalus are ruptured aneurysms (21 cases), arteriovenous malformations (2 cases), head trauma (1 case), cerebrovascular accidents (1 case) and idiopathie (8 cases). Sixteen of 33 patients showed marked improvement, five, moderate or minimal improvement, and twelve, no change. The results were compared with CT findings and clinical response to shunting. CT findings were classified into five types, bases on the degree of periventricular hypodensity (P.V.H.), the extent of brain damage by underlying diseases, and the degree of cortical atrophy. In 17 cases of type (I), CT shows the presence of P.V.H. with or without minimal frontal lobe damage and no cortical atrophy. The good surgical improvements were achieved in all cases of type (I) by shunting. In 4 cases of type (II), CT shows the presence of P.V.H. and severe brain damage without cortical atrophy. The fair clinical improvements were achieved in 2 cases (50%) by shunting. In one case of type (III), CT shows the absence of P.V.H. without brain damage nor cortical atrophy. No clinical improvement was obtained by shunting in this type. In 9 cases of type (IV) with mild cortical atrophy, the fair clinical improvement was achieved in two cases (22%) and no improvement in 7 cases. In 2 cases of type (V) with moderate or marked cortical atrophy, no clinical improvement was obtained by shunting. In conclusion, it appeared from the present study that there was a good correlation between the result of shunting and the type of CT, and clinical response to shunting operation might be predicted by classification of CT findings. (author)

  8. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  9. Proteins engineering

    International Nuclear Information System (INIS)

    2000-01-01

    At the - Departement d'Ingenierie et d'etudes de proteines (Deip) of the CEA more than seventy researchers are working hard to understand the function of proteins. For that they use the molecular labelling technique (F.M.)

  10. Whey Protein

    Science.gov (United States)

    ... reliable information about the safety of taking whey protein if you are pregnant or breast feeding. Stay on the safe side and avoid use. Milk allergy: If you are allergic to cow's milk, avoid using whey protein.

  11. Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase.

    OpenAIRE

    Reith, A D; Ellis, C; Lyman, S D; Anderson, D M; Williams, D E; Bernstein, A; Pawson, T

    1991-01-01

    Germline mutations at the Dominant White Spotting (W) and Steel (Sl) loci have provided conclusive genetic evidence that c-kit mediated signal transduction pathways are essential for normal mouse development. We have analysed the interactions of normal and mutant W/c-kit gene products with cytoplasmic signalling proteins, using transient c-kit expression assays in COS cells. In addition to the previously identified c-kit gene product (Kit+), a second normal Kit isoform (KitA+) containing an i...

  12. Glycoprotein biosynthesis by human normal platelets

    International Nuclear Information System (INIS)

    Rodriguez, P.; Bello, O.; Apitz-Castro, R.

    1987-01-01

    Incorporation of radioactive Man, Gal, Fuc, Glc-N, and NANA into washed human normal platelets and endogenous glycoproteins has been found. Both parameters were time dependent. Analysis of hydrolyzed labeled glycoproteins by paper chromatography revealed that the radioactive monosaccharide incubated with the platelets had not been converted into other sugars. Acid hydrolysis demonstrates the presence of a glycosidic linkage. All the effort directed to the demonstration of the existence of a lipid-sugar intermediate in intact human platelets yielded negative results for Man and Glc-N used as precursors. The incorporation of these sugars into glycoproteins is insensitive to bacitracin, suggesting no involvement of lipid-linked saccharides in the synthesis of glycoproteins in human blood platelets. The absence of inhibition of the glycosylation process in the presence of cycloheximide suggests that the sugars are added to proteins present in the intact platelets. These results support the contention that glycoprotein biosynthesis in human blood platelets observed under our experimental conditions is effected through direct sugar nucleotide glycosylation

  13. Normalization of emotion control scale

    Directory of Open Access Journals (Sweden)

    Hojatoolah Tahmasebian

    2014-09-01

    Full Text Available Background: Emotion control skill teaches the individuals how to identify their emotions and how to express and control them in various situations. The aim of this study was to normalize and measure the internal and external validity and reliability of emotion control test. Methods: This standardization study was carried out on a statistical society, including all pupils, students, teachers, nurses and university professors in Kermanshah in 2012, using Williams’ emotion control scale. The subjects included 1,500 (810 females and 690 males people who were selected by stratified random sampling. Williams (1997 emotion control scale, was used to collect the required data. Emotional Control Scale is a tool for measuring the degree of control people have over their emotions. This scale has four subscales, including anger, depressed mood, anxiety and positive affect. The collected data were analyzed by SPSS software using correlation and Cronbach's alpha tests. Results: The results of internal consistency of the questionnaire reported by Cronbach's alpha indicated an acceptable internal consistency for emotional control scale, and the correlation between the subscales of the test and between the items of the questionnaire was significant at 0.01 confidence level. Conclusion: The validity of emotion control scale among the pupils, students, teachers, nurses and teachers in Iran has an acceptable range, and the test itemswere correlated with each other, thereby making them appropriate for measuring emotion control.

  14. Digital Pupillometry in Normal Subjects

    Science.gov (United States)

    Rickmann, Annekatrin; Waizel, Maria; Kazerounian, Sara; Szurman, Peter; Wilhelm, Helmut; Boden, Karl T.

    2017-01-01

    ABSTRACT The aim of this study was to evaluate the pupil size of normal subjects at different illumination levels with a novel pupillometer. The pupil size of healthy study participants was measured with an infrared-video PupilX pupillometer (MEye Tech GmbH, Alsdorf, Germany) at five different illumination levels (0, 0.5, 4, 32, and 250 lux). Measurements were performed by the same investigator. Ninety images were executed during a measurement period of 3 seconds. The absolute linear camera resolution was approximately 20 pixels per mm. This cross-sectional study analysed 490 eyes of 245 subjects (mean age: 51.9 ± 18.3 years, range: 6–87 years). On average, pupil diameter decreased with increasing light intensities for both eyes, with a mean pupil diameter of 5.39 ± 1.04 mm at 0 lux, 5.20 ± 1.00 mm at 0.5 lux, 4.70 ± 0.97 mm at 4 lux, 3.74 ± 0.78 mm at 32 lux, and 2.84 ± 0.50 mm at 250 lux illumination. Furthermore, it was found that anisocoria increased by 0.03 mm per life decade for all illumination levels (R2 = 0.43). Anisocoria was higher under scotopic and mesopic conditions. This study provides additional information to the current knowledge concerning age- and light-related pupil size and anisocoria as a baseline for future patient studies. PMID:28228832

  15. Normal modes of Bardeen discs

    International Nuclear Information System (INIS)

    Verdaguer, E.

    1983-01-01

    The short wavelength normal modes of self-gravitating rotating polytropic discs in the Bardeen approximation are studied. The discs' oscillations can be seen in terms of two types of modes: the p-modes whose driving forces are pressure forces and the r-modes driven by Coriolis forces. As a consequence of differential rotation coupling between the two takes place and some mixed modes appear, their properties can be studied under the assumption of weak coupling and it is seen that they avoid the crossing of the p- and r-modes. The short wavelength analysis provides a basis for the classification of the modes, which can be made by using the properties of their phase diagrams. The classification is applied to the large wavelength modes of differentially rotating discs with strong coupling and to a uniformly rotating sequence with no coupling, which have been calculated in previous papers. Many of the physical properties and qualitative features of these modes are revealed by the analysis. (author)

  16. Use of wheat and maize protein mutants in breeding for improved protein quantity and quality

    International Nuclear Information System (INIS)

    Denic, M.; Dumanovic, J.; Misevic, D.; Konstantinov, K.; Fidler, D.; Stojanovic, Z.

    1984-01-01

    Selected offspring progenies (50 mutant lines) originating from mutation experiments with hexaploid wheat (cv. Bezostaya 1) were analysed for induced heritable variation in protein content, lysine content, grain yield and protein and lysine yields. Ten of these mutant lines were crossed with 11 local varieties. The protein and lysine contents were measured in the progenies of these crossings. The data showed better correlations of grain yield with protein and lysine yields than the protein and lysine contents with their corresponding yields. F 1 seeds showed higher lysine and protein contents than local varieties. Data with maize showed that: (1) the total endosperm protein content of modified opaque-2 types increases with an increase in the degree of normalization; (2) the lysine content in dry matter and protein in normalized o 2 kernels usually decreases with the increasing degree of normalization; (3) the lysine content in protein of modified o 2 kernels, is, in general, satisfactory up to the normalization of about 50% of endosperm. A desirable modification of o 2 endosperm within line A632o 2 was selected and crossed with o 2 lines. Most of the tested hybrids had a good protein quality, but endosperm modification was not evident in all hybrids. The o 2 gene was incorporated into high protein backgrounds. Besides a high protein content and quality, some of the hybrids tested had a comparable or higher yield than the o 2 check. (author)

  17. Sequence of activation of template biosyntheses in normal and transformed human cells after synchronization with a double thimidine block

    International Nuclear Information System (INIS)

    Alekseev, S.B.; Boikov, P.Ya.; Ebralidze, L.K.; Stepanova, L.G.

    1986-01-01

    The sequences of synthesis of DNA, RNA, and various groups of proteins in normal and transformed human fibroblasts was studied in the first mitotic cycle synchronization of the cells by a double thymidine block. Two peculiarities of the synthesis of acid-soluble histone and acid-insoluble proteins in the normal and transformed cells, were detected: (1) in normal fibroblasts the synthesis of the two groups of proteins is a minimum before DNA replication, and the greatest activity is achieved in the G 2 phase; in transformed cells protein synthesis is a maximum after the removal of the thymine block, while in the G 2 phase it is decreased; (2) in normal fibroblasts the synthesis of acid-insoluble proteins is a maximum before the maximum synthesis of DNA, and that of acid-soluble proteins is a maximum after the maximum of DNA synthesis. The opposite picture is observed in transformed cells. RNA synthesis in normal and transformed cells is activated at the end of the G 2 phase. In normal cells the synthesis of proteins is coupled with the activation of RNA synthesis, while in transformed cells protein synthesis is evidently transferred to the following mitotic cycle. Especially pronounced differences were detected in the expression of certain LMG proteins. Thus, in transformed cells the regulation of the coupling of the template syntheses is modified

  18. Defining the "normal" postejaculate urinalysis.

    Science.gov (United States)

    Mehta, Akanksha; Jarow, Jonathan P; Maples, Pat; Sigman, Mark

    2012-01-01

    Although sperm have been shown to be present in the postejaculate urinalysis (PEU) of both fertile and infertile men, the number of sperm present in the PEU of the general population has never been well defined. The objective of this study was to describe the semen and PEU findings in both the general and infertile population, in order to develop a better appreciation for "normal." Infertile men (n = 77) and control subjects (n = 71) were prospectively recruited. Exclusion criteria included azoospermia and medications known to affect ejaculation. All men underwent a history, physical examination, semen analysis, and PEU. The urine was split into 2 containers: PEU1, the initial voided urine, and PEU2, the remaining voided urine. Parametric statistical methods were applied for data analysis to compare sperm concentrations in each sample of semen and urine between the 2 groups of men. Controls had higher average semen volume (3.3 ± 1.6 vs 2.0 ± 1.4 mL, P sperm concentrations (112 million vs 56.2 million, P = .011), compared with infertile men. The presence of sperm in urine was common in both groups, but more prevalent among infertile men (98.7% vs 88.7%, P = .012), in whom it comprised a greater proportion of the total sperm count (46% vs 24%, P = .022). The majority of sperm present in PEU were seen in PEU1 of both controls (69%) and infertile men (88%). An association was noted between severe oligospermia (sperm counts in PEU (sperm in the urine compared with control, there is a large degree of overlap between the 2 populations, making it difficult to identify a specific threshold to define a positive test. Interpretation of a PEU should be directed by whether the number of sperm in the urine could affect subsequent management.

  19. Turbocharging Normalization in Highland Conditions

    Directory of Open Access Journals (Sweden)

    I. V. Filippov

    2017-01-01

    Full Text Available To ensure many production processes are used compressors of various types, including turbochargers, which produce compressed air. The actual performance values of turbochargers used in highlands are significantly different from the certified values, and parameters of compressed air do not always guarantee the smooth and efficient functioning for consumers.The paper presents research results of the turbochargers of 4CI 425MX4 type, a series of "CENTAC", manufactured by INGERSOL – RAND Company. The research has been conducted in industrial highland conditions in difficult climatic environment. There were almost no investigations of turbochargers running in highland conditions. The combination of low atmospheric pressure with high temperature of the intake air causes the abnormal operating conditions of a turbocharger. Only N. M. Barannikov in his paper shows the results of theoretical studies of such operating conditions, but as to the practical research, there is no information at all.To normalize the turbocharger operation an option of the mechanical pressurization in the suction pipe is adopted. As a result of theoretical research, a TurboMAX blower MAX500 was chosen as a supercharger. The next stage of theoretical research was to construct characteristics of the turbocharger 4CI 425MX4 with a mechanical supercharger in the suction pipe. The boost reduces to the minimum the time of using additional compressors when parameters of the intake air are changed and ensures the smooth and efficient functioning for consumers.To verify the results of theoretical studies, namely, the technique for recalculation of the turbocharger characteristics under the real conditions of suction, were carried out the experimental researches. The average error between experimental and theoretical data is 2,9783 %, which confirms the validity of the technique used for reduction of the turbocharger characteristics to those under the real conditions of suction.

  20. Perbedaan Kadar HSP90 pada Preeklamsi Berat dengan Kehamilan Normal

    Directory of Open Access Journals (Sweden)

    Soetrisno

    2015-06-01

    Full Text Available Severe pre-eclampsia is the second highest cause of maternal mortality. Free radicals that stimulate heat shock protein 90 (HSP 90 are believed to determine severe pre-eclampsia. HSP90 is an important protein that helps the establishment and maintenance of other proteins. It also increases the life time of cells after various pathological conditions (chaperone function. The chaperone function is the adaptation key factor to endogenous stress in tissues. By recognizing HSP90 level in early detection of severe pre-eclampsia, prevention and management can be started early. This study aimed to prove that the HSP90 level in pregnancy with severe pre-eclampsia is higher than normal pregnancy. This was a quantitative study using cross sectional approach by testing the HSP90 level. The study was conducted during the period of September to November 2013, at the Obstetrics and Gynecological Unit, Moewardi Hospital Surakarta and Prodia Laboratory Jakarta. The number of subjects was 30 patients, consisting of 15 normal pregnant mothers and 15 pregnant mothers with pre-eclampsia . The calculation of serum HSP90 level was conducted using enzyme-linked immunosorbent assay (ELISA. Data were analyzed using t-test using SPSS for Windows version 17 for Windows. The mean of HSP90 in the severe pre-eclampsia group was 131.91±26.66 while the mean in the normal pregnancy group was 80.28±13.39 with p=0.00 (p<0.05. Level of HSP90 serum in severe pre-eclampsia is higher than in normal pregnancy, due to the occurrence of oxidative stress in severe pre-eclampsia

  1. Vaginal Discharge: What's Normal, What's Not

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Vaginal Discharge: What's Normal, What's Not KidsHealth / For Teens / ... Discharge: What's Normal, What's Not Print What Is Vaginal Discharge? Vaginal discharge is fluid that comes from ...

  2. Should Japan Become a Normal Country

    National Research Council Canada - National Science Library

    Yildiz, Ahmet

    2005-01-01

    This thesis evaluates Japanese geopolitical change in the post-Cold War era. It does so by analyzing Japan's history, its foreign policy since 1945, its reasons for becoming a normal country, and the impact of its normalization...

  3. Normalization and experimental design for ChIP-chip data

    Directory of Open Access Journals (Sweden)

    Alekseyenko Artyom A

    2007-06-01

    Full Text Available Abstract Background Chromatin immunoprecipitation on tiling arrays (ChIP-chip has been widely used to investigate the DNA binding sites for a variety of proteins on a genome-wide scale. However, several issues in the processing and analysis of ChIP-chip data have not been resolved fully, including the effect of background (mock control subtraction and normalization within and across arrays. Results The binding profiles of Drosophila male-specific lethal (MSL complex on a tiling array provide a unique opportunity for investigating these topics, as it is known to bind on the X chromosome but not on the autosomes. These large bound and control regions on the same array allow clear evaluation of analytical methods. We introduce a novel normalization scheme specifically designed for ChIP-chip data from dual-channel arrays and demonstrate that this step is critical for correcting systematic dye-bias that may exist in the data. Subtraction of the mock (non-specific antibody or no antibody control data is generally needed to eliminate the bias, but appropriate normalization obviates the need for mock experiments and increases the correlation among replicates. The idea underlying the normalization can be used subsequently to estimate the background noise level in each array for normalization across arrays. We demonstrate the effectiveness of the methods with the MSL complex binding data and other publicly available data. Conclusion Proper normalization is essential for ChIP-chip experiments. The proposed normalization technique can correct systematic errors and compensate for the lack of mock control data, thus reducing the experimental cost and producing more accurate results.

  4. Fatty Acid Binding Proteins in Prostate Cancer

    National Research Council Canada - National Science Library

    Jett, Marti

    2000-01-01

    We have shown that there is a distinct pattern of fatty acid binding protein (FAEP) expression in prostate cancer vs normal cells and that finding has be confirmed in patient samples of biopsy specimens...

  5. A note on totally normal spaces

    International Nuclear Information System (INIS)

    Zougdani, H.K.

    1990-10-01

    In this note we give the necessary and sufficient condition for a topological space X such that the product space X x Y is totally normal for any (non discrete) metric space Y, and we show that a totally normal p-space need not be a perfectly normal in general, which makes Theorem 2 doubtful. (author). 6 refs

  6. Manufacturing technology for practical Josephson voltage normals

    International Nuclear Information System (INIS)

    Kohlmann, Johannes; Kieler, Oliver

    2016-01-01

    In this contribution we present the manufacturing technology for the fabrication of integrated superconducting Josephson serial circuits for voltage normals. First we summarize some foundations for Josephson voltage normals and sketch the concept and the setup of the circuits, before we describe the manufacturing technology form modern practical Josephson voltage normals.

  7. Neutron scattering by normal liquids

    Energy Technology Data Exchange (ETDEWEB)

    Gennes, P.G. de [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1961-07-01

    Neutron data on motions in normal liquids well below critical point are reviewed and classified according to the order of magnitude of momentum transfers {Dirac_h}q and energy transfers {Dirac_h}w. For large momentum transfers a perfect gas model is valid. For smaller q and incoherent scattering, the major effects are related to the existence of two characteristic times: the period of oscillation of an atom in its cell, and the average lifetime of the atom in a definite cell. Various interpolation schemes covering both time scales are discussed. For coherent scattering and intermediate q, the energy spread is expected to show a minimum whenever q corresponds to a diffraction peak. For very small q the standard macroscopic description of density fluctuations is applicable. The limits of the various (q) and (w) domains and the validity of various approximations are discussed by a method of moments. The possibility of observing discrete transitions due to internal degrees of freedom in polyatomic molecules, in spite of the 'Doppler width' caused by translational motions, is also examined. (author) [French] L'auteur examine les donnees neutroniques sur les mouvements dans les liquides normaux, bien au-dessous du point critique, et les classe d'apres l'ordre de grandeur des transferts de quantite de mouvement {Dirac_h}q et des transferts d'energie {Dirac_h}w. Pour les grands transferts de, quantite de mouvement, un modele de gaz parfait est valable. En ce qui concerne les faibles valeurs de q et la diffussion incoherente, les principaux effets sont lies a l'existence de deux temps caracteristiques: la periode d'oscillation d'un atome dans sa cellule et la duree moyenne de vie de l'atome dans une cellule determinee. L'auteur etudie divers systemes d'interpolation se rapportant aux deux echelles de temps. Pour la diffusion coherente et les valeurs intermediaires de q, on presume que le spectre d'energie accuse un minimum chaque fois que q correspond a un pic de

  8. Normal distal pulmonary vein anatomy

    Directory of Open Access Journals (Sweden)

    Wiesława Klimek-Piotrowska

    2016-01-01

    Full Text Available Background. It is well known that the pulmonary veins (PVs, especially their myocardial sleeves play a critical role in the initiation and maintenance of atrial fibrillation. Understanding the PV anatomy is crucial for the safety and efficacy of all procedures performed on PVs. The aim of this study was to present normal distal PV anatomy and to create a juxtaposition of all PV ostium variants.Methods. A total of 130 randomly selected autopsied adult human hearts (Caucasian were examined. The number of PVs ostia was evaluated and their diameter was measured. The ostium-to-last-tributary distance and macroscopic presence of myocardial sleeves were also evaluated.Results. Five hundred forty-one PV ostia were identified. Four classical PV ostia patterns (two left and two right PVs were observed in 70.8% of all cases. The most common variant was the classical pattern with additional middle right PV (19.2%, followed by the common ostium for the left superior and the inferior PVs (4.44%. Mean diameters of PV ostia (for the classical pattern were: left superior = 13.8 ± 2.9 mm; left inferior = 13.3 ± 3.4 mm; right superior = 14.3 ± 2.9 mm; right inferior = 13.7 ± 3.3 mm. When present, the additional middle right PV ostium had the smallest PV ostium diameter in the heart (8.2 ± 4.1 mm. The mean ostium-to-last-tributary (closest to the atrium distances were: left superior = 15.1 ± 4.6 mm; left inferior = 13.5 ± 4.0 mm; right superior = 11.8 ± 4.0 mm; right inferior = 11.0 ± 3.7 mm. There were no statistically significant differences between sexes in ostia diameters and ostium-to-last-tributary distances.Conclusion. Only 71% of the cases have four standard pulmonary veins. The middle right pulmonary vein is present in almost 20% of patients. Presented data can provide useful information for the clinicians during interventional procedures or radiologic examinations of PVs.

  9. Differential Gene Expression of Fibroblasts: Keloid versus Normal

    Directory of Open Access Journals (Sweden)

    Michael F. Angel

    2002-11-01

    Full Text Available Abstract: This study investigated gene regulation and unique gene products in both keloid (KDF and normal (NDF dermal fibroblasts in established cell lines. For gene regulation, NDF versus KDF were compared using Clontech's Atlas™ Human cDNA Expression Array while unique gene products were studied using RNA Fingerprinting Kit. RNA from each sample was converted to cDNA using oligo-dT primers. Down-regulated genes using Atlas Array in KDF were 1 60 S ribosomal protein, 2 Thioredoxin dependent peroxidase, 3 Nuclease sensitive element DNA binding protein, 4 c-myc purine-binding transcription factor, 5 c-AMP dependent protein kinase, and, 6 Heat Shock Protein 90 kDa. Genes that are up regulated in KDF were 1 Tubulin and 2 Heat Shock Protein 27 kDa. With the differential display, we found 17 bands unique to both KDF and NDF. The specific gene and the manner in which they were differentially regulated have direct implications to understanding keloid fibroblast proliferation.

  10. Role of Stroma-Derived Extracellular Matrix in Regulation of Growth and Hormonal Responsiveness of Normal and Cancerous Human Breast Epithelium

    National Research Council Canada - National Science Library

    Woodward, Terry

    1997-01-01

    Specific extracellular matrix (ECM) proteins and their cellular receptors (integrins) are required for normal mammary gland morphogenesis and differentiation, while their expression is dramatically altered during tumorigenesis...

  11. MR guided spatial normalization of SPECT scans

    International Nuclear Information System (INIS)

    Crouch, B.; Barnden, L.R.; Kwiatek, R.

    2010-01-01

    Full text: In SPECT population studies where magnetic resonance (MR) scans are also available, the higher resolution of the MR scans allows for an improved spatial normalization of the SPECT scans. In this approach, the SPECT images are first coregistered to their corresponding MR images by a linear (affine) transformation which is calculated using SPM's mutual information maximization algorithm. Non-linear spatial normalization maps are then computed either directly from the MR scans using SPM's built in spatial normalization algorithm, or, from segmented TI MR images using DARTEL, an advanced diffeomorphism based spatial normalization algorithm. We compare these MR based methods to standard SPECT based spatial normalization for a population of 27 fibromyalgia patients and 25 healthy controls with spin echo T 1 scans. We identify significant perfusion deficits in prefrontal white matter in FM patients, with the DARTEL based spatial normalization procedure yielding stronger statistics than the standard SPECT based spatial normalization. (author)

  12. Anomalous normal mode oscillations in semiconductor microcavities

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H. [Univ. of Oregon, Eugene, OR (United States). Dept. of Physics; Hou, H.Q.; Hammons, B.E. [Sandia National Labs., Albuquerque, NM (United States)

    1997-04-01

    Semiconductor microcavities as a composite exciton-cavity system can be characterized by two normal modes. Under an impulsive excitation by a short laser pulse, optical polarizations associated with the two normal modes have a {pi} phase difference. The total induced optical polarization is then expected to exhibit a sin{sup 2}({Omega}t)-like oscillation where 2{Omega} is the normal mode splitting, reflecting a coherent energy exchange between the exciton and cavity. In this paper the authors present experimental studies of normal mode oscillations using three-pulse transient four wave mixing (FWM). The result reveals surprisingly that when the cavity is tuned far below the exciton resonance, normal mode oscillation in the polarization is cos{sup 2}({Omega}t)-like, in contrast to what is expected form the simple normal mode model. This anomalous normal mode oscillation reflects the important role of virtual excitation of electronic states in semiconductor microcavities.

  13. Protein politics

    NARCIS (Netherlands)

    Vijver, Marike

    2005-01-01

    This study is part of the program of the interdisciplinary research group Profetas (protein foods, environment, technology and society). Profetas consists of technological, environmental and socio-economic research projects on protein food systems which result in the development of scenarios and

  14. Protein adhesives

    Science.gov (United States)

    Charles R. Frihart; Linda F. Lorenz

    2018-01-01

    Nature uses a wide variety of chemicals for providing adhesion internally (e.g., cell to cell) and externally (e.g., mussels to ships and piers). This adhesive bonding is chemically and mechanically complex, involving a variety of proteins, carbohydrates, and other compounds.Consequently,the effect of protein structures on adhesive properties is only partially...

  15. Tau protein

    DEFF Research Database (Denmark)

    Frederiksen, Jette Lautrup Battistini; Kristensen, Kim; Bahl, Jmc

    2011-01-01

    Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. Objective: To investigate the association between tau protein concentration and 14......-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review. Methods: A total of 66 patients with MS and/or ON from...... the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. Results: The study shows a significantly increased concentration of tau...

  16. Early Alzheimer-type lesions in cognitively normal subjects.

    Science.gov (United States)

    Tsartsalis, Stergios; Xekardaki, Aikaterini; Hof, Patrick R; Kövari, Enikö; Bouras, Constantin

    2018-02-01

    Amyloid deposits and tau-immunoreactive neurofibrillary tangles, together with neuronal and synaptic loss, are the neuropathological hallmarks of Alzheimer's disease (AD). Both proteins are present in the normal brain during aging. However, the temporal sequence of their involvement in the onset of AD pathology remains controversial. To define whether amyloid β protein deposits or tau protein lesions appear first during normal brain aging, we performed an immunohistological study on serial sections from 105 autopsy brains (age range: 40-104 years) from patients free of clinical signs of cognitive decline, using anti-tau (AT8) and anti-amyloid (4G8) antibodies in the hippocampus, entorhinal cortex, inferior temporal cortex (Brodmann area 20), prefrontal cortex (Brodmann area 9), occipital cortex (Brodmann areas 17 and 18), and in the brainstem. All cases older than 48 years displayed at least a few neurofibrillary tangles, which appeared more frequently in the entorhinal than in the transentorhinal cortex. Tau pathology in these areas preceded tau inclusions in the brainstem. Furthermore, the first site of the apparition of tau pathology is inconsistent, being the entorhinal cortex in most cases, and in fewer cases, the transentorhinal region. There was no case presenting with amyloid deposition in the absence of neurofibrillary tangles, lending evidence to the fact that neurofibrillary tangles appear earlier than amyloid plaques during normal brain aging. However, the role of amyloid in promoting tau deposition cannot be excluded in some cases but may not represent the sole mechanism of disease induction and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Correlated random sampling for multivariate normal and log-normal distributions

    International Nuclear Information System (INIS)

    Žerovnik, Gašper; Trkov, Andrej; Kodeli, Ivan A.

    2012-01-01

    A method for correlated random sampling is presented. Representative samples for multivariate normal or log-normal distribution can be produced. Furthermore, any combination of normally and log-normally distributed correlated variables may be sampled to any requested accuracy. Possible applications of the method include sampling of resonance parameters which are used for reactor calculations.

  18. An individual urinary proteome analysis in normal human beings to define the minimal sample number to represent the normal urinary proteome

    Directory of Open Access Journals (Sweden)

    Liu Xuejiao

    2012-11-01

    Full Text Available Abstract Background The urinary proteome has been widely used for biomarker discovery. A urinary proteome database from normal humans can provide a background for discovery proteomics and candidate proteins/peptides for targeted proteomics. Therefore, it is necessary to define the minimum number of individuals required for sampling to represent the normal urinary proteome. Methods In this study, inter-individual and inter-gender variations of urinary proteome were taken into consideration to achieve a representative database. An individual analysis was performed on overnight urine samples from 20 normal volunteers (10 males and 10 females by 1DLC/MS/MS. To obtain a representative result of each sample, a replicate 1DLCMS/MS analysis was performed. The minimal sample number was estimated by statistical analysis. Results For qualitative analysis, less than 5% of new proteins/peptides were identified in a male/female normal group by adding a new sample when the sample number exceeded nine. In addition, in a normal group, the percentage of newly identified proteins/peptides was less than 5% upon adding a new sample when the sample number reached 10. Furthermore, a statistical analysis indicated that urinary proteomes from normal males and females showed different patterns. For quantitative analysis, the variation of protein abundance was defined by spectrum count and western blotting methods. And then the minimal sample number for quantitative proteomic analysis was identified. Conclusions For qualitative analysis, when considering the inter-individual and inter-gender variations, the minimum sample number is 10 and requires a balanced number of males and females in order to obtain a representative normal human urinary proteome. For quantitative analysis, the minimal sample number is much greater than that for qualitative analysis and depends on the experimental methods used for quantification.

  19. Heat shock proteins of higher plants

    International Nuclear Information System (INIS)

    Key, J.L.; Lin, C.Y.; Chen, Y.M.

    1981-01-01

    The pattern of protein synthesis changes rapidly and dramatically when the growth temperture of soybean seedling tissue is increased from 28 0 C (normal) to about 40 0 C (heat shock). The synthesis of normal proteins is greatly decreased and a new set of proteins, heat shock proteins, is induced. The heat shock proteins of soybean consist of 10 new bands on one-dimensional NaDodSO 4 gels; a more complex pattern is observed on two-dimensional gels. when the tissue is returned to 28 0 C after 4 hr at 40 0 C, there is progressive decline in the synthesis of heat shock proteins and reappearance of a normal pattern of synthesis by 3 or 4 hr. In vitro translation of poly(A) + RNAs isolated from tissued grown at 28 and 40 0 C shows that the heat shock proteins are translated from a ndw set of mRNAs induced at 40 0 C; furthermore, the abundant class mRNAs for many of the normal proteins persist even though they are translated weakly (or not at all) in vivo at 40 or 42.5 0 C. The heat shock response in soybean appears similar to the much-studied heat shock phenomenon in Drosophila

  20. Normalizing biomedical terms by minimizing ambiguity and variability

    Directory of Open Access Journals (Sweden)

    McNaught John

    2008-04-01

    Full Text Available Abstract Background One of the difficulties in mapping biomedical named entities, e.g. genes, proteins, chemicals and diseases, to their concept identifiers stems from the potential variability of the terms. Soft string matching is a possible solution to the problem, but its inherent heavy computational cost discourages its use when the dictionaries are large or when real time processing is required. A less computationally demanding approach is to normalize the terms by using heuristic rules, which enables us to look up a dictionary in a constant time regardless of its size. The development of good heuristic rules, however, requires extensive knowledge of the terminology in question and thus is the bottleneck of the normalization approach. Results We present a novel framework for discovering a list of normalization rules from a dictionary in a fully automated manner. The rules are discovered in such a way that they minimize the ambiguity and variability of the terms in the dictionary. We evaluated our algorithm using two large dictionaries: a human gene/protein name dictionary built from BioThesaurus and a disease name dictionary built from UMLS. Conclusions The experimental results showed that automatically discovered rules can perform comparably to carefully crafted heuristic rules in term mapping tasks, and the computational overhead of rule application is small enough that a very fast implementation is possible. This work will help improve the performance of term-concept mapping tasks in biomedical information extraction especially when good normalization heuristics for the target terminology are not fully known.

  1. Normal form theory and spectral sequences

    OpenAIRE

    Sanders, Jan A.

    2003-01-01

    The concept of unique normal form is formulated in terms of a spectral sequence. As an illustration of this technique some results of Baider and Churchill concerning the normal form of the anharmonic oscillator are reproduced. The aim of this paper is to show that spectral sequences give us a natural framework in which to formulate normal form theory. © 2003 Elsevier Science (USA). All rights reserved.

  2. Denotational Aspects of Untyped Normalization by Evaluation

    DEFF Research Database (Denmark)

    Filinski, Andrzej; Rohde, Henning Korsholm

    2005-01-01

    of soundness (the output term, if any, is in normal form and ß-equivalent to the input term); identification (ß-equivalent terms are mapped to the same result); and completeness (the function is defined for all terms that do have normal forms). We also show how the semantic construction enables a simple yet...... formal correctness proof for the normalization algorithm, expressed as a functional program in an ML-like, call-by-value language. Finally, we generalize the construction to produce an infinitary variant of normal forms, namely Böhm trees. We show that the three-part characterization of correctness...

  3. Ultrasonographic features of normal lower ureters

    International Nuclear Information System (INIS)

    Kim, Young Soon; Bae, M. Y.; Park, K. J.; Jeon, H. S.; Lee, J. H.

    1990-01-01

    Although ultrasonographic evaluation of the normal ureters is difficult due to bowel gas, the lower segment of the normal ureters can be visualized using the urinary bladder as an acoustic window. Authors prospetively performed ultrasonography with the standard suprapubic technique and analyzed the ultrasonographic features of normal lower ureters in 79 cases(77%). Length of visualized segment of the distal ureter ranged frp, 1.5cm to 7.2 cm and the visualized segment did not exceed 3.9mm in maximum diameter. Knowledge of sonographic features of the normal lower ureters can be helpful in the evaluation of pathologic or suspected pathologic conditions of the lower ureters

  4. Linearization of the Bradford Protein Assay

    OpenAIRE

    Ernst, Orna; Zor, Tsaffrir

    2010-01-01

    Determination of microgram quantities of protein in the Bradford Coomassie brilliant blue assay is accomplished by measurement of absorbance at 590 nm. This most common assay enables rapid and simple protein quantification in cell lysates, cellular fractions, or recombinant protein samples, for the purpose of normalization of biochemical measurements. However, an intrinsic nonlinearity compromises the sensitivity and accuracy of this method. It is shown that under standard assay conditions, t...

  5. Characterization of tumour virus proteins, 2

    International Nuclear Information System (INIS)

    Higuchi, T.

    1977-01-01

    The structural protein in murine tumour virus P30 has been measured by radioiummunoassay. The titer of each serum was determined by using as antigen the purified Rauscher viral protein labeled with 125 iodine. Standard competition curve was constructed in order to determine the equivalent of protein to inhibit the precipitation reaction under limited antibody concentration. Competition by purified Kirsten virus suspension normal rat kidney cells, transformed-productive and transformed non-productive cells were measured in homologous and heterologous systems [pt

  6. Spinal cord normalization in multiple sclerosis.

    Science.gov (United States)

    Oh, Jiwon; Seigo, Michaela; Saidha, Shiv; Sotirchos, Elias; Zackowski, Kathy; Chen, Min; Prince, Jerry; Diener-West, Marie; Calabresi, Peter A; Reich, Daniel S

    2014-01-01

    Spinal cord (SC) pathology is common in multiple sclerosis (MS), and measures of SC-atrophy are increasingly utilized. Normalization reduces biological variation of structural measurements unrelated to disease, but optimal parameters for SC volume (SCV)-normalization remain unclear. Using a variety of normalization factors and clinical measures, we assessed the effect of SCV normalization on detecting group differences and clarifying clinical-radiological correlations in MS. 3T cervical SC-MRI was performed in 133 MS cases and 11 healthy controls (HC). Clinical assessment included expanded disability status scale (EDSS), MS functional composite (MSFC), quantitative hip-flexion strength ("strength"), and vibration sensation threshold ("vibration"). SCV between C3 and C4 was measured and normalized individually by subject height, SC-length, and intracranial volume (ICV). There were group differences in raw-SCV and after normalization by height and length (MS vs. HC; progressive vs. relapsing MS-subtypes, P normalization by length (EDSS:r = -.43; MSFC:r = .33; strength:r = .38; vibration:r = -.40), and height (EDSS:r = -.26; MSFC:r = .28; strength:r = .22; vibration:r = -.29), but diminished with normalization by ICV (EDSS:r = -.23; MSFC:r = -.10; strength:r = .23; vibration:r = -.35). In relapsing MS, normalization by length allowed statistical detection of correlations that were not apparent with raw-SCV. SCV-normalization by length improves the ability to detect group differences, strengthens clinical-radiological correlations, and is particularly relevant in settings of subtle disease-related SC-atrophy in MS. SCV-normalization by length may enhance the clinical utility of measures of SC-atrophy. Copyright © 2014 by the American Society of Neuroimaging.

  7. An atlas of normal skeletal scintigraphy

    International Nuclear Information System (INIS)

    Flanagan, J.J.; Maisey, M.N.

    1985-01-01

    This atlas was compiled to provide the neophyte as well as the experienced radiologist and the nuclear medicine physician with a reference on normal skeletal scintigraphy as an aid in distinguishing normal variations in skeletal uptake from abnormal findings. Each skeletal scintigraph is labeled, and utilizing an identical scale, a relevant skeletal photograph and radiograph are placed adjacent to the scintigraph

  8. On normal modes in classical Hamiltonian systems

    NARCIS (Netherlands)

    van Groesen, Embrecht W.C.

    1983-01-01

    Normal modes of Hamittonian systems that are even and of classical type are characterized as the critical points of a normalized kinetic energy functional on level sets of the potential energy functional. With the aid of this constrained variational formulation the existence of at least one family

  9. Computerized three-dimensional normal atlas

    International Nuclear Information System (INIS)

    Mano, Isamu; Suto, Yasuzo; Suzuki, Masataka; Iio, Masahiro.

    1990-01-01

    This paper presents our ongoing project in which normal human anatomy and its quantitative data are systematically arranged in a computer. The final product, the Computerized Three-Dimensional Normal Atlas, will be able to supply tomographic images in any direction, 3-D images, and coded information on organs, e.g., anatomical names, CT numbers, and T 1 and T 2 values. (author)

  10. Pseudo--Normals for Signed Distance Computation

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Bærentzen, Jakob Andreas

    2003-01-01

    the relation of a point to a mesh. At the vertices and edges of a triangle mesh, the surface is not \\$C\\^1\\$ continuous. Hence, the normal is undefined at these loci. Thürmer and Wüthrich proposed the \\$\\backslash\\$emph{angle weighted pseudo--normal} as a way to deal with this problem. In this paper, we...

  11. The lambda sigma calculus and strong normalization

    DEFF Research Database (Denmark)

    Schack-Nielsen, Anders; Schürmann, Carsten

    Explicit substitution calculi can be classified into several dis- tinct categories depending on whether they are confluent, meta-confluent, strong normalization preserving, strongly normalizing, simulating, fully compositional, and/or local. In this paper we present a variant of the λσ-calculus, ...

  12. a Recursive Approach to Compute Normal Forms

    Science.gov (United States)

    HSU, L.; MIN, L. J.; FAVRETTO, L.

    2001-06-01

    Normal forms are instrumental in the analysis of dynamical systems described by ordinary differential equations, particularly when singularities close to a bifurcation are to be characterized. However, the computation of a normal form up to an arbitrary order is numerically hard. This paper focuses on the computer programming of some recursive formulas developed earlier to compute higher order normal forms. A computer program to reduce the system to its normal form on a center manifold is developed using the Maple symbolic language. However, it should be stressed that the program relies essentially on recursive numerical computations, while symbolic calculations are used only for minor tasks. Some strategies are proposed to save computation time. Examples are presented to illustrate the application of the program to obtain high order normalization or to handle systems with large dimension.

  13. Normal zone soliton in large composite superconductors

    International Nuclear Information System (INIS)

    Kupferman, R.; Mints, R.G.; Ben-Jacob, E.

    1992-01-01

    The study of normal zone of finite size (normal domains) in superconductors, has been continuously a subject of interest in the field of applied superconductivity. It was shown that in homogeneous superconductors normal domains are always unstable, so that if a normal domain nucleates, it will either expand or shrink. While testing the stability of large cryostable composite superconductors, a new phenomena was found, the existence of stable propagating normal solitons. The formation of these propagating domains was shown to be a result of the high Joule power generated in the superconductor during the relatively long process of current redistribution between the superconductor and the stabilizer. Theoretical studies were performed in investigate the propagation of normal domains in large composite super conductors in the cryostable regime. Huang and Eyssa performed numerical calculations simulating the diffusion of heat and current redistribution in the conductor, and showed the existence of stable propagating normal domains. They compared the velocity of normal domain propagation with the experimental data, obtaining a reasonable agreement. Dresner presented an analytical method to solve this problem if the time dependence of the Joule power is given. He performed explicit calculations of normal domain velocity assuming that the Joule power decays exponentially during the process of current redistribution. In this paper, the authors propose a system of two one-dimensional diffusion equations describing the dynamics of the temperature and the current density distributions along the conductor. Numerical simulations of the equations reconfirm the existence of propagating domains in the cryostable regime, while an analytical investigation supplies an explicit formula for the velocity of the normal domain

  14. Study of chromium speciation in normal and diabetic rats by activable enriched stable isotope technique

    International Nuclear Information System (INIS)

    Feng, W.Y.; Qian, Q.F.; Ding, W.J.; Chai, Z.F.

    2000-01-01

    Chromium speciation was investigated in the liver cytosol, serum and urine of normal and diabetic rats after a single intravenous injection of enriched stable isotope 50 Cr tracer solution. Sephadex G-25 gel chromatography combined with instrumental neutron activation analysis was used to isolate and characterize protein-bound chromium in the above materials. The results indicate that Cr is mainly combined with a high-molecular-weight protein either in liver cytosol or serum. A low-molecular-weight, Cr-containing compound (LMWCr) was found in all the observed liver, serum and urine samples of both normal and diabetic rats. Chromium is excreted chiefly as LMWCr in urine. (author)

  15. Strength of Gamma Rhythm Depends on Normalization

    Science.gov (United States)

    Ray, Supratim; Ni, Amy M.; Maunsell, John H. R.

    2013-01-01

    Neuronal assemblies often exhibit stimulus-induced rhythmic activity in the gamma range (30–80 Hz), whose magnitude depends on the attentional load. This has led to the suggestion that gamma rhythms form dynamic communication channels across cortical areas processing the features of behaviorally relevant stimuli. Recently, attention has been linked to a normalization mechanism, in which the response of a neuron is suppressed (normalized) by the overall activity of a large pool of neighboring neurons. In this model, attention increases the excitatory drive received by the neuron, which in turn also increases the strength of normalization, thereby changing the balance of excitation and inhibition. Recent studies have shown that gamma power also depends on such excitatory–inhibitory interactions. Could modulation in gamma power during an attention task be a reflection of the changes in the underlying excitation–inhibition interactions? By manipulating the normalization strength independent of attentional load in macaque monkeys, we show that gamma power increases with increasing normalization, even when the attentional load is fixed. Further, manipulations of attention that increase normalization increase gamma power, even when they decrease the firing rate. Thus, gamma rhythms could be a reflection of changes in the relative strengths of excitation and normalization rather than playing a functional role in communication or control. PMID:23393427

  16. MR imaging of the ankle: Normal variants

    International Nuclear Information System (INIS)

    Noto, A.M.; Cheung, Y.; Rosenberg, Z.S.; Norman, A.; Leeds, N.E.

    1987-01-01

    Thirty asymptomatic ankles were studied with high-resolution surface coil MR imaging. The thirty ankles were reviewed for identification or normal structures. The MR appearance of the deltoid and posterior to talo-fibular ligaments, peroneous brevis and longus tendons, and posterior aspect of the tibial-talar joint demonstrated several normal variants not previously described. These should not be misinterpreted as pathologic processes. The specific findings included (1) cortical irregularity of the posterior tibial-talar joint in 27 of 30 cases which should not be mistaken for osteonecrois; (2) normal posterior talo-fibular ligament with irregular and frayed inhomogeneity, which represents a normal variant in seven of ten cases; and (3) fluid in the shared peroneal tendons sheath which may be confused for a longitudinal tendon tear in three of 30 cases. Ankle imaging with the use of MR is still a relatively new procedure. Further investigation is needed to better define normal anatomy as well as normal variants. The authors described several structures that normally present with variable MR imaging appearances. This is clinically significant in order to maintain a high sensitivity and specificity in MR imaging interpretation

  17. Protein space: a natural method for realizing the nature of protein universe.

    Science.gov (United States)

    Yu, Chenglong; Deng, Mo; Cheng, Shiu-Yuen; Yau, Shek-Chung; He, Rong L; Yau, Stephen S-T

    2013-02-07

    Current methods cannot tell us what the nature of the protein universe is concretely. They are based on different models of amino acid substitution and multiple sequence alignment which is an NP-hard problem and requires manual intervention. Protein structural analysis also gives a direction for mapping the protein universe. Unfortunately, now only a minuscule fraction of proteins' 3-dimensional structures are known. Furthermore, the phylogenetic tree representations are not unique for any existing tree construction methods. Here we develop a novel method to realize the nature of protein universe. We show the protein universe can be realized as a protein space in 60-dimensional Euclidean space using a distance based on a normalized distribution of amino acids. Every protein is in one-to-one correspondence with a point in protein space, where proteins with similar properties stay close together. Thus the distance between two points in protein space represents the biological distance of the corresponding two proteins. We also propose a natural graphical representation for inferring phylogenies. The representation is natural and unique based on the biological distances of proteins in protein space. This will solve the fundamental question of how proteins are distributed in the protein universe. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Defecography: A study of normal volunteers

    International Nuclear Information System (INIS)

    Shorvon, P.; Stevenson, G.W.; McHugh, S.; Somers, P.

    1987-01-01

    This study of young volunteers was set up in an effort to establish true normal measurements for defecography with minimum selection bias. The results describe the mean (and the range) for the following: anorectal angle; anorectal junction position at rest; excursion on lift, strain, and evacuation; anal canal length and degree of closure; and the frequency and degree of features such as rectocele and intussusception which have previously been called abnormalities. The results indicate that there is a very wide range of normal appearances. Knowledge of these normal variations is important to avoid overreporting and unnecessary surgery

  19. Nonlinear dynamics exploration through normal forms

    CERN Document Server

    Kahn, Peter B

    2014-01-01

    Geared toward advanced undergraduates and graduate students, this exposition covers the method of normal forms and its application to ordinary differential equations through perturbation analysis. In addition to its emphasis on the freedom inherent in the normal form expansion, the text features numerous examples of equations, the kind of which are encountered in many areas of science and engineering. The treatment begins with an introduction to the basic concepts underlying the normal forms. Coverage then shifts to an investigation of systems with one degree of freedom that model oscillations

  20. Normal-dispersion microresonator Kerr frequency combs

    Directory of Open Access Journals (Sweden)

    Xue Xiaoxiao

    2016-06-01

    Full Text Available Optical microresonator-based Kerr frequency comb generation has developed into a hot research area in the past decade. Microresonator combs are promising for portable applications due to their potential for chip-level integration and low power consumption. According to the group velocity dispersion of the microresonator employed, research in this field may be classified into two categories: the anomalous dispersion regime and the normal dispersion regime. In this paper, we discuss the physics of Kerr comb generation in the normal dispersion regime and review recent experimental advances. The potential advantages and future directions of normal dispersion combs are also discussed.

  1. Normal radiographic findings. 4. act. ed.

    International Nuclear Information System (INIS)

    Moeller, T.B.

    2003-01-01

    This book can serve the reader in three ways: First, it presents normal findings for all radiographic techniques including KM. Important data which are criteria of normal findings are indicated directly in the pictures and are also explained in full text and in summary form. Secondly, it teaches the systematics of interpreting a picture - how to look at it, what structures to regard in what order, and for what to look in particular. Checklists are presented in each case. Thirdly, findings are formulated in accordance with the image analysis procedure. All criteria of normal findings are defined in these formulations, which make them an important didactic element. (orig.)

  2. Normal radiographic findings. 4. act. ed.; Roentgennormalbefunde

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, T.B. [Gemeinschaftspraxis fuer Radiologie und Nuklearmedizin, Dillingen (Germany)

    2003-07-01

    This book can serve the reader in three ways: First, it presents normal findings for all radiographic techniques including KM. Important data which are criteria of normal findings are indicated directly in the pictures and are also explained in full text and in summary form. Secondly, it teaches the systematics of interpreting a picture - how to look at it, what structures to regard in what order, and for what to look in particular. Checklists are presented in each case. Thirdly, findings are formulated in accordance with the image analysis procedure. All criteria of normal findings are defined in these formulations, which make them an important didactic element. (orig.)

  3. The Glycome of Normal and Malignant Plasma Cells

    Science.gov (United States)

    Hose, Dirk; Andrulis, Mindaugas; Moreaux, Jèrôme; Hielscher, Thomas; Willhauck-Fleckenstein, Martina; Merling, Anette; Bertsch, Uta; Jauch, Anna; Goldschmidt, Hartmut; Klein, Bernard; Schwartz-Albiez, Reinhard

    2013-01-01

    The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10) and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i) malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii) be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii) Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14), t(4;14), hyperdiploidy, 1q21-gain and deletion of 13q14. iv) A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v) As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma. PMID:24386263

  4. The glycome of normal and malignant plasma cells.

    Directory of Open Access Journals (Sweden)

    Thomas M Moehler

    Full Text Available The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10 and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14, t(4;14, hyperdiploidy, 1q21-gain and deletion of 13q14. iv A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma.

  5. Imaging the corpus callosum, septum pellucidum and fornix in children: normal anatomy and variations of normality

    International Nuclear Information System (INIS)

    Griffiths, Paul D.; Batty, Ruth; Connolly, Dan J.A.; Reeves, Michael J.

    2009-01-01

    The midline structures of the supra-tentorial brain are important landmarks for judging if the brain has formed correctly. In this article, we consider the normal appearances of the corpus callosum, septum pellucidum and fornix as shown on MR imaging in normal and near-normal states. (orig.)

  6. [FTIR study on the normal and cancerous stomach tissues].

    Science.gov (United States)

    Tong, Y; Lin, Y

    2001-06-01

    Tissues of cancerous and corresponding normal stomach were studied by FTIR technique. The results showed that there are obvious differences between FTIR spectra of them in spectral parameters such as frequency, intensity and band shape etc. The changes involving the phosphate symmetric stretching nu s, PO2- and asymmetric stretching nu as, PO2- modes, the CH3 and CH2 groups stretching (nu s, CH2, nu as, CH3) and bending (delta CH2) modes and the C-O stretching nu C-O mode were discussed. In addition, the changes of structure of hydrogen-bonding of nucleic acid and cell proteins and the packing and the conformational structure of the membrance lipids were analysed further. The average wavenumber of band of nu s, PO2- shifted from 1,080.92 cm-1 to 1,085.93 cm-1 and that of nu as, PO2- shifted from 1,239.64 cm-1 to 1,238.73 cm-1 which indicated that the degree of hydrogen-bonding formed by oxygen atom of the phosphodiester groups of nucleic acids was increased. The average wavenumber of band of delta CH2 of membrance lipids shifted from 1,455.23 cm-1 to 1,457.37 cm-1 that suggested that the conformational structure of the methylene chains of membrance lipids is more disordered than in normal tissues. The shift of band of nu C-O of cell proteins from 1,166.08 cm-1 to 1,166.58 cm-1 indicated that the hydrogen-bond of cell proteins become weaker.

  7. The total plasmatic estriol on normal gestation

    International Nuclear Information System (INIS)

    Thiesen, A.L.

    1980-01-01

    The total plasmatic estriol in normal pregnants was determinated by radioimmunological method using estriol labelled with sup(125)I. The obtained results presented similar results in comparison with methods using sup(19)C and sup(3)H. (author)

  8. Terre Haute and the Normal School Fire

    Science.gov (United States)

    Ferreira, Allen

    1974-01-01

    This paper examines the short history of the Terre Haute Normal School before its tragic burning on April 9, 1888 and relates that story to the course of events immediately following the fire. (Author)

  9. Looking at Your Newborn: What's Normal

    Science.gov (United States)

    ... features that may make a normal newborn look strange are temporary. After all, babies develop while immersed ... sleepy during the first day or two of life. Many new parents become concerned about their newborn's ...

  10. Mental Health: What's Normal, What's Not?

    Science.gov (United States)

    Healthy Lifestyle Adult health Understanding what's considered normal mental health can be tricky. See how feelings, thoughts and behaviors determine mental health and how to recognize if you or a ...

  11. Compressed normalized block difference for object tracking

    Science.gov (United States)

    Gao, Yun; Zhang, Dengzhuo; Cai, Donglan; Zhou, Hao; Lan, Ge

    2018-04-01

    Feature extraction is very important for robust and real-time tracking. Compressive sensing provided a technical support for real-time feature extraction. However, all existing compressive tracking were based on compressed Haar-like feature, and how to compress many more excellent high-dimensional features is worth researching. In this paper, a novel compressed normalized block difference feature (CNBD) was proposed. For resisting noise effectively in a highdimensional normalized pixel difference feature (NPD), a normalized block difference feature extends two pixels in the original formula of NPD to two blocks. A CNBD feature can be obtained by compressing a normalized block difference feature based on compressive sensing theory, with the sparse random Gaussian matrix as the measurement matrix. The comparative experiments of 7 trackers on 20 challenging sequences showed that the tracker based on CNBD feature can perform better than other trackers, especially than FCT tracker based on compressed Haar-like feature, in terms of AUC, SR and Precision.

  12. Forced Normalization: Antagonism Between Epilepsy and Psychosis.

    Science.gov (United States)

    Kawakami, Yasuhiko; Itoh, Yasuhiko

    2017-05-01

    The antagonism between epilepsy and psychosis has been discussed for a long time. Landolt coined the term "forced normalization" in the 1950s to describe psychotic episodes associated with the remission of seizures and disappearance of epileptiform activity on electroencephalograms in individuals with epilepsy. Since then, neurologists and psychiatrists have been intrigued by this phenomenon. However, although collaborative clinical studies and basic experimental researches have been performed, the mechanism of forced normalization remains unknown. In this review article, we present a historical overview of the concept of forced normalization, and discuss potential pathogenic mechanisms and clinical diagnosis. We also discuss the role of dopamine, which appears to be a key factor in the mechanism of forced normalization. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Efficient CEPSTRAL Normalization for Robust Speech Recognition

    National Research Council Canada - National Science Library

    Liu, Fu-Hua; Stern, Richard M; Huang, Xuedong; Acero, Alejandro

    1993-01-01

    .... We compare the performance of these algorithms with the very simple RASTA and cepstral mean normalization procedures, describing the performance of these algorithms in the context of the 1992 DARPA...

  14. Evaluation of Normalization Methods on GeLC-MS/MS Label-Free Spectral Counting Data to Correct for Variation during Proteomic Workflows

    Science.gov (United States)

    Gokce, Emine; Shuford, Christopher M.; Franck, William L.; Dean, Ralph A.; Muddiman, David C.

    2011-12-01

    Normalization of spectral counts (SpCs) in label-free shotgun proteomic approaches is important to achieve reliable relative quantification. Three different SpC normalization methods, total spectral count (TSpC) normalization, normalized spectral abundance factor (NSAF) normalization, and normalization to selected proteins (NSP) were evaluated based on their ability to correct for day-to-day variation between gel-based sample preparation and chromatographic performance. Three spectral counting data sets obtained from the same biological conidia sample of the rice blast fungus Magnaporthe oryzae were analyzed by 1D gel and liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Equine myoglobin and chicken ovalbumin were spiked into the protein extracts prior to 1D-SDS- PAGE as internal protein standards for NSP. The correlation between SpCs of the same proteins across the different data sets was investigated. We report that TSpC normalization and NSAF normalization yielded almost ideal slopes of unity for normalized SpC versus average normalized SpC plots, while NSP did not afford effective corrections of the unnormalized data. Furthermore, when utilizing TSpC normalization prior to relative protein quantification, t-testing and fold-change revealed the cutoff limits for determining real biological change to be a function of the absolute number of SpCs. For instance, we observed the variance decreased as the number of SpCs increased, which resulted in a higher propensity for detecting statistically significant, yet artificial, change for highly abundant proteins. Thus, we suggest applying higher confidence level and lower fold-change cutoffs for proteins with higher SpCs, rather than using a single criterion for the entire data set. By choosing appropriate cutoff values to maintain a constant false positive rate across different protein levels (i.e., SpC levels), it is expected this will reduce the overall false negative rate, particularly for proteins with

  15. Normal and Abnormal Behavior in Early Childhood

    OpenAIRE

    Spinner, Miriam R.

    1981-01-01

    Evaluation of normal and abnormal behavior in the period to three years of age involves many variables. Parental attitudes, determined by many factors such as previous childrearing experience, the bonding process, parental psychological status and parental temperament, often influence the labeling of behavior as normal or abnormal. This article describes the forms of crying, sleep and wakefulness, and affective responses from infancy to three years of age.

  16. Right thoracic curvature in the normal spine

    Directory of Open Access Journals (Sweden)

    Masuda Keigo

    2011-01-01

    Full Text Available Abstract Background Trunk asymmetry and vertebral rotation, at times observed in the normal spine, resemble the characteristics of adolescent idiopathic scoliosis (AIS. Right thoracic curvature has also been reported in the normal spine. If it is determined that the features of right thoracic side curvature in the normal spine are the same as those observed in AIS, these findings might provide a basis for elucidating the etiology of this condition. For this reason, we investigated right thoracic curvature in the normal spine. Methods For normal spinal measurements, 1,200 patients who underwent a posteroanterior chest radiographs were evaluated. These consisted of 400 children (ages 4-9, 400 adolescents (ages 10-19 and 400 adults (ages 20-29, with each group comprised of both genders. The exclusion criteria were obvious chest and spinal diseases. As side curvature is minimal in normal spines and the range at which curvature is measured is difficult to ascertain, first the typical curvature range in scoliosis patients was determined and then the Cobb angle in normal spines was measured using the same range as the scoliosis curve, from T5 to T12. Right thoracic curvature was given a positive value. The curve pattern was organized in each collective three groups: neutral (from -1 degree to 1 degree, right (> +1 degree, and left ( Results In child group, Cobb angle in left was 120, in neutral was 125 and in right was 155. In adolescent group, Cobb angle in left was 70, in neutral was 114 and in right was 216. In adult group, Cobb angle in left was 46, in neutral was 102 and in right was 252. The curvature pattern shifts to the right side in the adolescent group (p Conclusions Based on standing chest radiographic measurements, a right thoracic curvature was observed in normal spines after adolescence.

  17. Advancing Normal Birth: Organizations, Goals, and Research

    OpenAIRE

    Hotelling, Barbara A.; Humenick, Sharron S.

    2005-01-01

    In this column, the support for advancing normal birth is summarized, based on a comparison of the goals of Healthy People 2010, Lamaze International, the Coalition for Improving Maternity Services, and the midwifery model of care. Research abstracts are presented to provide evidence that the midwifery model of care safely and economically advances normal birth. Rates of intervention experienced, as reported in the Listening to Mothers survey, are compared to the forms of care recommended by ...

  18. Distinguishing hyperhidrosis and normal physiological sweat production

    DEFF Research Database (Denmark)

    Thorlacius, Linnea; Gyldenløve, Mette; Zachariae, Claus

    2015-01-01

    of this study was to establish reference intervals for normal physiological axillary and palmar sweat production. METHODS: Gravimetric testing was performed in 75 healthy control subjects. Subsequently, these results were compared with findings in a cohort of patients with hyperhidrosis and with the results...... 100 mg/5 min. CONCLUSIONS: A sweat production rate of 100 mg/5 min as measured by gravimetric testing may be a reasonable cut-off value for distinguishing axillary and palmar hyperhidrosis from normal physiological sweat production....

  19. Normalization based K means Clustering Algorithm

    OpenAIRE

    Virmani, Deepali; Taneja, Shweta; Malhotra, Geetika

    2015-01-01

    K-means is an effective clustering technique used to separate similar data into groups based on initial centroids of clusters. In this paper, Normalization based K-means clustering algorithm(N-K means) is proposed. Proposed N-K means clustering algorithm applies normalization prior to clustering on the available data as well as the proposed approach calculates initial centroids based on weights. Experimental results prove the betterment of proposed N-K means clustering algorithm over existing...

  20. Sampling from the normal and exponential distributions

    International Nuclear Information System (INIS)

    Chaplin, K.R.; Wills, C.A.

    1982-01-01

    Methods for generating random numbers from the normal and exponential distributions are described. These involve dividing each function into subregions, and for each of these developing a method of sampling usually based on an acceptance rejection technique. When sampling from the normal or exponential distribution, each subregion provides the required random value with probability equal to the ratio of its area to the total area. Procedures written in FORTRAN for the CYBER 175/CDC 6600 system are provided to implement the two algorithms

  1. Protein and energy metabolism in two lines of chickens selected for growth on high or low protein diets

    DEFF Research Database (Denmark)

    Chwalibog, André; Eggum, B O; Sørensen, Peter

    1983-01-01

    Genetic adaptation was investigated in broilers selected for seven generations on a normal (A) or a low (B) protein diet. Protein and energy metabolism were studied in males from these selected lines fed on a diet of intermediate protein content. All selected birds retained more nitrogen than those...

  2. Papillomavirus E6 proteins

    International Nuclear Information System (INIS)

    Howie, Heather L.; Katzenellenbogen, Rachel A.; Galloway, Denise A.

    2009-01-01

    The papillomaviruses are small DNA viruses that encode approximately eight genes, and require the host cell DNA replication machinery for their viral DNA replication. Thus papillomaviruses have evolved strategies to induce host cell DNA synthesis balanced with strategies to protect the cell from unscheduled replication. While the papillomavirus E1 and E2 genes are directly involved in viral replication by binding to and unwinding the origin of replication, the E6 and E7 proteins have auxillary functions that promote proliferation. As a consequence of disrupting the normal checkpoints that regulate cell cycle entry and progression, the E6 and E7 proteins play a key role in the oncogenic properties of human papillomaviruses with a high risk of causing anogenital cancers (HR HPVs). As a consequence, E6 and E7 of HR HPVs are invariably expressed in cervical cancers. This article will focus on the E6 protein and its numerous activities including inactivating p53, blocking apoptosis, activating telomerase, disrupting cell adhesion, polarity and epithelial differentiation, altering transcription and reducing immune recognition

  3. Protein nanoparticles for therapeutic protein delivery.

    Science.gov (United States)

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  4. Differential expression of splicing variants of the human caldesmon gene (CALD1) in glioma neovascularization versus normal brain microvasculature

    NARCIS (Netherlands)

    P.P. Zheng (Pingpin); A.M. Sieuwerts (Anieta); T.M. Luider (Theo); M.M. van der Weiden (Marcel); J.M. Kros (Johan); P.A.E. Sillevis Smitt (Peter)

    2004-01-01

    textabstractCaldesmon is a cytoskeleton-associated protein which has not yet been related to neoplastic angiogenesis. In this study we investigated the expression of the caldesmon gene (CALD1) splicing variants and the protein expression level in glioma microvessels versus normal

  5. Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia

    Directory of Open Access Journals (Sweden)

    R. Walter Heinrichs

    2017-01-01

    Full Text Available This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB composite score (T=50 ± 10 and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n=39 had greater cortical thickness than both cognitively normal (n=17 and below-normal range (n=49 patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n=24 or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.

  6. Protein-Protein Interaction Databases

    DEFF Research Database (Denmark)

    Szklarczyk, Damian; Jensen, Lars Juhl

    2015-01-01

    Years of meticulous curation of scientific literature and increasingly reliable computational predictions have resulted in creation of vast databases of protein interaction data. Over the years, these repositories have become a basic framework in which experiments are analyzed and new directions...

  7. A phylogenetic analysis of normal modes evolution in enzymes and its relationship to enzyme function.

    Science.gov (United States)

    Lai, Jason; Jin, Jing; Kubelka, Jan; Liberles, David A

    2012-09-21

    Since the dynamic nature of protein structures is essential for enzymatic function, it is expected that functional evolution can be inferred from the changes in protein dynamics. However, dynamics can also diverge neutrally with sequence substitution between enzymes without changes of function. In this study, a phylogenetic approach is implemented to explore the relationship between enzyme dynamics and function through evolutionary history. Protein dynamics are described by normal mode analysis based on a simplified harmonic potential force field applied to the reduced C(α) representation of the protein structure while enzymatic function is described by Enzyme Commission numbers. Similarity of the binding pocket dynamics at each branch of the protein family's phylogeny was analyzed in two ways: (1) explicitly by quantifying the normal mode overlap calculated for the reconstructed ancestral proteins at each end and (2) implicitly using a diffusion model to obtain the reconstructed lineage-specific changes in the normal modes. Both explicit and implicit ancestral reconstruction identified generally faster rates of change in dynamics compared with the expected change from neutral evolution at the branches of potential functional divergences for the α-amylase, D-isomer-specific 2-hydroxyacid dehydrogenase, and copper-containing amine oxidase protein families. Normal mode analysis added additional information over just comparing the RMSD of static structures. However, the branch-specific changes were not statistically significant compared to background function-independent neutral rates of change of dynamic properties and blind application of the analysis would not enable prediction of changes in enzyme specificity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Parser Adaptation for Social Media by Integrating Normalization

    NARCIS (Netherlands)

    van der Goot, Rob; van Noord, Gerardus

    This work explores normalization for parser adaptation. Traditionally, normalization is used as separate pre-processing step. We show that integrating the normalization model into the parsing algorithm is beneficial. This way, multiple normalization candidates can be leveraged, which improves

  9. Linear regression and the normality assumption.

    Science.gov (United States)

    Schmidt, Amand F; Finan, Chris

    2017-12-16

    Researchers often perform arbitrary outcome transformations to fulfill the normality assumption of a linear regression model. This commentary explains and illustrates that in large data settings, such transformations are often unnecessary, and worse may bias model estimates. Linear regression assumptions are illustrated using simulated data and an empirical example on the relation between time since type 2 diabetes diagnosis and glycated hemoglobin levels. Simulation results were evaluated on coverage; i.e., the number of times the 95% confidence interval included the true slope coefficient. Although outcome transformations bias point estimates, violations of the normality assumption in linear regression analyses do not. The normality assumption is necessary to unbiasedly estimate standard errors, and hence confidence intervals and P-values. However, in large sample sizes (e.g., where the number of observations per variable is >10) violations of this normality assumption often do not noticeably impact results. Contrary to this, assumptions on, the parametric model, absence of extreme observations, homoscedasticity, and independency of the errors, remain influential even in large sample size settings. Given that modern healthcare research typically includes thousands of subjects focusing on the normality assumption is often unnecessary, does not guarantee valid results, and worse may bias estimates due to the practice of outcome transformations. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Quantitative thallium-201 myocardial exercise scintigraphy in normal subjects and patients with normal coronary arteries

    International Nuclear Information System (INIS)

    Niemeyer, M.G.; St. Antonius Hospital Nieuwegein; Laarman, G.J.; Lelbach, S.; Cramer, M.J.; Ascoop, C.A.P.L.; Verzijlbergen, J.F.; Wall, E.E. van der; Zwinderman, A.H.; Pauwels, E.K.J.

    1990-01-01

    Quantitative thallium-201 myocardial exercise scintigraphy was tested in two patient populations representing alternative standards for cardiac normality: group I comprised 18 male uncatherized patients with a low likelihood of coronary artery disease (CAD); group II contained 41 patients with normal coronary arteriograms. Group I patients were younger, they achieved a higher rate-pressure product than group II patients; all had normal findings by phisical examination and electrocardiography at rest and exercise. Group II patients comprised 21 females, 11 patients showed abnormal electrocardiography at rest, and five patients showed ischemic ST depression during exercise. Twelve patients had sign of minimal CAD. Twelve patients revealed abnormal visual and quantitative thallium findings, three of these patients had minimal CAD. Profiles of uptake and washout of thallium-201 were derived from both patient groups, and compared with normal limits developed by Maddahi et al. Furthermore, low likelihood and angiographically normal patients may differ substantially, and both sets of normal patients should be considered when establishing criteria of abnormality in exercise thallium imaging. When commercial software containing normal limits for quantitative analysis of exercise thallium-201 imaging is used in clinical practice, it is mandatory to compare these with normal limits of uptake and washout of thallium-201, derived from the less heterogeneous group of low-likelihood subjects, which should be used in selecting a normal population to define normality. (author). 37 refs.; 3 figs; 1 tab

  11. Immunologic analyses of mouse cystathionase in normal and leukemic cells

    International Nuclear Information System (INIS)

    Bikel, I.; Faibes, D.; Uren, J.R.; Livingston, D.M.

    1978-01-01

    Rabbit antisera have been raised against mouse liver cystathionase and shown to possess enzyme neutralizing activity. Agar gel double immunodiffusion analyses demonstrated that both mouse liver cystathionase and rat liver cystathionase react with the antisera, the latter enzyme being completely cross-reactive with the former. Following radioiodination of the purified rat liver enzyme, a double antibody radioimmunoassay was developed in which greater than 90% of the labeled protein could be specifically precipitated with the anti-mouse cystathionase antibodies. In this test the purified rat liver and mouse liver enzymes were virtually indistinguishable, generating superimposable competition displacement curves on a protein mass basis. These results indicate that both enzymes are immunologically identical, thus validating the use of the rat in lieu of the murine liver enzyme as radiolabeled tracer in an assay for mouse cystathionase. In addition, competition radioimmunoassays demonstrated that the immunological reactivities of both the purified rat liver and mouse liver enzymes were equally heat sensitive. The sensitivity of the assay was determined to be 1 ng of enzyme protein/0.22 mL of assay mixture, and the assay could be used to detect the presence of enzyme protein in tissue homogenates of single mouse organs. Mouse or rat cross-reactivity with human liver cystathionase was incomplete; but, with the exception of heart and spleen, parallel radioimmunoassay competition displacement curves were obtained for cystathionase from different mouse organs including thymus. Extracts of 7-, 9-, and 10-month-old spontaneous AKR mouse thymomas were tested in the radioimmunoassay along with extracts of age-matched thymuses which were grossly tumor free. A reaction of nonidentity was observed for all of the tumor extracts while a reaction identical with that of the pure liver enzyme was found with all of the normal thymus extracts

  12. Normal people working in normal organizations with normal equipment: system safety and cognition in a mid-air collision.

    Science.gov (United States)

    de Carvalho, Paulo Victor Rodrigues; Gomes, José Orlando; Huber, Gilbert Jacob; Vidal, Mario Cesar

    2009-05-01

    A fundamental challenge in improving the safety of complex systems is to understand how accidents emerge in normal working situations, with equipment functioning normally in normally structured organizations. We present a field study of the en route mid-air collision between a commercial carrier and an executive jet, in the clear afternoon Amazon sky in which 154 people lost their lives, that illustrates one response to this challenge. Our focus was on how and why the several safety barriers of a well structured air traffic system melted down enabling the occurrence of this tragedy, without any catastrophic component failure, and in a situation where everything was functioning normally. We identify strong consistencies and feedbacks regarding factors of system day-to-day functioning that made monitoring and awareness difficult, and the cognitive strategies that operators have developed to deal with overall system behavior. These findings emphasize the active problem-solving behavior needed in air traffic control work, and highlight how the day-to-day functioning of the system can jeopardize such behavior. An immediate consequence is that safety managers and engineers should review their traditional safety approach and accident models based on equipment failure probability, linear combinations of failures, rules and procedures, and human errors, to deal with complex patterns of coincidence possibilities, unexpected links, resonance among system functions and activities, and system cognition.

  13. Computed tomography of the normal sternum

    International Nuclear Information System (INIS)

    Goodman, L.R.; Teplick, S.K.; Kay, H.

    1983-01-01

    The normal CT anatomy of the sternum was studied in 35 patients. In addition to the normal appearance of the sternum, normal variants that may mimic desease were often noted. In the manubrium, part of the posterior cortical margin was unsharp and irregular in 34 of 35 patients. Part of the anterior cortical margin was indistinct in 20 of the 35 patients. Angulation of the CT gantry to a position more nearly perpendicular to the manubrium improved the definition of the cortical margins. The body of the sternum was ovoid to rectangular and usually had sharp cortical margins. Sections through the manubriosternal joint and xyphoid often demonstrated irregular mottled calcifications and indistinct margins again simulating bony lesions. The rib insertions, sternal clavicular joints, and adjacent soft-tissue appearance also were evaluated

  14. Masturbation, sexuality, and adaptation: normalization in adolescence.

    Science.gov (United States)

    Shapiro, Theodore

    2008-03-01

    During adolescence the central masturbation fantasy that is formulated during childhood takes its final form and paradoxically must now be directed outward for appropriate object finding and pair matching in the service of procreative aims. This is a step in adaptation that requires a further developmental landmark that I have called normalization. The path toward airing these private fantasies is facilitated by chumship relationships as a step toward further exposure to the social surround. Hartmann's structuring application of adaptation within psychoanalysis is used as a framework for understanding the process that simultaneously serves intrapsychic and social demands and permits goals that follow evolutionary principles. Variations in the normalization process from masturbatory isolation to a variety of forms of sexual socialization are examined in sociological data concerning current adolescent sexual behavior and in case examples that indicate some routes to normalized experience and practice.

  15. Asymptotic normalization coefficients and astrophysical factors

    International Nuclear Information System (INIS)

    Mukhamedzhanov, A.M.; Azhari, A.; Clark, H.L.; Gagliardi, C.A.; Lui, Y.-W.; Sattarov, A.; Trache, L.; Tribble, R.E.; Burjan, V.; Kroha, V.; Carstoiu, F.

    2000-01-01

    The S factor for the direct capture reaction 7 Be(p,γ) 8 B can be found at astrophysical energies from the asymptotic normalization coefficients (ANC's) which provide the normalization of the tails of the overlap functions for 8 B → 7 Be + p. Peripheral transfer reactions offer a technique to determine these ANC's. Using this technique, the 10 B( 7 Be, 8 B) 9 Be and 14 N( 7 Be, 8 B) 13 C reactions have been used to measure the asymptotic normalization coefficient for 7 Be(p, γ) 8 B. These results provide an indirect determination of S 17 (0). Analysis of the existing 9 Be(p, γ) 10 B experimental data within the framework of the R-matrix method demonstrates that experimentally measured ANC's can provide a reasonable determination of direct radiative capture rates. (author)

  16. Congenital anomalies and normal skeletal variants

    International Nuclear Information System (INIS)

    Guebert, G.M.; Yochum, T.R.; Rowe, L.J.

    1987-01-01

    Congenital anomalies and normal skeletal variants are a common occurrence in clinical practice. In this chapter a large number of skeletal anomalies of the spine and pelvis are reviewed. Some of the more common skeletal anomalies of the extremities are also presented. The second section of this chapter deals with normal skeletal variants. Some of these variants may simulate certain disease processes. In some instances there are no clear-cut distinctions between skeletal variants and anomalies; therefore, there may be some overlap of material. The congenital anomalies are presented initially with accompanying text, photos, and references, beginning with the skull and proceeding caudally through the spine to then include the pelvis and extremities. The normal skeletal variants section is presented in an anatomical atlas format without text or references

  17. X-ray emssion from normal galaxies

    International Nuclear Information System (INIS)

    Speybroeck, L. van; Bechtold, J.

    1981-01-01

    A summary of results obtained with the Einstein Observatory is presented. There are two general categories of normal galaxy investigation being pursued - detailed studies of nearby galaxies where individual sources can be detected and possibly correlated with galactic morphology, and shorter observations of many more distant objects to determine the total luminosity distribution of normal galaxies. The principal examples of the first type are the CFA study of M31 and the Columbia study of the Large Magellanic Cloud. The Columbia normal galaxy survey is the principal example of the second type, although there also are smaller CFA programs concentrating on early galaxies and peculiar galaxies, and MIT has observed some members of the local group. (Auth.)

  18. Quantum arrival times and operator normalization

    International Nuclear Information System (INIS)

    Hegerfeldt, Gerhard C.; Seidel, Dirk; Gonzalo Muga, J.

    2003-01-01

    A recent approach to arrival times used the fluorescence of an atom entering a laser illuminated region, and the resulting arrival-time distribution was close to the axiomatic distribution of Kijowski, but not exactly equal, neither in limiting cases nor after compensation of reflection losses by normalization on the level of expectation values. In this paper we employ a normalization on the level of operators, recently proposed in a slightly different context. We show that in this case the axiomatic arrival-time distribution of Kijowski is recovered as a limiting case. In addition, it is shown that Allcock's complex potential model is also a limit of the physically motivated fluorescence approach and connected to Kijowski's distribution through operator normalization

  19. Helicon normal modes in Proto-MPEX

    Science.gov (United States)

    Piotrowicz, P. A.; Caneses, J. F.; Green, D. L.; Goulding, R. H.; Lau, C.; Caughman, J. B. O.; Rapp, J.; Ruzic, D. N.

    2018-05-01

    The Proto-MPEX helicon source has been operating in a high electron density ‘helicon-mode’. Establishing plasma densities and magnetic field strengths under the antenna that allow for the formation of normal modes of the fast-wave are believed to be responsible for the ‘helicon-mode’. A 2D finite-element full-wave model of the helicon antenna on Proto-MPEX is used to identify the fast-wave normal modes responsible for the steady-state electron density profile produced by the source. We also show through the simulation that in the regions of operation in which core power deposition is maximum the slow-wave does not deposit significant power besides directly under the antenna. In the case of a simulation where a normal mode is not excited significant edge power is deposited in the mirror region. ).

  20. Normalization as a canonical neural computation

    Science.gov (United States)

    Carandini, Matteo; Heeger, David J.

    2012-01-01

    There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

  1. Normal stress Sestamibi study: why re inject?

    International Nuclear Information System (INIS)

    Unger, S.A.; Hughes, T.

    2000-01-01

    Full text: Myocardial perfusion imaging (MPI) is widely used for risk stratification of patients with known or suspected coronary artery disease. A normal MPI study predicts an annual cardiac event rate of 99 Tc m -Sestamibi (MIBI), omitting the rest study when the post-stress study is interpreted as normal. The safety of this approach has not been validated, all published reports utilising both rest and stress images to interpret a study as 'normal'. Between 1/1/98 and 30/8/98, 489 patients (patients) were referred to our department for stress MPI. Of these, 237 were interpreted as normal on the basis of their post-stress study, and did not undergo a rest study. 12 month clinical follow-up was available in 184 (78%) of these patients, representing the study group (82 males, 102 females; mean age 61±12 years). 156 of these patients were referred for assessment of chest pain, three for dyspnoea, six for abnormal ECGs, and 19 for pre-operative evaluation. At one year of follow-up, there were no myocardial infarcts or admissions for unstable angina, and no cardiac deaths. Three patients died of non-cardiac causes. Seven patients underwent coronary angiography: five were normal, one had a single 50% stenosis, and one had an 80% vein graft stenosis which was subsequently angioplastied. In conclusion, a normal stress MIBI image predicts an excellent prognosis and negates the need for a rest reinjection study, thus reducing patient camera time and radiation exposure, improving departmental throughput, and minimising public health expenditure. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  2. Normal modes of weak colloidal gels

    Science.gov (United States)

    Varga, Zsigmond; Swan, James W.

    2018-01-01

    The normal modes and relaxation rates of weak colloidal gels are investigated in calculations using different models of the hydrodynamic interactions between suspended particles. The relaxation spectrum is computed for freely draining, Rotne-Prager-Yamakawa, and accelerated Stokesian dynamics approximations of the hydrodynamic mobility in a normal mode analysis of a harmonic network representing several colloidal gels. We find that the density of states and spatial structure of the normal modes are fundamentally altered by long-ranged hydrodynamic coupling among the particles. Short-ranged coupling due to hydrodynamic lubrication affects only the relaxation rates of short-wavelength modes. Hydrodynamic models accounting for long-ranged coupling exhibit a microscopic relaxation rate for each normal mode, λ that scales as l-2, where l is the spatial correlation length of the normal mode. For the freely draining approximation, which neglects long-ranged coupling, the microscopic relaxation rate scales as l-γ, where γ varies between three and two with increasing particle volume fraction. A simple phenomenological model of the internal elastic response to normal mode fluctuations is developed, which shows that long-ranged hydrodynamic interactions play a central role in the viscoelasticity of the gel network. Dynamic simulations of hard spheres that gel in response to short-ranged depletion attractions are used to test the applicability of the density of states predictions. For particle concentrations up to 30% by volume, the power law decay of the relaxation modulus in simulations accounting for long-ranged hydrodynamic interactions agrees with predictions generated by the density of states of the corresponding harmonic networks as well as experimental measurements. For higher volume fractions, excluded volume interactions dominate the stress response, and the prediction from the harmonic network density of states fails. Analogous to the Zimm model in polymer

  3. Metabolomics data normalization with EigenMS.

    Directory of Open Access Journals (Sweden)

    Yuliya V Karpievitch

    Full Text Available Liquid chromatography mass spectrometry has become one of the analytical platforms of choice for metabolomics studies. However, LC-MS metabolomics data can suffer from the effects of various systematic biases. These include batch effects, day-to-day variations in instrument performance, signal intensity loss due to time-dependent effects of the LC column performance, accumulation of contaminants in the MS ion source and MS sensitivity among others. In this study we aimed to test a singular value decomposition-based method, called EigenMS, for normalization of metabolomics data. We analyzed a clinical human dataset where LC-MS serum metabolomics data and physiological measurements were collected from thirty nine healthy subjects and forty with type 2 diabetes and applied EigenMS to detect and correct for any systematic bias. EigenMS works in several stages. First, EigenMS preserves the treatment group differences in the metabolomics data by estimating treatment effects with an ANOVA model (multiple fixed effects can be estimated. Singular value decomposition of the residuals matrix is then used to determine bias trends in the data. The number of bias trends is then estimated via a permutation test and the effects of the bias trends are eliminated. EigenMS removed bias of unknown complexity from the LC-MS metabolomics data, allowing for increased sensitivity in differential analysis. Moreover, normalized samples better correlated with both other normalized samples and corresponding physiological data, such as blood glucose level, glycated haemoglobin, exercise central augmentation pressure normalized to heart rate of 75, and total cholesterol. We were able to report 2578 discriminatory metabolite peaks in the normalized data (p<0.05 as compared to only 1840 metabolite signals in the raw data. Our results support the use of singular value decomposition-based normalization for metabolomics data.

  4. Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.

    Science.gov (United States)

    Lee, Chi Fung; Chavez, Juan D; Garcia-Menendez, Lorena; Choi, Yongseon; Roe, Nathan D; Chiao, Ying Ann; Edgar, John S; Goo, Young Ah; Goodlett, David R; Bruce, James E; Tian, Rong

    2016-09-20

    Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also were tested. Increased NADH/NAD(+) and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are present in human failing hearts as well as in mouse hearts with pathologic hypertrophy. Elevation of NAD(+) levels by stimulating the NAD(+) salvage pathway suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and improved cardiac function in responses to stresses. Acetylome analysis identified a subpopulation of mitochondrial proteins that was sensitive to changes in the NADH/NAD(+) ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle proteins impaired the transport and oxidation of cytosolic NADH in the mitochondria, resulting in altered cytosolic redox state and energy deficiency. Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70 in adenosine triphosphate synthase complex promoted its interaction with cyclophilin D, and sensitized the opening of mitochondrial permeability transition pore. Both could be alleviated by normalizing the NAD(+) redox balance either genetically or pharmacologically. We show that mitochondrial protein hyperacetylation due to NAD(+) redox imbalance contributes to the pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical data demonstrate a clear benefit of normalizing NADH/NAD(+) imbalance in the failing hearts

  5. Computing Instantaneous Frequency by normalizing Hilbert Transform

    Science.gov (United States)

    Huang, Norden E.

    2005-05-31

    This invention presents Normalized Amplitude Hilbert Transform (NAHT) and Normalized Hilbert Transform(NHT), both of which are new methods for computing Instantaneous Frequency. This method is designed specifically to circumvent the limitation set by the Bedorsian and Nuttal Theorems, and to provide a sharp local measure of error when the quadrature and the Hilbert Transform do not agree. Motivation for this method is that straightforward application of the Hilbert Transform followed by taking the derivative of the phase-angle as the Instantaneous Frequency (IF) leads to a common mistake made up to this date. In order to make the Hilbert Transform method work, the data has to obey certain restrictions.

  6. Normal anatomy of lung perfusion SPECT scintigraphy

    International Nuclear Information System (INIS)

    Moskowitz, G.W.; Levy, L.M.

    1987-01-01

    Ten patients studies for possible pulmonary embolic disease had normal lung perfusion planar and SPECT scintigraphy. A computer program was developed to superimpose the CT scans on corresponding SPECT images. Superimposition of CT scans on corresponding SPECT transaxial cross-sectional images, when available, provides the needed definition and relationships of adjacent organs. SPECT transaxial sections provide clear anatomic definition of perfusion defects without foreground and background lung tissue superimposed. The location, shape, and size of the perfusion defects can be readily assessed by SPECT. An algorithm was developed for the differentiation of abnormal pulmonary perfusion patterns from normal structures on variation

  7. Anatomy, normal variants, and basic biomechanics

    International Nuclear Information System (INIS)

    Berquist, T.H.; Johnson, K.A.

    1989-01-01

    This paper reports on the anatomy and basic functions of the foot and ankle important to physicians involved in imaging procedures, clinical medicine, and surgery. New radiographic techniques especially magnetic resonance imaging, provide more diagnostic information owing to improved tissue contrast and the ability to obtain multiple image planes (axial, sagittal, coronal, oblique). Therefore, a thorough knowledge of skeletal and soft tissue anatomy is even more essential. Normal variants must also be understood in order to distinguish normal from pathologic changes in the foot and ankle. A basic understanding of biomechanics is also essential for selecting the proper diagnostic techniques

  8. Dlk1 in normal and abnormal hematopoiesis

    DEFF Research Database (Denmark)

    Sakajiri, S; O'kelly, J; Yin, D

    2005-01-01

    normals. Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of Dlk1 mRNA markedly increased during...... (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells....

  9. Statistical Theory of Normal Grain Growth Revisited

    International Nuclear Information System (INIS)

    Gadomski, A.; Luczka, J.

    2002-01-01

    In this paper, we discuss three physically relevant problems concerning the normal grain growth process. These are: Infinite vs finite size of the system under study (a step towards more realistic modeling); conditions of fine-grained structure formation, with possible applications to thin films and biomembranes, and interesting relations to superplasticity of materials; approach to log-normality, an ubiquitous natural phenomenon, frequently reported in literature. It turns out that all three important points mentioned are possible to be included in a Mulheran-Harding type behavior of evolving grains-containing systems that we have studied previously. (author)

  10. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

  11. Impairment of Vision in a Mouse Model of Usher Syndrome Type III.

    Science.gov (United States)

    Tian, Guilian; Lee, Richard; Ropelewski, Philip; Imanishi, Yoshikazu

    2016-03-01

    The purpose of this study was to obtain an Usher syndrome type III mouse model with retinal phenotype. Speed congenic method was used to obtain Clrn1 exon 1 knockout (Clrn1-/-) and Clrn1N48K knockin (Clrn1N48K/N48K) mice under A/J background. To study the retinal functions of these mice, we measured scotopic and photopic ERG responses. To observe if there are any structural abnormalities, we conducted light and transmission electron microscopy of fixed retinal specimens. In 3-month-old Clrn1-/- mice, scotopic b-wave amplitude was reduced by more than 25% at the light intensities from -2.2 to 0.38 log cd·s/m2, but scotopic a-wave amplitudes were comparable to those of age-matched wild type mice at all the light intensities tested. In 9-month-old Clrn1-/- mice, scotopic b-wave amplitudes were further reduced by more than 35%, and scotopic a-wave amplitude also showed a small decline as compared with wild type mice. Photopic ERG responses were comparable between Clrn1-/- and wild type mice. Those electrophysiological defects were not associated with a loss of rods. In Clrn1N48K/N48K mice, both a- and b-wave amplitudes were not discernable from those of wild type mice aged up to 10 months. Mutations that are Clrn1-/- biallelic cause visual defects when placed under A/J background. The absence of apparent rod degeneration suggests that the observed phenotype is due to functional defects, and not due to loss of rods. Biallelic Clrn1N48K/N48K mutations did not cause discernible visual defects, suggesting that Clrn1- allele is more severely dysfunctional than ClrnN48K allele.

  12. Dendronic trimaltoside amphiphiles (DTMs) for membrane protein study

    DEFF Research Database (Denmark)

    Sadaf, Aiman; Du, Yang; Santillan, Claudia

    2017-01-01

    The critical contribution of membrane proteins in normal cellular function makes their detailed structure and functional analysis essential. Detergents, amphipathic agents with the ability to maintain membrane proteins in a soluble state in aqueous solution, have key roles in membrane protein...... alkyl chains by introducing dendronic hydrophobic groups connected to a trimaltoside head group, designated dendronic trimaltosides (DTMs). Representative DTMs conferred enhanced stabilization to multiple membrane proteins compared to the benchmark conventional detergent, DDM. One DTM (i.e., DTM-A6...

  13. Normalization of Bilateral Adrenal Gland Enlargement after Treatment for Cryptococcosis

    Directory of Open Access Journals (Sweden)

    Yuka Muraoka

    2017-01-01

    Full Text Available Cryptococcosis usually occurs in immunocompromised patients and can cause enlargement of the adrenal glands, although the morphologic changes after treatment have not been reported in detail. We report the case of 24-year-old man with fevers, headaches, and impaired consciousness who had been treated with glucocorticoids for a protein-losing gastroenteropathy. The cerebrospinal fluid analysis revealed cryptococcal meningitis. Computed tomography showed bilateral adrenal enlargement. A retrospective analysis revealed that the enlargement had been detected 5 months before admission and gradually increased. The enlargement was improved with antifungal therapy and normalized 6 months later. This is the first report describing morphological changes in the adrenal glands associated with cryptococcal meningitis. Adrenal enlargement by cryptococcosis can be improved without any abnormal findings, including calcifications, which may be a unique characteristic from other diseases, including tuberculosis.

  14. Normal urinary albumin excretion in recently diagnosed type 1 diabetic patients

    DEFF Research Database (Denmark)

    Lind, B; Jensen, T; Feldt-Rasmussen, B

    1989-01-01

    of diabetes. Urinary albumin excretion (median and 95% confidence interval) was similar in the diabetic patients and normal control subjects (8 (6-11) vs 8 (6-11) mg 24-h-1, NS). Four diabetic patients had urinary albumin excretion in the microalbuminuric range of 30-300 mg 24-h-1. There was no significant...... difference between the two groups in urinary excretion of retinol binding protein. The distribution among the individuals of both urinary proteins was positively skewed and similar in the two groups. In conclusion, no significant differences in the urinary excretion of albumin and retinol binding protein...... were found between recently diagnosed Type 1 diabetic patients and normal subjects....

  15. Aquaporin Protein-Protein Interactions

    Directory of Open Access Journals (Sweden)

    Jennifer Virginia Roche

    2017-10-01

    Full Text Available Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein–protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein–protein interactions; dividing the interactions into three types: (1 interactions between aquaporin tetramers; (2 interactions between aquaporin monomers within a tetramer (hetero-tetramerization; and (3 transient interactions with regulatory proteins. We particularly focus on the structural aspects of the interactions, discussing the small differences within a conserved overall fold that allow for aquaporins to be differentially regulated in an organism-, tissue- and trigger-specific manner. A deep knowledge about these differences is needed to fully understand aquaporin function and regulation in many physiological processes, and may enable design of compounds targeting specific aquaporins for treatment of human disease.

  16. Protein immobilization strategies for protein biochips

    NARCIS (Netherlands)

    Rusmini, F.; Rusmini, Federica; Zhong, Zhiyuan; Feijen, Jan

    2007-01-01

    In the past few years, protein biochips have emerged as promising proteomic and diagnostic tools for obtaining information about protein functions and interactions. Important technological innovations have been made. However, considerable development is still required, especially regarding protein

  17. The claudin gene family: expression in normal and neoplastic tissues

    International Nuclear Information System (INIS)

    Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J

    2006-01-01

    The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4

  18. Automatic Radiometric Normalization of Multitemporal Satellite Imagery

    DEFF Research Database (Denmark)

    Canty, Morton J.; Nielsen, Allan Aasbjerg; Schmidt, Michael

    2004-01-01

    with normalization using orthogonal regression. The procedure is applied to Landsat TM images over Nevada, Landsat ETM+ images over Morocco, and SPOT HRV images over Kenya. Results from this new automatic, combined MAD/orthogonal regression method, based on statistical analysis of test pixels not used in the actual...

  19. Post-Normal science in practice

    NARCIS (Netherlands)

    Dankel, Dorothy J.; Vaage, Nora S.; van der Sluijs, Jeroen P.

    This special issue contains a selection of papers presented during the 2014 Bergen meeting, complemented with short perspectives by young PNS-inspired scholars, presented at a mini-symposium "Post-normal times? New thinking about science and policy advice" held on 21 October 2016 in celebration of

  20. Physical Development: What's Normal? What's Not?

    Science.gov (United States)

    ... Stages Listen Español Text Size Email Print Share Physical Development: What’s Normal? What’s Not? Page Content Article ... growth . The timing and speed of a child's physical development can vary a lot, because it is ...

  1. Visual attention and flexible normalization pools

    Science.gov (United States)

    Schwartz, Odelia; Coen-Cagli, Ruben

    2013-01-01

    Attention to a spatial location or feature in a visual scene can modulate the responses of cortical neurons and affect perceptual biases in illusions. We add attention to a cortical model of spatial context based on a well-founded account of natural scene statistics. The cortical model amounts to a generalized form of divisive normalization, in which the surround is in the normalization pool of the center target only if they are considered statistically dependent. Here we propose that attention influences this computation by accentuating the neural unit activations at the attended location, and that the amount of attentional influence of the surround on the center thus depends on whether center and surround are deemed in the same normalization pool. The resulting form of model extends a recent divisive normalization model of attention (Reynolds & Heeger, 2009). We simulate cortical surround orientation experiments with attention and show that the flexible model is suitable for capturing additional data and makes nontrivial testable predictions. PMID:23345413

  2. Achondroplasia in sibs of normal parents.

    Science.gov (United States)

    Philip, N; Auger, M; Mattei, J F; Giraud, F

    1988-01-01

    A new case of recurrent achondroplasia in sibs of normal parents is reported. Two sisters and a half sister were affected. Various mechanisms can be postulated to account for unexpected recurrence of achondroplasia in the same sibship. Germinal mosaicism and unstable premutation are discussed here. Images PMID:3236371

  3. Achondroplasia in sibs of normal parents.

    OpenAIRE

    Philip, N; Auger, M; Mattei, J F; Giraud, F

    1988-01-01

    A new case of recurrent achondroplasia in sibs of normal parents is reported. Two sisters and a half sister were affected. Various mechanisms can be postulated to account for unexpected recurrence of achondroplasia in the same sibship. Germinal mosaicism and unstable premutation are discussed here.

  4. Endoscopic third ventriculostomy in idiopathic normal pressure ...

    African Journals Online (AJOL)

    Mohammed Ahmed Eshra

    2013-12-22

    Dec 22, 2013 ... system of the brain causing ventricular enlargement. This is followed by gradual .... sion, not to decrease the pressure (which is already normal).8–15 ... So ETV must be performed in patients with clinical evolution of not more.

  5. Principal normal indicatrices of closed space curves

    DEFF Research Database (Denmark)

    Røgen, Peter

    1999-01-01

    A theorem due to J. Weiner, which is also proven by B. Solomon, implies that a principal normal indicatrix of a closed space curve with nonvanishing curvature has integrated geodesic curvature zero and contains no subarc with integrated geodesic curvature pi. We prove that the inverse problem alw...

  6. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

    Bach-Holm, Daniella; Kessing, Svend Vedel; Mogensen, Ulla Brasch

    2012-01-01

    Purpose: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). Methods: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet...

  7. Normal stresses in semiflexible polymer hydrogels

    Science.gov (United States)

    Vahabi, M.; Vos, Bart E.; de Cagny, Henri C. G.; Bonn, Daniel; Koenderink, Gijsje H.; MacKintosh, F. C.

    2018-03-01

    Biopolymer gels such as fibrin and collagen networks are known to develop tensile axial stress when subject to torsion. This negative normal stress is opposite to the classical Poynting effect observed for most elastic solids including synthetic polymer gels, where torsion provokes a positive normal stress. As shown recently, this anomalous behavior in fibrin gels depends on the open, porous network structure of biopolymer gels, which facilitates interstitial fluid flow during shear and can be described by a phenomenological two-fluid model with viscous coupling between network and solvent. Here we extend this model and develop a microscopic model for the individual diagonal components of the stress tensor that determine the axial response of semiflexible polymer hydrogels. This microscopic model predicts that the magnitude of these stress components depends inversely on the characteristic strain for the onset of nonlinear shear stress, which we confirm experimentally by shear rheometry on fibrin gels. Moreover, our model predicts a transient behavior of the normal stress, which is in excellent agreement with the full time-dependent normal stress we measure.

  8. Comparative ultrasound measurement of normal thyroid gland ...

    African Journals Online (AJOL)

    2011-08-31

    Aug 31, 2011 ... the normal thyroid gland has a homogenous increased medium level echo texture. The childhood thyroid gland dimension correlates linearly with age and body surface unlike adults. [14] Iodothyronine (T3) and thyroxine (T4) are thyroid hormones which function to control the basal metabolic rate (BMR).

  9. Mast cell distribution in normal adult skin

    NARCIS (Netherlands)

    A.S. Janssens (Artiena Soe); R. Heide (Rogier); J.C. den Hollander (Jan); P.G.M. Mulder (P. G M); B. Tank (Bhupendra); A.P. Oranje (Arnold)

    2005-01-01

    markdownabstract__AIMS:__ To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. __METHODS:__ Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults.

  10. Normal sleep and its neurophysiological regulation

    NARCIS (Netherlands)

    Hofman, W.F.; Talamini, L.M.; Watson, R.R.

    2015-01-01

    Normal sleep consists of two states: NREM (light and deep sleep) and REM, alternating in a cyclical pattern. The sleep/wake rhythm is regulated by two processes: the sleep propensity, building up during wake, and the circadian rhythm, imposed by the suprachiasmatic nucleus. The arousal pathways in

  11. Named entity normalization in user generated content

    NARCIS (Netherlands)

    Jijkoun, V.; Khalid, M.A.; Marx, M.; de Rijke, M.

    2008-01-01

    Named entity recognition is important for semantically oriented retrieval tasks, such as question answering, entity retrieval, biomedical retrieval, trend detection, and event and entity tracking. In many of these tasks it is important to be able to accurately normalize the recognized entities,

  12. Morphological evaluation of normal human corneal epithelium

    DEFF Research Database (Denmark)

    Ehlers, Niels; Heegaard, Steffen; Hjortdal, Jesper

    2010-01-01

    of corneas from 100 consecutively selected paraffin-embedded eyes were stained with hematoxylin-eosin and Periodic Acid-Schiff (PAS). All specimens were evaluated by light microscopy. The eyes were enucleated from patients with choroidal melanoma. Corneas were considered to be normal. RESULTS: Ninety of 100...

  13. Dissociative Functions in the Normal Mourning Process.

    Science.gov (United States)

    Kauffman, Jeffrey

    1994-01-01

    Sees dissociative functions in mourning process as occurring in conjunction with integrative trends. Considers initial shock reaction in mourning as model of normal dissociation in mourning process. Dissociation is understood to be related to traumatic significance of death in human consciousness. Discerns four psychological categories of…

  14. Hemoglobin levels in normal Filipino pregnant women.

    Science.gov (United States)

    Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P

    1981-09-01

    The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.

  15. Normalized compression distance of multisets with applications

    NARCIS (Netherlands)

    Cohen, A.R.; Vitányi, P.M.B.

    Pairwise normalized compression distance (NCD) is a parameter-free, feature-free, alignment-free, similarity metric based on compression. We propose an NCD of multisets that is also metric. Previously, attempts to obtain such an NCD failed. For classification purposes it is superior to the pairwise

  16. Limiting Normal Operator in Quasiconvex Analysis

    Czech Academy of Sciences Publication Activity Database

    Aussel, D.; Pištěk, Miroslav

    2015-01-01

    Roč. 23, č. 4 (2015), s. 669-685 ISSN 1877-0533 R&D Projects: GA ČR GA15-00735S Institutional support: RVO:67985556 Keywords : Quasiconvex function * Sublevel set * Normal operator Subject RIV: BA - General Mathematics Impact factor: 0.973, year: 2015 http://library.utia.cas.cz/separaty/2015/MTR/pistek-0453552.pdf

  17. Role of the normal gut microbiota.

    Science.gov (United States)

    Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Nageshwar Reddy, D

    2015-08-07

    Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

  18. Perturbations of normally solvable nonlinear operators, I

    Directory of Open Access Journals (Sweden)

    William O. Ray

    1985-01-01

    Full Text Available Let X and Y be Banach spaces and let ℱ and be Gateaux differentiable mappings from X to Y In this note we study when the operator ℱ+ is surjective for sufficiently small perturbations of a surjective operator ℱ The methods extend previous results in the area of normal solvability for nonlinear operators.

  19. Normal forms of Hopf-zero singularity

    International Nuclear Information System (INIS)

    Gazor, Majid; Mokhtari, Fahimeh

    2015-01-01

    The Lie algebra generated by Hopf-zero classical normal forms is decomposed into two versal Lie subalgebras. Some dynamical properties for each subalgebra are described; one is the set of all volume-preserving conservative systems while the other is the maximal Lie algebra of nonconservative systems. This introduces a unique conservative–nonconservative decomposition for the normal form systems. There exists a Lie-subalgebra that is Lie-isomorphic to a large family of vector fields with Bogdanov–Takens singularity. This gives rise to a conclusion that the local dynamics of formal Hopf-zero singularities is well-understood by the study of Bogdanov–Takens singularities. Despite this, the normal form computations of Bogdanov–Takens and Hopf-zero singularities are independent. Thus, by assuming a quadratic nonzero condition, complete results on the simplest Hopf-zero normal forms are obtained in terms of the conservative–nonconservative decomposition. Some practical formulas are derived and the results implemented using Maple. The method has been applied on the Rössler and Kuramoto–Sivashinsky equations to demonstrate the applicability of our results. (paper)

  20. Normal forms of Hopf-zero singularity

    Science.gov (United States)

    Gazor, Majid; Mokhtari, Fahimeh

    2015-01-01

    The Lie algebra generated by Hopf-zero classical normal forms is decomposed into two versal Lie subalgebras. Some dynamical properties for each subalgebra are described; one is the set of all volume-preserving conservative systems while the other is the maximal Lie algebra of nonconservative systems. This introduces a unique conservative-nonconservative decomposition for the normal form systems. There exists a Lie-subalgebra that is Lie-isomorphic to a large family of vector fields with Bogdanov-Takens singularity. This gives rise to a conclusion that the local dynamics of formal Hopf-zero singularities is well-understood by the study of Bogdanov-Takens singularities. Despite this, the normal form computations of Bogdanov-Takens and Hopf-zero singularities are independent. Thus, by assuming a quadratic nonzero condition, complete results on the simplest Hopf-zero normal forms are obtained in terms of the conservative-nonconservative decomposition. Some practical formulas are derived and the results implemented using Maple. The method has been applied on the Rössler and Kuramoto-Sivashinsky equations to demonstrate the applicability of our results.

  1. Sample normalization methods in quantitative metabolomics.

    Science.gov (United States)

    Wu, Yiman; Li, Liang

    2016-01-22

    To reveal metabolomic changes caused by a biological event in quantitative metabolomics, it is critical to use an analytical tool that can perform accurate and precise quantification to examine the true concentration differences of individual metabolites found in different samples. A number of steps are involved in metabolomic analysis including pre-analytical work (e.g., sample collection and storage), analytical work (e.g., sample analysis) and data analysis (e.g., feature extraction and quantification). Each one of them can influence the quantitative results significantly and thus should be performed with great care. Among them, the total sample amount or concentration of metabolites can be significantly different from one sample to another. Thus, it is critical to reduce or eliminate the effect of total sample amount variation on quantification of individual metabolites. In this review, we describe the importance of sample normalization in the analytical workflow with a focus on mass spectrometry (MS)-based platforms, discuss a number of methods recently reported in the literature and comment on their applicability in real world metabolomics applications. Sample normalization has been sometimes ignored in metabolomics, partially due to the lack of a convenient means of performing sample normalization. We show that several methods are now available and sample normalization should be performed in quantitative metabolomics where the analyzed samples have significant variations in total sample amounts. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Refixation saccades with normal gain values

    DEFF Research Database (Denmark)

    Korsager, Leise Elisabeth Hviid; Faber, Christian Emil; Schmidt, Jesper Hvass

    2017-01-01

    -ocular reflex. However, this partial deficit is in conflict with the current way of interpreting vHIT results in which the vestibular function is classified as either normal or pathological based only on the gain value. Refixation saccades, which are evident signs of vestibulopathy, are not considered...

  3. Hypervascular liver lesions in radiologically normal liver

    Energy Technology Data Exchange (ETDEWEB)

    Amico, Enio Campos; Alves, Jose Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; Joao, Samir Assi; Liguori, Adriano de Araujo Lima, E-mail: ecamic@uol.com.br [Hospital Universitario Onofre Lopes (HUOL/UFRN), Natal, RN (Brazil). Clinica Gastrocentro e Ambulatorios de Cirurgia do Aparelho Digestivo e de Cirurgia Hepatobiliopancreatica

    2017-09-01

    Background: The hypervascular liver lesions represent a diagnostic challenge. Aim: To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. Method: This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Results: Eighty eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p< 0.001), personal history of cancer (p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. Conclusion: It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine amino transaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. (author)

  4. KERNEL MAD ALGORITHM FOR RELATIVE RADIOMETRIC NORMALIZATION

    Directory of Open Access Journals (Sweden)

    Y. Bai

    2016-06-01

    Full Text Available The multivariate alteration detection (MAD algorithm is commonly used in relative radiometric normalization. This algorithm is based on linear canonical correlation analysis (CCA which can analyze only linear relationships among bands. Therefore, we first introduce a new version of MAD in this study based on the established method known as kernel canonical correlation analysis (KCCA. The proposed method effectively extracts the non-linear and complex relationships among variables. We then conduct relative radiometric normalization experiments on both the linear CCA and KCCA version of the MAD algorithm with the use of Landsat-8 data of Beijing, China, and Gaofen-1(GF-1 data derived from South China. Finally, we analyze the difference between the two methods. Results show that the KCCA-based MAD can be satisfactorily applied to relative radiometric normalization, this algorithm can well describe the nonlinear relationship between multi-temporal images. This work is the first attempt to apply a KCCA-based MAD algorithm to relative radiometric normalization.

  5. Robust glint detection through homography normalization

    DEFF Research Database (Denmark)

    Hansen, Dan Witzner; Roholm, Lars; García Ferreiros, Iván

    2014-01-01

    A novel normalization principle for robust glint detection is presented. The method is based on geometric properties of corneal reflections and allows for simple and effective detection of glints even in the presence of several spurious and identically appearing reflections. The method is tested...

  6. Power curve report - with turbulence intensity normalization

    DEFF Research Database (Denmark)

    Gómez Arranz, Paula; Wagner, Rozenn; Vesth, Allan

    , additional shear and turbulence intensitity filters are applied on the measured data. Secondly, the method for normalization to a given reference turbulence intensity level (as described in Annex M of the draft of IEC 61400-12-1 Ed.2 [3]) is applied. The measurements have been performed using DTU...

  7. Accounting for the Benefits of Database Normalization

    Science.gov (United States)

    Wang, Ting J.; Du, Hui; Lehmann, Constance M.

    2010-01-01

    This paper proposes a teaching approach to reinforce accounting students' understanding of the concept of database normalization. Unlike a conceptual approach shown in most of the AIS textbooks, this approach involves with calculations and reconciliations with which accounting students are familiar because the methods are frequently used in…

  8. Selective attention in normal and impaired hearing.

    Science.gov (United States)

    Shinn-Cunningham, Barbara G; Best, Virginia

    2008-12-01

    A common complaint among listeners with hearing loss (HL) is that they have difficulty communicating in common social settings. This article reviews how normal-hearing listeners cope in such settings, especially how they focus attention on a source of interest. Results of experiments with normal-hearing listeners suggest that the ability to selectively attend depends on the ability to analyze the acoustic scene and to form perceptual auditory objects properly. Unfortunately, sound features important for auditory object formation may not be robustly encoded in the auditory periphery of HL listeners. In turn, impaired auditory object formation may interfere with the ability to filter out competing sound sources. Peripheral degradations are also likely to reduce the salience of higher-order auditory cues such as location, pitch, and timbre, which enable normal-hearing listeners to select a desired sound source out of a sound mixture. Degraded peripheral processing is also likely to increase the time required to form auditory objects and focus selective attention so that listeners with HL lose the ability to switch attention rapidly (a skill that is particularly important when trying to participate in a lively conversation). Finally, peripheral deficits may interfere with strategies that normal-hearing listeners employ in complex acoustic settings, including the use of memory to fill in bits of the conversation that are missed. Thus, peripheral hearing deficits are likely to cause a number of interrelated problems that challenge the ability of HL listeners to communicate in social settings requiring selective attention.

  9. Superconvergent sum rules for the normal reflectivity

    International Nuclear Information System (INIS)

    Furuya, K.; Zimerman, A.H.; Villani, A.

    1976-05-01

    Families of superconvergent relations for the normal reflectivity function are written. Sum rules connecting the difference of phases of the reflectivities of two materials are also considered. Finally superconvergence relations and sum rules for magneto-reflectivity in the Faraday and Voigt regimes are also studied

  10. Effects of pions on normal tissues

    International Nuclear Information System (INIS)

    Tokita, N.

    1981-01-01

    Verification of the uniform biological effectiveness of pion beams of various dimensions produced at LAMPF has been made using cultured mammalian cells and mouse jejunum. Normal tissue radiobiology studies at LAMPF are reviewed with regard to biological beam characterization for the therapy program and the current status of acute and late effect studies on rodents

  11. Normal equivariant forms of vector fields

    International Nuclear Information System (INIS)

    Sanchez Bringas, F.

    1992-07-01

    We prove a theorem of linearization of type Siegel and a theorem of normal forms of type Poincare-Dulac for germs of holomorphic vector fields in the origin of C 2 , Γ -equivariants, where Γ is a finite subgroup of GL (2,C). (author). 5 refs

  12. Challenging the Ideology of Normal in Schools

    Science.gov (United States)

    Annamma, Subini A.; Boelé, Amy L.; Moore, Brooke A.; Klingner, Janette

    2013-01-01

    In this article, we build on Brantlinger's work to critique the binary of normal and abnormal applied in US schools that create inequities in education. Operating from a critical perspective, we draw from Critical Race Theory, Disability Studies in Education, and Cultural/Historical Activity Theory to build a conceptual framework for…

  13. Glymphatic MRI in idiopathic normal pressure hydrocephalus.

    Science.gov (United States)

    Ringstad, Geir; Vatnehol, Svein Are Sirirud; Eide, Per Kristian

    2017-10-01

    The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In

  14. Fast electron transfer through a single molecule natively structured redox protein

    DEFF Research Database (Denmark)

    Della Pia, Eduardo Antonio; Chi, Qijin; Macdonald, J. Emyr

    2012-01-01

    The electron transfer properties of proteins are normally measured as molecularly averaged ensembles. Through these and related measurements, proteins are widely regarded as macroscopically insulating materials. Using scanning tunnelling microscopy (STM), we present new measurements of the conduc...

  15. In vivo import of plastocyanin and a fusion protein into developmentally different plastids of transgenic plants

    NARCIS (Netherlands)

    Boer, Douwe de; Cremers, Fons; Teertstra, Renske; Smits, Lianne; Hille, Jacques; Smeekens, Sjef; Weisbeek, Peter

    1988-01-01

    Transgenic tomato plants that constitutively express a foreign plastocyanin gene were used to study protein transport in different tissues. Normally expression of endogenous plastocyanin genes in plants is restricted to photosynthetic tissues only, whereas this foreign plastocyanin protein is found

  16. Normalization for triple-target microarray experiments

    Directory of Open Access Journals (Sweden)

    Magniette Frederic

    2008-04-01

    Full Text Available Abstract Background Most microarray studies are made using labelling with one or two dyes which allows the hybridization of one or two samples on the same slide. In such experiments, the most frequently used dyes are Cy3 and Cy5. Recent improvements in the technology (dye-labelling, scanner and, image analysis allow hybridization up to four samples simultaneously. The two additional dyes are Alexa488 and Alexa494. The triple-target or four-target technology is very promising, since it allows more flexibility in the design of experiments, an increase in the statistical power when comparing gene expressions induced by different conditions and a scaled down number of slides. However, there have been few methods proposed for statistical analysis of such data. Moreover the lowess correction of the global dye effect is available for only two-color experiments, and even if its application can be derived, it does not allow simultaneous correction of the raw data. Results We propose a two-step normalization procedure for triple-target experiments. First the dye bleeding is evaluated and corrected if necessary. Then the signal in each channel is normalized using a generalized lowess procedure to correct a global dye bias. The normalization procedure is validated using triple-self experiments and by comparing the results of triple-target and two-color experiments. Although the focus is on triple-target microarrays, the proposed method can be used to normalize p differently labelled targets co-hybridized on a same array, for any value of p greater than 2. Conclusion The proposed normalization procedure is effective: the technical biases are reduced, the number of false positives is under control in the analysis of differentially expressed genes, and the triple-target experiments are more powerful than the corresponding two-color experiments. There is room for improving the microarray experiments by simultaneously hybridizing more than two samples.

  17. Fission cross-section normalization problems

    International Nuclear Information System (INIS)

    Wagemans, C.; Ghent Rijksuniversiteit; Deruytter, A.J.

    1983-01-01

    The present measurements yield σsub(f)-data in the neutron energy from 20 MeV to 30 keV directly normalized in the thermal region. In the keV-region these data are consistent with the absolute σsub(f)-measurements of Szabo and Marquette. For the secondary normalization integral I 2 values have been obtained in agreement with those of Gwin et al. and Czirr et al. which were also directly normalized in the thermal region. For the I 1 integral, however, puzzling low values have been obtained. This was also the case for σsub(f)-bar in neutron energy intervals containing strong resonances. Three additional measurements are planned to further investigate these observations: (i) maintaining the actual approx.2π-geometry but using a 10 B-foil for the neutron flux detection (ii) using a low detection geometry with a 10 B- as well as a 6 Li-flux monitor. Only after these measurements definite conclusions on the I 1 and I 2 integrals can be formulated and final σsub(f)-bar-values can be released. The present study also gives some evidence for a correlation between the integral I 2 and the neutron flux monitor used. The influence of a normalization via I 1 or I 2 on the final cross-section has been shown. The magnitude of possible normalization errors is illustrated. Finally, since 235 U is expected to be an ''easy'' nucleus (low α-activity high σsub(f)-values), there are some indications that the important discrepancies still present in 235 U(n,f) cross-section measurements might partially be due to errors in the neutron flux determination

  18. Spatial normalization of array-CGH data

    Directory of Open Access Journals (Sweden)

    Brennetot Caroline

    2006-05-01

    Full Text Available Abstract Background Array-based comparative genomic hybridization (array-CGH is a recently developed technique for analyzing changes in DNA copy number. As in all microarray analyses, normalization is required to correct for experimental artifacts while preserving the true biological signal. We investigated various sources of systematic variation in array-CGH data and identified two distinct types of spatial effect of no biological relevance as the predominant experimental artifacts: continuous spatial gradients and local spatial bias. Local spatial bias affects a large proportion of arrays, and has not previously been considered in array-CGH experiments. Results We show that existing normalization techniques do not correct these spatial effects properly. We therefore developed an automatic method for the spatial normalization of array-CGH data. This method makes it possible to delineate and to eliminate and/or correct areas affected by spatial bias. It is based on the combination of a spatial segmentation algorithm called NEM (Neighborhood Expectation Maximization and spatial trend estimation. We defined quality criteria for array-CGH data, demonstrating significant improvements in data quality with our method for three data sets coming from two different platforms (198, 175 and 26 BAC-arrays. Conclusion We have designed an automatic algorithm for the spatial normalization of BAC CGH-array data, preventing the misinterpretation of experimental artifacts as biologically relevant outliers in the genomic profile. This algorithm is implemented in the R package MANOR (Micro-Array NORmalization, which is described at http://bioinfo.curie.fr/projects/manor and available from the Bioconductor site http://www.bioconductor.org. It can also be tested on the CAPweb bioinformatics platform at http://bioinfo.curie.fr/CAPweb.

  19. Fusion and normalization to enhance anomaly detection

    Science.gov (United States)

    Mayer, R.; Atkinson, G.; Antoniades, J.; Baumback, M.; Chester, D.; Edwards, J.; Goldstein, A.; Haas, D.; Henderson, S.; Liu, L.

    2009-05-01

    This study examines normalizing the imagery and the optimization metrics to enhance anomaly and change detection, respectively. The RX algorithm, the standard anomaly detector for hyperspectral imagery, more successfully extracts bright rather than dark man-made objects when applied to visible hyperspectral imagery. However, normalizing the imagery prior to applying the anomaly detector can help detect some of the problematic dark objects, but can also miss some bright objects. This study jointly fuses images of RX applied to normalized and unnormalized imagery and has a single decision surface. The technique was tested using imagery of commercial vehicles in urban environment gathered by a hyperspectral visible/near IR sensor mounted in an airborne platform. Combining detections first requires converting the detector output to a target probability. The observed anomaly detections were fitted with a linear combination of chi square distributions and these weights were used to help compute the target probability. Receiver Operator Characteristic (ROC) quantitatively assessed the target detection performance. The target detection performance is highly variable depending on the relative number of candidate bright and dark targets and false alarms and controlled in this study by using vegetation and street line masks. The joint Boolean OR and AND operations also generate variable performance depending on the scene. The joint SUM operation provides a reasonable compromise between OR and AND operations and has good target detection performance. In addition, new transforms based on normalizing correlation coefficient and least squares generate new transforms related to canonical correlation analysis (CCA) and a normalized image regression (NIR). Transforms based on CCA and NIR performed better than the standard approaches. Only RX detection of the unnormalized of the difference imagery in change detection provides adequate change detection performance.

  20. Tissue protein metabolism in parasitized animals

    International Nuclear Information System (INIS)

    Symons, L.E.A.; Steel, J.W.; Jones, W.O.

    1981-01-01

    The effects of gastrointestinal nematode infection of mammals, particularly of the small intestine of the sheep, on protein metabolism of skeletal muscle, liver, the gastrointestinal tract and wool are described. These changes have been integrated to explain poor growth and production in the sheep heavily infected with Trichostrongylus colubriformis. The rates of both synthesis and catabolism of muscle protein are depressed, but nitrogen is lost from this tissue because the depression of synthesis exceeds that of catabolism. Anorexia is the major cause of these changes. Although the effect on liver protein synthesis is unclear, it is probable that the leakage of plasma proteins into the gastrointestinal tract stimulates an early increase in the rate of synthesis of these proteins, but this eventually declines and is insufficient to correct developing hypoalbuminaemia. Changes in the intestinal tract are complex. Exogenous nitrogen is reduced by anorexia, but the flow of nitrogen through the tract from abomasum to faeces is above normal because of the increase of endogenous protein from leakage of plasma protein and, presumably, from exfoliated epithelial cells. There is evidence that protein metabolism of intestinal tissue, particularly in the uninfected distal two-thirds, is increased. Synthesis of wool protein is decreased. As the result of anorexia, intestinal loss of endogenous protein and an increased rate of intestinal protein metabolism there is a net movement of amino nitrogen from muscle, liver and possibly skin to the intestine of the heavily infected sheep. Thus, the availability of amino nitrogen for growth and wool production is reduced. (author)

  1. Normal aging modulates the neurotoxicity of mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Elsa Diguet

    Full Text Available Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD, a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt, the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week and old (15 month rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.

  2. The mesangial matrix in the normal and sclerotic glomerulus.

    Science.gov (United States)

    Rosenblum, N D

    1994-02-01

    Mesangial sclerosis is a final common pathway to glomerular destruction in a variety of glomerular diseases. The expression of several classes of extracellular matrix (ECM) molecules has been defined in the normal and diseased mesangial matrix (MM). However, the manner in which these ECM components determine the three dimensional structure and function of the MM remains to be defined. Structural studies of the MM suggest that its constituent molecules are regionally organized into subcompartments with different three dimensional structures. The diversity of matrix molecules expressed within the MM as well as the organization of these components in nonrenal ECM's, such as the cornea, provides further support for this organizational model. The study of the cornea has also revealed that novel short chain collagenous proteins partially determine the three dimensional structure of the matrix. Recently, a novel collagen, type VIII collagen, has been described in mesangial cells and in the intact glomerulus. It is hypothesized that type VIII collagen is expressed both as a polymer and as a monomer within the glomerulus, and depending on its conformation, may serve unique functions. In the chronically diseased MM, normal MM components are overexpressed and fibrillar collagens are expressed de novo in a delayed fashion. Enhanced proteoglycan expression, observed early in disease, may determine increased volume of the mesangium. This, in turn, may stimulate the production of fibrillar collagens by mesangial cells resulting in a fibrillar noncompliant mesangial matrix.

  3. [Study on FTIR spectra of finger nails of normal people and patients of esophagus cancer].

    Science.gov (United States)

    Wang, Hong-Yan; Lü, Yin; Wang, Fan; Ma, Xiao-Dong; Jiang, Shi-Ping; Wang, Wei; Li, Cheng-Xiang

    2008-02-01

    To investigate the application of human finger nails in the diagnosis of cancer, Fourier transform infrared (FTIR) spectroscopy was employed to study the finger nails from some normal people and some with esophagus cancer and others with an operation for curing esophagus cancer five months ago. The results showed that there are obvious differences between FTIR spectra in them in spectral parameters such as frequency, intensity and band shape etc. The changes in the phosphate symmetric stretching vibration v(s) (PO2-) and asymmetric stretching vibration v(a)s(PO2-) modes are uniform, the v(s) (PO2-) and v(a)s(PO2-) absorption peaks of cancerous ones shift to high wave number compared with those of normal people, while those with operation shift to low wave number compared with those of cancerous ones. The C-O stretching vibration mode of protein located at 1 164 cm(-1) is composed of three absorption peaks located at 1 173.3, 1 158.0 and 1 151.1 cm(-1) respectively, meanwhile, the intensities and the wave numbers of the three peaks of cancerous ones all increase compared with normal people. The wave numbers of amide I and amide II of cancerous ones are both lower than those of normal people, while those with operation are between the cancerous ones and normal people, which suggest that the contents of protein and alpha-helix in finger nails of normal people, cancerous ones and the ones with operation are discriminative. The peak of bending vibration delta(CH2) mode of CH2 groups of protein lipid of cancerous ones shifts to high wave number slightly and the intensity of the peak weakens compared with that of normal people, which indicate that the methylene chain in the finger nails membrane lipids of cancerous ones is more ordered than that of normal people. Nevertheless, the peak of stretching vibration v(s) (CH2) of cancerous ones is lower than that of normal people, while that of the ones with operation is between cancerous ones and normal ones. As a result, the

  4. A new essential protein discovery method based on the integration of protein-protein interaction and gene expression data

    Directory of Open Access Journals (Sweden)

    Li Min

    2012-03-01

    Full Text Available Abstract Background Identification of essential proteins is always a challenging task since it requires experimental approaches that are time-consuming and laborious. With the advances in high throughput technologies, a large number of protein-protein interactions are available, which have produced unprecedented opportunities for detecting proteins' essentialities from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. However, the network topology-based centrality measures are very sensitive to the robustness of network. Therefore, a new robust essential protein discovery method would be of great value. Results In this paper, we propose a new centrality measure, named PeC, based on the integration of protein-protein interaction and gene expression data. The performance of PeC is validated based on the protein-protein interaction network of Saccharomyces cerevisiae. The experimental results show that the predicted precision of PeC clearly exceeds that of the other fifteen previously proposed centrality measures: Degree Centrality (DC, Betweenness Centrality (BC, Closeness Centrality (CC, Subgraph Centrality (SC, Eigenvector Centrality (EC, Information Centrality (IC, Bottle Neck (BN, Density of Maximum Neighborhood Component (DMNC, Local Average Connectivity-based method (LAC, Sum of ECC (SoECC, Range-Limited Centrality (RL, L-index (LI, Leader Rank (LR, Normalized α-Centrality (NC, and Moduland-Centrality (MC. Especially, the improvement of PeC over the classic centrality measures (BC, CC, SC, EC, and BN is more than 50% when predicting no more than 500 proteins. Conclusions We demonstrate that the integration of protein-protein interaction network and gene expression data can help improve the precision of predicting essential proteins. The new centrality measure, PeC, is an effective essential protein discovery method.

  5. Protein mislocalization: mechanisms, functions and clinical applications in cancer

    Science.gov (United States)

    Wang, Xiaohong; Li, Shulin

    2014-01-01

    The changes from normal cells to cancer cells are primarily regulated by genome instability, which foster hallmark functions of cancer through multiple mechanisms including protein mislocalization. Mislocalization of these proteins, including oncoproteins, tumor suppressors, and other cancer-related proteins, can interfere with normal cellular function and cooperatively drive tumor development and metastasis. This review describes the cancer-related effects of protein subcellular mislocalization, the related mislocalization mechanisms, and the potential application of this knowledge to cancer diagnosis, prognosis, and therapy. PMID:24709009

  6. Comparative proteomics of matrix fractions between pimpled and normal chicken eggshells.

    Science.gov (United States)

    Liu, Zhangguo; Song, Lingzi; Lu, Lizhi; Zhang, Xianfu; Zhang, Fuming; Wang, Kehua; Linhardt, Robert J

    2017-09-07

    Eggshell matrix can be dissociated into three matrix fractions: acid-insoluble matrix (M1), water-insoluble matrix (M2) and acid-water facultative-soluble matrix (M3). Matrix fractions from pimpled and normal eggshells were compared using label-free proteomic method to understand the differences among three matrix fractions and the proteins involved with eggshell quality. A total of 738 and 600 proteins were identified in the pimpled and normal calcified eggshells, respectively. Both eggshells showed a combined proteomic inventory of 769 proteins. In the same type of eggshell, a high similarity was present in the proteomes of three matrix fractions. These triply overlapped common proteins formed the predominant contributor to proteomic abundance in the matrix fractions. In each matrix fraction and between both eggshell models, normal and pimpled eggshells, a majority of the proteomes of the fractions were commonly observed. Forty-two common major proteins (iBAQ-derived abundance ≥0.095% of proteomic abundance) were identified throughout the three matrix fractions and these proteins might act as backbone constituents in chicken eggshell matrix. Finally, using 1.75-fold as up-regulated and using 0.57-fold as down-regulated cutoff values, twenty-five differential major proteins were screened and they all negatively influence and none showed any effect on eggshell quality. Overall, we uncovered the characteristics of proteomics of three eggshell matrix fractions and identified candidate proteins influencing eggshell quality. The next research on differential proteins will uncover the potential mechanisms underlying how proteins affect eggshell quality. It was reported that the proteins in an eggshell can be divided into insoluble and soluble proteins. The insoluble proteins are thought to be an inter-mineral matrix and acts as a structural framework, while the soluble proteins are thought as intra-mineral matrix that are embedded within the crystal during

  7. Protein-based nanotoxicology assessment strategy

    DEFF Research Database (Denmark)

    Elnegaard, Marlene Pedersen; List, Markus; Christiansen, Helle

    2017-01-01

    to improve selection of primary hits for subsequent analysis. As nanodrug mimics, we analyzed the effect of transiently transfected siRNAs in MCF7 breast cancer cells and normal MCF12A breast cells, resembling a differential screen. As a measure of cytotoxicity, we determined cell viability as well...... as protein expression of glyceraldehyde-3-phosphate dehydrogenase, transferrin receptor, and the proliferation marker Ki67. The evaluation of cell lethality and protein expression unraveled cellular effects overseen by one method alone....

  8. On the transition to the normal phase for superconductors surrounded by normal conductors

    DEFF Research Database (Denmark)

    Fournais, Søren; Kachmar, Ayman

    2009-01-01

    For a cylindrical superconductor surrounded by a normal material, we discuss transition to the normal phase of stable, locally stable and critical configurations. Associated with those phase transitions, we define critical magnetic fields and we provide a sufficient condition for which those...

  9. Inheritance of Properties of Normal and Non-Normal Distributions after Transformation of Scores to Ranks

    Science.gov (United States)

    Zimmerman, Donald W.

    2011-01-01

    This study investigated how population parameters representing heterogeneity of variance, skewness, kurtosis, bimodality, and outlier-proneness, drawn from normal and eleven non-normal distributions, also characterized the ranks corresponding to independent samples of scores. When the parameters of population distributions from which samples were…

  10. Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

    Science.gov (United States)

    Nordio, Laura; Marques, Andreia T; Lecchi, Cristina; Luciano, Alberto M; Stefanello, Damiano; Giudice, Chiara

    2018-04-01

    Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

  11. Effect of diet protein quality on growth and protein synthesis in rats

    International Nuclear Information System (INIS)

    Chinchalkar, D.V.; Mehta, S.L.

    1978-01-01

    The effect of diet protein quality on albino rats was studied by feeding normal and opaque-2 maize. The weight gain in rats was 60 percent higher on opaque-2 maize as compared to those fed on normal maize. Rats converted 1.0 g of dietary opaque-2 maize to 0.226 g weight gain as compared to 0.131 g for normal maize. The protein content per liver was higher with opaque-2 maize diet suggesting a higher net protein synthesis in opaque-2 maize fed rat livers. In vitro 14 C-phenylalanine incorporation showed that polysomes from opaque-2 maize fed rat livers were more efficient in protein synthesis than those from normal maize fed rat livers. Addition of poly-U resulted in more enhanced amino acid incorporation with polysomes from normal maize fed rats as compared to other group indicating greater limitation of mRNA in polysomes from normal maize fed rats. The total yield of liver polysomes from opaque-2 maize fed rats was substantially higher. (author)

  12. Normal gravity field in relativistic geodesy

    Science.gov (United States)

    Kopeikin, Sergei; Vlasov, Igor; Han, Wen-Biao

    2018-02-01

    Modern geodesy is subject to a dramatic change from the Newtonian paradigm to Einstein's theory of general relativity. This is motivated by the ongoing advance in development of quantum sensors for applications in geodesy including quantum gravimeters and gradientometers, atomic clocks and fiber optics for making ultra-precise measurements of the geoid and multipolar structure of the Earth's gravitational field. At the same time, very long baseline interferometry, satellite laser ranging, and global navigation satellite systems have achieved an unprecedented level of accuracy in measuring 3-d coordinates of the reference points of the International Terrestrial Reference Frame and the world height system. The main geodetic reference standard to which gravimetric measurements of the of Earth's gravitational field are referred is a normal gravity field represented in the Newtonian gravity by the field of a uniformly rotating, homogeneous Maclaurin ellipsoid of which mass and quadrupole momentum are equal to the total mass and (tide-free) quadrupole moment of Earth's gravitational field. The present paper extends the concept of the normal gravity field from the Newtonian theory to the realm of general relativity. We focus our attention on the calculation of the post-Newtonian approximation of the normal field that is sufficient for current and near-future practical applications. We show that in general relativity the level surface of homogeneous and uniformly rotating fluid is no longer described by the Maclaurin ellipsoid in the most general case but represents an axisymmetric spheroid of the fourth order with respect to the geodetic Cartesian coordinates. At the same time, admitting a post-Newtonian inhomogeneity of the mass density in the form of concentric elliptical shells allows one to preserve the level surface of the fluid as an exact ellipsoid of rotation. We parametrize the mass density distribution and the level surface with two parameters which are

  13. Radiation therapy and late reactions in normal tissues

    International Nuclear Information System (INIS)

    Aoyama, Takashi; Kuroda, Yasumasa

    1998-01-01

    Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)

  14. Deformation associated with continental normal faults

    Science.gov (United States)

    Resor, Phillip G.

    Deformation associated with normal fault earthquakes and geologic structures provide insights into the seismic cycle as it unfolds over time scales from seconds to millions of years. Improved understanding of normal faulting will lead to more accurate seismic hazard assessments and prediction of associated structures. High-precision aftershock locations for the 1995 Kozani-Grevena earthquake (Mw 6.5), Greece image a segmented master fault and antithetic faults. This three-dimensional fault geometry is typical of normal fault systems mapped from outcrop or interpreted from reflection seismic data and illustrates the importance of incorporating three-dimensional fault geometry in mechanical models. Subsurface fault slip associated with the Kozani-Grevena and 1999 Hector Mine (Mw 7.1) earthquakes is modeled using a new method for slip inversion on three-dimensional fault surfaces. Incorporation of three-dimensional fault geometry improves the fit to the geodetic data while honoring aftershock distributions and surface ruptures. GPS Surveying of deformed bedding surfaces associated with normal faulting in the western Grand Canyon reveals patterns of deformation that are similar to those observed by interferometric satellite radar interferometry (InSAR) for the Kozani Grevena earthquake with a prominent down-warp in the hanging wall and a lesser up-warp in the footwall. However, deformation associated with the Kozani-Grevena earthquake extends ˜20 km from the fault surface trace, while the folds in the western Grand Canyon only extend 500 m into the footwall and 1500 m into the hanging wall. A comparison of mechanical and kinematic models illustrates advantages of mechanical models in exploring normal faulting processes including incorporation of both deformation and causative forces, and the opportunity to incorporate more complex fault geometry and constitutive properties. Elastic models with antithetic or synthetic faults or joints in association with a master

  15. Polycomb group protein-mediated repression of transcription

    DEFF Research Database (Denmark)

    Morey, Lluís; Helin, Kristian

    2010-01-01

    The polycomb group (PcG) proteins are essential for the normal development of multicellular organisms. They form multi-protein complexes that work as transcriptional repressors of several thousand genes controlling differentiation pathways during development. How the PcG proteins work as transcri......The polycomb group (PcG) proteins are essential for the normal development of multicellular organisms. They form multi-protein complexes that work as transcriptional repressors of several thousand genes controlling differentiation pathways during development. How the PcG proteins work...... as transcriptional repressors is incompletely understood, but involves post-translational modifications of histones by two major PcG protein complexes: polycomb repressive complex 1 and polycomb repressive complex 2....

  16. The variability problem of normal human walking

    DEFF Research Database (Denmark)

    Simonsen, Erik B; Alkjær, Tine

    2012-01-01

    Previous investigations have suggested considerable inter-individual variability in the time course pattern of net joint moments during normal human walking, although the limited sample sizes precluded statistical analyses. The purpose of the present study was to obtain joint moment patterns from...... a group of normal subjects and to test whether or not the expected differences would prove to be statistically significant. Fifteen healthy male subjects were recorded on video while they walked across two force platforms. Ten kinematic and kinetic parameters were selected and input to a statistical...... cluster analysis to determine whether or not the 15 subjects could be divided into different 'families' (clusters) of walking strategy. The net joint moments showed a variability corroborating earlier reports. The cluster analysis showed that the 15 subjects could be grouped into two clusters of 5 and 10...

  17. Autobiographical Memory in Normal Ageing and Dementia

    Directory of Open Access Journals (Sweden)

    Harvey J. Sagar

    1991-01-01

    Full Text Available Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing.

  18. A Proposed Arabic Handwritten Text Normalization Method

    Directory of Open Access Journals (Sweden)

    Tarik Abu-Ain

    2014-11-01

    Full Text Available Text normalization is an important technique in document image analysis and recognition. It consists of many preprocessing stages, which include slope correction, text padding, skew correction, and straight the writing line. In this side, text normalization has an important role in many procedures such as text segmentation, feature extraction and characters recognition. In the present article, a new method for text baseline detection, straightening, and slant correction for Arabic handwritten texts is proposed. The method comprises a set of sequential steps: first components segmentation is done followed by components text thinning; then, the direction features of the skeletons are extracted, and the candidate baseline regions are determined. After that, selection of the correct baseline region is done, and finally, the baselines of all components are aligned with the writing line.  The experiments are conducted on IFN/ENIT benchmark Arabic dataset. The results show that the proposed method has a promising and encouraging performance.

  19. Zero cosmological constant from normalized general relativity

    International Nuclear Information System (INIS)

    Davidson, Aharon; Rubin, Shimon

    2009-01-01

    Normalizing the Einstein-Hilbert action by the volume functional makes the theory invariant under constant shifts in the Lagrangian. The associated field equations then resemble unimodular gravity whose otherwise arbitrary cosmological constant is now determined as a Machian universal average. We prove that an empty space-time is necessarily Ricci tensor flat, and demonstrate the vanishing of the cosmological constant within the scalar field paradigm. The cosmological analysis, carried out at the mini-superspace level, reveals a vanishing cosmological constant for a universe which cannot be closed as long as gravity is attractive. Finally, we give an example of a normalized theory of gravity which does give rise to a non-zero cosmological constant.

  20. Suitable Image Intensity Normalization for Arterial Visualization

    Directory of Open Access Journals (Sweden)

    Yara Omran

    2012-12-01

    Full Text Available Ultrasonic imaging is a widely used non-invasivemedical imaging procedure since it is economical, comparativelysafe, portable and adaptable. However, one of its main weaknessesis the poor quality of images, which makes the enhancementof image quality an important issue in order to have a moreaccurate diagnose of the disease, or for the transformation of theimage through telemedicine channel and in many other imageprocessing tasks [1]. The purpose of this paper is to automaticallyenhance the image quality after the automatic detection of theartery wall. This step is essential before subsequent measurementsof arterial parameters [9]. This was performed automaticallyby applying linear normalization, where results showedthat normalization of ultra sound images is an important step inenhancing the image quality for later processing. In comparisonwith other methods, our method is automatic. The evaluationof image quality was done mathematically by comparing pixelintensities of images before and after enhancement, in additionto a visual evaluation.

  1. Normal anatomical measurements in cervical computerized tomography

    International Nuclear Information System (INIS)

    Zaunbauer, W.; Daepp, S.; Haertel, M.

    1985-01-01

    Radiodiagnostically relevant normal values and variations for measurements of the cervical region, the arithmetical average and the standard deviation were determined from adequate computer tomograms on 60 healthy women and men, aged 20 to 83 years. The sagittal diameter of the prevertebral soft tissue and the lumina of the upper respiratory tract were evaluated at exactly defined levels between the hyoid bone and the incisura jugularis sterni. - The thickness of the aryepiglottic folds, the maximal sagittal and transverse diameters of the thyroid gland and the calibre of the great cervical vessels were defined. - To assess information about laryngeal function in computerized tomography, measurements of distances between the cervical spine and anatomical fixed points of the larynx and hypopharynx were made as well as of the degree of vocal cord movement during normal respiration and phonation. (orig.) [de

  2. Broad Ligament Haematoma Following Normal Vaginal Delivery.

    Science.gov (United States)

    Ibrar, Faiza; Awan, Azra Saeed; Fatima, Touseef; Tabassum, Hina

    2017-01-01

    A 37-year-old, patient presented in emergency with history of normal vaginal delivery followed by development of abdominal distention, vomiting, constipation for last 3 days. She was para 4 and had normal vaginal delivery by traditional birth attendant at peripheral hospital 3 days back. Imaging study revealed a heterogeneous complex mass, ascites, pleural effusion, air fluid levels with dilatation gut loops. Based upon pelvic examination by senior gynaecologist in combination with ultrasound; a clinical diagnosis of broad ligament haematoma was made. However, vomiting and abdominal distention raised suspicion of intestinal obstruction. Due to worsening abdominal distention exploratory laparotomy was carried out. It was pseudo colonic obstruction and caecostomy was done. Timely intervention by multidisciplinary approach saved patient life with minimal morbidity.

  3. Sphalerons, deformed sphalerons and normal modes

    International Nuclear Information System (INIS)

    Brihaye, Y.; Kunz, J.; Oldenburg Univ.

    1992-01-01

    Topological arguments suggest that tha Weinberg-Salam model posses unstable solutions, sphalerons, representing the top of energy barriers between inequivalent vacua of the gauge theory. In the limit of vanishing Weinberg angle, such unstable solutions are known: the sphaleron of Klinkhamer and Manton and at large values of the Higgs mass in addition the deformed sphalerons. Here a systematic study of the discrete normal modes about these sphalerons for the full range Higgs mass is presented. The emergence of deformed sphalerons at critical values of the Higgs mass is seem to be related to the crossing of zero of the eigenvalue of the particular normal modes about the sphaleron. 6 figs., 1 tab., 19 refs. (author)

  4. Normalizing the causality between time series

    Science.gov (United States)

    Liang, X. San

    2015-08-01

    Recently, a rigorous yet concise formula was derived to evaluate information flow, and hence the causality in a quantitative sense, between time series. To assess the importance of a resulting causality, it needs to be normalized. The normalization is achieved through distinguishing a Lyapunov exponent-like, one-dimensional phase-space stretching rate and a noise-to-signal ratio from the rate of information flow in the balance of the marginal entropy evolution of the flow recipient. It is verified with autoregressive models and applied to a real financial analysis problem. An unusually strong one-way causality is identified from IBM (International Business Machines Corporation) to GE (General Electric Company) in their early era, revealing to us an old story, which has almost faded into oblivion, about "Seven Dwarfs" competing with a giant for the mainframe computer market.

  5. Normal modes of vibration in nickel

    Energy Technology Data Exchange (ETDEWEB)

    Birgeneau, R J [Yale Univ., New Haven, Connecticut (United States); Cordes, J [Cambridge Univ., Cambridge (United Kingdom); Dolling, G; Woods, A D B

    1964-07-01

    The frequency-wave-vector dispersion relation, {nu}(q), for the normal vibrations of a nickel single crystal at 296{sup o}K has been measured for the [{zeta}00], [{zeta}00], [{zeta}{zeta}{zeta}], and [0{zeta}1] symmetric directions using inelastic neutron scattering. The results can be described in terms of the Born-von Karman theory of lattice dynamics with interactions out to fourth-nearest neighbors. The shapes of the dispersion curves are very similar to those of copper, the normal mode frequencies in nickel being about 1.24 times the corresponding frequencies in copper. The fourth-neighbor model was used to calculate the frequency distribution function g({nu}) and related thermodynamic properties. (author)

  6. The self-normalized Donsker theorem revisited

    OpenAIRE

    Parczewski, Peter

    2016-01-01

    We extend the Poincar\\'{e}--Borel lemma to a weak approximation of a Brownian motion via simple functionals of uniform distributions on n-spheres in the Skorokhod space $D([0,1])$. This approach is used to simplify the proof of the self-normalized Donsker theorem in Cs\\"{o}rg\\H{o} et al. (2003). Some notes on spheres with respect to $\\ell_p$-norms are given.

  7. Normal mode analysis for linear resistive magnetohydrodynamics

    International Nuclear Information System (INIS)

    Kerner, W.; Lerbinger, K.; Gruber, R.; Tsunematsu, T.

    1984-10-01

    The compressible, resistive MHD equations are linearized around an equilibrium with cylindrical symmetry and solved numerically as a complex eigenvalue problem. This normal mode code allows to solve for very small resistivity eta proportional 10 -10 . The scaling of growthrates and layer width agrees very well with analytical theory. Especially, both the influence of current and pressure on the instabilities is studied in detail; the effect of resistivity on the ideally unstable internal kink is analyzed. (orig.)

  8. On Normalized Compression Distance and Large Malware

    OpenAIRE

    Borbely, Rebecca Schuller

    2015-01-01

    Normalized Compression Distance (NCD) is a popular tool that uses compression algorithms to cluster and classify data in a wide range of applications. Existing discussions of NCD's theoretical merit rely on certain theoretical properties of compression algorithms. However, we demonstrate that many popular compression algorithms don't seem to satisfy these theoretical properties. We explore the relationship between some of these properties and file size, demonstrating that this theoretical pro...

  9. The J/$\\psi$ normal nuclear absorption

    CERN Document Server

    Alessandro, B; Arnaldi, R; Atayan, M; Beolè, S; Boldea, V; Bordalo, P; Borges, G; Castanier, C; Castor, J; Chaurand, B; Cheynis, B; Chiavassa, E; Cicalò, C; Comets, M P; Constantinescu, S; Cortese, P; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Fargeix, J; Force, P; Gallio, M; Gerschel, C; Giubellino, P; Golubeva, M B; Grigorian, A A; Grigorian, S; Guber, F F; Guichard, A; kanyan, H; ldzik, M; Jouan, D; Karavicheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Cormick, M M; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prino, F; Puddu, G; Quintans, C; Ramello, L; Ramos, S; Riccati, L; Santos, H; Saturnini, P; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, M F; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N; Wu T

    2005-01-01

    We present a new determination of the ratio of cross-sections (J/psi) /DY as expected for nucleus-nucleus reactions if J/psi would only be normally absorbed by nuclear matter. This anticipated behaviour is based on proton-nucleus data exclusively, and compared, as a function of centrality, with updated S-U results from experiment NA38 and with the most recent Pb-Pb results from experiment NA50.

  10. Research on Normal Human Plantar Pressure Test

    Directory of Open Access Journals (Sweden)

    Liu Xi Yang

    2016-01-01

    Full Text Available FSR400 pressure sensor, nRF905 wireless transceiver and MSP40 SCM are used to design the insole pressure collection system, LabVIEW is used to make HMI of data acquisition, collecting a certain amount of normal human foot pressure data, statistical analysis of pressure distribution relations about five stages of swing phase during walking, using the grid closeness degree to identify plantar pressure distribution pattern recognition, and the algorithm simulation, experimental results demonstrated this method feasible.

  11. The classification of normal screening mammograms

    Science.gov (United States)

    Ang, Zoey Z. Y.; Rawashdeh, Mohammad A.; Heard, Robert; Brennan, Patrick C.; Lee, Warwick; Lewis, Sarah J.

    2016-03-01

    Rationale and objectives: To understand how breast screen readers classify the difficulty of normal screening mammograms using common lexicon describing normal appearances. Cases were also assessed on their suitability for a single reader strategy. Materials and Methods: 15 breast readers were asked to interpret a test set of 29 normal screening mammogram cases and classify them by rating the difficulty of the case on a five-point Likert scale, identifying the salient features and assessing their suitability for single reading. Using the False Positive Fractions from a previous study, the 29 cases were classified into 10 "low", 10 "medium" and nine "high" difficulties. Data was analyzed with descriptive statistics. Spearman's correlation was used to test the strength of association between the difficulty of the cases and the readers' recommendation for single reading strategy. Results: The ratings from readers in this study corresponded to the known difficulty level of cases for the 'low' and 'high' difficulty cases. Uniform ductal pattern and density, symmetrical mammographic features and the absence of micro-calcifications were the main reasons associated with 'low' difficulty cases. The 'high' difficulty cases were described as having `dense breasts'. There was a statistically significant negative correlation between the difficulty of the cases and readers' recommendation for single reading (r = -0.475, P = 0.009). Conclusion: The findings demonstrated potential relationships between certain mammographic features and the difficulty for readers to classify mammograms as 'normal'. The standard Australian practice of double reading was deemed more suitable for most cases. There was an inverse moderate association between the difficulty of the cases and the recommendations for single reading.

  12. Geomagnetic reversal in brunhes normal polarity epoch.

    Science.gov (United States)

    Smith, J D; Foster, J H

    1969-02-07

    The magnetic stratigraphly of seven cores of deep-sea sediment established the existence of a short interval of reversed polarity in the upper part of the Brunches epoch of normal polarity. The reversed zone in the cores correlates well with paleontological boundaries and is named the Blake event. Its boundaries are estimated to be 108,000 and 114,000 years ago +/- 10 percent.

  13. Ureterocolonic anastomosis in clinically normal dogs

    International Nuclear Information System (INIS)

    Stone, E.A.; Walter, M.C.; Goldschmidt, M.H.; Biery, D.N.; Bovee, K.C.

    1988-01-01

    Ureterocolonic anastomosis was evaluated in 13 clinically normal dogs. Urinary continence was maintained after surgery, and the procedure was completed without technique errors in all but 2 dogs. Three dogs died within 5 weeks (2 of undetermined causes and 1 of aspiration pneumonia and neurologic disease), and 1 dog was euthanatized 4 months after surgery because of neurologic signs. Two healthy dogs were euthanatized 3 months after surgery for light microscopic evaluation of their kidneys. Five dogs were euthanatized 6 months after surgery for light microscopic evaluation of their kidneys. Gastrointestinal and neurologic disturbances developed in 4 dogs at various postoperative intervals. Plasma ammonia concentration measured in 2 dogs with neurologic signs was increased. Plasma ammonia concentration measured in 5 dogs without neurologic signs was within normal limits. All 5 dogs, in which metabolic acidosis was diagnosed, had high normal or above normal serum chloride concentration. Serum urea nitrogen values were increased after surgery because of colonic absorption of urea. Serum creatinine concentration was increased in 1 dog 6 months after surgery. Individual kidney glomerular filtration rate was reduced in 38% (3/8) of the kidneys from 4 other dogs at 6 months after surgery. Of 5 dogs euthanatized at 3 to 4 months after surgery, 4 had bilateral pyelitis, and 1 had unilateral pyelonephritis. Six months after surgery, pyelonephritis was diagnosed in 40% (4/10) of the kidneys from 5 dogs. The ureterocolonic anastomosis procedure is a salvage procedure that should allow complete cystectomy. However, variable degress of metabolic acidosis, hyperammonemia, and neurologic disease may result

  14. The thoracic paraspinal shadow: normal appearances.

    Science.gov (United States)

    Lien, H H; Kolbenstvedt, A

    1982-01-01

    The width of the right and left thoracic paraspinal shadows were measured at all levels in 200 presumably normal individuals. The paraspinal shadow could be identified in nearly all cases on the left side and in approximately one-third on the right. The range of variation was greater on the left side than one the right. The left paraspinal shadow was wider at the upper levels and in individuals above 40 years of age.

  15. Online Normalization Algorithm for Engine Turbofan Monitoring

    Science.gov (United States)

    2014-10-02

    Online Normalization Algorithm for Engine Turbofan Monitoring Jérôme Lacaille 1 , Anastasios Bellas 2 1 Snecma, 77550 Moissy-Cramayel, France...understand the behavior of a turbofan engine, one first needs to deal with the variety of data acquisition contexts. Each time a set of measurements is...it auto-adapts itself with piecewise linear models. 1. INTRODUCTION Turbofan engine abnormality diagnosis uses three steps: reduction of

  16. Comet Giacobini-Zinner - a normal comet?

    International Nuclear Information System (INIS)

    Cochran, A.L.; Barker, E.S.

    1987-01-01

    Observations of Comet Giacobini-Zinner were obtained during its 1985 apparition using an IDS spectrograph at McDonald Observatory. Column densities and production rates were computed. The production rates were compared to observations of other normal comets. Giacobini-Zinner is shown to be depleted in C2 and C3 relative to CN. These production rates are down by a factor of 5. 12 references

  17. Manual on environmental monitoring in normal operation

    International Nuclear Information System (INIS)

    1966-01-01

    Many establishments handling radioactive materials produce, and to some extent also discharge, radioactive waste as part of their normal operation. The radiation doses to which members of the public may be exposed during such operation must remain below the stipulated level. The purpose of this manual is to provide technical guidance for setting up programmes of routine environmental monitoring in the vicinity of nuclear establishment. The annex gives five examples of routine environmental monitoring programmes currently in use: these have been indexed separately.

  18. Normal Conducting RF Cavity for MICE

    International Nuclear Information System (INIS)

    Li, D.; DeMello, A.; Virostek, S.; Zisman, M.; Summers, D.

    2010-01-01

    Normal conducting RF cavities must be used for the cooling section of the international Muon Ionization Cooling Experiment (MICE), currently under construction at Rutherford Appleton Laboratory (RAL) in the UK. Eight 201-MHz cavities are needed for the MICE cooling section; fabrication of the first five cavities is complete. We report the cavity fabrication status including cavity design, fabrication techniques and preliminary low power RF measurements.

  19. Basic characterization of normal multifocal electroretinogram

    International Nuclear Information System (INIS)

    Fernandez Cherkasova, Lilia; Rojas Rondon, Irene; Castro Perez, Pedro Daniel; Lopez Felipe, Daniel; Santiesteban Freixas, Rosaralis; Mendoza Santiesteban, Carlos E

    2008-01-01

    A scientific literature review was made on the novel multifocal electroretinogram technique, the involved cell mechanisms and some of the factors modifying its results together with the form of presentation. The basic characteristics of this electrophysiological record obtained from several regions of the retina of normal subjects is important in order to create at a small scale a comparative database to evaluate pathological eye tracing. All this will greatly help in early less invasive electrodiagnosis of localized retinal lesions. (Author)

  20. Estimating the Heading Direction Using Normal Flow

    Science.gov (United States)

    1994-01-01

    understood (Faugeras and Maybank 1990), 3 Kinetic Stabilization under the assumption that optic flow or correspon- dence is known with some uncertainty...accelerometers can achieve very It can easily be shown (Koenderink and van Doom high accuracy, the same is not true for inexpensive 1975; Maybank 1985... Maybank . ’Motion from point matches: Multi- just don’t compute normal flow there (see Section 6). plicity of solutions". Int’l J. Computer Vision 4