WorldWideScience

Sample records for proximal regulatory region

  1. Characterization of the cis elements in the proximal promoter regions of the anthocyanin pathway genes reveals a common regulatory logic that governs pathway regulation.

    Science.gov (United States)

    Zhu, Zhixin; Wang, Hailong; Wang, Yiting; Guan, Shan; Wang, Fang; Tang, Jingyu; Zhang, Ruijuan; Xie, Lulu; Lu, Yingqing

    2015-07-01

    Cellular activities such as compound synthesis often require the transcriptional activation of an entire pathway; however, the molecular mechanisms underlying pathway activation have rarely been explained. Here, the cis regulatory architecture of the anthocyanin pathway genes targeted by the transcription factor (TF) complex including MYB, bHLH, and WDR was systematically analysed in one species and the findings extended to others. In Ipomoea purpurea, the IpMYB1-IpbHLH2-IpWDR1 (IpMBW) complex was found to be orthologous to the PAP1-GL3-TTG1 (AtPGT) complex of Arabidopsis thaliana, and interacted with a 7-bp MYB-recognizing element (MRE) and a 6-bp bHLH-recognizing element (BRE) at the proximal promoter region of the pathway genes. There was little transcription of the gene in the absence of the MRE or BRE. The cis elements identified experimentally converged on two syntaxes, ANCNNCC for MREs and CACN(A/C/T)(G/T) for BREs, and our bioinformatic analysis showed that these were present within anthocyanin gene promoters in at least 35 species, including both gymnosperms and angiosperms. For the anthocyanin pathway, IpMBW and AtPGT recognized the interspecific promoters of both early and later genes. In A. thaliana, the seed-specific TF complex (TT2, TT8, and TTG1) may regulate all the anthocyanin pathway genes, in addition to the proanthocyanidin-specific BAN. When multiple TF complexes in the anthocyanin pathway were compared, the cis architecture played a role larger than the TF complex in determining the variation in promoter activity. Collectively, a cis logic common to the pathway gene promoters was found, and this logic is essential for the trans factors to regulate the pathway. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  2. Regulatory Focus, Proximity to Goal Weight, and Weight Loss Maintenance.

    Science.gov (United States)

    Fuglestad, Paul T; Rothman, Alexander J; Jeffery, Robert W; Sherwood, Nancy E

    2015-09-01

    Regulatory focus theory proposes 2 self-regulatory orientations: promotion focus - related to achieving aspirations and positive outcomes - and prevention focus - related to fulfilling responsibilities and preventing negative outcomes. The investigation examined whether regulatory focus and proximity to goal weight moderated the effectiveness of a weight-loss maintenance intervention. Participants who lost ≥10% of their weight were assigned to guided or self-directed treatments and completed regulatory focus and weight goal measures. Across treatment groups, people who were more promotion-focused had better 2-year maintenance rates (defined as regain focused, especially if far from their goal weight (.59 versus .44). In the guided group, people who were more prevention-focused had better maintenance rates than people who were less prevention-focused if closer to their goal weight (.69 versus .42), but poorer maintenance rates if farther from their goal (.36 versus .72). In the self-directed group, prevention focus was unrelated to maintenance. Regulatory focus and proximity to goal weight moderated intervention effectiveness. Maintenance may be enhanced by tailoring treatments to regulatory focus and goal weight (eg, prevention-focused people far from their goals may need extra weight-loss support before focusing on maintenance).

  3. The regional dimension of intergenerational proximity in the Netherlands

    NARCIS (Netherlands)

    van der Pers, Marieke; Mulder, Clara H.

    Previous research has shown the impact of individual characteristics on intergenerational proximity but has largely ignored the regional dimension of such proximity. In this paper, we examine the regional variation in intergenerational proximity in the Netherlands. We address this issue by

  4. Federal Energy Regulatory Commission (FERC) Regions

    Data.gov (United States)

    Department of Homeland Security — Federal Energy Regulatory Commission (FERC) Regions. FERC is an independent agency that regulates the interstate transmission of electricity, natural gas, and oil....

  5. 75 FR 17793 - Public Federal Regulatory Enforcement Fairness Hearing; Region III Regulatory Fairness Board

    Science.gov (United States)

    2010-04-07

    ... ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing; Region III Regulatory Fairness Board.... Small Business Administration (SBA) Region III Regulatory Fairness Board and the SBA Office of the National Ombudsman will hold a National Regulatory Fairness Hearing on Tuesday, May 18, 2010, at 10 a.m...

  6. 78 FR 36011 - Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing

    Science.gov (United States)

    2013-06-14

    ... ADMINISTRATION Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing AGENCY: U.S... Business Regulatory Fairness Board. SUMMARY: The (SBA) Office of the National Ombudsman is issuing this notice to announce the location, date and time of the Regional Small Business Regulatory Fairness hearing...

  7. 75 FR 18245 - Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board

    Science.gov (United States)

    2010-04-09

    ... ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board.... Small Business Administration (SBA) Region IX Regulatory Fairness Board and the SBA Office of the National Ombudsman will hold a National Regulatory Fairness Hearing on Monday, April 26, 2010, at 1:30 p.m...

  8. 78 FR 30384 - Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board

    Science.gov (United States)

    2013-05-22

    ... ADMINISTRATION Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board AGENCY: U.S... Business Regulatory Fairness Board. SUMMARY: The (SBA) Office of the National Ombudsman is issuing this notice to announce the location, date and time of the Regional Small Business Regulatory Fairness hearing...

  9. [Ultrastructure of the proximal neurosecretory contact region in a sturgeon].

    Science.gov (United States)

    Belenkiĭ, M A

    1976-01-01

    The proximal neurosecretory contact region (PCR), a homologue of the tetrapoda median eminence occupies the rostral and chiefly the ventral surfaces of the hypothalamic tuber cinereum. Three types of granule-containing neurosecretory fibres and their terminals have been found in the PCR with the electron microscope. Peptidergic, A1 and A2 type fibres contain granules of 120--300 nm and 100--170 nm in diameter, correspondingly, and monoaminergic B fibres have granules of 80--100 nm in diameter. Neurosecretory terminals and tanycyte vascular "endfeet" make contacts with a 70 nm thick outer basement membrane of the primary portal capillaries. Some thin horizontally oriented tanycyte branches form a multiserial layer bordering the external zone of the PCR from the preoptico-hypophyseal tract. Few neuroglial cells with pale cytoplasm and numerous lysosomes and lipofuscin granules are seen there. It is hypothesized that, like in other vertebrates, in the PCR of Acipenseridae both peptide and monoamine hypophysiotropic neurohormones may be discharged in the portal circulation to affect the functional activity of glandular cells of the pars distalis.

  10. The theoretical simulation on electrostatic distribution of 1st proximity region in proximity focusing low-light-level image intensifier

    Science.gov (United States)

    Zhang, Liandong; Bai, Xiaofeng; Song, De; Fu, Shencheng; Li, Ye; Duanmu, Qingduo

    2015-03-01

    Low-light-level night vision technology is magnifying low light level signal large enough to be seen by naked eye, which uses the photons - photoelectron as information carrier. Until the micro-channel plate was invented, it has been possibility for the realization of high performance and miniaturization of low-light-level night vision device. The device is double-proximity focusing low-light-level image intensifier which places a micro-channel plate close to photocathode and phosphor screen. The advantages of proximity focusing low-light-level night vision are small size, light weight, small power consumption, no distortion, fast response speed, wide dynamic range and so on. It is placed parallel to each other for Micro-channel plate (both sides of it with metal electrode), the photocathode and the phosphor screen are placed parallel to each other. The voltage is applied between photocathode and the input of micro-channel plate when image intensifier works. The emission electron excited by photo on the photocathode move towards to micro-channel plate under the electric field in 1st proximity focusing region, and then it is multiplied through the micro-channel. The movement locus of emission electrons can be calculated and simulated when the distributions of electrostatic field equipotential lines are determined in the 1st proximity focusing region. Furthermore the resolution of image tube can be determined. However the distributions of electrostatic fields and equipotential lines are complex due to a lot of micro-channel existing in the micro channel plate. This paper simulates electrostatic distribution of 1st proximity region in double-proximity focusing low-light-level image intensifier with the finite element simulation analysis software Ansoft maxwell 3D. The electrostatic field distributions of 1st proximity region are compared when the micro-channel plates' pore size, spacing and inclination angle ranged. We believe that the electron beam movement

  11. 76 FR 26333 - National Federal Regulatory Enforcement Fairness Hearing Region III Regulatory Fairness Board

    Science.gov (United States)

    2011-05-06

    ... ADMINISTRATION National Federal Regulatory Enforcement Fairness Hearing Region III Regulatory Fairness Board... III) Small Business Regulatory Fairness Board. SUMMARY: The SBA, Office of the National Ombudsman is... Fairness Hearing. This hearing is open to the public. DATES: The hearing will be held on Tuesday, May 24...

  12. 76 FR 9630 - Federal Regulatory Enforcement Fairness Hearing; National Ombudsman and Region VI Regional Small...

    Science.gov (United States)

    2011-02-18

    ... ADMINISTRATION Federal Regulatory Enforcement Fairness Hearing; National Ombudsman and Region VI Regional Small Business Regulatory Fairness Board AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of open hearing of the Regional (Region VI) Small Business Regulatory Fairness Board. SUMMARY: The SBA, Office of...

  13. TGF-? maintains dormancy of prostatic stem cells in the proximal region of ducts

    OpenAIRE

    Salm, Sarah N.; Patricia E Burger; Coetzee, Sandra; Goto, Ken; Moscatelli, David; Wilson, E. Lynette

    2005-01-01

    We have previously shown that prostatic stem cells are located in the proximal region of mouse prostatic ducts. Here, we show that this region responds differently to transforming growth factor (TGF)-? than the distal ductal region and that under physiological conditions androgens and TGF-? are crucial overall regulators of prostatic tissue homeostasis. This conclusion is supported by the observations showing that high levels of TGF-? signaling are present in the quiescent proximal region of ...

  14. Sex combs reduced (Scr) regulatory region of Drosophila revisited.

    Science.gov (United States)

    Calvo-Martín, Juan M; Papaceit, Montserrat; Segarra, Carmen

    2017-08-01

    The Hox gene Sex combs reduced (Scr) is responsible for the differentiation of the labial and prothoracic segments in Drosophila. Scr is expressed in several specific tissues throughout embryonic development, following a complex path that must be coordinated by an equally complex regulatory region. Although some cis-regulatory modules (CRMs) have been identified in the Scr regulatory region (~75 kb), there has been no detailed and systematic study of the distinct regulatory elements present within this region. In this study, the Scr regulatory region was revisited with the aim of filling this gap. We focused on the identification of Initiator elements (IEs) that bind segmentation factors, Polycomb response elements (PREs) that are recognized by the Polycomb and Trithorax complexes, as well as insulators and tethering elements. To this end, we summarized all currently available information, mainly obtained from high throughput ChIP data projects. In addition, a bioinformatic analysis based on the evolutionary conservation of regulatory sequences using the software MOTEVO was performed to identify IE and PRE candidates in the Scr region. The results obtained by this combined strategy are largely consistent with the CRMs previously identified in the Scr region and help to: (i) delimit them more accurately, (ii) subdivide two of them into different independent elements, (iii) identify a new CRM, (iv) identify the composition of their binding sites and (v) better define some of their characteristics. These positive results indicate that an approach that integrates functional and bioinformatic data might be useful to characterize other regulatory regions.

  15. Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue

    OpenAIRE

    Patricia E Burger; Xiong, Xiaozhong; Coetzee, Sandra; Salm, Sarah N.; Moscatelli, David; Goto, Ken; Wilson, E. Lynette

    2005-01-01

    We previously showed that prostatic stem cells are concentrated in the proximal regions of prostatic ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of ducts was more effective in generating prostatic tissue than a comparable populat...

  16. Regulatory Regionalism and Education: The European Union in Central Asia

    Science.gov (United States)

    Jones, Peter

    2010-01-01

    This paper investigates the purchase which Jayasuriya's regulatory regionalism approach offers for an analysis of the European Union's engagement in Central Asia. The European Union has a clearly articulated strategy through which to pursue what it sees as its interests in Central Asia and the development of a range of EU-Central Asia education…

  17. Socio-cultural proximity, daily life and shopping tourism in the Dutch–German border region

    NARCIS (Netherlands)

    Szytniewski, Bianca B.; Spierings, Bas; van der Velde, Martin

    2017-01-01

    This paper analyses feelings of socio-cultural proximity and distance with a specific focus on the tourist experience in cross-border shopping and everyday life practices in border regions. We examined shopping practices of Dutch border crossers who visit the German town Kleve in the Dutch–German

  18. Proximal antecedents and correlates of adopted error approach: a self-regulatory perspective

    NARCIS (Netherlands)

    van Dyck, C.; van Hooft, E.; de Gilder, D.; Liesveld, L.C.

    2010-01-01

    The current study aims to further investigate earlier established advantages of an error mastery approach over an error aversion approach. The two main purposes of the study relate to (1) self-regulatory traits (i.e., goal orientation and action-state orientation) that may predict which error

  19. Proximal antecedents and correlates of adopted error approach: A self-regulatory perspective

    NARCIS (Netherlands)

    van Dyck, C.; van Hooft, E.A.J.; de Gilder, T.C.; Liesveld, L.C.

    2010-01-01

    The current study aims to further investigate earlier established advantages of an error mastery approach over an error aversion approach. The two main purposes of the study relate to (1) self-regulatory traits (i.e., goal orientation and action-state orientation) that may predict which error

  20. Proximity and scientific collaboration in Northern European “cross-border regional innovation systems”

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Williams, Allan

    2015-01-01

    A novel approach, namely cross-border regional innovation system, has been recently introduced to the literature on economic geography as a framework for studying innovation and scientific collaboration in a cross-border context. However, despite the importance of the topic for cross-border regions......, there are no existing empirical accounts comprehensively validating the concept. Here an attempt to shed some light into this “black box” is made by addressing this research gap via empirical material from Northern European cross-border regions. Specifically this is done by applying data on publications, sectoral...... and cultural statistics together with measures for accessibility and institutional and organisational similarity. These measures are linked to the varying types of proximity discussed in the literature on innovation and scientific collaboration; the impacts of proximity on the volume of cross-border scientific...

  1. Regionalization of municipal solid waste management in Japan: balancing the proximity principle with economic efficiency.

    Science.gov (United States)

    Okuda, Itaru; Thomson, Vivian E

    2007-07-01

    The proximity principle - disposing of waste close to its origin - has been a central value in municipal solid waste (MSW) management in Japan for the last 30 years and its widespread adoption has helped resolve numerous "Not in My Backyard" issues related to MSW management. However, MSW management costs have soared, in large part because of aggressive recycling efforts and because most MSW is incinerated in a country that has scarce landfill capacity. In addition, smaller, less sophisticated incinerators have been closed because of high dioxin emissions. Rising costs combined with the closure of smaller incinerators have shifted MSW management policy toward regionalization, which is the sharing of waste management facilities across municipalities. Despite the increased use of regionalized MSW facilities, the proximity principle remains the central value in Japanese MSW management. Municipal solid waste management has become increasingly regionalized in the United States, too, but different driving forces are at work in these two countries. The transition to regionalized MSW management in Japan results from strong governmental control at all levels, with the central government providing funds and policy direction and prefectures and municipalities being the primary implementing authorities. By contrast, market forces are a much stronger force with US MSW management, where local governments - with state government oversight - have primary responsibility for MSW management. We describe recent changes in Japan's MSW programs. We examine the connections between MSW facility regionalization, on the one hand, and, on the other hand, the proximity principle, coordination among local governments, central government control, and financing mechanisms.

  2. Conserved residues within the HIV-1 Vpu transmembrane-proximal hinge region modulate BST2 binding and antagonism.

    Science.gov (United States)

    Lukhele, Sabelo; Cohen, Éric A

    2017-03-14

    BST2 inhibits HIV-1 release by tethering nascent virions to the surface of infected cells. HIV-1 Vpu overcomes this restriction by removing BST2 from viral budding sites via BST2 intracellular trapping and sequestration, surface downregulation and/or displacement mechanisms. Vpu is composed of a short luminal tail, a transmembrane domain (TMD) and a cytoplasmic hinge region that is followed by two helices. BST2 counteraction relies on the ability of Vpu to physically bind BST2 through TMD interactions and recruit the clathrin-dependent trafficking machinery via a canonical acidic di-leucine signalling motif within the helix-2 of Vpu. The highly conserved Vpu transmembrane-proximal hinge region encompasses residues that resemble an acidic leucine-based trafficking motif, whose functional roles are currently ill-defined. In this study, we investigated the contribution of these residues towards Vpu-mediated BST2 antagonism. We show that while these conserved residues have no intrinsic activity on the cellular distribution of Vpu in the absence of BST2, they regulate the ability of Vpu to bind to BST2 and, consequently, govern both BST2-dependent trafficking properties of the protein as well as its co-localization with BST2. Moreover, these residues, particularly a glutamic acid residue positioned immediately following the TMD, are a determinant not only for efficient targeting of BST2, but also binding and degradation of CD4, another host membrane protein targeted by Vpu. Mechanistically, our data are consistent with a role of these residues in the maintenance of the Vpu TMD conformational configuration such that interactions with membrane-associated host targets are favoured. Altogether, this work demonstrates an important regulatory role of the transmembrane-proximal Vpu hinge region residues towards enabling the protein to efficiently engage its target host proteins. Thus, this highly conserved, cytosolic Vpu hinge region may represent an attractive target for the

  3. Selective constraints in experimentally defined primate regulatory regions.

    Directory of Open Access Journals (Sweden)

    Daniel J Gaffney

    2008-08-01

    Full Text Available Changes in gene regulation may be important in evolution. However, the evolutionary properties of regulatory mutations are currently poorly understood. This is partly the result of an incomplete annotation of functional regulatory DNA in many species. For example, transcription factor binding sites (TFBSs, a major component of eukaryotic regulatory architecture, are typically short, degenerate, and therefore difficult to differentiate from randomly occurring, nonfunctional sequences. Furthermore, although sites such as TFBSs can be computationally predicted using evolutionary conservation as a criterion, estimates of the true level of selective constraint (defined as the fraction of strongly deleterious mutations occurring at a locus in regulatory regions will, by definition, be upwardly biased in datasets that are a priori evolutionarily conserved. Here we investigate the fitness effects of regulatory mutations using two complementary datasets of human TFBSs that are likely to be relatively free of ascertainment bias with respect to evolutionary conservation but, importantly, are supported by experimental data. The first is a collection of almost >2,100 human TFBSs drawn from the literature in the TRANSFAC database, and the second is derived from several recent high-throughput chromatin immunoprecipitation coupled with genomic microarray (ChIP-chip analyses. We also define a set of putative cis-regulatory modules (pCRMs by spatially clustering multiple TFBSs that regulate the same gene. We find that a relatively high proportion ( approximately 37% of mutations at TFBSs are strongly deleterious, similar to that at a 2-fold degenerate protein-coding site. However, constraint is significantly reduced in human and chimpanzee pCRMS and ChIP-chip sequences, relative to macaques. We estimate that the fraction of regulatory mutations that have been driven to fixation by positive selection in humans is not significantly different from zero. We also find

  4. Identify fracture-critical regions inside the proximal femur using statistical parametric mapping.

    Science.gov (United States)

    Li, Wenjun; Kornak, John; Harris, Tamara; Keyak, Joyce; Li, Caixia; Lu, Ying; Cheng, Xiaoguang; Lang, Thomas

    2009-04-01

    We identified regions inside the proximal femur that are most strongly associated with hip fracture. Bone densitometry based on such fracture-critical regions showed improved power in discriminating fracture patients from controls. Hip fractures typically occur in lateral falls, with focal mechanical failure of the sub-volumes of tissue in which the applied stress exceeds the strength. In this study, we describe a new methodology to identify proximal femoral tissue elements with highest association with hip fracture. We hypothesize that bone mineral density (BMD) measured in such sub-volumes discriminates hip fracture risk better than BMD in standard anatomic regions such as the femoral neck and trochanter. We employed inter-subject registration to transform hip QCT images of 37 patients with hip fractures and 38 age-matched controls into a voxel-based statistical atlas. Within voxels, we performed t-tests between the two groups to identify the regions which differed most. We then randomly divided the 75 scans into a training set and a test set. From the training set, we derived a fracture-driven region of interest (ROI) based on association with fracture. In the test set, we measured BMD in this ROI to determine fracture discrimination efficacy using ROC analysis. Additionally, we compared the BMD distribution differences between the 29 patients with neck fractures and the 8 patients with trochanteric fractures. By evaluating fracture discrimination power based on ROC analysis, the fracture-driven ROI had an AUC (area under curve) of 0.92, while anatomic ROIs (including the entire proximal femur, the femoral neck, trochanter and their cortical and trabecular compartments) had AUC values between 0.78 and 0.87. We also observed that the neck fracture patients had lower BMD (p=0.014) in a small region near the femoral neck and the femoral head, and patients with trochanteric fractures had lower BMD in trochanteric regions such as in the internal calcar septum (p=0

  5. DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes.

    Science.gov (United States)

    Dougherty, Gerard W; Loges, Niki T; Klinkenbusch, Judith A; Olbrich, Heike; Pennekamp, Petra; Menchen, Tabea; Raidt, Johanna; Wallmeier, Julia; Werner, Claudius; Westermann, Cordula; Ruckert, Christian; Mirra, Virginia; Hjeij, Rim; Memari, Yasin; Durbin, Richard; Kolb-Kokocinski, Anja; Praveen, Kavita; Kashef, Mohammad A; Kashef, Sara; Eghtedari, Fardin; Häffner, Karsten; Valmari, Pekka; Baktai, György; Aviram, Micha; Bentur, Lea; Amirav, Israel; Davis, Erica E; Katsanis, Nicholas; Brueckner, Martina; Shaposhnykov, Artem; Pigino, Gaia; Dworniczak, Bernd; Omran, Heymut

    2016-08-01

    Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)-left-right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP-left-right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography.

  6. Microbial diversity in an anaerobic digester with biogeographical proximity to geothermally active region.

    Science.gov (United States)

    Mahajan, Rishi; Nikitina, Anna; Nozhevnikova, Alla; Goel, Gunjan

    2016-11-01

    Anaerobic digestion of agricultural biomass or wastes can offer renewable energy, to help meet the rise in energy demands. The performance of an anaerobic digester considerably depends upon the complex interactions between bacterial and archaeal microbiome, which is greatly influenced by environmental factors. In the present study, we evaluate a microbial community of digester located at two different geographical locations, to understand whether the biogeographical proximity of a digester to a geothermally active region has any influence on microbial composition. The comparative microbial community profiling, highlights coexistence of specific bacterial and archaeal representatives (especially, Prosthecochloris sp., Conexibacter sp., Crenarchaeota isolate (Caldivirga sp.), Metallosphaera sp., Pyrobaculum sp. and Acidianus sp.) in a digester with close proximity to geothermally active region (Site I) and their absence in a digester located far-off from geothermally active region (Site II). A Sörensen's index of similarity of 83.33% and 66.66% for bacterial and archaeal community was observed in both the reactors, respectively.

  7. Food irradiation: regulatory aspects in the Asia and Pacific region

    Energy Technology Data Exchange (ETDEWEB)

    Luckman, G.J. E-mail: gary.luckman@aqis.gov.au

    2002-03-01

    Irradiation treatment of food is becoming an increasingly accepted processing option for countries in the Asia Pacific region wishing to meet growing sanitary and phytosanitary requirements in international trade. There remain however, large differences between the regulatory requirements in the countries in this region. This paper gives an outline on existing food irradiation regulations in the separate countries of the Asia Pacific region. New developments such as the recent decision by the Australia New Zealand Food Authority to start assessing applications for food irradiation treatment are discussed. Australia's intention to regulate the export of food treated by irradiation will also be outlined. Details of the decision to harmonise food irradiation regulations by 13 countries in the Asia Pacific region based on conformance with Codex requirements is outlined. The likelihood of other Asia Pacific countries enacting similar harmonisation of their regulations will be examined. Future development such as certification of irradiation as a sanitary treatment for food are discussed. The expected result of these initiatives is a likely increase in irradiated foods traded within the Asia Pacific region.

  8. Food irradiation: regulatory aspects in the Asia and Pacific region

    Science.gov (United States)

    Luckman, Gary James

    2002-03-01

    Irradiation treatment of food is becoming an increasingly accepted processing option for countries in the Asia Pacific region wishing to meet growing sanitary and phytosanitary requirements in international trade. There remain however, large differences between the regulatory requirements in the countries in this region. This paper gives an outline on existing food irradiation regulations in the separate countries of the Asia Pacific region. New developments such as the recent decision by the Australia New Zealand Food Authority to start assessing applications for food irradiation treatment are discussed. Australia's intention to regulate the export of food treated by irradiation will also be outlined. Details of the decision to harmonise food irradiation regulations by 13 countries in the Asia Pacific region based on conformance with Codex requirements is outlined. The likelihood of other Asia Pacific countries enacting similar harmonisation of their regulations will be examined. Future development such as certification of irradiation as a sanitary treatment for food are discussed. The expected result of these initiatives is a likely increase in irradiated foods traded within the Asia Pacific region.

  9. Brain region's relative proximity as marker for Alzheimer's disease based on structural MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge Emil; Pai, Akshay Sadananda Uppinakudru

    2014-01-01

    brain structures like hippocampus, this paper investigates the relationship and proximity between regions in the brain and uses this information as a novel way of classifying normal control (NC), mild cognitive impaired (MCI), and AD subjects.METHODS:A longitudinal cohort of 528 subjects (170 NC, 240......BACKGROUND:Alzheimer's disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single...... MCI, and 114 AD) from ADNI at baseline and month 12 was studied. We investigated a marker based on Procrustes aligned center of masses and the percentile surface connectivity between regions. These markers were classified using a linear discriminant analysis in a cross validation setting and compared...

  10. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Julien; Louis, John M.; Aniana, Annie [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States); Ghirlando, Rodolfo [National Institutes of Health, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States)

    2015-04-15

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion.

  11. Learning by the Market: Regulatory Regionalism, Bologna, and Accountability Communities

    Science.gov (United States)

    Jayasuriya, Kanishka

    2010-01-01

    Over the last two decades institutions of higher education have been subject to new modes of regulatory governance. This essay applies a "regulatory lens" to higher education governance with a view to understanding the sometimes contradictory relationship between the globalisation and regionalisation of higher education and the…

  12. Catchment model regionalization approach based on spatial proximity: Does a neighbor catchment-based rainfall input strengthen the method?

    Directory of Open Access Journals (Sweden)

    Gilles Drogue

    2016-12-01

    New hydrological insights for the region: Results show that when streamflow is known at the outlet of a catchment, optimal rainfall input for a lumped catchment model is mostly computed with a subset of raingages. When streamflow is unkown at the outlet of a catchment, a regionalisation approach of model parameter values based on spatial proximity is not able to take advantage of a neighbor-catchment based knowledge of optimal rainfall input. This report encourages to search for a catchment model regionalization approach based on spatial proximity which makes no explicit use of measured rainfall to estimate streamflow at an ungauged location.

  13. 77 FR 38125 - Annual Meeting of the Regional Small Business Regulatory Fairness Boards Office of the National...

    Science.gov (United States)

    2012-06-26

    ... ADMINISTRATION Annual Meeting of the Regional Small Business Regulatory Fairness Boards Office of the National... Small Business Regulatory Fairness Boards. SUMMARY: The SBA, Office of the National Ombudsman is issuing... Regional Small Business Regulatory Fairness Boards (Regional Regulatory Fairness Boards). The meeting is...

  14. 75 FR 47651 - Annual Meeting of the Regional Small Business Regulatory Fairness Boards Office of the National...

    Science.gov (United States)

    2010-08-06

    ... ADMINISTRATION Annual Meeting of the Regional Small Business Regulatory Fairness Boards Office of the National... Small Business Regulatory Fairness Boards. SUMMARY: The SBA, Office of the National Ombudsman is issuing... Regional Small Business Regulatory Fairness Boards (Regional Regulatory Fairness Boards). The meeting is...

  15. 76 FR 54523 - Annual Meeting of the Regional Small Business Regulatory Fairness Boards, Office of the National...

    Science.gov (United States)

    2011-09-01

    ... ADMINISTRATION Annual Meeting of the Regional Small Business Regulatory Fairness Boards, Office of the National... Small Business Regulatory Fairness Boards. SUMMARY: The SBA, Office of the National Ombudsman is issuing... Regional Small Business Regulatory Fairness Boards (Regional Regulatory Fairness Boards). The meeting is...

  16. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity

    Directory of Open Access Journals (Sweden)

    Todd Bradley

    2016-10-01

    Full Text Available Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1 viruses or rare cases of vaccine-matched neutralization-resistant (tier-2 viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we isolated antibodies from an HIV-1-infected individual that targeted the gp41 membrane-proximal external region (MPER that may have selected single-residue changes in viral variants in the MPER that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change in the MPER in a second virus from another infected-individual also conferred enhanced neutralization sensitivity. These gp41 single-residue changes thus transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine-elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino acid changes within the MPER bnAb epitope of naturally-selected escape viruses can increase neutralization sensitivity to multiple types of neutralizing antibodies, and underscore the critical importance of the MPER for maintaining the integrity of the tier-2 HIV-1 trimer.

  17. Magnetic resonance study on the anatomical relationship between the posterior proximal region of the tibia and the popliteal artery ☆

    Directory of Open Access Journals (Sweden)

    Rogério Franco de Araujo Goes

    2015-08-01

    Full Text Available ABSTRACTOBJECTIVE: To analyze and describe the distance from the popliteal artery to three specific areas of the proximal region of the tibia, with the knee extended, by means of magnetic resonance. METHODS: Images of 100 knees of patients who underwent magnetic resonance examinations were analyzed. The location of the popliteal artery was measured in three different areas of the posterior proximal region of the tibia. The first measurement was made at the level of the knee joint (tibial plateau. The second was 9 mm distally to the tibial plateau. The third was at the level of the anterior tuberosity of the tibia (ATT. RESULTS: The distances between the popliteal artery and the tibial plateau and ATT region were significantly greater in males than in females. The distances between the popliteal artery and the regions 9 mm distally to the tibial plateau and the ATT were significantly greater in the age group over 36 years than in the group ≤36 years. CONCLUSION: Knowledge of the anatomical position of the popliteal artery, as demonstrated through magnetic resonance studies, is of great relevance in planning surgical procedures that involve the knee joint. In this manner, devastating iatrogenic injuries can be avoided, particularly in regions that are proximal to the tibial plateau and in young patients.

  18. Regional and International Networking to Support the Energy Regulatory Commission of Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Lavansiri, Direk; Bull, Trevor

    2010-09-15

    The Energy Regulatory Commission of Thailand is a new regulatory agency. The structure of the energy sector; the tradition of administration; and, the lack of access to experienced personnel in Thailand all pose particular challenges. The Commission is meeting these challenges through regional and international networking to assist in developing policies and procedures that allow it to meet international benchmarks.

  19. the principles of diversity and geographical proximity in an industrial ecosystem: social network analysis in the Toluca-Lerma region

    Directory of Open Access Journals (Sweden)

    Manuel Alexis Vazquez Zacarias

    2015-07-01

    Full Text Available Industrial ecology allows the traditional model of industrial activity, where individual manufacturing process that takes raw materials in order to generate products, to be transformed into a more comprehensive model of a regional economy named industrial ecosystem. This ecosystem functions through industrial symbiosis alliances formed by firms that cooperate through the exchange of residues in order to use them as inputs to transform them into valuable products. Moreover, the principles of geographical proximity and diversity of the firms have been found in successful ecosystems in developed countries. This study contributes empirically by using social network analysis (SNA methods to explore, the presence of these two principles in an industrial ecosystem in the Toluca-Lerma region in Mexico, consisting of 30 firms that have industrial symbiosis alliances. We conclude that in the context of developing countries, the symbiotic exchanges may not be fully explained with the principles of geographical proximity and diversity.

  20. 78 FR 51263 - Annual Meeting of the Regional Small Business Regulatory Fairness Boards Office of the National...

    Science.gov (United States)

    2013-08-20

    ... ADMINISTRATION Annual Meeting of the Regional Small Business Regulatory Fairness Boards Office of the National... Small Business Regulatory Fairness Boards. SUMMARY: The SBA, Office of the National Ombudsman is issuing... Regional Small Business Regulatory Fairness Boards (RegFair Boards). The meeting is open to the public...

  1. Proximity to mosquito breeding habitat and Ross River virus risk in the Peel region of Western Australia.

    Science.gov (United States)

    Jardine, Andrew; Neville, Peter J; Lindsay, Michael D A

    2015-02-01

    It is intuitive that vector-borne disease exposure risk is related to proximity to sources of vector breeding, but this aspect rarely receives empirical testing. The population of Western Australia (WA) is increasing rapidly, with many new residential developments proposed in close proximity to mosquito breeding habitat. However, potential mosquito-borne disease risks for future residents are given little consideration by planning authorities. The Peel region is one of the fastest growing regions in WA and regularly experiences a large number of cases of the mosquito-borne Ross River virus (RRV) disease with epidemics occuring in the region every few years. A spatial analysis of RRV disease data in the Peel region was undertaken to determine the risk associated with proximity to a mosquito breeding habitat. Geographic Information Systems (GIS) software was used to create buffers between 1 and 6 km from the breeding habitat. The number of cases per 1000 dwellings in each buffer was calculated between 2002/03 to 2011/12 for years with >100 cases across all buffers (n=5) in addition to the cumulative rate over the entire period in each buffer. Residents living within 1 km of a mosquito breeding habitat had a significantly higher rate of RRV disease compared to the background rate across the Peel region in all individual years investigated. The cumulative data over the 10-year study period showed that residents in the 1- and 2-km buffers had a significantly higher rate, whereas those living between 3 and 6 km away did not. This study demonstrates an increased mosquito-borne disease risk associated with living in close proximity to a mosquito breeding habitat in a rapidly expanding region of WA and highlights the importance of considering mosquito-borne disease risks when planning authorities assess new residential development applications. Known mosquito breeding wetlands should be incorporated into land use planning scheme maps to ensure that they are accurately

  2. Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Christian, S.L.; Huang, B.; Ledbetter, D.H. [National Institutes of Health, Bethesda, MD (United States)] [and others

    1995-07-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11{minus}q13. Approximately 70% of these patients have a large deletion of {approximately}4 Mb extending from D15S9 (ML34) through D15S12 (IR10A). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated for YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542. 46 refs., 2 figs., 3 tabs.

  3. A influência da proximidade tecnológica e geográfica sobre a inovação regional no Brasil The influence of the technological proximity and the geographical proximity on Brazilian regional innovation

    Directory of Open Access Journals (Sweden)

    Eduardo Gonçalves

    2011-04-01

    Full Text Available O objetivo deste trabalho é verificar a influência da proximidade geográfica e da proximidade tecnológica sobre a inovação regional no Brasil, medida por depósitos de patentes no período 1999-2001 para mesorregiões geográficas. Para tanto, utilizaram-se técnicas de Análise Exploratória de Dados Espaciais (AEDE e de econometria espacial. Os dados de patentes foram organizados em quatro clusters tecnológicos segundo critérios de proximidade cognitiva, como biofarmacêutico, desenvolvimento de novos materiais, bens mecânicos e de consumo e tecnologias eletroeletrônicas, revelando um padrão de concentração da atividade tecnológica em poucas mesorregiões brasileiras. Além disso, foi calculada a medida de proximidade tecnológica de Jaffe para ponderar a vizinhança geográfica pelo grau de similaridade tecnológica das mesorregiões. Os resultados confirmam a hipótese de transbordamentos de conhecimento mediados tecnológica e geograficamente.The aim of this paper is to determine the influence of technological proximity and geographical proximity on Brazilian regional innovation, measured by patent applications over the period 1999-2001 for Brazilian geographical mesoregions. First, the paper undertakes an Exploratory Spatial Data Analysis (ESDA and then uses spatial econometric techniques. According with procedures based on cognitive proximity the patent data are organized into four technological clusters such as chemical and bio-pharmaceutical, new materials, mechanical and process technologies and electrical and electronic technologies. The four aforementioned clusters exhibit a concentrated regional pattern of technological activity over few Brazilian mesoregions. Moreover, the paper uses a Jaffe's measure of technological distance in order to construct a matrix in which the technological similarity is weighted by the geographical proximity. The results corroborate the hypothesis of geographically and technologically

  4. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  5. Regionalization as an approach to regulatory systems strengthening: a case study in CARICOM member states.

    Science.gov (United States)

    Preston, Charles; Chahal, Harinder S; Porrás, Analia; Cargill, Lucette; Hinds, Maryam; Olowokure, Babatunde; Cummings, Rudolph; Hospedales, James

    2016-05-01

    Improving basic capacities for regulation of medicines and health technologies through regulatory systems strengthening is particularly challenging in resource-constrained settings. "Regionalization"-an approach in which countries with common histories, cultural values, languages, and economic conditions work together to establish more efficient systems-may be one answer. This report describes the Caribbean Regulatory System (CRS), a regionalization initiative being implemented in the mostly small countries of the Caribbean Community and Common Market (CARICOM). This initiative is an innovative effort to strengthen regulatory systems in the Caribbean, where capacity is limited compared to other subregions of the Americas. The initiative's concept and design includes a number of features and steps intended to enhance sustainability in resource-constrained contexts. The latter include 1) leveraging existing platforms for centralized cooperation, governance, and infrastructure; 2) strengthening regulatory capacities with the largest potential public health impact; 3) incorporating policies that promote reliance on reference authorities; 4) changing the system to encourage industry to market their products in CARICOM (e.g., using a centralized portal of entry to reduce regulatory burdens); and 5) building human resource capacity. If implemented properly, the CRS will be self-sustaining through user fees. The experience and lessons learned thus far in implementing this initiative, described in this report, can serve as a case study for the development of similar regulatory strengthening initiatives in resource-constrained environments.

  6. Evolution of Leukotoxin Regulatory regions in Genus Mannheimia by Interspecies Comparisons

    DEFF Research Database (Denmark)

    Larsen, Jesper; Pedersen, Anders Gorm; de Lichtenberg, Ulrik

    to -376 contains at least one positive regulatory element, suggesting early divergence within the promoter family and the emergence of a lineage with increased promoter strength. Tandem duplication of the pattern ACAAAAAACA has occurred in the ancestral Mhae1 promoter after the Mhae1 and Mhae2 ancestors......Comparisons of evolutionary divergent promoter sequences have revealed that gross rearrangements of pre-existing blocks into new combinations play a central role during the evolution of regulatory regions. The noncoding region upstream of the leukotoxin operon was analyzed in six Mannheimia strains...

  7. Lhx1 in the proximal region of the optic vesicle permits neural retina development in the chicken

    Directory of Open Access Journals (Sweden)

    Takumi Kawaue

    2012-08-01

    How the eye forms has been one of the fundamental issues in developmental biology. The retinal anlage first appears as the optic vesicle (OV evaginating from the forebrain. Subsequently, its distal portion invaginates to form the two-walled optic cup, which develops into the outer pigmented and inner neurosensory layers of the retina. Recent work has shown that this optic-cup morphogenesis proceeds as a self-organizing activity without any extrinsic molecules. However, intrinsic factors that regulate this process have not been elucidated. Here we show that a LIM-homeobox gene, Lhx1, normally expressed in the proximal region of the nascent OV, induces a second neurosensory retina formation from the outer pigmented retina when overexpressed in the chicken OV. Lhx2, another LIM-homeobox gene supposed to be involved in early OV formation, could not substitute this function of Lhx1, while Lhx5, closely related to Lhx1, could replace it. Conversely, knockdown of Lhx1 expression by RNA interference resulted in the formation of a small or pigmented vesicle. These results suggest that the proximal region demarcated by Lhx1 expression permits OV development, eventually dividing the two retinal domains.

  8. The punctate localization of rat Eag1 K+ channels is conferred by the proximal post-CNBHD region.

    Science.gov (United States)

    Chuang, Chao-Chin; Jow, Guey-Mei; Lin, Huei-Min; Weng, Yu-Han; Hu, Jui-Hsiang; Peng, Yi-Jheng; Chiu, Yi-Chih; Chiu, Mei-Miao; Jeng, Chung-Jiuan

    2014-02-04

    In mammals, Eag K+ channels (KV10) are exclusively expressed in the brain and comprise two isoforms: Eag1 (KV10.1) and Eag2 (KV10.2). Despite their wide presence in various regions of the brain, the functional role of Eag K+ channels remains obscure. Here we address this question by characterizing the subcellular localization of rat Eag1 (rEag1) and rat Eag2 (rEag2) in hippocampal neurons, as well as determining the structural basis underlying their different localization patterns. Immunofluorescence analysis of young and mature hippocampal neurons in culture revealed that endogenous rEag1 and rEag2 K+ channels were present in both the dendrosomatic and the axonal compartments. Only rEag1 channels displayed a punctate immunostaining pattern and showed significant co-localization with PSD-95. Subcellular fractionation analysis further demonstrated a distinct enrichment of rEag1 in the synaptosomal fraction. Over-expression of recombinant GFP-tagged Eag constructs in hippocampal neurons also showed a significant punctate localization of rEag1 channels. To identify the protein region dictating the Eag channel subcellular localization pattern, we generated a variety of different chimeric constructs between rEag1 and rEag2. Quantitative studies of neurons over-expressing these GFP-tagged chimeras indicated that punctate localization was conferred by a segment (A723-R807) within the proximal post-cyclic nucleotide-binding homology domain (post-CNBHD) region in the rEag1 carboxyl terminus. Our findings suggest that Eag1 and Eag2 K+ channels may modulate membrane excitability in both the dendrosomatic and the axonal compartments and that Eag1 may additionally regulate neurotransmitter release and postsynaptic signaling. Furthermore, we present the first evidence showing that the proximal post-CNBHD region seems to govern the Eag K+ channel subcellular localization pattern.

  9. Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.

    Directory of Open Access Journals (Sweden)

    Viviane Baral

    Full Text Available Waardenburg syndrome (WS is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2 can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.

  10. Conservation and implications of eukaryote transcriptional regulatory regions across multiple species

    Directory of Open Access Journals (Sweden)

    Deng Minghua

    2008-12-01

    Full Text Available Abstract Background Increasing evidence shows that whole genomes of eukaryotes are almost entirely transcribed into both protein coding genes and an enormous number of non-protein-coding RNAs (ncRNAs. Therefore, revealing the underlying regulatory mechanisms of transcripts becomes imperative. However, for a complete understanding of transcriptional regulatory mechanisms, we need to identify the regions in which they are found. We will call these transcriptional regulation regions, or TRRs, which can be considered functional regions containing a cluster of regulatory elements that cooperatively recruit transcriptional factors for binding and then regulating the expression of transcripts. Results We constructed a hierarchical stochastic language (HSL model for the identification of core TRRs in yeast based on regulatory cooperation among TRR elements. The HSL model trained based on yeast achieved comparable accuracy in predicting TRRs in other species, e.g., fruit fly, human, and rice, thus demonstrating the conservation of TRRs across species. The HSL model was also used to identify the TRRs of genes, such as p53 or OsALYL1, as well as microRNAs. In addition, the ENCODE regions were examined by HSL, and TRRs were found to pervasively locate in the genomes. Conclusion Our findings indicate that 1 the HSL model can be used to accurately predict core TRRs of transcripts across species and 2 identified core TRRs by HSL are proper candidates for the further scrutiny of specific regulatory elements and mechanisms. Meanwhile, the regulatory activity taking place in the abundant numbers of ncRNAs might account for the ubiquitous presence of TRRs across the genome. In addition, we also found that the TRRs of protein coding genes and ncRNAs are similar in structure, with the latter being more conserved than the former.

  11. A 5'-proximal region of the Citrus tristeza virus genome encoding two leader proteases is involved in virus superinfection exclusion.

    Science.gov (United States)

    Atallah, Osama O; Kang, Sung-Hwan; El-Mohtar, Choaa A; Shilts, Turksen; Bergua, María; Folimonova, Svetlana Y

    2016-02-01

    Superinfection exclusion (SIE), a phenomenon in which a primary virus infection prevents a secondary infection with the same or closely related virus, has been observed with various viruses. Earlier we demonstrated that SIE by Citrus tristeza virus (CTV) requires viral p33 protein. In this work we show that p33 alone is not sufficient for virus exclusion. To define the additional viral components that are involved in this phenomenon, we engineered a hybrid virus in which a 5'-proximal region in the genome of the T36 isolate containing coding sequences for the two leader proteases L1 and L2 has been substituted with a corresponding region from the genome of a heterologous T68-1 isolate. Sequential inoculation of plants pre-infected with the CTV L1L2T68 hybrid with T36 CTV resulted in superinfection with the challenge virus, which indicated that the substitution of the L1-L2 coding region affected SIE ability of the virus. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Antibody humanization by redesign of complementarity-determining region residues proximate to the acceptor framework.

    Science.gov (United States)

    Hanf, Karl J M; Arndt, Joseph W; Chen, Ling Ling; Jarpe, Matthew; Boriack-Sjodin, P Ann; Li, You; van Vlijmen, Herman W T; Pepinsky, R Blake; Simon, Kenneth J; Lugovskoy, Alexey

    2014-01-01

    Antibodies are key components of the adaptive immune system and are well-established protein therapeutic agents. Typically high-affinity antibodies are obtained by immunization of rodent species that need to be humanized to reduce their immunogenicity. The complementarity-determining regions (CDRs) contain the residues in a defined loop structure that confer antigen binding, which must be retained in the humanized antibody. To design a humanized antibody, we graft the mature murine CDRs onto a germline human acceptor framework. Structural defects due to mismatches at the graft interface can be fixed by mutating some framework residues to murine, or by mutating some residues on the CDRs' backside to human or to a de novo designed sequence. The first approach, framework redesign, can yield an antibody with binding better than the CDR graft and one equivalent to the mature murine, and reduced immunogenicity. The second approach, CDR redesign, is presented here as a new approach, yielding an antibody with binding better than the CDR graft, and immunogenicity potentially less than that from framework redesign. Application of both approaches to the humanization of anti-α4 integrin antibody HP1/2 is presented and the concept of the hybrid humanization approach that retains "difficult to match" murine framework amino acids and uses de novo CDR design to minimize murine amino acid content and reduce cell-mediated cytotoxicity liabilities is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Signals emanating from the membrane proximal region of the thrombopoietin receptor (mpl) support hematopoietic stem cell self-renewal.

    Science.gov (United States)

    Tong, Wei; Ibarra, Yessenia M; Lodish, Harvey F

    2007-09-01

    Studies using thrombopoietin -/- (TPO(-/-)) or TPO receptor, mpl(-/-) mice have established a critical role for TPO/mpl signaling in hematopoietic stem cell (HSC) development. In this study, we further dissected mpl signaling in both megakaryopoiesis and HSC function, using mice bearing a truncated mpl receptor lacking the distal 60 amino acids (Delta60). This deletion removes three major signaling tyrosines on the mpl cytoplasmic domain, but retains the membrane proximal Box1 and Box2 domains required for JAK2 activation. Competitive bone marrow transplantations (BMT) and serial BMTs were performed to study HSC function. Western blot analysis was used to study TPO-stimulated signaling pathways. BM cell cultures in the presence of TPO were used to study megakaryocyte development. In agreement with prior findings, we show that Delta60 BM cells cultured in TPO generated normal numbers of megakaryocytes, but with greatly reduced ploidy. As expected from the deletion of three signaling tyrosine residues, freshly isolated Delta60 megakaryocytes showed marked reduction in all known TPO-stimulated signaling pathways tested, including signal transducers and activators of transcription (Stat) 5, Stat3, Akt, and p42/44 mitogen-activated kinase. We found that Delta60 mice displayed normal short-term (ST-HSC) activities and marginally compromised long-term (LT-HSC) stem cell activities in primary transplantation. In addition, Delta60 mice supported HSC self-renewal for at least two serial BMTs. Our data reveal a pivotal role for an unknown signal emanating from the membrane proximal region of the mpl receptor or from JAK2 itself in maintaining stem cell activity and self-renewal, in addition to its role in megakaryocytopoiesis and thrombopoiesis.

  14. Regulatory regions of SERPINC1 gene: identification of the first mutation associated with antithrombin deficiency.

    Science.gov (United States)

    de la Morena-Barrio, María Eugenia; Antón, Ana Isabel; Martínez-Martínez, Irene; Padilla, José; Miñano, Antonia; Navarro-Fernández, José; Águila, Sonia; López, María Fernanda; Fontcuberta, Jordi; Vicente, Vicente; Corral, Javier

    2012-03-01

    Antithrombin is the main endogenous anticoagulant. Impaired function or deficiency of this molecule significantly increases the risk of thrombosis. We studied the genetic variability of SERPINC1 , the gene encoding antithrombin, to identify mutations affecting regulatory regions with functional effect on its levels. We sequenced 15,375 bp of this gene, including the potential promoter region, in three groups of subjects: five healthy subjects with antithrombin levels in the lowest (75%) and highest (115%) ranges of our population, 14 patients with venous thrombosis and a moderate antithrombin deficiency as the single thrombophilic defect, and two families with type I antithrombin deficiency who had neither mutations affecting exons or flanking regions, nor gross gene deletions. Our study confirmed the low genetic variability of SERPINC1 , particularly in the coding region, and its minor influence in the heterogeneity of antithrombin levels. Interestingly, in one family, we identified a g.2143 C>G transversion, located 170 bp upstream from the translation initiation codon. This mutation affected one of the four regions located in the minimal promoter that have potential regulatory activity according to previous DNase footprinting protection assays. Genotype-phenotype analysis in the affected family and reporter analysis in different hepatic cell lines demonstrated that this mutation significantly impaired, although it did not abolish, the downstream transcription. Therefore, this is the first mutation affecting a regulatory region of the SERPINC1 gene associated with antithrombin deficiency. Our results strongly sustain the inclusion of the promoter region of SERPINC1 in the molecular analysis of patients with antithrombin deficiency.

  15. Engineering Recombinant Reoviruses To Display gp41 Membrane-Proximal External-Region Epitopes from HIV-1.

    Science.gov (United States)

    Boehme, Karl W; Ikizler, Mine'; Iskarpatyoti, Jason A; Wetzel, J Denise; Willis, Jordan; Crowe, James E; LaBranche, Celia C; Montefiori, David C; Wilson, Gregory J; Dermody, Terence S

    2016-01-01

    The gp41 membrane-proximal external region (MPER) is a target for broadly neutralizing antibody responses against human immunodeficiency virus type 1 (HIV-1). However, replication-defective virus vaccines currently under evaluation in clinical trials do not efficiently elicit MPER-specific antibodies. Structural modeling suggests that the MPER forms an α-helical coiled coil that is required for function and immunogenicity. To maintain the native MPER conformation, we used reverse genetics to engineer replication-competent reovirus vectors that displayed MPER sequences in the α-helical coiled-coil tail domain of viral attachment protein σ1. Sequences in reovirus strain type 1 Lang (T1L) σ1 were exchanged with sequences encoding HIV-1 strain Ba-L MPER epitope 2F5 or the entire MPER. Individual 2F5 or MPER substitutions were introduced at virion-proximal or virion-distal sites in the σ1 tail. Recombinant reoviruses containing heterologous HIV-1 sequences were viable and produced progeny yields comparable to those with wild-type virus. HIV-1 sequences were retained following 10 serial passages in cell culture, indicating that the substitutions were genetically stable. Recombinant viruses engineered to display the 2F5 epitope or full-length MPER in σ1 were recognized by purified 2F5 antibody. Inoculation of mice with 2F5-containing vectors or rabbits with 2F5- or MPER-containing vectors elicited anti-reovirus antibodies, but HIV-1-specific antibodies were not detected. Together, these findings indicate that heterologous sequences that form α-helices can functionally replace native sequences in the α-helical tail domain of reovirus attachment protein σ1. However, although these vectors retain native antigenicity, they were not immunogenic, illustrating the difficulty of experimentally inducing immune responses to this essential region of HIV-1. IMPORTANCE Vaccines to protect against HIV-1, the causative agent of AIDS, are not approved for use. Antibodies that

  16. Uncovering the DNA methylation landscape in key regulatory regions within the FADS cluster.

    Science.gov (United States)

    Rahbar, Elaheh; Ainsworth, Hannah C; Howard, Timothy D; Hawkins, Gregory A; Ruczinski, Ingo; Mathias, Rasika; Seeds, Michael C; Sergeant, Susan; Hixson, James E; Herrington, David M; Langefeld, Carl D; Chilton, Floyd H

    2017-01-01

    Genetic variants near and within the fatty acid desaturase (FADS) cluster are associated with polyunsaturated fatty acid (PUFA) biosynthesis, levels of several disease biomarkers and risk of human disease. However, determining the functional mechanisms by which these genetic variants impact PUFA levels remains a challenge. Utilizing an Illumina 450K array, we previously reported strong allele-specific methylation (ASM) associations (p = 2.69×10-29) between a single nucleotide polymorphism (SNP) rs174537 and DNA methylation of CpG sites located in the putative enhancer region between FADS1 and FADS2, in human liver tissue. However, this array only featured 20 CpG sites within this 12kb region. To better understand the methylation landscape within this region, we conducted bisulfite sequencing of the region between FADS1 and FADS2. Liver tissues from 50 male subjects (27 European Americans, 23 African Americans) were obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, and used to ascertain the genotype at rs174537 and methylation status across the region of interest. Associations between rs174537 genotype and methylation status of 136 CpG sites were determined. Age-adjusted linear regressions were used to assess ASM associations with rs174537 genotype. The majority of CpG sites (117 out of 136, 86%) exhibited high levels of methylation with the greatest variability observed at three key regulatory regions-the promoter regions for FADS1 and FADS2 and a putative enhancer site between the two genes. Eight CpG sites within the putative enhancer region displayed significant (FDR p <0.05) ASM associations with rs174537. These data support the concept that both genetic and epigenetic factors regulate PUFA biosynthesis, and raise fundamental questions as to how genetic variants such as rs174537 impact DNA methylation in distant regulatory regions, and ultimately the capacity of tissues to synthesize PUFAs.

  17. Uncovering the DNA methylation landscape in key regulatory regions within the FADS cluster.

    Directory of Open Access Journals (Sweden)

    Elaheh Rahbar

    Full Text Available Genetic variants near and within the fatty acid desaturase (FADS cluster are associated with polyunsaturated fatty acid (PUFA biosynthesis, levels of several disease biomarkers and risk of human disease. However, determining the functional mechanisms by which these genetic variants impact PUFA levels remains a challenge. Utilizing an Illumina 450K array, we previously reported strong allele-specific methylation (ASM associations (p = 2.69×10-29 between a single nucleotide polymorphism (SNP rs174537 and DNA methylation of CpG sites located in the putative enhancer region between FADS1 and FADS2, in human liver tissue. However, this array only featured 20 CpG sites within this 12kb region. To better understand the methylation landscape within this region, we conducted bisulfite sequencing of the region between FADS1 and FADS2. Liver tissues from 50 male subjects (27 European Americans, 23 African Americans were obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY study, and used to ascertain the genotype at rs174537 and methylation status across the region of interest. Associations between rs174537 genotype and methylation status of 136 CpG sites were determined. Age-adjusted linear regressions were used to assess ASM associations with rs174537 genotype. The majority of CpG sites (117 out of 136, 86% exhibited high levels of methylation with the greatest variability observed at three key regulatory regions-the promoter regions for FADS1 and FADS2 and a putative enhancer site between the two genes. Eight CpG sites within the putative enhancer region displayed significant (FDR p <0.05 ASM associations with rs174537. These data support the concept that both genetic and epigenetic factors regulate PUFA biosynthesis, and raise fundamental questions as to how genetic variants such as rs174537 impact DNA methylation in distant regulatory regions, and ultimately the capacity of tissues to synthesize PUFAs.

  18. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu

    2016-03-15

    The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.

  19. Exploring the determinants of health and wellbeing in communities living in proximity to coal seam gas developments in regional Queensland

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    Fiona Mactaggart

    2017-08-01

    Full Text Available Abstract Background There is some concern that coal seam gas mining may affect health and wellbeing through changes in social determinants such as living and working conditions, local economy and the environment. The onward impact of these conditions on health and wellbeing is often not monitored to the same degree as direct environmental health impacts in the mining context, but merits attention. This study reports on the findings from a recurrent theme that emerged from analysis of the qualitative component of a comprehensive Health Needs Assessment (HNA conducted in regional Queensland: that health and wellbeing of communities was reportedly affected by nearby coal seam gas (CSG development beyond direct environmental impacts. Methods Qualitative analysis was initially completed using the Framework Method to explore key themes from 11 focus group discussions, 19 in-depth interviews, and 45 key informant interviews with health and wellbeing service providers and community members. A key theme emerged from the analysis that forms the basis of this paper. This study is part of a larger comprehensive HNA involving qualitative and quantitative data collection to explore the health and wellbeing needs of three communities living in proximity to CSG development in regional Queensland, Australia. Results Communities faced social, economic and environmental impacts from the rapid growth of CSG development, which were perceived to have direct and indirect effects on individual lifestyle factors such as alcohol and drug abuse, family relationships, social capital and mental health; and community-level factors including social connectedness, civic engagement and trust. Conclusions Outer regional communities discussed the effects of mining activity on the fabric of their town and community, whereas the inner regional community that had a longer history of industrial activity discussed the impacts on families and individual health and wellbeing. The

  20. Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions

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    Kostas C. Nikolaou

    2017-07-01

    Full Text Available H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. Here, we show that, in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted in an energy starvation condition partially compensated by AMP-activated protein kinase (AMPK activation and increased mitochondrial activity. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage. The results illustrate how defects in the general process of RNA Pol II transition into a productive elongation phase can trigger specific metabolic changes and genome instability.

  1. Locational response to regulatory policy: a regional analysis of energy facility location

    Energy Technology Data Exchange (ETDEWEB)

    Meier, P.M.; Hobbs, B.F.

    1978-01-01

    The Brookhaven Regional Energy Facility Siting Model has been applied to a simulation of a number of alternative regulatory strategies that affect the location of power plants. An analysis of alternative definitions of Best Available Control Technology, as called for by the 1977 Amendments to the Clean Air Act, and associated revisions of New Source Performance Standards, are shown to have significant influence over least-cost locations of coal-burning power plants, with the result that despite large reductions of SO/sub 2/ emissions under the more-stringent emissions limitations, the locational shifts under cost-minimizing behavior results in higher population exposure to SO/sub 2/. The impacts of River Basin Commission policy on low-flow objectives and on state regulatory policy in limiting interstate power transfers are also examined.

  2. Beyond regional clusters: On the importance of geographical proximity for R&D collaborations in a global economy - the case of the flemisch biotech sector

    NARCIS (Netherlands)

    Herrmann, A.M.; Taks, J.L.; Moors, E.H.M.

    2012-01-01

    When internal knowledge bases are insufficient for developing innovations, companies tend to collaborate with external R&D partners. According to a long-standing literature on “clusters”, “industrial districts”, “local production systems” and “regional innovation systems”, geographical proximity

  3. Tropical Texture Determination by Proximal Sensing Using a Regional Spectral Library and Its Relationship with Soil Classification

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    Marilusa P. C. Lacerda

    2016-08-01

    Full Text Available The search for sustainable land use has increased in Brazil due to the important role that agriculture plays in the country. Soil detailed classification is related with texture attribute. How can one discriminate the same soil class with different textures using proximal soil sensing, as to reach surveys, land use planning and increase crop productivity? This study aims to evaluate soil texture using a regional spectral library and its usefulness on classification. We collected 3750 soil samples covering 3 million ha within strong soil class variations in São Paulo State. The spectral analyses of soil samples from topsoil and subsoil were measured in laboratory (400–2500 nm. The potential of a regional soil spectral library was evaluated on the discrimination of soil texture. We considered two types of soil texture systems, one related with soil classification and another with soil managements. The soil line technique was used to assess differentiation between soil textural groups. Soil spectra were summarized by principal component analysis (PCA to select relevant information on the spectra. Partial least squares regression (PLSR was used to predict texture. Spectral curves indicated different shapes according to soil texture and discriminated particle size classes from clayey to sandy soils. In the visible region, differences were small because of the organic matter, while the short wave infrared (SWIR region showed more differences; thus, soil texture variation could be differentiated by quartz. Angulation differences are on a spectral curve from NIR to SWIR. The statistical models predicted clay and sand levels with R2 = 0.93 and 0.96, respectively. Indeed, we achieved a difference of 1.2% between laboratory and spectroscopy measurement for clay. The spectral information was useful to classify Ferralsols with different texture classification. In addition, the spectra differentiated Lixisols from Ferralsols and Arenosols. This work can

  4. De Novo Identification of Regulatory Regions in Intergenic Spaces of Prokaryotic Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Chain, P; Garcia, E; Mcloughlin, K; Ovcharenko, I

    2007-02-20

    This project was begun to implement, test, and experimentally validate the results of a novel algorithm for genome-wide identification of candidate transcription-factor binding sites in prokaryotes. Most techniques used to identify regulatory regions rely on conservation between different genomes or have a predetermined sequence motif(s) to perform a genome-wide search. Therefore, such techniques cannot be used with new genome sequences, where information regarding such motifs has not yet been discovered. This project aimed to apply a de novo search algorithm to identify candidate binding-site motifs in intergenic regions of prokaryotic organisms, initially testing the available genomes of the Yersinia genus. We retrofitted existing nucleotide pattern-matching algorithms, analyzed the candidate sites identified by these algorithms as well as their target genes to screen for meaningful patterns. Using properly annotated prokaryotic genomes, this project aimed to develop a set of procedures to identify candidate intergenic sites important for gene regulation. We planned to demonstrate this in Yersinia pestis, a model biodefense, Category A Select Agent pathogen, and then follow up with experimental evidence that these regions are indeed involved in regulation. The ability to quickly characterize transcription-factor binding sites will help lead to a better understanding of how known virulence pathways are modulated in biodefense-related organisms, and will help our understanding and exploration of regulons--gene regulatory networks--and novel pathways for metabolic processes in environmental microbes.

  5. Footprinting the 'essential regulatory region' of the retinoblastoma gene promoter in intact human cells.

    Science.gov (United States)

    Temple, Mark D; Murray, Vincent

    2005-03-01

    The retinoblastoma tumour suppressor protein is a key cell cycle regulator. Protein-DNA interactions at the retinoblastoma (RB1) promoter, including the 'essential regulatory region', were investigated using novel DNA-targeted nitrogen mustards in intact human cells. The footprinting experiments were carried out in two different environments: in intact HeLa and K562 cells where the access of DNA-targeted probes to chromatin is affected by cellular protein-DNA interactions associated with gene regulation; and in purified DNA where their access is unencumbered by protein-DNA interactions. Using the ligation-mediated PCR (LMPCR) technique, the sites of damage were determined at base pair resolution on DNA sequencing gels. Our results demonstrate that, in intact cells, footprints were observed at the E2F, ATF and RBF1/Sp1 DNA binding motifs in the RB1 promoter. In addition, a novel footprint was observed at a previously unidentified cycle homology region (CHR) and at four uncharacterised protein-DNA binding sites. In further experiments, nitrogen mustard-treated cells were FACS sorted into G1, S and G2/M phases of the cell cycle prior to LMPCR analysis. Expression of the RB1 gene is cell cycle-regulated and footprinting studies of the promoter in FACS-sorted cells indicated that transcription factor binding at the GC box, CHR binding motif and the 'essential regulatory region' are cell cycle dependent.

  6. The correlation between regulatory conditions and antibiotic consumption within the WHO European Region.

    Science.gov (United States)

    Mueller, Tanja; Östergren, Per-Olof

    2016-08-01

    In a global perspective, bacterial infections are still a major cause of morbidity and mortality; therefore, effective antibiotics are needed. However, the emergence of antibiotic resistance due to irrational use has now become a serious public health problem. Hence, the objective of this study was to analyse the association of regulatory aspects with antibiotic consumption. A data set representing 20 countries throughout the WHO European Region was chosen based on data availability so as to analyse the correlation between specific regulatory conditions and antibiotic consumption, using total consumption data for 2011 and information about national provisions regarding rational use of medicines. Linear regression models were designed in order to evaluate individual aspects as well as the overall level of regulation. A high level of regulation, assessed by an overall index, was significantly correlated with lower antibiotic consumption; however, of all individual items analysed, only the presence of Standard Treatment Guidelines for hospital care as well as paediatric conditions, the non-availability of antibiotics without a prescription, and the existence of training modules for pharmacists covering rational use of medicines gave significant results, i.e. lower use of antibiotics, when regarded in isolation. Although national regulatory conditions intended to foster rational use of antibiotics seem to be correlated with antibiotic consumption, this association is potentially influenced by a wide range of contextual aspects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. The role of CTCF binding sites in the 3’ immunoglobulin heavy chain regulatory region

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    Barbara K Birshtein

    2012-11-01

    Full Text Available The immunoglobulin heavy chain locus undergoes a series of DNA rearrangements and modifications to achieve the construction and expression of individual antibody heavy chain genes in B cells. These events affect variable regions, through VDJ joining and subsequent somatic hypermutation, and constant regions through class switch recombination. Levels of IgH expression are also regulated during B cell development, resulting in high levels of secreted antibodies from fully-differentiated plasma cells. Regulation of these events has been attributed primarily to two cis-elements that work from long distances on their target sequences, i.e., an ~1 kb intronic enhancer, Eμ, located between the V region segments and the most 5′ constant region gene, Cμ; and an ~40 kb 3′ regulatory region (3′ RR that is located downstream of the most 3′ CH gene, Cα. The 3′ RR is a candidate for an end of B cell-specific regulation of the Igh locus. The 3′ RR contains several B cell-specific enhancers associated with DNase I hypersensitive sites (hs1-4, which are essential for class switch recombination and for high levels of IgH expression in plasma cells. Downstream of this enhancer-containing region is a region of high-density CTCF binding sites, which extends through hs5, 6, and 7 and further downstream. CTCF, with its enhancer-blocking activities, has been associated with all mammalian insulators and implicated in multiple chromosomal interactions. Here we address the 3′ RR CTCF-binding region as a potential insulator of the Igh locus, an independent regulatory element and a predicted modulator of the activity of 3’ RR enhancers. Using chromosome conformation capture technology, chromatin immunoprecipitation and genetic approaches, we have found that the 3’ RR with its CTCF binding region interacts with target sequences in the VH, Eμ and CH regions through DNA looping as regulated by protein binding. This region impacts on B cell-specific Igh

  8. Targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus.

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    Donatien Kamdem Toukam

    Full Text Available Although human immunodeficiency type 1 (HIV-1 infection induces strong antibody responses to the viral envelope glycoprotein (Env only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10 target the short and hidden membrane proximal external region (MPER of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N-terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP. Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined.

  9. Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region

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    Kashork Catherine D

    2008-01-01

    Full Text Available Abstract Background Prader-Willi syndrome (PWS is a neurobehavioral disorder characterized by neonatal hypotonia, childhood obesity, dysmorphic features, hypogonadism, mental retardation, and behavioral problems. Although PWS is most often caused by a paternal interstitial deletion of a 6-Mb region of chromosome 15q11-q13, the identity of the exact protein coding or noncoding RNAs whose deficiency produces the PWS phenotype is uncertain. There are also reports describing a PWS-like phenotype in a subset of patients with full mutations in the FMR1 (fragile X mental retardation 1 gene. Taking advantage of the human genome sequence, we have performed extensive sequence analysis and molecular studies for the PWS candidate region. Results We have characterized transcripts for the first time for two UCSC Genome Browser predicted protein-coding genes, GOLGA8E (golgin subfamily a, 8E and WHDC1L1 (WAS protein homology region containing 1-like 1 and have further characterized two previously reported genes, CYF1P1 and NIPA2; all four genes are in the region close to the proximal/centromeric deletion breakpoint (BP1. GOLGA8E belongs to the golgin subfamily of coiled-coil proteins associated with the Golgi apparatus. Six out of 16 golgin subfamily proteins in the human genome have been mapped in the chromosome 15q11-q13 and 15q24-q26 regions. We have also identified more than 38 copies of GOLGA8E-like sequence in the 15q11-q14 and 15q23-q26 regions which supports the presence of a GOLGA8E-associated low copy repeat (LCR. Analysis of the 15q11-q13 region by PFGE also revealed a polymorphic region between BP1 and BP2. WHDC1L1 is a novel gene with similarity to mouse Whdc1 (WAS protein homology region 2 domain containing 1 and human JMY protein (junction-mediating and regulatory protein. Expression analysis of cultured human cells and brain tissues from PWS patients indicates that CYFIP1 and NIPA2 are biallelically expressed. However, we were not able to

  10. The oil rich Niger Delta region: a framework for improved performance of the Nigerian regulatory process.

    Science.gov (United States)

    Onu, N Chukemeka Hemanachi

    2003-06-01

    The adoption of this policy framework has the ability to reconcile industry, the environment and community interests, taking into account all factors that are relevant to managing developments that are both sustainable and contributory to the achievement of industrial and community stability. The management of resource development is crucial in sustaining the Niger Delta ecosystem and the human population resident in the Niger Delta region. If these separate bodies are constituted they would have the potential to reduce and discourage: i) the vulnerability of the regulatory body to influential and powerful multinational oil companies; ii) the proclivity for unaccountability to the people of the Niger Delta region, since the people of the Niger Delta would have access to the regulatory body's classified and unclassified information, and are part of the decision-making process; and iii) a reduction in conflict between the oil mining companies and the aggrieved youths of the oil rich Niger Delta region. This policy framework also has the added advantage of producing high quality decisions and more acceptable decisions than those for which the people of the Niger Delta region are excluded from the processes that concern their existence. The agency decision-making could now become a multilateral process and thus promote and enhance the accurate, impartial and rational application of legislative directives to given cases or classes of cases. Most importantly, the Minister of Petroleum Resources should be empowered by legislation to revoke any license or lease in respect of an area designated as marginal if left undeveloped for a period of 5 years and grant a lease or license for the area to a more responsible oil company.

  11. Telecommunications Liberalisation in Africa: Proposed Regulatory Model for the SADC Region

    Directory of Open Access Journals (Sweden)

    Z. Ntozintle Jobodwana

    2009-12-01

    Full Text Available The liberalisation of the telecommunication industry in Africa, and the further development of the region’s physical infrastructure was accompanied by the further development of Africa’s information, communication and technology infrastructure. Competition within the industry stimulated heavy economic investment in other sectors of the economy. The outcome of liberalisation also included the establishment of community-based structures that continue to enable communities to manage their own development and gain access to information and communication technologies (ICTs in an unprecedented manner. The telecommunication infrastructure further stimulated the fast development of other related services, for example, e-commerce and mobile commerce (m-commerce, e-government, internet banking, mobile banking etcetera. Latest reports and statistics disclose that in Africa m-commerce is set to even overtake the development of e-commerce, through the popular use and penetration of mobile telephony whilst e-commerce development is constrained by difficulties in rolling out speedily fixed telephone lines. These new methods of communication have so intensified that there is hope that further penetration of mobile telephony would leap-frog economic growth and development in Africa, especially in rural communities. Therefore, innovations and investment in ICT’s are changing the world in a number of ways, resulting in a globally connected digital economy.  However, there are regulatory challenges that need to be addressed as a matter of urgency. Certain sections of the continent’s population, especially those in rural areas, have very limited access to ICT’s. This prevents them from exploiting opportunities offered by ICT’s. The main barriers to ICT access relate to inadequate regimes and their supporting legal frameworks, high cost of internet access, connectivity problems, the lack of technical skills to support

  12. WeederH: an algorithm for finding conserved regulatory motifs and regions in homologous sequences

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    Pesole Graziano

    2007-02-01

    Full Text Available Abstract Background This work addresses the problem of detecting conserved transcription factor binding sites and in general regulatory regions through the analysis of sequences from homologous genes, an approach that is becoming more and more widely used given the ever increasing amount of genomic data available. Results We present an algorithm that identifies conserved transcription factor binding sites in a given sequence by comparing it to one or more homologs, adapting a framework we previously introduced for the discovery of sites in sequences from co-regulated genes. Differently from the most commonly used methods, the approach we present does not need or compute an alignment of the sequences investigated, nor resorts to descriptors of the binding specificity of known transcription factors. The main novel idea we introduce is a relative measure of conservation, assuming that true functional elements should present a higher level of conservation with respect to the rest of the sequence surrounding them. We present tests where we applied the algorithm to the identification of conserved annotated sites in homologous promoters, as well as in distal regions like enhancers. Conclusion Results of the tests show how the algorithm can provide fast and reliable predictions of conserved transcription factor binding sites regulating the transcription of a gene, with better performances than other available methods for the same task. We also show examples on how the algorithm can be successfully employed when promoter annotations of the genes investigated are missing, or when regulatory sites and regions are located far away from the genes.

  13. Nef decreases HIV-1 sensitivity to neutralizing antibodies that target the membrane-proximal external region of TMgp41.

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    Rachel P J Lai

    2011-12-01

    Full Text Available Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs that target the membrane proximal external region (MPER of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly

  14. Mitotic binding of Esrrb marks key regulatory regions of the pluripotency network.

    Science.gov (United States)

    Festuccia, Nicola; Dubois, Agnès; Vandormael-Pournin, Sandrine; Gallego Tejeda, Elena; Mouren, Adrien; Bessonnard, Sylvain; Mueller, Florian; Proux, Caroline; Cohen-Tannoudji, Michel; Navarro, Pablo

    2016-11-01

    Pluripotent mouse embryonic stem cells maintain their identity throughout virtually infinite cell divisions. This phenomenon, referred to as self-renewal, depends on a network of sequence-specific transcription factors (TFs) and requires daughter cells to accurately reproduce the gene expression pattern of the mother. However, dramatic chromosomal changes take place in mitosis, generally leading to the eviction of TFs from chromatin. Here, we report that Esrrb, a major pluripotency TF, remains bound to key regulatory regions during mitosis. We show that mitotic Esrrb binding is highly dynamic, driven by specific recognition of its DNA-binding motif and is associated with early transcriptional activation of target genes after completion of mitosis. These results indicate that Esrrb may act as a mitotic bookmarking factor, opening another perspective to molecularly understand the role of sequence-specific TFs in the epigenetic control of self-renewal, pluripotency and genome reprogramming.

  15. DNA Methylation of Regulatory Regions of Imprinted Genes at Birth and Its Relation to Infant Temperament

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    Bernard F. Fuemmeler

    2016-01-01

    Full Text Available BACKGROUND DNA methylation of the differentially methylated regions (DMRs of imprinted genes is relevant to neurodevelopment. METHODS DNA methylation status of the DMRs of nine imprinted genes in umbilical cord blood leukocytes was analyzed in relation to infant behaviors and temperament (n = 158. RESULTS MEG3 DMR levels were positively associated with internalizing ( β = 0.15, P = 0.044 and surgency ( β = 0.19, P = 0.018 behaviors, after adjusting for birth weight, gender, gestational age at birth, maternal age at delivery, race/ethnicity, education level, smoking status, parity, and a history of anxiety or depression. Higher methylation levels at the intergenic MEG3-IG methylation regions were associated with surgency ( β = 0.28, P = 0.0003 and PEG3 was positively related to externalizing ( β = 0.20, P = 0.01 and negative affectivity ( β = 0.18, P = 0.02. CONCLUSION While the small sample size limits inference, these pilot data support gene-specific associations between epigenetic differences in regulatory regions of imprinted domains at birth and later infant temperament.

  16. Proximal Hypospadias

    Science.gov (United States)

    Kraft, Kate H.; Shukla, Aseem R.; Canning, Douglas A.

    2011-01-01

    Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatal position may be located anywhere along the penile shaft, but more severe forms of hypospadias may have a urethral meatus located at the scrotum or perineum. The spectrum of abnormalities may also include ventral curvature of the penis, a dorsally redundant prepuce, and atrophic corpus spongiosum. Due to the severity of these abnormalities, proximal hypospadias often requires more extensive reconstruction in order to achieve an anatomically and functionally successful result. We review the spectrum of proximal hypospadias etiology, presentation, correction, and possible associated complications. PMID:21516286

  17. Phylogenetic and regulatory region analysis of Wnt5 genes reveals conservation of a regulatory module with putative implication in pancreas development

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    Arhondakis Stilianos

    2010-08-01

    Full Text Available Abstract Background Wnt5 genes belong to the large Wnt family, encoding proteins implicated into several tumorigenic and developmental processes. Phylogenetic analyses showed that Wnt5 gene has been duplicated at the divergence time of gnathostomata from agnatha. Interestingly, experimental data for some species indicated that only one of the two Wnt5 paralogs participates in the development of the endocrine pancreas. The purpose of this paper is to reexamine the phylogenetic history of the Wnt5 developmental regulators and investigate the functional shift between paralogs through comparative genomics. Results In this study, the phylogeny of Wnt5 genes was investigated in species belonging to protostomia and deuterostomia. Furthermore, an in silico regulatory region analysis of Wnt5 paralogs was conducted, limited to those species with insulin producing cells and pancreas, covering the evolutionary distance from agnatha to gnathostomata. Our results confirmed the Wnt5 gene duplication and additionally revealed that this duplication event included also the upstream region. Moreover, within this latter region, a conserved module was detected to which a complex of transcription factors, known to be implicated in embryonic pancreas formation, bind. Conclusions Results and observations presented in this study, allow us to conclude that during evolution, the Wnt5 gene has been duplicated in early vertebrates, and that some paralogs conserved a module within their regulatory region, functionally related to embryonic development of pancreas. Interestingly, our results allowed advancing a possible explanation on why the Wnt5 orthologs do not share the same function during pancreas development. As a final remark, we suggest that an in silico comparative analysis of regulatory regions, especially when associated to published experimental data, represents a powerful approach for explaining shift of roles among paralogs. Reviewers This article was reviewed

  18. Phylogenetic and regulatory region analysis of Wnt5 genes reveals conservation of a regulatory module with putative implication in pancreas development.

    Science.gov (United States)

    Kapasa, Maria; Arhondakis, Stilianos; Kossida, Sophia

    2010-08-04

    Wnt5 genes belong to the large Wnt family, encoding proteins implicated into several tumorigenic and developmental processes. Phylogenetic analyses showed that Wnt5 gene has been duplicated at the divergence time of gnathostomata from agnatha. Interestingly, experimental data for some species indicated that only one of the two Wnt5 paralogs participates in the development of the endocrine pancreas. The purpose of this paper is to reexamine the phylogenetic history of the Wnt5 developmental regulators and investigate the functional shift between paralogs through comparative genomics. In this study, the phylogeny of Wnt5 genes was investigated in species belonging to protostomia and deuterostomia. Furthermore, an in silico regulatory region analysis of Wnt5 paralogs was conducted, limited to those species with insulin producing cells and pancreas, covering the evolutionary distance from agnatha to gnathostomata. Our results confirmed the Wnt5 gene duplication and additionally revealed that this duplication event included also the upstream region. Moreover, within this latter region, a conserved module was detected to which a complex of transcription factors, known to be implicated in embryonic pancreas formation, bind. Results and observations presented in this study, allow us to conclude that during evolution, the Wnt5 gene has been duplicated in early vertebrates, and that some paralogs conserved a module within their regulatory region, functionally related to embryonic development of pancreas. Interestingly, our results allowed advancing a possible explanation on why the Wnt5 orthologs do not share the same function during pancreas development. As a final remark, we suggest that an in silico comparative analysis of regulatory regions, especially when associated to published experimental data, represents a powerful approach for explaining shift of roles among paralogs.

  19. The rs1024611 regulatory region polymorphism is associated with CCL2 allelic expression imbalance.

    Directory of Open Access Journals (Sweden)

    Minh-Hieu T Pham

    Full Text Available CC chemokine ligand 2 (CCL2 is the most potent monocyte chemoattractant and inter-individual differences in its expression level have been associated with genetic variants mapping to the cis-regulatory regions of the gene. An A to G polymorphism in the CCL2 enhancer region at position -2578 (rs1024611; A>G, was found in most studies to be associated with higher serum CCL2 levels and increased susceptibility to a variety of diseases such as HIV-1 associated neurological disorders, tuberculosis, and atherosclerosis. However, the precise mechanism by which rs1024611influences CCL2 expression is not known. To address this knowledge gap, we tested the hypothesis that rs1024611G polymorphism is associated with allelic expression imbalance (AEI of CCL2. We used haplotype analysis and identified a transcribed SNP in the 3'UTR (rs13900; C>T can serve as a proxy for the rs1024611 and demonstrated that the rs1024611G allele displayed a perfect linkage disequilibrium with rs13900T allele. Allele-specific transcript quantification in lipopolysaccharide treated PBMCs obtained from heterozygous donors showed that rs13900T allele were expressed at higher levels when compared to rs13900C allele in all the donors examined suggesting that CCL2 is subjected to AEI and that that the allele containing rs1024611G is preferentially transcribed. We also found that AEI of CCL2 is a stable trait and could be detected in newly synthesized RNA. In contrast to these in vivo findings, in vitro assays with haplotype-specific reporter constructs indicated that the haplotype bearing rs1024611G had a lower or similar transcriptional activity when compared to the haplotype containing rs1024611A. This discordance between the in vivo and in vitro expression studies suggests that the CCL2 regulatory region polymorphisms may be functioning in a complex and context-dependent manner. In summary, our studies provide strong functional evidence and a rational explanation for the phenotypic

  20. Tetrahelical structural family adopted by AGCGA-rich regulatory DNA regions

    Science.gov (United States)

    Kocman, Vojč; Plavec, Janez

    2017-05-01

    Here we describe AGCGA-quadruplexes, an unexpected addition to the well-known tetrahelical families, G-quadruplexes and i-motifs, that have been a focus of intense research due to their potential biological impact in G- and C-rich DNA regions, respectively. High-resolution structures determined by solution-state nuclear magnetic resonance (NMR) spectroscopy demonstrate that AGCGA-quadruplexes comprise four 5'-AGCGA-3' tracts and are stabilized by G-A and G-C base pairs forming GAGA- and GCGC-quartets, respectively. Residues in the core of the structure are connected with edge-type loops. Sequences of alternating 5'-AGCGA-3' and 5'-GGG-3' repeats could be expected to form G-quadruplexes, but are shown herein to form AGCGA-quadruplexes instead. Unique structural features of AGCGA-quadruplexes together with lower sensitivity to cation and pH variation imply their potential biological relevance in regulatory regions of genes responsible for basic cellular processes that are related to neurological disorders, cancer and abnormalities in bone and cartilage development.

  1. Identification and Characterization of 5′ Untranslated Regions (5′UTRs in Zymomonas mobilis as Regulatory Biological Parts

    Directory of Open Access Journals (Sweden)

    Seung Hee Cho

    2017-12-01

    Full Text Available Regulatory RNA regions within a transcript, particularly in the 5′ untranslated region (5′UTR, have been shown in a variety of organisms to control the expression levels of these mRNAs in response to various metabolites or environmental conditions. Considering the unique tolerance of Zymomonas mobilis to ethanol and the growing interest in engineering microbial strains with enhanced tolerance to industrial inhibitors, we searched natural cis-regulatory regions in this microorganism using transcriptomic data and bioinformatics analysis. Potential regulatory 5′UTRs were identified and filtered based on length, gene function, relative gene counts, and conservation in other organisms. An in vivo fluorescence-based screening system was developed to confirm the responsiveness of 36 5′UTR candidates to ethanol, acetate, and xylose stresses. UTR_ZMO0347 (5′UTR of gene ZMO0347 encoding the RNA binding protein Hfq was found to down-regulate downstream gene expression under ethanol stress. Genomic deletion of UTR_ZMO0347 led to a general decrease of hfq expression at the transcript level and increased sensitivity for observed changes in Hfq expression at the protein level. The role of UTR_ZMO0347 and other 5′UTRs gives us insight into the regulatory network of Z. mobilis in response to stress and unlocks new strategies for engineering robust industrial strains as well as for harvesting novel responsive regulatory biological parts for controllable gene expression platforms in this organism.

  2. Organ-specific activity of the 5' regulatory region of the glutamine synthetase gene in developing mice

    NARCIS (Netherlands)

    Lie-Venema, H.; de Boer, P. A.; Moorman, A. F.; Lamers, W. H.

    1997-01-01

    Glutamine synthetase (GS) converts ammonia and glutamate into glutamine. We assessed the activity of the 5' regulatory region of the GS gene in developing transgenic mice carrying the chloramphenicol acetyltransferase (CAT) gene under the control of 3150 bp of the upstream sequence of the rat GS

  3. Humoral Immunogenicity of an HIV-1 Envelope Residue 649-684 Membrane-proximal Region Peptide Fused to the Plague Antigen F1-V

    OpenAIRE

    Matoba, Nobuyuki; Shah, Namrata Rahul; Tsafrir S. Mor

    2011-01-01

    The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR649-684 (F1-V-MPR649-684). We employed systemic im...

  4. Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

    KAUST Repository

    Othoum, Ghofran K

    2013-05-01

    Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

  5. Proteins that bind regulatory regions identified by histone modification chromatin immunoprecipitations and mass spectrometry

    Science.gov (United States)

    Engelen, Erik; Brandsma, Johannes H.; Moen, Maaike J.; Signorile, Luca; Dekkers, Dick H. W.; Demmers, Jeroen; Kockx, Christel E. M.; Ozgür, Zehila; van IJcken, Wilfred F. J.; van den Berg, Debbie L. C.; Poot, Raymond A.

    2015-01-01

    The locations of transcriptional enhancers and promoters were recently mapped in many mammalian cell types. Proteins that bind those regulatory regions can determine cell identity but have not been systematically identified. Here we purify native enhancers, promoters or heterochromatin from embryonic stem cells by chromatin immunoprecipitations (ChIP) for characteristic histone modifications and identify associated proteins using mass spectrometry (MS). 239 factors are identified and predicted to bind enhancers or promoters with different levels of activity, or heterochromatin. Published genome-wide data indicate a high accuracy of location prediction by ChIP-MS. A quarter of the identified factors are important for pluripotency and includes Oct4, Esrrb, Klf5, Mycn and Dppa2, factors that drive reprogramming to pluripotent stem cells. We determined the genome-wide binding sites of Dppa2 and find that Dppa2 operates outside the classical pluripotency network. Our ChIP-MS method provides a detailed read-out of the transcriptional landscape representative of the investigated cell type. PMID:25990348

  6. CpG traffic lights are markers of regulatory regions in humans

    KAUST Repository

    Khamis, Abdullah M.

    2016-12-29

    DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.

  7. Genotoxic effects and serum abnormalities in residents of regions proximal to e-waste disposal facilities in Jinghai, China.

    Science.gov (United States)

    Li, KeQiu; Liu, ShaSha; Yang, QiaoYun; Zhao, YuXia; Zuo, JunFang; Li, Ran; Jing, YaQing; He, XiaoBo; Qiu, XingHua; Li, Guang; Zhu, Tong

    2014-07-01

    Electronic waste (e-waste) disposal is a growing problem in China, and its effects on human health are a concern. To determine the concentrations of pollutants in peripheral blood and genetic aberrations near an e-waste disposal area in Jinghai, China, blood samples were collected from 30 (age: 41±11.01 years) and 28 (age: 33±2.14 years) individuals residing within 5 and 40km of e-waste disposal facilities in Jinghai (China), respectively, during the week of October 21-28, 2011. Levels of inorganic pollutants (calcium, copper, iron, lead, magnesium, selenium, and zinc) and malondialdehyde (MDA), identities of persistent organic pollutants (POPs), micronucleus rates, and lymphocyte subsets were analyzed in individuals. Total RNA expression profiles were analyzed by group and gender. The population group living in proximity to the e-waste site displayed significantly higher mean levels of copper, zinc, lead, MDAs, POPs (B4-6DE, B7-9DE, total polychlorinated biphenyls, and BB-153). In addition, micronucleus rates of close-proximity group were higher compared with the remote group (18.27% vs. 7.32%). RNA expression of genes involved in metal ion binding and transport, oxidation/reduction, immune defense, and tumorigenesis varied between groups, with men most detrimentally affected (pe-waste group (pe-waste disposal facilities (≤5km) may be associated with the accumulation of potentially harmful inorganic/organic compounds and gender-preferential genetic aberrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

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    Adriana eBarman

    2014-04-01

    Full Text Available The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT and the logical memory section of the Wechsler Memory Scale (WMS. Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e. the myopia risk allele showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point towards pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.

  9. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    Science.gov (United States)

    Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I.; Schott, Björn H.

    2014-01-01

    The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

  10. Balancing Selection on a Regulatory Region Exhibiting Ancient Variation That Predates Human–Neandertal Divergence

    Science.gov (United States)

    Iskow, Rebecca C.; Austermann, Christian; Scharer, Christopher D.; Raj, Towfique; Boss, Jeremy M.; Sunyaev, Shamil; Price, Alkes; Stranger, Barbara; Simon, Viviana; Lee, Charles

    2013-01-01

    Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10−15). Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human–Neandertal divergence and is evolving under balancing selection, especially among European populations. PMID

  11. Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence.

    Science.gov (United States)

    Gokcumen, Omer; Zhu, Qihui; Mulder, Lubbertus C F; Iskow, Rebecca C; Austermann, Christian; Scharer, Christopher D; Raj, Towfique; Boss, Jeremy M; Sunyaev, Shamil; Price, Alkes; Stranger, Barbara; Simon, Viviana; Lee, Charles

    2013-04-01

    Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (pNeandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human-Neandertal divergence and is evolving under balancing selection, especially among European populations.

  12. Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence.

    Directory of Open Access Journals (Sweden)

    Omer Gokcumen

    2013-04-01

    Full Text Available Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10⁻¹⁵. Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003 and positive Tajima's D (p = 0.00285 statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human-Neandertal divergence and is evolving under balancing selection, especially among European

  13. Importance of a distal proximal contact on load transfer by implant-supported single adjacent crowns in posterior region of the mandible: a photoelastic study

    Science.gov (United States)

    de AGUIAR JÚNIOR, Fábio Afrânio; TIOSSI, Rodrigo; MACEDO, Ana Paula; de MATTOS, Maria da Gloria Chiarello; RIBEIRO, Ricardo Faria; RODRIGUES, Renata Cristina Silveira

    2013-01-01

    Objective This study aimed to evaluate the importance of a distal proximal contact on the load transfer to the posterior region of the mandible by non-splinted adjacent implant-supported crowns using photoelastic stress analysis. Material and Methods A rectangular model (68x30x15 mm) was made of polymethylmethacrylate resin to simulate half of the mandibular arch. One model was completed with resin replicas representing the first premolar and second molar and with two 3.75 mm dia.x11 mm internal hexagon threaded implants replacing the second premolar and first molar. The other model was manufactured in the same way but without the second molar. Both models were duplicated using photoelastic resin. The roots of the teeth replicas were covered with a layer of polyether impression material to simulate the periodontal ligament. Two different vertical loads were applied to the crowns as follows: 1 - single static point load alternately applied to the crowns replacing the second premolar and first molar (50 N); 2 - simultaneous static point loads applied to both of the crowns replacing the second premolar and first molar (100 N). The resulting isochromatic fringe pattern in the photoelastic model was monitored and photographed. Results All loading conditions studied showed that the presence of the second molar has changed the load transmission and the pattern of stresses. Conclusion Results showed that the presence of a second molar proximal contact can help minimize the stresses around the implants. PMID:24212984

  14. Importance of a distal proximal contact on load transfer by implant-supported single adjacent crowns in posterior region of the mandible: a photoelastic study

    Directory of Open Access Journals (Sweden)

    Fabio Afranio de Aguiar Junior

    2013-09-01

    Full Text Available OBJECTIVE: This study aimed to evaluate the importance of a distal proximal contact on the load transfer to the posterior region of the mandible by non-splinted adjacent implant-supported crowns using photoelastic stress analysis. MATERIAL AND METHODS: A rectangular model (68x30x15 mm was made of polymethylmethacrylate resin to simulate half of the mandibular arch. One model was completed with resin replicas representing the first premolar and second molar and with two 3.75 mm dia.x11 mm internal hexagon threaded implants replacing the second premolar and first molar. The other model was manufactured in the same way but without the second molar. Both models were duplicated using photoelastic resin. The roots of the teeth replicas were covered with a layer of polyether impression material to simulate the periodontal ligament. Two different vertical loads were applied to the crowns as follows: 1 - single static point load alternately applied to the crowns replacing the second premolar and first molar (50 N; 2 - simultaneous static point loads applied to both of the crowns replacing the second premolar and first molar (100 N. The resulting isochromatic fringe pattern in the photoelastic model was monitored and photographed. RESULTS: All loading conditions studied showed that the presence of the second molar has changed the load transmission and the pattern of stresses. CONCLUSION: Results showed that the presence of a second molar proximal contact can help minimize the stresses around the implants.

  15. Epigenetic regulation of individual modules of the immunoglobulin heavy chain locus 3’ regulatory region (3’ RR

    Directory of Open Access Journals (Sweden)

    Barbara K Birshtein

    2014-04-01

    Full Text Available The Igh locus undergoes an amazing array of DNA rearrangements and modifications during B cell development. During early stages, the variable region gene is constructed from constituent variable (V, diversity (D and joining (J segments (VDJ joining. B cells that successfully express an antibody can be activated, leading to somatic hypermutation (SHM focused on the variable region, and class switch recombination (CSR, which substitutes downstream constant region genes for the originally used Cμ constant region gene. Many investigators, ourselves included, have sought to understand how these processes specifically target the Igh locus and avoid other loci and potential deleterious consequences of malignant transformation. Our laboratory has concentrated on a complex regulatory region (RR that is located downstream of Cα, the most 3’ of the Igh constant region genes. The ~40 kb 3’ RR, which is predicted to serve as a downstream major regulator of the Igh locus, contains two distinct segments: an ~28 kb region of four enhancers and an adjacent ~12 kb region containing multiple CTCF and Pax5 binding sites. Analysis of targeted mutations in mice by a number of investigators has concluded that the entire 3’ RR enhancer region is essential for SHM and CSR (but not for VDJ joining and for high levels of expression of multiple isotypes. The CTCF/Pax5 binding region is a candidate for influencing VDJ joining early in B cell development and serving as a potential insulator of the Igh locus. Components of the 3’ RR are subject to a variety of epigenetic changes during B cell development, i.e., DNAse I hypersensitivity, histone modifications and DNA methylation, in association with transcription factor binding. We propose that these changes provide a foundation by which regulatory elements in modules of the 3’ RR function by interacting with each other and with target sequences of the Igh locus.

  16. The role of a static bend in the DNA of the aroF regulatory region of Escherichia coli.

    Science.gov (United States)

    Cobbett, C; Dickson, B; Farmer, L

    1989-01-30

    DNA fragments containing the regulatory regions of two genes repressed by the tyrR gene product exhibit retarded electrophoretic mobility in polyacrylamide gels indicating the presence of static bends in the DNA. In the aroF gene this bend has been localized to a region containing two TyrR protein-binding sites. A point mutation between these two sites reduced the degree of bending observed but did not reduce the level of repression, indicating the static bend may not be an important component of the repression mechanism.

  17. SNPs in putative regulatory regions identified by human mouse comparative sequencing and transcription factor binding site data

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Poulabi; Bahlo, Melanie; Schwartz, Jody R.; Loots, Gabriela G.; Houston, Kathryn A.; Dubchak, Inna; Speed, Terence P.; Rubin, Edward M.

    2002-01-01

    Genome wide disease association analysis using SNPs is being explored as a method for dissecting complex genetic traits and a vast number of SNPs have been generated for this purpose. As there are cost and throughput limitations of genotyping large numbers of SNPs and statistical issues regarding the large number of dependent tests on the same data set, to make association analysis practical it has been proposed that SNPs should be prioritized based on likely functional importance. The most easily identifiable functional SNPs are coding SNPs (cSNPs) and accordingly cSNPs have been screened in a number of studies. SNPs in gene regulatory sequences embedded in noncoding DNA are another class of SNPs suggested for prioritization due to their predicted quantitative impact on gene expression. The main challenge in evaluating these SNPs, in contrast to cSNPs is a lack of robust algorithms and databases for recognizing regulatory sequences in noncoding DNA. Approaches that have been previously used to delineate noncoding sequences with gene regulatory activity include cross-species sequence comparisons and the search for sequences recognized by transcription factors. We combined these two methods to sift through mouse human genomic sequences to identify putative gene regulatory elements and subsequently localized SNPs within these sequences in a 1 Megabase (Mb) region of human chromosome 5q31, orthologous to mouse chromosome 11 containing the Interleukin cluster.

  18. The CD4 and CD3δε Cytosolic Juxtamembrane Regions Are Proximal within a Compact TCR-CD3-pMHC-CD4 Macrocomplex.

    Science.gov (United States)

    Glassman, Caleb R; Parrish, Heather L; Deshpande, Neha R; Kuhns, Michael S

    2016-06-01

    TCRs relay information about peptides embedded within MHC molecules (pMHC) to the ITAMs of the associated CD3γε, CD3δε, and CD3ζζ signaling modules. CD4 then recruits the Src kinase p56(Lck) (Lck) to the TCR-CD3 complex to phosphorylate the ITAMs, initiate intracellular signaling, and drive CD4(+) T cell fate decisions. Whereas the six ITAMs of CD3ζζ are key determinants of T cell development, activation, and the execution of effector functions, multiple models predict that CD4 recruits Lck proximal to the four ITAMs of the CD3 heterodimers. We tested these models by placing FRET probes at the cytosolic juxtamembrane regions of CD4 and the CD3 subunits to evaluate their relationship upon pMHC engagement in mouse cell lines. The data are consistent with a compact assembly in which CD4 is proximal to CD3δε, CD3ζζ resides behind the TCR, and CD3γε is offset from CD3δε. These results advance our understanding of the architecture of the TCR-CD3-pMHC-CD4 macrocomplex and point to regions of high CD4-Lck + ITAM concentrations therein. The findings thus have implications for TCR signaling, as phosphorylation of the CD3 ITAMs by CD4-associated Lck is important for CD4(+) T cell fate decisions. Copyright © 2016 by The American Association of Immunologists, Inc.

  19. [Cloning and comparative characterization of the rIGS regulatory regions in humans and the pygmy chimpanzee Pan paniscus].

    Science.gov (United States)

    Kupriianova, N S; Nechvolodov, K K; Voronov, A S; Shibalev, D V; Ryskov, A P

    2002-08-01

    Investigation of randomly cloned genomic and chromosome-specific sequences of ribosomal DNA (rDNA) from different organisms show that different regions of this long repeat unit evolve at different rates. This proves to be true not only with regard to evolutionary variability of transcribed and nontranscribed intergenic (spacer) regions of rDNA. The intergenic spacer (rIGS) of human ribosomal DNA contains both highly variable and more conservative regions with putative regulatory functions. In the present study a comparative analysis of some segments of the rIGS pre-promoter (regulatory) region in human and pygmy chimpanzee (Pan paniscus) was carried out. For these purposes, the corresponding DNA fragments were amplified in PCR with oligonucleotide primers specific to human rIGS and sequenced. Our results show that at the background of substantial structural similarity of these regions in man and chimpanzee, i.e., the presence of highly homologous sequences and similar repetitive units, there are substantial differences between them. These differences are associated with point mutations, insertions, deletions, and complex structural rearrangements.

  20. Regulatory Design of Capacity Remuneration Mechanisms in Regional and Low-Carbon Electric Power Markets

    NARCIS (Netherlands)

    Mastropietro, P.

    2016-01-01

    Capacity remuneration mechanisms (CRMs) are “climbing” regulatory agendas in all liberalised power sectors, especially in the European Union. CRMs are introduced to improve system reliability and to minimise power shortages to an economically efficient extent. These schemes will have a central role

  1. Potential novel mechanism for Axenfeld-Rieger syndrome: deletion of a distant region containing regulatory elements of PITX2.

    Science.gov (United States)

    Volkmann, Bethany A; Zinkevich, Natalya S; Mustonen, Aki; Schilter, Kala F; Bosenko, Dmitry V; Reis, Linda M; Broeckel, Ulrich; Link, Brian A; Semina, Elena V

    2011-03-01

    Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. Conserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes. Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13. These data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion.

  2. The air quality and regional climate effects of widespread solar power generation under a changing regulatory environment

    Science.gov (United States)

    Millstein, D.; Zhai, P.; Menon, S.

    2011-12-01

    Over the past decade significant reductions of NOx and SOx emissions from coal burning power plants in the U.S. have been achieved due to regulatory action and substitution of new generation towards natural gas and wind power. Low natural gas prices, ever decreasing solar generation costs, and proposed regulatory changes, such as to the Cross State Air Pollution Rule, promise further long-run coal power plant emission reductions. Reduced power plant emissions have the potential to affect ozone and particulate air quality and influence regional climate through aerosol cloud interactions and visibility effects. Here we investigate, on a national scale, the effects on future (~2030) air quality and regional climate of power plant emission regulations in contrast to and combination with policies designed to aggressively promote solar electricity generation. A sophisticated, economic and engineering based, hourly power generation dispatch model is developed to explore the integration of significant solar generation resources (>10% on an energy basis) at various regions across the county, providing detailed estimates of substitution of solar generation for fossil fuel generation resources. Future air pollutant emissions from all sectors of the economy are scaled based on the U.S. Environmental Protection Agency's National Emission Inventory to account for activity changes based on population and economic projections derived from county level U.S. Census data and the Energy Information Administration's Annual Energy Outlook. Further adjustments are made for technological and regulatory changes applicable within various sectors, for example, emission intensity adjustments to on-road diesel trucking due to exhaust treatment and improved engine design. The future year 2030 is selected for the emissions scenarios to allow for the development of significant solar generation resources. A regional climate and air quality model (Weather Research and Forecasting, WRF model) is

  3. Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Joshi NV

    2009-01-01

    Full Text Available Abstract Background Regulation of gene expression in Plasmodium falciparum (Pf remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS; this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

  4. Preliminary Prioritization of California Oil and Gas Fields for Regional Groundwater Monitoring Based on Intensity of Petroleum Resource Development and Proximity to Groundwater Resources

    Science.gov (United States)

    Davis, T. A.; Landon, M. K.; Bennett, G.

    2016-12-01

    The California State Water Resources Control Board is collaborating with the U.S. Geological Survey to implement a Regional Monitoring Program (RMP) to assess where and to what degree groundwater resources may be at risk of contamination from oil and gas development activities including stimulation, well integrity issues, produced water ponds, and underground injection. A key issue in the implementation of the RMP is that the state has 487 onshore oil fields covering 8,785 square kilometers but detailed characterization work can only be done in a few oil fields annually. The first step in the RMP is to prioritize fields using available data that indicate potential risk to groundwater from oil and gas development, including vertical proximity of groundwater and oil/gas resources, density of petroleum and water wells, and volume of water injected in oil fields. This study compiled data for these factors, computed summary metrics for each oil field, analyzed statewide distributions of summary metrics, used those distributions to define relative categories of potential risk for each factor, and combined these into an overall priority ranking. Aggregated results categorized 22% (107 fields) of the total number of onshore oil and gas fields in California as high priority, 23% as moderate priority, and 55% as low priority. On an area-weighted basis, 41% of the fields ranked high, 30% moderate, and 29% low, highlighting that larger fields tend to have higher potential risk because of greater intensity of development, sometimes coupled with closer proximity to groundwater. More than half of the fields ranked as high priority were located in the southern Central Valley or the Los Angeles Basin. The prioritization does not represent an assessment of groundwater risk from oil and gas development; rather, such assessments are planned to follow based on detailed analysis of data from the RMP near the oil fields selected for study in the future.

  5. Screening of the transcriptional regulatory regions of vascular endothelial growth factor receptor 2 (VEGFR2 in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Hartley Judith

    2007-04-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF has neurotrophic activity which is mediated by its main agonist receptor, VEGFR2. Dysregulation of VEGF causes motor neurone degeneration in a mouse model of amyotrophic lateral sclerosis (ALS, and expression of VEGFR2 is reduced in motor neurones and spinal cord of patients with ALS. Methods We have screened the promoter region and 4 exonic regions of functional significance of the VEGFR2 gene in a UK population of patients with ALS, for mutations and polymorphisms that may affect expression or function of this VEGF receptor. Results No mutations were identified in the VEGFR2 gene. We found no association between polymorphisms in the regulatory regions of the VEGFR2 gene and ALS. Conclusion Mechanisms other than genetic variation may downregulate expression or function of the VEGFR2 receptor in patients with ALS.

  6. An adaptive transposable element insertion in the regulatory region of the EO gene in the domesticated silkworm, Bombyx mori.

    Science.gov (United States)

    Sun, Wei; Shen, Yi-Hong; Han, Min-Jin; Cao, Yun-Feng; Zhang, Ze

    2014-12-01

    Although there are many studies to show a key role of transposable elements (TEs) in adaptive evolution of higher organisms, little is known about the molecular mechanisms. In this study, we found that a partial TE (Taguchi) inserted in the cis-regulatory region of the silkworm ecdysone oxidase (EO) gene, which encodes a crucial enzyme to reduce the titer of molting hormone (20-hydroxyecdysone, 20E). The TE insertion occurred during domestication of silkworm and the frequency of the TE insertion in the domesticated silkworm (Bombyx mori) is high, 54.24%. The linkage disequilibrium in the TE inserted strains of the domesticated silkworm was elevated. Molecular population genetics analyses suggest that this TE insertion is adaptive for the domesticated silkworm. Luminescent reporter assay shows that the TE inserted in the cis-regulatory region of the EO gene functions as a 20E-induced enhancer of the gene expression. Further, phenotypic bioassay indicates that the silkworm with the TE insertion exhibited more stable developmental phenotype than the silkworm without the TE insertion when suffering from food shortage. Thus, the inserted TE in the cis-regulatory region of the EO gene increased developmental uniformity of silkworm individuals through regulating 20E metabolism, partially explaining transformation of a domestication developmental trait in the domesticated silkworm. Our results emphasize the exceptional role of gene expression regulation in developmental transition of domesticated animals. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. ARTIST (Asian regional tobacco industry scientist team): Philip Morris' attempt to exert a scientific and regulatory agenda on Asia.

    Science.gov (United States)

    Tong, E K; Glantz, S A

    2004-12-01

    To describe how the transnational tobacco industry has collaborated with local Asian tobacco monopolies and companies to promote a scientific and regulatory agenda. Analysis of previously secret tobacco industry documents. Transnational tobacco companies began aggressively entering the Asia market in the 1980s, and the current tobacco industry in Asia is a mix of transnational and local monopolies or private companies. Tobacco industry documents demonstrate that, in 1996, Philip Morris led an organisation of scientific representatives from different tobacco companies called the Asian Regional Tobacco Industry Science Team (ARTIST), whose membership grew to include monopolies from Korea, China, Thailand, and Taiwan and a company from Indonesia. ARTIST was initially a vehicle for PM's strategies against anticipated calls for global smoke-free areas from a World Health Organization secondhand smoke study. ARTIST evolved through 2001 into a forum to present scientific and regulatory issues faced primarily by Philip Morris and other transnational tobacco companies. Philip Morris' goal for the organisation became to reach the external scientific and public health community and regulators in Asia. The Asian tobacco industry has changed from an environment of invasion by transnational tobacco companies to an environment of participation with Philip Morris' initiated activities. With this participation, tobacco control efforts in Asia face new challenges as Philip Morris promotes and integrates its scientific and regulatory agenda into the local Asian tobacco industry. As the local Asian tobacco monopolies and companies can have direct links with their governments, future implementation of effective tobacco control may be at odds with national priorities.

  8. Regulatory elements in the 5'region of 16SrRNA gene of Bacillus sp. strain SJ-101.

    Science.gov (United States)

    Singh, Braj R; Al-Khedhairy, Abdulaziz A; Alarifi, Saud A; Musarrat, Javed

    2009-06-13

    Advancement in bioinformatics with the development of computational tools has enabled the in-silico prediction and identification of transcription regulatory factors and other genetic elements with great ease. In this study, computational analysis of sequence homology of 546 bp 5' region of 16SrRNA gene of Bacillus sp. strain SJ-101 resulted in identification of promoter-like sequences within the rrn gene. Using BPROM tool, the regulatory motifs like -35 and -10 boxes were mapped at 392 and 411 positions, respectively. Furthermore, the cis-acting elements as the binding sites for transcription factors (TF) cpxR and argR were identified at positions 413 and 416 at the upstream of an open reading frame (ORF). The probable functions of the putative TFs were predicted through the Uni-Prot/Swiss-Prot protein database. Search for the Shine-Dalgarno sequence (SD) found the presence of highly conserved SD sequence (AATACC), and a short 42 bp coding sequence/ORF bounded with characteristic transcription start site (AAC) and a stop codon (TGA) at positions 426 and 465 downstream to the promoter elements. A 13 amino acid long translation product of a short ORF has exhibited 100% homology with protein sequences of Bacillus spp., while showing some degree of polymorphism with other reference strains. The comparative homology of the small protein exhibited maximum similarity with Prolyl-4 hydroxylase of Chlamydomonas reinhardtii with 4.11 ZSCORE. The highly conserved regulatory elements and the putative ORF predicted within the 16SrRNA gene may help understand the role of relatively unexplored short ORFs within rrn operon, and their functional products in genetic regulatory mechanisms in eubacteria.

  9. Gene-scrambling mutagenesis: generation and analysis of insertional mutations in the alginate regulatory region of Pseudomonas aeruginosa.

    Science.gov (United States)

    Mohr, C D; Deretic, V

    1990-11-01

    A novel method for random mutagenesis of targeted chromosomal regions in Pseudomona aeruginosa was developed. This method can be used with a cloned DNA fragment of indefinite size that contains a putative gene of interest. Cloned DNA is digested to produce small fragments that are then randomly reassembled into long DNA inserts by using cosmid vectors and lambda packaging reaction. This DNA is then transferred into P. aeruginosa and forced into the chromosome via homologous recombination, producing in a single step a random set of insertional mutants along a desired region of the chromosome. Application of this method to extend the analysis of the alginate regulatory region, using a cloned 6.2-kb fragment with the algR gene and the previously uncharacterized flanking regions, produced several insertional mutations. One mutation was obtained in algR, a known transcriptional regulatory of mucoidy in P. aeruginosa. The null mutation of algR was generated in a mucoid derivative of the standard genetic strain PAO responsive to different environmental factors. This mutation was used to demonstrate that the algR gene product was not essential for the regulation of its promoters. Additional insertions were obtained in regions downstream and upstream of algR. A mutation that did not affect mucoidy was generated in a gene located 1 kb upstream of algR. This gene was transcribed in the direction opposite that of algR transcription and encoded a polypeptide of 47 kDa. Partial nucleotide sequence analysis revealed strong homology of its predicted gene product with the human and yeast argininosuccinate lyases. An insertion downstream of algR produced a strain showing reduced induction of mucoidy in response to growth on nitrate as the nitrogen source.

  10. Evolution of transcription factor binding sites in mammalian gene regulatory regions: handling counterintuitive results.

    Science.gov (United States)

    Balmer, James E; Blomhoff, Rune

    2009-06-01

    The remodeling of transcription factor binding sites is one of the major engines of evolutionary change, yet almost all available examples of this involve sites from regulatory modules brought online during development. Developmental modules are known to enjoy some type of canalization, which allows considerably more cryptic change than would be assumed for nondevelopmental modules. It remains an open question, then, how frequently binding site remodeling occurs in general. There are strong intuitive reasons to expect that regulatory constancy, and hence binding site conservation in general, is the rule, yet little systematic work has been done to verify this. In the present article, we show that the most obvious way of approaching this problem--which is simply to collect experimentally verified binding sites from the literature without further analysis, create multispecies alignments, and apply conservation algorithms--leads to counterintuitive and ultimately inaccurate results. This is because of the low complexity of typical binding sites and, consequently, because of the frequency with which strings resembling legitimate sites occur throughout the genome. In vitro results can easily be confounded by this. Applying one traditional conservation algorithm and two novel algorithms to a data set that ought to be representative of binding sites in general, but which is taken from the literature directly, we find that only 58% of sites appear to be conserved. However, after the data set is carefully vetted against binding site overloading, and after the likelihood of a specific type of compensatory evolution is evaluated, conservation rates as high as 94% appear reasonable.

  11. Relationship of regulatory T cells to Plasmodium falciparum malaria symptomatology in a hypoendemic region.

    Science.gov (United States)

    Torres, Katherine J; Villasis, Elizabeth; Bendezú, Jorge; Chauca, José; Vinetz, Joseph M; Gamboa, Dionicia

    2014-03-19

    Previous data have suggested that regulatory T cells (Tregs) balance protective immune responses with immune mediated pathology in malaria. This study aimed to determine to test the hypothesis that Treg proportions or absolute levels are associated with parasitaemia and malaria symptoms. Treg cells were quantified by flow cytometry as CD4+ CD25+, Foxp3+, CD127(low) T cells. Three patient groups were assessed: patients with symptomatic Plasmodium falciparum malaria (S), subjects with asymptomatic P. falciparum parasitaemia (AS) and uninfected control individuals (C). S, AS and C groups had similar absolute numbers and percentage of Tregs (3.9%, 3.5% and 3.5% respectively). Levels of parasitaemia were not associated with Treg percentage (p = 0.47). Neither relative nor absolute regulatory T cell numbers were found to be associated with malaria-related symptomatology in this study. Immune mechanisms other than Tregs are likely to be responsible for the state of asymptomatic P. falciparum parasitaemia in the Peruvian Amazon; but further study to explore these mechanisms is needed.

  12. Discovery of transcription factors and regulatory regions driving in vivo tumor development by ATAC-seq and FAIRE-seq open chromatin profiling.

    Directory of Open Access Journals (Sweden)

    Kristofer Davie

    2015-02-01

    Full Text Available Genomic enhancers regulate spatio-temporal gene expression by recruiting specific combinations of transcription factors (TFs. When TFs are bound to active regulatory regions, they displace canonical nucleosomes, making these regions biochemically detectable as nucleosome-depleted regions or accessible/open chromatin. Here we ask whether open chromatin profiling can be used to identify the entire repertoire of active promoters and enhancers underlying tissue-specific gene expression during normal development and oncogenesis in vivo. To this end, we first compare two different approaches to detect open chromatin in vivo using the Drosophila eye primordium as a model system: FAIRE-seq, based on physical separation of open versus closed chromatin; and ATAC-seq, based on preferential integration of a transposon into open chromatin. We find that both methods reproducibly capture the tissue-specific chromatin activity of regulatory regions, including promoters, enhancers, and insulators. Using both techniques, we screened for regulatory regions that become ectopically active during Ras-dependent oncogenesis, and identified 3778 regions that become (over-activated during tumor development. Next, we applied motif discovery to search for candidate transcription factors that could bind these regions and identified AP-1 and Stat92E as key regulators. We validated the importance of Stat92E in the development of the tumors by introducing a loss of function Stat92E mutant, which was sufficient to rescue the tumor phenotype. Additionally we tested if the predicted Stat92E responsive regulatory regions are genuine, using ectopic induction of JAK/STAT signaling in developing eye discs, and observed that similar chromatin changes indeed occurred. Finally, we determine that these are functionally significant regulatory changes, as nearby target genes are up- or down-regulated. In conclusion, we show that FAIRE-seq and ATAC-seq based open chromatin profiling

  13. HLA-E regulatory and coding region variability and haplotypes in a Brazilian population sample.

    Science.gov (United States)

    Ramalho, Jaqueline; Veiga-Castelli, Luciana C; Donadi, Eduardo A; Mendes-Junior, Celso T; Castelli, Erick C

    2017-11-01

    The HLA-E gene is characterized by low but wide expression on different tissues. HLA-E is considered a conserved gene, being one of the least polymorphic class I HLA genes. The HLA-E molecule interacts with Natural Killer cell receptors and T lymphocytes receptors, and might activate or inhibit immune responses depending on the peptide associated with HLA-E and with which receptors HLA-E interacts to. Variable sites within the HLA-E regulatory and coding segments may influence the gene function by modifying its expression pattern or encoded molecule, thus, influencing its interaction with receptors and the peptide. Here we propose an approach to evaluate the gene structure, haplotype pattern and the complete HLA-E variability, including regulatory (promoter and 3'UTR) and coding segments (with introns), by using massively parallel sequencing. We investigated the variability of 420 samples from a very admixed population such as Brazilians by using this approach. Considering a segment of about 7kb, 63 variable sites were detected, arranged into 75 extended haplotypes. We detected 37 different promoter sequences (but few frequent ones), 27 different coding sequences (15 representing new HLA-E alleles) and 12 haplotypes at the 3'UTR segment, two of them presenting a summed frequency of 90%. Despite the number of coding alleles, they encode mainly two different full-length molecules, known as E*01:01 and E*01:03, which corresponds to about 90% of all. In addition, differently from what has been previously observed for other non classical HLA genes, the relationship among the HLA-E promoter, coding and 3'UTR haplotypes is not straightforward because the same promoter and 3'UTR haplotypes were many times associated with different HLA-E coding haplotypes. This data reinforces the presence of only two main full-length HLA-E molecules encoded by the many HLA-E alleles detected in our population sample. In addition, this data does indicate that the distal HLA-E promoter is by

  14. Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.

    Directory of Open Access Journals (Sweden)

    Lynn Morris

    Full Text Available Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER. We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673-680 and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (V(H1-69 and variable kappa light chain (V(K3-20 gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672-680. These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection.

  15. Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting

    Science.gov (United States)

    Morris, Lynn; Chen, Xi; Alam, Munir; Tomaras, Georgia; Zhang, Ruijun; Marshall, Dawn J.; Chen, Bing; Parks, Robert; Foulger, Andrew; Jaeger, Frederick; Donathan, Michele; Bilska, Mira; Gray, Elin S.; Abdool Karim, Salim S.; Kepler, Thomas B.; Whitesides, John; Montefiori, David; Moody, M. Anthony; Liao, Hua-Xin; Haynes, Barton F.

    2011-01-01

    Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673–680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (VH1-69) and variable kappa light chain (VK3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672–680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection. PMID:21980336

  16. Multiple interactions between regulatory regions are required to stabilize an active chromatin hub.

    NARCIS (Netherlands)

    G.P. Patrinos (George); M. de Krom (Mariken); E. de Boer (Ernie); A. Langeveld (An); A.M.A. Imam (Ali); J. Strouboulis (John); W.L. de Laat (Wouter); F.G. Grosveld (Frank)

    2004-01-01

    textabstractThe human beta-globin locus control region (LCR) is required for the maintenance of an open chromatin configuration of the locus. It interacts with the genes and the hypersensitive regions flanking the locus to form an active chromatin hub (ACH) transcribing the genes. Proper

  17. 10 CFR Appendix D to Part 20 - United States Nuclear Regulatory Commission Regional Offices

    Science.gov (United States)

    2010-01-01

    ... 19406-1415 (610) 337-5000(800) 432-1156 TDD: (301) 415-5575 [email protected] Region II..., 61 Forsyth Street, SW, Atlanta, GA 30303-8931 (404) 562-4400(800) 877-8510 TDD: (301) 415-5575 Rids...-3025 TDD: (301) 415-5575 [email protected] Region IV: Alaska, Arizona, Arkansas, California...

  18. Proximal femoral fractures

    DEFF Research Database (Denmark)

    Palm, Henrik; Teixidor, Jordi

    2015-01-01

    -displaced femoral neck fractures and prosthesis for displaced among the elderly; and sliding hip screw for stabile- and intramedullary nails for unstable- and sub-trochanteric fractures) but they are based on a variety of criteria and definitions - and often leave wide space for the individual surgeons' subjective...... guidelines for hip fracture surgery and discuss a method for future pathway/guideline implementation and evaluation. METHODS: By a PubMed search in March 2015 six studies of surgical treatment pathways covering all types of proximal femoral fractures with publication after 1995 were identified. Also we...... searched the homepages of the national heath authorities and national orthopedic societies in West Europe and found 11 national or regional (in case of no national) guidelines including any type of proximal femoral fracture surgery. RESULTS: Pathway consensus is outspread (internal fixation for un...

  19. Regulatory Elements Located in the Upstream Region of the Rhizobium leguminosarum rosR Global Regulator Are Essential for Its Transcription and mRNA Stability

    Directory of Open Access Journals (Sweden)

    Kamila Rachwał

    2017-12-01

    Full Text Available Rhizobium leguminosarum bv. trifolii is a soil bacterium capable of establishing a symbiotic relationship with clover (Trifolium spp.. Previously, the rosR gene, encoding a global regulatory protein involved in motility, synthesis of cell-surface components, and other cellular processes was identified and characterized in this bacterium. This gene possesses a long upstream region that contains several regulatory motifs, including inverted repeats (IRs of different lengths. So far, the role of these motifs in the regulation of rosR transcription has not been elucidated in detail. In this study, we performed a functional analysis of these motifs using a set of transcriptional rosR-lacZ fusions that contain mutations in these regions. The levels of rosR transcription for different mutant variants were evaluated in R. leguminosarum using both quantitative real-time PCR and β-galactosidase activity assays. Moreover, the stability of wild type rosR transcripts and those with mutations in the regulatory motifs was determined using an RNA decay assay and plasmids with mutations in different IRs located in the 5′-untranslated region of the gene. The results show that transcription of rosR undergoes complex regulation, in which several regulatory elements located in the upstream region and some regulatory proteins are engaged. These include an upstream regulatory element, an extension of the -10 element containing three nucleotides TGn (TGn-extended -10 element, several IRs, and PraR repressor related to quorum sensing.

  20. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  1. Calreticulin discriminates the proximal region at the N-glycosylation site of Glc1Man9GlcNAc2 ligand

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Makoto; Adachi, Yuka [Department of Materials and Life Science, Seikei University, 3-3-1 Kichijoji-kita, Musashino, Tokyo 180-8633 (Japan); Ito, Yukishige [Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); ERATO, Japan Science and Technology Agency, Ito Glycotrilogy Project, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Totani, Kiichiro, E-mail: ktotani@st.seikei.ac.jp [Department of Materials and Life Science, Seikei University, 3-3-1 Kichijoji-kita, Musashino, Tokyo 180-8633 (Japan)

    2015-10-23

    Calreticulin (CRT) is well known as a lectin-like chaperone that recognizes Glc1Man9GlcNAc2 (G1M9)-glycoproteins in the endoplasmic reticulum (ER). However, whether CRT can directly interact with the aglycone moiety (protein portion) of the glycoprotein remains controversial. To improve our understanding of CRT interactions, structure-defined G1M9-derivatives with different aglycones (–OH, –Gly–NH{sub 2}, and –Gly–Glu–{sup t}Bu) were used as CRT ligands, and their interactions with recombinant CRT were analyzed using thermal shift analysis. The results showed that CRT binds strongly to a G1M9-ligand in the order –Gly–Glu–{sup t}Bu > –Gly–NH{sub 2} > –OH, which is the same as that of the reglucosylation of Man9GlcNAc2 (M9)-derivatives by the folding sensor enzyme UGGT (UDP-glucose: glycoprotein glucosyltransferase). Our results indicate that, similar to UGGT, CRT discriminates the proximal region at the N-glycosylation site, suggesting a similar mechanism mediating the recognition of aglycone moieties in the ER glycoprotein quality control system. - Highlights: • Glc1Man9GlcNAc2 (G1M9) ligands with different aglycones were chemically prepared. • Calreticulin (CRT) discriminates the aglycone of Glc1Man9GlcNAc2 (G1M9) ligand. • CRT binds with G1M9 ligands in a similar manner to folding sensor enzyme.

  2. Humoral Immunogenicity of an HIV-1 Envelope Residue 649-684 Membrane-proximal Region Peptide Fused to the Plague Antigen F1-V

    Science.gov (United States)

    Matoba, Nobuyuki; Shah, Namrata Rahul; Mor, Tsafrir S

    2011-01-01

    The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR649-684 (F1-V-MPR649-684). We employed systemic immunization for initial feasibility analyses. Despite strong immunogenicity demonstrated for the immunogen, repeated systemic immunizations of mice with F1-V-MPR649-684 hardly induced MPR649-684-specific IgG. In contrast, a single immunization with F1-V-MPR649-684 mounted a significant anti-MPR649-684 IgG response in animals that were primed with another MPR649-684 fusion protein based on the cholera toxin B subunit. Additional boost immunizations with F1-V-MPR649-684 recalled and maintained the antibody response and expanded the number of specific antibody-secreting B cells. Thus, while F1-V-MPR649-684 alone was not sufficiently immunogenic to induce detectable levels of MPR649-684-specific antibodies, these results suggest that prime-boost immunization using heterologous antigen-display platforms may overcome the poor humoral immunogenicity of MPR649-684 for the induction of durable humoral immunity. Further studies are warranted to evaluate the feasibility of this strategy in mucosal immunization. Lastly, our findings add to a growing body of evidence in support of this strategy for immunogen design for poorly immunogenic epitopes besides the MPR of HIV-1's transmembrane envelope protein. PMID:21693158

  3. Transcytosis-blocking abs elicited by an oligomeric immunogen based on the membrane proximal region of HIV-1 gp41 target non-neutralizing epitopes.

    Science.gov (United States)

    Matoba, Nobuyuki; Griffin, Tagan A; Mittman, Michele; Doran, Jeffrey D; Alfsen, Annette; Montefiori, David C; Hanson, Carl V; Bomsel, Morgane; Mor, Tsafrir S

    2008-05-01

    CTB-MPR(649-684), a translational fusion protein consisting of cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produced CTB MPR(649-684) was purified to homogeneity by two affinity chromatography steps. Similar to gp41 and derivatives thereof, the MPR domain can specifically and reversibly self-associate. The affinities of the broadly-neutralizing monoclonal Abs 4E10 and 2F5 to CTB MPR(649-684) were equivalent to their nanomolar affinities toward an MPR peptide. The fusion protein's affinity to GM1 ganglioside was comparable to that of native CTB. Rabbits immunized with CTB-MPR(649-684) raised only a modest level of anti-MPR(649-684) Abs. However, a prime-boost immunization with CTB-MPR(649-684) and a second MPR(649-684)-based immunogen elicited a more productive anti-MPR(649-684) antibody response. These Abs strongly blocked the epithelial transcytosis of a primary subtype B HIV-1 isolate in a human tight epithelial model, expanding our previously reported results using a clade D virus. The Abs recognized epitopes at the N-terminal portion of the MPR peptide, away from the 2F5 and 4E10 epitopes and were not effective in neutralizing infection of CD4+ cells. These results indicate distinct vulnerabilities of two separate interactions of HIV-1 with human cells - Abs against the C-terminal portion of the MPR can neutralize CD4+-dependent infection, while Abs targeting the MPR's N-terminal portion can effectively block galactosyl ceramide dependent transcytosis. We propose that Abs induced by MPR(649-684)-based immunogens may provide broad protective value independent of infection neutralization.

  4. Stormwater Infrastructure in the Los Angeles Region: Are Regulatory Drivers and Opportunism the Best Approach to Clean Water?

    Science.gov (United States)

    Mika, K.; Gold, M.

    2016-12-01

    The Los Angeles region has invested nearly a billion dollars in stormwater infrastructure projects over the last 15 years. The primary drivers for these projects have been regulatory requirements under the Los Angeles County MS4 permit and Total Maximum Daily Loads (TMDLs) for over 150 impaired water bodies in the region. In addition, voters in the state of California have approved five separate water bonds over the last 15 years totaling nearly 21 billion. The City of Los Angeles approved a 500 million stormwater bond in 2004 to construct best management practices (BMPs) to help the city comply with water quality standards. There have also been numerous comprehensive Low Impact Development (LID) ordinances approved in the region that are designed to ensure that new and redevelopment capture for reuse or infiltrate 100% of the runoff generated from the 85th percentile storm. This presentation will overview an assessment of decision-making related to the funding of stormwater BMPs in the region. Specific examples of constructed BMPs, including their performance for meeting water quality standards, will be provided. Among the shortcomings of relying on a bond funding approach to new stormwater infrastructure is a California statutory prohibition on using bond funds for BMP operations and maintenance. The advantages of a systematic structural BMP sizing, designing and siting approach based on optimizing multiple beneficial uses (water quality, flood control, water supply, habitat and recreation) across watersheds or subwatersheds will also be discussed. Integration of stormwater infrastructure construction with transportation improvement projects, as well as building retrofit upon sale requirements, will greatly expedite regional transformation to green stormwater infrastructure.

  5. PuF, an antimetastatic and developmental signaling protein, interacts with the Alzheimer’s amyloid-β precursor protein via a tissue-specific proximal regulatory element (PRE

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    Lahiri Debomoy K

    2013-01-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is intimately tied to amyloid-β (Aβ peptide. Extraneuronal brain plaques consisting primarily of Aβ aggregates are a hallmark of AD. Intraneuronal Aβ subunits are strongly implicated in disease progression. Protein sequence mutations of the Aβ precursor protein (APP account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or “proximal regulatory element” (PRE, at −76/−47, from the +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay (EMSA and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. Results EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 (AP2, nm23 nucleoside diphosphate kinase/metastatic inhibitory protein (PuF, and specificity protein 1 (SP1. These sites crossed a known single nucleotide polymorphism (SNP. EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. Conclusions We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also

  6. The regulatory role of the state strategic management in the development of the regional entrepreneurial sphere

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    Yukhneva Nina

    2017-01-01

    Full Text Available The system of state strategic management (SGSO today is an Outpost of the state, exercising the functions of strategic management, development and predicates, and conducting an evaluation of the effectiveness and quality of the planned trajectories of economic development of the regions, regions and the state as a whole. It SGSW today is designed to ensure that the nationally oriented domestic policies that contribute to progressive and bold actions of the Russian Federation on the world stage. SHSU today is to create conditions for the development of science, research training, new knowledge-based economy. SHSU should form a system of state orders, which is of fundamental importance for the development of strategic projects in the field of medicine and health, agriculture, defense industry, etc. And, most importantly, SHSU needs today and support the process of re-industrialization of the country, technical re-equipment of all areas of production and management. In the new knowledge economy SHSU performs the role of the intellectual and information center regulation and strategic planning of development of the entire socio-economic sphere of the society centre to ensure the development of a database of fundamental and applied research, development, centre, guaranteeing the protection of copyright and introduction of innovative products, including new technical and technological solutions.

  7. Regulatory aspects of food irradiation in the Asia-Pacific region

    Science.gov (United States)

    Roberts, Peter B.

    2000-03-01

    The latest information on the countries in the Asia/Pacific region with approvals for food to be irradiated is provided. Differences in the type of regulations used are contrasted. However, progress has been made towards greater uniformity in regulations based around the Codex General Standard for Irradiated Food. Australia and New Zealand instituted, respectively, a moratorium and a ban on food irradiation in 1988. Australia has proposed a new draft Standard for food irradiation and this is the subject of public discussion under the Australia New Zealand Food Authority. The draft Standard is a prohibition with the possibility of exemptions being given on a case-by-case basis. Some details of the draft Standard are provided.

  8. Regulatory aspects of food irradiation in the Asia-Pacific region

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Peter B. E-mail: p.roberts@gns.cri.nz

    2000-03-01

    The latest information on the countries in the Asia/Pacific region with approvals for food to be irradiated is provided. Differences in the type of regulations used are contrasted. However, progress has been made towards greater uniformity in regulations based around the Codex General Standard for Irradiated Food. Australia and New Zealand instituted, respectively, a moratorium and a ban on food irradiation in 1988. Australia has proposed a new draft Standard for food irradiation and this is the subject of public discussion under the Australia New Zealand Food Authority. The draft Standard is a prohibition with the possibility of exemptions being given on a case-by-case basis. Some details of the draft Standard are provided. (author)

  9. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

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    Carl O Olson

    Full Text Available MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum, whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute

  10. Brain Region-Specific Expression of MeCP2 Isoforms Correlates with DNA Methylation within Mecp2 Regulatory Elements

    Science.gov (United States)

    Liyanage, Vichithra R. B.; Rastegar, Mojgan

    2014-01-01

    MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs) within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum), whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute towards characterizing

  11. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, Wendy R.; Roy, Monideepa; Vardar-Ulu, Didem; Garfinkel, Megan; Mansour, Marc R.; Aster, Jon C.; Blacklow, Stephen C.; (BWH); (Wellesley); (UCL)

    2009-09-02

    Proteolytic resistance of Notch prior to ligand binding depends on the structural integrity of a negative regulatory region (NRR) of the receptor that immediately precedes the transmembrane segment. The NRR includes the 3 Lin12/Notch repeats and the juxtamembrane heterodimerization domain, the region of Notch1 most frequently mutated in T-cell acute lymphoblastic leukemia lymphoma (T-ALL). Here, we report the x-ray structure of the Notch1 NRR in its autoinhibited conformation. A key feature of the Notch1 structure that maintains its closed conformation is a conserved hydrophobic plug that sterically occludes the metalloprotease cleavage site. Crystal packing interactions involving a highly conserved, exposed face on the third Lin12/Notch repeat suggest that this site may normally be engaged in intermolecular or intramolecular protein-protein interactions. The majority of known T-ALL-associated point mutations map to residues in the hydrophobic interior of the Notch1 NRR. A novel mutation (H1545P), which alters a residue at the crystal-packing interface, leads to ligand-independent increases in signaling in reporter gene assays despite only mild destabilization of the NRR, suggesting that it releases the autoinhibitory clamp on the heterodimerization domain imposed by the Lin12/Notch repeats. The Notch1 NRR structure should facilitate a search for antibodies or compounds that stabilize the autoinhibited conformation.

  12. Exhaustion-associated regulatory regions in CD8+tumor-infiltrating T cells.

    Science.gov (United States)

    Mognol, Giuliana P; Spreafico, Roberto; Wong, Victor; Scott-Browne, James P; Togher, Susan; Hoffmann, Alexander; Hogan, Patrick G; Rao, Anjana; Trifari, Sara

    2017-03-28

    T-cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8 + tumor-infiltrating lymphocytes (TILs) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, nonexhausted TILs and in acutely restimulated CD8 + T cells, we define a pattern of chromatin accessibility specific for T-cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors. Anti-PD-L1 treatment of tumor-bearing mice results in cessation of tumor growth and partial rescue of cytokine production by the dysfunctional TILs, with only limited changes in gene expression and chromatin accessibility. Our studies provide a valuable resource for the molecular understanding of T-cell exhaustion in cancer and other inflammatory settings.

  13. DNaseI hypersensitivity and ultraconservation reveal novel, interdependent long-range enhancers at the complex Pax6 cis-regulatory region.

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    David J McBride

    Full Text Available The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR, allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing

  14. Proximity sensor technology for manipulator end effectors

    Science.gov (United States)

    Johnston, A. R.

    1975-01-01

    Optical proximity sensing techniques which could be used to help control the critical grasping phase of a remote manipulation are described. The proximity sensors described use a triangulation geometry to detect a surface located in a pre-determined region. The design of the proximity sensors themselves is discussed, as well as their application to manipulator control with a local control loop, and possibilities for future development are discussed.

  15. Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region

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    Alonso Ángel

    2006-03-01

    Full Text Available Abstract Background Papillomaviruses (PVs infect stratified squamous epithelia in warm-blooded vertebrates and have undergone a complex evolutionary process. The control of the expression of the early ORFs in PVs depends on the binding of cellular and viral transcription factors to the upstream regulatory region (URR of the virus. It is believed that there is a core of transcription factor binding sites (TFBS common to all PVs, with additional individual differences, although most of the available information focuses only on a handful of viruses. Results We have studied the URR of sixty-one PVs, covering twenty different hosts. We have predicted the TFBS present in the URR and analysed these results by principal component analysis and genetic algorithms. The number and nature of TFBS in the URR might be much broader than thus far described, and different PVs have different repertoires of TFBS. Conclusion There are common fingerprints in the URR in PVs that infect primates, although the ancestors of these viruses diverged a long time ago. Additionally, there are obvious differences between the URR of alpha and beta PVs, despite these PVs infect similar histological cell types in the same host, i.e. human. A thorough analysis of the TFBS in the URR might provide crucial information about the differential biology of cancer-associated PVs.

  16. Transcriptional features of genomic regulatory blocks.

    Science.gov (United States)

    Akalin, Altuna; Fredman, David; Arner, Erik; Dong, Xianjun; Bryne, Jan Christian; Suzuki, Harukazu; Daub, Carsten O; Hayashizaki, Yoshihide; Lenhard, Boris

    2009-01-01

    Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. The tight regulation of target genes, complex arrangement of regulatory inputs, and the differential responsiveness of genes in the region call for the examination of fundamental rules governing transcriptional activity in GRBs. Here we use extensive CAGE tag mapping of transcription start sites across different human tissues and differentiation stages combined with expression data and a number of sequence and epigenetic features to discover these rules and patterns. We show evidence that GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region. Additionally, target gene promoters have a distinct combination of activating and repressing histone modifications in mouse embryonic stem cell lines. GRB targets are genes with a number of unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances.

  17. Combined Analysis of Variation in Core, Accessory and Regulatory Genome Regions Provides a Super-Resolution View into the Evolution of Bacterial Populations.

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    Alan McNally

    2016-09-01

    Full Text Available The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug-resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.

  18. MAGNETIC RESONANCE IMAGING, GROSS POSTMORTEM, AND HISTOLOGICAL FINDINGS FOR SOFT TISSUES OF THE PLANTAR ASPECT OF THE TARSUS AND PROXIMAL METATARSAL REGION IN NON-LAME HORSES.

    Science.gov (United States)

    Dyson, Sue; Blunden, Anthony; Murray, Rachel

    2017-03-01

    Injuries of the plantar soft tissues of the tarsus and proximal metatarsus can be a source of lameness in horses, however published information is lacking on high field MRI characteristics of these tissues. Objectives of the current anatomic study were to (1) describe high-field MRI features of the plantar tarsal and proximal metatarsal soft tissues; and (2) compare MRI findings with gross and histological appearances of selected structures for a sample of cadaver limbs from non-lame horses. Single hindlimbs for 42 horses, and right and left hindlimbs for eight horses were scanned using high-field MRI. The MRI findings were described for the 50 single limbs; and the MRI, gross postmortem and histological findings were compared for the eight pairs of hindlimbs. The superficial digital flexor tendon had uniform low signal intensity, surrounded by the flexor retinaculum of intermediate to high signal intensity on all sequences. The lateral digital flexor tendon had slightly higher signal intensity, enclosed on the plantaromedial aspects by the low signal intensity metatarsocalcaneal ligament. The accessory ligament of the deep digital flexor tendon varied in size and signal intensity. The proximal and distal plantar ligaments, accessory ligament of the suspensory ligament, and calcaneoquartal ligament had low signal intensity. The long plantar ligament comprised a number of related parts, separated by lines of high signal intensity corresponding with fibrous septae seen in gross anatomical specimens. The plantar aspect of the ligament had uniform low signal intensity in all sequences, but the dorsal half was more heterogeneous with multifocal spots or lines of higher signal intensity. © 2016 American College of Veterinary Radiology.

  19. Multiset proximity spaces

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    A. Kandil

    2016-10-01

    Full Text Available A multiset is a collection of objects in which repetition of elements is essential. This paper is an attempt to explore the theoretical aspects of multiset by extending the notions of compact, proximity relation and proximal neighborhood to the multiset context. Examples of new multiset topologies, open multiset cover, compact multiset and many identities involving the concept of multiset have been introduced. Further, an integral examples of multiset proximity relations are obtained. A multiset topology induced by a multiset proximity relation on a multiset M has been presented. Also the concept of multiset δ- neighborhood in the multiset proximity space which furnishes an alternative approach to the study of multiset proximity spaces has been mentioned. Finally, some results on this new approach have been obtained and one of the most important results is: every T4- multiset space is semi-compatible with multiset proximity relation δ on M (Theorem 5.10.

  20. Human ciliary neurotrophic factor: Localization to the proximal region of the long arm of chromosome 11 and association with CA/GT dinucleotide repeat

    Energy Technology Data Exchange (ETDEWEB)

    Lev, A.A.; Rosen, D.R.; Kos, C.; Brown, R.H. Jr.; Clifford, E.; Landes, G.; Hauser, S.L.

    1993-05-01

    Ciliary neurotrophic factor (CNTF) promotes survival and differentiation of several types of sensory, motor, sympathetic, and parasympathetic neurons. The authors have used the polymerase chain reaction to amplify, clone, and partially sequence CNTF cDNA from human muscle. Using a rodent-human mapping panel and fluorescence in situ hybridization, they have localized a single copy of the gene for human CNTF to the proximal long arm of chromosome 11. They have also identified a polymorphic tandem CA/GT dinucleotide repeat associated with the human CNTF gene. 14 refs., 1 fig.

  1. Regulatory feedback loop of two phz gene clusters through 5'-untranslated regions in Pseudomonas sp. M18.

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    Yaqian Li

    Full Text Available BACKGROUND: Phenazines are important compounds produced by pseudomonads and other bacteria. Two phz gene clusters called phzA1-G1 and phzA2-G2, respectively, were found in the genome of Pseudomonas sp. M18, an effective biocontrol agent, which is highly homologous to the opportunistic human pathogen P. aeruginosa PAO1, however little is known about the correlation between the expressions of two phz gene clusters. METHODOLOGY/PRINCIPAL FINDINGS: Two chromosomal insertion inactivated mutants for the two gene clusters were constructed respectively and the correlation between the expressions of two phz gene clusters was investigated in strain M18. Phenazine-1-carboxylic acid (PCA molecules produced from phzA2-G2 gene cluster are able to auto-regulate expression itself and activate the expression of phzA1-G1 gene cluster in a circulated amplification pattern. However, the post-transcriptional expression of phzA1-G1 transcript was blocked principally through 5'-untranslated region (UTR. In contrast, the phzA2-G2 gene cluster was transcribed to a lesser extent and translated efficiently and was negatively regulated by the GacA signal transduction pathway, mainly at a post-transcriptional level. CONCLUSIONS/SIGNIFICANCE: A single molecule, PCA, produced in different quantities by the two phz gene clusters acted as the functional mediator and the two phz gene clusters developed a specific regulatory mechanism which acts through 5'-UTR to transfer a single, but complex bacterial signaling event in Pseudomonas sp. strain M18.

  2. ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA-binding ChIP-seq experiments.

    Science.gov (United States)

    Chèneby, Jeanne; Gheorghe, Marius; Artufel, Marie; Mathelier, Anthony; Ballester, Benoit

    2018-01-04

    With this latest release of ReMap (http://remap.cisreg.eu), we present a unique collection of regulatory regions in human, as a result of a large-scale integrative analysis of ChIP-seq experiments for hundreds of transcriptional regulators (TRs) such as transcription factors, transcriptional co-activators and chromatin regulators. In 2015, we introduced the ReMap database to capture the genome regulatory space by integrating public ChIP-seq datasets, covering 237 TRs across 13 million (M) peaks. In this release, we have extended this catalog to constitute a unique collection of regulatory regions. Specifically, we have collected, analyzed and retained after quality control a total of 2829 ChIP-seq datasets available from public sources, covering a total of 485 TRs with a catalog of 80M peaks. Additionally, the updated database includes new search features for TR names as well as aliases, including cell line names and the ability to navigate the data directly within genome browsers via public track hubs. Finally, full access to this catalog is available online together with a TR binding enrichment analysis tool. ReMap 2018 provides a significant update of the ReMap database, providing an in depth view of the complexity of the regulatory landscape in human. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Evidence of young, proximal and primary (YPP diamond source occurring in alluviums in the Santo Antônio do Bonito, Santo Inácio and Douradinho rivers in Coromandel region, Minas Gerais

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    Rogério Silvestre Pereira

    Full Text Available ABSTRACT: Magmatism associated with the Alto Paranaíba structural high comprises kimberlites, kamafugites, and alkaline complexes, forming an approximately 400 x 150 km NW-SE belt in the southern São Francisco Craton. Dating of some intrusions reveals ages between 120 and 75 Ma. Chemical analyses of garnet recovered in alluvium from traditional diamond digging areas indicate peridotitic garnet windows in Três Ranchos and Coromandel. Six hundred and eighty (680 diamonds acquired or recovered during mineral exploration in the digging areas of Romaria, Estrela do Sul, Três Ranchos and Coromandel show unique characteristics, certain populations indicating young, proximal and primary sources (YPP. Analyses of 201 stones from Santo Antônio do Bonito, Santo Inácio and Douradinho rivers alluvium, Coromandel, present no evidence of transport, characterizing a proximal source. Within these river basins, exposures of the Late Cretaceous Capacete Formation basal conglomerate contain mainly small rounded and/or angular quartzite pebbles and of basic and ultrabasic rocks, as well as kimberlite minerals (garnet, ilmenite, spinel, sometimes diamond. A magnetotelluric profile between the Paraná and Sanfranciscana basins shows that the thick underlying lithosphere in the Coromandel region coincides with the peridotitic garnet window and with a diamond population displaying proximal source characteristics. Diamond-bearing kimberlite intrusions occur in different areas of Alto Paranaíba.

  4. The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies

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    Burt Austin

    2009-07-01

    Full Text Available Abstract Background Germline specific promoters are an essential component of potential vector control strategies which function by genetic drive, however suitable promoters are not currently available for the main human malaria vector Anopheles gambiae. Results We have identified the Anopheles gambiae vasa-like gene and found its expression to be specifically localized to both the male and female gonads in adult mosquitoes. We have functionally characterised using transgenic reporter lines the regulatory regions required for driving transgene expression in a pattern mirroring that of the endogenous vasa locus. Two reporter constructs indicate the existence of distinct vasa regulatory elements within the 5' untranslated regions responsible not only for the spatial and temporal but also for the sex specific germline expression. vasa driven eGFP expression in the ovary of heterozygous mosquitoes resulted in the progressive accumulation of maternal protein and transcript in developing oocytes that were then detectable in all embryos and neonatal larvae. Conclusion We have characterized the vasa regulatory regions that are not only suited to drive transgenes in the early germline of both sexes but could also be utilized to manipulate the zygotic genome of developing embryos via maternal deposition of active molecules. We have used computational models to show that a homing endonuclease-based gene drive system can function in the presence of maternal deposition and describe a novel non-invasive control strategy based on early vasa driven homing endonuclease expression.

  5. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M

    2009-08-13

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198CG SNP (odds ratio8.6; P0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5?-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198CG SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression. © 2010 Macmillan Publishers Limited. All rights reserved.

  6. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P

    1995-01-01

    have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes......The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...

  7. Polymorphism in the regulatory region located more than 1.1 kilobases 5' to the start site of transcription, the promoter region, and exon 1 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Sørensen, Steen; Morling, N

    1999-01-01

    in certain disorders of pregnancy. We have studied the DNA sequences of the putative regulatory region located more than 1.1 kilobases 5' from the start site of transcription (a 244 bp HindIII/EcoRI fragment) of the HLA-G gene and of the promoter region to detect any possible polymorphism. We detected one...... into two groups based on the detected polymorphism. The nucleotide substitutions may have implications for the binding of nuclear factors to the regulatory regions. To our knowledge this is the first study of any polymorphism in the 5'-flanking sequences to the HLA-G gene. Further studies are needed......The non-classic Human Leucocyte Antigen class Ib molecule, HLA-G, is expressed on the invasive, extra-villous cytotrophoblast in human placenta. HLA-G protects against natural killer (NK)-cell-mediated lysis and may modulate the secretion of cytokines. Aberrant expression of HLA-G has been reported...

  8. Proximal Probes Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Proximal Probes Facility consists of laboratories for microscopy, spectroscopy, and probing of nanostructured materials and their functional properties. At the...

  9. Position and sequence conservation in Amniota of polymorphic enhancer HS1.2 within the palindrome of IgH 3'Regulatory Region.

    OpenAIRE

    Rocchi Mariano; Giambra Vincenzo; Scascitelli Moira; D'Addabbo Pietro; Frezza Domenico

    2011-01-01

    Abstract Background The Immunoglobulin heavy chain (IgH) 3' Regulatory Region (3'RR), located at the 3' of the constant alpha gene, plays a crucial role in immunoglobulin production. In humans, there are 2 copies of the 3'RR, each composed of 4 main elements: 3 enhancers and a 20 bp tandem repeat. The single mouse 3'RR differs from the two human ones for the presence of 4 more regulative elements with the double copy of one enhancer at the border of a palindromic region. Results We compared t...

  10. Mapping of PARK2 and PACRG overlapping regulatory region reveals LD structure and functional variants in association with leprosy in unrelated indian population groups.

    Science.gov (United States)

    Chopra, Rupali; Ali, Shafat; Srivastava, Amit K; Aggarwal, Shweta; Kumar, Bhupender; Manvati, Siddharth; Kalaiarasan, Ponnusamy; Jena, Mamta; Garg, Vijay K; Bhattacharya, Sambit N; Bamezai, Rameshwar N K

    2013-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations.

  11. Comparison of fatty acid and proximate compositions of the body and claw of male and female blue crabs (Callinectes sapidus) from different regions of the Mediterranean coast.

    Science.gov (United States)

    Kuley, Esmeray; Ozoğul, Fatih; Ozogul, Yesim; Olgunoglu, A Ilkan

    2008-01-01

    Fatty acid and proximate compositions of the body and claw of male and female blue crabs from Akyatan Lagoon and Hurma strait were investigated. Male blue crab meat had a higher protein and fat content, and lower moisture and ash content, than that of the female from Akyatan Lagoon. Moreover, there were variations of protein and fat amounts in both female crab meats between Akyatan Lagoon and Hurma strait. The dominant saturated fatty acids were palmitic acid (16:0; range from approximately 12% to 15%) and stearic acid (18:0; range from approximately 7.5% to 16.1%) for all samples. The total monounsaturated fatty acid content in the body of female crabs from Akyatan Lagoon was higher than those of Hurma Strait (22.04% versus 7.55%). There were no statistically significant differences (P>0.05) between eicosapentaenoic acid concentrations in body meat of the male crab than those of female crab meat from Akyatan Lagoon (Pcrabs from Akyatan Lagoon and those of female crabs from Hurma strait. The total n3 was detected as 27.33% in body meat whereas it was 24.39% in claw meat of the male crab from Akyatan Lagoon. Those values were almost similar in the body and claw meat of female crab from Akyatan Lagoon.

  12. Enhancers located in heavy chain regulatory region (hs3a, hs1,2, hs3b, and hs4) are dispensable for diversity of VDJ recombination.

    Science.gov (United States)

    Rouaud, Pauline; Vincent-Fabert, Christelle; Fiancette, Remi; Cogné, Michel; Pinaud, Eric; Denizot, Yves

    2012-03-09

    V(D)J recombination occurs during the antigen-independent early steps of B-cell ontogeny. Multiple IgH cis-regulatory elements control B-cell ontogeny. IGCR1 (intergenic control region 1), the DQ52 promoter/enhancer, and the intronic Emu enhancer, all three located upstream of Cmu, have important roles during V(D)J recombination, whereas there is no clue about a role of the IgH regulatory region (RR) encompassing the four transcriptional enhancers hs3a, hs1,2, hs3b, and hs4 during these early stages. To clarify the role of the RR in V(D)J recombination, we totally deleted it in the mouse genome. Here, we show that V(D)J recombination is unaffected by the complete absence of the IgH RR, highlighting that this region only orchestrates IgH locus activity during the late stages of B-cell differentiation. In contrast, the earliest antigen-independent steps of B-cell ontogeny would be under the control of only the upstream Cmu elements of the locus.

  13. Enhancers Located in Heavy Chain Regulatory Region (hs3a, hs1,2, hs3b, and hs4) Are Dispensable for Diversity of VDJ Recombination*

    Science.gov (United States)

    Rouaud, Pauline; Vincent-Fabert, Christelle; Fiancette, Remi; Cogné, Michel; Pinaud, Eric; Denizot, Yves

    2012-01-01

    V(D)J recombination occurs during the antigen-independent early steps of B-cell ontogeny. Multiple IgH cis-regulatory elements control B-cell ontogeny. IGCR1 (intergenic control region 1), the DQ52 promoter/enhancer, and the intronic Emu enhancer, all three located upstream of Cmu, have important roles during V(D)J recombination, whereas there is no clue about a role of the IgH regulatory region (RR) encompassing the four transcriptional enhancers hs3a, hs1,2, hs3b, and hs4 during these early stages. To clarify the role of the RR in V(D)J recombination, we totally deleted it in the mouse genome. Here, we show that V(D)J recombination is unaffected by the complete absence of the IgH RR, highlighting that this region only orchestrates IgH locus activity during the late stages of B-cell differentiation. In contrast, the earliest antigen-independent steps of B-cell ontogeny would be under the control of only the upstream Cmu elements of the locus. PMID:22270371

  14. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  15. Chronic Stress and Peripheral Pain: Evidence for Distinct, Region-specific Changes in Visceral and Somatosensory Pain Regulatory Pathways

    Science.gov (United States)

    Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

    2015-01-01

    Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control L4-L5 DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. PMID:26408049

  16. Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

    Science.gov (United States)

    Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

    2017-09-01

    N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m6A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m6A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m6A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m6A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

  17. Capacitive proximity sensor

    Science.gov (United States)

    Kronberg, James W.

    1994-01-01

    A proximity sensor based on a closed field circuit. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change.

  18. Neighborhoods and manageable proximity

    Directory of Open Access Journals (Sweden)

    Stavros Stavrides

    2011-08-01

    Full Text Available The theatricality of urban encounters is above all a theatricality of distances which allow for the encounter. The absolute “strangeness” of the crowd (Simmel 1997: 74 expressed, in its purest form, in the absolute proximity of a crowded subway train, does not generally allow for any movements of approach, but only for nervous hostile reactions and submissive hypnotic gestures. Neither forced intersections in the course of pedestrians or vehicles, nor the instantaneous crossing of distances by the technology of live broadcasting and remote control give birth to places of encounter. In the forced proximity of the metropolitan crowd which haunted the city of the 19th and 20th century, as well as in the forced proximity of the tele-presence which haunts the dystopic prospect of the future “omnipolis” (Virilio 1997: 74, the necessary distance, which is the stage of an encounter between different instances of otherness, is dissipated.

  19. Atrofia muscular proximal familiar

    Directory of Open Access Journals (Sweden)

    José Antonio Levy

    1962-09-01

    Full Text Available Os autores relatam dois casos de atrofia muscular proximal familiar, moléstia caracterizada por déficit motor e atrofias musculares de distribuição proximal, secundárias a lesão de neurônios periféricos. Assim, como em outros casos descritos na literatura, foi feito inicialmente o diagnóstico de distrofia muscular progressiva. O diagnóstico correto foi conseguido com auxílio da eletromiografia e da biopsia muscular.

  20. Localization of a gene for autosomal dominant Larsen syndrome to chromosome region 3p21.1-14.1 in the proximity of, but distinct from the COL7A1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Vujic, M.; Hallstensson, K.; Wahlstroem, J. [East Hospital, Gothenburg (Sweden)] [and others

    1995-11-01

    Larsen syndrome (LS) is a skeletal dysplasia (osteochondrodysplasia) in which multiple dislocations of the large joints are the major feature. Nosology in this group of diseases, which constitutes 8% of Mendelian disorders in man, is primarily based on clinical and radiographic features. Hopes for more accurate classification grounds are currently being met by progress in elucidation of underlying genetic defects. We have performed linkage analysis in a large Swedish kindred with autosomal dominant LS and found the gene (LAR1) to be strongly linked to chromosome 3p markers (Z{sub max} = 13.4 at {theta} = .00). Recombination analysis indicates that the LAR1 locus is located in a region defined distally by D3S1581 and proximally by D3S1600, which cytogenetically maps to chromosome region 3p21.1-14.1. Linkage and recombination analysis of a COL7A1 PvuII intragenic polymorphism versus LS and chromosome 3 markers indicate that COL7A1 is located close to, but distinct from, the LAR1 locus. 33 refs., 6 figs., 3 tabs.

  1. [Experimental proximal carpectomy. Biodynamics].

    Science.gov (United States)

    Kuhlmann, J N

    1992-01-01

    Proximal carpectomy was performed in 10 fresh cadavre wrists. Dynamic x-rays were taken and the forces necessary to obtain different movements before and after the operation were measured. Comparison of these parameters clearly defines the advantages and limitations of carpectomy and indicates the reasons.

  2. Proximate Analysis of Coal

    Science.gov (United States)

    Donahue, Craig J.; Rais, Elizabeth A.

    2009-01-01

    This lab experiment illustrates the use of thermogravimetric analysis (TGA) to perform proximate analysis on a series of coal samples of different rank. Peat and coke are also examined. A total of four exercises are described. These are dry exercises as students interpret previously recorded scans. The weight percent moisture, volatile matter,…

  3. Proximal Tibial Bone Graft

    Science.gov (United States)

    ... the Big Toe Ailments of the Smaller Toes Diabetic Foot Treatments Currently selected Injections and other Procedures Treatments ... from which the bone was taken if the foot/ankle surgeries done at the same time allow for it. ... problems after a PTBG include infection, fracture of the proximal tibia and pain related ...

  4. A 5'-regulatory region and two coding region polymorphisms modulate promoter activity and gene expression of the growth suppressor gene ZBED6 in cattle.

    Directory of Open Access Journals (Sweden)

    Yong-Zhen Huang

    Full Text Available Zinc finger, BED-type containing 6 (ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. Polymorphisms in its promoter and coding regions are likely to impact ZBED6 transcription and growth traits. In this study, rapid amplification of 5' cDNA ends (5'-RACE analysis revealed two transcription start sites (TSS for the bovine ZBED6 starting within exon 1 of the ZC3H11A gene (TSS-1 and upstream of the translation start codon of the ZBED6 gene (TSS-2. There was one SNP in the promoter and two missense mutations in the coding region of the bovine ZBED6 by sequencing of the pooled DNA samples (Pool-Seq, n = 100. The promoter and coding region are the key regions for gene function; polymorphisms in these regions can alter gene expression. Quantitative real-time PCR (qPCR analysis showed that ZBED6 has a broad tissue distribution in cattle and is highly expressed in skeletal muscle. Eleven promoter-detection vectors were constructed, which enabled the cloning of putative promoter sequences and analysis of ZBED6 transcriptional activity by luciferase reporter gene assays. The core region of the basal promoter of bovine ZBED6 is located within region -866 to -556. The activity of WT-826G-pGL3 in driving reporter gene transcription is significantly higher than that of the M-826A-pGL3 construct (P < 0.01. Analysis of gene expression patterns in homozygous full-sibling Chinese Qinchuan cattle showed that the mutant-type Hap-AGG exhibited a lower mRNA level than the wild-type Hap-GCA (P < 0.05 in longissimus dorsi muscle (LDM. Moreover, ZBED6 mRNA expression was low in C2C12 cells overexpressing the mutant-type ZBED6 (pcDNA3.1(+-Hap-GG (P < 0.01. Our results suggest that the polymorphisms in the promoter and coding regions may modulate the promoter activity and gene expression of bovine ZBED6 in the skeletal muscles of these cattle breeds.

  5. Variations at regulatory regions of the milk protein genes are associated with milk traits and coagulation properties in the Sarda sheep.

    Science.gov (United States)

    Noce, A; Pazzola, M; Dettori, M L; Amills, M; Castelló, A; Cecchinato, A; Bittante, G; Vacca, G M

    2016-12-01

    Regulatory variation at the ovine casein genes could have important effects on the composition and coagulation properties of milk. Herewith, we have partially resequenced the promoters and the 3'-UTR of the four casein genes in 25 Sarda sheep. Alignment of these sequences allowed us to identify a total of 29 SNPs. This level of polymorphism (one SNP every 250 bp) is remarkably high if compared with SNP densities estimated in human genic regions (approximately one SNP per bp). The 29 SNPs identified in our resequencing experiment, plus three previously reported SNPs mapping to the lactalbumin, alpha (LALBA) and β-lactoglobulin (BLG, also known as progestagen-associated endometrial protein, PAEP) genes, were genotyped with a multiplex TaqMan Open Array Real-Time PCR assay in 760 Sarda sheep with records for milk composition and coagulation properties. Association analysis revealed the existence of significant associations of CSN1S2 and CSN3 genotypes with milk protein and casein contents. Moreover, genotypes at CSN1S1 were significantly associated with rennet coagulation time, curd firming time and curd firmness, whereas CSN2 was associated with curd firming time. These results suggest that SNPs mapping to the promoters and 3'-UTRs of ovine casein genes may exert regulatory effects on gene expression and that they could be used for improving sheep milk quality and technological traits at the population level through marker assisted selection. © 2016 Stichting International Foundation for Animal Genetics.

  6. Regulatory elements in the promoter region of the rat gene encoding the acyl-CoA-binding protein

    DEFF Research Database (Denmark)

    Elholm, M; Bjerking, G; Knudsen, J

    1996-01-01

    Acyl-CoA-binding protein (ACBP) is an ubiquitously expressed 10-kDa protein which is present in high amounts in cells involved in solute transport or secretion. Rat ACBP is encoded by a gene containing the typical hallmarks of a housekeeping gene. Analysis of the promoter region of the rat ACBP g...

  7. Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development.

    Science.gov (United States)

    Kim, Gwang-Jin; Sock, Elisabeth; Buchberger, Astrid; Just, Walter; Denzer, Friederike; Hoepffner, Wolfgang; German, James; Cole, Trevor; Mann, Jillian; Seguin, John H; Zipf, William; Costigan, Colm; Schmiady, Hardi; Rostásy, Moritz; Kramer, Mildred; Kaltenbach, Simon; Rösler, Bernd; Georg, Ina; Troppmann, Elke; Teichmann, Anne-Christin; Salfelder, Anika; Widholz, Sebastian A; Wieacker, Peter; Hiort, Olaf; Camerino, Giovanna; Radi, Orietta; Wegner, Michael; Arnold, Hans-Henning; Scherer, Gerd

    2015-04-01

    SOX9 mutations cause the skeletal malformation syndrome campomelic dysplasia in combination with XY sex reversal. Studies in mice indicate that SOX9 acts as a testis-inducing transcription factor downstream of SRY, triggering Sertoli cell and testis differentiation. An SRY-dependent testis-specific enhancer for Sox9 has been identified only in mice. A previous study has implicated copy number variations (CNVs) of a 78 kb region 517-595 kb upstream of SOX9 in the aetiology of both 46,XY and 46,XX disorders of sex development (DSD). We wanted to better define this region for both disorders. By CNV analysis, we identified SOX9 upstream duplications in three cases of SRY-negative 46,XX DSD, which together with previously reported duplications define a 68 kb region, 516-584 kb upstream of SOX9, designated XXSR (XX sex reversal region). More importantly, we identified heterozygous deletions in four families with SRY-positive 46,XY DSD without skeletal phenotype, which define a 32.5 kb interval 607.1-639.6 kb upstream of SOX9, designated XY sex reversal region (XYSR). To localise the suspected testis-specific enhancer, XYSR subfragments were tested in cell transfection and transgenic experiments. While transgenic experiments remained inconclusive, a 1.9 kb SRY-responsive subfragment drove expression specifically in Sertoli-like cells. Our results indicate that isolated 46,XY and 46,XX DSD can be assigned to two separate regulatory regions, XYSR and XXSR, far upstream of SOX9. The 1.9 kb SRY-responsive subfragment from the XYSR might constitute the core of the Sertoli-cell enhancer of human SOX9, representing the so far missing link in the genetic cascade of male sex determination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Mammals of Australia's tropical savannas: a conceptual model of assemblage structure and regulatory factors in the Kimberley region.

    Directory of Open Access Journals (Sweden)

    Ian J Radford

    Full Text Available We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011 were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:--low numbers of mammals, State II:--dominated by omnivorous rodents and State III:--dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but-unlike arid regions-were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the

  9. Mammals of Australia's tropical savannas: a conceptual model of assemblage structure and regulatory factors in the Kimberley region.

    Science.gov (United States)

    Radford, Ian J; Dickman, Christopher R; Start, Antony N; Palmer, Carol; Carnes, Karin; Everitt, Corrin; Fairman, Richard; Graham, Gordon; Partridge, Thalie; Thomson, Allan

    2014-01-01

    We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011) were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:--low numbers of mammals, State II:--dominated by omnivorous rodents and State III:--dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I) did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but-unlike arid regions-were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the already-articulated cat

  10. Regulatory elements in the 3' untranslated region of the GP82 glycoprotein are responsible for its stage-specific expression in Trypanosoma cruzi metacyclic trypomastigotes.

    Science.gov (United States)

    Bayer-Santos, Ethel; Gentil, Luciana Girotto; Cordero, Esteban Maurício; Corrêa, Paulo Roberto Ceridório; da Silveira, José Franco

    2012-09-01

    Gene expression in Trypanosoma cruzi is regulated at the post-transcriptional level and cis-acting elements present in the 3' untranslated region (3'UTR) play an important role by interacting with regulatory proteins. Previous studies demonstrated that the GP82 surface glycoprotein, which is involved in host cell invasion, is up-regulated in the infective metacyclic trypomastigote form, and that GP82 mRNA half-life is longer in this form compared to the non-infective epimastigote form. Here, we demonstrate that the 3'UTR of the GP82 transcript is involved in this developmental regulation, promoting higher expression of the green fluorescent protein (GFP) reporter in metacyclic trypomastigotes than in epimastigotes. A series of stepwise deletions in the 3'UTR was created and results suggest that the mechanism regulating GP82 expression involves multiple elements in the 3'UTR. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Mammals of Australia's Tropical Savannas: A Conceptual Model of Assemblage Structure and Regulatory Factors in the Kimberley Region

    Science.gov (United States)

    Radford, Ian J.; Dickman, Christopher R.; Start, Antony N.; Palmer, Carol; Carnes, Karin; Everitt, Corrin; Fairman, Richard; Graham, Gordon; Partridge, Thalie; Thomson, Allan

    2014-01-01

    We construct a state-and-transition model for mammals in tropical savannas in northern Australia to synthesize ecological knowledge and understand mammalian declines. We aimed to validate the existence of alternative mammal assemblage states similar to those in arid Australian grasslands, and to speculate on transition triggers. Based on the arid grassland model, we hypothesized that assemblages are partitioned across rainfall gradients and between substrates. We also predicted that assemblages typical of arid regions in boom periods would be prevalent in savannas with higher and more regular rainfall. Data from eight mammal surveys from the Kimberley region, Western Australia (1994 to 2011) were collated. Survey sites were partitioned across rainfall zones and habitats. Data allowed us to identify three assemblage states: State 0:- low numbers of mammals, State II:- dominated by omnivorous rodents and State III:- dominated by rodents and larger marsupials. Unlike arid grasslands, assemblage dominance by insectivorous dasyurids (State I) did not occur in savannas. Mammal assemblages were partitioned across rainfall zones and between substrates as predicted, but—unlike arid regions—were not related strongly to yearly rainfall. Mammal assemblage composition showed high regional stability, probably related to high annual rainfall and predictable wet season resource pulses. As a consequence, we speculate that perpetually booming assemblages in savannas allow top-down control of the ecosystem, with suppression of introduced cats by the dingo, the region's top predator. Under conditions of low or erratic productivity, imposed increasingly by intense fire regimes and introduced herbivore grazing, dingoes may not limit impacts of cats on native mammals. These interacting factors may explain contemporary declines of savanna mammals as well as historical declines in arid Australia. The cat-ecosystem productivity hypothesis raised here differs from the already

  12. Functional footprinting of regulatory DNA.

    Science.gov (United States)

    Vierstra, Jeff; Reik, Andreas; Chang, Kai-Hsin; Stehling-Sun, Sandra; Zhou, Yuanyue; Hinkley, Sarah J; Paschon, David E; Zhang, Lei; Psatha, Nikoletta; Bendana, Yuri R; O'Neil, Colleen M; Song, Alexander H; Mich, Andrea K; Liu, Pei-Qi; Lee, Gary; Bauer, Daniel E; Holmes, Michael C; Orkin, Stuart H; Papayannopoulou, Thalia; Stamatoyannopoulos, George; Rebar, Edward J; Gregory, Philip D; Urnov, Fyodor D; Stamatoyannopoulos, John A

    2015-10-01

    Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution. We demonstrate the approach on a human erythroid enhancer, revealing single TF recognition sites that gate the majority of downstream regulatory function.

  13. The Calponin Regulatory Region Is Intrinsically Unstructured: Novel Insight into Actin-Calponin and Calmodulin-Calponin Interfaces Using NMR Spectroscopy

    Science.gov (United States)

    Pfuhl, Mark; Al-Sarayreh, Sameeh; El-Mezgueldi, Mohammed

    2011-01-01

    Calponin is an actin- and calmodulin-binding protein believed to regulate the function of actin. Low-resolution studies based on proteolysis established that the recombinant calponin fragment 131–228 contained actin and calmodulin recognition sites but failed to precisely identify the actin-binding determinants. In this study, we used NMR spectroscopy to investigate the structure of this functionally important region of calponin and map its interaction with actin and calmodulin at amino-acid resolution. Our data indicates that the free calponin peptide is largely unstructured in solution, although four short amino-acid stretches corresponding to residues 140–146, 159–165, 189–195, and 199–205 display the propensity to form α-helices. The presence of four sequential transient helices probably provides the conformational malleability needed for the promiscuous nature of this region of calponin. We identified all amino acids involved in actin binding and demonstrated for the first time, to our knowledge, that the N-terminal flanking region of Lys137-Tyr144 is an integral part of the actin-binding site. We have also delineated the second actin-binding site to amino acids Thr180-Asp190. Ca2+-calmodulin binding extends beyond the previously identified minimal sequence of 153–163 and includes most amino acids within the stretch 143–165. In addition, we found that calmodulin induces chemical shift perturbations of amino acids 188–190 demonstrating for the first time, to our knowledge, an effect of Ca2+-calmodulin on this region. The spatial relationship of the actin and calmodulin contacts as well as the transient α-helical structures within the regulatory region of calponin provides a structural framework for understanding the Ca2+-dependent regulation of the actin-calponin interaction by calmodulin. PMID:21463585

  14. Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region.

    Science.gov (United States)

    Banerjee, Saikat; Shi, Heliang; Banasik, Marisa; Moon, Hojin; Lees, William; Qin, Yali; Harley, Andrew; Shepherd, Adrian; Cho, Michael W

    2017-05-01

    The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone. MPER-specific rabbit monoclonal antibodies were generated, including 9F6. Although it lacked neutralizing activity, the target epitope profile of 9F6 closely resembled those of 4E10 and 10E8 ((671)NWFDITNWLWYIK(683)). B-cell repertoire analyses suggested the importance of co-immunizations for maturation of 9F6, which warrants further evaluation of our IPAS-RAM vaccine strategy using an improved priming immunogen. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Proximal humeral fractures

    OpenAIRE

    Mauro, Craig S.

    2011-01-01

    Proximal humeral fractures may present with many different configurations in patients with varying co-morbities and expectations. As a result, the treating physician must understand the fracture pattern, the quality of the bone, other patient-related factors, and the expanding range of reconstructive options to achieve the best functional outcome and to minimize complications. Current treatment options range from non-operative treatment with physical therapy to fracture fixation using percuta...

  16. UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs

    Science.gov (United States)

    Mignone, Flavio; Grillo, Giorgio; Licciulli, Flavio; Iacono, Michele; Liuni, Sabino; Kersey, Paul J.; Duarte, Jorge; Saccone, Cecilia; Pesole, Graziano

    2005-01-01

    The 5′ and 3′ untranslated regions of eukaryotic mRNAs play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5′ and 3′ untranslated sequences of eukaryotic mRNAs, derived from several sources of primary data. Experimentally validated functional motifs are annotated (and also collated as the UTRsite database) and cross-links to genomic and protein data are provided. The integration of UTRdb with genomic and protein data has allowed the implementation of a powerful retrieval resource for the selection and extraction of UTR subsets based on their genomic coordinates and/or features of the protein encoded by the relevant mRNA (e.g. GO term, PFAM domain, etc.). All internet resources implemented for retrieval and functional analysis of 5′ and 3′ untranslated regions of eukaryotic mRNAs are accessible at http://www.ba.itb.cnr.it/UTR/. PMID:15608165

  17. Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion.

    Science.gov (United States)

    Camp, Shelley; Zhang, Limin; Marquez, Michael; de la Torre, Brian; Long, Jeffery M; Bucht, Goran; Taylor, Palmer

    2005-12-15

    AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced, and this sequence is responsible for catalytic function. The 3' alternatively spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J. Massoulie, The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11 (3) (2002) 130-143; Y. Li, S. Camp, P. Taylor, Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790-5797]. The splice to exon 5 produces the GPI anchored form of AChE found in the hematopoietic system, whereas the splice to exon 6 produces a sequence that binds to the structural subunits PRiMA and ColQ, producing AChE expression in brain and muscle. A third alternative RNA species is present that is not spliced at the 3' end; the intron 3' of exon 4 is used as coding sequence and produces the read-through, unanchored form of AChE. In order to further understand the role of alternative splicing in the expression of the AChE gene, we have used homologous recombination in stem cells to produce gene specific deletions in mice. Alternatively and together exon 5 and exon 6 were deleted. A cassette containing the neomycin gene flanked by loxP sites was used to replace the exon(s) of interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette retained showed very low levels of AChE expression, far less than would have been anticipated. Only the read-through species of the enzyme was produced; clearly the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6. The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and muscle has been analyzed. Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B

  18. Polymorphism in the 5' upstream regulatory and 3' untranslated regions of the HLA-G gene in relation to soluble HLA-G and IL-10 expression

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F; Rizzo, Roberta; Melchiorri, Loredana

    2006-01-01

    -G mRNA isoform expression patterns have been associated with HLA-G polymorphism, especially with a 14-bp insertion deletion polymorphism in the 3' untranslated region (3'UTR) of the HLA-G gene. A significantly high level of interleukin-10 (IL-10) secretion is observed in homozygous +14/+14-bp HLA......-G peripheral blood mononuclear cells after lipopolysaccharide (LPS) stimulation. This study finds that polymorphism in the 5' upstream regulatory region (5'URR) of the HLA-G gene may also be implicated in differences in IL-10 secretion. However, this may also be due to linkage disequilibrium with the 14-bp...... polymorphism. A single-nucleotide polymorphism located -477 bp from the start site of exon 1 had a significant association with IL-10 concentrations but not after correction (p=0.011; pc=0.154). This polymorphism is located next to a heat shock element. Eighteen 5'-URR/3'-UTR HLA-G haplotypes were defined; one...

  19. CREME: Cis-Regulatory Module Explorer for the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Loots, G G; Sharan, R; Ovcharenko, I; Ben-Hur, A

    2004-02-11

    The binding of transcription factors to specific regulatory sequence elements is a primary mechanism for controlling gene transcription. Eukaryotic genes are often regulated by several transcription factors, whose binding sites are tightly clustered and form cis-regulatory modules. In this paper we present a web-server, CREME, for identifying and visualizing cis-regulatory modules in the promoter regions of a given set of potentially co-regulated genes. CREME relies on a database of putative transcription factor binding sites that have been annotated across the human genome using a library of position weight matrices and evolutionary conservation with the mouse and rat genomes. A search algorithm is applied to this dataset to identify combinations of transcription factors whose binding sites tend to co-occur in close proximity in the promoter regions of the input gene set. The identified cis-regulatory modules are statistically scored and significant combinations are reported and graphically visualized. Our web-server is available at http://creme.dcode.org/.

  20. Position and sequence conservation in Amniota of polymorphic enhancer HS1.2 within the palindrome of IgH 3'Regulatory Region

    Directory of Open Access Journals (Sweden)

    Rocchi Mariano

    2011-03-01

    Full Text Available Abstract Background The Immunoglobulin heavy chain (IgH 3' Regulatory Region (3'RR, located at the 3' of the constant alpha gene, plays a crucial role in immunoglobulin production. In humans, there are 2 copies of the 3'RR, each composed of 4 main elements: 3 enhancers and a 20 bp tandem repeat. The single mouse 3'RR differs from the two human ones for the presence of 4 more regulative elements with the double copy of one enhancer at the border of a palindromic region. Results We compared the 3'RR organization in genomes of vertebrates to depict the evolutionary history of the region and highlight its shared features. We found that in the 8 species in which the whole region was included in a fully assembled contig (mouse, rat, dog, rabbit, panda, orangutan, chimpanzee, and human, the shared elements showed synteny and a highly conserved sequence, thus suggesting a strong evolutionary constraint. In these species, the wide 3'RR (~30 kb in human bears a large palindromic sequence, consisting in two ~3 kb complementary branches spaced by a ~3 kb sequence always including the HS1.2 enhancer. In mouse and rat, HS3 is involved by the palindrome so that one copy of the enhancer is present on each side. A second relevant feature of our present work concerns human polymorphism of the HS1.2 enhancer, associated to immune diseases in our species. We detected a similar polymorphism in all the studied Catarrhini (a primate parvorder. The polymorphism consists of multiple copies of a 40 bp element up to 12 in chimpanzees, 8 in baboons, 6 in macaque, 5 in gibbons, 4 in humans and orangutan, separated by stretches of Cytosine. We show specific binding of this element to nuclear factors. Conclusions The nucleotide sequence of the palindrome is not conserved among evolutionary distant species, suggesting pressures for the maintenance of two self-matching regions driving a three-dimensional structure despite of the inter-specific divergence at sequence level. The

  1. Position and sequence conservation in Amniota of polymorphic enhancer HS1.2 within the palindrome of IgH 3'Regulatory Region.

    Science.gov (United States)

    D'Addabbo, Pietro; Scascitelli, Moira; Giambra, Vincenzo; Rocchi, Mariano; Frezza, Domenico

    2011-03-15

    The Immunoglobulin heavy chain (IgH) 3' Regulatory Region (3'RR), located at the 3' of the constant alpha gene, plays a crucial role in immunoglobulin production. In humans, there are 2 copies of the 3'RR, each composed of 4 main elements: 3 enhancers and a 20 bp tandem repeat. The single mouse 3'RR differs from the two human ones for the presence of 4 more regulative elements with the double copy of one enhancer at the border of a palindromic region. We compared the 3'RR organization in genomes of vertebrates to depict the evolutionary history of the region and highlight its shared features. We found that in the 8 species in which the whole region was included in a fully assembled contig (mouse, rat, dog, rabbit, panda, orangutan, chimpanzee, and human), the shared elements showed synteny and a highly conserved sequence, thus suggesting a strong evolutionary constraint. In these species, the wide 3'RR (~30 kb in human) bears a large palindromic sequence, consisting in two ~3 kb complementary branches spaced by a ~3 kb sequence always including the HS1.2 enhancer. In mouse and rat, HS3 is involved by the palindrome so that one copy of the enhancer is present on each side. A second relevant feature of our present work concerns human polymorphism of the HS1.2 enhancer, associated to immune diseases in our species. We detected a similar polymorphism in all the studied Catarrhini (a primate parvorder). The polymorphism consists of multiple copies of a 40 bp element up to 12 in chimpanzees, 8 in baboons, 6 in macaque, 5 in gibbons, 4 in humans and orangutan, separated by stretches of Cytosine. We show specific binding of this element to nuclear factors. The nucleotide sequence of the palindrome is not conserved among evolutionary distant species, suggesting pressures for the maintenance of two self-matching regions driving a three-dimensional structure despite of the inter-specific divergence at sequence level. The information about the conservation of the palindromic

  2. The -1997 G/T polymorphism in the COLIA1 upstream regulatory region is associated with hip bone mineral density (BMD) in Chinese nuclear families.

    Science.gov (United States)

    Zhang, Yuan-Yuan; Lei, Shu-Feng; Mo, Xiao-Yang; Wang, Yan-Bo; Li, Miao-Xin; Deng, Hong-Wen

    2005-02-01

    Type I collagen is the most abundant protein of bone matrix, and the collagen type I alpha 1(COLIA1) gene has been considered one of the most important candidate genes for osteoporosis. In this study, we simultaneously tested linkage and/or association of the -1997 G/T polymorphism in the COLIA1 upstream regulatory region with the variation of bone mineral density (BMD) in 1263 subjects from 402 Chinese nuclear families, consisted of both parents and at least one healthy female offspring from 20 to 45 years of age. All the subjects were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD of the lumbar spine (L1-L4) and hip (respective and combined phenotype of the femoral neck, trochanter, and intertrochanter) was measured by dual-energy X-ray absorptiometry (DXA). By using the tests implemented in program QTDT (quantitative transmission disequilibrium test), we found significant within-family association (via TDT) between the -1997 G/T polymorphism with BMD variation at all the hip sites (respective and combined phenotypes, P 1997 G/T polymorphism in the COLIA1 gene is likely to be in linkage disequilibrium with a nearby functional polymorphism affecting hip BMD, or the -1997 G/T polymorphism itself may have an important effect on the variation of hip BMD in our Chinese sample.

  3. Effects of polymorphic microsatellites in the regulatory region of IGF1 and GHR on growth and carcass traits in beef cattle.

    Science.gov (United States)

    Curi, R A; Oliveira, H N; Silveira, A C; Lopes, C R

    2005-02-01

    Growth hormone (GH), insulin-like growth factors 1 and 2 (IGF1 and IGF2) and their associated binding proteins and transmembrane receptors (GHR, IGF1R and IGF2R) play an important role in the physiology of mammalian growth. The objectives of the present study were to estimate the allele and genotype frequencies of microsatellite markers located in the 5'-regulatory region of the IGF1 and GHR genes in beef cattle belonging to different genetic groups and to determine effects of these markers on growth and carcass traits in these animals under an intensive production system. For this purpose, genotyping was performed on 384 bulls including 79 Nellore, 30 Canchim (5/8 Charolais + 3/8 Zebu) and 275 crossbred animals originating from crosses of Simmental (1/2 Simmental, n = 30) and Angus (1/2 Angus, n = 245) sires with Nellore females. The effects of substituting L allele for S allele of GHR microsatellite across Nellore, Canchim and 1/2 Angus were significant for weight gain and body weight (P Nellore group and of 225 for 229 within 1/2 Angus were not significant for any of the traits.

  4. Inducible CTCF insulator delays the IgH 3' regulatory region-mediated activation of germline promoters and alters class switching.

    Science.gov (United States)

    Braikia, Fatima-Zohra; Oudinet, Chloé; Haddad, Dania; Oruc, Zeliha; Orlando, Domenico; Dauba, Audrey; Le Bert, Marc; Khamlichi, Ahmed Amine

    2017-06-06

    Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3' regulatory region (3'RR) in a stimulus-dependent manner. Why the 3'RR-mediated up-regulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the α constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells. Moreover, insertion of a GL promoter downstream of the CTCF insulator led to premature activation of the ectopic promoter. This study provides functional evidence that the 3'RR has a developmentally controlled potential to constitutively activate GL promoters but that this activity is delayed, at least in part, by the CTCF insulator, which borders a transcriptionally active domain established by the 3'RR in developing B cells.

  5. Polymorphism in the upstream regulatory region of DQA1 genes and DRB1, QAP, DQA1, and DQB1 haplotypes in the German population.

    Science.gov (United States)

    Haas, J P; Kimura, A; Andreas, A; Hochberger, M; Keller, E; Brünnler, G; Bettinotti, M P; Nevinny-Stickel, C; Hildebrandt, B; Sierp, G

    1994-01-01

    Polymorphism in the URR of the MHC class II DQA1 gene defines ten different alleles named QAP. Oligotyping for the alleles of DRB1, QAP, DQA1, and DQB1 have been performed in 210 unrelated healthy controls from Germany. Moreover, 83 HTCs from the Tenth IHWS have been tested. Four point loci haplotypes (DRB1, QAP, DQA1, and DQB1) have been analyzed in the unrelated healthy population sample. Computer analysis of the linkage disequilibria leads to the conclusion that QAP alleles are in strong linkage disequilibrium with alleles either the DQA1 or the DRB1 locus. One typical ("common") haplotype was found to be associated with each DRB1 allele in the majority (86%) of the tested persons. Apart from that, 25 other less frequent ("unusual") haplotypes, with an overall frequency of 14% have been defined. Some of these "unusual" MHC class II haplotypes were found to differ only in the regulatory alleles of DQA1 (QAP alleles) while they are identical for the alleles coding for structural elements (DRB1, DQA1, and DQB1). Most of the "unusual" haplotypes were found to carry HLA-DQ6. Assuming that "unusual" (= rare) haplotypes have arisen from "common" (= frequent) haplotypes by point mutation and recombination, we propose the existence of three recombination sites in the MHC DR-DQ region: one between DRB1 and QAP, the second between QAP and DQA1, and the third between DQA1 and DQB1.

  6. Female-to-male sex reversal associated with unique Xp21.2 deletion disrupting genomic regulatory architecture of the dosage-sensitive sex reversal region.

    Science.gov (United States)

    Dangle, Pankaj; Touzon, María Sol; Reyes-Múgica, Miguel; Witchel, Selma F; Rajkovic, Aleksandar; Schneck, Francis X; Yatsenko, Svetlana A

    2017-10-01

    The XX male disorder of sex development (DSD) is a rare condition that is most commonly associated with the presence of the SRY gene on one of the X chromosomes due to unequal crossing-over between sex chromosomes during spermatogenesis. However, in about 20% of the XX male individuals, SRY is missing, although these persons have at least some testis differentiation. The genetic basis of genital ambiguity and the mechanisms triggering testis development in such patients remain unknown. The proband with 46,XX SRY -negative testicular DSD was screened for point mutations by whole exome sequencing and CNVs using a high-resolution DSD gene-targeted and whole genome array comparative genomic hybridisation. The identified Xp21.2 genomic alteration was further characterised by direct sequencing of the breakpoint junctions and bioinformatics analysis. A unique, 80 kb microdeletion removing the regulatory sequences and the NR0B1 gene was detected by microarray analysis. This deletion disturbs the human-specific genomic architecture of the Xp21.2 dosage-sensitive sex (DSS) reversal region in the XX patient with male-appearing ambiguous genitalia and ovotestis. Duplication of the DSS region containing the MAGEB and NR0B1 genes has been implicated in testis repression and sex reversal. Identification of this microdeletion highlights the importance of genomic integrity in the regulation and interaction of sex determining genes during gonadal development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Some Properties of Fuzzy Soft Proximity Spaces

    Science.gov (United States)

    Demir, İzzettin; Özbakır, Oya Bedre

    2015-01-01

    We study the fuzzy soft proximity spaces in Katsaras's sense. First, we show how a fuzzy soft topology is derived from a fuzzy soft proximity. Also, we define the notion of fuzzy soft δ-neighborhood in the fuzzy soft proximity space which offers an alternative approach to the study of fuzzy soft proximity spaces. Later, we obtain the initial fuzzy soft proximity determined by a family of fuzzy soft proximities. Finally, we investigate relationship between fuzzy soft proximities and proximities. PMID:25793224

  8. PROXIMITY MANAGEMENT IN CRISIS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Ion Dorin BUMBENECI

    2010-01-01

    Full Text Available The purpose of this study is to evaluate the level of assimilation for the terms "Proximity Management" and "Proximity Manager", both in the specialized literature and in practice. The study has two parts: the theoretical research of the two terms, and an evaluation of the use of Proximity management in 32 companies in Gorj, Romania. The object of the evaluation resides in 27 companies with less than 50 employees and 5 companies with more than 50 employees.

  9. Effects of boiling and roasting on proximate composition, lipid oxidation, fatty acid profile and mineral content of two sesame varieties commercialized and consumed in Far-North Region of Cameroon.

    Science.gov (United States)

    Tenyang, Noël; Ponka, Roger; Tiencheu, Bernard; Djikeng, Fabrice T; Azmeera, Thirupathi; Karuna, Mallampalli S L; Prasad, Rachapudi B N; Womeni, Hilaire M

    2017-04-15

    The aim of this study was to determine the effect of boiling and roasting on the proximate, lipid oxidation, fatty acid profile and mineral content of two sesame seeds varieties. The proximate composition was significantly affected (Psesame oil after processing was significantly increased (Psesame varieties. C16:0, C18:0, C18:1 and C18:2 were quantitatively the most important fatty acids in sesame oil. Boiling appeared to be the best processing method for cooking the two sesame varieties concerning oxidative stability and fatty acid profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. RevSex duplication-induced and sex-related differences in the SOX9 regulatory region chromatin landscape in human fibroblasts.

    Science.gov (United States)

    Lybæk, Helle; de Bruijn, Diederik; den Engelsman-van Dijk, Anke H A; Vanichkina, Darya; Nepal, Chirag; Brendehaug, Atle; Houge, Gunnar

    2014-03-01

    It was recently shown that duplications of the RevSex element, located 0.5 Mb upstream of SOX9, cause XX-disorder of sex development (DSD), and that deletions cause XY-DSD. To explore how a 148 kb RevSex duplication could have turned on gonadal SOX9 expression in the absence of SRY in an XX-male, we examined the chromatin landscape in primary skin fibroblast cultures from the index, his RevSex duplication-carrier father and six controls. The ENCODE project supports the notion that chromatin state maps show overlap between different cell types, i.e., that our study of fibroblasts could be of biological relevance. We examined the SOX9 regulatory region by high-resolution ChIP-on-chip experiments (a kind of "chromatin-CGH") and DNA methylation investigations. The RevSex duplication was associated with chromatin changes predicting better accessibility of the SRY-responsive TESCO enhancer region 14-15 kb upstream of SOX9. Four kb downstream of the TESCO evolutionary conserved region, a peak of the enhancer/promoter-associated H3K4me3 mark was found together with a major dip of the repressive H3K9me3 chromatin mark. Similar differences were also found when three control males were compared with three control females. A marked male/female difference was a more open chromatin signature in males starting ~400 kb upstream of SOX9 and increasing toward the SOX9 promoter. In the RevSex duplication-carrier father, two positions of DNA hypomethylation were also found, one corresponding to the H3K4me3 peak mentioned above. Our results suggest that the RevSex duplication could operate by inducing long-range epigenetic changes. Furthermore, the differences in chromatin state maps between males and females suggest that the Y chromosome or X chromosome dosage may affect chromatin conformation, i.e., that sex-dependent gene regulation may take place by chromatin modification.

  11. RevSex duplication-induced and sex-related differences in the SOX9 regulatory region chromatin landscape in human fibroblasts

    Science.gov (United States)

    Lybæk, Helle; de Bruijn, Diederik; den Engelsman-van Dijk, Anke HA; Vanichkina, Darya; Nepal, Chirag; Brendehaug, Atle; Houge, Gunnar

    2014-01-01

    It was recently shown that duplications of the RevSex element, located 0.5 Mb upstream of SOX9, cause XX-disorder of sex development (DSD), and that deletions cause XY-DSD. To explore how a 148 kb RevSex duplication could have turned on gonadal SOX9 expression in the absence of SRY in an XX-male, we examined the chromatin landscape in primary skin fibroblast cultures from the index, his RevSex duplication-carrier father and six controls. The ENCODE project supports the notion that chromatin state maps show overlap between different cell types, i.e., that our study of fibroblasts could be of biological relevance. We examined the SOX9 regulatory region by high-resolution ChIP-on-chip experiments (a kind of “chromatin-CGH”) and DNA methylation investigations. The RevSex duplication was associated with chromatin changes predicting better accessibility of the SRY-responsive TESCO enhancer region 14–15 kb upstream of SOX9. Four kb downstream of the TESCO evolutionary conserved region, a peak of the enhancer/promoter-associated H3K4me3 mark was found together with a major dip of the repressive H3K9me3 chromatin mark. Similar differences were also found when three control males were compared with three control females. A marked male/female difference was a more open chromatin signature in males starting ~400 kb upstream of SOX9 and increasing toward the SOX9 promoter. In the RevSex duplication-carrier father, two positions of DNA hypomethylation were also found, one corresponding to the H3K4me3 peak mentioned above. Our results suggest that the RevSex duplication could operate by inducing long-range epigenetic changes. Furthermore, the differences in chromatin state maps between males and females suggest that the Y chromosome or X chromosome dosage may affect chromatin conformation, i.e., that sex-dependent gene regulation may take place by chromatin modification. PMID:24351654

  12. Capacitive Proximity Sensor Has Longer Range

    Science.gov (United States)

    Vranish, John M.

    1992-01-01

    Capacitive proximity sensor on robot arm detects nearby object via capacitive effect of object on frequency of oscillator. Sensing element part of oscillator circuit operating at about 20 kHz. Total capacitance between sensing element and ground constitutes tuning capacitance of oscillator. Sensor circuit includes shield driven by replica of alternating voltage applied to sensing element. Driven shield concentrates sensing electrostatic field in exterior region to enhance sensitivity to object. Sensitivity and dynamic range has corresponding 12-to-1 improvement.

  13. ChIP-Seq-Annotated Heliconius erato Genome Highlights Patterns of cis-Regulatory Evolution in Lepidoptera

    Directory of Open Access Journals (Sweden)

    James J. Lewis

    2016-09-01

    Full Text Available Uncovering phylogenetic patterns of cis-regulatory evolution remains a fundamental goal for evolutionary and developmental biology. Here, we characterize the evolution of regulatory loci in butterflies and moths using chromatin immunoprecipitation sequencing (ChIP-seq annotation of regulatory elements across three stages of head development. In the process we provide a high-quality, functionally annotated genome assembly for the butterfly, Heliconius erato. Comparing cis-regulatory element conservation across six lepidopteran genomes, we find that regulatory sequences evolve at a pace similar to that of protein-coding regions. We also observe that elements active at multiple developmental stages are markedly more conserved than elements with stage-specific activity. Surprisingly, we also find that stage-specific proximal and distal regulatory elements evolve at nearly identical rates. Our study provides a benchmark for genome-wide patterns of regulatory element evolution in insects, and it shows that developmental timing of activity strongly predicts patterns of regulatory sequence evolution.

  14. Sequence analysis of the MYC oncogene involved in the t(8; 14)(q24; q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered

    Energy Technology Data Exchange (ETDEWEB)

    Finver, S.N.; Nishikura, K.; Finger, L.R.; Haluska, F.G.; Finan, J.; Nowell, P.C.; Croce, C.M.

    1988-05-01

    The authors cloned the translocation-associated and homologous normal MYC alleles from SKW-3, a leukemia T-cell line with the t(8; 14)(q24; q11) translocation, and determined the sequence of the MYC oncogene first exon and flanking 5' putative regulatory regions. S1 nuclease protection experiments utilizing a MYC first exon probe demonstrated transcriptional deregulation of the MYC gene associated with the T-cell receptor ..cap alpha.. locus on the 8q + chromosome of SKW-3 cells. Nucleotide sequence analysis of the translocation-associated (8q +) MYC allele identified a single base substitution within the upstream flanking region; the homologous nontranslocated allele contained an additional substitution and a two-base deletion. None of the deletions or substitutions localized to putative 5' regulatory regions. The MYC first exon sequence was germ line in both alleles. These results demonstrate that alterations within the putative 5' MYC regulatory regions are not necessarily involved in MYC deregulation in T-cell leukemias, and they show that juxtaposition of the T-cell receptor ..cap alpha.. locus to a germ-line MYC oncogene results in MYC deregulation.

  15. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

  16. [A case of proximal type epithelioid sarcoma of the perineum].

    Science.gov (United States)

    Murashima, Takaya; Kamibeppu, Toyoharu; Hiromasa, Tukino; Mukai, Syoichiro; Kamoto, Toshiyuki

    2013-11-01

    Epithelioid sarcomas are rare soft tissue neoplasms which occur more often in young people. They tend to relapse, metastatize and show poor prognosis. Proximal-type epithelioid sarcomas arise from the more proximal part of body and are more malignant than distal-type epithelioid sarcomas. We present a case of proximal-type epithelioid sarcoma which occurred in the perineum. A 24-year-old male visited our hospital with the chief complaint of pain in the perineum. Computed tomography and magnetic resonance imaging showed a tumor 30×23×17 mm in diameter in the perineal region. The tumor was excised regionally and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. The patient is free of recurrence and metastasis one year after local excision.

  17. Human galectin-3 (Mac-2 antigen): Defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region

    NARCIS (Netherlands)

    Krzeminski, M.N.; Singh, T.; André, S.; Lensch, M.; Wu, A.M.; Bonvin, A.M.J.J.; Gabius, H.-J.

    2011-01-01

    Background: Human galectin-3 (Mac-2 antigen) is a cell-type-specific multifunctional effector owing to selective binding of distinct cell-surface glycoconjugates harboring β-galactosides. The structural basis underlying the apparent preferences for distinct glycoproteins and for expression is so far

  18. Novel 5' untranslated region directed blockers of iron-regulatory protein-1 dependent amyloid precursor protein translation: implications for down syndrome and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Sanghamitra Bandyopadhyay

    Full Text Available We reported that iron influx drives the translational expression of the neuronal amyloid precursor protein (APP, which has a role in iron efflux. This is via a classic release of repressor interaction of APP mRNA with iron-regulatory protein-1 (IRP1 whereas IRP2 controls the mRNAs encoding the L- and H-subunits of the iron storage protein, ferritin. Here, we identified thirteen potent APP translation blockers that acted selectively towards the uniquely configured iron-responsive element (IRE RNA stem loop in the 5' untranslated region (UTR of APP mRNA. These agents were 10-fold less inhibitory of 5'UTR sequences of the related prion protein (PrP mRNA. Western blotting confirmed that the 'ninth' small molecule in the series selectively reduced neural APP production in SH-SY5Y cells at picomolar concentrations without affecting viability or the expression of α-synuclein and ferritin. APP blocker-9 (JTR-009, a benzimidazole, reduced the production of toxic Aβ in SH-SY5Y neuronal cells to a greater extent than other well tolerated APP 5'UTR-directed translation blockers, including posiphen, that were shown to limit amyloid burden in mouse models of Alzheimer's disease (AD. RNA binding assays demonstrated that JTR-009 operated by preventing IRP1 from binding to the IRE in APP mRNA, while maintaining IRP1 interaction with the H-ferritin IRE RNA stem loop. Thus, JTR-009 constitutively repressed translation driven by APP 5'UTR sequences. Calcein staining showed that JTR-009 did not indirectly change iron uptake in neuronal cells suggesting a direct interaction with the APP 5'UTR. These studies provide key data to develop small molecules that selectively reduce neural APP and Aβ production at 10-fold lower concentrations than related previously characterized translation blockers. Our data evidenced a novel therapeutic strategy of potential impact for people with trisomy of the APP gene on chromosome 21, which is a phenotype long associated with Down

  19. Novel 5' untranslated region directed blockers of iron-regulatory protein-1 dependent amyloid precursor protein translation: implications for down syndrome and Alzheimer's disease.

    Science.gov (United States)

    Bandyopadhyay, Sanghamitra; Cahill, Catherine; Balleidier, Amelie; Huang, Conan; Lahiri, Debomoy K; Huang, Xudong; Rogers, Jack T

    2013-01-01

    We reported that iron influx drives the translational expression of the neuronal amyloid precursor protein (APP), which has a role in iron efflux. This is via a classic release of repressor interaction of APP mRNA with iron-regulatory protein-1 (IRP1) whereas IRP2 controls the mRNAs encoding the L- and H-subunits of the iron storage protein, ferritin. Here, we identified thirteen potent APP translation blockers that acted selectively towards the uniquely configured iron-responsive element (IRE) RNA stem loop in the 5' untranslated region (UTR) of APP mRNA. These agents were 10-fold less inhibitory of 5'UTR sequences of the related prion protein (PrP) mRNA. Western blotting confirmed that the 'ninth' small molecule in the series selectively reduced neural APP production in SH-SY5Y cells at picomolar concentrations without affecting viability or the expression of α-synuclein and ferritin. APP blocker-9 (JTR-009), a benzimidazole, reduced the production of toxic Aβ in SH-SY5Y neuronal cells to a greater extent than other well tolerated APP 5'UTR-directed translation blockers, including posiphen, that were shown to limit amyloid burden in mouse models of Alzheimer's disease (AD). RNA binding assays demonstrated that JTR-009 operated by preventing IRP1 from binding to the IRE in APP mRNA, while maintaining IRP1 interaction with the H-ferritin IRE RNA stem loop. Thus, JTR-009 constitutively repressed translation driven by APP 5'UTR sequences. Calcein staining showed that JTR-009 did not indirectly change iron uptake in neuronal cells suggesting a direct interaction with the APP 5'UTR. These studies provide key data to develop small molecules that selectively reduce neural APP and Aβ production at 10-fold lower concentrations than related previously characterized translation blockers. Our data evidenced a novel therapeutic strategy of potential impact for people with trisomy of the APP gene on chromosome 21, which is a phenotype long associated with Down syndrome (DS

  20. Developing survey metrics for analysing cross-border proximity

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Williams, Allan

    2017-01-01

    Cross-border innovation cooperation (CBIC) has been heralded as one of the corner stones of innovation-driven growth opportunities for firms located in cross-border regions (CBRs). The success of this cooperation is affected by varying types of proximities identified in the literature....... The findings indicate that the developed survey metrics are effective in depicting the phenomenon of proximity. The foundational work undertaken in this research note provides a platform, and catalyst, for more extensive investigations of the topic....

  1. Fractures of the proximal humerus

    DEFF Research Database (Denmark)

    Brorson, Stig

    2013-01-01

    . The bandages were further supported by splints made of wood or coarse grass. Healing was expected in forty days. Different fracture patterns have been discussed and classified since Ancient Greece. Current classification of proximal humeral fractures mainly relies on the classifications proposed by Charles......, classification of proximal humeral fractures remains a challenge for the conduct, reporting, and interpretation of clinical trials. The evidence for the benefits of surgery in complex fractures of the proximal humerus is weak. In three systematic reviews I studied the outcome after locking plate osteosynthesis......Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate...

  2. The infrastructure of psychological proximity

    DEFF Research Database (Denmark)

    Nickelsen, Niels Christian Mossfeldt

    2015-01-01

    ). The experience of psychological proximity between patient and nurse is provided through confidence, continuity and the practical set-up. This constitutes an important enactment of skillfulness, which may render telemedicine a convincing health service in the future. Methodology: The study draws on a pilot...... (Langstrup & Winthereik 2008). This study contributes by showing the infrastructure of psychological proximity, which is provided by way of device, confidence, continuity and accountability....

  3. Regulatory modules in the developing heart

    NARCIS (Netherlands)

    Habets, Petra E. M. H.; Moorman, Antoon F. M.; Christoffels, Vincent M.

    2003-01-01

    Fragments of regulatory DNA of cardiac genes drive reporter gene expression in sometimes unexpected subdomains of the heart. These patterns have revealed that the regulatory DNA of genes consists of distinct subfragments (regulatory modules) that are active in different regions of the developing

  4. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  5. ChIP-seq analysis of genomic binding regions of five major transcription factors highlights a central role for ZIC2 in the mouse epiblast stem cell gene regulatory network

    Science.gov (United States)

    Matsuda, Kazunari; Oki, Shinya; Iida, Hideaki; Andrabi, Munazah; Yamaguchi, Katsushi

    2017-01-01

    To obtain insight into the transcription factor (TF)-dependent regulation of epiblast stem cells (EpiSCs), we performed ChIP-seq analysis of the genomic binding regions of five major TFs. Analysis of in vivo biotinylated ZIC2, OTX2, SOX2, POU5F1 and POU3F1 binding in EpiSCs identified several new features. (1) Megabase-scale genomic domains rich in ZIC2 peaks and genes alternate with those rich in POU3F1 but sparse in genes, reflecting the clustering of regulatory regions that act at short and long-range, which involve binding of ZIC2 and POU3F1, respectively. (2) The enhancers bound by ZIC2 and OTX2 prominently regulate TF genes in EpiSCs. (3) The binding sites for SOX2 and POU5F1 in mouse embryonic stem cells (ESCs) and EpiSCs are divergent, reflecting the shift in the major acting TFs from SOX2/POU5F1 in ESCs to OTX2/ZIC2 in EpiSCs. (4) This shift in the major acting TFs appears to be primed by binding of ZIC2 in ESCs at relevant genomic positions that later function as enhancers following the disengagement of SOX2/POU5F1 from major regulatory functions and subsequent binding by OTX2. These new insights into EpiSC gene regulatory networks gained from this study are highly relevant to early stage embryogenesis. PMID:28455373

  6. Transverse Stress Fracture of the Proximal Patella

    Science.gov (United States)

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu

    2016-01-01

    Abstract Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year-old athlete. A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity. Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90°, so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90°, during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws. PMID:26871789

  7. Proximal iliotibial band syndrome: case report

    Directory of Open Access Journals (Sweden)

    Guilherme Guadagnini Falotico

    2013-08-01

    Full Text Available OBJECTIVE: The overuse injuries in the hip joint occur commonly in sports practitioners and currently due to technical advances in diagnostic imaging, especially magnetic resonance imaging (MRI, are often misdiagnosed. Recently, a group of people were reported, all female, with pain and swelling in the pelvic region.T2-weighted MRI showed increased signal in the enthesis of the iliotibial band (ITB along the lower border of the iliac tubercle. We report a case of a 34 year old woman, non-professional runner, with pain at the iliac crest with no history of trauma and whose MRI was compatible with the proximal iliotibial band syndrome.

  8. Cubesat Proximity Operations Demonstration (CPOD)

    Science.gov (United States)

    Villa, Marco; Martinez, Andres; Petro, Andrew

    2015-01-01

    The CubeSat Proximity Operations Demonstration (CPOD) project will demonstrate rendezvous, proximity operations and docking (RPOD) using two 3-unit (3U) CubeSats. Each CubeSat is a satellite with the dimensions 4 inches x 4 inches x 13 inches (10 centimeters x 10 centimeters x 33 centimeters) and weighing approximately 11 pounds (5 kilograms). This flight demonstration will validate and characterize many new miniature low-power proximity operations technologies applicable to future missions. This mission will advance the state of the art in nanosatellite attitude determination,navigation and control systems, in addition to demonstrating relative navigation capabilities.The two CPOD satellites are scheduled to be launched together to low-Earth orbit no earlier than Dec. 1, 2015.

  9. The regulatory element 3' to the A gamma-globin gene binds to the nuclear matrix and interacts with special A-T-rich binding protein 1 (SATB1), an SAR/MAR-associating region DNA binding protein.

    Science.gov (United States)

    Cunningham, J M; Purucker, M E; Jane, S M; Safer, B; Vanin, E F; Ney, P A; Lowrey, C H; Nienhuis, A W

    1994-08-15

    A cis-acting DNA regulatory element 3' to the A gamma-globin gene contains eight distinct regions of DNA-protein interaction distributed over 750 bp of DNA. The sequences of two foot-printed regions (sites I and IV) are A-T rich and generate a highly retarded complex on gel shift analysis with nuclear extract from human erythroleukemia (K562) cells. We have purified a 98-kD protein that reproduces this gel shift. Tryptic cleavage and peptide sequence analysis demonstrated that the 98-kD protein is identical to a recently cloned protein, special A-T-rich binding protein 1 (SATB1), that binds selectively to nuclear matrix/scaffold-associated regions of DNA (MARs/SARs). We have shown by functional analysis that the 3' A gamma regulatory element associates with the nuclear matrix. SATB1 mRNA was identified in K562 cells, and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated its transcript in several other hematopoietic lines. Antisera to SATB1 caused ablation of the gel shift complex generated by both the crude nuclear extract and the purified 98-kD protein with the site I oligonucleotide. Furthermore, oligonucleotides that bind SATB1 inhibited formation of the site I gel shift complex when added as excess unlabeled competitor. An immunoblot analysis of the site I gel shift complex documented the presence of SATB1. Binding of SATB1 to two sites within the 3' A gamma regulatory element and its MAR/SAR activity suggests that this element may influence gene expression through interaction with the nuclear matrix.

  10. A Genome-Wide Search for Ionizing-Radiation-Responsive Elements in Deinococcus radiodurans Reveals a Regulatory Role for the DNA Gyrase Subunit A Gene's 5' Untranslated Region in the Radiation and Desiccation Response.

    Science.gov (United States)

    Villa, Jordan K; Amador, Paul; Janovsky, Justin; Bhuyan, Arijit; Saldanha, Roland; Lamkin, Thomas J; Contreras, Lydia M

    2017-06-15

    Tight regulation of gene expression is important for the survival of Deinococcus radiodurans, a model bacterium of extreme stress resistance. Few studies have examined the use of regulatory RNAs as a possible contributing mechanism to ionizing radiation (IR) resistance, despite their proffered efficient and dynamic gene expression regulation under IR stress. This work presents a transcriptome-based approach for the identification of stress-responsive regulatory 5' untranslated region (5'-UTR) elements in D. radiodurans R1 that can be broadly applied to other bacteria. Using this platform and an in vivo fluorescence screen, we uncovered the presence of a radiation-responsive regulatory motif in the 5' UTR of the DNA gyrase subunit A gene. Additional screens under H2O2-induced oxidative stress revealed the specificity of the response of this element to IR stress. Further examination of the sequence revealed a regulatory motif of the radiation and desiccation response (RDR) in the 5' UTR that is necessary for the recovery of D. radiodurans from high doses of IR. Furthermore, we suggest that it is the preservation of predicted RNA structure, in addition to DNA sequence consensus of the motif, that permits this important regulatory ability.IMPORTANCEDeinococcus radiodurans is an extremely stress-resistant bacterium capable of tolerating up to 3,000 times more ionizing radiation than human cells. As an integral part of the stress response mechanism of this organism, we suspect that it maintains stringent control of gene expression. However, understanding of its regulatory pathways remains incomplete to date. Untranslated RNA elements have been demonstrated to play crucial roles in gene regulation throughout bacteria. In this work, we focus on searching for and characterizing responsive RNA elements under radiation stress and propose that multiple levels of gene regulation work simultaneously to enable this organism to efficiently recover from exposure to ionizing

  11. Congenital anomalies and proximity to landfill sites.

    LENUS (Irish Health Repository)

    Boyle, E

    2004-01-01

    The occurrence of congenital anomalies in proximity to municipal landfill sites in the Eastern Region (counties Dublin, Kildare, Wicklow) was examined by small area (district electoral division), distance and clustering tendancies in relation to 83 landfills, five of which were major sites. The study included 2136 cases of congenital anomaly, 37,487 births and 1423 controls between 1986 and 1990. For the more populous areas of the region 50% of the population lived within 2-3 km of a landfill and within 4-5 km for more rural areas. In the area-level analysis, the standardised prevalence ratios, empirical and full Bayesian modelling, and Kulldorff\\'s spatial scan statistic found no association between the residential area of cases and location of landfills. In the case control analysis, the mean distance of cases and controls from the nearest landfill was similar. The odds ratios of cases compared to controls for increasing distances from all landfills and major landfills showed no significant difference from the baseline value of 1. The kernel and K methods showed no tendency of cases to cluster in relationship to landfills. In conclusion, congenital anomalies were not found to occur more commonly in proximity to municipal landfills.

  12. Scattering Effects in Proximity Effect Tunneling Spectroscopy.

    Science.gov (United States)

    Gai, Wei

    PETS (Proximity Effect Tunneling Spectroscopy) technique has been applied to Niobium/Yttrium and Niobium/Lutetium bilayers. We have determined electron - phonon interaction parameter lambda_{rm e -ph} is 0.55 for Yttrium and 0.67 for Lutetium. Spin fluctuations parameter lambda_{ rm S} is 0.20 for Yttrium and 0.33 for Lutetium. We found that the large spin fluctuations in Yttrium and Lutetium has responsibility to the absence of superconductivity in them. Our results have given a reasonable explanation of high superconducting transition temperature in them under high pressure. The large reflection coefficient and strong diffuse scattering at Nb/Y and Nb/Lu interface has been discovered and it should have strong influence on the transport properties of metallic superlattices. From the modeling study of elastic scattering in proximity effect tunnel junctions, we have explained why some conventional made high {rm T_{C}} superconducting tunnel junctions give ideal like characteristics in the gap region but variable strength phonon structures in the phonon region.

  13. In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population

    Directory of Open Access Journals (Sweden)

    Huang Xiangsheng

    2012-12-01

    Full Text Available Abstract Background The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. Methods We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25 in Gabonese individuals exposed to plentiful parasitic infections. Results We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576 for IL2 and -409C/T (ss410961577 for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (Prs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein and C/EBP beta (CCAAT/enhancer binding protein beta that are believed to regulate the Treg function. Conclusions The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.

  14. In-vitro characterization of novel and functional regulatory SNPs in the promoter region of IL2 and IL2R alpha in a Gabonese population.

    Science.gov (United States)

    Huang, Xiangsheng; Kühne, Vera; Kun, Jürgen F J; Soboslay, Peter T; Lell, Bertrand; Tp, Velavan

    2012-12-07

    The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections. We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576) for IL2 and -409C/T (ss410961577) for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T) of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (P<0.05). In addition, the rs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function. The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.

  15. SHORT COMMUNICATION PROXIMATE COMPOSITION, MINERAL ...

    African Journals Online (AJOL)

    Preferred Customer

    SHORT COMMUNICATION. PROXIMATE COMPOSITION, MINERAL CONTENT AND ANTINUTRITIONAL. FACTORS OF SOME CAPSICUM (Capsicum annum) VARIETIES GROWN IN. ETHIOPIA. Esayas K.1, Shimelis A.2, Ashebir F.3, Negussie R.3, Tilahun B.4 and Gulelat D.4*. 1Hawassa University, Department of Food ...

  16. The potential risk of left subclavian artery injury from excessively long thoracic pedicle screws placed in the proximal thoracic regions of Lenke type 2 adolescent idiopathic scoliosis patients and normal teenagers: an anatomical study.

    Science.gov (United States)

    Jiang, Jun; Qian, Bang-Ping; Qiu, Yong; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang

    2016-10-01

    The altered anatomic positions of important structures adjacent to the vertebrae in adolescent idiopathic scoliosis (AIS) patients have been comprehensively investigated by previous radiographic studies. However, no study has evaluated the altered position of left subclavian artery (SA) in these patients. The purpose of this study is to evaluate the altered position of left subclavian artery in AIS patients with a double thoracic curve pattern. Nineteen Lenke type 2 AIS patients and thirteen normal teenagers were included in this study. Axial computed tomography images at T2 and T3 levels were obtained in all these subjects to evaluate the subclavian artery-vertebral angle (SAVA, defined as 0° when the artery was located directly lateral to the left and 180° when directly lateral to the right) and subclavian artery-vertebral distance (SAVD, the shortest distance between the artery and vertebral body). The percentage of left subclavian arteries at potential risk of injury from excessively long pedicle screws was calculated. The SAVA was significantly larger in AIS patients than that in normal teenagers at both T2 and T3 levels (P teenagers at both T2 and T3 levels (P teenagers. The left SA is located much closer to the vertebrae in the proximal thoracic curve of Lenke type 2 AIS patients when compared with normal teenagers. The spine surgeons should be aware of such altered position of left SA and choose appropriate pedicle length to avoid anterior cortical penetration in Lenke type 2 AIS patients.

  17. ChIP-seq analysis of genomic binding regions of five major transcription factors highlights a central role for ZIC2 in the mouse epiblast stem cell gene regulatory network.

    Science.gov (United States)

    Matsuda, Kazunari; Mikami, Tomoyuki; Oki, Shinya; Iida, Hideaki; Andrabi, Munazah; Boss, Jeremy M; Yamaguchi, Katsushi; Shigenobu, Shuji; Kondoh, Hisato

    2017-06-01

    To obtain insight into the transcription factor (TF)-dependent regulation of epiblast stem cells (EpiSCs), we performed ChIP-seq analysis of the genomic binding regions of five major TFs. Analysis of in vivo biotinylated ZIC2, OTX2, SOX2, POU5F1 and POU3F1 binding in EpiSCs identified several new features. (1) Megabase-scale genomic domains rich in ZIC2 peaks and genes alternate with those rich in POU3F1 but sparse in genes, reflecting the clustering of regulatory regions that act at short and long-range, which involve binding of ZIC2 and POU3F1, respectively. (2) The enhancers bound by ZIC2 and OTX2 prominently regulate TF genes in EpiSCs. (3) The binding sites for SOX2 and POU5F1 in mouse embryonic stem cells (ESCs) and EpiSCs are divergent, reflecting the shift in the major acting TFs from SOX2/POU5F1 in ESCs to OTX2/ZIC2 in EpiSCs. (4) This shift in the major acting TFs appears to be primed by binding of ZIC2 in ESCs at relevant genomic positions that later function as enhancers following the disengagement of SOX2/POU5F1 from major regulatory functions and subsequent binding by OTX2. These new insights into EpiSC gene regulatory networks gained from this study are highly relevant to early stage embryogenesis. © 2017. Published by The Company of Biologists Ltd.

  18. Cloning of the pig aminopeptidase N gene. Identification of possible regulatory elements and the exon distribution in relation to the membrane-spanning region

    DEFF Research Database (Denmark)

    Sjöström, H; Norén, O; Olsen, Jørgen

    1989-01-01

    We have isolated four lambda-phages covering the complete pig aminopeptidase N/CD13 gene. The sequence of 2.85 kbp encompasses 1.18 kbp of the 5' upstream region and 1.67 kbp of the structural gene. In the promoter region we find a TATA box and potential binding sites for CTF-1/NF-1 and AP-2...

  19. Photoactivated In Vivo Proximity Labeling.

    Science.gov (United States)

    Beck, David B; Bonasio, Roberto

    2017-06-19

    Identification of molecular interactions is paramount to understanding how cells function. Most available technologies rely on co-purification of a protein of interest and its binding partners. Therefore, they are limited in their ability to detect low-affinity interactions and cannot be applied to proteins that localize to difficult-to-solubilize cellular compartments. In vivo proximity labeling (IPL) overcomes these obstacles by covalently tagging proteins and RNAs based on their proximity in vivo to a protein of interest. In IPL, a heterobifunctional probe comprising a photoactivatable moiety and biotin is recruited by a monomeric streptavidin tag fused to a protein of interest. Following UV irradiation, candidate interacting proteins and RNAs are covalently biotinylated with tight spatial and temporal control and subsequently recovered using biotin as an affinity handle. Here, we describe experimental protocols to discover novel protein-protein and protein-RNA interactions using IPL. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  20. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  1. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  2. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  3. Prox-1 Automated Proximity Operations

    Science.gov (United States)

    2016-01-13

    on demonstrating the functionality required to meet minimum mission success criteria. The minimum mission includes on- orbit spacecraft checkout of...also includes deployment of LightSail-B from the P-POD, and imaging of LightSail-B for 20 minutes as it recedes from Prox-1. small satellite ; proximity...criteria. The minimum mission includes on- orbit spacecraft checkout of all spacecraft subsystems, including flight qualification of the following new

  4. Ectoderm from various regions of the developing chick limb bud differentially regulates the expression of the chicken homeobox-containing genes GHox-7 and GHox-8 by limb mesenchymal cells.

    Science.gov (United States)

    Coelho, C N; Upholt, W B; Kosher, R A

    1993-03-01

    The apical ectodermal ridge expresses high amounts of the homeobox gene GHox-8 when placed upon dissociated limb mesenchymal cells in culture and induces high expression of GHox-7, but only low expression of GHox-8, in the underlying mesenchymal cells. Ectoderm from the proximal anterior border of the limb induces high expression of both GHox-7 and GHox-8, while ectoderm from the proximal posterior border does not induce expression of either gene. Thus, ectoderm in various regions of the limb bud has distinct regulatory activities and may be involved in controlling the regionally specific expression of GHox-7 and GHox-8 in the mesoderm.

  5. Proximal focal humeral deficiency in a large breed dog.

    Science.gov (United States)

    Kalff, S; Gemmill, T

    2012-01-01

    A 26-week-old female Boerboel was referred for evaluation of progressive left thoracic limb lameness. Computed tomography and radiographic evaluation revealed radiolucency of the caudal region of the proximal humeral metaphysis, absence of the humeral head, and gross distortion of the glenoid. Given the severe glenohumeral deformation, arthrodesis of the left shoulder was performed using orthogonal locking bone plates, lag screw fixation, and bone grafting. Despite late implant failure, arthrodesis was successful in this case, and satisfactory limb function was restored. To the author's knowledge, this is the first report of a case of a focal developmental deficiency of the proximal humerus reported in a dog.

  6. PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS

    African Journals Online (AJOL)

    DR. AMINU

    PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS. 1 Alhassan, A. J. 1M .S. Sule, 1J. ... ABSTRACT. This study determined the proximate and mineral element composition of whole white grubs using standard methods of analysis. Proximate ... days, before pulverized to powder and kept in plastic container.

  7. Differential acetylation of histone H3 at the regulatory region of OsDREB1b promoter facilitates chromatin remodelling and transcription activation during cold stress.

    Directory of Open Access Journals (Sweden)

    Dipan Roy

    Full Text Available The rice ortholog of DREB1, OsDREB1b, is transcriptionally induced by cold stress and over-expression of OsDREB1b results in increase tolerance towards high salt and freezing stress. This spatio-temporal expression of OsDREB1b is preceded by the change in chromatin structure at the promoter and the upstream region for gene activation. The promoter and the upstream region of OsDREB1b genes appear to be arranged into a nucleosome array. Nucleosome mapping of ∼ 700 bp upstream region of OsDREB1b shows two positioned nucleosomes between -610 to -258 and a weakly positioned nucleosome at the core promoter and the TSS. Upon cold stress, there is a significant change in the nucleosome arrangement at the upstream region with increase in DNaseI hypersensitivity or MNase digestion in the vicinity of cis elements and TATA box at the core promoter. ChIP assays shows hyper-acetylation of histone H3K9 throughout the locus whereas region specific increase was observed in H3K14ac and H3K27ac. Moreover, there is an enrichment of RNA PolII occupancy at the promoter region during transcription activation. There is no significant change in the H3 occupancy in OsDREB1b locus negating the possibility of nucleosome loss during cold stress. Interestingly, cold induced enhanced transcript level of OsDREB1b as well as histone H3 acetylation at the upstream region was found to diminish when stressed plants were returned to normal temperature. The result indicates absolute necessity of changes in chromatin conformation for the transcription up-regulation of OsDREB1b gene in response to cold stress. The combined results show the existence of closed chromatin conformation at the upstream and promoter region of OsDREB1b in the transcription "off" state. During cold stress, changes in region specific histone modification marks promote the alteration of chromatin structure to facilitate the binding of transcription machinery for proper gene expression.

  8. The 5S rDNA gene family in mollusks: characterization of transcriptional regulatory regions, prediction of secondary structures, and long-term evolution, with special attention to Mytilidae mussels.

    Science.gov (United States)

    Vizoso, Miguel; Vierna, Joaquín; González-Tizón, Ana M; Martínez-Lage, Andrés

    2011-01-01

    Several reports on the characterization of 5S ribosomal DNA (5S rDNA) in various animal groups have been published to date, but there is a lack of studies analyzing this gene family in a much broader context. Here, we have studied 5S rDNA variation in several molluskan species, including bivalves, gastropods, and cephalopods. The degree of conservation of transcriptional regulatory regions was analyzed in these lineages, revealing a conserved TATA-like box in the upstream region. The evolution of the 120 bp coding region (5S) was also studied, suggesting the occurrence of paralogue groups in razor clams, clams, and cockles. In addition, 5S rDNA sequences from 11 species and 7 genus of Mytilidae Rafinesque, 1815 mussels were sampled and studied in detail. Four different 5S rDNA types, based on the nontranscribed spacer region were identified. The phylogenetic analyses performed within each type showed a between-species gene clustering pattern, suggesting ancestral polymorphism. Moreover, some putative pseudogenized 5S copies were also identified. Our report, together with previous studies that found high degree of intragenomic divergence in bivalve species, suggests that birth-and-death evolution may be the main force driving the evolution of 5S rDNA in these animals, even at the genus level.

  9. Systematic screening for mutations in the 5{prime}-regulatory region of the human dopamine D{sub 1} receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder

    Energy Technology Data Exchange (ETDEWEB)

    Cichon, S.; Noethen, M.M.; Stoeber, G. [Univ. of Bonn (Germany)] [and others

    1996-07-26

    A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study we systematically searched for the presence of mutations in the 5{prime}-flanking region of the dopamine D{sub 1} receptor (DRD1) gene. This region has previously been shown to contain a functional promoter. We investigated 119 unrelated individuals (including 36 schizophrenic patients, 38 bipolar affective patients, and 45 healthy controls) using single-strand conformation analysis (SSCA). Eleven overlapping PCR fragments covered 2,189 bp of DNA sequence. We identified six single base substitutions: -2218T/C, -2102C/A, -2030T/C, -1992G/A, -1251G/C, and -800T/C. None of the mutations was found to be located in regions which have important influence on the level of transcriptional activity. Allele frequencies were similar in patients and controls, indicating that genetic variation in the 5{prime}-regulatory region of the DRD1 gene is unlikely to play a frequent, major role in the genetic predisposition to either schizophrenia or bipolar affective disorder. 31 refs., 3 tabs.

  10. Rehabilitation and Prevention of Proximal Hamstring Tendinopathy.

    Science.gov (United States)

    Beatty, Nicholas R; Félix, Ioonna; Hettler, Jessica; Moley, Peter J; Wyss, James F

    Proximal hamstring tendinopathy (PHT) comprises a small but significant portion of hamstring injuries in athletes, especially runners. PHT is a chronic condition that is clinically diagnosed but can be supported with imaging. The main presenting complaint is pain in the lower gluteal or ischial region that may or may not radiate along the hamstrings in the posterior thigh. There is little scientific evidence on which to base the rehabilitation management of PHT. Treatment is almost always conservative, with a focus on activity modification, addressing contributing biomechanical deficiencies, effective tendon loading including eccentric training, and ultrasound-guided interventional procedures which may facilitate rehabilitation. Surgery is limited to recalcitrant cases or those involving concomitant high-grade musculotendinous pathology. The keys to PHT management include early and accurate diagnosis, optimal rehabilitation to allow for a safe return to preinjury activity level, and preventative strategies to reduce risk of reinjury.

  11. Sequential Proximal Tibial Stress Fractures associated with Prolonged usage of Methotrexate and Corticosteroids: A Case Report

    Directory of Open Access Journals (Sweden)

    Tan TJL

    2015-11-01

    Full Text Available Stress fractures of the proximal tibia metaphysis are rare in the elderly. We present a case of a 65-year old male who developed sequential proximal tibia stress fractures associated with prolonged usage of methotrexate and prednisolone within a span of 18 months. Magnetic Resonance Imaging revealed an incomplete stress fracture involving the medial proximal tibial region. The patient was treated with stemmed total knee arthroplasty (TKA bilaterally. Stress fractures should be considered in patients with atypical knee pain who have a history of methotrexate and prednisolone usage. TKA is an effective treatment in stress fractures of the proximal tibia.

  12. Finger Proximal Interphalangeal Joint Dislocation.

    Science.gov (United States)

    Ramponi, Denise; Cerepani, Mary Jo

    2015-01-01

    Finger dislocations are common injuries that are often managed by emergency nurse practitioners. A systematic physical examination following these injuries is imperative to avoid complications. Radiographic views, including the anteroposterior, lateral, and oblique views, are imperative to evaluate these finger dislocations. A dorsal dislocation of the proximal interphalangeal (PIP) joint is the most common finger dislocation type often easily reduced. A volar PIP dislocation can often be difficult to reduce and may result in finger deformity. Finger dislocations should be reduced promptly. Referral to an orthopedic hand specialist is required if the dislocation is unable to be reduced or if the finger joint is unstable following reduction attempts.

  13. Equilibrium properties of proximity effect

    Energy Technology Data Exchange (ETDEWEB)

    Esteve, D.; Pothier, H.; Gueron, S.; Birge, N.O.; Devoret, M.

    1996-12-31

    The proximity effect in diffusive normal-superconducting (NS) nano-structures is described by the Usadel equations for the electron pair correlations. We show that these equations obey a variational principle with a potential which generalizes the Ginzburg-Landau energy functional. We discuss simple examples of NS circuits using this formalism. In order to test the theoretical predictions of the Usadel equations, we have measured the density of states as a function of energy on a long N wire in contact with a S wire at one end, at different distances from the NS interface. (authors). 12 refs.

  14. Human papillomavirus vaccines, complex regional pain syndrome, postural orthostatic tachycardia syndrome, and autonomic dysfunction - a review of the regulatory evidence from the European Medicines Agency

    DEFF Research Database (Denmark)

    Jefferson, Tom; Jørgensen, Lars

    2017-01-01

    Recent concerns about a possible association between exposure of young women to human papillomavirus (HPV) vaccines and two "dysautonomic syndromes" (a collection of signs and symptoms thought to be caused by autoimmunity) - complex regional pain syndrome (CRPS) and postural orthostatic tachycardia...

  15. The mitogenic function of hepatitis B virus X protein resides within amino acids 51 to 140 and is modulated by N- and C-terminal regulatory regions.

    Science.gov (United States)

    Li, Huajie; Chi, Chia-Yi; Lee, Sook; Andrisani, Ourania M

    2006-11-01

    The hepatitis B virus (HBV) X protein (pX) is implicated in hepatocarcinogenesis by an unknown mechanism. pX variants encoded by HBV genomes found integrated in genomic DNA from liver tumors of patients with hepatocellular carcinoma (HCC) generally lack amino acids 134 to 154. Since deregulation of mitogenic pathways is linked to oncogenic transformation, herein we define the pX region required for mitogenic pathway activation. A series of pX deletions was used to construct tetracycline-regulated pX-expressing cell lines. The activation of the mitogenic pathways by these pX deletions expressed in the constructed cell lines was measured by transient transreporter assays, effects on endogenous cyclin A expression, and apoptosis. Conditional expression of pX51-140 in AML12 clone 4 cell line activates the mitogenic pathways, induces endogenous cyclin A expression, and sensitizes cells to apoptosis, similar to wild-type (WT) pX. By contrast, pX1-115 is inactive, supporting the idea that amino acids 116 to 140 are required for mitogenic pathway activation. Moreover, this pX deletion analysis demonstrates that WT pX function is modulated by two regions spanning amino acids 1 to 78 and 141 to 154. The N-terminal X1-78, expressed via a retroviral vector in WT pX-expressing 4pX-1 cells, coimmunoprecipitates with WT pX, indicating this pX region participates in protein-protein interactions leading to pX oligomerization. Interestingly, pX1-78 interferes with WT pX in mediating mitogenic pathway activation, endogenous gene expression, and apoptosis. The C-terminal pX region spanning amino acids 141 to 154 decreases pX stability, determined by pulse-chase studies of WT pX and pX1-140, suggesting that increased stability of naturally occurring pX variants lacking amino acids 134 to 154 may play a role in HCC development.

  16. The effect of modular tapered fluted stems on proximal stress shielding in the human femur.

    Science.gov (United States)

    Hnat, William P; Conway, Justin S; Malkani, Arthur L; Yakkanti, Madhu R; Voor, Michael J

    2009-09-01

    The purpose of this study was to show a change in proximal femur surface strains following total hip arthroplasty and after the addition of BoneSource hydroxyapatite bone cement in the proximal region of an instrumented femur and to measure the surface strain on the proximal body. Seven third-generation composite femurs (Pacific Research Laboratories, Vashon, Wash) were instrumented with 12 uniaxial strain gages, 6 gages on the anterior face, and 6 gages on the posterior face of each femur. All femurs exhibited stress shielding since the strains in the proximal region were drastically reduced. There was a large decrease in strain in the mid-shaft region and small changes in strain in the distal region. The surface strains on the modular implant were relatively low.

  17. Complications in proximal humeral fractures.

    Science.gov (United States)

    Calori, Giorgio Maria; Colombo, Massimiliano; Bucci, Miguel Simon; Fadigati, Piero; Colombo, Alessandra Ines Maria; Mazzola, Simone; Cefalo, Vittorio; Mazza, Emilio

    2016-10-01

    Necrosis of the humeral head, infections and non-unions are among the most dangerous and difficult-to-treat complications of proximal humeral fractures. The aim of this work was to analyse in detail non-unions and post-traumatic bone defects and to suggest an algorithm of care. Treatment options are based not only on the radiological frame, but also according to a detailed analysis of the patient, who is classified using a risk factor analysis. This method enables the surgeon to choose the most suitable treatment for the patient, thereby facilitating return of function in the shortest possible time. The treatment of such serious complications requires the surgeon to be knowledgeable about the following possible solutions: increased mechanical stability; biological stimulation; and reconstructive techniques in two steps, with application of biotechnologies and prosthetic substitution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients.

    Science.gov (United States)

    Haschemi Nassab, Mani; Rhein, Mathias; Hagemeier, Lars; Kaeser, Marius; Muschler, Marc; Glahn, Alexander; Pich, Andreas; Heberlein, Annemarie; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas

    2016-01-01

    Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort. © 2015 S. Karger AG, Basel.

  19. Comparative bioinformatics and experimental analysis of the intergenic regulatory regions of Bacillus cereus hbl and nhe enterotoxin operons and the impact of CodY on virulence heterogeneity

    Directory of Open Access Journals (Sweden)

    Maria-Elisabeth eBöhm

    2016-05-01

    Full Text Available Bacillus cereus is a food contaminant with greatly varying enteropathogenic potential. Almost all known strains harbor the genes for at least one of the three enterotoxins Nhe, Hbl and CytK. While some strains show no cytotoxicity, others have caused outbreaks, in rare cases even with lethal outcome. The reason for these differences in cytotoxicity is unknown. To gain insight into the origin of enterotoxin expression heterogeneity in different strains, the architecture and role of 5’ intergenic regions (5’IGRs upstream of the nhe and hbl operons was investigated. In silico comparison of 142 strains of all seven phylogenetic groups of B. cereus sensu lato proved the presence of long 5’IGRs upstream of the nheABC and hblCDAB operons, which harbor recognition sites for several transcriptional regulators, including the virulence regulator PlcR, redox regulators ResD and Fnr, the nutrient-sensitive regulator CodY as well as the master regulator for biofilm formation SinR. By determining transcription start sites, unusually long 5’ untranslated regions (5’UTRs upstream of the nhe and hbl start codons were identified, which are not present upstream of cytK-1 and cytK-2. Promoter fusions lacking various parts of the nhe and hbl 5’UTR in B. cereus INRA C3 showed that the entire 331 bp 5’UTR of nhe is necessary for full promoter activity, while the presence of the complete 606 bp hbl 5’UTR lowers promoter activity. Repression was caused by a 268 bp sequence directly upstream of the hbl transcription start. Luciferase activity of reporter strains containing nhe and hbl 5’IGR lux fusions provided evidence that toxin gene transcription is upregulated by the depletion of free amino acids. Electrophoretic mobility shift assays showed that the branched-chain amino acid sensing regulator CodY binds to both nhe and hbl 5’UTR downstream of the promoter, potentially acting as a nutrient-responsive roadblock repressor of toxin gene transcription

  20. Comparative Bioinformatics and Experimental Analysis of the Intergenic Regulatory Regions of Bacillus cereus hbl and nhe Enterotoxin Operons and the Impact of CodY on Virulence Heterogeneity

    Science.gov (United States)

    Böhm, Maria-Elisabeth; Krey, Viktoria M.; Jeßberger, Nadja; Frenzel, Elrike; Scherer, Siegfried

    2016-01-01

    Bacillus cereus is a food contaminant with greatly varying enteropathogenic potential. Almost all known strains harbor the genes for at least one of the three enterotoxins Nhe, Hbl, and CytK. While some strains show no cytotoxicity, others have caused outbreaks, in rare cases even with lethal outcome. The reason for these differences in cytotoxicity is unknown. To gain insight into the origin of enterotoxin expression heterogeneity in different strains, the architecture and role of 5′ intergenic regions (5′ IGRs) upstream of the nhe and hbl operons was investigated. In silico comparison of 142 strains of all seven phylogenetic groups of B. cereus sensu lato proved the presence of long 5′ IGRs upstream of the nheABC and hblCDAB operons, which harbor recognition sites for several transcriptional regulators, including the virulence regulator PlcR, redox regulators ResD and Fnr, the nutrient-sensitive regulator CodY as well as the master regulator for biofilm formation SinR. By determining transcription start sites, unusually long 5′ untranslated regions (5′ UTRs) upstream of the nhe and hbl start codons were identified, which are not present upstream of cytK-1 and cytK-2. Promoter fusions lacking various parts of the nhe and hbl 5′ UTR in B. cereus INRA C3 showed that the entire 331 bp 5′ UTR of nhe is necessary for full promoter activity, while the presence of the complete 606 bp hbl 5′ UTR lowers promoter activity. Repression was caused by a 268 bp sequence directly upstream of the hbl transcription start. Luciferase activity of reporter strains containing nhe and hbl 5′ IGR lux fusions provided evidence that toxin gene transcription is upregulated by the depletion of free amino acids. Electrophoretic mobility shift assays showed that the branched-chain amino acid sensing regulator CodY binds to both nhe and hbl 5′ UTR downstream of the promoter, potentially acting as a nutrient-responsive roadblock repressor of toxin gene transcription. Plc

  1. Proximate composition and antinutrient content of pumpkin ...

    African Journals Online (AJOL)

    Proximate composition and antinutrient content of pumpkin ( Cucurbita pepo ) and sorghum ( Sorghum bicolor ) flour blends fermented with Lactobacillus plantarum , Aspergillus niger and Bacillus subtilis.

  2. The AP-1 binding sites located in the pol gene intragenic regulatory region of HIV-1 are important for viral replication.

    Directory of Open Access Journals (Sweden)

    Laurence Colin

    Full Text Available Our laboratory has previously identified an important intragenic region in the human immunodeficiency virus type 1 (HIV-1 genome, whose complete functional unit is composed of the 5103 fragment, the DNaseI-hypersensitive site HS7 and the 5105 fragment. These fragments (5103 and 5105 both exhibit a phorbol 12-myristate 13-acetate (PMA-inducible enhancer activity on the herpes simplex virus thymidine kinase promoter. Here, we characterized the three previously identified AP-1 binding sites of fragment 5103 by showing the PMA-inducible in vitro binding and in vivo recruitment of c-Fos, JunB and JunD to this fragment located at the end of the pol gene. Functional analyses demonstrated that the intragenic AP-1 binding sites are fully responsible for the PMA-dependent enhancer activity of fragment 5103. Moreover, infection of T-lymphoid Jurkat and promonocytic U937 cells with wild-type and mutant viruses demonstrated that mutations of the intragenic AP-1 sites individually or in combination altered HIV-1 replication. Importantly, mutations of the three intragenic AP-1 sites led to a decreased in vivo recruitment of RNA polymerase II to the viral promoter, strongly supporting that the deleterious effect of these mutations on viral replication occurs, at least partly, at the transcriptional level. Single-round infections of monocyte-derived macrophages confirmed the importance of intragenic AP-1 sites for HIV-1 infectivity.

  3. A positioned +1 nucleosome enhances promoter-proximal pausing

    OpenAIRE

    Jimeno-Gonz?lez, Silvia; Ceballos-Ch?vez, Mar?a; Reyes, Jos? C.

    2015-01-01

    Chromatin distribution is not uniform along the human genome. In most genes there is a promoter-associated nucleosome free region (NFR) followed by an array of nucleosomes towards the gene body in which the first (+1) nucleosome is strongly positioned. The function of this characteristic chromatin distribution in transcription is not fully understood. Here we show in vivo that the +1 nucleosome plays a role in modulating RNA polymerase II (RNAPII) promoter-proximal pausing. When a +1 nucleoso...

  4. Proximal location of mouse prostate epithelial stem cells

    OpenAIRE

    Tsujimura, Akira; Koikawa, Yasuhiro; Salm, Sarah; Takao, Tetsuya; Coetzee, Sandra; Moscatelli, David; Shapiro, Ellen; Lepor, Herbert; Sun, Tung-Tien; Wilson, E. Lynette

    2002-01-01

    Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propos...

  5. Xylem specific activation of 5' upstream regulatory region of two NAC transcription factors (MusaVND6 and MusaVND7) in banana is regulated by SNBE-like sites.

    Science.gov (United States)

    Negi, Sanjana; Tak, Himanshu; Ganapathi, T R

    2018-01-01

    Deposition of secondary cell wall in the xylem elements is controlled by a subgroup of NAC (NAM, ATAF, CUC) family, known as vascular-related NAC transcription factors (VNDs). In the present study, we analyzed the 5' upstream regulatory region of two banana NAC transcription factors (MusaVND6 and MusaVND7) for tissue specific expression and presence of 19-bp secondary-wall NAC binding element (SNBE)-like motifs. Transgenic banana plants of Musa cultivar Rasthali harboring either PMusaVND7::GUS or PMusaVND6::GUS showed specific GUS (β-D-Glucuronidase) activity in cells of the xylem tissue. Approximately 1.2kb promoter region of either MusaVND6 or MusaVND7 showed presence of at least two SNBE-like motifs. This 1.2kb promoter region was retarded in a gel shift assay by three banana VND protein (VND1,VND2 and VND3). The banana VND1-VND3 could also retard the mobility of isolated SNBE-like motifs of MusaVND6 or MusaVND7 in a gel shift assay. Transcript levels of MusaVND6 and MusaVND7 were elevated in transgenic banana overexpressing either banana VND1, VND2 or VND3. Present study suggested a probable regulation of banana VND6 and VND7 expression through direct interaction of banana VND1- VND3 with SNBE-like motifs. Our study also indicated two promoter elements for possible utilization in cell wall modifications in plants especially banana, which is being recently considered as a potential biofuel crop.

  6. Proximity to coast is linked to climate change belief.

    Science.gov (United States)

    Milfont, Taciano L; Evans, Laurel; Sibley, Chris G; Ries, Jan; Cunningham, Andrew

    2014-01-01

    Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local.

  7. Proximity to coast is linked to climate change belief.

    Directory of Open Access Journals (Sweden)

    Taciano L Milfont

    Full Text Available Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local.

  8. Functional outcome following proximal humeral interlocking system plating for displaced proximal humeral fractures

    OpenAIRE

    Thyagarajan David; Haridas Samarth; Jones Denise; Dent Colin; Evans Richard; Williams Rhys

    2009-01-01

    Aim: To assess the functional outcome following internal fixation with the PHILOS (proximal humeral interlocking system) for displaced proximal humeral fractures. Patients and Methods: We reviewed 30 consecutive patients treated surgically with the proximal humeral locking plate for a displaced proximal humeral fracture. Functional outcome was determined using the American Shoulder and Elbow Society (ASES) score and Constant Murley score. Results: Average age of the patients was 58 years...

  9. Best Proximity Points for a New Class of Generalized Proximal Mappings

    Directory of Open Access Journals (Sweden)

    Tayyab Kamran

    2017-03-01

    Full Text Available The best proximity points are usually used to find the optimal approximate solution of the operator equation Tx = x, when T has no fixed point. In this paper, we prove some best proximity point theorems for nonself multivalued operators, following the foot steps of Basha and Shahzad [Best proximity point theorems for generalized proximal contractions, Fixed Point Theory Appl., 2012, 2012:42].

  10. Preliminary phytochemical screening, proximate and elemental ...

    African Journals Online (AJOL)

    The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the following proximate ...

  11. Bimalleolar ankle fracture with proximal fibular fracture

    NARCIS (Netherlands)

    Colenbrander, R. J.; Struijs, P. A. A.; Ultee, J. M.

    2005-01-01

    A 56-year-old female patient suffered a bimalleolar ankle fracture with an additional proximal fibular fracture. This is an unusual fracture type, seldom reported in literature. It was operatively treated by open reduction and internal fixation of the lateral malleolar fracture. The proximal fibular

  12. Grouping by Proximity in Haptic Contour Detection

    Science.gov (United States)

    Overvliet, Krista E.; Krampe, Ralf Th.; Wagemans, Johan

    2013-01-01

    We investigated the applicability of the Gestalt principle of perceptual grouping by proximity in the haptic modality. To do so, we investigated the influence of element proximity on haptic contour detection. In the course of four sessions ten participants performed a haptic contour detection task in which they freely explored a haptic random dot display that contained a contour in 50% of the trials. A contour was defined by a higher density of elements (raised dots), relative to the background surface. Proximity of the contour elements as well as the average proximity of background elements was systematically varied. We hypothesized that if proximity of contour elements influences haptic contour detection, detection will be more likely when contour elements are in closer proximity. This should be irrespective of the ratio with the proximity of the background elements. Results showed indeed that the closer the contour elements were, the higher the detection rates. Moreover, this was the case independent of the contour/background ratio. We conclude that the Gestalt law of proximity applies to haptic contour detection. PMID:23762364

  13. Proximate analysis on four edible mushrooms ADEDAYO ...

    African Journals Online (AJOL)

    Michael Horsfall

    Vol. 15 (1) 9 - 11. Full-text Available Online at www.bioline.org.br/ja. Proximate analysis on four edible mushrooms. ADEDAYO, MAJEKODUNMI RACHEL. Nigerian Stored Product Research Institute, P.M.B.3032, Kano. ABSTRACT: Proximate study was conducted on four edible mushrooms commonly found in farmlands in.

  14. Proximate Sources of Collective Teacher Efficacy

    Science.gov (United States)

    Adams, Curt M.; Forsyth, Patrick B.

    2006-01-01

    Purpose: Recent scholarship has augmented Bandura's theory underlying efficacy formation by pointing to more proximate sources of efficacy information involved in forming collective teacher efficacy. These proximate sources of efficacy information theoretically shape a teacher's perception of the teaching context, operationalizing the difficulty…

  15. Phytochemical screening, proximate analysis and anticonvulsant ...

    African Journals Online (AJOL)

    Spigelia anthelmia is used traditionally in Southern Nigeria for the treatment of infant convulsion and epilepsy. This study investigated the phytochemical constituents, proximate analysis and anticonvulsant effect of the methanolic extract of Spigelia anthelmia. Phytochemical evaluation and proximate analysis was carried ...

  16. Intramedullary compression device for proximal ulna fracture.

    Science.gov (United States)

    Hong, Choon Chiet; Han, Fucai; Decruz, Joshua; Pannirselvam, Vinodhkumar; Murphy, Diarmuid

    2015-02-01

    Proximal ulna fractures account for 20% of all proximal forearm fractures. Many treatment options are available for such fractures, such as cast immobilisation, plate and screw fixation, tension band wiring and intramedullary screw fixation, depending on the fracture pattern. Due to the subcutaneous nature of the proximal forearm, it is vulnerable to open injuries over the dorsal aspect of the proximal ulna. This may in turn prove challenging, as it is critical to obtain adequate soft tissue coverage to reduce the risk of implant exposure and bony infections. We herein describe a patient with a Gustillo III-B open fracture of the proximal ulna, treated with minimally invasive intramedullary screw fixation using a 6.0-mm cannulated headless titanium compression screw (FusiFIX, Péronnas, France).

  17. Internationalization of regulatory requirements.

    Science.gov (United States)

    Juillet, Y

    2003-02-01

    The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

  18. Exploring spatially adjacent TFBS-clustered regions with Hi-C data.

    Science.gov (United States)

    Chen, Hebing; Jiang, Shuai; Zhang, Zhuo; Li, Hao; Lu, Yiming; Bo, Xiaochen

    2017-09-01

    Transcription factor binding sites (TFBSs) are clustered in the human genome, forming the TFBS-clustered regions that regulate gene transcription, which requires dynamic chromatin configurations between promoters and distal regulatory elements. Here, we propose a regulatory model called spatially adjacent TFBS-clustered regions (SATs), in which TFBS-clustered regions are connected by spatial proximity as identified by high-resolution Hi-C data. TFBS-clustered regions forming SATs appeared less frequently in gene promoters than did isolated TFBS-clustered regions, whereas SATs as a whole appeared more frequently. These observations indicate that multiple distal TFBS-clustered regions combined to form SATs to regulate genes. Further examination confirmed that a substantial portion of genes regulated by SATs were located between the paired TFBS-clustered regions instead of the downstream. We reconstructed the chromosomal conformation of the H1 human embryonic stem cell line using the ShRec3D algorithm and proposed the SAT regulatory model. ylu.phd@gmail.com or boxc@bmi.ac.cn. Supplementary data are available at Bioinformatics online.

  19. A study of the association between chronic superficial keratitis and polymorphisms in the upstream regulatory regions of DLA-DRB1, DLA-DQB1 and DLA-DQA1.

    Science.gov (United States)

    Barrientos, Laura S; Zapata, Gustavo; Crespi, Julian A; Posik, Diego M; Díaz, Silvina; It, Veronica; Peral-García, Pilar; Giovambattista, Guillermo

    2013-12-15

    Canine chronic superficial keratitis (CSK) is an inflammatory corneal disease that primarily occurs in German shepherd dogs (GSDs). Several studies support the hypothesis that CSK is an immune-mediated disease. To investigate the genetic factors associated with CSK development, the upstream regulatory regions (URRs) of the DLA-DRB, -DQA and -DQB genes were genotyped in 60 dogs, including 32 CSK animals. LD analysis identified two blocks (r(2)≤45), with two DLA-DRB1 and five DLA-DQB1 haplotypes. Analysis of DLA-URR alleles/haplotypes showed a significant association between DQB1*-154 [C/T] (p=0.016) and CSK, suggesting that the T variant may increase the risk for developing CSK disease (OR=3, 95% CI=1.25-7.68). When haplotype associations were performed, the URR-DQB*CATT haplotype was significantly associated with CSK (p=0.016), increasing the risk of develop this disease over two-fold (OR=3, 95%, CI=1.25-7.68). These results showed that dogs homozygous at DRB1*69 [C/T] had a risk for developing CSK disease that was over four times the risk for heterozygotes. This genetic association supports the previous clinical, histological and pharmacological studies that suggest that CSK is an immune-mediated disease, and this association could potentially be used to identify susceptible animals. © 2013 Elsevier B.V. All rights reserved.

  20. 3 CFR - Regulatory Review

    Science.gov (United States)

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Regulatory Review Presidential Documents Other Presidential Documents Memorandum of January 30, 2009 Regulatory Review Memorandum for the Heads of Executive Departments and Agencies For well over two decades, the Office of Information and Regulatory Affairs (OIRA) at...

  1. Proximal Alternating Direction Method with Relaxed Proximal Parameters for the Least Squares Covariance Adjustment Problem

    Directory of Open Access Journals (Sweden)

    Minghua Xu

    2014-01-01

    Full Text Available We consider the problem of seeking a symmetric positive semidefinite matrix in a closed convex set to approximate a given matrix. This problem may arise in several areas of numerical linear algebra or come from finance industry or statistics and thus has many applications. For solving this class of matrix optimization problems, many methods have been proposed in the literature. The proximal alternating direction method is one of those methods which can be easily applied to solve these matrix optimization problems. Generally, the proximal parameters of the proximal alternating direction method are greater than zero. In this paper, we conclude that the restriction on the proximal parameters can be relaxed for solving this kind of matrix optimization problems. Numerical experiments also show that the proximal alternating direction method with the relaxed proximal parameters is convergent and generally has a better performance than the classical proximal alternating direction method.

  2. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

    Science.gov (United States)

    Glinsky, Gennadi V

    2016-09-19

    Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of

  3. The Life Saving Effects of Hospital Proximity

    DEFF Research Database (Denmark)

    Bertoli, Paola; Grembi, Veronica

    We assess the lifesaving effect of hospital proximity using data on fatality rates of road-traffic accidents. While most of the literature on this topic is based on changes in distance to the nearest hospital triggered by hospital closures and use OLS estimates, our identification comes from......) increases the fatality rate by 13.84% on the sample average. This is equal to a 0.92 additional death per every 100 accidents. We show that OLS estimates provide a downward biased measure of the real effect of hospital proximity because they do not fully solve spatial sorting problems. Proximity matters...

  4. Copper in silicon: Quantitative analysis of internal and proximity gettering

    Energy Technology Data Exchange (ETDEWEB)

    McHugo, S.A. [Lawrence Berkeley National Lab., CA (United States); Flink, C.; Weber, E.R. [Univ. of California, Berkeley, CA (United States)] [and others

    1997-08-01

    The behavior of copper in the presence of a proximity gettering mechanism and a standard internal gettering mechanism in silicon was studied. He implantation-induced cavities in the near surface region were used as a proximity gettering mechanism and oxygen precipitates in the bulk of the material provided internal gettering sites. Moderate levels of copper contamination were introduced by ion implantation such that the copper was not supersaturated during the anneals, thus providing realistic copper contamination/gettering conditions. Copper concentrations at cavities and internal gettering sites were quantitatively measured after the annealings. In this manner, the gettering effectiveness of cavities was measured when in direct competition with internal gettering sites. The cavities were found to be the dominant gettering mechanism with only a small amount of copper gettered at the internal gettering sites. These results reveal the benefits of a segregation-type gettering mechanism for typical contamination conditions.

  5. The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity.

    Directory of Open Access Journals (Sweden)

    Slavé Petrovski

    2015-09-01

    Full Text Available Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene's proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS, termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene's regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1 genes that are known to cause disease through haploinsufficiency, 2 genes curated as dosage sensitive in ClinGen's Genome Dosage Map, 3 genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4 genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding

  6. The Effect of Cement Placement on Augmentation of the Osteoporotic Proximal Femur

    OpenAIRE

    Sutter, Edward G.; Wall, Simon J.; Mears, Simon C; Belkoff, Stephen M.

    2010-01-01

    Femoroplasty, the augmentation of the proximal femur, has been shown in biomechanical studies to increase the energy required to produce a fracture and therefore may reduce the risk of such injuries. The purpose of our study was to test the hypotheses that: (1) 15 mL of cement was sufficient to mechanically augment the proximal femur, (2) there was no difference in augmentation effect between cement placement in the intertrochanteric region and in the femoral neck, and (3) cement placement in...

  7. Does Proximity Matter for Knowledge Transfer from Public Institutes and Universities to Firms?

    OpenAIRE

    Anthony Arundel; Aldo Geuna

    2001-01-01

    'National Innovation Systems' theories are built upon the assumption that linkages among organisations matter to innovation. Specifically, proximity is a crucial factor in most of the explanations of regional innovation systems. Yet several thing, such as the rapid growth of the internet and email, suggest that the role of proximity could be breaking down, particularly for large firms with the financial resources to seek out knowledge anywhere in the world.However, the need to access tacit kn...

  8. Proximity and Collaboration in European Nanotechnology

    NARCIS (Netherlands)

    Cunningham, S.W.; Werker, C.

    2011-01-01

    Collaborations are particularly important for the development and deployment of technology. We analyze the influence of organizational, technological and geographical proximity on European nanotechnology collaborations with the help of a publication dataset and additional geographical information.

  9. Promoting proximal formative assessment with relational discourse

    Science.gov (United States)

    Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.

    2012-02-01

    The practice of proximal formative assessment - the continual, responsive attention to students' developing understanding as it is expressed in real time - depends on students' sharing their ideas with instructors and on teachers' attending to them. Rogerian psychology presents an account of the conditions under which proximal formative assessment may be promoted or inhibited: (1) Normal classroom conditions, characterized by evaluation and attention to learning targets, may present threats to students' sense of their own competence and value, causing them to conceal their ideas and reducing the potential for proximal formative assessment. (2) In contrast, discourse patterns characterized by positive anticipation and attention to learner ideas increase the potential for proximal formative assessment and promote self-directed learning. We present an analysis methodology based on these principles and demonstrate its utility for understanding episodes of university physics instruction.

  10. Ammonia transport in the proximal tubule.

    Science.gov (United States)

    Hamm, L L; Simon, E E

    1990-01-01

    The transport of ammonia in the proximal tubule is a complex interaction of a number of processes. Ammonia transport in the proximal tubule is clearly bidirectional; ammonia is secreted into the early proximal tubule lumen, but later in the proximal tubule, efflux out of the lumen may result in net ammonia reabsorption. Two mechanisms of ammonia transport have clearly been established: NH3 diffusion and NH4+ transport on the Na(+)-H+ exchanger. The relative contribution of these pathways to ammonia transport is still unsettled. Other pathways for ammonia transport, particularly NH4+ efflux out of the lumen, may be important as well. A variety of factors may modulate ammonia transport: plasma, cell and luminal pH, luminal flow rate, luminal potassium, and angiotensin II. Each of these factors also alters ammonia production rates and in most circumstances, ammonia transport appears to follow ammonia production rates.

  11. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

    DWB) for raw and fried samples, respectively, but decreased to 295.20 ... Key words: Rhynchophorus phoenicis, Oryctes monoceros, proximate composition, cholesterol, heat treatment. INTRODUCTION. Insects have played ...

  12. COMPARATIVE ANALYSIS OF PROXIMATE COMPOSITIONS OF ...

    African Journals Online (AJOL)

    Babatunde Emmanuel

    2011-10-06

    Oct 6, 2011 ... Fish allows for protein improved nutrition in that it has a high biological value in terms of high ... marine algae upon which the fish feed [11]. ... Proximate composition of catfish Clarias gariepinus and Tarpon atlanticus were.

  13. Phytochemical screening, proximate analysis and acute toxicity ...

    African Journals Online (AJOL)

    Phytochemical screening, proximate analysis and acute toxicity studies were carried out on the leaf extract of Cola lepidota, in accordance with established standard procedures. The proximate analysis reveals a moisture content of 27.43 ± 3.11 % w/w, total ash value 9.32 ± 0.27 % w/w, acid insoluble ash 3.12 ± 1.05 % w/w ...

  14. Proximate, Mineral and Phytochemical Composition of Dioscorea ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: Proximate, mineral and phytochemical composition of Dioscorea dumetorum tubers was investigated using standard procedures. Proximate analysis included in g% dry weight: crude protein (6.44 ± 0.32), crude fat (0.75 ± 0.04), crude fibre (15.00 ± 0.56), total ash. (3.45 ± 0.20) and a moisture content of 70.04 ...

  15. Painful Spastic Hip Dislocation: Proximal Femoral Resection

    OpenAIRE

    Albiñana, Javier; Gonzalez-Moran, Gaspar

    2002-01-01

    The dislocated hip in a non-ambulatory child with spastic paresis tends to be a painful interference to sleep, sitting upright, and perineal care. Proximal femoral resection-interposition arthroplasty is one method of treatment for this condition. We reviewed eight hips, two bilateral cases, with a mean follow-up of 30 months. Clinical improvement was observed in all except one case, with respect to pain relief and sitting tolerance. Some proximal migration was observed in three cases, despit...

  16. Proximity sensor system development. CRADA final report

    Energy Technology Data Exchange (ETDEWEB)

    Haley, D.C. [Oak Ridge National Lab., TN (United States); Pigoski, T.M. [Merrit Systems, Inc. (United States)

    1998-01-01

    Lockheed Martin Energy Research Corporation (LMERC) and Merritt Systems, Inc. (MSI) entered into a Cooperative Research and Development Agreement (CRADA) for the development and demonstration of a compact, modular proximity sensing system suitable for application to a wide class of manipulator systems operated in support of environmental restoration and waste management activities. In teleoperated modes, proximity sensing provides the manipulator operator continuous information regarding the proximity of the manipulator to objects in the workspace. In teleoperated and robotic modes, proximity sensing provides added safety through the implementation of active whole arm collision avoidance capabilities. Oak Ridge National Laboratory (ORNL), managed by LMERC for the United States Department of Energy (DOE), has developed an application specific integrated circuit (ASIC) design for the electronics required to support a modular whole arm proximity sensing system based on the use of capacitive sensors developed at Sandia National Laboratories. The use of ASIC technology greatly reduces the size of the electronics required to support the selected sensor types allowing deployment of many small sensor nodes over a large area of the manipulator surface to provide maximum sensor coverage. The ASIC design also provides a communication interface to support sensor commands from and sensor data transmission to a distributed processing system which allows modular implementation and operation of the sensor system. MSI is a commercial small business specializing in proximity sensing systems based upon infrared and acoustic sensors.

  17. Transformations through Proximity Flying: A Phenomenological Investigation

    Science.gov (United States)

    Holmbom, Maria; Brymer, Eric; Schweitzer, Robert D.

    2017-01-01

    Participation in extreme sports has been linked to personal transformations in everyday life. Descriptions of lived experience resulting from transformative experiences are limited. Proximity flying, a relatively new discipline involving BASE jumping with a wingsuit where participants fly close to solid structures, is arguably one of the most extreme of extreme sports. The aim of this paper, part of a larger phenomenological study on the lived experience of proximity flying, is to explicate the ways in which participating in proximity flying influences the everyday lives of participants. Interpretative phenomenological analysis was used to explicate the lived experience of six proximity pilots. An analysis of interview transcripts revealed three significant themes describing the lived experience of participants. First, experiences of change were described as positive and skills developed through proximity flying were transferable into everyday life. Second, transformative experiences were considered fundamental to participants’ perspectives on life. Third, experience of transformation influenced their sense of personal identity and facilitated flourishing in other aspects of everyday life. Participants were clear that their experiences in proximity flying facilitated a profound process of transformation which manifest as changes in everyday capabilities and behaviors, values and sense of identity. PMID:29104552

  18. Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility.

    Science.gov (United States)

    Cukier, Holly N; Skaar, David A; Rayner-Evans, Melissa Y; Konidari, Ioanna; Whitehead, Patrice L; Jaworski, James M; Cuccaro, Michael L; Pericak-Vance, Margaret A; Gilbert, John R

    2009-10-01

    Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint ( approximately 108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation.

  19. Treatment of three- and four-part proximal humeral fractures with locking proximal humerus plate.

    Science.gov (United States)

    Sun, Jing-Cheng; Li, Yu-Lin; Ning, Guang-Zhi; Wu, Qiang; Feng, Shi-Qing

    2013-08-01

    The purpose of this study was to evaluate the effectiveness and complications of the locking proximal humerus plate to treat proximal humerus fractures. A retrospective clinical trial. Department of Orthopaedics, Tianjin Medical University General Hospital. Sixty-eight consecutive patients with three- or four-part fractures of the proximal humerus were treated with locking proximal humerus plates. The deltopectoral anterolateral acromial approach was used to the proximal humerus; open reduction and locking proximal humerus plate were applied. Constant Score was used to measure the shoulder functional recovery, and Visual Analog Scale (VAS) was used to measure subjective evaluation of pain. The radiology was observed. After average 26.7 months, the average Constant Score was 72.6 ± 13.2 points and the average VAS was 1.2 ± 0.8 points. All the complications such as screw perforation into the glenohumeral joint, screws loosening, soft tissue infections, avascular necrosis and delayed union occurred in eight cases (11.8 %). The effectiveness of the locking proximal humerus plate was similar to other published literatures on treating fractures of the proximal humerus; however, a lower complications rate in short follow-up time was observed in this study. It may potentially provide a favorable option for treating three- or four-part fractures of the proximal humerus. Dealing with each particular fracture pattern, surgeons should have a decision of appropriate way to internal fixation.

  20. Regulatory Information By Sector

    Science.gov (United States)

    Find environmental regulatory, compliance, & enforcement information for various business, industry and government sectors, listed by NAICS code. Sectors include agriculture, automotive, petroleum manufacturing, oil & gas extraction & other manufacturing

  1. Transverse Stress Fracture of the Proximal Patella: A Case Report.

    Science.gov (United States)

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu

    2016-02-01

    Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year-old athlete.A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity.Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90°, so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90°, during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws.

  2. An upstream regulatory element confers orientation-independent enhancement of the TSG101 promoter activity in transformed cells.

    Science.gov (United States)

    Hsu, Shih-Fang; Goan, Yih-Gang; Tsai, Hsien-Yu; Lin, Yi-Ru; Liu, Rue-Tsuan; Cheng, Jiin-Tsuey

    2012-01-01

    Tumor susceptibility gene 101 (TSG101), a mammalian homologue of yeast vps23, is involved in protein sorting, vesicular trafficking and maintenance of genomic integrity. Upregulation of the TSG101 gene was found in human thyroid papillary and breast tumors. Here, we define the proximal promoter of human TSG101 at -1 to -436 by reporter assay. Intact Sp1 and MAZ binding sequences within this region are essential, and mutation of both sites eliminates proximal promoter activity implying cooperation between these two cis-elements. Chromatin immunoprecipitation and DNA affinity precipitation assay confirmed in vivo Sp1 binding on the GGGGCGGGTT sequence. MAZ protein was essential for TSG101 promoter activity because its knockdown using siRNA decreased reporter activity. An upstream regulatory element (URE) at the -1280 to -1757 region was identified to confer the orientation-independent enhancement of the promoter activity in transformed COS-1, ARO and WRO cell lines but not in a normal thyroid FRTL cell line. The sequence of this URE region contains putative binding sites for thyroid transcription factor 2 (TTF-2) and thyroid hormone receptor (T3R), which might be relevant to differential regulation of TSG101 promoter activity in transformed and primary cells.

  3. Factors affecting minority population proximity to hazardous facilities

    Energy Technology Data Exchange (ETDEWEB)

    Nieves, L.A. [Argonne National Lab., IL (United States); Nieves, A.L. [Wheaton Coll., IL (United States)]|[Argonne National Lab., IL (United States)

    1995-04-01

    Disproportionate exposure of minority groups to environmental hazards has been attributed to ``environmental racism`` by some authors, without systematic investigation of the factors underlying this exposure pattern. This study examines regional differences in the proximity of African-Americans, Hispanics, Asians, and non-Hispanic Whites to a broad range of facility types and explores the effects of urban and income factors. A statistically significant inverse relationship is found between the percentage of non-Hispanic Whites and virtually all facility categories in all regions. Except for Hispanics in the South, all such associations for minority groups show a direct relationship, though some are nonsignificant. The geographic concentration of facilities is more closely tied to urbanization than to economic factors. Controlling for both urban and economic factors, minority population concentration is still a significant explanatory variable for some facility types in some regions. This finding is most consistent for African-Americans.

  4. Locking plate fixation for proximal humerus fractures.

    LENUS (Irish Health Repository)

    Burke, Neil G

    2012-02-01

    Locking plates are increasingly used to surgically treat proximal humerus fractures. Knowledge of the bone quality of the proximal humerus is important. Studies have shown the medial and dorsal aspects of the proximal humeral head to have the highest bone strength, and this should be exploited by fixation techniques, particularly in elderly patients with osteoporosis. The goals of surgery for proximal humeral fractures should involve minimal soft tissue dissection and achieve anatomic reduction of the head complex with sufficient stability to allow for early shoulder mobilization. This article reviews various treatment options, in particular locking plate fixation. Locking plate fixation is associated with a high complication rate, such as avascular necrosis (7.9%), screw cutout (11.6%), and revision surgery (13.7%). These complications are frequently due to the varus deformation of the humeral head. Strategic screw placement in the humeral head would minimize the possibility of loss of fracture reduction and potential hardware complications. Locking plate fixation is a good surgical option for the management of proximal humerus fractures. Complications can be avoided by using better bone stock and by careful screw placement in the humeral head.

  5. The effect of geographical proximity on scientific cooperation among Chinese cities from 1990 to 2010.

    Directory of Open Access Journals (Sweden)

    Haitao Ma

    Full Text Available The relations between geographical proximity and spatial distance constitute a popular topic of concern. Thus, how geographical proximity affects scientific cooperation, and whether geographically proximate scientific cooperation activities in fact exhibit geographic scale features should be investigated.Selected statistics from the ISI database on cooperatively authored papers, the authors of which resided in 60 typical cites in China, and which were published in the years 1990, 1995, 2000, 2005, and 2010, were used to establish matrices of geographic distance and cooperation levels between cities. By constructing a distance-cooperation model, the degree of scientific cooperation based on spatial distance was calculated. The relationship between geographical proximity and scientific cooperation, as well as changes in that relationship, was explored using the fitting function.(1 Instead of declining, the role of geographical proximity in inter-city scientific cooperation has increased gradually but significantly with the popularization of telecommunication technologies; (2 the relationship between geographical proximity and scientific cooperation has not followed a perfect declining curve, and at certain spatial scales, the distance-decay regularity does not work; (3 the Chinese scientific cooperation network gathers around different regional center cities, showing a trend towards a regional network; within this cooperation network the amount of inter-city cooperation occurring at close range increased greatly.The relationship between inter-city geographical distance and scientific cooperation has been enhanced and strengthened over time.

  6. The effect of geographical proximity on scientific cooperation among Chinese cities from 1990 to 2010.

    Science.gov (United States)

    Ma, Haitao; Fang, Chuanglin; Pang, Bo; Li, Guangdong

    2014-01-01

    The relations between geographical proximity and spatial distance constitute a popular topic of concern. Thus, how geographical proximity affects scientific cooperation, and whether geographically proximate scientific cooperation activities in fact exhibit geographic scale features should be investigated. Selected statistics from the ISI database on cooperatively authored papers, the authors of which resided in 60 typical cites in China, and which were published in the years 1990, 1995, 2000, 2005, and 2010, were used to establish matrices of geographic distance and cooperation levels between cities. By constructing a distance-cooperation model, the degree of scientific cooperation based on spatial distance was calculated. The relationship between geographical proximity and scientific cooperation, as well as changes in that relationship, was explored using the fitting function. (1) Instead of declining, the role of geographical proximity in inter-city scientific cooperation has increased gradually but significantly with the popularization of telecommunication technologies; (2) the relationship between geographical proximity and scientific cooperation has not followed a perfect declining curve, and at certain spatial scales, the distance-decay regularity does not work; (3) the Chinese scientific cooperation network gathers around different regional center cities, showing a trend towards a regional network; within this cooperation network the amount of inter-city cooperation occurring at close range increased greatly. The relationship between inter-city geographical distance and scientific cooperation has been enhanced and strengthened over time.

  7. Industrial Computed Tomography using Proximal Algorithm

    KAUST Repository

    Zang, Guangming

    2016-04-14

    In this thesis, we present ProxiSART, a flexible proximal framework for robust 3D cone beam tomographic reconstruction based on the Simultaneous Algebraic Reconstruction Technique (SART). We derive the proximal operator for the SART algorithm and use it for minimizing the data term in a proximal algorithm. We show the flexibility of the framework by plugging in different powerful regularizers, and show its robustness in achieving better reconstruction results in the presence of noise and using fewer projections. We compare our framework to state-of-the-art methods and existing popular software tomography reconstruction packages, on both synthetic and real datasets, and show superior reconstruction quality, especially from noisy data and a small number of projections.

  8. Correlation between social proximity and mobility similarity.

    Science.gov (United States)

    Fan, Chao; Liu, Yiding; Huang, Junming; Rong, Zhihai; Zhou, Tao

    2017-09-20

    Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

  9. [Disorders of sex development and proximal hypospadias].

    Science.gov (United States)

    Oswald, J

    2016-01-01

    Children with ambiguous genitalia due to different chromosome or gonadal sex are a particular challenge concerning the diagnostic and therapeutic implications. Proximal hypospadias patients with normal gonadal development should be distinguished from children with DSD (disorders of sex development) to guarantee normal gender identity and the best possible surgical therapy. This paper focuses on the terminology, embryology, and pathophysiology of the different manifestations of DSD. The state of knowledge about this disease pattern with particular emphasis on proximal hypospadias based on national and international scientific discussions is presented. The different clinical pictures as well as therapeutic options of DSD with a special focus on recent literature and giving particular attention to patients with proximal hypospadias are presented. Because of the complexity of patients suffering from disorders of sex development an interdisciplinary DSD healthcare team including a paediatric endocrinologist as well as paediatric urologist should be provided. These specialists enable an accurate diagnosis in severe hypospadias patients without reference to DSD diseases patterns.

  10. Infiltrating/sealing proximal caries lesions

    DEFF Research Database (Denmark)

    Martignon, S; Ekstrand, K R; Gomez, J

    2012-01-01

    This randomized split-mouth controlled clinical trial aimed at assessing the therapeutic effects of infiltration vs. sealing for controlling caries progression on proximal surfaces. Out of 90 adult students/patients assessed at university clinics and agreeing to participate, 39, each with 3...... differences in lesion progression between infiltration and placebo (P = 0.0012) and between sealing and placebo (P = 0.0269). The study showed that infiltration and sealing are significantly better than placebo treatment for controlling caries progression on proximal lesions. No significant difference...... proximal lesions identified radiographically around the enamel-dentin junction to the outer third of the dentin, were included. Lesions were randomly allocated for treatment to test-A (Infiltration: ICON-pre-product; DMG), test-B (Sealing: Prime-Bond-NT; Dentsply), or control-C (Placebo). Primary outcome...

  11. Knowledge networks in the Dutch aviation industry: The proximity paradox

    NARCIS (Netherlands)

    Broekel, T.; Boschma, R.A.

    2012-01-01

    The importance of geographical proximity for interaction and knowledge sharing has been discussed extensively in recent years. There is increasing consensus that geographical proximity is just one out of many types of proximities that might be relevant. We argue that proximity may be a crucial

  12. The developmental spectrum of proximal radioulnar synostosis

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Alison M. [University of Manitoba, Winnipeg Regional Health Association Program of Genetics and Metabolism, Winnipeg, MB (Canada); University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, WRHA Program of Genetics and Metabolism, Departments of Paediatrics and Child Health, Biochemistry and Medical Genetics, Winnipeg, MB (Canada); Kibria, Lisa [University of Manitoba, Department of School of Medical Rehabilitation, Winnipeg, MB (Canada); Reed, Martin H. [University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, Department of Diagnostic Imaging, Winnipeg, MB (Canada)

    2010-01-15

    Proximal radioulnar synostosis is a rare upper limb malformation. The elbow is first identifiable at 35 days (after conception), at which stage the cartilaginous anlagen of the humerus, radius and ulna are continuous. Subsequently, longitudinal segmentation produces separation of the distal radius and ulna. However, temporarily, the proximal ends are united and continue to share a common perichondrium. We investigated the hypothesis that posterior congenital dislocation of the radial head and proximal radioulnar fusion are different clinical manifestations of the same primary developmental abnormality. Records were searched for ''proximal radioulnar fusion/posterior radial head dislocation'' in patients followed at the local Children's Hospital and Rehabilitation Centre for Children. Relevant radiographic, demographic and clinical data were recorded. Ethics approval was obtained through the University Research Ethics Board. In total, 28 patients met the inclusion criteria. The majority of patients (16) had bilateral involvement; eight with posterior dislocation of the radial head only; five had posterior radial head dislocation with radioulnar fusion and two had radioulnar fusion without dislocation. One patient had bilateral proximal radioulnar fusion and posterior dislocation of the left radial head. Nine patients had only left-sided involvement, and three had only right-sided involvement.The degree of proximal fusion varied, with some patients showing 'complete' proximal fusion and others showing fusion that occurred slightly distal to the radial head: 'partially separated.' Associated disorders in our cohort included Poland syndrome (two patients), Cornelia de Lange syndrome, chromosome anomalies (including tetrasomy X) and Cenani Lenz syndactyly. The suggestion of a developmental relationship between posterior dislocation of the radial head and proximal radioulnar fusion is supported by the fact that both anomalies

  13. The in vivo dissection of direct RFX-target gene promoters in C. elegans reveals a novel cis-regulatory element, the C-box.

    Science.gov (United States)

    Burghoorn, Jan; Piasecki, Brian P; Crona, Filip; Phirke, Prasad; Jeppsson, Kristian E; Swoboda, Peter

    2012-08-15

    At the core of the primary transcriptional network regulating ciliary gene expression in Caenorhabditis elegans sensory neurons is the RFX/DAF-19 transcription factor, which binds and thereby positively regulates 13-15 bp X-box promoter motifs found in the cis-regulatory regions of many ciliary genes. However, the variable expression of direct RFX-target genes in various sets of ciliated sensory neurons (CSNs) occurs through as of yet uncharacterized mechanisms. In this study the cis-regulatory regions of 41 direct RFX-target genes are compared using in vivo genetic analyses and computational comparisons of orthologous nematode sequences. We find that neither the proximity to the translational start site nor the exact sequence composition of the X-box promoter motif of the respective ciliary gene can explain the variation in expression patterns observed among different direct RFX-target genes. Instead, a novel enhancer element appears to co-regulate ciliary genes in a DAF-19 dependent manner. This cytosine- and thymidine-rich sequence, the C-box, was found in the cis-regulatory regions in close proximity to the respective X-box motif for 84% of the most broadly expressed direct RFX-target genes sampled in this study. Molecular characterization confirmed that these 8-11 bp C-box sequences act as strong enhancer elements for direct RFX-target genes. An artificial promoter containing only an X-box promoter motif and two of the C-box enhancer elements was able to drive strong expression of a GFP reporter construct in many C. elegans CSNs. These data provide a much-improved understanding of how direct RFX-target genes are differentially regulated in C. elegans and will provide a molecular model for uncovering the transcriptional network mediating ciliary gene expression in animals. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Method to measure tone of axial and proximal muscle.

    Science.gov (United States)

    Gurfinkel, Victor S; Cacciatore, Timothy W; Cordo, Paul J; Horak, Fay B

    2011-12-14

    The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention.

  15. Method to Measure Tone of Axial and Proximal Muscle

    Science.gov (United States)

    Gurfinkel, Victor S.; Cacciatore, Timothy W.; Cordo, Paul J.; Horak, Fay B.

    2011-01-01

    The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs1, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention. PMID:22214974

  16. Thumb proximal phalanx reconstruction with nonvascularized corticocancellous olecranon bone graft.

    Science.gov (United States)

    Soong, Maximillian

    2015-01-01

    Large segmental bone defects of the phalanges reportedly have been treated with free vascularized grafts from the hand, foot, or knee, or with nonvascularized grafts from the iliac crest. A nonvascularized structural corticocancellous graft from a local site would be advantageous. The olecranon has been used as a source of both cancellous and corticocancellous graft. The authors describe a unique case of the use of nonvascularized corticocancellous olecranon bone graft for structural purposes in a mutilating thumb injury. The patient injured the left thumb with a miter saw, resulting in a large degloving wound over a severely comminuted fracture of the proximal phalanx, with segmental bone loss between a base fragment and displaced condylar fragments. Provisional pin fixation was performed at the time of initial emergent irrigation and debridement, along with repairs of the extensor pollicis longus, radial digital nerve, and dorsal digital nerve. This was followed 3 weeks later by non-vascularized corticocancellous bone grafting from the olecranon to the proximal phalanx under regional anesthesia. The thumb was mobilized at 11 weeks, and solid union was radiographically confirmed at 6 months. The patient achieved moderate active range of motion and was able to return to work as a physical therapist. The elbow healed uneventfully and without pain or fracture at the donor site. This case shows that robust structural bone graft for the phalanges may be obtained from the nearby olecranon, under regional anesthesia, without microsurgery, and with potential advantages over the iliac crest. Copyright 2015, SLACK Incorporated.

  17. preliminary phytochemical screening, proximate and elemental

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the ...

  18. Proximate, mineral composition, antioxidant activity, and total ...

    African Journals Online (AJOL)

    Four varieties of the red pepper fruits (Capsicum species) were evaluated for chemical composition, antioxidant activity and total phenolic contents using standard analytical technique, ferric-ion reducing antioxidant potential (FRAP) assay and Folin-Colcalteau method respectively. The proximate composition values ...

  19. 9__43 - 50__Tijjani_Proximate

    African Journals Online (AJOL)

    User

    Sena et al., 1998). In Nigeria, the plant is commonly consumed by the Hausa speaking communities as a spice and a sauce (Ibrahim et al., 2012). However, during preparation the leaves and stem are not carefully separated before processing of food. Thus, the present study was aimed at evaluating the proximate, minerals ...

  20. Phytochemistry and proximate composition of ginger ( Zingiber ...

    African Journals Online (AJOL)

    ... a little crude fibre content of 0.92 %. The results indicated that ginger rhizome is an excellent natural remedy for a wide range of ailments. Keywords: Zingiber officinale, spice, rhizome, phytochemistry, proximate analysis, Zingiberaceae, zingerone, methanolic extraction. Journal of Pharmaceutical and Allied Sciences, Vol.

  1. DEPRESSIONARY EFFECT OF PROXIMITY OF RESIDENTIAL ...

    African Journals Online (AJOL)

    Osondu

    2012-10-24

    Oct 24, 2012 ... opinions are analyzed and it revealed that the site has major impacts on the residents perceived quality of life, security and ... Key words: Landfill, Property value, Health and safety, Residential property, Solous. Introduction. The location ... Proximity to landfills and hazardous waste sites can severely affect ...

  2. Renal fibrosis: Primacy of the proximal tubule.

    Science.gov (United States)

    Gewin, Leslie S

    2018-02-06

    Tubulointerstitial fibrosis (TIF) is the hallmark of chronic kidney disease and best predictor of renal survival. Many different cell types contribute to TIF progression including tubular epithelial cells, myofibroblasts, endothelia, and inflammatory cells. Previously, most of the attention has centered on myofibroblasts given their central importance in extracellular matrix production. However, emerging data focuses on how the response of the proximal tubule, a specialized epithelial segment vulnerable to injury, plays a central role in TIF progression. Several proximal tubular responses such as de-differentiation, cell cycle changes, autophagy, and metabolic changes may be adaptive initially, but can lead to maladaptive responses that promote TIF both through autocrine and paracrine effects. This review discusses the current paradigm of TIF progression and the increasingly important role of the proximal tubule in promoting TIF both in tubulointerstitial and glomerular injuries. A better understanding and appreciation of the role of the proximal tubule in TIF has important implications for therapeutic strategies to halt chronic kidney disease progression. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  3. 182 179 Comparative Study on the Proximate

    African Journals Online (AJOL)

    2008-12-02

    Dec 2, 2008 ... Key words: Annona squamosa, Fruits, Proximate, Minerals, nutrient density. INTRODUCTION. Sugar apple (Annona squamosa) also called. “Gwanda masar” in Hausa belong to the family. Annonacae. The most widely grown of all the species are A. muricata, A. cherimola, A reticulata, A. senegalensis and ...

  4. Phytochemical Screening, Proximate and Mineral Composition of ...

    African Journals Online (AJOL)

    Leaves of sweet potato (Ipomoea batatas) grown in Tepi area was studied for their class of phytochemicals, mineral and proximate composition using standard analytical methods. The phytochemical screening revealed the presence of alkaloids, flavonoid, terpenoids, saponins, quinones, phenol, tannins, amino acid and ...

  5. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Citrus sinensis was screened for its phytochemical composition and was evaluated for the proximate and elemental analysis. The phytochemical analysis indicated the presence of reducing sugar, saponins, cardiac glycosides, tannins and flavonoids. The elemental analysis indicated the presence of the following mineral ...

  6. Phytochemical Screening and Proximate Analysis of Newbouldia ...

    African Journals Online (AJOL)

    The study was conducted to assess the phytochemical and proximate composition of Newboudia laevis leaves and Allium sativum bulb extracts. The leaves and bulbs extracts were analyzed for their chemical composition and antinutritional factors (ANFs) which include moisture, crude protein, crude fat, crude fiber, total ash ...

  7. Disability occurrence and proximity to death

    NARCIS (Netherlands)

    Klijs, Bart; Mackenbach, Johan P.; Kunst, Anton E.

    2010-01-01

    Purpose. This paper aims to assess whether disability occurrence is related more strongly to proximity to death than to age. Method. Self reported disability and vital status were available from six annual waves and a subsequent 12-year mortality follow-up of the Dutch GLOBE longitudinal study.

  8. [Four family members with proximal myotonic myopathy

    NARCIS (Netherlands)

    Tieleman, A.A.; Velden, M.P. van der; Visser, M.C.; Wokke, J.H.J.; Scheffer, H.; Engelen, B.G.M. van

    2004-01-01

    A 41-year-old woman had a 15-year history of pain in her thighs and arms, which also became weaker, and a decrease in visual acuity. Her 35-year-old brother, their 38-year-old sister and their 64-year-old mother also had myalgia, myotonia and proximal muscle weakness, and the women also had

  9. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    ... was about 0.01 in concentration. Proximate analysis also shows that it has a high nutritional value such as carbohydrate, fibre, Ash, fat and protein. These results recommended the consumption of these peels of desired physiochemical properties as sources of food fibres or low-calorie bulk ingredients in food applications ...

  10. Proximate composition and consumer acceptability of African ...

    African Journals Online (AJOL)

    The aim of the study was to assess the organoleptic differences of Clarias gariepinus smoked with two different energy sources, Anogeissus leiocarpus and Tamarindus indica with the help of a hedonic scale and to determine possible proximate composition difference between the smoked products. Smoking of the fishes ...

  11. Controllable proximity effect in superconducting hybrid devices

    NARCIS (Netherlands)

    Bakurskiy, S.V.

    2015-01-01

    This thesis is devoted to the study of controllable proximity effects in superconductors, both in terms of fundamental aspects and applications. As a part of this thesis theoretical description was suggested for a number of structures with superconducting electrodes and multiple interlayers. These

  12. Proximate, chemical compositions and sulphur concentrations on ...

    African Journals Online (AJOL)

    0, 10, 20, 50, 100, 150, 200, 250 and 300 ppm) on the nutritional value and the proximate composition of six selected mango cultivars (Tommy Atkins, Peach, Saber, Sunshine, Keitt and Vhavenda) grown in South Africa. The study shows that ...

  13. Proximate composition, bread characteristics and sensory ...

    African Journals Online (AJOL)

    This study was carried out to investigate proximate composition, bread characteristics and sensory evaluation of cocoyam-wheat composite breads at different levels of cocoyam flour substitution for human consumption.A whole wheat bread (WWB) and cocoyam-composite breads (CCB1,CCB 2 and CCB 3) were prepared ...

  14. Evaluation of the Proximate, Chemical and Phytochemical ...

    African Journals Online (AJOL)

    The increased interest in the utilization of the leaves of Moringa oleifera necessitated this study which evaluated the proximate, chemical and phytochemical composition, especially the presence of anti- physiological and toxic factors in the leaves. The results of the phytochemical analyses were: alkaloid 1.24 ± 0.141%; ...

  15. comparative proximate composition and antioxidant vitamins

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The proximate composition and antioxidant vitamins analysis of two varieties of honey (dark amber and light amber) were carried out using standard methods. The values for moisture, ash, crude lipid, crude protein and crude carbohydrate contents of the two honeys, (light amber and dark amber) are 9.39 ...

  16. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    Proximate composition and cholesterol concentrations of Rhynchophorus phoenicis and Oryctes monoceros larvae subjected to different heat treatments. ... 514.63 mg/100g dry weight basis (DWB) for raw and fried samples, respectively, but decreased to 295.20 mg/100 g DWB in the smoke-dried samples. Similarly, the ...

  17. Preliminary Phytochemical Screening, Elemental and Proximate ...

    African Journals Online (AJOL)

    The study aimed at phytochemical screening, elemental and proximate composition of two varieties of Cyperus esculentus (tiger nut) big yellow and small brown nuts using standard methods. The phytochemicals tested for were alkaloid, saponin, tannin, glycoside, flavonoid, steroid and resin. All the aforementioned ...

  18. Protein biomarker validation via proximity ligation assays.

    Science.gov (United States)

    Blokzijl, A; Nong, R; Darmanis, S; Hertz, E; Landegren, U; Kamali-Moghaddam, M

    2014-05-01

    The ability to detect minute amounts of specific proteins or protein modifications in blood as biomarkers for a plethora of human pathological conditions holds great promise for future medicine. Despite a large number of plausible candidate protein biomarkers published annually, the translation to clinical use is impeded by factors such as the required size of the initial studies, and limitations of the technologies used. The proximity ligation assay (PLA) is a versatile molecular tool that has the potential to address some obstacles, both in validation of biomarkers previously discovered using other techniques, and for future routine clinical diagnostic needs. The enhanced specificity of PLA extends the opportunities for large-scale, high-performance analyses of proteins. Besides advantages in the form of minimal sample consumption and an extended dynamic range, the PLA technique allows flexible assay reconfiguration. The technology can be adapted for detecting protein complexes, proximity between proteins in extracellular vesicles or in circulating tumor cells, and to address multiple post-translational modifications in the same protein molecule. We discuss herein requirements for biomarker validation, and how PLA may play an increasing role in this regard. We describe some recent developments of the technology, including proximity extension assays, the use of recombinant affinity reagents suitable for use in proximity assays, and the potential for single cell proteomics. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2013.

  19. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Michael Horsfall

    2009). The aim of this study was to analyses the extract of. Citrus sinensis peels for the phytochemical, proximate and elemental composition. MATERIALS AND METHODS. Plant materials Fresh peels of Citrus sinensis were collected from Uselu market in Benin City, Edo. State, Nigeria. It was identified and authenticated by.

  20. Keldysh proximity action for disordered superconductors

    Indian Academy of Sciences (India)

    Abstract. We review a novel approach to the superconductive proximity effect in dis- ordered normal–superconducting (N–S) structures. The method is based on the multi- charge Keldysh action and is suitable for the treatment of interaction and fluctuation effects. As an application of the formalism, we study the subgap ...

  1. Goal-Proximity Decision-Making

    Science.gov (United States)

    Veksler, Vladislav D.; Gray, Wayne D.; Schoelles, Michael J.

    2013-01-01

    Reinforcement learning (RL) models of decision-making cannot account for human decisions in the absence of prior reward or punishment. We propose a mechanism for choosing among available options based on goal-option association strengths, where association strengths between objects represent previously experienced object proximity. The proposed…

  2. Study on the establishment of efficient plan for regulatory activities at NPPs

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hun; Son, Mun Gyu [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Kang, Chang Sun; Yun, Jeong Ik; Ko, Hyun Seok; Lee, Young Wook [Seoul National Univ., Seoul (Korea, Republic of)

    2001-03-15

    In-operation regulatory activities at sites are very important and it should be improved to cope with accidents efficiently and quickly. In case of site survey and safety regulatory inspection regulatory system based on not regulatory headquarter but site regional office should be constructed. In other words, safety assurance and pending problem management considering site situation are needed. In this study, regulatory system at Nuclear Power Plant sites all over the world were reviewed and effective regulatory system of Korea are suggested to maximize the efficiency of license and regulatory manpower and consider the interest of local government and residents.

  3. Effects of proximal and distal robot-assisted upper limb rehabilitation on chronic stroke recovery.

    Science.gov (United States)

    Mazzoleni, Stefano; Sale, Patrizio; Franceschini, Marco; Bigazzi, Samuele; Carrozza, Maria Chiara; Dario, Paolo; Posteraro, Federico

    2013-01-01

    To evaluate the effects of add-on distal upper limb robot-assisted treatment on the outcome of proximal regions. 64 chronic stroke patients divided into two groups participated in the study. Group A was assigned to the proximal robot-assisted rehabilitation, Group B to the proximal and distal. Shoulder/elbow subsection of Fugl-Meyer Assessment scale was collected for Group A, whereas for Group B wrist subsection was also collected. Motricity Index was used and a set of kinematic parameters was computed for both groups. A decrease in impairment after the treatment in both groups of patients (Group A: Shoulder/elbow FM p robot-assisted treatment in both groups; group B showed a greater improvement in velocity. Robotic treatment is effective to reduce motor impairment in chronic stroke patients even if distal training added to proximal segments in the Group B does not provide any incremental benefit to the proximal segments. It remains unclear if the effectiveness of robot-assisted treatment is directly related to the upper limb segment specifically treated and which order may lead to better outcome. Our study suggests that kinematic parameters should be computed in order to better clarify the role of distal training (wrist) on proximal segments (shoulder/elbow) as well.

  4. NRC regulatory initiatives

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, T.C. [Nuclear Regulatory Commission (United States)

    1989-11-01

    The US Nuclear Regulatory Commission (NRC) is addressing several low-level waste disposal issues that will be important to waste generators and to States and Compacts developing new disposal capacity. These issues include Greater-Than-Class C (GTCC) waste, mixed waste, below regulatory concern (BRC) waste, and the low-level waste data base. This paper discusses these issues and their current status.

  5. Regulatory unbundling in telecommunications

    OpenAIRE

    Knieps, Günter

    2011-01-01

    Due to its dynamic nature, and the increasing importance of competitive sub-parts, the telecommunications sector provides particularly interesting insights for studying regulatory unbundling. Based on the theory of monopolistic bottle-necks the fallacies of overregulation by undue unbundling obligations are indicated. Neither the promotion of infrastructure competition by mandatory un-bundling of competitive subparts of telecommunications infrastructure, nor regulatory induced network fragmen...

  6. Canadian drug regulatory framework.

    Science.gov (United States)

    Kelly, L; Lazzaro, M; Petersen, C

    2007-03-01

    The role of regulatory drug submission evaluators in Canada is to critically assess both the data submitted and the sponsor's interpretation of the data in order to reach an evidence-, and context-based recommendation as to the potential benefits and potential harms (i.e., risks) associated with taking the drug under the proposed conditions of use. The purpose of this document is to outline the regulatory framework in which this assessment occurs, including: defining what "authorization to market a drug in Canada" means, in terms of the role of the sponsor, the responsibility of Health Canada in applying the Food and Drugs Act prior to and after marketing authorization, and the distinction between regulatory authorization versus physician authorization; highlighting organizational, process and legal factors within Health Canada related to authorization of clinical trials and authorization to market a drug; considerations during the review process, such as regulatory and scientific issues related to the drug, patient populations and trial designs; application of international guidelines, and decisions from other jurisdictions; regulatory realities regarding drug authorization, including the requirement for wording in the Product Monograph to accurately reflect the information currently available on the safe and effective use of a drug, and that hypothesis-confirming studies are essential to regulatory endorsement; current issues related to the review of therapies for dementia, such as assessing preventative treatments, and therapies that have symptomatic versus disease-modifying effects, statistical issues regarding missing data, and trial design issues.

  7. Internal fixation of proximal humerus fractures using the T2-proximal humeral nail.

    Science.gov (United States)

    Popescu, Dragos; Fernandez-Valencia, Jenaro A; Rios, Moisés; Cuñé, Jordi; Domingo, Anna; Prat, Salvi

    2009-09-01

    Surgical management of proximal humerus fractures remains controversial and there is an increasing interest in intramedullary nailing. Created to improve previous designs, the T2-proximal humeral nail (PHN) (Stryker) has been recently released, and the English literature lacks a series evaluating its results. We present a clinical prospective study evaluating this implant for proximal humeral fractures. We evaluated the functional and radiological results and possible complications. Twenty-nine patients with displaced fractures of the proximal humerus were treated with this nail. One patient was lost right after surgery and excluded from the assessment. Eighteen patients were older than 70 years. There were 21 fractures of the proximal part of the humerus and 7 fractures that also involved the shaft; 15 of the fractures were two-part fractures (surgical neck), 5 were three-part fractures, and 1 was a four-part fracture. All fractures healed in a mean period of 2.7 months. There was one delayed union that healed in 4 months. One case of avascular necrosis of the humeral head was observed (a four-part fracture), but remained asymptomatic and did not require further treatment. In one case a back-out of one proximal screw was observed. A final evaluation with a minimum 1 year follow-up was performed by an independent observer; in 18 patients, the mean Constant score was 65.7 or 76.1% with the adjustment of age and gender; in 19 patients, the mean Oxford Shoulder Score was 21.7. The results obtained with the T2-PHN nail indicate that it represents a safe and reliable method in the treatment of two- and three-part fractures of the proximal humerus. The proximal fixation mechanism diminishes the rate of back-out of the screws, a frequent complication described in the literature. Better functional results were obtained from the patients younger than 70 years, but these were not statistically significant.

  8. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

    Directory of Open Access Journals (Sweden)

    Ana Tobar

    Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

  9. [Arthroscopic fracture management in proximal humeral fractures].

    Science.gov (United States)

    Lill, H; Katthagen, C; Jensen, G; Voigt, C

    2013-04-01

    Arthroscopy has become increasingly more established in the treatment of proximal humeral fractures. In addition to the known advantages of minimally invasive surgery fracture and implant positioning can be optimized and controlled arthroscopically and relevant intra-articular concomitant pathologies (e.g. biceps tendon complex and rotator cuff) can be diagnosed and treated. Arthroscopic techniques have proven to be advantageous in the treatment of various entities of greater tuberosity fractures, lesser tuberosity fractures (suture bridging technique) and subcapital humeral fractures (arthroscopic nailing). This article presents an overview on innovative arthroscopic modalities for treating proximal humeral fractures, describes the surgical techniques and the advantages compared to open procedures as well as initial clinical results.

  10. SINA: A test system for proximity fuses

    Science.gov (United States)

    Ruizenaar, M. G. A.

    1989-04-01

    SINA, a signal generator that can be used for testing proximity fuses, is described. The circuitry of proximity fuses is presented; the output signal of the RF circuit results from a mixing of the emitted signal and received signal that is Doppler shifted in frequency by the relative motion of the fuse with respect to the reflecting target of surface. With SINA, digitized and stored target and clutter signals (previously measured) can be transformed to Doppler signals, for example during a real flight. SINA can be used for testing fuse circuitry, for example in the verification of results of computer simulations of the low frequency Doppler signal processing. The software of SINA and its use are explained.

  11. Tunable Magnetic Proximity Effects in Graphene Junctions

    Science.gov (United States)

    Lazic, Predrag; Belashchenko, Kirill; Zutic, Igor

    2015-03-01

    The characteristic length of the magnetic proximity effects exceed the thickness of a graphene layer leading to an important, but typically overlooked, modifications of equilibrium and transport properties, as well as the implications for graphene spintronics. Using the first-principles studies that integrate a real space density functional theory (GPAW) with the state-of-the art boundary elements electrostatic code based on the Robin Hood method, we explore tunable electronic structure and magnetic proximity effects in the ferromagnet/insulator/graphene junctions. We show that the inclusion of a finite-size gate electrodes and van der Walls interaction lead to nontrivial effects that could also be important in other two-dimensional materials beyond graphene. Work supported by US ONR, NSF-DMR and Nebraska NSF MRSEC.

  12. Management of Proximal Third Arm Replantation

    Directory of Open Access Journals (Sweden)

    Süleyman Taş

    2017-12-01

    Full Text Available Notwithstanding the recent success in major limb replantation achieved through the advancements in microsurgical techniques, the viability of the extremity is still relatively low at the transhumeral level following a replantation. There are no exact guidelines for deciding whether to undertake a stump repair or a replantation in such amputations at the proximal level. However, a highly motivated patient with realistic expectations and protected shoulder function can be a candidate to undergo replantation. The replanted arm may help the uninjured arm in daily activities. In this report we present the case of a 47-year-old man whose arm was amputated at proximal third level by an asphalt machine and successfully replanted together with the encountered problems and their solutions. The roadmap followed in this rare case may be a guide for hand surgeons.

  13. Dedifferentiated chondrosarcoma of right proximal femur

    Directory of Open Access Journals (Sweden)

    Sachin A Badge

    2016-01-01

    Full Text Available Dedifferentiated chondrosarcoma (DDCS comprises approximately 10% of all chondrosarcomas. The tumor generally occurs after the age of 50 years, with equal distribution among males and females. It is most often located in the bones of the pelvis, the proximal femur or humerus, the distal femur, and the ribs. Regardless of treatment, the prognosis is ominous with 90% of patients dying with distant metastases within 2 years. We report a case of DDCS of right proximal femur in a 73-year-old woman. The most important factors affecting survival are early recognition of the radiographic features, adequate histological sampling, and wide-margin resection of the lesion. So for the correct histopathological diagnosis the biopsy sample should be adequate to visualize both cartilaginous and noncartilaginous sarcomatous component which helps to increase the survival of patients before the distant metastasis occurs.

  14. 78 FR 44279 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... July 23, 2013 Part XI Department of Justice Semiannual Regulatory Agenda #0;#0;Federal Register / Vol... CFR Ch. I 27 CFR Ch. II 28 CFR Ch. I, V Regulatory Agenda AGENCY: Department of Justice. ACTION: Semiannual regulatory agenda. SUMMARY: The Department of Justice is publishing its spring 2013 regulatory...

  15. 77 FR 8018 - Regulatory Agenda

    Science.gov (United States)

    2012-02-13

    ... February 13, 2012 Part XVIII National Aeronautics and Space Administration Semiannual Regulatory Agenda #0... AERONAUTICS AND SPACE ADMINISTRATION 14 CFR Ch. V Regulatory Agenda AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Semiannual regulatory agenda. SUMMARY: NASA's regulatory agenda describes those...

  16. 75 FR 79759 - Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... Energy ###Semiannual Regulatory Agenda### ] DEPARTMENT OF ENERGY (DOE) DEPARTMENT OF ENERGY Semiannual Regulatory Agenda 10 CFR Chs. II, III, and X 48 CFR Ch. 9 Regulatory Agenda AGENCY: Department of Energy. ACTION: Notice of semiannual regulatory agenda. SUMMARY: The Department of Energy (DOE) has prepared and...

  17. 78 FR 1634 - Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... January 8, 2013 Part XVII National Aeronautics and Space Administration Semiannual Regulatory Agenda #0;#0... AERONAUTICS AND SPACE ADMINISTRATION 14 CFR Ch. V Regulatory Agenda AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Semiannual regulatory agenda. SUMMARY: NASA's regulatory agenda describes those...

  18. 75 FR 79799 - Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... Justice ###Semiannual Regulatory Agenda### ] DEPARTMENT OF JUSTICE (DOJ) DEPARTMENT OF JUSTICE 8 CFR Ch. V 21 CFR Ch. I 27 CFR Ch. II 28 CFR Ch. I, V Regulatory Agenda AGENCY: Department of Justice. ACTION: Semiannual regulatory agenda. SUMMARY: The Department of Justice is publishing its fall 2010 regulatory...

  19. 77 FR 7972 - Regulatory Agenda

    Science.gov (United States)

    2012-02-13

    ... February 13, 2012 Part XI Department of Justice Semiannual Regulatory Agenda #0;#0;Federal Register / Vol... CFR Ch. I 27 CFR Ch. II 28 CFR Ch. I, V Regulatory Agenda AGENCY: Department of Justice. ACTION: Semiannual regulatory agenda. SUMMARY: The Department of Justice is publishing its fall 2011 regulatory...

  20. 78 FR 44329 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... July 23, 2013 Part XVIII National Aeronautics and Space Administration Semiannual Regulatory Agenda #0... AERONAUTICS AND SPACE ADMINISTRATION 14 CFR Ch. V Regulatory Agenda AGENCY: National Aeronautics and Space Administration (NASA). ACTION: Semiannual regulatory agenda. SUMMARY: NASA's regulatory agenda describes those...

  1. The Impact of Proximity to Urban Center on Crop Production Choice ...

    African Journals Online (AJOL)

    This article attempts to demonstrate how proximity to urban centers influences households' decision to allot their agricultural land to the production of either staple crops or high value cash crops. By applying fractional logit estimation technique on data collected from villages in Wollo of the Amhara Regional State in 2006, ...

  2. Case report A Rare Cause of Sub-Acute Proximal Intestinal ...

    African Journals Online (AJOL)

    KIGZ

    A Rare Cause of Sub-Acute Proximal Intestinal Obstruction Due to Annular Pancreas. Weledji EP, Ngowe M, Mokake M. Department of Surgery, Regional Hospital Buea, Cameroon. Correspondence to: E P Weledji, P.O Box 126, Limbe, Cameroon. Email:elroypat@yahoo.co.uk. Summary. Background: Annular pancreas is a ...

  3. Management of Acute Proximal Humeral Fractures.

    Science.gov (United States)

    Kancherla, Vamsi Krishna; Singh, Anshuman; Anakwenze, Oke A

    2017-01-01

    Proximal humeral fractures, which typically occur in elderly persons, are among the most common fractures. A myriad of nonsurgical and surgical treatment options exist for these injuries, including short-term immobilization and early physical therapy, percutaneous fixation, plate osteosynthesis, intramedullary nailing, hemiarthroplasty, and reverse shoulder arthroplasty. The choice of treatment depends on the fracture type and severity, surgeon expertise, patient age, and patient health status.

  4. Superconducting proximity effect in clean ferromagnetic layers

    OpenAIRE

    Zareyan, M.; Belzig, W.; Nazarov, Yu. V.

    2002-01-01

    We investigate the superconducting proximity effect in clean ferromagnetic layers with rough boundaries. The subgap density of states is formed by Andreev bound states at energies which depend on trajectory length and the ferromagnetic exchange field. At energies above the gap, the spectrum is governed by resonant scattering states. The resulting density of states, measurable by tunneling spectroscopy, exhibits a rich structure, which allows us to connect the theoretical parameters from exper...

  5. Alternating proximal algorithm for blind image recovery

    OpenAIRE

    Bolte, Jérôme; Combettes, Patrick Louis; Pesquet, Jean-Christophe

    2010-01-01

    International audience; We consider a variational formulation of blind image recovery problems. A novel iterative proximal algorithm is proposed to solve the associated nonconvex minimization problem. Under suitable assumptions, this algorithm is shown to have better convergence properties than standard alternating minimization techniques. The objective function includes a smooth convex data fidelity term and nonsmooth convex regularization terms modeling prior information on the data and on ...

  6. Isolated Proximal Tibiofibular Dislocation during Soccer

    Directory of Open Access Journals (Sweden)

    Casey Chiu

    2015-01-01

    Full Text Available Proximal tibiofibular dislocations are rarely encountered in the Emergency Department (ED. We present a case involving a man presenting to the ED with left knee pain after making a sharp left turn on the soccer field. His physical exam was only remarkable for tenderness over the lateral fibular head. His X-rays showed subtle abnormalities of the tibiofibular joint. The dislocation was reduced and the patient was discharged from the ED with orthopedic follow-up.

  7. THE PROXIMATE COMPOSITION OF AFRICAN BUSH MANGO ...

    African Journals Online (AJOL)

    BIG TIMMY

    The proximate analysis (moisture, crude protein, crude fat, mineral ash and total carbohydrates) in the kernels and flour of African Bush Mango (. ) were investigated. The results revealed that the kernels contained moisture (2.5 g/100 g), crude protein (8.9 g/100 g), crude fat (68.4 g/100 g), mineral ash (2.3 g/100 g) and total ...

  8. [Proximity and breastfeeding at the maternity hospital].

    Science.gov (United States)

    Fradin-Charrier, Anne-Claire

    2015-01-01

    The establishment of breastfeeding, as well as its duration, are facilitated through the proximity of the mother with her new baby. However, in maternity hospitals, breastfeeding mothers very often leave their baby in the nursery at night time. A study carried out in 2014 in several maternity hospitals put forward suggestions and highlighted areas to improve in everyday practice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. rSNPBase: a database for curated regulatory SNPs

    Science.gov (United States)

    Guo, Liyuan; Du, Yang; Chang, Suhua; Zhang, Kunlin; Wang, Jing

    2014-01-01

    In recent years, human regulatory SNPs (rSNPs) have been widely studied. Here, we present database rSNPBase, freely available at http://rsnp.psych.ac.cn/, to provide curated rSNPs that analyses the regulatory features of all SNPs in the human genome with reference to experimentally supported regulatory elements. In contrast with previous SNP functional annotation databases, rSNPBase is characterized by several unique features. (i) To improve reliability, all SNPs in rSNPBase are annotated with reference to experimentally supported regulatory elements. (ii) rSNPBase focuses on rSNPs involved in a wide range of regulation types, including proximal and distal transcriptional regulation and post-transcriptional regulation, and identifies their potentially regulated genes. (iii) Linkage disequilibrium (LD) correlations between SNPs were analysed so that the regulatory feature is annotated to SNP-set rather than a single SNP. (iv) rSNPBase provides the spatio-temporal labels and experimental eQTL labels for SNPs. In summary, rSNPBase provides more reliable, comprehensive and user-friendly regulatory annotations on rSNPs and will assist researchers in selecting candidate SNPs for further genetic studies and in exploring causal SNPs for in-depth molecular mechanisms of complex phenotypes. PMID:24285297

  10. Proximal Gastrojejunal Reconstruction after Pancreaticoduodenal Resection

    Directory of Open Access Journals (Sweden)

    M. Wayne

    2012-01-01

    Full Text Available Introduction. Reconstruction by proximal gastrojejunostomy, and distal biliary and pancreatic anastomoses is infrequently used after resection of the head of the pancreas because of fear of fistulas and cholangitis. Pancreaticoduodenectomy is being performed more frequently for cystic malignant and premalignant lesions. Because of this there is a need for endoscopic visualization and biopsy of the residual pancreatic duct, since multi-centricity is characteristic of some of these malignancies. Since endoscopic access of the bile duct and pancreatic duct is difficult and unsuccessful in 50–70% after B II or Roux Y reconstruction, we prospectively studied the merit and complications (early and late of proximal gastrojejunal (PGJ reconstruction after pancreaticoduodenal resection. Material and Methods. Thirty nine consecutive, non-radomized patients underwent pancreaticoduodenectomy and PGJ reconstruction over 14 mos. There were 21 males and 18 females. Results. 7 patients with IPMN have undergone repeat CT scanning for surveillance, with 3 requiring repeat EUS and ERCP. There were no technical difficulties accessing the pancreas or the pancreatic duct, supporting the PGJ reconstruction. Conclusion. Proximal gastrojejunal reconstruction following pancreaticoduodenal resection may be safely done with similar morbidity to traditional pancreaticojejunal reconstructions. PGJ reconstruction may be of greater value when direct visual access to the bile duct or pancreatic duct is necessary, and should be considered when doing resection for mucinous cysts or IPMN of the head of the pancreas.

  11. Bilateral, atraumatic, proximal tibiofibular joint instability.

    Science.gov (United States)

    Morrison, Troy D; Shaer, James A; Little, Jill E

    2011-01-01

    Dislocation of the tibiofibular joint is rare and usually results from a traumatic event. Only 1 case of atraumatic proximal tibiofibular joint instability in a 14-year-old girl has been reported in the literature, however this condition might occur more frequently than once thought. A wide range of treatment options exist for tibiofibular dislocations. Currently, the first choice is a conservative approach, and when this fails, surgical means such as resection of the fibula head, arthrodesis, and reconstruction are considered. However, no consensus exists on the most effective treatment. This article reports a unique case of bilateral, atraumatic, proximal tibia and fibular joint instability involving a 30-year-old man with a 20-year history of pain and laxity in the right knee. The patient had no trauma to his knees; he reported 2 immediate family members with similar complaints, which suggests that this case is likely congenital. After conservative approaches proved to be ineffective, the patient underwent capsular reconstruction using free autologous gracilis tendon. At 6-month postoperative follow-up, the patient was pain free with no locking and instability. He then underwent surgery on the left knee. At 1-year follow-up after the second surgery, the patient had no symptoms or restrictions in mobility. We provide an alternative surgical approach to arthrodesis and resection for the treatment of chronic proximal tibiofibular instability. In the treatment of chronic tibiofibular instability, we believe that reconstruction of the tibiofibular joint is a safe and effective choice. Copyright 2011, SLACK Incorporated.

  12. Molecular organization of the vestigial region in Drosophila melanogaster.

    Science.gov (United States)

    Williams, J A; Bell, J B

    1988-05-01

    The vestigial (vg) locus of Drosophila melanogaster is involved in wing margin development. In the absence of a vg+ gene, extensive cell death occurs in third instar imaginal discs which results in a complete loss of adult wing margin structures. P-element tagging was used to obtain a molecular clone of the vg locus, which led to the molecular characterization of approximately 46 kb of DNA from the region. Deficiency analysis and molecular mapping identified sequences, spanning approximately 20 kb of DNA within the larger region, which are necessary for vg function. The molecular map was oriented with respect to a pre-existing genetic fine structure map of the locus. The centromere distal limits of the locus were defined by deficiency analyses while the proximal end has not yet been conclusively established. However, three transcripts, that are apparently unrelated to vg, provide circumstantial evidence for the proximal limits of the vg locus. The nature of the molecular lesions for several extant recessive or lethal vg alleles was determined, and these were placed on the vg molecular map. The characterization of the lesions associated with two dominant vg alleles and one complex vg allele imply interesting regulatory mechanisms for this locus. As well, a revertant of a 412 insertion mutant allele was shown to have resulted from a further insertion of a roo element into the 412 element.

  13. Calibrating animal-borne proximity loggers.

    Science.gov (United States)

    Rutz, Christian; Morrissey, Michael B; Burns, Zackory T; Burt, John; Otis, Brian; St Clair, James J H; James, Richard

    2015-06-01

    Growing interest in the structure and dynamics of animal social networks has stimulated efforts to develop automated tracking technologies that can reliably record encounters in free-ranging subjects. A particularly promising approach is the use of animal-attached 'proximity loggers', which collect data on the incidence, duration and proximity of spatial associations through inter-logger radio communication. While proximity logging is based on a straightforward physical principle - the attenuation of propagating radio waves with distance - calibrating systems for field deployment is challenging, since most study species roam across complex, heterogeneous environments.In this study, we calibrated a recently developed digital proximity-logging system ('Encounternet') for deployment on a wild population of New Caledonian crows Corvus moneduloides. Our principal objective was to establish a quantitative model that enables robust post hoc estimation of logger-to-logger (and, hence, crow-to-crow) distances from logger-recorded signal-strength values. To achieve an accurate description of the radio communication between crow-borne loggers, we conducted a calibration exercise that combines theoretical analyses, field experiments, statistical modelling, behavioural observations, and computer simulations.We show that, using signal-strength information only, it is possible to assign crow encounters reliably to predefined distance classes, enabling powerful analyses of social dynamics. For example, raw data sets from field-deployed loggers can be filtered at the analysis stage to include predominantly encounters where crows would have come to within a few metres of each other, and could therefore have socially learned new behaviours through direct observation. One of the main challenges for improving data classification further is the fact that crows - like most other study species - associate across a wide variety of habitats and behavioural contexts, with different signal

  14. Proximate chemical composition and fatty acid profiles of ...

    African Journals Online (AJOL)

    Proximate chemical composition and fatty acid profiles of Longissimus Proximate chemical composition and fatty acid profiles of Longissimus thoracis from pasture fed LHRH immunocastrated, castrated and intact Bos indicus bulls.

  15. Proximate Analysis and Total Lycopene Content of Some Tomato ...

    African Journals Online (AJOL)

    MBI

    2017-06-05

    Jun 5, 2017 ... Standard analytical techniques were employed to determine the proximate composition and lycopene content of three tomato cultivars namely: ... Keywords: Antioxidant, lycopene content, proximate composition, tomato cultivars. INTRODUCTION ..... from oranges, tomatoes and carrots. African. Journal of ...

  16. A Regularized Algorithm for the Proximal Split Feasibility Problem

    Directory of Open Access Journals (Sweden)

    Zhangsong Yao

    2014-01-01

    Full Text Available The proximal split feasibility problem has been studied. A regularized method has been presented for solving the proximal split feasibility problem. Strong convergence theorem is given.

  17. Quality Assessment and Proximate Analysis of Amaranthus hybridus ...

    African Journals Online (AJOL)

    The aim of this research is to determine the quality and proximate composition of Amaranthus hybridus, Celosia argentea, and Talinum triangulare obtained from open markets in Benin City, Nigeria. Microbiological and proximate analysis were carried out using standard methods. Results of the proximate analysis revealed ...

  18. Proximal femur geometry in the adult Kenyan femur and its ...

    African Journals Online (AJOL)

    Background: Numerous orthopaedic procedures are carried out on the proximal femur. For optimal hip function, these procedures must restore the anatomy of the proximal femur to as near normal as possible. There are currently no local studies that have described in detail the normal anatomy of the proximal femur and its ...

  19. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  20. Evolutionary rewiring of bacterial regulatory networks

    Directory of Open Access Journals (Sweden)

    Tiffany B. Taylor

    2015-07-01

    Full Text Available Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks – homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015, 347(6225] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.

  1. Minimally Invasive Fixation for Proximal Humeral Fracture: A Review on the use of T2 Proximal Humeral Nail

    Directory of Open Access Journals (Sweden)

    Sze-Ling Iris Ngai

    2013-12-01

    Discussion and conclusion: With the proper surgical technique high union rate, good functional recovery, and low complication rate can be achieved by using T2 Proximal Humeral Nail in managing traumatic proximal humeral fracture.

  2. A review of progress in identifying and characterizing biocrusts using proximal and remote sensing

    Science.gov (United States)

    Rozenstein, Offer; Adamowski, Jan

    2017-05-01

    Biocrusts are critical components of desert ecosystems, significantly modifying the surfaces they occupy. The mixture of biological components and soil particles that form the crust, in conjunction with moisture, determines the biocrusts' spectral signatures. Proximal and remote sensing in complementary spectral regions, namely the reflective region, and the thermal region, have been used to study biocrusts in a non-destructive manner, in the laboratory, in the field, and from space. The objectives of this review paper are to present the spectral characteristics of biocrusts across the optical domain, and to discuss significant developments in the application of proximal and remote sensing for biocrust studies in the last few years. The motivation for using proximal and remote sensing in biocrust studies is discussed. Next, the application of reflectance spectroscopy to the study of biocrusts is presented followed by a review of the emergence of high spectral resolution thermal remote sensing, which facilitates the application of thermal spectroscopy for biocrust studies. Four specific topics at the forefront of proximal and remote sensing of biocrusts are discussed: (1) The use of remote sensing in determining the role of biocrusts in global biogeochemical cycles; (2) Monitoring the inceptive establishment of biocrusts; (3) Identifying and characterizing biocrusts using Longwave infrared spectroscopy; and (4) Diurnal emissivity dynamics of biocrusts in a sand dune environment. The paper concludes by identifying innovative technologies such as low altitude and high resolution imagery that are increasingly used in remote sensing science, and are expected to be used in future biocrusts studies.

  3. Maturational timing does not predict HSA estimated adult bone geometry at the proximal femur.

    Science.gov (United States)

    Jackowski, Stefan A; Kontulainen, Saija A; Cooper, David M L; Lanovaz, Joel L; Baxter-Jones, Adam D G

    2011-12-01

    Late maturational timing is documented to be detrimental to bone strength primarily at the distal radius. Studies at the proximal femur have focused on bone mass and the results remain controversial. The purpose of this study was to examine the long term relationship between the onset of maturation and the development of estimated cross sectional area (CSA) and section modulus (Z) at the proximal femur. Two hundred and twenty six individuals (108 males and 118 females) from the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS) were classified into maturity groups based on age of attainment of peak height velocity. CSA and Z were serially assessed at the narrow neck (NN), intertrochanter (IT) and proximal shaft (S) sites using hip structural analysis (HSA). Multilevel models were constructed to examine the development of CSA and Z by maturity group. Cross sectional observations indicated that during adolescence, early maturing males had significantly greater CSA and Z than late maturing males at all sites of the proximal femur, while early maturing females had greater Z at the NN and S, and greater CSA at the NN, IT and S sites compared to late maturing females. When age, body size, body composition, physical activity and dietary intake were controlled no significant effects of maturational timing were found at the NN, IT or S regions (p>0.05) in either males or females. In this population of healthy individuals there appears to be no effect of the onset of maturation on estimated CSA and Z development at the proximal femur in both males and females. This may be a result of the proximal femur's loading environment. Future research is required to determine the role of loading on the relationship between maturational timing and bone structure and strength development at the proximal femur. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Childhood leukemia and residential proximity to industrial and urban sites

    Energy Technology Data Exchange (ETDEWEB)

    García-Pérez, Javier, E-mail: jgarcia@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); López-Abente, Gonzalo, E-mail: glabente@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); Gómez-Barroso, Diana, E-mail: dgomez@externos.isciii.es [CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); Morales-Piga, Antonio, E-mail: amorales@isciii.es [Rare Disease Research Institute (IIER), Carlos III Institute of Health, Madrid (Spain); Consortium for Biomedical Research in Rare Diseases (CIBERER), Madrid (Spain); Pardo Romaguera, Elena, E-mail: elena.pardo@uv.es [Spanish Registry of Childhood Tumors (RETI-SEHOP), University of Valencia, Valencia (Spain); Tamayo, Ibon, E-mail: ibontama@gmail.com [Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, Donostia (Spain); Fernández-Navarro, Pablo, E-mail: pfernandezn@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); and others

    2015-07-15

    Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in

  5. Delayed homicides and the proximate cause.

    Science.gov (United States)

    Lin, Peter; Gill, James R

    2009-12-01

    Delayed homicides result from complications of remote injuries inflicted by "the hands of another." The investigation of delayed homicides may be a challenge due to a number of factors including: failure to report the death to the proper authorities, lack of ready and adequate documentation of the original injury and circumstances, and jurisdictional differences between the places of injury and death. The certification of these deaths also requires the demonstration of a pathophysiologic link between the remote injury and death. In sorting through these issues, it is helpful to rely upon the definition of the proximate cause of death. Over a 2-year period in New York City, there were 1211 deaths certified as homicide of which 42 were due to injuries sustained greater than 1 year before death. The survival interval ranged from 1.3 to 43.2 years. The most common immediate causes of death were: infections (22), seizures (7), and intestinal obstructions/hernias (6). Common patterns of complications included infection following a gunshot wound of the spinal cord, seizure disorder due to blunt head trauma, and intestinal obstruction/hernia due to adhesions from an abdominal stab wound. Spinal cord injuries resulted in paraplegia in 14 instances and quadriplegia in 8. The mean survival interval for paraplegics was 20.3 years and 14.8 years for quadriplegics; infections were a frequent immediate cause of death in both groups, particularly infections due to chronic bladder catheterization. The definition of proximate cause originated with civil law cases and was later applied to death certification as the proximate cause of death. The gradual extinction of the "year and a day rule" for the limitation of bringing homicide charges in delayed deaths may result in more of these deaths going to trial. Medical examiners/coroners must be able to explain the reasoning behind these death certifications and maintain consistent standards for the certification of all delayed deaths due

  6. Laparoscopic proximal gastrectomy with oblique jejunogastrostomy.

    Science.gov (United States)

    Tanaka, Kimitaka; Ebihara, Yuma; Kurashima, Yo; Nakanishi, Yoshitsugu; Asano, Toshimichi; Noji, Takehiro; Murakami, Soichi; Nakamura, Toru; Tsuchikawa, Takahiro; Okamura, Keisuke; Shichinohe, Toshiaki; Hirano, Satoshi

    2017-05-10

    Proximal early gastric cancer is a good indication for totally laparoscopic proximal gastrectomy (TLPG) with double-tract reconstruction (DTR). However, when most of the dietary intake passes through the escape route of the jejunum, the functional benefits of proximal gastrectomy might be similar to those after total gastrectomy. Our DTR procedure was improved for easy passage through the remnant stomach. The purposes of this study were to present a novel technique for intracorporeal DTR using linear staplers after TLPG and to investigate surgical outcomes. DTR was performed using linear staplers only. A side-to-side jejunogastrostomy with twisting of both the remnant stomach and the anal jejunum was performed for the purpose of passing meals through the remnant stomach (an oblique jejunogastrostomy technique). The ten patients who underwent TLPG with DTR from January 2011 to August 2016 in Hokkaido University Hospital were retrospectively reviewed. Their clinicopathological characteristics and surgical and postoperative outcomes were collected and analyzed. The median duration of operation was 285 (range 146-440) min. No patients required blood transfusions. The number of dissected lymph nodes was 32 (range 22-56). There were no intraoperative complications, and no cases were converted to open surgery. All the patients were pT1N0M0 stage IA. No anastomotic leakage or complications were detected. Postoperative gastrography after reconstruction showed that contrast medium flowed mainly to the remnant stomach. The average percentage body weight loss was 14.0 ± 7.1% at 10 months. The average percentage decrease in serum hemoglobin was 5.4 ± 10.4% at 12 months. This novel technique for intracorporeal DTR provided a considerable advantage by the passage of dietary intake to the remnant stomach after LPG.

  7. Bicarbonate secretion by rabbit proximal colon.

    Science.gov (United States)

    Sullivan, S K; Smith, P L

    1986-10-01

    Stripped segments of proximal colon (1-6 cm distal to the ampulla caecalis coli) were studied in vitro in Ussing chambers under short-circuit conditions using the pH-stat technique. With glucose and HCO3-CO2 present in the serosal bathing solution only, proximal colon alkalinizes the luminal bathing solution at a rate of 2.1 +/- 0.2 mu eq X h-1 X cm-2 (n = 36). With HCO3-CO2 present in the luminal bathing solution alone, proximal colon does not significantly acidify or alkalinize the serosal bathing solution. Addition of glucose (10 mM) to the luminal bathing solution abolished luminal alkalinization. Removal of HCO3 and CO2 from the serosal bathing solution or replacement of O2 with N2 also abolished luminal alkalinization. Acetazolamide (0.1 mM) added to both bathing solutions did not alter the rate of luminal alkalinization. Ion-replacement studies revealed that the alkalinization process was highly dependent on the presence of Na in the bathing solutions and much less dependent on the presence of Cl. Furthermore, ouabain (0.1 mM) significantly reduced luminal alkalinization. As in rabbit ileum, serosal epinephrine (0.1 mM) did not alter luminal alkalinization but increased serosal alkalinization by a Na-dependent mechanism. These results suggest that luminal alkalinization results from a Na-dependent, active transcellular HCO3 transport process and that a Na-dependent HCO3 absorptive process is activated by adrenergic stimuli.

  8. Temporal Proximity Promotes Integration of Overlapping Events.

    Science.gov (United States)

    Zeithamova, Dagmar; Preston, Alison R

    2017-08-01

    Events with overlapping elements can be encoded as two separate representations or linked into an integrated representation, yet we know little about the conditions that promote one form of representation over the other. Here, we tested the hypothesis that the proximity of overlapping events would increase the probability of integration. Participants first established memories for house-object and face-object pairs; half of the pairs were learned 24 hr before an fMRI session, and the other half 30 min before the session. During scanning, participants encoded object-object pairs that overlapped with the initial pairs acquired on the same or prior day. Participants were also scanned as they made inference judgments about the relationships among overlapping pairs learned on the same or different day. Participants were more accurate and faster when inferring relationships among memories learned on the same day relative to those acquired across days, suggesting that temporal proximity promotes integration. Evidence for reactivation of existing memories-as measured by a visual content classifier-was equivalent during encoding of overlapping pairs from the two temporal conditions. In contrast, evidence for integration-as measured by a mnemonic strategy classifier from an independent study [Richter, F. R., Chanales, A. J. H., & Kuhl, B. A. Predicting the integration of overlapping memories by decoding mnemonic processing states during learning. Neuroimage, 124, 323-335, 2016]-was greater for same-day overlapping events, paralleling the behavioral results. During inference itself, activation patterns further differentiated when participants were making inferences about events acquired on the same day versus across days. These findings indicate that temporal proximity of events promotes integration and further influences the neural mechanisms engaged during inference.

  9. [Angle-stable intramedullary nailing of proximal humerus fractures with the PHN (proximal humeral nail)].

    Science.gov (United States)

    Blum, Jochen; Hansen, Matthias; Rommens, Pol Maria

    2009-09-01

    Stable fixation of two- and three-part fractures of the proximal humerus through minimally invasive operative technique and rapid bone healing as well as restoration of original anatomy. Early functional training with the goal of restoration of former mobility and daily activities. Unstabile two- and three-part fractures of the proximal humerus (AO classification: 11-A2, 11-A3, 11-B1, 11-B2, 11-B3). Subcapital nonunion of the humerus. Pathologic fractures. Pediatric fractures of the proximal humerus. Fractures of the proximal humerus types 11-C2 und 11-C3 according to the AO classification. Active local infection, e.g., after former operation. Closed reduction. Anterior acromial incision, splitting of the deltoid muscle and the rotator cuff. Opening of the medullary canal with the awl. Nail introduction. Spiral blade introduction in cannulated technique through stab incision. Distal interlocking through aiming device, angle-stable blocking of nail and blade through end cap. Postoperative fixation in Gilchrist sling until 2nd postoperative day; then physiotherapy respecting fracture type and stability, local swelling, patient's age and compliance, and concomitant injuries. 151 proximal humeral fractures were treated with a proximal humeral nail (PHN). 108 patients could be followed up 1 year postoperatively. Significant complications were perforation of the articular surface through bolts or blades (n = 8), implant-related pain (n = 10), fragment dislocation (n = 2), nonunion (n = 2), humeral head necrosis (n = 3), and superficial infection (n = 1). 1 year after the operation, the Constant-Murley Score showed a median value of 75.3 in the injured shoulder and of 89.9 in the uninjured shoulder. The DASH (Disability of the Arm, Shoulder and Hand) Score was 5.9 preoperatively and 9.3 at 1 year postoperatively. The worst results regarding the Constant-Murley Score as well as the DASH Score were found in C-type fractures.

  10. Impacted valgus fractures of the proximal humerus

    Directory of Open Access Journals (Sweden)

    Fabiano Rebouças Ribeiro

    2016-04-01

    Full Text Available Impacted valgus fractures of the proximal humerus are considered to be a special type fracture, since impaction of the humeral head on the metaphysis with maintenance of the posteromedial periosteum improves the prognosis regarding occurrences of avascular necrosis. This characteristic can also facilitate the reduction maneuver and increase the consolidation rate of these fractures, even in more complex cases. The studies included were obtained by searching the Bireme, Medline, PubMed, Cochrane Library and Google Scholar databases for those published between 1991 and 2013. The objective of this study was to identify the most common definitions, classifications and treatment methods used for these fractures in the orthopedic medical literature.

  11. Management of posttraumatic proximal interphalangeal joint contracture.

    Science.gov (United States)

    Houshian, Shirzad; Jing, Shan Shan; Chikkamuniyappa, Chandrasekar; Kazemian, Gholam Hussein; Emami-Moghaddam-Tehrani, Mohammad

    2013-08-01

    Chronic flexion contracture of the proximal interphalangeal (PIP) joint presents a common yet challenging problem to hand surgeons. Over the years, multiple treatment modalities have been described for this problem, producing limited results. Nonoperative treatment using serial casting and splints should be tried before attempting open surgical release, which should be done in selected patients. The use of external fixation for treating PIP contracture has been encouraging and can be a useful alterative. This review provides an update on the current management of PIP joint contractures and presents a flowchart of treatment to aid decision making. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  12. Ontogeny of rabbit proximal tubule urea permeability

    Science.gov (United States)

    QUIGLEY, RAYMOND; LISEC, AMBER; BAUM, MICHEL

    2014-01-01

    Urea transport in the proximal tubule is passive and is dependent on the epithelial permeability. The present study examined the maturation of urea permeability (Purea) in in vitro perfused proximal convoluted tubules (PCT) and basolateral membrane vesicles (BLMV) from rabbit renal cortex. Urea transport was lower in neonatal than adult PCT at both 37 and 25°C. The PCT Purea was also lower in the neonates than the adults (37°C: 45.4 ± 10.8 vs. 88.5 ± 15.2 × 10−6 cm/s, P 0.05). The activation energy for PCT Purea was not different between the neonatal and adult groups. BLMV Purea was determined by measuring vesicle shrinkage, due to efflux of urea, using a stop-flow instrument. Neonatal BLMV Purea was not different from adult BLMV Purea at 37°C [1.14 ± 0.05 × 10−6 vs. 1.25 ± 0.05 × 10−6 cm/s; P = not significant (NS)] or 25°C (0.94 ± 0.06 vs. 1.05 ± 0.10 × 10−6 cm/s; P = NS). There was no effect of 250 μM phloretin, an inhibitor of the urea transporter, on Purea in either adult or neonatal BLMV. The activation energy for urea diffusion was also identical in the neonatal and adult BLMV. These findings in the BLMV are in contrast to the brush-border membrane vesicles (BBMV) where we have previously demonstrated that urea transport is lower in the neonate than the adult. Urea transport is lower in the neonatal proximal tubule than the adult. This is due to a lower rate of apical membrane urea transport, whereas basolateral urea transport is the same in neonates and adults. The lower Purea in neonatal proximal tubules may play a role in overall urea excretion and in developing and maintaining a high medullary urea concentration and thus in the ability to concentrate the urine during renal maturation. PMID:11353675

  13. A method for designing plates in treatments of proximal humeral fracture and distal radial fracture

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    Lin Wang

    2016-11-01

    Full Text Available The purpose of this paper was to quickly design fixation plates for fractured proximal humerus and distal radius according to the requirements of surgical treatment. Therefore, a new method to quickly design cloverleaf plate appropriate for proximal humerus and volar plate appropriate for distal radius is put forward. First, three-dimensional (3D reconstruction models of fractured proximal humerus and distal radius were generated based on deforming mean parametric models of proximal humerus and distal radius, respectively. Second, based on region-of-interest marked on the 3D reconstruction model of proximal humerus and distal radius, abutted surfaces of cloverleaf plate and volar plate were established, respectively. Then, parametric abutted surface was established after setting rational parameters for the surface of the cloverleaf plate. Parametric abutted surface of volar plate was established using the same method. Finally, parametric cloverleaf plate and volar plate are generated through thickening their respective parametric abutted surfaces. The parametric plates, acting as templates, accelerate and simplify the design process and therefore allow users to construct plate with editing valid parameters easily. Group of cloverleaf plates and volar plates with different sizes were generated quickly, showing that the proposed method is feasible and effective.

  14. Proximity effect in Nb/Al, AlOxide, Al/Nb Josephson tunnel junctions

    Science.gov (United States)

    Houwman, E. P.; Gijsbertsen, J. G.; Flokstra, J.; Rogalla, H.; Le Grand, J. B.; de Korte, P. A. J.; Golubov, A. A.

    1993-03-01

    Regions with reduced energy gap induced by the proximity effect give rise to quasi-particle loss in Josephson-junction X-ray detectors, but may also be used advantageously for quasi-particle collection. The influence of the thickness of the Al proximity layers in Nb/Al1,AlO(x),Al2/Nb Josephson tunnel junctions on the electrical characteristics has been investigated theoretically and experimentally. Theoretically it is found that the strength of the proximity effect is mainly determined by the proximity parameters gammaM1 (gammaM2) of the electrodes. Good fits of the measured I-V curves with theory were obtained for junctions with thicknesses dA11 ranging from 4 to 25 nm and dA12 = 3 nm, with gammaM2 about 0.12 and gammaM1/gammaM2 = dA11/dA12. For all junctions the proximity knee remains more pronounced than predicted.

  15. Impairment of the proximal to distal tonic gradient in the human diabetic stomach.

    Science.gov (United States)

    Min, Y W; Hong, Y S; Ko, E-J; Lee, J Y; Min, B-H; Sohn, T S; Kim, J J; Rhee, P-L

    2014-02-01

    Little has been known about the contractile characteristics of diabetic stomach. We investigated spontaneous contractions and responses to acetylcholine in the gastric muscle in diabetic patients and non-diabetic control subjects according to the region of stomach. Gastric specimens were obtained from 26 diabetics and 55 controls who underwent gastrectomy at Samsung Medical Center between February 2008 and November 2011. Isometric force measurements were performed using circular muscle strips from the different regions of stomach under basal condition and in response to acetylcholine. Basal tone of control was higher in the proximal stomach than in the distal (0.63 g vs 0.46 g, p = 0.027). However, in diabetics, basal tone was not significantly different between the proximal and distal stomach (0.75 g vs 0.62 g, p = 0.32). The distal stomach of diabetics had higher basal tone and lower frequency than that of control (0.62 g vs 0.46 g, p = 0.049 and 4.0/min vs 4.9/min, p = 0.049, respectively). After exposure to acetylcholine, dose-dependent increases of basal tone, peak, and area under the curve (AUC) were noticed in both proximal and distal stomach of the two groups. In the proximal stomach, however, the dose-dependent increase of basal tone and AUC was less prominent in diabetics than in control. On the contrary to control, the proximal to distal tonic gradient was not observed in diabetic stomach. Diabetic stomach also had lower frequency of spontaneous contraction in the distal stomach and less acetylcholine-induced positive inotropic effect in the proximal stomach than control. © 2013 John Wiley & Sons Ltd.

  16. Genome-wide discovery of drug-dependent human liver regulatory elements.

    Directory of Open Access Journals (Sweden)

    Robin P Smith

    2014-10-01

    Full Text Available Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR and three active regulatory marks (p300, H3K4me1, H3K27ac on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4% that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

  17. Spatial resolution of the pain system: a proximal-to-distal gradient of sensitivity revealed with psychophysical testing.

    Science.gov (United States)

    Weissman-Fogel, Irit; Brayer-Zwi, Nurit; Defrin, Ruth

    2012-01-01

    The spatial resolution of the pain system has not been studied in depth, and results are contradictory regarding the gradient of spatial resolution. Microneurographic recordings have revealed smaller receptive fields and higher density of nociceptors in more distal than proximal leg regions, whereas histological studies report higher density of C-fibers in more proximal than distal body regions. Due to this controversy, we conducted various psychophysical tests in order to examine the nociceptive spatial resolution and its gradient. Heat-pain threshold (HPT), perceived pain intensity, spatial summation (SS) of pain, two-point discrimination (2PD) of pain, and pain localization were measured in four body regions: upper back, thigh, lower leg, and foot. The highest HPT was demonstrated in the lower leg as compared with more proximal regions (P resolution has a proximal-to-distal pattern of performance, namely that the spatial resolution of pain is finer in more distal than proximal body regions, similar to that of the touch system.

  18. Functional anatomy and ion regulatory mechanisms of the antennal gland in a semi-terrestrial crab, Ocypode stimpsoni

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    Jyuan-Ru Tsai

    2014-05-01

    Full Text Available Brachyuran crabs from diverse habitats show great differences in their osmoregulatory processes, especially in terms of the structural and physiological characteristics of the osmoregulatory organs. In crustaceans, the antennal glands are known to be important in osmoregulation, and they play a functional role analogous to that of the vertebrate kidney. Nevertheless, the detailed structure and function of the antennal glands in different species have rarely been described. The aim of this study is to investigate the role of the antennal gland in ion regulation by examining the ultrastructure of the cells and the distribution of the ion regulatory proteins in each cell type in the antennal gland of a semi-terrestrial crab. The results showed that Na+, K+-ATPase activity significantly increased in the antennal gland after a 4-day acclimation in dilute seawater and returned to its original (day 0 level after 7 days. Three major types of cells were identified in the antennal gland, including coelomic cells (COEs, labyrinthine cells (LBRs and end-labyrinthine cells (ELBRs. The proximal tubular region (PT and distal tubular region (DT of the antennal gland consist of LBRs and COEs, whereas the end tubular region (ET consists of all three types of cells, with fewer COEs and more ELBRs. We found a non-uniform distribution of NKA immunoreactivity, with increasing intensity from the proximal to the distal regions of the antennal gland. We summarise our study with a proposed model for the urine reprocessing pathway and the role of each cell type or segment of the antennal gland.

  19. Regulatory regimes and bank behavior

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    Seok Weon Lee

    2011-12-01

    Full Text Available The purpose of this paper is to examine how the risk-taking behavior differed between Korean regional banks and national banks for the two different regulatory regimes; a very loose regulation period (1994-1997 and a very tightened regulation period (1998-2005. From the panel analysis over the period 1994-2005, we found that regional banks took riskier strategies than national banks when banking regulations are loose. Moreover, their higher risk-taking contributed to higher profit under the period of loose regulation. However, after the banking regulations were tightened after financial crisis around the late 1990s, this phenomenon disappeared and the tendency of regional banks to take greater risk than national banks was not observed any more. Also, the positive relationship between risk-taking and profitability was not observed either after regulations were tightened. These empirical findings would have the following policy implications. When the economic conditions are good, and therefore, banking regulations are relatively loose, the greater risk-taking of regional banks could be profitable, because regional banks are in a better situation in terms of maintaining their market share based on the close ties with their regional clients, and can be protected from excessive competition with national banks. But, if the economic conditions get worse and financial crisis occurs, and therefore, banking regulations get tightened, regional banks are more adversely and sensitively affected by these shocks than national banks because their size is small and their assets are less diversified than national banks, especially being concentrated on loans to small and medium size business sector and real estate loans, which are very sensitive to the fluctuation of the economy. Furthermore, if these adverse economic and financial shocks continue long, the probability of regional banks to fail would be substantially higher and it can cause a serious damage to

  20. Universal Proximity Effect in Target Search Kinetics in the Few-Encounter Limit

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    Aljaž Godec

    2016-11-01

    Full Text Available When does a diffusing particle reach its target for the first time? This first-passage time (FPT problem is central to the kinetics of molecular reactions in chemistry and molecular biology. Here, we explain the behavior of smooth FPT densities, for which all moments are finite, and demonstrate universal yet generally non-Poissonian long-time asymptotics for a broad variety of transport processes. While Poisson-like asymptotics arise generically in the presence of an effective repulsion in the immediate vicinity of the target, a time-scale separation between direct and reflected indirect trajectories gives rise to a universal proximity effect: Direct paths, heading more or less straight from the point of release to the target, become typical and focused, with a narrow spread of the corresponding first-passage times. Conversely, statistically dominant indirect paths exploring the entire system tend to be massively dissimilar. The initial distance to the target particularly impacts gene regulatory or competitive stochastic processes, for which few binding events often determine the regulatory outcome. The proximity effect is independent of details of the transport, highlighting the robust character of the FPT features uncovered here.

  1. Leaving home, family support and intergenerational ties in Italy: Some regional differences

    Directory of Open Access Journals (Sweden)

    Elisabetta Santarelli

    2009-07-01

    Full Text Available In Italy conditions at leaving home are characterized by high age at exit, high proximity with parents and widespread intergenerational support, showing important regional differences. According to the "familistic" approach such conditions spread from strong intergenerational ties. Proximity and support are considered proxies of ties' strength so that different regional proximity and support correspond to different ties' intensities. The study aims at analyzing similarities and differences about parent-child ties, proximity and support in selected Italian regions, Liguria, Umbria, Sicily and Sardinia. Results show important differences among regions with respect to proximity and support, suggesting different intensity of intergenerational ties.

  2. Proteomics of Primary Cilia by Proximity Labeling.

    Science.gov (United States)

    Mick, David U; Rodrigues, Rachel B; Leib, Ryan D; Adams, Christopher M; Chien, Allis S; Gygi, Steven P; Nachury, Maxence V

    2015-11-23

    While cilia are recognized as important signaling organelles, the extent of ciliary functions remains unknown because of difficulties in cataloguing proteins from mammalian primary cilia. We present a method that readily captures rapid snapshots of the ciliary proteome by selectively biotinylating ciliary proteins using a cilia-targeted proximity labeling enzyme (cilia-APEX). Besides identifying known ciliary proteins, cilia-APEX uncovered several ciliary signaling molecules. The kinases PKA, AMPK, and LKB1 were validated as bona fide ciliary proteins and PKA was found to regulate Hedgehog signaling in primary cilia. Furthermore, proteomics profiling of Ift27/Bbs19 mutant cilia correctly detected BBSome accumulation inside Ift27(-/-) cilia and revealed that β-arrestin 2 and the viral receptor CAR are candidate cargoes of the BBSome. This work demonstrates that proximity labeling can be applied to proteomics of non-membrane-enclosed organelles and suggests that proteomics profiling of cilia will enable a rapid and powerful characterization of ciliopathies. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Empathy: Its ultimate and proximate bases.

    Science.gov (United States)

    Preston, Stephanie D; de Waal, Frans B M

    2002-02-01

    There is disagreement in the literature about the exact nature of the phenomenon of empathy. There are emotional, cognitive, and conditioning views, applying in varying degrees across species. An adequate description of the ultimate and proximate mechanism can integrate these views. Proximately, the perception of an object's state activates the subject's corresponding representations, which in turn activate somatic and autonomic responses. This mechanism supports basic behaviors (e.g., alarm, social facilitation, vicariousness of emotions, mother-infant responsiveness, and the modeling of competitors and predators) that are crucial for the reproductive success of animals living in groups. The Perception-Action Model (PAM), together with an understanding of how representations change with experience, can explain the major empirical effects in the literature (similarity, familiarity, past experience, explicit teaching, and salience). It can also predict a variety of empathy disorders. The interaction between the PAM and prefrontal functioning can also explain different levels of empathy across species and age groups. This view can advance our evolutionary understanding of empathy beyond inclusive fitness and reciprocal altruism and can explain different levels of empathy across individuals, species, stages of development, and situations.

  4. Proximal femoral osteotomy in cerebral palsy.

    Science.gov (United States)

    Tylkowski, C M; Rosenthal, R K; Simon, S R

    1980-09-01

    The purpose of this study was to examine the results of the proximal femoral osteotomy for the management of hip deformity in 32 children, aged 4 to 15 years. Twenty-two bilateral and ten unilateral procedures were performed. The indications for surgery were subluxation in 16, dislocation in two, and intoeing and femoral anteversion in 14. The average follow-up was two years and 11 months. CE angle of Wiberg, acetabular index and neck shaft angle were evaluated. The average time to regain preoperative ambulatory status was six months with intensive physical therapy. In osteotomies performed for subluxation, dislocation did not occur; roentgenographic indices showed variability in the degree of subluxation. Osteotomy performed in children older than 8 years of age produced no evidence of acetabular remodeling. THere was no recurrence with osteotomies for dislocation. In those patients with internal rotation gait, improvement resulted. Complications were few and minor. Hip dislocation in children with progressive subluxation, in spite of previous soft-tissue releases, is preventable by proximal femoral osteotomy. The inability of the roentgenographic indices to quantitate the increased stability indicates the procedure's major effect is to realign muscle forces about the hip. Treatment of the intoeing gait produced improvement of rotational deformity.

  5. Obesity and supermarket access: proximity or price?

    Science.gov (United States)

    Drewnowski, Adam; Aggarwal, Anju; Hurvitz, Philip M; Monsivais, Pablo; Moudon, Anne V

    2012-08-01

    We examined whether physical proximity to supermarkets or supermarket price was more strongly associated with obesity risk. The Seattle Obesity Study (SOS) collected and geocoded data on home addresses and food shopping destinations for a representative sample of adult residents of King County, Washington. Supermarkets were stratified into 3 price levels based on average cost of the market basket. Sociodemographic and health data were obtained from a telephone survey. Modified Poisson regression was used to test the associations between obesity and supermarket variables. Only 1 in 7 respondents reported shopping at the nearest supermarket. The risk of obesity was not associated with street network distances between home and the nearest supermarket or the supermarket that SOS participants reported as their primary food source. The type of supermarket, by price, was found to be inversely and significantly associated with obesity rates, even after adjusting for individual-level sociodemographic and lifestyle variables, and proximity measures (adjusted relative risk=0.34; 95% confidence interval=0.19, 0.63) Improving physical access to supermarkets may be one strategy to deal with the obesity epidemic; improving economic access to healthy foods is another.

  6. Demonstration of automated proximity and docking technology

    Science.gov (United States)

    Anderson, Robert L.; Tsugawa, Roy K.; Bryan, Thomas C.

    1991-01-01

    Automated spacecraft docking operations are being performed using a full scale motion based simulator and an optical sensor. This presentation will discuss the work in progress at TRW and MSFC facilities to study the problem of automated proximity and docking operations. The docking sensor used in the MSFC Optical Sensor and simulation runs are performed using the MSFC Flat Floor Facility. The control algorithms and six degrees of freedom (6DOF) simulation software were developed at TRW and integrated into the MSFC facility. Key issues being studied are the quantification of docking sensor requirements and operational constraints necessary to perform automated docking maneuvers, control algorithms capable of performing automated docking in the presence of sensitive and noisy sensor data, and sensor technologies for automated proximity and docking operations. As part of this study the MSFC sensor characteristics were analyzed and modeled so that off line simulation runs can be performed for control algorithm testing. Our goal is to develop and demonstrate full 6DOF docking capabilities with actual sensors on the MSFC motion based simulator. We present findings from actual docking simulation runs which show sensor and control loop performance as well as problem areas which require close attention. The evolution of various control algorithms using both phase plane and Clohessy-Wiltshire techniques are discussed. In addition, 6DOF target acquisition and control strategies are described.

  7. Assignment of human protein phosphatase 2A regulatory subunit genes B56{alpha}, B56{beta}, B56{gamma}, B56{delta}, and B56{epsilon} (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.1 {r_arrow} p12

    Energy Technology Data Exchange (ETDEWEB)

    McCright, B.; Virshup, D.M.; Brothman, A.R. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)

    1996-08-15

    The activity of the major intracellular protein phosphatase, protein phosphatase 2A WPM, is determined by the nature of the associated regulatory subunit. A new family of human PP2A regulatory subunits has recently been identified. Three of these subunits, B56{beta}, B56{delta}, and B56{epsilon}, are most highly expressed in brain, while the B56{alpha} and B56{gamma} isoforms are highly expressed in cardiac and skeletal muscle. Genes PPP2R5A-PPP2R5E encoding the phosphatase regulatory proteins B56{alpha}, B56{beta}, B56{gamma}, B56{delta}, and B56{epsilon} have now been mapped by fluorescence in situ hybridization to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2-p12, respectively. 16 refs., 1 fig.

  8. Pathological fractures of the proximal humerus treated with a proximal humeral locking plate and bone cement.

    Science.gov (United States)

    Siegel, H J; Lopez-Ben, R; Mann, J P; Ponce, B A

    2010-05-01

    Bone loss secondary to primary or metastatic lesions of the proximal humerus remains a challenging surgical problem. Options include preservation of the joint with stabilisation using internal fixation or resection of the tumour with prosthetic replacement. Resection of the proximal humerus often includes the greater tuberosity and adjacent diaphysis, which may result in poor function secondary to loss of the rotator cuff and/or deltoid function. Preservation of the joint with internal fixation may reduce the time in hospital and peri-operative morbidity compared with joint replacement, and result in a better functional outcome. We included 32 patients with pathological fractures of the proximal humerus in this study. Functional and radiological assessments were performed. At a mean follow-up of 17.6 months (8 to 61) there was no radiological evidence of failure of fixation. The mean revised musculoskeletal Tumour Society functional score was 94.6% (86% to 99%). There was recurrent tumour requiring further surgery in four patients (12.5%). Of the 22 patients who were employed prior to presentation all returned to work without restrictions. The use of a locking plate combined with augmentation with cement extends the indications for salvage of the proximal humerus with good function in patients with pathological and impending pathological fractures.

  9. 76 FR 3825 - Regulatory Compliance

    Science.gov (United States)

    2011-01-21

    ... Documents#0;#0; ] Memorandum of January 18, 2011 Regulatory Compliance Memorandum for the Heads of Executive... accessible to the public, information concerning their regulatory compliance and enforcement activities, such... enforcement actions). Greater disclosure of regulatory compliance information fosters fair and consistent...

  10. A device for in vivo measurements of quantitative ultrasound variables at the human proximal femur.

    Science.gov (United States)

    Barkmann, Reinhard; Laugier, Pascal; Moser, Urs; Dencks, Stefanie; Klausner, Michael; Padilla, Frédéric; Haïat, Guilleaume; Glüer, Claus-C

    2008-01-01

    Quantitative ultrasound (QUS) at the calcaneus has similar power as a bone mineral density (BMD)- measurement using DXA for the prediction of osteoporotic fracture risk. Ultrasound equipment is less expensive than DXA and free of ionizing radiation. As a mechanical wave, QUS has the potential of measuring different bone properties than dual X-ray absorptiometry (DXA,) which depends on X-ray attenuation and might be developed into a tool of comprehensive assessment of bone strength. However, site-specific DXA at the proximal femur shows best performance in the prediction of hip fractures. To combine the potential of QUS with measurements directly at the femur, we developed a device for in vivo QUS measurements at this site. Methods comprise ultrasound transmission through the bone, reflection from the bone surface, and backscatter from the inner trabecular structure. The complete area of the proximal femur can be scanned except at the femoral head, which interferes with the ilium. To avoid edge artifacts, a subregion of the proximal femur in the trochanteric region was selected as measurement region. First, in vivo measurements demonstrate a good signal to noise ratio and proper depiction of the proximal femur on an attenuation image. Our results demonstrate the feasibility of in vivo measurements. Further improvements can be expected by refinement of the scanning technique and data evaluation method to enhance the potential of the new method for the estimation of bone strength.

  11. Proximity-dependent labeling methods for proteomic profiling in living cells.

    Science.gov (United States)

    Chen, Chiao-Lin; Perrimon, Norbert

    2017-07-01

    Characterizing the proteome composition of organelles and subcellular regions of living cells can facilitate the understanding of cellular organization as well as protein interactome networks. Proximity labeling-based methods coupled with mass spectrometry (MS) offer a high-throughput approach for systematic analysis of spatially restricted proteomes. Proximity labeling utilizes enzymes that generate reactive radicals to covalently tag neighboring proteins with biotin. The biotinylated endogenous proteins can then be isolated for further analysis by MS. To analyze protein-protein interactions or identify components that localize to discrete subcellular compartments, spatial expression is achieved by fusing the enzyme to specific proteins or signal peptides that target to particular subcellular regions. Although these technologies have only been introduced recently, they have already provided deep insights into a wide range of biological processes. Here, we describe and compare current methods of proximity labeling as well as their applications. As each method has its own unique features, the goal of this review is to describe how different proximity labeling methods can be used to answer different biological questions. WIREs Dev Biol 2017, 6:e272. doi: 10.1002/wdev.272 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  12. Digital camera resolution and proximal caries detection.

    Science.gov (United States)

    Prapayasatok, S; Janhom, A; Verochana, K; Pramojanee, S

    2006-07-01

    To evaluate the diagnostic accuracy of proximal caries detection from digitized film images captured by a digital camera at different resolution settings. Twenty-five periapical radiographs of 50 premolar and 25 molar teeth were photographed using a digital camera, Sony Cyber-shot, DSC-S75 at three different resolution settings: 640 x 480, 1280 x 960 and 1600 x 1200. Seventy-five digital images were transferred to a computer, saved and opened using ACDSee software. In addition, a PowerPoint slide was made from each digital image. Five observers scored three groups of images (the films, the displayed 1:1 digital images on the ACDSee software, and the PowerPoint slides) for the existence of proximal caries using a 5-point confidence scale, and the depth of caries on a 4-point scale. Ground sections of the teeth were used as the gold standard. Az values under the receiver operating characteristic (ROC) curve of each group of images and at different resolutions were compared using the Friedman and Wilcoxon signed rank tests. Mean different values between the lesions' depth interpreted by the observers and that of the gold standard were analysed. Films showed the highest Az values. Only the 1280 x 960 images on the ACDSee software showed no significant difference of the Az value from the films (P=0.28). The digital images from three resolution settings on the PowerPoint slides showed no significant differences, either among each other or between them and the films. For caries depth, the 1280 x 960 images showed lower values of mean difference in enamel lesions compared with the other two resolution groups. This study showed that in order to digitize conventional films, it was not necessary to use the highest camera resolution setting to achieve high diagnostic accuracy for proximal caries detection. The 1280 x 960 resolution setting of the digital camera demonstrated comparable diagnostic accuracy with film and was adequate for digitizing radiographs for caries

  13. Characteristics of regulatory regimes

    Directory of Open Access Journals (Sweden)

    Noralv Veggeland

    2013-03-01

    Full Text Available The overarching theme of this paper is institutional analysis of basic characteristics of regulatory regimes. The concepts of path dependence and administrative traditions are used throughout. Self-reinforcing or positive feedback processes in political systems represent a basic framework. The empirical point of departure is the EU public procurement directive linked to OECD data concerning use of outsourcing among member states. The question is asked: What has caused the Nordic countries, traditionally not belonging to the Anglo-Saxon market-centred administrative tradition, to be placed so high on the ranking as users of the Market-Type Mechanism (MTM of outsourcing in the public sector vs. in-house provision of services? A thesis is that the reason may be complex, but might be found in an innovative Scandinavian regulatory approach rooted in the Nordic model.

  14. The non-operative resin treatment of proximal caries lesions.

    Science.gov (United States)

    Ekstrand, Kim; Martignon, Stefania; Bakhshandeh, Azam; Ricketts, David N J

    2012-11-01

    Epidemiological data show that the prevalence of caries on proximal surfaces in need of operative treatment is very high around the world, both in the primary and the permanent dentition. This article presents two new treatment methods: proximal sealing and proximal infiltration. The indications are progressing proximal caries lesions, radiographically with a depth around the enamel-dentine junction. A small number of studies regarding the effect of sealing and infiltration on proximal caries versus the use of fluoride varnish, placebo treatment and flossing instructions have been carried out. About half of the studies disclose a not significant difference between test and control treatment. In the other half, the therapeutic effect is significant and corresponds to about 30% reduction in lesion progression. However, longitudinal studies of longer duration are lacking. Proximal sealing and proximal infiltration may have a place in the treatment of non-cavitated proximal lesions. Proximal caries is a problem in both primary and permanent dentitions. Proximal sealants or lesion infiltration are possible treatments.

  15. Regulatory functions of microtubules.

    Science.gov (United States)

    Vasiliev, J M; Samoylov, V I

    2013-01-01

    This mini-review summarizes literature and original data about the role of microtubules in interphase animal cells. Recent data have shown that functioning of microtubules is essential for such diverse phenomena as directional cell movements, distribution of organelles in the cytoplasm, and neuronal memory in the central nervous system. It is suggested that microtubules can act as an important regulatory system in eukaryotic cells. Possible mechanisms of these functions are discussed.

  16. Regulatory aspects on nanomedicines.

    Science.gov (United States)

    Sainz, Vanessa; Conniot, João; Matos, Ana I; Peres, Carina; Zupancic, Eva; Moura, Liane; Silva, Liana C; Florindo, Helena F; Gaspar, Rogério S

    2015-12-18

    Nanomedicines have been in the forefront of pharmaceutical research in the last decades, creating new challenges for research community, industry, and regulators. There is a strong demand for the fast development of scientific and technological tools to address unmet medical needs, thus improving human health care and life quality. Tremendous advances in the biomaterials and nanotechnology fields have prompted their use as promising tools to overcome important drawbacks, mostly associated to the non-specific effects of conventional therapeutic approaches. However, the wide range of application of nanomedicines demands a profound knowledge and characterization of these complex products. Their properties need to be extensively understood to avoid unpredicted effects on patients, such as potential immune reactivity. Research policy and alliances have been bringing together scientists, regulators, industry, and, more frequently in recent years, patient representatives and patient advocacy institutions. In order to successfully enhance the development of new technologies, improved strategies for research-based corporate organizations, more integrated research tools dealing with appropriate translational requirements aiming at clinical development, and proactive regulatory policies are essential in the near future. This review focuses on the most important aspects currently recognized as key factors for the regulation of nanomedicines, discussing the efforts under development by industry and regulatory agencies to promote their translation into the market. Regulatory Science aspects driving a faster and safer development of nanomedicines will be a central issue for the next years. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Comparative analysis on the structural features of the 5' flanking region of κ-casein genes from six different species

    Directory of Open Access Journals (Sweden)

    Whitelaw C Bruce A

    2002-01-01

    Full Text Available Abstract κ-casein plays an essential role in the formation, stabilisation and aggregation of milk micelles. Control of κ-casein expression reflects this essential role, although an understanding of the mechanisms involved lags behind that of the other milk protein genes. We determined the 5'-flanking sequences for the murine, rabbit and human κ-casein genes and compared them to the published ruminant sequences. The most conserved region was not the proximal promoter region but an approximately 400 bp long region centred 800 bp upstream of the TATA box. This region contained two highly conserved MGF/STAT5 sites with common spacing relative to each other. In this region, six conserved short stretches of similarity were also found which did not correspond to known transcription factor consensus sites. On the contrary to ruminant and human 5' regulatory sequences, the rabbit and murine 5'-flanking regions did not harbour any kind of repetitive elements. We generated a phylogenetic tree of the six species based on multiple alignment of the κ-casein sequences. This study identified conserved candidate transcriptional regulatory elements within the κ-casein gene promoter.

  18. Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

    Science.gov (United States)

    Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

    2012-04-01

    The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

  19. DC Proximal Newton for Nonconvex Optimization Problems.

    Science.gov (United States)

    Rakotomamonjy, Alain; Flamary, Rémi; Gasso, Gilles

    2016-03-01

    We introduce a novel algorithm for solving learning problems where both the loss function and the regularizer are nonconvex but belong to the class of difference of convex (DC) functions. Our contribution is a new general purpose proximal Newton algorithm that is able to deal with such a situation. The algorithm consists in obtaining a descent direction from an approximation of the loss function and then in performing a line search to ensure a sufficient descent. A theoretical analysis is provided showing that the iterates of the proposed algorithm admit as limit points stationary points of the DC objective function. Numerical experiments show that our approach is more efficient than the current state of the art for a problem with a convex loss function and a nonconvex regularizer. We have also illustrated the benefit of our algorithm in high-dimensional transductive learning problem where both the loss function and regularizers are nonconvex.

  20. Proximity Effects in Superconductor-Graphene Junctions

    Science.gov (United States)

    Cuellar, Fabian A.; Perconte, David; Martin, Marie-Blandine; Dlubak, Bruno; Piquemail, Maelis; Bernard, Rozenn; Trastoy, Juan; Moreau-Luchaire, Constance; Seneor, Pierre; Villegas, Javier E.; Kidambi, Piran; Hofmann, Stephan; Robertson, John

    2015-03-01

    Superconducting proximity effects are of particular interest in graphene: because of its band structure, an unconventional (specular) Andreev reflection is expected. In this context, high-Tc superconductor-graphene junctions are especially attractive. In these, the size of the superconducting energy-gap may exceed the graphene doping inhomogeneities around the Dirac point, which should favor the observation of the specular Andreev reflection. Yet, the fabrication of high-Tc superconductor-graphene junctions is challenging: the usual growth and lithography processes in both materials are incompatible. We report here on a fabrication method that allow us to fabricate planar cuprate superconductor-graphene junctions, which we characterize via conductance spectroscopy. We analyze the features in the conductance spectra as a function of graphene doping, and discuss them in the framework of the Andreev reflection. Work supported by Labex Nanosaclay.

  1. Phonon engineering in proximity enhanced superconductor heterostructures.

    Science.gov (United States)

    Tang, Yong-Chao; Kwon, Sangil; Mohebbi, Hamid R; Cory, David G; Miao, Guo-Xing

    2017-06-27

    In this research, we tailor the phonon density of states (DOS) in thin superconducting films to suppress quasiparticle losses. We examine a model system of a proximity-enhanced three-layered Al/Nb/Al heterostructure and show that the local quantized phonon spectrum of the ultrathin Al cladding layers in the heterostructure has a pronounced effect on the superconducting resonator's quality factors. Instead of a monotonic increase of quality factors with decreasing temperatures, we observe the quality factor reaches a maximum at 1.2 K in 5/50/5 nm Al/Nb/Al microstrip resonators, because of a quantized phonon ladder. The phonon DOS may be engineered to enhance the performance of quantum devices.

  2. Mouse model of proximal tubule endocytic dysfunction.

    Science.gov (United States)

    Weyer, Kathrin; Storm, Tina; Shan, Jingdong; Vainio, Seppo; Kozyraki, Renata; Verroust, Pierre J; Christensen, Erik I; Nielsen, Rikke

    2011-11-01

    Several studies have indicated the central role of the megalin/cubilin multiligand endocytic receptor complex in protein reabsorption in the kidney proximal tubule. However, the poor viability of the existing megalin-deficient mice precludes further studies and comparison of homogeneous groups of mice. Megalin- and/or cubilin-deficient mice were generated using a conditional Cre-loxP system, where the Cre gene is driven by the Wnt4 promoter. Kidney tissues from the mice were analysed for megalin and cubilin expression by quantitative reverse transcription-polymerase chain reaction, western blotting and immunohistochemistry. Renal albumin uptake was visualized by immunohistochemistry. Twenty-four-hour urine samples were collected in metabolic cages and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting. Urinary albumin/creatinine ratios were measured by ELISA and the alkaline picrate method. The Meg(lox/lox);Cre(+), Cubn(lox/lox);Cre(+) and Meg(lox/lox), Cubn(lox/lox);Cre(+) mice were all viable, fertile and developed normal kidneys. Megalin and/or cubilin expression, assessed by immunohistology and western blotting, was reduced by >89%. Consistent with this observation, the mice excreted megalin and cubilin ligands such as transferrin and albumin in addition to low-molecular weight proteins. We further show that megalin/cubilin double-deficient mice excrete albumin with an average of 1.45 ± 0.54 mg/day, suggesting a very low albumin concentration in the glomerular ultrafiltrate. We report here the efficient genetic ablation of megalin, cubilin or both, using a Cre transgene driven by the Wnt4 promoter. The viable megalin/cubilin double-deficient mice now allow for detailed large-scale group analysis, and we anticipate that the mice will be of great value as an animal model for proximal tubulopathies with disrupted endocytosis.

  3. A scale-space curvature matching algorithm for the reconstruction of complex proximal humeral fractures.

    Science.gov (United States)

    Vlachopoulos, Lazaros; Székely, Gábor; Gerber, Christian; Fürnstahl, Philipp

    2018-01-01

    The optimal surgical treatment of complex fractures of the proximal humerus is controversial. It is proven that best results are obtained if an anatomical reduction of the fragments is achieved and, therefore, computer-assisted methods have been proposed for the reconstruction of the fractures. However, complex fractures of the proximal humerus are commonly accompanied with a relevant displacement of the fragments and, therefore, algorithms relying on the initial position of the fragments might fail. The state-of-the-art algorithm for complex fractures of the proximal humerus requires the acquisition of a CT scan of the (healthy) contralateral anatomy as a reconstruction template to address the displacement of the fragments. Pose-invariant fracture line based reconstruction algorithms have been applied successful for reassembling broken vessels in archaeology. Nevertheless, the extraction of the fracture lines and the necessary computation of their curvature are susceptible to noise and make the application of previous approaches difficult or even impossible for bone fractures close to the joints, where the cortical layer is thin. We present a novel scale-space representation of the curvature, permitting to calculate the correct alignment between bone fragments solely based on corresponding regions of the fracture lines. The fractures of the proximal humerus are automatically reconstructed based on iterative pairwise reduction of the fragments. The validation of the presented method was performed on twelve clinical cases, surgically treated after complex proximal humeral fracture, and by cadaver experiments. The accuracy of our approach was compared to the state-of-the-art algorithm for complex fractures of the proximal humerus. All reconstructions of the clinical cases resulted in an accurate approximation of the pre-traumatic anatomy. The accuracy of the reconstructed cadaver cases outperformed the current state-of-the-art algorithm. Copyright © 2017 Elsevier B

  4. Maternal residential proximity to nuclear facilities and low birth weight in offspring in Texas

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Xi; Lin, Yan [University of New Mexico, Department of Geography and Environmental Studies, Albuquerque, NM (United States); Benjamin Zhan, F. [Texas State University, Department of Geography, Texas Center for Geographic Information Science, San Marcos, TX (United States)

    2017-03-15

    Health effects of close residential proximity to nuclear facilities have been a concern for both the general public and health professionals. Here, a study is reported examining the association between maternal residential proximity to nuclear facilities and low birth weight (LBW) in offspring using data from 1996 through 2008 in Texas, USA. A case-control study design was used together with a proximity-based model for exposure assessment. First, the LBW case/control births were categorized into multiple proximity groups based on distances between their maternal residences and nuclear facilities. Then, a binary logistic regression model was used to examine the association between maternal residential proximity to nuclear facilities and low birth weight in offspring. The odds ratios were adjusted for birth year, public health region of maternal residence, child's sex, gestational weeks, maternal age, education, and race/ethnicity. In addition, sensitivity analyses were conducted for the model. Compared with the reference group (more than 50 km from a nuclear facility), the exposed groups did not show a statistically significant increase in LBW risk [adjusted odds ratio (aOR) 0.91 (95% confidence interval (CI): 0.81, 1.03) for group 40-50 km; aOR 0.98 (CI 0.84, 1.13) for group 30-40 km; aOR 0.95 (CI 0.79, 1.15) for group 20-30 km; aOR 0.86 (CI 0.70, 1.04) for group 10-20 km; and aOR 0.98 (CI 0.59, 1.61) for group 0-10 km]. These results were also confirmed by results of the sensitivity analyses. The results suggest that maternal residential proximity to nuclear facilities is not a significant factor for LBW in offspring. (orig.)

  5. Maternal residential proximity to nuclear facilities and low birth weight in offspring in Texas.

    Science.gov (United States)

    Gong, Xi; Benjamin Zhan, F; Lin, Yan

    2017-03-01

    Health effects of close residential proximity to nuclear facilities have been a concern for both the general public and health professionals. Here, a study is reported examining the association between maternal residential proximity to nuclear facilities and low birth weight (LBW) in offspring using data from 1996 through 2008 in Texas, USA. A case-control study design was used together with a proximity-based model for exposure assessment. First, the LBW case/control births were categorized into multiple proximity groups based on distances between their maternal residences and nuclear facilities. Then, a binary logistic regression model was used to examine the association between maternal residential proximity to nuclear facilities and low birth weight in offspring. The odds ratios were adjusted for birth year, public health region of maternal residence, child's sex, gestational weeks, maternal age, education, and race/ethnicity. In addition, sensitivity analyses were conducted for the model. Compared with the reference group (more than 50 km from a nuclear facility), the exposed groups did not show a statistically significant increase in LBW risk [adjusted odds ratio (aOR) 0.91 (95% confidence interval (CI): 0.81, 1.03) for group 40-50 km; aOR 0.98 (CI 0.84, 1.13) for group 30-40 km; aOR 0.95 (CI 0.79, 1.15) for group 20-30 km; aOR 0.86 (CI 0.70, 1.04) for group 10-20 km; and aOR 0.98 (CI 0.59, 1.61) for group 0-10 km]. These results were also confirmed by results of the sensitivity analyses. The results suggest that maternal residential proximity to nuclear facilities is not a significant factor for LBW in offspring.

  6. Proximal and distal muscle fatigue differentially affect movement coordination.

    Science.gov (United States)

    Cowley, Jeffrey C; Gates, Deanna H

    2017-01-01

    Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor) or distal (finger flexor) muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p fatigue caused small but significant changes in trunk angles (2°, p fatigue protocols (p fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks.

  7. Proximal and distal muscle fatigue differentially affect movement coordination

    Science.gov (United States)

    Cowley, Jeffrey C.

    2017-01-01

    Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor) or distal (finger flexor) muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p fatigue caused small but significant changes in trunk angles (2°, p fatigue protocols (p fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks. PMID:28235005

  8. Spatial Proximity and Intercompany Communication: Myths and Realities

    OpenAIRE

    Aguilera, Anne; Lethiais, Virginie; Alain RALLET

    2015-01-01

    Spatial proximity is credited with numerous virtues in the economic literature. In particular, for a company to be located near other companies is seen as conducive to the development of business relations. Spatial proximity is also considered to contribute to the quality and efficiency of these relations by facilitating face-to-face meetings that foster the exchange of complex knowledge and, in particular, the emergence of innovation. This article explores the notion of spatial proximity in ...

  9. Diagnosis of Proximal Caries in Primary Molars with DIAGNOdent pen

    OpenAIRE

    Ermler, Romy

    2010-01-01

    Proximal surfaces, together with fissures, are the areas where most primary caries occur. Due to the anatomy of the deciduous molars, proximal caries cannot be detected at an early stage in crowded teeth by simply using a mirror and probe. Therefore, additional methods to find early proximal caries have to be used. KaVo uses laser fluorescence to detect caries. Originally, the DIAGNOdent devices were able to detect only occlusal caries (56, 61, 62, 65, 66). New results are now also available ...

  10. Inexact proximal Newton methods for self-concordant functions

    DEFF Research Database (Denmark)

    Li, Jinchao; Andersen, Martin Skovgaard; Vandenberghe, Lieven

    2016-01-01

    with an application to L1-regularized covariance selection, in which prior constraints on the sparsity pattern of the inverse covariance matrix are imposed. In the numerical experiments the proximal Newton steps are computed by an accelerated proximal gradient method, and multifrontal algorithms for positive definite......We analyze the proximal Newton method for minimizing a sum of a self-concordant function and a convex function with an inexpensive proximal operator. We present new results on the global and local convergence of the method when inexact search directions are used. The method is illustrated...

  11. Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

    Directory of Open Access Journals (Sweden)

    Allan Andrew C

    2008-07-01

    Full Text Available Abstract Background Transcription factors (TFs co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1 leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA

  12. Interstitial duplication of proximal 22q: phenotypic overlap with cat eye syndrome.

    Science.gov (United States)

    Knoll, J H; Asamoah, A; Pletcher, B A; Wagstaff, J

    1995-01-16

    We describe a child with downslanting palpebral fissures, preauricular malfunctions, congenital heart defect (total anomalous pulmonary venous return), unilateral absence of a kidney, and developmental delay with an apparent interstitial duplication of proximal 22q. Fluorescent in situ hybridization (FISH) analysis showed duplication of the IGLC locus, and C-banding of the duplicated region was negative. The duplication appears to involve 22q11.2-q12. Although the child has neither colobomas nor microphthalmia, he shows phenotypic overlap with the cat eye syndrome, which is caused by a supernumerary bisatellited chromosome arising from inverted duplication of the short arm and proximal long arm of chromosome 22. Further molecular studies of this patient should help to define the regions responsible for the manifestations of cat eye syndrome.

  13. Systematic identification of regulatory variants associated with cancer risk.

    Science.gov (United States)

    Liu, Song; Liu, Yuwen; Zhang, Qin; Wu, Jiayu; Liang, Junbo; Yu, Shan; Wei, Gong-Hong; White, Kevin P; Wang, Xiaoyue

    2017-10-23

    Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities. From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375-and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach. By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.

  14. Nuclear safety assessment of nuclear power plants and nuclear risk in Eastern Europe and other regions. Scientific-technical cooperation with nuclear regulatory authorities and technical support organizations (TSOs); Einschaetzung der nuklearen Sicherheit von Kernkraftwerken sowie nuklearer Risiken in Osteuropa und anderen Regionen. Wissenschaftlich-technische Zusammenarbeit mit atomrechtlichen Behoerden und deren Sachverstaendigenorganisationen (TSO)

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, Holger

    2014-09-15

    The BMUB/BfS project 3611I01512 formed the frame of the GRS for the scientifictechnical cooperation with Technical Support Organisations and Nuclear Regulatory Authorities in the field of nuclear safety of NPPs and for the evaluation of nuclear risks in Eastern Europe and other regions for the period from September 2011 till June 2014. In the present final report main results of the project are described. The project comprised the following technical topics: - Record status of NPP modernisation programs, Monitoring and evaluation of modernisation programs; - Design basis and severe accident analyses for NPP with PWR (WWER-440, WWER-1000); - Cooperation with INSC partner countries on DBA, BDBA and severe accident analyses for WWER plants of generation 3+ and on building NRA and safety evaluation capacities; - Decommissioning of nuclear facilities and disposal of radioactive waste; - Evaluation of new reactor concepts and their safety design; Panels at regulatory level. The work results are preceded by a summary on the activities related to the project management and to the planning of the bilateral work.

  15. Progeria syndrome with characteristic deformation of proximal radius observed on CT

    Energy Technology Data Exchange (ETDEWEB)

    Sood, S.; Rao, R.C.K.; Ragav, B.; Berry, M. (All India Inst. of Medical Sciences, New Delhi (India). Dept. of Radio-Diagnosis)

    1991-01-01

    The progeria syndrome (Hutchinson-Gilford) is an uncommon disease. A peculiar shape of the proximal radial metaphyseal region caused by an infolding of the cortex was observed on CT in 2 brothers suffering from this disorder, a feature not previously reported. A brief review of the radiologic literature was undertaken. This new observation needs to be further evaluated as it may provide a clinching diagnostic feature of this disease. (orig.).

  16. Use of proximity focused HPDs for the inner trigger detector of the FINUDA experiment

    CERN Document Server

    Marchesotti, M

    2000-01-01

    A barrel scintillator detector viewed by proximity focused HPDs will be employed in the inner region of the FINUDA experiment inside a 1.1 T magnetic field to provide a fast first level trigger, the common stop for drift chambers and straw tubes and the start signal for Time-of-Flight (ToF) measurements. The overall performances have been tested with a laser system and sup 9 sup 0 Sr radiation source.

  17. Characterization of interactions between transcription factors and a regulatory region spanning nt-320 to-281 of the HIV-1 LTR in T-lymphoid and non-T-lymphoid cells

    NARCIS (Netherlands)

    Pereira, LA; Churchill, MJ; Elefanty, AG; Gouskos, T; Lambert, PF; Ramsay, RG; Deacon, NJ

    2002-01-01

    HIV-1 gene expression is regulated by the interplay of transcription factors with multiple binding motifs present within the U3, R and U5 regions of the long terminal repeat (LTR). Here we report novel DNA binding complexes (termed 9a, 9b and 9c) between nuclear proteins from T-lymphoid and

  18. Long endomedullary nail in proximal third humeral shaft fractures.

    Science.gov (United States)

    Caforio, Marco; Maniscalco, Pietro; Colombo, Massimiliano; Calori, Giorgio Maria

    2016-10-01

    Proximal humeral fractures with a spiral line of fracture extending from the humeral head to the diaphyseal region are increasing. Treatment for these fractures is comparable to that for shaft fractures. The purpose of this study was to evaluate the use of a new "Long" humeral nail for this type of lesion and identify the best distal locking. Forty-three patients treated with a Long Diphos Nail® were selected for this study: main exclusion criteria were poor cognitive and responsive ability to physical therapy, four-part fracture requiring humeral head replacement, an isolated greater or lesser tubercle fracture and a head-splitting fracture. All patients were divided into two groups according to the distal locking (single or double) and clinically evaluated at 1, 3, 6 and 12 months after surgery. The following parameters were evaluated: fracture healing on radiographic images every month; level of pain with Visual Analogue Scale (VAS); recovery of shoulder function or ability to resume normal daily activities according to the Constant Scoring System (CSS); patient satisfaction; and complications, like fracture consolidation defect or delay. A statistical analysis was performed. Improvements in pain, satisfaction and shoulder functional recovery were recorded. Patients reached fracture healing in two to six months. The mean healing time was better for double distal locking (p=0.04).There was a clinically greater difference (p=0.006) between the groups for the mean Constant score at 3 months follow-up, with better results for the double distal locking group. Complications were: one patient with a consolidation delay with a single distal locking screw breakage; it was necessary to remove the nail and perform a second treatment. The results of the study indicate the efficacy of Long Diphos Nail® in the treatment of fractures with a line of fracture extending to the proximal diaphyseal region. The features of a multiplane stabilisation above the fracture and a distal

  19. Treatment of proximal fifth metatarsal bone fractures in athletes.

    Science.gov (United States)

    Japjec, M; Starešinić, M; Starjački, M; Žgaljardić, I; Štivičić, J; Šebečić, B

    2015-11-01

    Proximal fifth metatarsal (V MT) bone fractures are common injuries that are a major diagnostic and therapeutic challenge. Lawrence and Botte considered different treatment options and the possibility of recovery and divided these fractures into three different regions: tuberosity avulsion fractures (zone I), acute fractures of the metaphysis at the level of the intermetatarsal junction (zone II) and proximal diaphysis stress fracture (zone III). A total of 42 athletes with fracture of the V MT bone in zone II and III were treated in our institution during a 6-year period. All patients were offered surgical treatment, but nine patients refused surgery. Thus, the patients were divided into two groups: group 1 comprised 33 patients who underwent an intramedullary screw fixation operation under regional anaesthesia immediately after the fracture was diagnosed; group 2 contained the remaining nine patients who had refused surgery and received conservative therapy with non-weight-bearing short-leg casts or orthosis. Follow-up ranged from 6 to 24 months. All fractures healed in group 1: healing occurred within 8 weeks in 26 patients and was prolonged to 16 to 18 weeks in four patients. In group 2, fractures healed in four patients but did not heal in five patients even after 6 months. Four of the five patients in whom the fracture did not heal required subsequent osteosynthesis because they had constant problems that caused absence from sport. After the operation, their fractures healed in an average of 10 weeks. One patient decided not to undergo the operation due to the absence of subjective symptoms. Three patients in group 1 who started intensive training sustained a refracture and underwent re-operation in which osteosynthesis was performed with a stronger screw. The fractures then healed again. Treatment results were evaluated radiologically and clinically using the Modified Foot Score. Results in group 1 were significantly better than those in group 2 and there

  20. On blockage effects for a marine hydrokinetic turbine in free surface proximity

    Science.gov (United States)

    Banerjee, A.; Kolekar, N.

    2016-12-01

    Experimental investigation was carried out with a three-bladed, constant chord marine hydrokinetic turbine to understand the influence of free surface proximity on blockage effects and near wake flow field. The turbine was placed at various depths of immersion as rotational speeds and flow speeds were varied; thrust and torque data was acquired through a submerged thrust torque sensor positioned in-line with the turbine axis. Blockage effects were quantified in terms of changes in power coefficient and were found to be dependent on flow velocity, rotational speed and blade-tip clearence (from free-surface). Flow acceleration near turbine rotation plane was attributed to blockage offered by the rotor, wake, and free surface deformation; the resulting performance improvements were calculated based on the measured thrust values. In addition, stereoscopic particle imaging velocimetry was carried out in the near-wake region using time-averaged and phase-averaged techniques to understand the mechanism responsible for variation of torque (and power coefficient) with rotational speed and free-surface proximity. Flow vizualisation revealed slower wake propagation for higher rotational velocities and increased assymetry in the wake with increasing free surface proximity. Improved performance at high rotational speed was attributed to enhanced wake blockage; performance enhancements with free-surface proximity was attributed to additional blockage effects caused by free surface deformation.

  1. Congenital anomalies, prematurity, and low birth weight rates in relation to nuclear power plant proximity1).

    Science.gov (United States)

    Mangones, Tania; Visintainer, Paul; Brumberg, Heather L

    2013-07-01

    The objective of this study was to determine whether maternal residential proximity to a nuclear reactor is associated with prevalence of certain birth defects. The New York State Vital Statistics and Congenital Malformations Registry data (1992-2001) were analyzed for five Hudson Valley counties in a 20-mile radius from the Indian Point nuclear reactor (Buchanan, NY, USA). Four zones of 5-mile increments were used to categorize proximity to the reactor. Data included congenital anomalies, low birth weight, and prematurity. Over the 10-year period, 702 malformations in 666 children were identified from a birth population of 328,124, yielding a regional rate of 2.1 major malformations per 1000 births. The prevalence of defects, low birth weight, and prematurity were not related to proximity to the nuclear power plant. These data did not substantiate an association between maternal proximity to the reactor and certain birth defects and provide baseline data for comparison in the event of a nuclear accident.

  2. Meeting Regulatory Needs.

    Science.gov (United States)

    Weber, Michael Fred

    2017-02-01

    The world is experiencing change at an unprecedented pace, as reflected in social, cultural, economic, political, and technological advances around the globe. Regulatory agencies, like the U.S. Nuclear Regulatory Commission (NRC), must also transform in response to and in preparation for these changes. In 2014, the NRC staff commenced Project Aim 2020 to transform the agency by enhancing efficiency, agility, and responsiveness, while accomplishing NRC's safety and security mission. Following Commission review and approval in 2015, the NRC began implementing the approved strategies, including strategic workforce planning to provide confidence that NRC will have employees with the right skills and talents at the right time to accomplish the agency's mission. Based on the work conducted so far, ensuring an adequate pipeline of radiation protection professionals is a significant need that NRC shares with states and other government agencies, private industry, academia, as well as international counterparts. NRC is working to ensure that sufficient radiation protection professionals will be available to fulfill its safety and security mission and leverage the work of the National Council on Radiation Protection and Measurements, the Conference of Radiation Control Program Directors, the Health Physics Society, the Organization of Agreement States, the International Atomic Energy Agency, the Nuclear Energy Agency, and others.

  3. Imaging of rectus femoris proximal tendinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Pesquer, Lionel; Poussange, Nicolas; Meyer, Philippe; Dallaudiere, Benjamin; Feldis, Matthieu [Clinique du Sport de Bordeaux, Centre d' Imagerie Osteo-articulaire, Merignac (France); Sonnery-Cottet, Bertrand [Groupe Ramsay Generale de Sante - Hopital Prive Jean Mermoz, Centre Orthopedique Santy, Lyon (France); Graveleau, Nicolas [Clinique du Sport de Bordeaux, Centre de Chirurgie Orthopedique et Sportive, Merignac (France)

    2016-07-15

    The rectus femoris is the most commonly injured muscle of the anterior thigh among athletes, especially soccer players. Although the injury pattern of the muscle belly is well documented, less is known about the anatomy and specific lesions of the proximal tendons. For each head, three distinctive patterns may be encountered according to the location of the injury, which can be at the enthesis, within the tendon, or at the musculotendinous junction. In children, injuries correspond most commonly to avulsion of the anteroinferior iliac spine from the direct head and can lead to subspine impingement. Calcific tendinitis and traumatic tears may be encountered in adults. Recent studies have shown that traumatic injuries of the indirect head may be underdiagnosed and that injuries of both heads may have a surgical issue. Finally, in the case of tears, functional outcome and treatment may vary if the rupture involves one or both tendons and if the tear is partial or complete. Thus, it is mandatory for the radiologist to know the different ultrasound and magnetic resonance imaging (MRI) patterns of these lesions in order to provide accurate diagnosis and treatment. The purpose of this article is to recall the anatomy of the two heads of rectus femoris, describe a reliable method of assessment with ultrasound and MRI and know the main injury patterns, through our own experience and literature review. (orig.)

  4. Proximate industrial activity and psychological distress

    Science.gov (United States)

    Downey, Liam; Jackson, James S.; Merrill, J. Bryce; Saint Onge, Jarron M.; Williams, David R.

    2009-01-01

    This paper examines the role that gender, occupational status, and family status play in moderating the effect of industrial activity on the psychological well-being of nearby residents. Using a unique spatial assessment of industrial activity and an environmental risk/social stressor framework in conjunction with individual-level data from the Detroit Area Study (DAS) and demographic data from the U.S. census, we find that residents of neighborhoods in close proximity to industrial activity report elevated levels of psychological distress compared to residents of neighborhoods removed from this type of activity. These influences are more pronounced among women but gender differences are also contingent upon occupational and family statuses. We show that specific combinations of work and family statuses make persons particularly vulnerable to the influence of this environmental stressor and women are two and a half times more likely than men to have these vulnerable statuses. This study makes an important contribution to the environmental health literature because it reminds researchers of the fundamental influence of social roles when examining the link between environmental risks and mental health. PMID:19444334

  5. [Ophthalmologists in the proximity of Adolf Hitler].

    Science.gov (United States)

    Rohrbach, J M

    2012-10-01

    Adolf Hitler met or at least knew about 5 ophthalmologists. The chair of ophthalmology in Berlin, Walther Löhlein, personally examined Hitler's eyes at least two times. The chair of ophthalmology in Breslau, Walter Dieter, developed "air raid protection spectacles" with the aid of high representatives of the NS-system and probably Adolf Hitler himself. Heinrich Wilhelm Kranz became rector of the universities of Giessen and Frankfurt/Main. He was known as a very strict advocate of the NS-race hygiene. Werner Zabel made plans for Hitler's diet and tried to interfere with Hitler's medical treatment. Finally, Hellmuth Unger was an influential representative of the medical press and a famous writer. Three of his novels with medical topics were made into a film which Hitler probably saw. Hitler had, so to say, a small "ophthalmological proximity" which, however, did not play a significant role for himself or the NS-state. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Proximity coupling in superconductor-graphene heterostructures.

    Science.gov (United States)

    Lee, Gil-Ho; Lee, Hu-Jong

    2018-02-16

    This review discusses the electronic properties and the prospective research directions of superconductor-graphene heterostructures. The basic electronic properties of graphene are introduced to highlight the unique possibility of combining two seemingly unrelated physics, superconductivity and relativity. We then focus on graphene-based Josephson junctions, one of the most versatile superconducting quantum devices. The various theoretical methods that have been developed to describe graphene Josephson junctions are examined, together with their advantages and limitations, followed by a discussion on the advances in device fabrication and the relevant length scales. The phase-sensitive properties and phase-particle dynamics of graphene Josephson junctions are examined to provide an understanding of the underlying mechanisms of Josephson coupling via graphene. Thereafter, microscopic transport of correlated quasiparticles produced by Andreev reflections at superconducting interfaces and their phase-coherent behaviors are discussed. Quantum phase transitions studied with graphene as an electrostatically tunable two-dimensional platform are reviewed. The interplay between proximity-induced superconductivity and the quantum-Hall phase is discussed as a possible route to study topological superconductivity and non-Abelian physics. Finally, a brief summary on the prospective future research directions is given. © 2018 IOP Publishing Ltd.

  7. Semiconductor detectors with proximity signal readout

    Energy Technology Data Exchange (ETDEWEB)

    Asztalos, Stephen J. [XIA, LLC, Hayward, CA (United States)

    2014-01-30

    Semiconductor-based radiation detectors are routinely used for the detection, imaging, and spectroscopy of x-rays, gamma rays, and charged particles for applications in the areas of nuclear and medical physics, astrophysics, environmental remediation, nuclear nonproliferation, and homeland security. Detectors used for imaging and particle tracking are more complex in that they typically must also measure the location of the radiation interaction in addition to the deposited energy. In such detectors, the position measurement is often achieved by dividing or segmenting the electrodes into many strips or pixels and then reading out the signals from all of the electrode segments. Fine electrode segmentation is problematic for many of the standard semiconductor detector technologies. Clearly there is a need for a semiconductor-based radiation detector technology that can achieve fine position resolution while maintaining the excellent energy resolution intrinsic to semiconductor detectors, can be fabricated through simple processes, does not require complex electrical interconnections to the detector, and can reduce the number of required channels of readout electronics. Proximity electrode signal readout (PESR), in which the electrodes are not in physical contact with the detector surface, satisfies this need.

  8. Altruism by age and social proximity.

    Science.gov (United States)

    Long, Mark C; Krause, Eleanor

    2017-01-01

    This study evaluates the extent to which an individual's stated altruistic sentiments can be influenced by context-most importantly, by the age and social proximity of the other person and by the nature of what is being sacrificed. We measure willingness to sacrifice own health for another person's health and willingness to sacrifice own wealth for another person's wealth. To evaluate these sentiments, two surveys were administered to representative samples of Americans which contained hypothetical scenarios with context randomly assigned; the first survey posed a dictator game question and the second survey was designed to elicit marginal rates of substitution between own and other's health/wealth. As expected, we find less altruism towards those who are more socially distant (e.g., strangers relative to family). We find individuals are more health altruistic towards young children and more wealth altruistic towards adults, and health altruism tends to be lowest for survey respondents near retirement age. We find no relationship between levels of altruism and the distance between the respondent's state of birth and state of current residence. These findings improve society's understanding of situational altruism and kinship and reciprocity as motivations for altruism, and they have practical implications concerning the economic valuation of human lives used to guide public policy-making.

  9. Proximal spinal muscular atrophy: current orthopedic perspective

    Directory of Open Access Journals (Sweden)

    Haaker G

    2013-11-01

    Full Text Available Gerrit Haaker, Albert Fujak Department of Orthopaedic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Abstract: Spinal muscular atrophy (SMA is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective "survival motor neuron" (SMN protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. Keywords: spinal muscular atrophy, scoliosis, contractures, fractures, lung function, treatment, rehabilitation, surgery, ventilation, nutrition, perioperative management

  10. Optical proximity correction with principal component regression

    Science.gov (United States)

    Gao, Peiran; Gu, Allan; Zakhor, Avideh

    2008-03-01

    An important step in today's Integrated Circuit (IC) manufacturing is optical proximity correction (OPC). In model based OPC, masks are systematically modified to compensate for the non-ideal optical and process effects of optical lithography system. The polygons in the layout are fragmented, and simulations are performed to determine the image intensity pattern on the wafer. Then the mask is perturbed by moving the fragments to match the desired wafer pattern. This iterative process continues until the pattern on the wafer matches the desired one. Although OPC increases the fidelity of pattern transfer to the wafer, it is quite CPU intensive; OPC for modern IC designs can take days to complete on computer clusters with thousands of CPU. In this paper, techniques from statistical machine learning are used to predict the fragment movements. The goal is to reduce the number of iterations required in model based OPC by using a fast and efficient solution as the initial guess to model based OPC. To determine the best model, we train and evaluate several principal component regression models based on prediction error. Experimental results show that fragment movement predictions via regression model significantly decrease the number of iterations required in model based OPC.

  11. Altruism by age and social proximity.

    Directory of Open Access Journals (Sweden)

    Mark C Long

    Full Text Available This study evaluates the extent to which an individual's stated altruistic sentiments can be influenced by context-most importantly, by the age and social proximity of the other person and by the nature of what is being sacrificed. We measure willingness to sacrifice own health for another person's health and willingness to sacrifice own wealth for another person's wealth. To evaluate these sentiments, two surveys were administered to representative samples of Americans which contained hypothetical scenarios with context randomly assigned; the first survey posed a dictator game question and the second survey was designed to elicit marginal rates of substitution between own and other's health/wealth. As expected, we find less altruism towards those who are more socially distant (e.g., strangers relative to family. We find individuals are more health altruistic towards young children and more wealth altruistic towards adults, and health altruism tends to be lowest for survey respondents near retirement age. We find no relationship between levels of altruism and the distance between the respondent's state of birth and state of current residence. These findings improve society's understanding of situational altruism and kinship and reciprocity as motivations for altruism, and they have practical implications concerning the economic valuation of human lives used to guide public policy-making.

  12. Altruism by age and social proximity

    Science.gov (United States)

    2017-01-01

    This study evaluates the extent to which an individual’s stated altruistic sentiments can be influenced by context–most importantly, by the age and social proximity of the other person and by the nature of what is being sacrificed. We measure willingness to sacrifice own health for another person’s health and willingness to sacrifice own wealth for another person’s wealth. To evaluate these sentiments, two surveys were administered to representative samples of Americans which contained hypothetical scenarios with context randomly assigned; the first survey posed a dictator game question and the second survey was designed to elicit marginal rates of substitution between own and other’s health/wealth. As expected, we find less altruism towards those who are more socially distant (e.g., strangers relative to family). We find individuals are more health altruistic towards young children and more wealth altruistic towards adults, and health altruism tends to be lowest for survey respondents near retirement age. We find no relationship between levels of altruism and the distance between the respondent’s state of birth and state of current residence. These findings improve society’s understanding of situational altruism and kinship and reciprocity as motivations for altruism, and they have practical implications concerning the economic valuation of human lives used to guide public policy-making. PMID:28837557

  13. Regulatory elements in molecular networks.

    Science.gov (United States)

    Doane, Ashley S; Elemento, Olivier

    2017-05-01

    Regulatory elements determine the connectivity of molecular networks and mediate a variety of regulatory processes ranging from DNA looping to transcriptional, posttranscriptional, and posttranslational regulation. This review highlights our current understanding of the different types of regulatory elements found in molecular networks with a focus on DNA regulatory elements. We highlight technical advances and current challenges for the mapping of regulatory elements at the genome-wide scale, and describe new computational methods to uncover these elements via reconstructing regulatory networks from large genomic datasets. WIREs Syst Biol Med 2017, 9:e1374. doi: 10.1002/wsbm.1374 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  14. On the existence of best proximity points for generalized contractions

    Directory of Open Access Journals (Sweden)

    V. Vetrivel

    2014-04-01

    Full Text Available In this article we establish the existence of a unique best proximity point for some generalized non self contractions on a metric space in a simpler way using a geometric result. Our results generalize some recent best proximity point theorems and several fixed point theorems proved by various authors.

  15. Phytochemical, Proximate and Toxicity Studies of Aqueous Extract of ...

    African Journals Online (AJOL)

    Phytochemical, Proximate and Toxicity Studies of Aqueous Extract of Crinum ornatum (Toad's Onion) ... The results indicate that, the bulbs can be considered as a spice that could serve as potential sources of flavouring agent with medicinal benefits. Keywords: Crinum ornatum, Phytochemical, Proximate, Toxicity ...

  16. Proximity and inter-organizational collaboration: a literature review

    NARCIS (Netherlands)

    Knoben, J.; Oerlemans, L.A.G.

    2006-01-01

    The proximity concept is used in many different ways in the literature. These dimensions of proximity are, however, defined and measured in many different (sometimes even contradictory) ways, show large amounts of overlap, and often are under- or over-specified. The goal of this paper is to specify

  17. Proximate composition and levels of some toxicants in four ...

    African Journals Online (AJOL)

    Proximate composition and levels of some toxicants (anti-nutrients) in four commonly consumed spices were investigated. The spices were garlic (Allium sativum), ginger (Zingiber officinale), onion (Allium cepa var. cepa), and Piper guineense seeds (Ashanti pepper). Proximate analyses showed the spices to contain (on ...

  18. Proximal and distal muscle fatigue differentially affect movement coordination.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Cowley

    Full Text Available Muscle fatigue can cause people to change their movement patterns and these changes could contribute to acute or overuse injuries. However, these effects depend on which muscles are fatigued. The purpose of this study was to determine the differential effects of proximal and distal upper extremity muscle fatigue on repetitive movements. Fourteen subjects completed a repetitive ratcheting task before and after a fatigue protocol on separate days. The fatigue protocol either fatigued the proximal (shoulder flexor or distal (finger flexor muscles. Pre/Post changes in trunk, shoulder, elbow, and wrist kinematics were compared to determine how proximal and distal fatigue affected multi-joint movement patterns and variability. Proximal fatigue caused a significant increase (7°, p < 0.005 in trunk lean and velocity, reduced humeral elevation (11°, p < 0.005, and increased elbow flexion (4°, p < 0.01. In contrast, distal fatigue caused small but significant changes in trunk angles (2°, p < 0.05, increased velocity of wrench movement relative to the hand (17°/s, p < 0.001, and earlier wrist extension (4%, p < 0.005. Movement variability increased at proximal joints but not distal joints after both fatigue protocols (p < 0.05. Varying movements at proximal joints may help people adapt to fatigue at either proximal or distal joints. The identified differences between proximal and distal muscle fatigue adaptations could facilitate risk assessment of occupational tasks.

  19. Properties of Sn-Ag proximity effect bridges

    Energy Technology Data Exchange (ETDEWEB)

    Fan Hongchang; Yu Zheng

    1983-09-01

    We have measured the I-V characteristics, I/sub c/(t) and T/sub c/ of Sn-Ag proximity effect bridges, obtaining some interesting results. We have also analyzed and tried to explain the results in terms of phenomenological theories, believing that microbridge theories of Skocpol, Beasley and Tinkham (SBT) also apply to our proximity effect bridges.

  20. Determination of Proximate Composition and Amino Acid Profile of ...

    African Journals Online (AJOL)

    The proximate composition and amino acid profile of the seed of 30 Nigerian sesame genotypes were determined based on the standard methods of the Association of Official Analytical Chemists (AOAC) and the Sequential Multi- sample amino acid Analyzer (TSM). Proximate analysis showed that sesame seed contained ...

  1. Management of proximal interphalangeal joint dislocations in athletes.

    Science.gov (United States)

    Bindra, Randy R; Foster, Brian J

    2009-08-01

    Proximal interphalangeal joint dislocations are common athletic injuries. In dislocations and fracture dislocations, the most important treatment principle is congruent joint reduction and maintenance of stability. This article reviews the relevant anatomy, injury characteristics, and treatment options for proximal interphalangeal joint dislocations and fracture dislocations. Treatment methods discussed include closed reduction, percutaneous fixation, and open reduction.

  2. Water Balance and Proximate Composition in Cowpea ( vigna ...

    African Journals Online (AJOL)

    Studying the water balance and proximate composition in plants subjected to these stresses compared the influence of drought and flooding on cowpea seedlings. In drought plants the leaf water potential, its components and the proximate composition were markedly reduced by the end of the experimental period.

  3. Cast index in predicting outcome of proximal pediatric forearm fractures

    Directory of Open Access Journals (Sweden)

    Hassaan Qaiser Sheikh

    2015-01-01

    Conclusion: Cast index is useful in predicting redisplacement of manipulated distal forearm fractures. We found that in proximal half forearm fractures it is difficult to achieve a CI of <0.8, but increased CI does not predict loss of position in these fractures. We therefore discourage the use of CI in proximal half forearm fractures.

  4. Proximate composition and mineral contents of Pebbly fish, Alestes ...

    African Journals Online (AJOL)

    ACSS

    The objective of this study was to determine the proximate composition and mineral contents of A. ... and also develop suitable processing method. This study determined the proximate composition and mineral contents of A. baremoze fillets based on fish size. Materials and .... moisture contents can vary with sex of the fish ...

  5. proximal femur geometry in the adult kenyan femur and its ...

    African Journals Online (AJOL)

    implications considering that the implants used to treat fractures in the proximal femur would usually traverse the neck and lodge in the femoral head. A very narrow neck may not allow adequate implant placement especially for those implants that employ two proximal locking screws. This has been shown, in a study by ...

  6. Spontaneous Healing of a Pediatric Scaphoid Proximal Pole Fracture Nonunion.

    Science.gov (United States)

    Rupani, Neal; Riley, Nicholas; McNab, Ian

    2018-02-01

    Background  Scaphoid fractures in the pediatric population are rare. The majority of nondisplaced fractures tend to unite; however, there is an increased risk of nonunion in proximal pole fractures. Limited evidence exists in their outcomes, owing to the scarcity of the fracture pattern. Case Description  A 13-year-old boy who presented late after developing a traumatic proximal pole scaphoid fracture developed nonunion. He was treated conservatively owing to it being asymptomatic and developed union at 18 months. Literature Review  No previous case of proximal pole pediatric scaphoid fractures with established nonunion that has developed union with conservative management has been described. Clinical Relevance  The authors highlight a unique case of an established proximal pole scaphoid nonunion in a child progressing to union with nonoperative intervention. Owing to its rarity and difficulty in obtaining research, we recommend consideration of nonoperative management of asymptomatic nondisplaced proximal pole fractures in children.

  7. 78 FR 62417 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Science.gov (United States)

    2013-10-22

    ... Part 324 RIN 3064-AD95 Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III... Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy, Transition Provisions...

  8. Incidence, mode, and location of acute proximal junctional failures after surgical treatment of adult spinal deformity.

    Science.gov (United States)

    Hostin, Richard; McCarthy, Ian; OʼBrien, Michael; Bess, Shay; Line, Breton; Boachie-Adjei, Oheneba; Burton, Doug; Gupta, Munish; Ames, Christopher; Deviren, Vedat; Kebaish, Khaled; Shaffrey, Christopher; Wood, Kirkham; Hart, Robert

    2013-05-20

    Multicenter, retrospective series. To analyze the incidence, mode, and location of acute proximal junctional failures (APJFs) after surgical treatment of adult spinal deformity. Early proximal junctional failures above adult deformity constructs are a serious clinical problem; however, the incidence and nature of early APJFs remain unclear. A total of 1218 consecutive adult spinal deformity surgeries across 10 deformity centers were retrospectively reviewed to evaluate the incidence and nature of APJF, defined as any of the following within 28 weeks of index procedure: minimum 15° post-operative increase in proximal junctional kyphosis, vertebral fracture of upper instrumented vertebrae (UIV) or UIV + 1, failure of UIV fixation, or need for proximal extension of fusion within 6 months of surgery. Sixty-eight APJF cases were identified out of 1218 consecutive surgeries (5.6%). Patients had a mean age of 63 years (range, 26-82 yr), mean fusion levels of 9.8 (range, 4-18), and mean time to APJF of 11.4 weeks (range, 1.5-28 wk). Fracture was the most common failure mode (47%), followed by soft-tissue failure (44%). Failures most often occurred in the thoracolumbar region (TL-APJF) compared with the upper thoracic region (UT-APJF), with 66% of patients experiencing TL-APJF compared with 34% experiencing UT-APJF. Fracture was significantly more common for TL-APJF relative to UT-APJF (P = 0.00), whereas soft-tissue failure was more common for UT-APJF (P failures occurring primarily in the TL region of the spine. There is evidence that the mode of failure differs depending on the location of UIV, with TL failures more likely due to fracture and UT failures more likely due to soft-tissue failures.

  9. Event-triggered Decision Propagation in Proximity Networks

    Directory of Open Access Journals (Sweden)

    Soumik eSarkar

    2014-12-01

    Full Text Available This paper proposes a novel event-triggered formulation as an extension of the recently develo-ped generalized gossip algorithm for decision/awareness propagation in mobile sensor networksmodeled as proximity networks. The key idea is to expend energy for communication (messagetransmission and reception only when there is any event of interest in the region of surveillance.The idea is implemented by using an agent’s belief about presence of a hotspot as feedback tochange its probability of (communication activity. In the original formulation, the evolution ofnetwork topology and the dynamics of decision propagation were completely decoupled whichis no longer the case as a consequence of this feedback policy. Analytical results and numeri-cal experiments are presented to show a significant gain in energy savings with no change inthe first moment characteristics of decision propagation. However, numerical experiments showthat the second moment characteristics may change and theoretical results are provided forupper and lower bounds for second moment characteristics. Effects of false alarms on networkformation and communication activity are also investigated.

  10. Proximity graphs based multi-scale image segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Skurikhin, Alexei N [Los Alamos National Laboratory

    2008-01-01

    We present a novel multi-scale image segmentation approach based on irregular triangular and polygonal tessellations produced by proximity graphs. Our approach consists of two separate stages: polygonal seeds generation followed by an iterative bottom-up polygon agglomeration into larger chunks. We employ constrained Delaunay triangulation combined with the principles known from the visual perception to extract an initial ,irregular polygonal tessellation of the image. These initial polygons are built upon a triangular mesh composed of irregular sized triangles and their shapes are ad'apted to the image content. We then represent the image as a graph with vertices corresponding to the polygons and edges reflecting polygon relations. The segmentation problem is then formulated as Minimum Spanning Tree extraction. We build a successive fine-to-coarse hierarchy of irregular polygonal grids by an iterative graph contraction constructing Minimum Spanning Tree. The contraction uses local information and merges the polygons bottom-up based on local region-and edge-based characteristics.

  11. Quasiclassical theory for the superconducting proximity effect in Dirac materials

    Science.gov (United States)

    Hugdal, Henning G.; Linder, Jacob; Jacobsen, Sol H.

    2017-06-01

    We derive the quasiclassical nonequilibrium Eilenberger and Usadel equations to first order in quantities small compared to the Fermi energy, valid for Dirac edge and surface electrons with spin-momentum locking p .σ ¯ , as relevant for topological insulators. We discuss in detail several of the key technical points and assumptions of the derivation, and provide a Riccati parametrization of the equations. Solving first the equilibrium equations for S/N and S/F bilayers and Josephson junctions, we study the superconducting proximity effect in Dirac materials. Similarly to related works, we find that the effect of an exchange field depends strongly on the direction of the field. Only components normal to the transport direction lead to attenuation of the Cooper pair wave function inside the F. Fields parallel to the transport direction lead to phase shifts in the dependence on the superconducting phase difference for both the charge current and density of states in an S/F/S junction. Moreover, we compute the differential conductance in S/N and S/F bilayers with an applied voltage bias and determine the dependence on the length of the N and F regions and the exchange field.

  12. Nanocrystal Bioassembly: Asymmetry, Proximity, and Enzymatic Manipulation

    Energy Technology Data Exchange (ETDEWEB)

    Claridge, Shelley A. [Univ. of California, Berkeley, CA (United States)

    2008-05-01

    Research at the interface between biomolecules and inorganic nanocrystals has resulted in a great number of new discoveries. In part this arises from the synergistic duality of the system: biomolecules may act as self-assembly agents for organizing inorganic nanocrystals into functional materials; alternatively, nanocrystals may act as microscopic or spectroscopic labels for elucidating the behavior of complex biomolecular systems. However, success in either of these functions relies heavily uponthe ability to control the conjugation and assembly processes.In the work presented here, we first design a branched DNA scaffold which allows hybridization of DNA-nanocrystal monoconjugates to form discrete assemblies. Importantly, the asymmetry of the branched scaffold allows the formation of asymmetric2assemblies of nanocrystals. In the context of a self-assembled device, this can be considered a step toward the ability to engineer functionally distinct inputs and outputs.Next we develop an anion-exchange high performance liquid chromatography purification method which allows large gold nanocrystals attached to single strands of very short DNA to be purified. When two such complementary conjugates are hybridized, the large nanocrystals are brought into close proximity, allowing their plasmon resonances to couple. Such plasmon-coupled constructs are of interest both as optical interconnects for nanoscale devices and as `plasmon ruler? biomolecular probes.We then present an enzymatic ligation strategy for creating multi-nanoparticle building blocks for self-assembly. In constructing a nanoscale device, such a strategy would allow pre-assembly and purification of components; these constructs can also act as multi-label probes of single-stranded DNA conformational dynamics. Finally we demonstrate a simple proof-of-concept of a nanoparticle analog of the polymerase chain reaction.

  13. Translational Imaging Spectroscopy for Proximal Sensing.

    Science.gov (United States)

    Rogass, Christian; Koerting, Friederike M; Mielke, Christian; Brell, Maximilian; Boesche, Nina K; Bade, Maria; Hohmann, Christian

    2017-08-11

    Proximal sensing as the near field counterpart of remote sensing offers a broad variety of applications. Imaging spectroscopy in general and translational laboratory imaging spectroscopy in particular can be utilized for a variety of different research topics. Geoscientific applications require a precise pre-processing of hyperspectral data cubes to retrieve at-surface reflectance in order to conduct spectral feature-based comparison of unknown sample spectra to known library spectra. A new pre-processing chain called GeoMAP-Trans for at-surface reflectance retrieval is proposed here as an analogue to other algorithms published by the team of authors. It consists of a radiometric, a geometric and a spectral module. Each module consists of several processing steps that are described in detail. The processing chain was adapted to the broadly used HySPEX VNIR/SWIR imaging spectrometer system and tested using geological mineral samples. The performance was subjectively and objectively evaluated using standard artificial image quality metrics and comparative measurements of mineral and Lambertian diffuser standards with standard field and laboratory spectrometers. The proposed algorithm provides highly qualitative results, offers broad applicability through its generic design and might be the first one of its kind to be published. A high radiometric accuracy is achieved by the incorporation of the Reduction of Miscalibration Effects (ROME) framework. The geometric accuracy is higher than 1 μpixel. The critical spectral accuracy was relatively estimated by comparing spectra of standard field spectrometers to those from HySPEX for a Lambertian diffuser. The achieved spectral accuracy is better than 0.02% for the full spectrum and better than 98% for the absorption features. It was empirically shown that point and imaging spectrometers provide different results for non-Lambertian samples due to their different sensing principles, adjacency scattering impacts on the signal

  14. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  15. Observer differentiation of proximal enamel mechanical defects versus natural proximal dental caries with computed dental radiography.

    Science.gov (United States)

    Kang, B C; Farman, A G; Scarfe, W C; Goldsmith, L J

    1996-10-01

    Various models have been used to study the accuracy of imaging systems for detection of dental caries. This study compares the ability of dentists to detect mechanically created defects versus natural dental caries cavitations on the proximal surfaces of extracted teeth with Computed Dental Radiography (Schick Industries, Long Island City, N.Y.). Detection rates are investigated according to lesion depth to permit comparisons to be made between studies in the literature with other mechanical defects or natural caries models. Discrimination of natural caries versus artificial defects with Computed Dental Radiography is also compared with a previous report that used standard dental film. Fifty-two extracted molar and premolar teeth were mounted into representative sets of maxillary and mandibular posterior arches for bite-wing radiography. There were 16 proximal surfaces with natural caries and 28 proximal surfaces with mechanical defects. An optical bench was used to ensure constant beam geometry. A 1.8 cm acrylic soft tissue equivalent attenuator was placed in front of the receptor. Thirty dentists acted independently as observers to differentiate between sound proximal tooth surfaces, natural dental caries, and mechanical defects. Evaluation of intra- and interobserver variability was made with use of the kappa statistic. The Zelen test of odds ratios was used to test for homogeneity, and the Mantel-Haenszel analysis plus stratified logistic regression were used for inference about the common odds ratio. Significance was set at p detection was 74% for mechanical defects and 67% for natural caries. The odds of detecting a mechanical defect were 1.40 times the odds of finding natural dental caries cavitation of the same depth. Lesion depth did influence the probability of correctly identifying the presence of a lesion; the odds of identifying cavitation increased 1.41 times with every 0.1 mm increase in lesion depth. Correct designation of lesion type was 1.42 times

  16. Regulatory considerations for biosimilars

    Directory of Open Access Journals (Sweden)

    Ranjani Nellore

    2010-01-01

    Full Text Available Currently there is considerable interest in the legislative debate around generic biological drugs or "biosimilars" in the EU and US due to the large, lucrative market that it offers to the industry. While some countries have issued a few regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism similar to the bioequivalence determination that leads to approval of generic small molecules all over the world. The inherent complex nature of the molecules, along with complicated manufacturing and analytical techniques to characterize them make it difficult to rely on a single human pharmacokinetic study for assurance of safety and efficacy. In general, the concept of comparability has been used for evaluation of the currently approved "similar" biological where a step by step assessment on the quality, preclinical and clinical aspects is made. In India, the focus is primarily on the availability and affordability of life-saving drugs. In this context every product needs to be evaluated on its own merit irrespective of the innovator brand. The formation of the National Biotechnology Regulatory Authority may provide a step in the right direction for regulation of these complex molecules. However, in order to have an efficient machinery for initial approval and ongoing oversight with a country-specific focus, cooperation with international authorities for granting approvals and continuous risk-benefit review is essential. Several steps are still needed for India to be perceived as a country that leads the world in providing quality biological products.

  17. Numerical Optimization of the Position in Femoral Head of Proximal Locking Screws of Proximal Femoral Nail System; Biomechanical Study.

    Science.gov (United States)

    Konya, Mehmet Nuri; Verim, Özgür

    2017-09-29

    Proximal femoral fracture rates are increasing due to osteoporosis and traffic accidents. Proximal femoral nails are routinely used in the treatment of these fractures in the proximal femur. To compare various combinations and to determine the ideal proximal lag screw position in pertrochanteric fractures (Arbeitsgemeinschaft für Osteosynthesefragen classification 31-A1) of the femur by using optimized finite element analysis. Biomechanical study. Computed tomography images of patients' right femurs were processed with Mimics. Afterwards a solid femur model was created with SolidWorks 2015 and transferred to ANSYS Workbench 16.0 for response surface optimization analysis which was carried out according to anterior-posterior (-10°0) and posterior-anterior directions of the femur neck significantly increased these stresses. The most suitable position of the proximal lag screw was confirmed as the middle of the femoral neck by using optimized finite element analysis.

  18. Universal proximity effect in target search kinetics in the few-encounter limit

    CERN Document Server

    Godec, A

    2016-01-01

    When does a diffusing particle reach its target for the first time? This first-passage time (FPT) problem is central to the kinetics of molecular reactions in chemistry and molecular biology. Here we explain the behavior of smooth FPT densities, for which all moments are finite, and demonstrate universal yet generally non-Poissonian long-time asymptotics for a broad variety of transport processes. While Poisson-like asymptotics arise generically in the presence of an effective repulsion in the immediate vicinity of the target, a time-scale separation between direct and reflected indirect trajectories gives rise to a universal proximity effect: Direct paths, heading more or less straight from the point of release to the target, become typical and focused, with a narrow spread of the corresponding first passage times. Conversely, statistically dominant indirect paths exploring the system size tend to be massively dissimilar. The initial distance to the target particularly impacts gene regulatory or competitive ...

  19. The Hounsfield value for cortical bone geometry in the proximal humerus - an in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Lim Fat, Daren; Kennedy, Jim; Galvin, Rose; O' Brien, Fergal; Mc Grath, Frank; Mullett, Hannan [Royal College of Surgeons in Ireland, Investigations Carried Out at Anatomy Lab, Dublin (Ireland)

    2012-05-15

    Fractures of the proximal humerus represent a major osteoporotic burden. Recent developments in CT imaging have emphasized the importance of cortical bone thickness distribution in the prevention and management of fragility fractures. We aimed to experimentally define the CT density of cortical bone in the proximal humerus for building cortical geometry maps. With ethical approval, we used ten fresh-frozen human proximal humeri. These were stripped of all soft tissue and high-resolution CT images were then taken. The humeral heads were then subsequently resected to allow access to the metaphyseal area. Using curettes, cancellous bone was removed down to hard cortical bone. Another set of CT images of the reamed specimen was then taken. Using CT imaging software and a CAD interface, we then compared cortical contours at different CT density thresholds to the reference inner cortical contour of our reamed specimens. Working with 3D model representations of these cortical maps, we were able to accurately make distance comparison analyses based on different CT thresholds. We could compute a single closest value at 700 HU. No difference was found in the HU-based contours generated along the 500-900 HU pixels (p = 1.000). The contours were significantly different from those generated at 300, 400, 1,000, and 1,100 HU. A Hounsfield range of 500-900 HU can accurately depict cortical bone geometry in the proximal humerus. Thresholding outside this range leads to statistically significant inaccuracies. Our results concur with a similar range reported in the literature for the proximal femur. Knowledge of regional variations in cortical bone thickness has direct implications for basic science studies on osteoporosis and its treatment, but is also important for the orthopedic surgeon since our decision for treatment options is often guided by local bone quality. (orig.)

  20. Functional significance of muscarinic receptor expression within the proximal and distal rat vagina.

    Science.gov (United States)

    Basha, Maureen; Labelle, Edward F; Northington, Gina M; Wang, Tanchun; Wein, Alan J; Chacko, Samuel

    2009-11-01

    Information regarding the role of cholinergic nerves in mediating vaginal smooth muscle contraction is sparse, and in vitro studies of the effects of muscarinic agonists on vaginal smooth muscle are discrepant. The goal of this study was to determine the expression of muscarinic receptors in the vaginal wall of the rat. In addition, we sought to determine the effect of the muscarinic receptor agonist carbachol on contractility and inositol phosphate production of the proximal and distal rat vaginal muscularis. RT-PCR analysis indicated that both M(2) and M(3) receptor transcripts were expressed within the proximal and distal rat vagina. Carbachol dose-dependently (10(-7)-10(-4) M) contracted the rat vaginal muscularis with a greater maximal contractile response in the proximal vagina (P vagina. The contractile responses of the rat vaginal muscularis to carbachol were dose dependently inhibited by the M(3) antagonist para-fluoro-hexahydrosiladefenidol, and a pK(B) of 7.78 and 7.95 was calculated for the proximal and distal vagina, respectively. Inositol phosphate production was significantly increased in both regions of the vagina following 20-min exposure to 50 muM carbachol with higher levels detected in the proximal vagina compared with the distal (P < 0.05). Preliminary experiments indicated the presence of M(2) and M(3) receptors in the human vaginal muscularis as well as contraction of human vaginal muscularis to carbachol, indicating that our animal studies are relevant to human tissue. Our results provide strong evidence for the functional significance of M(3) receptor expression in the vaginal muscularis.

  1. Proximal gastric motor activity in response to a liquid meal in type I diabetes mellitus with autonomic neuropathy

    NARCIS (Netherlands)

    Samsom, M.; Roelofs, J. M.; Akkermans, L. M.; van Berge Henegouwen, G. P.; Smout, A. J.

    1998-01-01

    Disordered gastric emptying occurs in 30-50% of patients with diabetes mellitus. Although the rate of gastric emptying is dependent on the integration of motor activity in different regions of the stomach, there is limited information about the function of the proximal stomach in diabetes mellitus.

  2. Exploring the Effect of Geographical Proximity and University Quality on University-Industry Collaboration in the United Kingdom

    DEFF Research Database (Denmark)

    Laursen, Keld; Reichstein, Toke; Salter, Ammon

    2011-01-01

    Exploring the effect of geographical proximity and university quality on university–industry collaboration in the United Kingdom, Regional Studies. This paper concerns the geographical distance between a firm and the universities in its local area. It is argued that firms' decisions to collaborat...

  3. Characterization of noncoding regulatory DNA in the human genome.

    Science.gov (United States)

    Elkon, Ran; Agami, Reuven

    2017-08-08

    Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

  4. Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer

    Directory of Open Access Journals (Sweden)

    Matloob Khushi

    2014-11-01

    Full Text Available Chromatin factors interact with each other in a cell and sequence-specific manner in order to regulate transcription and a wealth of publically available datasets exists describing the genomic locations of these interactions. Our recently published BiSA (Binding Sites Analyser database contains transcription factor binding locations and epigenetic modifications collected from published studies and provides tools to analyse stored and imported data. Using BiSA we investigated the overlapping cis-regulatory role of estrogen receptor alpha (ERα and progesterone receptor (PR in the T-47D breast cancer cell line. We found that ERα binding sites overlap with a subset of PR binding sites. To investigate further, we re-analysed raw data to remove any biases introduced by the use of distinct tools in the original publications. We identified 22,152 PR and 18,560 ERα binding sites (<5% false discovery rate with 4,358 overlapping regions among the two datasets. BiSA statistical analysis revealed a non-significant overall overlap correlation between the two factors, suggesting that ERα and PR are not partner factors and do not require each other for binding to occur. However, Monte Carlo simulation by Binary Interval Search (BITS, Relevant Distance, Absolute Distance, Jaccard and Projection tests by Genometricorr revealed a statistically significant spatial correlation of binding regions on chromosome between the two factors. Motif analysis revealed that the shared binding regions were enriched with binding motifs for ERα, PR and a number of other transcription and pioneer factors. Some of these factors are known to co-locate with ERα and PR binding. Therefore spatially close proximity of ERα binding sites with PR binding sites suggests that ERα and PR, in general function independently at the molecular level, but that their activities converge on a specific subset of transcriptional targets.

  5. Instrument access device for instrument access system, has connector member connecting proximal member with instrument seals, where proximal member and connector member are configured to retain proximal end of retractor member

    OpenAIRE

    Bonadio, Frank; Vaugh, Trevor; McManus, Ronan; MacNally, Shane

    2010-01-01

    The device (203) has instrument seals sealingly arranged in a body of a patient, and a distal anchoring member located in a wound interior. A retractor member is proximally extended from a distal anchoring member to retract sides of a wound opening. A proximal member is adopted for locating an external part of the wound opening. A connector member connects the proximal member with the instrument seals. The proximal member and the connector member are configured to retain a proximal end of the...

  6. Testing a family intervention hypothesis: the contribution of mother-infant skin-to-skin contact (kangaroo care) to family interaction, proximity, and touch.

    Science.gov (United States)

    Feldman, Ruth; Weller, Aron; Sirota, Lea; Eidelman, Arthur I

    2003-03-01

    The provision of maternal-infant body contact during a period of maternal separation was examined for its effects on parent-infant and triadic interactions. Participants were 146 three-month-old preterm infants and their parents, half of whom received skin-to-skin contact, or kangaroo care (KC), in the neonatal nursery. Global relational style and micro-patterns of proximity and touch were coded. Following KC, mothers and fathers were more sensitive and less intrusive, infants showed less negative affect, and family style was more cohesive. Among KC families, maternal and paternal affectionate touch of infant and spouse was more frequent, spouses remained in closer proximity, and infant proximity position was conducive to mutual gaze and touch during triadic play. The role of touch as a constituent of the co-regulatory parent-infant and triadic systems and the effects of maternal contact on mothering, co-parenting, and family processes are discussed.

  7. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    May, Peter J.; Winter, Søren

    2000-01-01

    This study addresses enforcement styles of regulatory inspectors, based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about...

  8. Disclosure as a regulatory tool

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2006-01-01

    The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law.......The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law....

  9. Regulatory focus in groupt contexts

    NARCIS (Netherlands)

    Faddegon, Krispijn Johannes

    2009-01-01

    The thesis examines the influence of group processes on the regulatory focus of individual group members. It is demonstrated that the group situation can affect group members' regulatory focus both in a top-down fashion (via the identitiy of the group) and in a bottom-up fashion (emerging from the

  10. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    J. May, Peter; Winter, Søren

    2007-01-01

    This study addresses enforcement styles of regulatory inspectors based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about...

  11. Proximally Based Anterolateral-Thigh (ALT) Flap for Knee Reconstruction: An Advancement Propeller Perforator Flap.

    Science.gov (United States)

    Cadenelli, Pierfrancesco; Bordoni, Daniele; Radaelli, Stefano; Marchesi, Andrea

    2015-10-01

    Adequate coverage of the knee region is often challenging for plastic and orthopedic surgeons. In the last decade, among several reconstructive techniques, local perforator flaps have become useful reconstructive units. After a wide resection for soft-tissue sarcoma, the knee vascular web may be reasonably damaged and, consequently, perforator flaps based on a local pedicle [such as the distally based anterolateral thigh (ALT) flap] are not reliable. Thus, we harvested a proximally based ALT for knee coverage. A 52-year-old man underwent local radiation therapy and a wide resection of a soft-tissue sarcoma on the anterior-lateral aspect of the left knee, which resulted in a 15 × 10 cm defect. The defect was covered with a proximally based ALT, through an advancement and propeller relocation of its skin paddle. All margins were tumor free. After 5 days, the donor site was closed primarily because of edema. Neither necrosis of the flap nor dehiscence of the wound was detected. No local relapses were detected at 6-month follow-up. In case of soft-tissue defects of the knee region, with likely involvement of the local vascular web, a local perforator solution is the advancement and propeller proximally based ALT flap. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  12. Effect of age on proximal esophageal response to swallowing

    Directory of Open Access Journals (Sweden)

    Roberto Oliveira Dantas

    2010-12-01

    Full Text Available CONTEXT: It has been demonstrated that the ageing process affects esophageal motility. OBJECTIVES: To evaluate the effect of the age on the proximal esophageal response to wet swallows. METHOD: We measured the proximal esophageal response to swallows of a 5 mL bolus of water in 69 healthy volunteers, 20 of them aged 18-30 years (group I, 27 aged 31-50 years (group II, and 22 aged 51-74 years (group III. We used the manometric method with continuous perfusion. The proximal esophageal contractions were recorded 5 cm from a pharyngeal recording site located 1 cm above the upper esophageal sphincter. The time between the onset of the pharyngeal and of the proximal esophageal recording (pharyngeal-esophageal time and the amplitude, duration and area under the curve of the proximal esophageal contraction were measured. RESULTS: The pharyngeal-esophageal time was shorter in group I subjects than in group II and III subjects (P<0.05. The duration of proximal esophageal contractions was longer in group I than in groups II and III (P<0.001. There was no differences between groups in the amplitude or area under the curve of contractions. There were no differences between groups II and III for any of the measurements. CONCLUSION: We conclude that the age may affects the response of the proximal esophagus to wet swallows.

  13. Dual pathology proximal median nerve compression of the forearm.

    LENUS (Irish Health Repository)

    Murphy, Siun M

    2013-12-01

    We report an unusual case of synchronous pathology in the forearm- the coexistence of a large lipoma of the median nerve together with an osteochondroma of the proximal ulna, giving rise to a dual proximal median nerve compression. Proximal median nerve compression neuropathies in the forearm are uncommon compared to the prevalence of distal compression neuropathies (eg Carpal Tunnel Syndrome). Both neural fibrolipomas (Refs. 1,2) and osteochondromas of the proximal ulna (Ref. 3) in isolation are rare but well documented. Unlike that of a distal compression, a proximal compression of the median nerve will often have a definite cause. Neural fibrolipoma, also called fibrolipomatous hamartoma are rare, slow-growing, benign tumours of peripheral nerves, most often occurring in the median nerve of younger patients. To our knowledge, this is the first report of such dual pathology in the same forearm, giving rise to a severe proximal compression of the median nerve. In this case, the nerve was being pushed anteriorly by the osteochondroma, and was being compressed from within by the intraneural lipoma. This unusual case highlights the advantage of preoperative imaging as part of the workup of proximal median nerve compression.

  14. Digital contrast subtraction radiography for proximal caries diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Byung Cheol; Yoon, Suk Ja [Department of Dental Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2002-06-15

    To determine whether subtraction images utilizing contrast media can improve the diagnostic performance of proximal caries diagnosis compared to conventional periapical radiographic images. Thirty-six teeth with 57 proximal surfaces were radiographied using a size no.2 RVG-ui sensor (Trophy Radiology, Marne-la-Vallee, France). The teeth immersed in water-soluble contrast media and subtraction images were taken. Each tooth was then sectioned for histologic examination. The digital radiographic images and subtraction images were examined and interpreted by three dentists for proximal caries. The results of the proximal caries diagnosis were then verified with the results of the histologic examination. The proximal caries sensitivity using digital subtraction radiography was significantly higher than simply examining a single digital radiograph. The sensitivity of the proximal dentinal carious lesion when analyzed with the subtraction radiograph and the radiograph together was higher than with the subtraction radiograph or the radiograph alone. The use of subtraction radiography with contrast media may be useful for detecting proximal dentinal carious lesions.

  15. Proximity to urban parks and mental health.

    Science.gov (United States)

    Sturm, Roland; Cohen, Deborah

    2014-03-01

    Urban parks have received attention in recent years as a possible environmental factor that could encourage physical activity, prevent obesity, and reduce the incidence of chronic conditions. Despite long hypothesized benefits of parks for mental health, few park studies incorporate mental health measures. To test the association between proximity to urban parks and psychological distress. Cross-sectional analysis of individual health survey responses. Data were collected for a study of capital improvements of neighborhood parks in Los Angeles. A survey was fielded on a sample of residential addresses, stratified by distance from the park (within 400m, 800m, 1.6 km, and 3.2km; N=1070). We used multiple regression to estimate the relationship between the psychological distress as measured by the MHI-5 (outcome variable) and distance to parks (main explanatory variable), controlling for observed individual characteristics. Mental health is significantly related to residential distance from parks, with the highest MHI-5 scores among residents within short walking distance from the park (400m) and decreasing significantly over the next distances. The number of visits and physical activity minutes are significantly and independently related to distance, although controlling for them does not reduce the association between distance and mental health. This paper provides a new data point for an arguably very old question, but for which empirical data are sparse for the US. A nearby urban park is associated with the same mental health benefits as decreasing local unemployment rates by 2 percentage points, suggesting at least the potential of environmental interventions to improve mental health. The analysis is cross-sectional, making it impossible to control for important confounders, including residential selection. Mental health policy has traditionally focused on individual-centered interventions. Just as health policy for preventable chronic illnesses has shifted

  16. mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells.

    Science.gov (United States)

    Grahammer, Florian; Ramakrishnan, Suresh K; Rinschen, Markus M; Larionov, Alexey A; Syed, Maryam; Khatib, Hazim; Roerden, Malte; Sass, Jörn Oliver; Helmstaedter, Martin; Osenberg, Dorothea; Kühne, Lucas; Kretz, Oliver; Wanner, Nicola; Jouret, Francois; Benzing, Thomas; Artunc, Ferruh; Huber, Tobias B; Theilig, Franziska

    2017-01-01

    Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR-dependent regulatory network for nutrient transport in renal proximal tubular cells. Copyright © 2016 by the American Society of Nephrology.

  17. Proximal caries detection: Sirona Sidexis versus Kodak Ektaspeed Plus.

    Science.gov (United States)

    Khan, Emad A; Tyndall, Donald A; Ludlow, John B; Caplan, Daniel

    2005-01-01

    This study compared the accuracy of intraoral film and a charge-coupled device (CCD) receptor for proximal caries detection. Four observers evaluated images of the proximal surfaces of 40 extracted posterior teeth. The presence or absence of caries was scored using a five-point confidence scale. The actual status of each surface was determined from ground section histology. Responses were evaluated by means of receiver operating characteristic (ROC) analysis. Areas under ROC curves (Az) were assessed through a paired t-test. The performance of the CCD-based intraoral sensor was not different statistically from Ektaspeed Plus film in detecting proximal caries.

  18. Proximal third humeral shaft fractures -- a fracture entity not fully characterized by conventional AO classification.

    Science.gov (United States)

    Stedtfeld, H W; Biber, R

    2014-01-01

    The retrospective study was made to evaluate the fracture patterns at the proximal humeral shaft for which the long version of a standard proximal humeral nail (PHNLV) has been used. The indication has been decided by the individual surgeons. Over a five year period 72 consecutive PHNLV cases of an acute fracture were identified and were included in the study. Mean patient age was 68.9 years. Gender ratio was m/f=22/50. 86.1% of the patients fractured their humerus by a fall, the rest by a high velocity accident. We analysed patient comorbidity, ASA score, osteoporosis, social status before accident, additional injuries affecting local soft tissues or other anatomic regions. We analysed the expansion of the fractures, dividing the humerus into five zones. Fracture morphology was categorized according to the standard AO/ASIF classification (if applicable). Comorbidities were found in 76.4% of the patients. Almost all patients (93.1%) had been living independently at home before the accident. 47.2% of patients had osteoporosis in their medical history. Five patients (6.9%) had a primary palsy of the radial nerve. Six fractures chosen for PHNLV fixation were clearly restricted to the humeral head. The remaining 66 fractures were located in the humeral shaft (AO region 12). There were 5 segmental fractures. Of the remaining 67 fractures affecting the proximal third of the humeral shaft 49.3 percent extended into the humeral head. 98 percent of these fractures displayed spiral morphology. Proximal humeral shaft fractures are amazingly similar to subtrochanteric and distal tibial shaft fractures: Spiral fracture types with different grades of comminution are absolutely dominant; a great proportion of the fractures extend into the humeral head with growing tendency of displacement if located closer to the humeral head. Diverging traction of deltoid and pectoralis muscle causes typical displacement if the fracture line runs in between their attachments substantiating the

  19. Is central skeleton bone quality a predictor of the severity of proximal humeral fractures?

    Science.gov (United States)

    Lee, Seung Yeol; Kwon, Soon-Sun; Kim, Tae Hoon; Shin, Sang-Jin

    2016-12-01

    The objectives of this study were to evaluate the correlation between bone attenuation around the shoulder joint assessed on conventional computed tomography (CT) and bone mineral density (BMD) based on dual-energy X-ray absorptiometry (DEXA) of the central skeleton and the correlation between the bone quality around the shoulder joint and the severity of the fracture pattern of the proximal humerus. A total of 200 patients with proximal humeral fracture who underwent preoperative 3-dimensional shoulder CT as well as DEXA within 3 months of the CT examination were included. Fracture types were divided into simple and comminuted fracture based on the Neer classification. After reliability testing, bone attenuation of the glenoid, three portions of the humeral head, and metaphysis was measured by placing a circular region of interest on the center of each bony region on CT images. Partial correlation analysis was used to assess the correlation between the bone quality around the shoulder joint on CT and the BMD on the central skeleton after adjusting for age and body mass index. Partial correlations between fracture classification and CT/DEXA results were also evaluated. Bone attenuation measurements of the glenoid and humeral head showed good to excellent reliability (intraclass correlation coefficient, 0.623-0.998). Bone attenuation of the central portion of the humeral head on CT showed a significant correlation with the BMD of L1, L4, the femoral neck, and femoral trochanter (correlation coefficient, 0.269-0.431). Bone attenuation of other areas showed a lower correlation with BMD by DEXA. As the level of the Neer classification increased from a 2 to 4-part fracture, bone attenuation of the central humeral head decreased significantly (r=-0.150, p=0.034). However, the BMD on DEXA was not a predictive factor for comminuted fracture of the proximal humerus. DEXA examination of the central skeleton may not reflect the bone quality of the proximal humerus and

  20. The African Health Profession Regulatory Collaborative for Nurses and Midwives

    Directory of Open Access Journals (Sweden)

    McCarthy Carey F

    2012-08-01

    Full Text Available Abstract Background More than thirty-five sub-Saharan African countries have severe health workforce shortages. Many also struggle with a mismatch between the knowledge and competencies of health professionals and the needs of the populations they serve. Addressing these workforce challenges requires collaboration among health and education stakeholders and reform of health worker regulations. Health professional regulatory bodies, such as nursing and midwifery councils, have the mandate to reform regulations yet often do not have the resources or expertise to do so. In 2011, the United States of America Centers for Disease Control and Prevention began a four-year initiative to increase the collaboration among national stakeholders and help strengthen the capacity of health professional regulatory bodies to reform national regulatory frameworks. The initiative is called the African Health Regulatory Collaborative for Nurses and Midwives. This article describes the African Health Regulatory Collaborative for Nurses and Midwives and discusses its importance in implementing and sustaining national, regional, and global workforce initiatives. Discussion The African Health Profession Regulatory Collaborative for Nurses and Midwives convenes leaders responsible for regulation from 14 countries in East, Central and Southern Africa. It provides a high profile, south-to-south collaboration to assist countries in implementing joint approaches to problems affecting the health workforce. Implemented in partnership with Emory University, the Commonwealth Secretariat, and the East, Central and Southern African College of Nursing, this initiative also supports four to five countries per year in implementing locally-designed regulation improvement projects. Over time, the African Health Regulatory Collaborative for Nurses and Midwives will help to increase the regulatory capacity of health professional organizations and ultimately improve regulation and

  1. Regulatory Streamlining and Improvement

    Energy Technology Data Exchange (ETDEWEB)

    Mark A. Carl

    2006-07-11

    The Interstate Oil and Gas Compact Commission (IOGCC) engaged in numerous projects outlined under the scope of work discussed in the United States Department of Energy (DOE) grant number DE-FC26-04NT15456 awarded to the IOGCC. Numerous projects were completed that were extremely valuable to state oil and gas agencies as a result of work performed utilizing resources provided by the grant. There are numerous areas in which state agencies still need assistance. This additional assistance will need to be addressed under future scopes of work submitted annually to DOE's Project Officer for this grant. This report discusses the progress of the projects outlined under the grant scope of work for the 2005-2006 areas of interest, which are as follows: Area of Interest No. 1--Regulatory Streamlining and Improvement: This area of interest continues to support IOGCC's regulatory streamlining efforts that include the identification and elimination of unnecessary duplications of efforts between and among state and federal programs dealing with exploration and production on public lands. Area of Interest No. 2--Technology: This area of interest seeks to improve efficiency in states through the identification of technologies that can reduce costs. Area of Interest No. 3--Training and Education: This area of interest is vital to upgrading the skills of regulators and industry alike. Within the National Energy Policy, there are many appropriate training and education opportunities. Education was strongly endorsed by the President's National Energy Policy Development group. Acting through the governors offices, states are very effective conduits for the dissemination of energy education information. While the IOGCC favors the development of a comprehensive, long-term energy education plan, states are also supportive of immediate action on important concerns, such as energy prices, availability and conservation. Area of Interest No. 4--Resource Assessment and

  2. The transcriptional regulatory network mediated by banana (Musa acuminata) dehydration-responsive element binding (MaDREB) transcription factors in fruit ripening.

    Science.gov (United States)

    Kuang, Jian-Fei; Chen, Jian-Ye; Liu, Xun-Cheng; Han, Yan-Chao; Xiao, Yun-Yi; Shan, Wei; Tang, Yang; Wu, Ke-Qiang; He, Jun-Xian; Lu, Wang-Jin

    2017-04-01

    Fruit ripening is a complex, genetically programmed process involving the action of critical transcription factors (TFs). Despite the established significance of dehydration-responsive element binding (DREB) TFs in plant abiotic stress responses, the involvement of DREBs in fruit ripening is yet to be determined. Here, we identified four genes encoding ripening-regulated DREB TFs in banana (Musa acuminata), MaDREB1, MaDREB2, MaDREB3, and MaDREB4, and demonstrated that they play regulatory roles in fruit ripening. We showed that MaDREB1-MaDREB4 are nucleus-localized, induced by ethylene and encompass transcriptional activation activities. We performed a genome-wide chromatin immunoprecipitation and high-throughput sequencing (ChIP-Seq) experiment for MaDREB2 and identified 697 genomic regions as potential targets of MaDREB2. MaDREB2 binds to hundreds of loci with diverse functions and its binding sites are distributed in the promoter regions proximal to the transcriptional start site (TSS). Most of the MaDREB2-binding targets contain the conserved (A/G)CC(G/C)AC motif and MaDREB2 appears to directly regulate the expression of a number of genes involved in fruit ripening. In combination with transcriptome profiling (RNA sequencing) data, our results indicate that MaDREB2 may serve as both transcriptional activator and repressor during banana fruit ripening. In conclusion, our study suggests a hierarchical regulatory model of fruit ripening in banana and that the MaDREB TFs may act as transcriptional regulators in the regulatory network. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  3. Sequence of the human glycogen-associated regulatory subunit of type 1 protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with NIDDM

    DEFF Research Database (Denmark)

    Chen, Y H; Hansen, L; Chen, Min

    1994-01-01

    of protein phosphatase 1 (PP1 G-subunit) plays a key role in the insulin stimulation of glycogen synthesis and the activity of PP1 is decreased in insulin-resistant subjects, we have now cloned the human G-subunit cDNA to search for abnormalities in the corresponding gene (designated PPP1R3 in the human...... genome nomenclature) in patients with NIDDM. The human cDNA was isolated from a skeletal muscle cDNA library and was found to encode a 126-kDa protein, which shows 73% amino acid identity to the rabbit PP1 G-subunit. The human G-subunit cDNA from 30 insulin-resistant NIDDM patients was analyzed...... for genetic variations in the G-subunit by using single-stranded conformation polymorphism (SSCP) scanning of reversely transcribed mRNA. One variant SSCP profile was detected in the region encoding the COOH-terminal part of the PP1 G-subunit in only one NIDDM patient, and subsequent nucleotide sequencing...

  4. The role of veterinary medicine regulatory agencies.

    Science.gov (United States)

    Smith, M V

    2013-08-01

    An effective animal medicine regulatory programme includes a systematic, evidence-based means of documenting the safety and effectiveness of products before they are produced, marketed or used in a particular country or region. The programme must also include adequate monitoring and controls over the use of these substances. It is clearthat such programmes provide veterinarians, farmers and other animal medicine users with greater assurance that veterinary drugs and biologicals will be safe and effective in preventing and mitigating disease. It is important that these regulatory controls include programmes to ensure that human food obtained from treated animals is safe and that all potential toxicological and microbiological hazards that may be associated with the use of veterinary medicines have been adequately evaluated. There is a great need worldwide for veterinary medicines that provide needed therapies for vast numbers of animals and animal species and, in the case of food-producing animals, for medicinal products that enhance the productivity and efficiency of food production and ensure food safety when they are used in accordance with their approval specifications. The public health mission of regulatory agencies succeeds when they are able to put into the hands of the user an approved, safe and effective, well-manufactured and appropriately labelled medicine, and when there are adequate controls in place to assure proper compliance.

  5. Nanomedicines in the EU-Regulatory Overview.

    Science.gov (United States)

    Pita, Ruben; Ehmann, Falk; Papaluca, Marisa

    2016-11-01

    This article provides an overview of the European Union (EU) framework for the marketing authorisation of medicinal products, at both European and National level, and aims to demonstrate the current position and experience with nanomedicines. It will be described how the EU promotes the development of new nanomedicines by publishing guidance, providing scientific advice and engaging with multiple regions for the convergence of scientific requirements to support the quality, safety and efficacy of nanomedicines. It will also be highlighted the regulatory challenges deriving from the use of an innovative technology that crosses different platforms and the importance of overcoming challenges for the benefit of public health.

  6. Identification of DVA interneuron regulatory sequences in Caenorhabditis elegans.

    Science.gov (United States)

    Puckett Robinson, Carmie; Schwarz, Erich M; Sternberg, Paul W

    2013-01-01

    The identity of each neuron is determined by the expression of a distinct group of genes comprising its terminal gene battery. The regulatory sequences that control the expression of such terminal gene batteries in individual neurons is largely unknown. The existence of a complete genome sequence for C. elegans and draft genomes of other nematodes let us use comparative genomics to identify regulatory sequences directing expression in the DVA interneuron. Using phylogenetic comparisons of multiple Caenorhabditis species, we identified conserved non-coding sequences in 3 of 10 genes (fax-1, nmr-1, and twk-16) that direct expression of reporter transgenes in DVA and other neurons. The conserved region and flanking sequences in an 85-bp intronic region of the twk-16 gene directs highly restricted expression in DVA. Mutagenesis of this 85 bp region shows that it has at least four regions. The central 53 bp region contains a 29 bp region that represses expression and a 24 bp region that drives broad neuronal expression. Two short flanking regions restrict expression of the twk-16 gene to DVA. A shared GA-rich motif was identified in three of these genes but had opposite effects on expression when mutated in the nmr-1 and twk-16 DVA regulatory elements. We identified by multi-species conservation regulatory regions within three genes that direct expression in the DVA neuron. We identified four contiguous regions of sequence of the twk-16 gene enhancer with positive and negative effects on expression, which combined to restrict expression to the DVA neuron. For this neuron a single binding site may thus not achieve sufficient specificity for cell specific expression. One of the positive elements, an 8-bp sequence required for expression was identified in silico by sequence comparisons of seven nematode species, demonstrating the potential resolution of expanded multi-species phylogenetic comparisons.

  7. Deciphering the Combinatorial DNA-binding Code of the CCAAT-binding Complex and the Iron-regulatory Basic Region Leucine Zipper (bZIP) Transcription Factor HapX*

    Science.gov (United States)

    Hortschansky, Peter; Ando, Eriko; Tuppatsch, Katja; Arikawa, Hisashi; Kobayashi, Tetsuo; Kato, Masashi; Haas, Hubertus; Brakhage, Axel A.

    2015-01-01

    The heterotrimeric CCAAT-binding complex (CBC) is evolutionarily conserved in eukaryotic organisms, including fungi, plants, and mammals. The CBC consists of three subunits, which are named in the filamentous fungus Aspergillus nidulans HapB, HapC, and HapE. HapX, a fourth CBC subunit, was identified exclusively in fungi, except for Saccharomyces cerevisiae and the closely related Saccharomycotina species. The CBC-HapX complex acts as the master regulator of iron homeostasis. HapX belongs to the class of basic region leucine zipper transcription factors. We demonstrated that the CBC and HapX bind cooperatively to bipartite DNA motifs with a general HapX/CBC/DNA 2:1:1 stoichiometry in a class of genes that are repressed by HapX-CBC in A. nidulans during iron limitation. This combinatorial binding mode requires protein-protein interaction between the N-terminal domain of HapE and the N-terminal CBC binding domain of HapX as well as sequence-specific DNA binding of both the CBC and HapX. Initial binding of the CBC to CCAAT boxes is mandatory for DNA recognition of HapX. HapX specifically targets the minimal motif 5′-GAT-3′, which is located at a distance of 11–12 bp downstream of the respective CCAAT box. Single nucleotide substitutions at the 5′- and 3′-end of the GAT motif as well as different spacing between the CBC and HapX DNA-binding sites revealed a remarkable promiscuous DNA-recognition mode of HapX. This flexible DNA-binding code may have evolved as a mechanism for fine-tuning the transcriptional activity of CBC-HapX at distinct target promoters. PMID:25589790

  8. On Optimal Fuzzy Best Proximity Coincidence Points of Proximal Contractions Involving Cyclic Mappings in Non-Archimedean Fuzzy Metric Spaces

    Directory of Open Access Journals (Sweden)

    Manuel De la Sen

    2017-04-01

    Full Text Available The main objective of this paper is to deal with some properties of interest in two types of fuzzy ordered proximal contractions of cyclic self-mappings T integrated in a pair ( g , T of mappings. In particular, g is a non-contractive fuzzy self-mapping, in the framework of non-Archimedean ordered fuzzy complete metric spaces and T is a p -cyclic proximal contraction. Two types of such contractions (so called of type I and of type II are dealt with. In particular, the existence, uniqueness and limit properties for sequences to optimal fuzzy best proximity coincidence points are investigated for such pairs of mappings.

  9. Population Exposure Estimates in Proximity to Nuclear Power Plants, Locations

    Data.gov (United States)

    National Aeronautics and Space Administration — The Population Exposure Estimates in Proximity to Nuclear Power Plants, Locations data set combines information from a global data set developed by Declan Butler of...

  10. Transverse Stress Fracture of the Proximal Patella: A Case Report

    National Research Council Canada - National Science Library

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu

    2016-01-01

    .... Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella...

  11. Genetics Home Reference: proximal 18q deletion syndrome

    Science.gov (United States)

    ... can range from mild to severe. In particular, vocabulary and the production of speech (expressive language skills) ... Some affected individuals have an unusually large head size ( macrocephaly ). People with proximal 18q deletion syndrome often ...

  12. Perinatal mortality and residential proximity to an industrial park.

    Science.gov (United States)

    Sarov, Batia; Bentov, Yaakov; Kordysh, Ella; Karakis, Isabella; Bolotin, Arkady; Hershkovitz, Reli; Belmaker, Ilana

    2008-01-01

    The authors' objective was to determine whether residential proximity to an industrial park (IP) is associated with increased perinatal mortality (PM). This semiecological study included 63,850 delivered births with 840 cases of PM (1995-2000). The authors categorized the study populations by ethnicity (ie, Bedouin and Jewish) and type of locality. Residential distance from the IP served as a surrogate indicator of exposure. Among Bedouin newborns, proximity to the IP was associated with increased PM rates (relative risk = 1.45; 95% confidence interval = 1.22-1.72). The excess in PM was not related to maternal or newborn physical characteristics that the authors observed. The risk of PM and its components in the Jewish localities was not associated with IP proximity. The association between residential proximity to the IP and excess in PM among only Bedouin newborns may be related to vulnerability caused by the nomadic nature of the society.

  13. Computational proximity excursions in the topology of digital images

    CERN Document Server

    Peters, James F

    2016-01-01

    This book introduces computational proximity (CP) as an algorithmic approach to finding nonempty sets of points that are either close to each other or far apart. Typically in computational proximity, the book starts with some form of proximity space (topological space equipped with a proximity relation) that has an inherent geometry. In CP, two types of near sets are considered, namely, spatially near sets and descriptivelynear sets. It is shown that connectedness, boundedness, mesh nerves, convexity, shapes and shape theory are principal topics in the study of nearness and separation of physical aswell as abstract sets. CP has a hefty visual content. Applications of CP in computer vision, multimedia, brain activity, biology, social networks, and cosmology are included. The book has been derived from the lectures of the author in a graduate course on the topology of digital images taught over the past several years. Many of the students have provided important insights and valuable suggestions. The topics in ...

  14. Proximate and Amino Acid Composition of Celosia argentea Leaves ...

    African Journals Online (AJOL)

    % respectively while ... were analyzed using flame photometer for K and ... low in methionine. Table 1: Proximate Composition of C. argentea. Parameter. Composition (%). Moisture content. Crude Fat. Crude protein. Crude fibre. Ash. Nitrogen ...

  15. Effect of processing method on the Proximate composition, mineral ...

    African Journals Online (AJOL)

    Effect of processing method on the Proximate composition, mineral content and antinutritional factors of Taro (Colocasia esculenta, L.) growth in Ethiopia. T Adane, A Shimelis, R Negussie, B Tilahun, GD Haki ...

  16. TETRAPOLIS - an exercise in building the complexities of proximity space

    National Research Council Canada - National Science Library

    Cristian Blidariu; Diana Giurea

    2017-01-01

    ... student’s intuitive ways for understanding these vicinities, their physical and symbolic proximities, through participatory tactics and certain poetic/architectural tools required in the phenomenological build-up of space...

  17. XcisClique: analysis of regulatory bicliques

    Directory of Open Access Journals (Sweden)

    Grene Ruth

    2006-04-01

    Full Text Available Abstract Background Modeling of cis-elements or regulatory motifs in promoter (upstream regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. Methods XcisClique, the system developed in this work, is a comprehensive infrastructure that associates annotated genome and gene expression data, models known cis-elements as regular expressions, identifies maximal bicliques in a bipartite gene-motif graph; and ranks bicliques based on their computed statistical significance. Significance is a function of the probability of occurrence of those motifs in a biclique (a hypergeometric distribution, and on the new sum of absolute values statistic (SAV that uses Spearman correlations of gene expression vectors. SAV is a statistic well-suited for this purpose as described in the discussion. Results XcisClique identifies new motif and gene combinations that might indicate as yet unidentified involvement of sets of genes in biological functions and processes. It currently supports Arabidopsis thaliana and can be adapted to other organisms, assuming the existence of annotated genomic sequences, suitable gene expression data, and identified regulatory motifs. A subset of Xcis Clique functionalities, including the motif visualization component MotifSee, source code, and supplementary material are available at https://bioinformatics.cs.vt.edu/xcisclique/.

  18. AGRIS: Arabidopsis gene regulatory information server, an information resource of Arabidopsis cis-regulatory elements and transcription factors.

    Science.gov (United States)

    Davuluri, Ramana V; Sun, Hao; Palaniswamy, Saranyan K; Matthews, Nicole; Molina, Carlos; Kurtz, Mike; Grotewold, Erich

    2003-06-23

    The gene regulatory information is hardwired in the promoter regions formed by cis-regulatory elements that bind specific transcription factors (TFs). Hence, establishing the architecture of plant promoters is fundamental to understanding gene expression. The determination of the regulatory circuits controlled by each TF and the identification of the cis-regulatory sequences for all genes have been identified as two of the goals of the Multinational Coordinated Arabidopsis thaliana Functional Genomics Project by the Multinational Arabidopsis Steering Committee (June 2002). AGRIS is an information resource of Arabidopsis promoter sequences, transcription factors and their target genes. AGRIS currently contains two databases, AtTFDB (Arabidopsis thaliana transcription factor database) and AtcisDB (Arabidopsis thaliana cis-regulatory database). AtTFDB contains information on approximately 1,400 transcription factors identified through motif searches and grouped into 34 families. AtTFDB links the sequence of the transcription factors with available mutants and, when known, with the possible genes they may regulate. AtcisDB consists of the 5' regulatory sequences of all 29,388 annotated genes with a description of the corresponding cis-regulatory elements. Users can search the databases for (i) promoter sequences, (ii) a transcription factor, (iii) a direct target genes for a specific transcription factor, or (vi) a regulatory network that consists of transcription factors and their target genes. AGRIS provides the necessary software tools on Arabidopsis transcription factors and their putative binding sites on all genes to initiate the identification of transcriptional regulatory networks in the model dicotyledoneous plant Arabidopsis thaliana. AGRIS can be accessed from http://arabidopsis.med.ohio-state.edu.

  19. Orthopaedic approaches to proximal humeral fractures following trauma.

    OpenAIRE

    Mafi, R.; Khan, W.; Mafi, P; Hindocha, S.

    2014-01-01

    Proximal humeral fractures have been a topic of discussion in medical literature dating back as far as 3rd century BC. Today, these fractures are the most common type of humeral fractures and account for about 5-6% of all fractures in adults with the incidence rising rapidly with age. In broad terms the management of proximal humeral fractures can be divided into two categories: conservative versus surgical intervention. The aim of treatment is to stabilize the fracture, aid better union and ...

  20. Conservative Treatment for Bilateral Displaced Proximal Humerus Head Fracture

    OpenAIRE

    Rodriguez-Corlay, Ruy E; Velutini-Becker, Ricardo; Aguilar-Alcal?, Luis D

    2016-01-01

    Proximal humerus fracture represents five to eight percent of all fractures and is twice as common in women than in men. Most cases of displaced fracture of the proximal humerus are treated surgically; it is probable that more cases are preferred to be treated surgically greater than required. The optimal treatment for these fractures remains controversial, but physicians have a tendency to treat via open reduction and fixation with angular locking plates or glenohumeral arthroplasty.? We pre...