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Sample records for human amphiphysin-1 sh3

  1. Structural recognition mechanisms between human Src homology domain 3 (SH3) and ALG-2-interacting protein X (Alix).

    Science.gov (United States)

    Shi, Xiaoli; Betzi, Stephane; Lugari, Adrien; Opi, Sandrine; Restouin, Audrey; Parrot, Isabelle; Martinez, Jean; Zimmermann, Pascale; Lecine, Patrick; Huang, Mingdong; Arold, Stefan T; Collette, Yves; Morelli, Xavier

    2012-06-21

    The functions of Src family kinases are tightly regulated through Src homology (SH) domain-mediated protein-protein interactions. We previously reported the biophysical characteristics of the apoptosis-linked gene 2-interacting protein X (Alix) in complex with the haemopoietic cell kinase (Hck) SH3 domain. In the current study, we have combined ITC, NMR, SAXS and molecular modeling to determine a 3D model of the complex. We demonstrate that Hck SH3 recognizes an extended linear proline-rich region of Alix. This particular binding mode enables Hck SH3 to sense a specific non-canonical residue situated in the SH3 RT-loop of the kinase. The resulting model helps clarify the mechanistic insights of Alix-Hck interaction. Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

  2. A unique set of SH3-SH3 interactions controls IB1 homodimerization

    DEFF Research Database (Denmark)

    Kristensen, Ole; Guenat, Sylvie; Dar, Imran

    2006-01-01

    Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components...... and secretion. IB1 has been shown to homodimerize, but neither the molecular mechanisms nor the function of dimerization have yet been characterized. Here, we show that IB1 homodimerizes through a novel and unique set of Src homology 3 (SH3)-SH3 interactions. X-ray crystallography studies show that the dimer...... interface covers a region usually engaged in PxxP-mediated ligand recognition, even though the IB1 SH3 domain lacks this motif. The highly stable IB1 homodimer can be significantly destabilized in vitro by three individual point mutations directed against key residues involved in dimerization. Each mutation...

  3. Engineered regulation of lysozyme by the SH3-CB1 binding interaction.

    Science.gov (United States)

    Pham, Elizabeth; Truong, Kevin

    2012-06-01

    The ability to design proteins with desired properties by using protein structural information will allow us to create high-value therapeutic and diagnostic products. Using the protein structures of lambda lysozyme and the SH3 domain of human Crk, we designed a synthetic protein switch that controls the activity of lysozyme by sterically hindering its active cleft through the binding of SH3 to its CB1 peptide-binding partner. First, several fusion protein designs with lysozyme and CB1 were modeled to determine the one with greatest steric effect in the presence of SH3. Next, the selected fusion protein was created and tested in vitro. In the absence of SH3, the lysozyme-CB1 fusion protein functioned normally. In the presence of SH3, the lysozyme activity was inhibited and with the addition of excess CB1 peptides to compete for SH3 binding, the lysozyme activity was restored. Lastly, this structure-based strategy can be used to engineer synthetic regulation by peptide-domain-binding interfaces into a variety of proteins.

  4. $\\mathit {SH}(3)$-move and other local moves on knots

    OpenAIRE

    Kanenobu, Taizo

    2014-01-01

    An $\\SH(3)$-move is an unknotting operation on oriented knots introduced by Hoste, Nakanishi and Taniyama. We consider some relationships to other local moves such as a band surgery, $\\Gamma_{0}$-move, and $\\Delta$-move, and give some criteria for estimating the $\\SH(3)$-unknotting number using the Jones, HOMFLYPT, Q polynomials. We also show a table of $\\SH(3)$-unknotting numbers for knots with up to 9 crossings.

  5. SH(3)-MOVE AND OTHER LOCAL MOVES ON KNOTS

    OpenAIRE

    Kanenobu, Taizo

    2014-01-01

    An SH(3)-move is an unknotting operation on oriented knots introduced by Hoste, Nakanishi and Taniyama. We consider some relationships to other local moves such as a band surgery, Γ_0-move, and Δ-move, and give some criteria for estimating the SH(3)-unknotting number using the Jones, HOMFLYPT, Q polynomials. We also show a table of SH(3)-unknotting numbers for knots with up to 9 crossings.

  6. Cherubism gene Sh3bp2 is important for optimal bone formation, osteoblast differentiation, and function.

    Science.gov (United States)

    Mukherjee, Padma M; Wang, Chiachien J; Chen, I-Ping; Jafarov, Toghrul; Olsen, Bjorn R; Ueki, Yasuyoshi; Reichenberger, Ernst J

    2010-08-01

    Cherubism is a human genetic disorder that causes bilateral symmetrical enlargement of the maxilla and the mandible in children. It is caused by mutations in SH3BP2. The exact pathogenesis of the disorder is an area of active research. Sh3bp2 knock-in mice were developed by introducing a Pro416Arg mutation (Pro418Arg in humans) in the mouse genome. The osteoclast phenotype of this mouse model was recently described. We examined the bone phenotype of the cherubism mouse model, the role of Sh3bp2 during bone formation, osteoblast differentiation, and osteoblast function. We observed delays in early postnatal development of homozygous Sh3bp2(KI/KI) mice, which exhibited increased growth plate thickness and significantly decreased trabecular bone thickness and bone mineral density. Histomorphometric and microcomputed tomography analyses showed bone loss in the cranial and appendicular skeletons. Sh3bp2(KI/KI) mice also exhibited a significant decrease in osteoid formation that indicated a defect in osteoblast function. Calvarial osteoblast cell cultures had decreased alkaline phosphatase expression and mineralization, suggesting reduced differentiation potential. Gene expression of osteoblast differentiation markers such as collagen type I, alkaline phosphatase, and osteocalcin were decreased in osteoblast cultures from Sh3bp2(KI/KI) mice. These data suggest that Sh3bp2 regulates bone homeostasis through not only osteoclast-specific effects, but also through effects on osteoblast differentiation and function. Copyright (c) 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  7. Loss of Sh3gl2/Endophilin A1 Is a Common Event in Urothelial Carcinoma that Promotes Malignant Behavior

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    Shyama Majumdar

    2013-07-01

    Full Text Available Urothelial carcinoma (UC causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying urothelial cancer development and tumor progression are still largely unknown. Using informatics analysis, we identified Sh3gl2 (endophilin A1 as a bladder urothelium-enriched transcript. The gene encoding Sh3gl2 is located on chromosome 9p, a region frequently altered in UC. Sh3gl2 is known to regulate endocytosis of receptor tyrosine kinases implicated in oncogenesis, such as the epidermal growth factor receptor (EGFR and c-Met. However, its role in UC pathogenesis is unknown. Informatics analysis of expression profiles as well as immunohistochemical staining of tissue microarrays revealed Sh3gl2 expression to be decreased in UC specimens compared to nontumor tissues. Loss of Sh3gl2 was associated with increasing tumor grade and with muscle invasion, which is a reliable predictor of metastatic disease and cancer-derived mortality. Sh3gl2 expression was undetectable in 19 of 20 human UC cell lines but preserved in the low-grade cell line RT4. Stable silencing of Sh3gl2 in RT4 cells by RNA interference 1 enhanced proliferation and colony formation in vitro, 2 inhibited EGF-induced EGFR internalization and increased EGFR activation, 3 stimulated phosphorylation of Src family kinases and STAT3, and 4 promoted growth of RT4 xenografts in subrenal capsule tissue recombination experiments. Conversely, forced re-expression of Sh3gl2 in T24 cells and silenced RT4 clones attenuated oncogenic behaviors, including growth and migration. Together, these findings identify loss of Sh3gl2 as a frequent event in UC development that promotes disease progression.

  8. Loss of Sh3gl2/endophilin A1 is a common event in urothelial carcinoma that promotes malignant behavior.

    Science.gov (United States)

    Majumdar, Shyama; Gong, Edward M; Di Vizio, Dolores; Dreyfuss, Jonathan; Degraff, David J; Hager, Martin H; Park, Peter J; Bellmunt, Joaquim; Matusik, Robert J; Rosenberg, Jonathan E; Adam, Rosalyn M

    2013-07-01

    Urothelial carcinoma (UC) causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying urothelial cancer development and tumor progression are still largely unknown. Using informatics analysis, we identified Sh3gl2 (endophilin A1) as a bladder urothelium-enriched transcript. The gene encoding Sh3gl2 is located on chromosome 9p, a region frequently altered in UC. Sh3gl2 is known to regulate endocytosis of receptor tyrosine kinases implicated in oncogenesis, such as the epidermal growth factor receptor (EGFR) and c-Met. However, its role in UC pathogenesis is unknown. Informatics analysis of expression profiles as well as immunohistochemical staining of tissue microarrays revealed Sh3gl2 expression to be decreased in UC specimens compared to nontumor tissues. Loss of Sh3gl2 was associated with increasing tumor grade and with muscle invasion, which is a reliable predictor of metastatic disease and cancer-derived mortality. Sh3gl2 expression was undetectable in 19 of 20 human UC cell lines but preserved in the low-grade cell line RT4. Stable silencing of Sh3gl2 in RT4 cells by RNA interference 1) enhanced proliferation and colony formation in vitro, 2) inhibited EGF-induced EGFR internalization and increased EGFR activation, 3) stimulated phosphorylation of Src family kinases and STAT3, and 4) promoted growth of RT4 xenografts in subrenal capsule tissue recombination experiments. Conversely, forced re-expression of Sh3gl2 in T24 cells and silenced RT4 clones attenuated oncogenic behaviors, including growth and migration. Together, these findings identify loss of Sh3gl2 as a frequent event in UC development that promotes disease progression.

  9. The role of SH3BP2 in the pathophysiology of cherubism.

    Science.gov (United States)

    Reichenberger, Ernst J; Levine, Michael A; Olsen, Bjorn R; Papadaki, Maria E; Lietman, Steven A

    2012-05-24

    Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans.

  10. The role of SH3BP2 in the pathophysiology of cherubism

    Directory of Open Access Journals (Sweden)

    Reichenberger Ernst J

    2012-05-01

    Full Text Available Abstract Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans.

  11. Loss of Sh3gl2/Endophilin A1 Is a Common Event in Urothelial Carcinoma that Promotes Malignant Behavior12

    Science.gov (United States)

    Majumdar, Shyama; Gong, Edward M; Di Vizio, Dolores; Dreyfuss, Jonathan; DeGraff, David J; Hager, Martin H; Park, Peter J; Bellmunt, Joaquim; Matusik, Robert J; Rosenberg, Jonathan E; Adam, Rosalyn M

    2013-01-01

    Urothelial carcinoma (UC) causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying urothelial cancer development and tumor progression are still largely unknown. Using informatics analysis, we identified Sh3gl2 (endophilin A1) as a bladder urothelium-enriched transcript. The gene encoding Sh3gl2 is located on chromosome 9p, a region frequently altered in UC. Sh3gl2 is known to regulate endocytosis of receptor tyrosine kinases implicated in oncogenesis, such as the epidermal growth factor receptor (EGFR) and c-Met. However, its role in UC pathogenesis is unknown. Informatics analysis of expression profiles as well as immunohistochemical staining of tissue microarrays revealed Sh3gl2 expression to be decreased in UC specimens compared to nontumor tissues. Loss of Sh3gl2 was associated with increasing tumor grade and with muscle invasion, which is a reliable predictor of metastatic disease and cancer-derived mortality. Sh3gl2 expression was undetectable in 19 of 20 human UC cell lines but preserved in the low-grade cell line RT4. Stable silencing of Sh3gl2 in RT4 cells by RNA interference 1) enhanced proliferation and colony formation in vitro, 2) inhibited EGF-induced EGFR internalization and increased EGFR activation, 3) stimulated phosphorylation of Src family kinases and STAT3, and 4) promoted growth of RT4 xenografts in subrenal capsule tissue recombination experiments. Conversely, forced re-expression of Sh3gl2 in T24 cells and silenced RT4 clones attenuated oncogenic behaviors, including growth and migration. Together, these findings identify loss of Sh3gl2 as a frequent event in UC development that promotes disease progression. PMID:23814487

  12. SH3BP2 cherubism mutation potentiates TNF-α-induced osteoclastogenesis via NFATc1 and TNF-α-mediated inflammatory bone loss.

    Science.gov (United States)

    Mukai, Tomoyuki; Ishida, Shu; Ishikawa, Remi; Yoshitaka, Teruhito; Kittaka, Mizuho; Gallant, Richard; Lin, Yi-Ling; Rottapel, Robert; Brotto, Marco; Reichenberger, Ernst J; Ueki, Yasuyoshi

    2014-12-01

    Cherubism (OMIM# 118400) is a genetic disorder with excessive jawbone resorption caused by mutations in SH3 domain binding protein 2 (SH3BP2), a signaling adaptor protein. Studies on the mouse model for cherubism carrying a P416R knock-in (KI) mutation have revealed that mutant SH3BP2 enhances tumor necrosis factor (TNF)-α production and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in myeloid cells. TNF-α is expressed in human cherubism lesions, which contain a large number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, and TNF-α plays a critical role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2(KI/KI) ). The data suggest a pathophysiological relationship between mutant SH3BP2 and TNF-α-mediated bone loss by osteoclasts. Therefore, we investigated whether P416R mutant SH3BP2 is involved in TNF-α-mediated osteoclast formation and bone loss. Here, we show that bone marrow-derived M-CSF-dependent macrophages (BMMs) from the heterozygous cherubism mutant (Sh3bp2(KI/+) ) mice are highly responsive to TNF-α and can differentiate into osteoclasts independently of RANKL in vitro by a mechanism that involves spleen tyrosine kinase (SYK) and phospholipase Cγ2 (PLCγ2) phosphorylation, leading to increased nuclear translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone loss with increased osteoclast formation in a mouse calvarial TNF-α injection model as well as in a human TNF-α transgenic mouse model (hTNFtg). SH3BP2 knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated cell formation. These findings suggest that the SH3BP2 cherubism mutation can cause jawbone destruction by promoting osteoclast formation in response to TNF-α expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF-α-induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast progenitors could be a potential strategy for

  13. The dominant folding route minimizes backbone distortion in SH3.

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    Heiko Lammert

    Full Text Available Energetic frustration in protein folding is minimized by evolution to create a smooth and robust energy landscape. As a result the geometry of the native structure provides key constraints that shape protein folding mechanisms. Chain connectivity in particular has been identified as an essential component for realistic behavior of protein folding models. We study the quantitative balance of energetic and geometrical influences on the folding of SH3 in a structure-based model with minimal energetic frustration. A decomposition of the two-dimensional free energy landscape for the folding reaction into relevant energy and entropy contributions reveals that the entropy of the chain is not responsible for the folding mechanism. Instead the preferred folding route through the transition state arises from a cooperative energetic effect. Off-pathway structures are penalized by excess distortion in local backbone configurations and contact pair distances. This energy cost is a new ingredient in the malleable balance of interactions that controls the choice of routes during protein folding.

  14. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners.

    Science.gov (United States)

    Gemperle, Jakub; Hexnerová, Rozálie; Lepšík, Martin; Tesina, Petr; Dibus, Michal; Novotný, Marian; Brábek, Jan; Veverka, Václav; Rosel, Daniel

    2017-08-14

    CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.

  15. SH3BP2 cherubism mutation potentiates TNF-α-induced osteoclastogenesis via NFATc1 and TNF-α-mediated inflammatory bone loss

    Science.gov (United States)

    Mukai, Tomoyuki; Ishida, Shu; Ishikawa, Remi; Yoshitaka, Teruhito; Kittaka, Mizuho; Gallant, Richard; Lin, Yi-Ling; Rottapel, Robert; Brotto, Marco; Reichenberger, Ernst J.; Ueki, Yasuyoshi

    2014-01-01

    Cherubism (OMIM#118400) is a genetic disorder with excessive jawbone resorption caused by mutations in the signaling adaptor protein SH3BP2. Studies on the mouse model for cherubism carrying a P416R knock-in mutation have revealed that mutant SH3BP2 enhances TNF-α production and RANKL-induced osteoclast differentiation in myeloid cells. TNF-α is expressed in human cherubism lesions, which contain a large number of TRAP-positive multinucleated cells, and TNF-α plays a critical role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2KI/KI). The data suggest a pathophysiological relationship between mutant SH3BP2 and TNF-α-mediated bone loss by osteoclasts. Therefore, we investigated whether P416R mutant SH3BP2 is involved in TNF-α-mediated osteoclast formation and bone loss. Here, we show that bone marrow-derived M-CSF-dependent macrophages (BMMs) from the heterozygous cherubism mutant (Sh3bp2KI/+) mice are highly responsive to TNF-α and can differentiate into osteoclasts independently of RANKL in vitro by a mechanism that involves SYK and PLCγ2 phosphorylation, leading to increased nuclear translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone loss with increased osteoclast formation in a mouse calvarial TNF-α injection model as well as in a human TNF-α transgenic mouse model (hTNFtg). SH3BP2 knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated cell formation. These findings suggest that the SH3BP2 cherubism mutation can cause jawbone destruction by promoting osteoclast formation in response to TNF-α expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF-α-induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast progenitors could be a potential strategy for the treatment of bone loss in cherubism as well as in other inflammatory bone disorders. PMID:24916406

  16. Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila.

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    Coyle, Ian P; Koh, Young-Ho; Lee, Wyan-Ching Mimi; Slind, Jessica; Fergestad, Tim; Littleton, J Troy; Ganetzky, Barry

    2004-02-19

    We describe the isolation and characterization of nwk (nervous wreck), a temperature-sensitive paralytic mutant that causes excessive growth of larval neuromuscular junctions (NMJs), resulting in increased synaptic bouton number and branch formation. Ultrastructurally, mutant boutons have reduced size and fewer active zones, associated with a reduction in synaptic transmission. nwk encodes an FCH and SH3 domain-containing adaptor protein that localizes to the periactive zone of presynaptic terminals and binds to the Drosophila ortholog of Wasp (Wsp), a key regulator of actin polymerization. wsp null mutants display synaptic overgrowth similar to nwk and enhance the nwk morphological phenotype in a dose-dependent manner. Evolutionarily, Nwk belongs to a previously undescribed family of adaptor proteins that includes the human srGAPs, which regulate Rho activity downstream of Robo receptors. We propose that Nwk controls synapse morphology by regulating actin dynamics downstream of growth signals in presynaptic terminals.

  17. SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

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    Sai Krishnan

    Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

  18. Insights into Substrate Specificity of NlpC/P60 Cell Wall Hydrolases Containing Bacterial SH3 Domains

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.; Patin, Delphine; Farr, Carol L.; Grant, Joanna C.; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Knuth, Mark W.; Godzik, Adam; Lesley, Scott A.; Elsliger, Marc-André; Deacon, Ashley M.; Wilson, Ian A.

    2015-09-15

    ABSTRACT

    Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. These enzymes all have γ-d-Glu-A2pm (A2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structure consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.

    IMPORTANCEPeptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural

  19. Differential Sensitivity of Src-Family Kinases to Activation by SH3 Domain Displacement

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    Moroco, Jamie A.; Craigo, Jodi K.; Iacob, Roxana E.; Wales, Thomas E.; Engen, John R.; Smithgall, Thomas E.

    2014-01-01

    Src-family kinases (SFKs) are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12) to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo. PMID:25144189

  20. Differential sensitivity of Src-family kinases to activation by SH3 domain displacement.

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    Jamie A Moroco

    Full Text Available Src-family kinases (SFKs are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12 to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo.

  1. SH3BP2 is rarely mutated in exon 9 in giant cell lesions outside cherubism.

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    Lietman, Steven A; Prescott, Nichole L; Hicks, David G; Westra, William H; Levine, Michael A

    2007-06-01

    Giant cell tumor of bone and giant cell reparative granuloma are benign lesions with prominent giant (multinucleated) cells, and an understanding of the molecular biology and genetics of these lesions will likely aid in more effective treatment. Cherubism is a benign lesion of the maxilla and mandible histologically similar to giant cell tumor of bone and giant cell reparative granuloma. Germline mutations in exon 9 of the gene encoding Src homology 3 binding protein 2 (SH3BP2) occur in most patients with cherubism. We therefore hypothesized SH3BP2 and its putative downstream effector nuclear factor of activated T cells c1 isoform (NFATc1) are highly expressed in sporadic nonsyndromic giant cell lesions and associated with somatic SH3BP2 mutations. We analyzed giant cell lesions for SH3BP2 and NFATc1 expression by RNA blot and/or immunohistochemistry and for exon 9 SH3BP2 mutations. We found the SH3BP2 transcripts and protein were abundantly expressed in giant cell tumors of bone, as well as NFATc1 protein. Sequencing of exon 9 of SH3BP2 was normal in all sporadic nonsyndromic giant cell lesions. Although many multinucleated giant cell lesions of bone share histologic features, the primary genetic defect in cherubism and these other giant cell lesions appears different.

  2. [Gene mutation and expression of SH-3BP-2 in cherubism].

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    Li, You-wei; Meng, Xue-mei; Yu, Shi-feng; Gao, Ping

    2009-04-01

    To detect the mutation and expression of SH-3BP-2 in Chinese patients of cherubism and to investigate the possible relationship of gene mutation and multinucleated giant cells in lesions. Genomic DNA was extracted from paraffin-imbedded tissues and peripheral blood samples of 10 cases of cherubism (6 familial cherubism and 4 sporadic cherubism). SH-3BP-2 mutations were detected by PCR-direct sequencing. The nature of multinucleated giant cells in lesions was detected by enzyme histochemical staining and immunohistochemical staining using paraffin-imbedded tissues sections. The SH-3BP-2 protein was detected by immunohistochemical staining. Three missense mutations (G1520A, G1505A, G1505C) in exon 9 of SH-3BP-2 were identified which led to 3 transitions (Gly420Glu, Arg415Gln, Arg415Pro). There were no abnormalities in exon 3 of SH-3BP-2 except 1 case which had not PCR products. The protein SH-3BP-2, the calcitonin receptor and the tartrate-resistant acid phosphatase were detected in the cytoplasm of all multinucleated giant cells and parts of monokaryon matrix cells in 8 paraffin-imbedded samples. The SH-3BP-2 mutation may participate in the differentiation and maturation of osteoclast-like cells in the lesion of cherubism.

  3. Mutations of the SH3BP2 gene in 2 families of cherubism.

    Science.gov (United States)

    Tuna, Elif Bahar; Shimizu, Takehiko; Seymen, Figen; Yildirim, Mine; Gencay, Koray; Maeda, Takahide

    2012-01-01

    Cherubism is a rare autosomal dominant syndrome characterized by abnormal bone tissue in the lower part of the face. Mutations in the gene coding for SH3BP2 have been identified in about 80% of people with cherubism. The aim of this study was to determine whether a mutation in the SH3BP2 gene was the molecular basis of cherubism in two unrelated families. Two cases of the aggressive form of Cherubism were described in two Turkish families with extensive bilateral swelling in the mandible, typical pathological features and familial history. Genomic DNA was extracted from six affected and three unaffected individuals from two families, and mutations in the SH3BP2 were detected by PCR, and direct DNA sequencing was carried out. In the first family, a missense mutation Arg415Gln was found in exon 9 of the SH3BP2 in all affected individuals. The unaffected individuals did not have this mutation. In the second family, another missense mutation Pro418Thr was identified in exon 9 of the SH3BP2 in the patient and his mother with cherubism. We detected the point mutations in the SH3BP2 gene in the patients with multiple affected individuals. Genotype-phenotype association studies in individuals with cherubism are necessary to provide important knowledge about molecular mechanisms of the disease.

  4. From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors.

    Directory of Open Access Journals (Sweden)

    Ana Zafra Ruano

    2016-05-01

    Full Text Available Src Homology 3 domains are ubiquitous small interaction modules known to act as docking sites and regulatory elements in a wide range of proteins. Prior experimental NMR work on the SH3 domain of Src showed that ligand binding induces long-range dynamic changes consistent with an induced fit mechanism. The identification of the residues that participate in this mechanism produces a chart that allows for the exploration of the regulatory role of such domains in the activity of the encompassing protein. Here we show that a computational approach focusing on the changes in side chain dynamics through ligand binding identifies equivalent long-range effects in the Src SH3 domain. Mutation of a subset of the predicted residues elicits long-range effects on the binding energetics, emphasizing the relevance of these positions in the definition of intramolecular cooperative networks of signal transduction in this domain. We find further support for this mechanism through the analysis of seven other publically available SH3 domain structures of which the sequences represent diverse SH3 classes. By comparing the eight predictions, we find that, in addition to a dynamic pathway that is relatively conserved throughout all SH3 domains, there are dynamic aspects specific to each domain and homologous subgroups. Our work shows for the first time from a structural perspective, which transduction mechanisms are common between a subset of closely related and distal SH3 domains, while at the same time highlighting the differences in signal transduction that make each family member unique. These results resolve the missing link between structural predictions of dynamic changes and the domain sectors recently identified for SH3 domains through sequence analysis.

  5. Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation.

    Science.gov (United States)

    Lietman, Steven A; Kalinchinko, Natasha; Deng, Xichao; Kohanski, Ronald; Levine, Michael A

    2006-07-01

    We describe a novel missense mutation (Aspartic acid to Asparagine, p.D419N (g.1371G>A, c.1255G>A) within exon 9 of SH3BP2 in a patient with cherubism, an autosomal dominant syndrome characterized by excessive osteoclastic bone resorption of the jaw. Two siblings and the father were carriers but lacked phenotypic features. Transient expression of p.D419N (c.1255G>A), as well as three previously described exon 9 mutations from cherubism patients (p.R415Q (c.1244G>A), p.D420E (c.1259G>A), and p.P418R (c.1253C>G)) increased activity of NFAT (nuclear factor of activated T-cells), an osteoclastogenic mediator, indicating that cherubism results from gain of function mutations in SH3BP2.

  6. Solution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP

    Energy Technology Data Exchange (ETDEWEB)

    Roldan, Jose L. Ortega [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain); Blackledge, Martin [Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, UJF UMR 5075, Protein Dynamics and Flexibility by NMR (France); Nuland, Nico A. J. van, E-mail: nvnuland@vub.ac.be [Vrije Universiteit Brussel, Structural Biology Brussels (Belgium); Azuaga, Ana I. [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain)

    2011-06-15

    CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney function. It contains three N-terminal SH3 domains that are able to interact among others with CD2, ALIX, c-Cbl and Ubiquitin. To understand the role of the individual SH3 domains of this adaptor protein we have performed a complete structural, thermodynamic and dynamic characterization of the separate domains using NMR and DSC. The energetic contributions to the stability and the backbone dynamics have been related to the structural features of each domain using the structure-based FoldX algorithm. We have found that the N-terminal SH3 domain of both adaptor proteins CD2AP and CIN85 are the most stable SH3 domains that have been studied until now. This high stability is driven by a more extensive network of intra-molecular interactions. We believe that this increased stabilization of N-terminal SH3 domains in adaptor proteins is crucial to maintain the necessary conformation to establish the proper interactions critical for the recruitment of their natural targets.

  7. Bone marrow transplantation improves autoinflammation and inflammatory bone loss in SH3BP2 knock-in cherubism mice.

    Science.gov (United States)

    Yoshitaka, Teruhito; Kittaka, Mizuho; Ishida, Shu; Mizuno, Noriyoshi; Mukai, Tomoyuki; Ueki, Yasuyoshi

    2015-02-01

    Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2(KI/KI)) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2(KI/KI) mice. Bone marrow (BM) cells from wild-type (Sh3bp2(+/+)) mice were transplanted to 6-week-old Sh3bp2(KI/KI) mice with developing inflammation and to 10-week-old Sh3bp2(KI/KI) mice with established inflammation. Six-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10weeks after BMT compared to Sh3bp2(KI/KI) mice transplanted with Sh3bp2(KI/KI) BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20weeks in 6-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2(KI/KI) mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients. Copyright © 2013. Published by Elsevier Inc.

  8. A novel mutation in the SH3BP2 gene causes cherubism: case report

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    Yu Shi-Feng

    2006-12-01

    Full Text Available Abstract Background Cherubism is a rare hereditary multi-cystic disease of the jaws, characterized by its typical appearance in early childhood, and stabilization and remission after puberty. It is genetically transmitted in an autosomal dominant fashion and the gene coding for SH3-binding protein 2 (SH3BP2 may be involved. Case presentation We investigated a family consisting of 21 members with 3 female affected individuals with cherubism from Northern China. Of these 21 family members, 17 were recruited for the genetic analysis. We conducted the direct sequence analysis of the SH3BP2 gene among these 17 family members. A disease-causing mutation was identified in exon 9 of the gene. It was an A1517G base change, which leads to a D419G amino acid substitution. Conclusion To our knowledge, the A1517G mutation has not been reported previously in cherubism. This finding is novel.

  9. A novel mutation in the SH3BP2 gene causes cherubism: case report.

    Science.gov (United States)

    Li, Cui-Ying; Yu, Shi-Feng

    2006-12-05

    Cherubism is a rare hereditary multi-cystic disease of the jaws, characterized by its typical appearance in early childhood, and stabilization and remission after puberty. It is genetically transmitted in an autosomal dominant fashion and the gene coding for SH3-binding protein 2 (SH3BP2) may be involved. We investigated a family consisting of 21 members with 3 female affected individuals with cherubism from Northern China. Of these 21 family members, 17 were recruited for the genetic analysis. We conducted the direct sequence analysis of the SH3BP2 gene among these 17 family members. A disease-causing mutation was identified in exon 9 of the gene. It was an A1517G base change, which leads to a D419G amino acid substitution. To our knowledge, the A1517G mutation has not been reported previously in cherubism. This finding is novel.

  10. High frequency of SH3TC2 mutations in Czech HMSN I patients.

    Science.gov (United States)

    Laššuthová, P; Mazanec, R; Vondráček, P; Sišková, D; Haberlová, J; Sabová, J; Seeman, P

    2011-10-01

    Charcot-Marie-Tooth (CMT) neuropathy type 4C (CMT4C) is an autosomal recessive (AR), demyelinating neuropathy with early spine deformities caused by mutations in the SH3TC2 gene. To determine the spectrum of SH3TC2 mutations in the Czech population, the entire coding region of SH3TC2 was sequenced in 60 unrelated Czech patients. The prevalent mutation was shown to be the p.Arg954Stop. Therefore, 412 additional patients referred for CMT testing were tested for the presence of p.Arg954Stop only. Of 60 patients in whom the SH3TC2 gene was sequenced, at least one mutation was detected in 13 (21.7%) patients and biallelic pathogenic mutations were detected in 7 (11.6%) patients. Of the 412 patients tested for p.Arg954Stop, the mutation was found in 8 patients (1.94%), 6 were homozygous and 2 were heterozygous. The second causative mutation was detected by sequencing in one of the patients but not in the other. Nine novel sequence variants were detected. Their pathogenicity was further tested in silico and in control samples. Mutations in the SH3TC2 gene are a frequent cause of demyelinating hereditary neuropathy among Czech patients. In total, at least one mutation was found in 21 unrelated patients. CMT4C seems to be the most frequent type of AR CMT and one of the most frequent of all CMT types. Mutation p.Arg954Stop is highly prevalent in the Czech population. Patients with demyelinating neuropathy along with non-dominant mode of inheritance and negative for CMT1A/hereditary neuropathy with liability to pressure palsy should be tested for the presence of the p.Arg954Stop mutation or other mutations in the SH3TC2 gene. © 2011 John Wiley & Sons A/S.

  11. Comparative Genomics and Disorder Prediction Identify Biologically Relevant SH3 Protein Interactions.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Protein interaction networks are an important part of the post-genomic effort to integrate a part-list view of the cell into system-level understanding. Using a set of 11 yeast genomes we show that combining comparative genomics and secondary structure information greatly increases consensus-based prediction of SH3 targets. Benchmarking of our method against positive and negative standards gave 83% accuracy with 26% coverage. The concept of an optimal divergence time for effective comparative genomics studies was analyzed, demonstrating that genomes of species that diverged very recently from Saccharomyces cerevisiae(S. mikatae, S. bayanus, and S. paradoxus, or a long time ago (Neurospora crassa and Schizosaccharomyces pombe, contain less information for accurate prediction of SH3 targets than species within the optimal divergence time proposed. We also show here that intrinsically disordered SH3 domain targets are more probable sites of interaction than equivalent sites within ordered regions. Our findings highlight several novel S. cerevisiae SH3 protein interactions, the value of selection of optimal divergence times in comparative genomics studies, and the importance of intrinsic disorder for protein interactions. Based on our results we propose novel roles for the S. cerevisiae proteins Abp1p in endocytosis and Hse1p in endosome protein sorting.

  12. Comparative genomics and disorder prediction identify biologically relevant SH3 protein interactions.

    Directory of Open Access Journals (Sweden)

    Pedro Beltrao

    2005-08-01

    Full Text Available Protein interaction networks are an important part of the post-genomic effort to integrate a part-list view of the cell into system-level understanding. Using a set of 11 yeast genomes we show that combining comparative genomics and secondary structure information greatly increases consensus-based prediction of SH3 targets. Benchmarking of our method against positive and negative standards gave 83% accuracy with 26% coverage. The concept of an optimal divergence time for effective comparative genomics studies was analyzed, demonstrating that genomes of species that diverged very recently from Saccharomyces cerevisiae(S. mikatae, S. bayanus, and S. paradoxus, or a long time ago (Neurospora crassa and Schizosaccharomyces pombe, contain less information for accurate prediction of SH3 targets than species within the optimal divergence time proposed. We also show here that intrinsically disordered SH3 domain targets are more probable sites of interaction than equivalent sites within ordered regions. Our findings highlight several novel S. cerevisiae SH3 protein interactions, the value of selection of optimal divergence times in comparative genomics studies, and the importance of intrinsic disorder for protein interactions. Based on our results we propose novel roles for the S. cerevisiae proteins Abp1p in endocytosis and Hse1p in endosome protein sorting.

  13. Docking and molecular dynamics simulations of the Fyn-SH3 domain with free and phospholipid bilayer-associated 18.5-kDa myelin basic protein (MBP)-Insights into a noncanonical and fuzzy interaction.

    Science.gov (United States)

    Bessonov, Kyrylo; Vassall, Kenrick A; Harauz, George

    2017-07-01

    The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a "sandwich"-like structure. In the membrane context, the xα2-peptide interacts with the Fyn-SH3 domain via the proline-rich region and the β-sheets of Fyn-SH3, with the latter wrapping around the proline-rich region in a form of a clip. Moreover, the simulations corroborate prior experimental evidence of the importance of upstream segments beyond the canonical SH3-ligand. This study thus provides a more-detailed glimpse into the context-dependent interaction dynamics and importance of the β-sheets in Fyn-SH3 and proline-rich region of MBP. Proteins 2017; 85:1336-1350. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Investigation of the SH3BP2 gene mutation in cherubism.

    Science.gov (United States)

    Lee, Ji-Young; Jung, Yang-Seok; Kim, Soo-A; Lee, Sang-Ho; Ahn, Sang-Gun; Yoon, Jung-Hoon

    2008-06-01

    Cherubism is a rare developmental lesion of the jaw that is generally inherited as an autosomal dominant trait. Recent studies have revealed point mutations in the SH3BP2 gene in cherubism patients. In this study, we examined a 6-year-old Korean boy and his family. We found a Pro418Arg mutation in the SH3BP2 gene of the patient and his mother. A father and his 30-month-old younger brother had no mutations. Immunohistochemically, the multinucleated giant cells proved positive for CD68 and tartrate-resistant acid phosphatase (TRAP). Numerous spindle-shaped stromal cells expressed a ligand for receptor activator of nuclear factor kB (RANKL), but not in multinucleated giant cells. These results provide evidence that RANKL plays a critical role in the differentiation of osteoclast precursor cells to multinucleated giant cells in cherubism. Additionally, genetic analysis may be a useful method for differentiation of cherubism.

  15. DNA analysis of the SH3BP2 gene in patients with aggressive central giant cell granuloma

    NARCIS (Netherlands)

    de Lange, Jan; van Maarle, Merel C.; van den Akker, Hans P.; Redeker, Egbert J. W.

    2007-01-01

    A mutation of the SH3BP2 gene is known to cause cherubism. As there are clinical and histopathological similarities between central giant cell granuloma and cherubism, we made a constitutional DNA analysis of the SH3BP2 gene in four patients with aggressive giant cell granuloma (having one or more

  16. NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3 domain

    OpenAIRE

    Ahn, Hee-Chul; Le, Yen T.H.; Nagchowdhuri, Partha S.; DeRose, Eugene F.; Putnam-Evans, Cindy; London, Robert E.; Markley, John L.; Lim, Kwang Hun

    2006-01-01

    Amyloid formation is associated with structural changes of native polypeptides to monomeric intermediate states and their self-assembly into insoluble aggregates. Characterizations of the amyloidogenic intermediate state are, therefore, of great importance in understanding the early stage of amyloidogenesis. Here, we present NMR investigations of the structural and dynamic properties of the acid-unfolded amyloidogenic intermediate state of the phosphatidylinositol 3-kinase (PI3K) SH3 domain—a...

  17. Concentration-dependent binding of CdSe quantum dots on the SH3 domain.

    Science.gov (United States)

    Bell, David R; Kang, Seung-Gu; Huynh, Tien; Zhou, Ruhong

    2017-12-21

    Quantum dots (QDs) are being used increasingly in applications for solar panels, consumer electronics, and biomedical imaging. For biomedical applications, QDs are typically coated with a biocompatible molecule for the system of interest. Experiments have indicated a QD dose-dependent and surface coating-dependent toxicity, with a portion of the toxicity being ascribed to interference with biomolecules. In this work, the interaction of trioctylphosphine oxide (TOPO) coated (CdSe) 13 QDs with the SRC homology 3 domain (SH3) protein domain are explored using molecular dynamics simulations. The results of this research agree well with experiments that show that at the lowest concentration, the QDs have little affinity for the native proline-rich motif (PRM) binding site of SH3. At higher concentrations, the QDs aggregate and increasingly prefer the PRM binding site, indicating that the normal SH3 function is impeded. This binding dependence is attributed to changes in the local density of the surface coated TOPO molecules upon aggregation. These results present possible interesting QD toxicity patterns and reveal the interdependence between dose and surface coating effects in QD toxicity.

  18. Candida albicans SH3-domain proteins involved in hyphal growth, cytokinesis, and vacuolar morphology.

    Science.gov (United States)

    Reijnst, Patrick; Jorde, Sigyn; Wendland, Jürgen

    2010-08-01

    This report describes the analyses of three Candida albicans genes that encode Src Homology 3 (SH3)-domain proteins. Homologs in Saccharomyces cerevisiae are encoded by the SLA1, NBP2, and CYK3 genes. Deletion of CYK3 in C. albicans was not feasible, suggesting it is essential. Promoter shutdown experiments of CaCYK3 revealed cytokinesis defects, which are in line with the localization of GFP-tagged Cyk3 at septal sites. Deletion of SLA1 resulted in strains with decreased ability to form hyphal filaments. The number of cortical actin patches was strongly reduced in Deltasla1 strains during all growth stages. Sla1-GFP localizes in patches that are found concentrated at the hyphal tip. Deletion of the first two SH3-domains of Sla1 still resulted in cortical localization of the truncated protein. However, the actin cytoskeleton in this strain was aberrant like in the Deltasla1 deletion mutant indicating a function of these SH3 domains to recruit actin nucleation to sites of endocytosis. Deletion of NBP2 resulted in a defect in vacuolar fusion in hyphae. Germ cells of Deltanbp2 strains lacked a large vacuole but initiated several germ tubes. The mutant phenotypes of Deltanbp2 and Deltasla1 could be corrected by reintegration of the wild-type genes.

  19. Functional analysis of SH3 domain containing ring finger 2 during the myogenic differentiation of quail myoblast cells

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    Si Won Kim

    2017-08-01

    Full Text Available Objective Owing to the public availability of complete genome sequences, including avian species, massive bioinformatics analyses may be conducted for computational gene prediction and the identification of gene regulatory networks through various informatics tools. However, to evaluate the biofunctional activity of a predicted target gene, in vivo and in vitro functional genomic analyses should be a prerequisite. Methods Due to a lack of quail genomic sequence information, we first identified the partial genomic structure and sequences of the quail SH3 domain containing ring finger 2 (SH3RF2 gene. Subsequently, SH3RF2 was knocked out using clustered regularly interspaced short palindromic repeat/Cas9 technology and single cell-derived SH3RF2 mutant sublines were established to study the biofunctional activity of SH3RF2 in quail myoblast (QM7 cells during muscle differentiation. Results Through a T7 endonuclease I assay and genotyping analysis, we established an SH3RF2 knockout (KO QM7#4 subline with 61 and 155 nucleotide deletion mutations in SH3RF2. After the induction of myotube differentiation, the expression profiles were analyzed and compared between regular QM7 and SH3RF2 KO QM7#4 cells by global RNA sequencing and bioinformatics analysis. Conclusion We did not detect any statistically significant role of SH3RF2 during myotube differentiation in QM7 myoblast cells. However, additional experiments are necessary to examine the biofunctional activity of SH3RF2 in cell proliferation and muscle growth.

  20. BAR-SH3 sorting nexins are conserved interacting proteins of Nervous wreck that organize synapses and promote neurotransmission.

    Science.gov (United States)

    Ukken, Fiona P; Bruckner, Joseph J; Weir, Kurt L; Hope, Sarah J; Sison, Samantha L; Birschbach, Ryan M; Hicks, Lawrence; Taylor, Kendra L; Dent, Erik W; Gonsalvez, Graydon B; O'Connor-Giles, Kate M

    2016-01-01

    Nervous wreck (Nwk) is a conserved F-BAR protein that attenuates synaptic growth and promotes synaptic function in Drosophila. In an effort to understand how Nwk carries out its dual roles, we isolated interacting proteins using mass spectrometry. We report a conserved interaction between Nwk proteins and BAR-SH3 sorting nexins, a family of membrane-binding proteins implicated in diverse intracellular trafficking processes. In mammalian cells, BAR-SH3 sorting nexins induce plasma membrane tubules that localize NWK2, consistent with a possible functional interaction during the early stages of endocytic trafficking. To study the role of BAR-SH3 sorting nexins in vivo, we took advantage of the lack of genetic redundancy in Drosophila and employed CRISPR-based genome engineering to generate null and endogenously tagged alleles of SH3PX1. SH3PX1 localizes to neuromuscular junctions where it regulates synaptic ultrastructure, but not synapse number. Consistently, neurotransmitter release was significantly diminished in SH3PX1 mutants. Double-mutant and tissue-specific-rescue experiments indicate that SH3PX1 promotes neurotransmitter release presynaptically, at least in part through functional interactions with Nwk, and might act to distinguish the roles of Nwk in regulating synaptic growth and function. © 2016. Published by The Company of Biologists Ltd.

  1. The high-resolution NMR structure of the R21A Spc-SH3:P41 complex: Understanding the determinants of binding affinity by comparison with Abl-SH3

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    van Nuland Nico AJ

    2007-04-01

    Full Text Available Abstract Background SH3 domains are small protein modules of 60–85 amino acids that bind to short proline-rich sequences with moderate-to-low affinity and specificity. Interactions with SH3 domains play a crucial role in regulation of many cellular processes (some are related to cancer and AIDS and have thus been interesting targets in drug design. The decapeptide APSYSPPPPP (p41 binds with relatively high affinity to the SH3 domain of the Abl tyrosine kinase (Abl-SH3, while it has a 100 times lower affinity for the α-spectrin SH3 domain (Spc-SH3. Results Here we present the high-resolution structure of the complex between the R21A mutant of Spc-SH3 and p41 derived from NMR data. Thermodynamic parameters of binding of p41 to both WT and R21A Spc-SH3 were measured by a combination of isothermal titration and differential scanning calorimetry. Mutation of arginine 21 to alanine in Spc-SH3 increases 3- to 4-fold the binding affinity for p41 due to elimination at the binding-site interface of the steric clash produced by the longer arginine side chain. Amide hydrogen-deuterium experiments on the free and p41-bound R21A Spc-SH3 domain indicate that binding elicits a strong reduction in the conformational flexibility of the domain. Despite the great differences in the thermodynamic magnitudes of binding, the structure of the R21A Spc-SH3:P41 complex is remarkably similar to that of the Abl-SH3:P41 complex, with only few differences in protein-ligand contacts at the specificity pocket. Using empirical methods for the prediction of binding energetics based on solvent-accessible surface area calculations, the differences in experimental energetics of binding between the two complexes could not be properly explained only on the basis of the structural differences observed between the complexes. We suggest that the experimental differences in binding energetics can be at least partially ascribed to the absence in the R21A Spc-SH3:P41 complex of several

  2. Experimental characterization of electrostatic and conformational heterogeneity in an SH3 domain.

    Science.gov (United States)

    Adhikary, Ramkrishna; Zimmermann, Jörg; Liu, Jian; Dawson, Philip E; Romesberg, Floyd E

    2013-10-24

    Electrostatic and conformational heterogeneity make central contributions to protein function, but their experimental characterization requires a combination of spatial and temporal resolution that is challenging to achieve. Src homology 3 (SH3) domains mediate protein-protein interactions, and NMR studies have demonstrated that most possess conformational heterogeneity, which could be critical for their function. Here, we use the IR absorptions of carbon-deuterium (C-D) bonds site-selectively incorporated throughout the N-terminal SH3 domain from the murine adapter protein Crk-II to characterize its different microenvironments with high spatial and temporal resolution. The C-D absorptions are only differentiated in the folded state of the protein where they show evidence of significant environmental heterogeneity. However, the spectra of the folded state are independent of temperature, and upon thermal denaturation the protein undergoes a single, global unfolding transition. While some evidence of conformational heterogeneity is found within the peptide backbone, the majority of the environmental heterogeneity appears to result from electrostatics.

  3. Regulation of the interaction between the neuronal BIN1 isoform 1 and Tau proteins - role of the SH3 domain.

    Science.gov (United States)

    Malki, Idir; Cantrelle, François-Xavier; Sottejeau, Yoann; Lippens, Guy; Lambert, Jean-Charles; Landrieu, Isabelle

    2017-10-01

    Bridging integrator 1 (bin1) gene is a genetic determinant of Alzheimer's disease (AD) and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well as the molecular details of this interaction are still not fully resolved. As a consequence, how BIN1 through its interaction with Tau affects AD risk is also still not determined. To progress in this understanding, interaction of Tau with two BIN1 isoforms was investigated using Nuclear Magnetic Resonance spectroscopy. 1 H, 15 N spectra showed that the C-terminal SH3 domain of BIN1 isoform 1 (BIN1Iso1) is not mobile in solution but locked with the core of the protein. In contrast, the SH3 domain of BIN1 isoform 9 (BIN1Iso9) behaves as an independent mobile domain. This reveals an equilibrium between close and open conformations for the SH3 domain. Interestingly, a 334-376 peptide from the clathrin and AP-2-binding domain (CLAP) domain of BIN1Iso1, which contains a SH3-binding site, is able to compete with BIN1-SH3 intramolecular interaction. For both BIN1 isoforms, the SH3 domain can interact with Tau(210-240) sequence. Tau(210-240) peptide can indeed displace the intramolecular interaction of the BIN1-SH3 of BIN1Iso1 and form a complex with the released domain. The measured Kd were in agreement with a stronger affinity of Tau peptide. Both CLAP and Tau peptides occupied the same surface on the BIN1-SH3 domain, showing that their interaction is mutually exclusive. These results emphasize an additional level of complexity in the regulation of the interaction between BIN1 and Tau dependent of the BIN1 isoforms. © 2017 Federation of European Biochemical Societies.

  4. Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4C locus SH3TC2

    NARCIS (Netherlands)

    Brewer, Megan Hwa; Ma, Ki Hwan; Beecham, Gary W.; Gopinath, Chetna; Baas, Frank; Choi, Byung-Ok; Reilly, Mary M.; Shy, Michael E.; Züchner, Stephan; Svaren, John; Antonellis, Anthony

    2014-01-01

    Loss-of-function mutations in the Src homology 3 (SH3) domain and tetratricopeptide repeats 2 (SH3TC2) gene cause autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy. The SH3TC2 protein has been implicated in promyelination signaling through axonal neuregulin-1 and the ERBB2 Schwann

  5. Enhanced TLR-MYD88 Signaling Stimulates Autoinflammation in SH3BP2 Cherubism Mice and Defines the Etiology of Cherubism

    OpenAIRE

    Yoshitaka, Teruhito; Mukai, Tomoyuki; Kittaka, Mizuho; Alford, Lisa M.; Masrani, Salome; Ishida, Shu; Yamaguchi, Ken; YAMADA, Motohiko; Mizuno, Noriyoshi; Olsen, Bjorn R.; Reichenberger, Ernst J.; Ueki, Yasuyoshi

    2014-01-01

    Cherubism is caused by mutations in SH3BP2. Studies of cherubism mice showed that tumor necrosis factor α (TNF-α)-dependent autoinflammation is a major cause of the disorder but failed to explain why human cherubism lesions are restricted to jaws and regress after puberty. We demonstrate that the inflammation in cherubism mice is MYD88 dependent and is rescued in the absence of TLR2 and TLR4. However, germ-free cherubism mice also develop inflammation. Mutant macrophages are hyperresponsive t...

  6. SH3BP2 gain-of-function mutation exacerbates inflammation and bone loss in a murine collagen-induced arthritis model.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Mukai

    Full Text Available SH3BP2 is a signaling adapter protein which regulates immune and skeletal systems. Gain-of-function mutations in SH3BP2 cause cherubism, characterized by jawbone destruction. This study was aimed to examine the role of SH3BP2 in inflammatory bone loss using a collagen-induced arthritis (CIA model.CIA was induced in wild-type (Sh3bp2(+/+ and heterozygous P416R SH3BP2 cherubism mutant knock-in (Sh3bp2(KI/+ mice, an SH3BP2 gain-of-function model. Severity of the arthritis was determined by assessing the paw swelling and histological analyses of the joints. Micro-CT analysis was used to determine the levels of bone loss. Inflammation and osteoclastogenesis in the joints were evaluated by quantitating the gene expression of inflammatory cytokines and osteoclast markers. Furthermore, involvement of the T- and B-cell responses was determined by draining lymph node cell culture and measurement of the serum anti-mouse type II collagen antibody levels, respectively. Finally, roles of the SH3BP2 mutation in macrophage activation and osteoclastogenesis were determined by evaluating the TNF-α production levels and osteoclast formation in bone marrow-derived M-CSF-dependent macrophage (BMM cultures.Sh3bp2(KI/+ mice exhibited more severe inflammation and bone loss, accompanying an increased number of osteoclasts. The mRNA levels for TNF-α and osteoclast marker genes were higher in the joints of Sh3bp2(KI/+ mice. Lymph node cell culture showed that lymphocyte proliferation and IFN-γ and IL-17 production were comparable between Sh3bp2(+/+ and Sh3bp2(KI/+ cells. Serum anti-type II collagen antibody levels were comparable between Sh3bp2(+/+ and Sh3bp2(KI/+ mice. In vitro experiments showed that TNF-α production in Sh3bp2(KI/+ BMMs is elevated compared with Sh3bp2(+/+ BMMs and that RANKL-induced osteoclastogenesis is enhanced in Sh3bp2(KI/+ BMMs associated with increased NFATc1 nuclear localization.Gain-of-function of SH3BP2 augments inflammation and bone loss

  7. Enhanced TLR-MYD88 signaling stimulates autoinflammation in SH3BP2 cherubism mice and defines the etiology of cherubism.

    Science.gov (United States)

    Yoshitaka, Teruhito; Mukai, Tomoyuki; Kittaka, Mizuho; Alford, Lisa M; Masrani, Salome; Ishida, Shu; Yamaguchi, Ken; Yamada, Motohiko; Mizuno, Noriyoshi; Olsen, Bjorn R; Reichenberger, Ernst J; Ueki, Yasuyoshi

    2014-09-25

    Cherubism is caused by mutations in SH3BP2. Studies of cherubism mice showed that tumor necrosis factor α (TNF-α)-dependent autoinflammation is a major cause of the disorder but failed to explain why human cherubism lesions are restricted to jaws and regress after puberty. We demonstrate that the inflammation in cherubism mice is MYD88 dependent and is rescued in the absence of TLR2 and TLR4. However, germ-free cherubism mice also develop inflammation. Mutant macrophages are hyperresponsive to PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) that activate Toll-like receptors (TLRs), resulting in TNF-α overproduction. Phosphorylation of SH3BP2 at Y183 is critical for the TNF-α production. Finally, SYK depletion in macrophages prevents the inflammation. These data suggest that the presence of a large amount of TLR ligands, presumably oral bacteria and DAMPs during jawbone remodeling, may cause the jaw-specific development of human cherubism lesions. Reduced levels of DAMPs after stabilization of jaw remodeling may contribute to the age-dependent regression. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Enhanced TLR-MYD88 Signaling Stimulates Autoinflammation in SH3BP2 Cherubism Mice and Defines the Etiology of Cherubism

    Directory of Open Access Journals (Sweden)

    Teruhito Yoshitaka

    2014-09-01

    Full Text Available Cherubism is caused by mutations in SH3BP2. Studies of cherubism mice showed that tumor necrosis factor α (TNF-α-dependent autoinflammation is a major cause of the disorder but failed to explain why human cherubism lesions are restricted to jaws and regress after puberty. We demonstrate that the inflammation in cherubism mice is MYD88 dependent and is rescued in the absence of TLR2 and TLR4. However, germ-free cherubism mice also develop inflammation. Mutant macrophages are hyperresponsive to PAMPs (pathogen-associated molecular patterns and DAMPs (damage-associated molecular patterns that activate Toll-like receptors (TLRs, resulting in TNF-α overproduction. Phosphorylation of SH3BP2 at Y183 is critical for the TNF-α production. Finally, SYK depletion in macrophages prevents the inflammation. These data suggest that the presence of a large amount of TLR ligands, presumably oral bacteria and DAMPs during jawbone remodeling, may cause the jaw-specific development of human cherubism lesions. Reduced levels of DAMPs after stabilization of jaw remodeling may contribute to the age-dependent regression.

  9. SH3b Cell wall binding domains can enhance anti-staphylococcal activity of endolysin lytic domains.

    Science.gov (United States)

    Bacteriophage endolysins are peptidoglycan hydrolases and a potential new source of antimicrobials. A large subset of these proteins contain a C-terminal SH3b_5 cell wall binding domain that has been shown [for some] to be essential for accurate cell wall recognition and subsequent staphylolytic ac...

  10. Crystal structure of the PEG-bound SH3 domain of myosin IB from Entamoeba histolytica reveals its mode of ligand recognition.

    Science.gov (United States)

    Gautam, Gunjan; Rehman, Syed Arif Abdul; Pandey, Preeti; Gourinath, Samudrala

    2017-08-01

    The versatility in the recognition of various interacting proteins by the SH3 domain drives a variety of cellular functions. Here, the crystal structure of the C-terminal SH3 domain of myosin IB from Entamoeba histolytica (EhMySH3) is reported at a resolution of 1.7 Å in native and PEG-bound states. Comparisons with other structures indicated that the PEG molecules occupy protein-protein interaction pockets similar to those occupied by the peptides in other peptide-bound SH3-domain structures. Also, analysis of the PEG-bound EhMySH3 structure led to the recognition of two additional pockets, apart from the conventional polyproline and specificity pockets, that are important for ligand interaction. Molecular-docking studies combined with various comparisons revealed structural similarity between EhMySH3 and the SH3 domain of β-Pix, and this similarity led to the prediction that EhMySH3 preferentially binds targets containing type II-like PXXP motifs. These studies expand the understanding of the EhMySH3 domain and provide extensive structural knowledge, which is expected to help in predicting the interacting partners which function together with myosin IB during phagocytosis in E. histolytica infections.

  11. Inhibition of CIN85-mediated invasion by a novel SH3 domain binding motif in the lysyl oxidase propeptide.

    Directory of Open Access Journals (Sweden)

    Seiichi Sato

    Full Text Available The lysyl oxidase gene inhibits Ras signaling in transformed fibroblasts and breast cancer cells. Its activity was mapped to the 162 amino acid propeptide domain (LOX-PP of the lysyl oxidase precursor protein. LOX-PP inhibited the Her-2/Ras signaling axis in breast cancer cells, and reduced the Her-2-driven breast tumor burden in a xenograft model. Since its mechanism of action is largely unknown, co-affinity-purification/mass spectrometry was performed and the "Cbl-interacting protein of 85-kDa" (CIN85 identified as an associating protein. CIN85 is an SH3-containing adapter protein that is overexpressed in invasive breast cancers. The CIN85 SH3 domains interact with c-Cbl, an E3 ubiquitin ligase, via an unconventional PxxxPR ligand sequence, with the highest affinity displayed by the SH3-B domain. Interaction with CIN85 recruits c-Cbl to the AMAP1 complex where its ubiquitination activity is necessary for cancer cells to develop an invasive phenotype and to degrade the matrix. Direct interaction of LOX-PP with CIN85 was confirmed using co-immunoprecipitation analysis of lysates from breast cancer cells and of purified expressed proteins. CIN85 interaction with c-Cbl was reduced by LOX-PP. Domain specific CIN85 regions and deletion mutants of LOX-PP were prepared and used to map the sites of interaction to the SH3-B domain of CIN85 and to an epitope encompassing amino acids 111 to 116 of LOX-PP. Specific LOX-PP point mutant proteins P111A and R116A failed to interact with CIN85 or to compete for CIN85 binding with c-Cbl. Structural modeling identified a new atypical PxpxxRh SH3-binding motif in this region of LOX-PP. The LOX-PP interaction with CIN85 was shown to reduce the invasive phenotype of breast cancer cells, including their ability to degrade the surrounding extracellular matrix and for Matrigel outgrowth. Thus, LOX-PP interacts with CIN85 via a novel SH3-binding motif and this association reduces CIN85-promoted invasion by breast cancer

  12. Novel nucleotide mutation leading to a recurrent amino acid alteration in SH3BP2 in a patient with cherubism.

    Science.gov (United States)

    Sangu, Noriko; Shimosato, Tsuyoshi; Inoda, Hirosato; Shimada, Shino; Shimojima, Keiko; Ando, Tomohiro; Yamamoto, Toshiyuki

    2013-12-01

    Cherubism is a rare genetic disorder characterized by progressive facial deformity caused by non-neoplastic bone lesions in the mandible and/or the maxilla. Src homology-3 binding protein 2 gene (SH3BP2) has been found to be the responsible gene, with alterations in six amino acids noted in patients with this condition. Recently, mutations in this domain have been found to cause stabilization of SH3BP2 by uncoupling with tankyrase. In this study, we identified a new 2-bp mutation that led to a recurrent amino acid change in a sporadic case of cherubism. Our findings indicate that it is important to understand the pattern of progress in typical cherubism. © 2013 The Authors. Congenital Anomalies © 2013 Japanese Teratology Society.

  13. The cyanobacterial cytochrome b6f subunit PetP adopts an SH3 fold in solution.

    Science.gov (United States)

    Veit, Sebastian; Nagadoi, Aritaka; Rögner, Matthias; Rexroth, Sascha; Stoll, Raphael; Ikegami, Takahisa

    2016-06-01

    PetP is a peripheral subunit of the cytochrome b(6)f complex (b(6)f) present in both, cyanobacteria and red algae. It is bound to the cytoplasmic surface of this membrane protein complex where it greatly affects the efficiency of the linear photosynthetic electron flow although it is not directly involved in the electron transfer reactions. Despite the crystal structures of the b(6)f core complex, structural information for the transient regulatory b(6)f subunits is still missing. Here we present the first structure of PetP at atomic resolution as determined by solution NMR. The protein adopts an SH3 fold, which is a common protein motif in eukaryotes but comparatively rare in prokaryotes. The structure of PetP enabled the identification of the potential interaction site for b(6)f binding by conservation mapping. The interaction surface is mainly formed by two large loop regions and one short 310 helix which also exhibit an increased flexibility as indicated by heteronuclear steady-state {(1)H}-(15)N NOE and random coil index parameters. The properties of this potential b(6)f binding site greatly differ from the canonical peptide binding site which is highly conserved in eukaryotic SH3 domains. Interestingly, three other proteins of the photosynthetic electron transport chain share this SH3 fold with PetP: NdhS of the photosynthetic NADH dehydrogenase-like complex (NDH-1), PsaE of the photosystem 1 and subunit α of the ferredoxin-thioredoxin reductase have, similar to PetP, a great impact on the photosynthetic electron transport. Finally, a model is presented to illustrate how SH3 domains modulate the photosynthetic electron transport processes in cyanobacteria. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Etanercept administration to neonatal SH3BP2 knock-in cherubism mice prevents TNF-α-induced inflammation and bone loss.

    Science.gov (United States)

    Yoshitaka, Teruhito; Ishida, Shu; Mukai, Tomoyuki; Kittaka, Mizuho; Reichenberger, Ernst J; Ueki, Yasuyoshi

    2014-01-01

    Cherubism is a genetic disorder of the craniofacial skeleton caused by gain-of-function mutations in the signaling adaptor protein, SH3-domain binding protein 2 (SH3BP2). In a knock-in mouse model for cherubism, we previously demonstrated that homozygous mutant mice develop T/B cell-independent systemic macrophage inflammation leading to bone erosion and joint destruction. Homozygous mice develop multiostotic bone lesions whereas cherubism lesions in humans are limited to jawbones. We identified a critical role of tumor necrosis factor α (TNF-α) in the development of autoinflammation by creating homozygous TNF-α-deficient cherubism mutants, in which systemic inflammation and bone destruction were rescued. In this study, we examined whether postnatal administration of an anti-TNF-α antagonist can prevent or ameliorate the disease progression in cherubism mice. Neonatal homozygous mutants, in which active inflammation has not yet developed, were treated with a high dose of etanercept (25 mg/kg, twice/week) for 7 weeks. Etanercept-treated neonatal mice showed strong rescue of facial swelling and bone loss in jaws and calvariae. Destruction of joints was fully rescued in the high-dose group. Moreover, the high-dose treatment group showed a significant decrease in lung and liver inflammatory lesions. However, inflammation and bone loss, which were successfully treated by etanercept administration, recurred after etanercept discontinuation. No significant effect was observed in low-dose-treated (0.5 mg/kg, twice/week) and vehicle-treated groups. In contrast, when 10-week-old cherubism mice with fully active inflammation were treated with etanercept for 7 weeks, even the high-dose administration did not decrease bone loss or lung or liver inflammation. Taken together, the results suggest that anti-TNF-α therapy may be effective in young cherubism patients, if treated before the inflammatory phase or bone resorption occurs. Therefore, early genetic diagnosis and

  15. Etanercept Administration to Neonatal SH3BP2 Knock-In Cherubism Mice Prevents TNF-α-induced Inflammation and Bone Loss

    Science.gov (United States)

    Yoshitaka, Teruhito; Ishida, Shu; Mukai, Tomoyuki; Kittaka, Mizuho; Reichenberger, Ernst J.; Ueki, Yasuyoshi

    2014-01-01

    Cherubism is a genetic disorder of the craniofacial skeleton caused by gain-of-function mutations in the signaling adaptor protein, SH3-domain binding protein 2 (SH3BP2). In a knock-in mouse model for cherubism, we previously demonstrated that homozygous mutant mice develop T/B cell-independent systemic macrophage inflammation leading to bone erosion and joint destruction. Homozygous mice develop multiostotic bone lesions while cherubism lesions in humans are limited to jawbones. We identified a critical role of TNF-α in the development of autoinflammation by creating homozygous TNF-α-deficient cherubism mutants, where systemic inflammation and bone destruction were rescued. In the current study, we examined whether postnatal administration of an anti-TNF-α antagonist can prevent or ameliorate the disease progression in cherubism mice. Neonatal homozygous mutants, where active inflammation has not yet developed, were treated with a high dose of etanercept (25 mg/kg, twice/week) for 7 weeks. Etanercept-treated neonatal mice showed strong rescue of facial swelling and bone loss in jaws and calvariae. Destruction of joints was fully rescued in the high dose group. Moreover, the high dose treatment group showed a significant decrease in lung and liver inflammatory lesions. However, inflammation and bone loss, which were successfully treated by etanercept administration recurred after etanercept discontinuation. No significant effect was observed in low dose- (0.5 mg/kg, twice/week) and vehicle-treated groups. In contrast, when 10-week-old cherubism mice with fully active inflammation were treated with etanercept for 7 weeks, even the high dose administration did not decrease bone loss, lung or liver inflammation. Taken together, the results suggest that anti-TNF-α therapy may be effective in young cherubism patients, if treated before the inflammatory phase or bone resorption occurs. Therefore, early genetic diagnosis and early treatment with anti

  16. Thermodynamic contribution of backbone conformational entropy in the binding between SH3 domain and proline-rich motif.

    Science.gov (United States)

    Zeng, Danyun; Shen, Qingliang; Cho, Jae-Hyun

    2017-02-26

    Biological functions of intrinsically disordered proteins (IDPs), and proteins containing intrinsically disordered regions (IDRs) are often mediated by short linear motifs, like proline-rich motifs (PRMs). Upon binding to their target proteins, IDPs undergo a disorder-to-order transition which is accompanied by a large conformational entropy penalty. Hence, the molecular mechanisms underlying control of conformational entropy are critical for understanding the binding affinity and selectivity of IDPs-mediated protein-protein interactions (PPIs). Here, we investigated the backbone conformational entropy change accompanied by binding of the N-terminal SH3 domain (nSH3) of CrkII and PRM derived from guanine nucleotide exchange factor 1 (C3G). In particular, we focused on the estimation of conformational entropy change of disordered PRM upon binding to the nSH3 domain. Quantitative characterization of conformational dynamics of disordered peptides like PRMs is limited. Hence, we combined various methods, including NMR model-free analysis, δ2D, DynaMine, and structure-based calculation of entropy loss. This study demonstrates that the contribution of backbone conformational entropy change is significant in the PPIs mediated by IDPs/IDRs. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. SH3BP2-encoding exons involved in cherubism are not associated with central giant cell granuloma.

    Science.gov (United States)

    Teixeira, R C; Horz, H P; Damante, J H; Garlet, G P; Santos, C F; Nogueira, R L M; Cavalcante, R B; Conrads, G

    2011-08-01

    Central giant cell granuloma (CGCG) is a benign lesion with unpredictable biological behaviour ranging from a slow-growing asymptomatic swelling to an aggressive lesion associated with pain, bone and root resorption and also tooth displacement. The aetiology of the disease is unclear with controversies in the literature on whether it is mainly of reactional, inflammatory, infectious, neoplasic or genetic origin. To test the hypothesis that mutations in the SH3BP2 gene, as the principal cause of cherubism, are also responsible for, or at least associated with, giant cell lesions, 30 patients with CGCG were recruited for this study and subjected to analysis of germ line and/or somatic alterations. In the blood samples of nine patients, one codon alteration in exon 4 was found, but this alteration did not lead to changes at the amino acid level. In conclusion, if a primary genetic defect is the cause for CGCG it is either located in SH3BP2 gene exons not yet related to cherubism or in a different gene. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism.

    Science.gov (United States)

    Carvalho, V M; Perdigão, P F; Amaral, F R; de Souza, P E A; De Marco, L; Gomez, R S

    2009-01-01

    Central giant cell lesion (CGCL) is a reactive bone lesion that occurs mainly in the mandible, characterized by the multinucleated osteoclast-like giant cells in a background of oval to spindle-shaped mononuclear cells. The etiology is unknown and occurs more commonly in young adults. Cherubism, a rare disease found predominantly in females has histologic characteristics indistinguishable from those of CGCL and is caused by mutations mostly present in exon 9 of the SH3BP2 gene. In this study, we investigated four cases of CGCL and one case of cherubism. DNA was extracted from peripheral blood and tumor tissue and all coding and flanking regions of the SH3BP2 amplified by PCR and directly sequenced to identify underlying mutations. Two novel mutations were found; a heterozygous missense mutation c.1442A>T (Q481L) in exon 11 in one sporadic case of CGCL and a heterozygous germline and tumor tissue missense mutation c.320C>T (T107M) in exon 4 in one patient with cherubism. These findings open a new window to investigate the possible relationship between the pathogenesis of the cherubism and CGCL.

  19. Mobility of TOAC spin-labelled peptides binding to the Src SH3 domain studied by paramagnetic NMR

    Energy Technology Data Exchange (ETDEWEB)

    Lindfors, Hanna E. [Leiden University, Leiden Institute of Chemistry, Gorlaeus Laboratories (Netherlands); Koning, Peter E. de; Wouter Drijfhout, Jan [Leiden University Medical Centre, Department of Immunohematology and Blood Transfusion (Netherlands); Venezia, Brigida; Ubbink, Marcellus [Leiden University, Leiden Institute of Chemistry, Gorlaeus Laboratories (Netherlands)], E-mail: m.ubbink@chem.leidenuniv.nl

    2008-07-15

    Paramagnetic relaxation enhancement provides a tool for studying the dynamics as well as the structure of macromolecular complexes. The application of side-chain coupled spin-labels is limited by the mobility of the free radical. The cyclic, rigid amino acid spin-label TOAC (2,2,6,6-Tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), which can be incorporated straightforwardly by peptide synthesis, provides an attractive alternative. In this study, TOAC was incorporated into a peptide derived from focal adhesion kinase (FAK), and the interaction of the peptide with the Src homology 3 (SH3) domain of Src kinase was studied, using paramagnetic NMR. Placing TOAC within the binding motif of the peptide has a considerable effect on the peptide-protein binding, lowering the affinity substantially. When the TOAC is positioned just outside the binding motif, the binding constant remains nearly unaffected. Although the SH3 domain binds weakly and transiently to proline-rich peptides from FAK, the interaction is not very dynamic and the relative position of the spin-label to the protein is well-defined. It is concluded that TOAC can be used to generate reliable paramagnetic NMR restraints.

  20. Mutations in SH3BP2, the cherubism gene, were not detected in central or peripheral giant cell tumours of the jaw.

    Science.gov (United States)

    Idowu, Bernadine D; Thomas, Garreth; Frow, Richard; Diss, Timothy C; Flanagan, Adrienne M

    2008-04-01

    Giant cell granulomas of the jaw (GCGJ) are non-familial, generally unilateral osteoclast-rich lesions that are histopathologically indistinguishable from cherubism. Cherubism is an autosomal dominant disease that is characterised by bilateral radiolucencies of the jaw, and caused by mutations that occur in SH3BP2 exon 10. The aim of the study was to screen lesional GCGJ tissue for SH3BP2 mutations. Lesional mononuclear stromal or spindle cells were microdissected from paraffin-embedded tissue from GCGJ, and DNA was then extracted and sequenced for SH3BP2 mutations associated with cherubism. No mutations were detected in 26 GCGJ (15 central, 11 peripheral), which indicated that people with GCGJ do not harbour cherubism-related germline SH3BP2 mutations, and that GCGJ do not harbour somatic SH3BP2 mutations. This suggests that cherubism and GCGJ arise on a different genetic background, and therefore detection of SH3BP2 mutations can be a useful means of distinguishing between them.

  1. Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features.

    Science.gov (United States)

    Kobayashi, Kyoko; Yamaguchi, Motoko; Miyazaki, Kana; Imai, Hiroshi; Yokoe, Kaori; Ono, Ryoichi; Nosaka, Tetsuya; Katayama, Naoyuki

    2016-08-01

    Diffuse large B-cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5-positive (CD5(+) ) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5(+) DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5, LMO3, SNAP25, SYT5, SV2C, CABP1, FGF1, FGFR2, NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B-cell-like DLBCL (P = 0.046). Compared to the SH3BP5-negative group, the SH3BP5(+) group was correlated with elderly onset (>60 years, P = 0.0096) and advanced-stage disease (stage III/IV, P = 0.037). The LMO3(+) group showed a worse performance status (>1, P = 0.0004). The SH3BP5(+) group and the LMO3(+) group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab-containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. Screening for SH3TC2 gene mutations in a series of demyelinating recessive Charcot-Marie-Tooth disease (CMT4).

    Science.gov (United States)

    Piscosquito, Giuseppe; Saveri, Paola; Magri, Stefania; Ciano, Claudia; Gandioli, Claudia; Morbin, Michela; Bella, Daniela D; Moroni, Isabella; Taroni, Franco; Pareyson, Davide

    2016-09-01

    Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive (AR) demyelinating neuropathy associated to SH3TC2 mutations, characterized by early onset, spine deformities, and cranial nerve involvement. We screened 43 CMT4 patients (36 index cases) with AR inheritance, demyelinating nerve conductions, and negative testing for PMP22 duplication, GJB1 and MPZ mutations, for SH3TC2 mutations. Twelve patients (11 index cases) had CMT4C as they carried homozygous or compound heterozygous mutations in SH3TC2. We found six mutations: three nonsense (p.R1109*, p.R954*, p.Q892*), one splice site (c.805+2T>C), one synonymous variant (p.K93K) predicting altered splicing, and one frameshift (p.F491Lfs*32) mutation. The splice site and the frameshift mutations are novel. Mean onset age was 7 years (range: 1-14). Neuropathy was moderate-to-severe. Scoliosis was present in 11 patients (severe in 4), and cranial nerve deficits in 9 (hearing loss in 7). Scoliosis and cranial nerve involvement are frequent features of this CMT4 subtype, and their presence should prompt the clinician to look for SH3TC2 gene mutations. In our series of undiagnosed CMT4 patients, SH3TC2 mutation frequency is 30%, confirming that CMT4C may be the most common AR-CMT type. © 2016 Peripheral Nerve Society.

  3. The neuronal proteins CIPP, Cypin and IRSp53 form a tripartite complex mediated by PDZ and SH3 domains.

    Science.gov (United States)

    Barilari, Manuela; Dente, Luciana

    2010-10-01

    Here we report the dissection of a tripartite complex formed by CIPP (channel-interacting PDZ protein), IRSp53 (insulin receptor tyrosine kinase substrate protein) and Cypin (cytosolic PSD-95 interactor) in cultured cells. The three proteins are expressed in similar neuronal districts, where CIPP binds to different membrane channels and receptors, IRSp53 regulates the morphogenesis of actin-rich dendritic spines, and Cypin promotes dendrite branching and patterning by binding to tubulin heterodimers. We observed that the interaction among the three proteins is mediated by small binding domains: CIPP works as a bridge, linking the carboxy-termini of IRSp53 and Cypin with its PDZ domains; IRSp53 connects Cypin, through an unusual SH3-mediated association, which can be impaired by substituting two crucial positively charged residues of Cypin. The observation that the three engineered proteins co-localize in the cytoplasm, and at the tip of induced neurites in neuronal cells, raises the interesting possibility that they work together in the formation of neuronal protrusions.

  4. Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins

    Czech Academy of Sciences Publication Activity Database

    Palani, Kirubakaran; Pfeiferová, Lucie; Boušová, Kristýna; Bednárová, Lucie; Obšilová, V.; Vondrášek, Jiří

    2016-01-01

    Roč. 84, č. 10 (2016), s. 1358-1374 ISSN 0887-3585 Institutional support: RVO:61388963 Keywords : protein design * fusion proteins * PDZ3 * SH3 * Trp-cage * two domain proteins Subject RIV: CE - Biochemistry Impact factor: 2.289, year: 2016

  5. Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins

    Czech Academy of Sciences Publication Activity Database

    Palani, K.; Pfeiferová, L.; Boušová, Kristýna; Bednárová, L.; Obšilová, Veronika; Vondrášek, J.

    2016-01-01

    Roč. 84, č. 10 (2016), s. 1358-1374 ISSN 0887-3585 Institutional support: RVO:67985823 Keywords : protein design * fusion proteins * PDZ3 * SH3 * Trp-cage * two domain proteins * molecular dynamics simulation * circular dichroism Subject RIV: BO - Biophysics Impact factor: 2.289, year: 2016

  6. Identification of Xin-repeat proteins as novel ligands of the SH3 domains of nebulin and nebulette and analysis of their interaction during myofibril formation and remodeling

    Science.gov (United States)

    Eulitz, Stefan; Sauer, Florian; Pelissier, Marie-Cecile; Boisguerin, Prisca; Molt, Sibylle; Schuld, Julia; Orfanos, Zacharias; Kley, Rudolf A.; Volkmer, Rudolf; Wilmanns, Matthias; Kirfel, Gregor; van der Ven, Peter F. M.; Fürst, Dieter O.

    2013-01-01

    The Xin actin-binding repeat–containing proteins Xin and XIRP2 are exclusively expressed in striated muscle cells, where they are believed to play an important role in development. In adult muscle, both proteins are concentrated at attachment sites of myofibrils to the membrane. In contrast, during development they are localized to immature myofibrils together with their binding partner, filamin C, indicating an involvement of both proteins in myofibril assembly. We identify the SH3 domains of nebulin and nebulette as novel ligands of proline-rich regions of Xin and XIRP2. Precise binding motifs are mapped and shown to bind both SH3 domains with micromolar affinity. Cocrystallization of the nebulette SH3 domain with the interacting XIRP2 peptide PPPTLPKPKLPKH reveals selective interactions that conform to class II SH3 domain–binding peptides. Bimolecular fluorescence complementation experiments in cultured muscle cells indicate a temporally restricted interaction of Xin-repeat proteins with nebulin/nebulette during early stages of myofibril development that is lost upon further maturation. In mature myofibrils, this interaction is limited to longitudinally oriented structures associated with myofibril development and remodeling. These data provide new insights into the role of Xin actin-binding repeat–containing proteins (together with their interaction partners) in myofibril assembly and after muscle damage. PMID:23985323

  7. An image-based RNAi screen identifies SH3BP1 as a key effector of Semaphorin 3E–PlexinD1 signaling

    Science.gov (United States)

    Tata, Aleksandra; Stoppel, David C.; Hong, Shangyu; Ben-Zvi, Ayal; Xie, Tiao

    2014-01-01

    Extracellular signals have to be precisely interpreted intracellularly and translated into diverse cellular behaviors often mediated by cytoskeletal changes. Semaphorins are one of the largest families of guidance cues and play a critical role in many systems. However, how different cell types translate extracellular semaphorin binding into intracellular signaling remains unclear. Here we developed and performed a novel image-based genome-wide functional RNAi screen for downstream signaling molecules that convert the interaction between Semaphorin 3E (Sema3E) and PlexinD1 into cellular behaviors. One of the genes identified in this screen is a RhoGAP protein, SH3-domain binding protein 1 (SH3BP1). We demonstrate that SH3BP1 mediates Sema3E-induced cell collapse through interaction with PlexinD1 and regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1) activity. The identification and characterization of SH3BP1 as a novel downstream effector of Sema3E-PlexinD1 provides an explanation for how extracellular signals are translated into cytoskeletal changes and unique cell behavior, but also lays the foundation for characterizing other genes identified from our screen to obtain a more complete picture of plexin signaling. PMID:24841563

  8. An image-based RNAi screen identifies SH3BP1 as a key effector of Semaphorin 3E-PlexinD1 signaling.

    Science.gov (United States)

    Tata, Aleksandra; Stoppel, David C; Hong, Shangyu; Ben-Zvi, Ayal; Xie, Tiao; Gu, Chenghua

    2014-05-26

    Extracellular signals have to be precisely interpreted intracellularly and translated into diverse cellular behaviors often mediated by cytoskeletal changes. Semaphorins are one of the largest families of guidance cues and play a critical role in many systems. However, how different cell types translate extracellular semaphorin binding into intracellular signaling remains unclear. Here we developed and performed a novel image-based genome-wide functional RNAi screen for downstream signaling molecules that convert the interaction between Semaphorin 3E (Sema3E) and PlexinD1 into cellular behaviors. One of the genes identified in this screen is a RhoGAP protein, SH3-domain binding protein 1 (SH3BP1). We demonstrate that SH3BP1 mediates Sema3E-induced cell collapse through interaction with PlexinD1 and regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1) activity. The identification and characterization of SH3BP1 as a novel downstream effector of Sema3E-PlexinD1 provides an explanation for how extracellular signals are translated into cytoskeletal changes and unique cell behavior, but also lays the foundation for characterizing other genes identified from our screen to obtain a more complete picture of plexin signaling. © 2014 Tata et al.

  9. Comparison of the frequency of functional SH3 domains with different limited sets of amino acids using mRNA display.

    Directory of Open Access Journals (Sweden)

    Junko Tanaka

    Full Text Available Although modern proteins consist of 20 different amino acids, it has been proposed that primordial proteins consisted of a small set of amino acids, and additional amino acids have gradually been recruited into the genetic code. This hypothesis has recently been supported by comparative genome sequence analysis, but no direct experimental approach has been reported. Here, we utilized a novel experimental approach to test a hypothesis that native-like globular proteins might be easily simplified by a set of putative primitive amino acids with retention of its structure and function than by a set of putative new amino acids. We performed in vitro selection of a functional SH3 domain as a model from partially randomized libraries with different sets of amino acids using mRNA display. Consequently, a library rich in putative primitive amino acids included a larger number of functional SH3 sequences than a library rich in putative new amino acids. Further, the functional SH3 sequences were enriched from the primitive library slightly earlier than from a randomized library with the full set of amino acids, while the function and structure of the selected SH3 proteins with the primitive alphabet were comparable with those from the 20 amino acid alphabet. Application of this approach to various combinations of codons in protein sequences may be useful not only for clarifying the precise order of the amino acid expansion in the early stages of protein evolution but also for efficiently creating novel functional proteins in the laboratory.

  10. The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers.

    Science.gov (United States)

    He, Ping; Tan, De-Li; Liu, Hong-Xiang; Lv, Feng-Lin; Wu, Wei

    2015-04-01

    The short isoform of Rho guanine nucleotide exchange factor ARHGEF5 is known as TIM, which plays diverse roles in, for example, tumorigenesis, neuronal development and Src-induced podosome formation through the activation of its substrates, the Rho family of GTPases. The activation is auto-inhibited by a putative helix N-terminal to the DH domain of TIM, which is stabilized by the intramolecular interaction of C-terminal SH3 domain with a poly-proline sequence between the putative helix and the DH domain. In this study, we systematically investigated the structural basis, energetic landscape and biological implication underlying TIM auto-inhibition by using atomistic molecular dynamics simulations and binding free energy analysis. The computational study revealed that the binding of SH3 domain to poly-proline sequence is the prerequisite for the stabilization of TIM auto-inhibition. Thus, it is suggested that targeting SH3 domain with competitors of the poly-proline sequence would be a promising strategy to relieve the auto-inhibitory state of TIM. In this consideration, we rationally designed a number of peptide aptamers for competitively inhibiting the SH3 domain based on modeled TIM structure and computationally generated data. Peptide binding test and guanine nucleotide exchange analysis solidified that these designed peptides can both bind to the SH3 domain potently and activate TIM-catalyzed RhoA exchange reaction effectively. Interestingly, a positive correlation between the peptide affinity and induced exchange activity was observed. In addition, separate mutation of three conserved residues Pro49, Pro52 and Lys54 - they are required for peptide recognition by SH3 domain -- in a designed peptide to Ala would completely abolish the capability of this peptide activating TIM. All these come together to suggest an intrinsic relationship between peptide binding to SH3 domain and the activation of TIM. Copyright © 2015 Elsevier B.V. and Société Française de

  11. Pro416Arg cherubism mutation in Sh3bp2 knock-in mice affects osteoblasts and alters bone mineral and matrix properties.

    Science.gov (United States)

    Wang, Chiachien J; Chen, I-Ping; Koczon-Jaremko, Boguslawa; Boskey, Adele L; Ueki, Yasuyoshi; Kuhn, Liisa; Reichenberger, Ernst J

    2010-05-01

    Cherubism is an autosomal dominant disorder in children characterized by unwarranted symmetrical bone resorption of the jaws with fibrous tissue deposition. Mutations causing cherubism have been identified in the adaptor protein SH3BP2. Knock-in mice with a Pro416Arg mutation in Sh3bp2 exhibit a generalized osteoporotic bone phenotype. In this study, we examined the effects of this "cherubism" mutation on spectroscopic indices of "bone quality" and on osteoblast differentiation. Fourier-transform infrared imaging (FTIRI) analysis of femurs from wild-type and Sh3bp2 knock-in mice showed decreased mineral content, decreased mineral crystallinity/crystal size, and increased collagen maturity in homozygous mutants. To assess osteoblast maturation in vivo, knock-in mice were crossed with transgenic mice over-expressing GFP driven by 3.6-kb or 2.3-kb Col1a1 promoter fragments. Reduced numbers of mature osteoblasts were observed in homozygous mice. Neonatal calvarial cultures, which were enriched for osteoblasts by depletion of hematopoietic cells (negative selection for Ter119- and CD45-positive cells) were investigated for osteoblast-specific gene expression and differentiation, which demonstrated that differentiation and mineralization in homozygous osteoblast cultures was impaired. Co-cultures with calvarial osteoblasts and bone marrow macrophages showed that mutant osteoblasts appear to increase osteoclastogenesis resulting in increased bone resorption on bone chips. In summary, the Sh3bp2 mutation in cherubism mice alters bone quality, reduces osteoblast function, and may contribute to excessive bone resorption by osteoclasts. Our data, together with previous osteoclast studies, demonstrate a critical role of Sh3bp2 in bone remodeling and osteoblast differentiation. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  12. Role of SH3b binding domain in a natural deletion mutant of Kayvirus endolysin LysF1 with a broad range of lytic activity.

    Science.gov (United States)

    Benešík, Martin; Nováček, Jiří; Janda, Lubomír; Dopitová, Radka; Pernisová, Markéta; Melková, Kateřina; Tišáková, Lenka; Doškař, Jiří; Žídek, Lukáš; Hejátko, Jan; Pantůček, Roman

    2018-02-01

    The spontaneous host-range mutants 812F1 and K1/420 are derived from polyvalent phage 812 that is almost identical to phage K, belonging to family Myoviridae and genus Kayvirus. Phage K1/420 is used for the phage therapy of staphylococcal infections. Endolysin of these mutants designated LysF1, consisting of an N-terminal cysteine-histidine-dependent aminohydrolase/peptidase (CHAP) domain and C-terminal SH3b cell wall-binding domain, has deleted middle amidase domain compared to wild-type endolysin. In this work, LysF1 and both its domains were prepared as recombinant proteins and their function was analyzed. LysF1 had an antimicrobial effect on 31 Staphylococcus species of the 43 tested. SH3b domain influenced antimicrobial activity of LysF1, since the lytic activity of the truncated variant containing the CHAP domain alone was decreased. The results of a co-sedimentation assay of SH3b domain showed that it was able to bind to three types of purified staphylococcal peptidoglycan 11.2, 11.3, and 11.8 that differ in their peptide bridge, but also to the peptidoglycan type 11.5 of Streptococcus uberis, and this capability was verified in vivo using the fusion protein with GFP and fluorescence microscopy. Using several different approaches, including NMR, we have not confirmed the previously proposed interaction of the SH3b domain with the pentaglycine bridge in the bacterial cell wall. The new naturally raised deletion mutant endolysin LysF1 is smaller than LysK, has a broad lytic spectrum, and therefore is an appropriate enzyme for practical use. The binding spectrum of SH3b domain covering all known staphylococcal peptidoglycan types is a promising feature for creating new chimeolysins by combining it with more effective catalytic domains.

  13. The Role of Human Spectrin SH3 Domain Binding Protein 1 (HSSH3BPl) in Prostatic Adenocarcinoma

    Science.gov (United States)

    2004-09-01

    and tumors, and will test potential tumor suppressive role of Hssh3bpl in nude mice. Hssh3bpl is a potential regulator of macropinocytosis ... Macropinocytosis can be upregulated by growth factors, which in turn promote tumor growth; we propose that Hssh3bpl is a negative regulator of macropinocytosis ... macropinocytosis of prostate cells and determine molecular events underlying this effect. Although it is possible that Hssh3bpl is not involved in

  14. A novel c.1255G>T (p.D419Y) mutation in SH3BP2 gene causes cherubism in a Turkish family.

    Science.gov (United States)

    Dinckan, Nuriye; Guven, Yeliz; Kayserili, Hulya; Aktoren, Oya; Uyguner, Oya Zehra

    2012-11-01

    Cherubism (MIM no. 118400) is a rare autosomal dominant disorder characterized by bilateral multilocular lesions of the upper and lower jaws. The lesions usually manifest clinically during early childhood, progress until puberty, and regress in adulthood. SH3BP2 is the only gene currently known to be associated with cherubism. This study began with an 8-year-old boy who was referred owing to overgrowth of mandible. A panoramic radiograph revealed multilocular radiolucent lesions of the upper/lower jaws, suggestive of cherubism. Sequence analysis of SH3BP2 revealed a novel c.G1255T change in exon 9 of the gene where 80% of the disease-causing mutations were observed. We report here the clinical and molecular findings of a family with 3 affected members in two generations showing variable clinical expressivity with the regression of symptoms with advancing age and the lack of penetrance. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Residue-specific description of non-native transient structures in the ensemble of acid-denatured structures of the all-beta protein c-src SH3

    DEFF Research Database (Denmark)

    Rösner, Heike I; Poulsen, Flemming Martin

    2010-01-01

    Secondary chemical shift analysis has been used to characterize the unfolded state of acid-denatured c-src SH3. Even though native c-src SH3 adopts an all-beta fold, we found evidence of transient helicity in regions corresponding to native loops. In particular, residues 40-46, connecting the n...

  16. LysGH15B, the SH3b domain of staphylococcal phage endolysin LysGH15, retains high affinity to staphylococci.

    Science.gov (United States)

    Gu, Jingmin; Lu, Rong; Liu, Xiaohe; Han, Wenyu; Lei, Liancheng; Gao, Yu; Zhao, Honglei; Li, Yue; Diao, Yuwen

    2011-12-01

    LysGH15, a phage endolysin, exhibits a particularly broad lytic spectrum against Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA). Sequence analysis reveals that this endolysin contains a C-terminal cell wall binding domain (SH3b), which causes the endolysin to bind to host strains. In this study, the substrate binding affinity of the SH3b domain (LysGH15B) was evaluated. A fusion protein of LysGH15B and green fluorescent protein (LysGH15B-GFP) were cloned and expressed in Escherichia coli. Laser scanning confocal microscopy was used to detect the fluorescence of the treated cells irradiated at different excitation wavelengths and to determine the binding activity of LysGH15B-GFP and GFP. We found that LysGH15B-GFP not only generated green fluorescence, but, more importantly, also displayed specific affinity to staphylococcal isolates, especially MRSA. In contrast, the single GFP did not display any binding activity. The high affinity was attributed to the portion of LysGH15B and the binding activity of the fusion protein was specific to staphylococci. This study provides an insight into the SH3b domain of LysGH15. The specific binding activity may cause LysGH15B to serve as an anchoring device, and offer an alternative approach for cell surface attachment onto staphylococci.

  17. Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)*

    Science.gov (United States)

    Rouka, Evgenia; Simister, Philip C.; Janning, Melanie; Kumbrink, Joerg; Konstantinou, Tassos; Muniz, João R. C.; Joshi, Dhira; O'Reilly, Nicola; Volkmer, Rudolf; Ritter, Brigitte; Knapp, Stefan; von Delft, Frank; Kirsch, Kathrin H.; Feller, Stephan M.

    2015-01-01

    CD2AP is an adaptor protein involved in membrane trafficking, with essential roles in maintaining podocyte function within the kidney glomerulus. CD2AP contains three Src homology 3 (SH3) domains that mediate multiple protein-protein interactions. However, a detailed comparison of the molecular binding preferences of each SH3 remained unexplored, as well as the discovery of novel interactors. Thus, we studied the binding properties of each SH3 domain to the known interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the recognition motif PxPxPR and identified 40 known or novel candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar characteristics and specificities, whereas the SH3-3 domain bound more weakly to most peptide ligands tested yet recognized an unusually extended sequence in ALG-2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP binding sites, recognized by all three SH3 domains, but SH3-3 appeared non-functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive early endosomes via these interaction sites. Permutation arrays and isothermal titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR. Two high-resolution crystal structures (1.65 and 1.11 Å) of CD2AP SH3-1 and SH3-2 solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that another extended motif is relevant in epitope 2. In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3. PMID:26296892

  18. Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3).

    Science.gov (United States)

    Rouka, Evgenia; Simister, Philip C; Janning, Melanie; Kumbrink, Joerg; Konstantinou, Tassos; Muniz, João R C; Joshi, Dhira; O'Reilly, Nicola; Volkmer, Rudolf; Ritter, Brigitte; Knapp, Stefan; von Delft, Frank; Kirsch, Kathrin H; Feller, Stephan M

    2015-10-16

    CD2AP is an adaptor protein involved in membrane trafficking, with essential roles in maintaining podocyte function within the kidney glomerulus. CD2AP contains three Src homology 3 (SH3) domains that mediate multiple protein-protein interactions. However, a detailed comparison of the molecular binding preferences of each SH3 remained unexplored, as well as the discovery of novel interactors. Thus, we studied the binding properties of each SH3 domain to the known interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the recognition motif PxPxPR and identified 40 known or novel candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar characteristics and specificities, whereas the SH3-3 domain bound more weakly to most peptide ligands tested yet recognized an unusually extended sequence in ALG-2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP binding sites, recognized by all three SH3 domains, but SH3-3 appeared non-functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive early endosomes via these interaction sites. Permutation arrays and isothermal titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR. Two high-resolution crystal structures (1.65 and 1.11 Å) of CD2AP SH3-1 and SH3-2 solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that another extended motif is relevant in epitope 2. In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Characterization of Oligomers of Heterogeneous Size as Precursors of Amyloid Fibril Nucleation of an SH3 Domain: An Experimental Kinetics Study

    Science.gov (United States)

    Ruzafa, David; Morel, Bertrand; Varela, Lorena; Azuaga, Ana I.; Conejero-Lara, Francisco

    2012-01-01

    Understanding the earliest molecular events during nucleation of the amyloid aggregation cascade is of fundamental significance to prevent amyloid related disorders. We report here an experimental kinetic analysis of the amyloid aggregation of the N47A mutant of the α-spectrin SH3 domain (N47A Spc-SH3) under mild acid conditions, where it is governed by rapid formation of amyloid nuclei. The initial rates of formation of amyloid structures, monitored by thioflavine T fluorescence at different protein concentrations, agree quantitatively with high-order kinetics, suggesting an oligomerization pre-equilibrium preceding the rate-limiting step of amyloid nucleation. The curves of native state depletion also follow high-order irreversible kinetics. The analysis is consistent with the existence of low-populated and heterogeneous oligomeric precursors of fibrillation that form by association of partially unfolded protein monomers. An increase in NaCl concentration accelerates fibrillation but reduces the apparent order of the nucleation kinetics; and a double mutant (K43A, N47A) Spc-SH3 domain, largely unfolded under native conditions and prone to oligomerize, fibrillates with apparent first order kinetics. On the light of these observations, we propose a simple kinetic model for the nucleation event, in which the monomer conformational unfolding and the oligomerization of an amyloidogenic intermediate are rapidly pre-equilibrated. A conformational change of the polypeptide chains within any of the oligomers, irrespective of their size, is the rate-limiting step leading to the amyloid nuclei. This model is able to explain quantitatively the initial rates of aggregation and the observed variations in the apparent order of the kinetics and, more importantly, provides crucial thermodynamic magnitudes of the processes preceding the nucleation. This kinetic approach is simple to use and may be of general applicability to characterize the amyloidogenic intermediates and

  20. Association between receptor protein-tyrosine phosphatase RPTPalpha and the Grb2 adaptor. Dual Src homology (SH) 2/SH3 domain requirement and functional consequences

    DEFF Research Database (Denmark)

    Su, J; Yang, L T; Sap, J

    1996-01-01

    Receptor protein-tyrosine phosphatase RPTPalpha is found associated in vivo with the adaptor protein Grb2. Formation of this complex, which contains no detectable levels of Sos, is known to depend on a C-terminal phosphorylated tyrosine residue (Tyr798) in RPTPalpha and on the Src homology (SH) 2...... in vivo. These observations constitute a novel mode of Grb2 association and suggest a model in which association with a tyrosine-phosphorylated protein restricts the repertoire of SH3 binding proteins with which Grb2 can simultaneously interact. The function of the Tyr798 tyrosine phosphorylation/Grb2...

  1. A Biochemical/Biophysical Assay Dyad for HTS-Compatible Triaging of Inhibitors of the HIV-1 Nef/Hck SH3 Interaction

    KAUST Repository

    Breuer, Sebastian

    2013-07-26

    The current treatment regimens for HIV include over 20 anti-retrovirals. However, adverse drug effects and the emergence of drug resistance necessitates the continued improvement of the existing drug classes as well as the development of novel drugs that target as yet therapeutically unexploited viral and cellular pathways. Here we demonstrate a strategy for the discovery of protein-protein interaction inhibitors of the viral pathogenicity factor HIV-1 Nef and its interaction with the host factor SH3. A combination of a time-resolved fluorescence resonance energy resonance energy transfer-based assay and a label-free resonant waveguide grating-based assay was optimized for high-throughput screening formats.

  2. Accelerated materials design approaches based on structural classification: application to low enthalpy high pressure phases of SH3 and SeH3

    Science.gov (United States)

    Flores-Livas, José A.; Sanna, Antonio; Goedecker, Stefan

    2017-01-01

    We propose a methodology that efficiently asseses major characteristics in the energy landscape for a given space of configurations (crystal structures) under pressure. In this work we study SH3 and SeH3 , both of fundamental interest due to their superconducting properties. Starting from the crystal fingerprint, which defines configurational distances between crystalline structures, we introduce an optimal one dimensional metric space that is used to both classify and characterize the structures. Furthermore, this is correlated to the electronic structure. Our analysis highlights the uniqueness of the Im - 3m phase of H3S and H33Se for superconductivity. This approach is an useful tool for future material design applications.

  3. Automated Fmoc-based solid-phase synthesis of peptide thioesters with self-purification effect and application in the construction of immobilized SH3 domains.

    Science.gov (United States)

    Mende, Franziska; Beisswenger, Michael; Seitz, Oliver

    2010-08-18

    truncation products can resist extraction and contaminate full-length thioesters obtained after TFA cleavage. It is shown that significant enhancements of the purity were achieved when mild acidic extractions were included in the wash protocols after thiolysis. The potential of the method was demonstrated in the parallel synthesis of 20-40 amino acid long peptide thioesters, which were obtained in excellent purities. The thioesters and cysteinyl peptides were used without purification in the assembly of immobilized SH3 protein domains of SHO1 in yeast. A cysteine scan by native chemical ligation suggested single amino acid to cysteine substitutions that (a) confer useful ligation yields, (b) support correct folding, and (c) sustain the function of the folded protein domain. The chemical synthesis of the SH3-domain of SHO1 succeeded in highest yields when cysteine placements at positions S23, F24, and E36 were avoided. The synthetic SH3 mutants were examined in a binding assay, which indicated that N27C, L30C, and D34C mutations provide functional SH3-domain.

  4. Critical evaluation of the two-state model describing the equilibrium unfolding of the PI3K SH3 domain by time-resolved fluorescence resonance energy transfer.

    Science.gov (United States)

    Kishore, Megha; Krishnamoorthy, G; Udgaonkar, Jayant B

    2013-12-31

    It appears that equilibrium unfolding transitions of many small proteins can be described as two-state transitions, because the probes commonly used to measure such transitions cannot detect the underlying heterogeneity inherent in protein folding and unfolding reactions. Time-resolved fluorescence or Forster resonance energy transfer (TRFRET) measurements have the potential to uncover such heterogeneity and to test the cooperativity of protein folding reactions. Here, TRFRET measurements have been used to study the equilibrium unfolding of the SH3 domain of PI3 kinase. The single tryptophan residue (W53) was used as the FRET donor, and a covalently attached thionitrobenzoate moiety at either of two sites (C17 and C70) was used as the FRET acceptor. The individual lifetime and amplitude components estimated from fitting the fluorescence decay kinetics to the sum of three or four exponentials were determined over a range of denaturant concentrations. The equilibrium unfolding transitions reported by these components were found to be noncoincident, suggesting the presence of multiple conformations in equilibrium during the course of unfolding. Fluorescence lifetime distributions were also generated by the model-free maximum entropy method of analysis. Different segments of the protein were found to show differences in the expansion of the native state at low denaturant concentrations, suggestive of gradual structural transitions. The unfolded protein was found to swell at increasingly high denaturant concentrations. The evolution of the fluorescence lifetime distributions with increasing denaturant concentration was also found to be incompatible with a two-state equilibrium unfolding model.

  5. Lytic activity of the staphylolytic Twort phage endolysin CHAP domain is enhanced by the SH3b cell wall binding domain.

    Science.gov (United States)

    Becker, Stephen C; Swift, Steven; Korobova, Olga; Schischkova, Nina; Kopylov, Pavel; Donovan, David M; Abaev, Igor

    2015-01-01

    Increases in the prevalence of antibiotic-resistant strains of Staphylococcus aureus have elicited efforts to develop novel antimicrobials to treat these drug-resistant pathogens. One potential treatment repurposes the lytic enzymes produced by bacteriophages as antimicrobials. The phage Twort endolysin (PlyTW) harbors three domains, a cysteine, histidine-dependent amidohydrolases/peptidase domain (CHAP), an amidase-2 domain and a SH3b-5 cell wall binding domain (CBD). Our results indicate that the CHAP domain alone is necessary and sufficient for lysis of live S. aureus, while the amidase-2 domain is insufficient for cell lysis when provided alone. Loss of the CBD results in ∼10X reduction of enzymatic activity in both turbidity reduction and plate lysis assays compared to the full length protein. Deletion of the amidase-2 domain resulted in a protein (PlyTW Δ172-373) with lytic activity that exceeded the activity of the full length construct in both the turbidity reduction and plate lysis assays. Addition of Ca(2+) enhanced the turbidity reduction activity of both the full length protein and truncation constructs harboring the CHAP domain. Chelation by addition of EDTA or the addition of zinc inhibited the activity of all PlyTW constructs. Published by Oxford University Press on behalf of FEMS 2014. This work is written by US Government employees and is in the public domain in the US.

  6. eEF2 and Ras-GAP SH3 domain-binding protein (G3BP1) modulate stress granule assembly during HIV-1 infection

    Science.gov (United States)

    Valiente-Echeverría, Fernando; Melnychuk, Luca; Vyboh, Kishanda; Ajamian, Lara; Gallouzi, Imed Eddine; Bernard, Nicole; Mouland, Andrew J.

    2016-01-01

    Stress granules (SG) are translationally silent sites of RNA triage induced by environmental stresses including viral infection. Here we show that HIV-1 Gag blocks SG assembly irrespective of eIF2α-phosphorylation and even when SG assembly is forced by overexpression of Ras-GAP SH3 domain-binding protein (G3BP1) or TIAR. The overexposed loops in the N-terminal Capsid domain of Gag and host eukaryotic elongation factor 2 (eEF2) are found to be critical for the SG blockade via interaction. Moreover, Cyclophilin A (CypA) stabilizes the Gag-eEF2 association. eEF2 depletion not only lifts the SG blockade but also results in impaired virus production and infectivity. Gag also disassembles pre-formed SGs by recruiting G3BP1 thereby displacing eEF2, revealing another unsuspected virus-host interaction involved in this mechanism. Understanding how HIV-1 counters anti-viral stress responses will lay the groundwork for new therapeutic strategies to bolster host cell immune defences against HIV-1 and other pathogens. PMID:25229650

  7. Role of hepatitis B virus X protein in regulating LIM and SH3 protein 1 (LASP-1 expression to mediate proliferation and migration of hepatoma cells

    Directory of Open Access Journals (Sweden)

    Tang Renxian

    2012-08-01

    Full Text Available Abstract Background Hepatitis B virus X protein (HBx has been shown to be responsible for the development of hepatocellular carcinoma (HCC caused by Hepatitis B virus infection. However, its potential effect on the progression of hepatocellular carcinoma remains yet unclear. LIM and SH3 protein 1 (LASP-1, a focal adhesion protein, is expressed in an up-regulation manner in the HCC tissues. LASP-1 plays an important role in the regulation of proliferation and migration of HCC. In this study, we investigated the effect of LASP-1 involved in HBx-related tumor progression. Methods LASP-1 levels in the HBx stable transfected HepG2 and Huh-7 cells were detected by RT-PCR and western blot analysis. The cellular localization of LASP-1 was assessed by immunofluorescence analysis. The activity of phosphatidylinositol 3-kinase (PI3-K pathway was demonstrated by western blot assay. The HBx-expressing cells were transfected with specific small interference RNA (siRNA against LASP-1. The proliferation and migration ability of cells were evaluated by cell viability assay and plate clone formation assay. The migration ability of cells was detected by transwell assay and wound healing assay. Results RT-PCR and western blot analysis indicated the expression of LASP-1 was increased in the stable HBx-expressing cells compared with the control cells. Immunofluorescence study revealed that the distributions of LASP-1 in HepG2-HBX cells were mainly in pseudopods and the cytoplasm while they were mainly localized in the cytoplasm of HepG2-Mock cells. The cellular localizations of LASP-1 in Huh-7-HBX cells were in the perinuclear fractions while they were mainly localized in the cytoplasm of Huh-7-Mock cells. The upregulation of LASP-1 was inhibited after treatment with LY294002, PI3-K pathway inhibitor. Overexpression of LASP-1 in the stable HBx-expressing cells enhanced the proliferation and migration ability of hepatocellular cells. siRNA-mediated LASP-1 knowdown in

  8. Avaliação e seleção de progênies F3 de cafeeiros de porte baixo com o gene SH3 de resistência a Hemileia vastatrix Berk. et Br. Evaluation and selection of Coffea arabica F3 progenies with low height and the leaf-rust SH3 resistence gene

    Directory of Open Access Journals (Sweden)

    Albano Silva da Conceição

    2005-01-01

    Full Text Available Com o objetivo de avaliar e selecionar progênies F3 de cafeeiros de porte baixo com o gene SH3 de resistência à ferrugem, foram estudadas 36 progênies de cafeeiros tipo arábica (Coffea arabica L. , em geração F3, resultantes dos cruzamentos dirigidos entre as cultivares Catuaí Vermelho IAC 46 e Catuaí Vermelho IAC 81 com o acesso IAC 1110 (BA-10. Esse último, originário da Índia, é fonte dos genes SH2SH3 que conferem resistência a Hemileia vastatrix. O experimento, estabelecido em 1988 no Centro Experimental do Instituto Agronômico, em Campinas (SP, no delineamento experimental em blocos ao acaso com seis repetições, duas plantas por parcela e no espaçamento 3,0 x 1,8 m, utilizou como testemunha a cultivar Catuaí Vermelho IAC 81, totalizando 37 tratamentos. Avaliaram-se no campo, a produção de café (média de sete colheitas, vigor vegetativo, resistência à ferrugem, porte da planta, coloração das folhas novas e maturação dos frutos. Os frutos das plantas mais produtivas foram analisados em laboratório quanto ao rendimento, tipos de sementes, peneira média e massa de 1000 grãos. A análise da variância dos dados de produção das progênies evidenciou que houve diferenças significativas entre as progênies, ao nível de 1% de probabilidade, pelo teste F. Foram selecionadas 11 progênies com média superior à testemunha e dentro dessas, 39 cafeeiros. Das 25 progênies restantes foram selecionados mais 15 cafeeiros produtivos e resistentes ao agente da ferrugem. Desses 54 cafeeiros, foram selecionados os 18 que apresentaram peneira média acima de 15,5 e maior freqüência de grãos normais do tipo chato. As progênies dessas plantas selecionadas foram avaliadas na geração F4, em fase de mudas, quando se verificou que dez delas estavam em homozigoze para porte baixo. Com as 18 plantas, o Programa de Melhoramento do Café, no IAC, terá continuidade como progênies F4, visando à obtenção de nova cultivar de

  9. A c.1244G>A (p.Arg415Gln) mutation in SH3BP2 gene causes cherubism in a Turkish family: report of a family with review of the literature.

    Science.gov (United States)

    Sekerci, Ahmet-Ercan; Balta, Burhan; Dundar, Munis; Hu, Ying; Reichenberger, Ernst-J; Etoz, Osman-A; Nazlim, Sinan; Bayrakdar, Ibrahim-Sevki

    2014-07-01

    The present study was aimed at advancing the understanding of the pathogenesis of cherubism by presenting a case study based on history, physical examination, typical radiological features, molecular and histopathological laboratory tests and a review of the literature. This study began with a 7-year-old boy who was referred due to mandibular overgrowth. A panoramic radiograph revealed multilocular radiolucent lesions of the upper/lower jaws suggestive of cherubism. Overall, a total of four family members were tested for SH3BP2 mutations, namely two siblings and their parents. Both siblings had been clinically diagnosed with cherubism; however, the parents were clinically normal. Peripheral blood was collected from all participants and genomic DNA sequencing was carried out. A missense mutation was found in the two affected siblings and their asymptomatic mother. The mutation was a 1244 G>A transversion which resulted in an amino acid substitution from arginine to glutamine (p.Arg415Gln) in exon 9. The present study emphasized the importance of further clinical and molecular investigation even when only a single case of cherubism is identified within a family. Genotype-phenotype association studies in individuals with cherubism are necessary to provide important insights into the molecular mechanisms associated with this disease.

  10. Transferência de fatores genéticos de resistência a Hemileia vastatrix para o cultivar mundo novo Transference of the genes SH2 and SH3 for resistance to Hemileia vastatrix to the mundo novo cultivar of C. arabica

    Directory of Open Access Journals (Sweden)

    A. Carvalho

    1977-01-01

    Full Text Available Cafeeiros portadores dos fatores genéticos SH2 ou SH2 e SH3, simultaneamente, que conferem resistência a várias raças de Hemileia vastatrix, foram cruzados com plantas selecionadas do cultivar mundo novo de Coffea arabica a fim de se obter, em F2, recombinações com resistência a esse patógeno e elevada produtividade. Analisaram-se 14 populações F2 segregando apenas para o fator SH2, oito para os fatores SH2 e HS3, e três populações que dão, em sua descendência, plantas do grupo A, resistentes a todas as raças do patógeno até agora conhecidas. De 22.356 cafeeiros originalmente plantados em ensaio, a duas mudas por cova, em parcelas casualizadas, fez-se uma primeira seleção deixando apenas um cafeeiro por cova, reduzindo-se para 11.178 as plantas em estudo. Com base no aspecto vegetativo, na produtividade, na ausência de defeitos nos frutos e na reação de resistência ao agente causal da ferrugem, realizaram-se sucessivas seleções escolhendo-se finalmente, apenas 100 cafeeiros do tipo mundo novo e resistentes a H. vastatrix para derivação das populações F2 e prosseguimento da seleção.Coffee trees homozygous for the alleles SH2 or SH2 and SH3 which confer resistance to several physiological races of Hemileia vastatrix, were crossed to selected plants of Mundo Novo cultivar of Coffea arabica and the F2 generations were studied aiming to develop new high yielding and resistant coffee recombinations. A complete randomized field trial was stablished including 14 F2 populations segregating for SH2, eight populations segregating for SH2 and SH3 genes, and three populations segregating for plants of the A group of reaction to the H. vastatrix attack. A total of 22,356 F2 plants were analysed. Based on the plant vigor, yield capacity, percentage of normal developed seeds and resistance reaction to H. vastatrix, three successive series of selection were undertaken leaving only 100 coffee trees for development of F3 populations

  11. Comprehensive analysis of interactions between the Src-associated protein in mitosis of 68 kDa and the human Src-homology 3 proteome.

    Directory of Open Access Journals (Sweden)

    Benedikt Asbach

    Full Text Available The protein Sam68 is involved in many cellular processes such as cell-cycle regulation, RNA metabolism, or signal transduction. Sam68 comprises a central RNA-binding domain flanked by unstructured tails containing docking sites for signalling proteins including seven proline-rich sequences (denoted P0 to P6 as potential SH3-domain binding motifs. To comprehensively assess Sam68-SH3-interactions, we applied a phage-display screening of a library containing all approx. 300 human SH3 domains. Thereby we identified five new (from intersectin 2, the osteoclast stimulating factor OSF, nephrocystin, sorting nexin 9, and CIN85 and seven already known high-confidence Sam68-ligands (mainly from the Src-kinase family, as well as several lower-affinity binders. Interaction of the high-affinity Sam68-binders was confirmed in independent assays in vitro (phage-ELISA, GST-pull-down and in vivo (FACS-based FRET-analysis with CFP- and YFP-tagged proteins. Fine-mapping analyses with peptides established P0, P3, P4, and P5 as exclusive docking-sites for SH3 domains, which showed varying preferences for these motifs. Mutational analyses identified individual residues within the proline-rich motifs being crucial for the interactions. Based on these data, we generated a Sam68-mutant incapable of interacting with SH3 domains any more, as subsequently demonstrated by FRET-analyses. In conclusion, we present a thorough characterization of Sam68's interplay with the SH3 proteome. The observed interaction between Sam68 and OSF complements the known Sam68-Src and OSF-Src interactions. Thus, we propose, that Sam68 functions as a classical scaffold protein in this context, assembling components of an osteoclast-specific signalling pathway.

  12. Trafficking of human ADAM 12-L: retention in the trans-Golgi network

    DEFF Research Database (Denmark)

    Hougaard, S; Loechel, F; Xu, X

    2000-01-01

    We have investigated the trafficking of the membrane-anchored form of human ADAM 12 (ADAM 12-L) fused to a green fluorescence protein tag. Subcellular localization of the protein in transiently transfected cells was determined by fluorescence microscopy and trypsin sensitivity. Full-length ADAM 12...... the cytoplasmic and transmembrane domains, but not the Src homology 3 domain (SH3) binding sites. These results raise the possibility that a trafficking checkpoint in the trans-Golgi network is one of the cellular mechanisms for regulation of ADAM 12-L function, by allowing a rapid release of ADAM 12-L...

  13. NCBI nr-aa BLAST: CBRC-MMUS-10-0044 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUS-10-0044 ref|NP_001092759.1| SH3 multiple domains 4 [Homo sapiens] sp|Q8TEJ3|SH3D4_HUMAN SH3 multip...le domains protein 4 precursor (Plenty of SH3s 2) NP_001092759.1 2e-77 79% ...

  14. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners

    Czech Academy of Sciences Publication Activity Database

    Gemperle, J.; Hexnerová, Rozálie; Lepšík, Martin; Těšina, Petr; Dibus, M.; Novotný, M.; Brábek, J.; Veverka, Václav; Rösel, D.

    2017-01-01

    Roč. 7, Aug 14 (2017), č. článku 8057. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GBP208/12/G016; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : focal adhesion kinase * Src-transformed cells * tyrosine phosphorylation Subject RIV: CE - Biochemistry Impact factor: 4.259, year: 2016 https://www.nature.com/articles/s41598-017-08303-4

  15. Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup Repeat Specificity

    DEFF Research Database (Denmark)

    Vognsen, Tina Reinholdt; Möller, Ingvar Rúnar; Kristensen, Ole

    2013-01-01

    Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat...... peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded...

  16. Differential expression profiling of membrane proteins by quantitative proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation

    DEFF Research Database (Denmark)

    Foster, Leonard J; Zeemann, Patricia A; Li, Chen

    2005-01-01

    useful for analyzing complex protein expression patterns and, when applied quantitatively, can be used to resolve subtle differences between samples. Thus, we used MS to characterize changes in expression of membrane protein markers before and after short-term induction of osteoblast (OB) differentiation...... in a cell model of hMSCs established by overexpression of human telomerase reverse-transcriptase gene. We identified 463 unique proteins with extremely high confidence, including all known markers of hMSCs (e.g., SH3 [CD71], SH2 [CD105], CD166, CD44, Thy1, CD29, and HOP26 [CD63]) among 148 integral membrane...... or membrane-anchored proteins and 159 membrane-associated proteins. Twenty-nine integrins and cell adhesion molecules, 20 receptors, and 18 Ras-related small GTPases were also identified. Upon OB differentiation, the expression levels of 83 proteins increased by at least twofold whereas the levels of another...

  17. Sab (Sh3bp5) dependence of JNK mediated inhibition of mitochondrial respiration in palmitic acid induced hepatocyte lipotoxicity.

    Science.gov (United States)

    Win, Sanda; Than, Tin Aung; Le, Bao Han Allison; García-Ruiz, Carmen; Fernandez-Checa, Jose C; Kaplowitz, Neil

    2015-06-01

    Sustained c-Jun N-terminal kinase (JNK) activation by saturated fatty acids plays a role in lipotoxicity and the pathogenesis of non-alcoholic steatohepatitis (NASH). We have reported that the interaction of JNK with mitochondrial Sab leads to inhibition of respiration, increased reactive oxygen species (ROS), cell death and hepatotoxicity. We tested whether this pathway underlies palmitic acid (PA)-induced lipotoxicity in hepatocytes. Primary mouse hepatocytes (PMH) from adeno-shlacZ or adeno-shSab treated mice and HuH7 cells were used. In PMH, PA dose-dependently up to 1mM stimulated oxygen consumption rate (OCR) due to mitochondrial β-oxidation. At ⩾1.5mM, PA gradually reduced OCR, followed by cell death. Inhibition of JNK, caspases or treatment with antioxidant butylated hydroxyanisole (BHA) protected PMH against cell death. Sab knockdown or a membrane permeable Sab blocking peptide prevented PA-induced mitochondrial impairment, but inhibited only the late phase of both JNK activation (beyond 4h) and cell death. In PMH, PA increased p-PERK and its downstream target CHOP, but failed to activate the IRE-1α arm of the UPR. However, Sab silencing did not affect PA-induced PERK activation. Conversely, specific inhibition of PERK prevented JNK activation and cell death, indicating a major role upstream of JNK activation. The effect of p-JNK on mitochondria plays a key role in PA-mediated lipotoxicity. The interplay of p-JNK with mitochondrial Sab leads to impaired respiration, ROS production, sustained JNK activation, and apoptosis. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations.

    NARCIS (Netherlands)

    Azzedine, H.; Ravise, N.; Verny, C.; Gabreëls-Festen, A.A.W.M.; Lammens, M.M.Y.; Grid, D.; Vallat, J.M.; Durosier, G.; Senderek, J.; Nouioua, S.; Hamadouche, T.; Bouhouche, A.; Guilbot, A.; Stendel, C.; Ruberg, M.; Brice, A.; Birouk, N.; Dubourg, O.; Tazir, M.; LeGuern, E.

    2006-01-01

    BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies with several modes of inheritance: autosomal dominant, X-linked, and autosomal recessive (AR) CMT. A locus responsible for the demyelinating form of ARCMT was assigned to the

  19. GTPase-activating protein SH2-SH3 domains induce gene expression in a Ras-dependent fashion

    NARCIS (Netherlands)

    Medema, R.H.; Laat, W.L. de; Martin, G.A.; Mccormick, F.; Bos, J.L.

    1992-01-01

    The p21ras GTPase-activating protein (GAP) is thought to function as both a negative regulator and a downstream target of p21ras. Here, we have investigated the role of GAP by using a transient expression assay with a fos luciferase reporter plasmid. We used GAP deletion mutants that lack the domain

  20. Molecular cloning of the human homolog of a striatum-enriched phosphatase (STEP) gene and chromosomal mapping of the human and murine loci

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xu; Luna, J. [Stanford Univ. Medical Center, CA (United States); Francke, U. [Stanford Univ. Medical Center, CA (United States)]|[Yale Univ. School of Medicine, New Haven, CT (United States)

    1995-08-10

    A gene for a protein tyrosine phosphatase (PTPase) was isolated from a human fetal brain cDNA library by PCR amplification. Sequence analysis revealed that the PTPase has a single phosphatase catalytic domain located at the C-terminus that includes the highly conserved amino acid domain [I/V]HCXAGXXR[S/T]GX[F/Y] found in all tyrosine phosphatases. Two proline-rich regions located at the N-terminus may contain putative Src homology domain 3 (SH3) binding motifs. Comparison of the PTPase with a previously cloned striatum enriched phosphatase (STEP) from rat and from mouse exhibited a high degree of identity ({approximately}85-90%) at both the nucleotide and the amino acid levels, indicating that the human PTPase is the homolog of the rat and murine STEP gene. By using a combination of somatic cell hybrid analysis and fluorescence in situ hybridization, we have mapped the human STEP locus to chromosome 11p15.2-p15.1 and the murine STEP gene to chromosome 7B3-B5. These are two regions of known conserved synteny, providing further evidence that the human STEP is a true homolog of the murine STEP gene. Candidate disease genes in the vicinity include Usher syndrome type 1C in human and a mouse mutant locus, twister (twt). 50 refs., 3 figs.

  1. On the role of NR3A in human NMDA receptors

    DEFF Research Database (Denmark)

    Eriksson, Maria; Nilsson, Anna; Samuelsson, Helena

    2007-01-01

    binding site, with similar affinity as the glycine binding site of NR1 subunits. This suggests that NR3A may replace one of the two NR1 subunits in native NMDA receptors. Cloning of hNR3A showed a human-specific polyproline-sequence in the intracellular C-terminus, that may bind to SH3-domains. We......In the present paper we describe our on-going project investigating the functional roles of the N-methyl-D-aspartate (NMDA) receptor subunit NR3A. We find that NR3A mRNA is abundant both in embryonic and adult human brain, in contrast to the almost non-existing expression in adult rodent brain....... Human NR3A (hNR3A) protein expression is particularly abundant in the cerebral cortex, as shown by western blot using NR3A-specific antibodies. Distribution of hNR3A in adult human brain shows a similar pattern as NR3A in post-natal rodent brain. We have previously reported that NR3A contains a glycine...

  2. Enhancement of B-cell receptor signaling by a point mutation of adaptor protein 3BP2 identified in human inherited disease cherubism.

    Science.gov (United States)

    Ogi, Kazuhiro; Nakashima, Kenji; Chihara, Kazuyasu; Takeuchi, Kenji; Horiguchi, Tomoko; Fujieda, Shigeharu; Sada, Kiyonao

    2011-09-01

    Tyrosine phosphorylation of adaptor protein c-Abl-Src homology 3 (SH3) domain-binding protein-2 (3BP2, also referred to SH3BP2) positively regulates the B-cell antigen receptor (BCR)-mediated signal transduction, leading to the activation of nuclear factor of activated T cells (NFAT). Here we showed the effect of the proline to arginine substitution of 3BP2 in which is the most common mutation in patients with cherubism (P418R) on B-cell receptor signaling. Comparing to the wild type, overexpression of the mutant form of 3BP2 (3BP2-P416R, corresponding to P418R in human protein) enhanced BCR-mediated activation of NFAT. 3BP2-P416R increased the signaling complex formation with Syk, phospholipase C-γ2 (PLC-γ2), and Vav1. In contrast, 3BP2-P416R could not change the association with the negative regulator 14-3-3. Loss of the association mutant that was incapable to associate with 14-3-3 could not mimic BCR-mediated NFAT activation in Syk-deficient cells. Moreover, BCR-mediated phosphorylation of extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was not affected by P416R mutation. These results showed that P416R mutation of 3BP2 causes the gain of function in B cells by increasing the interaction with specific signaling molecules. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

  3. Loss of Expression of Human Spectrin Src Homology Domain Binding Protein 1 is Associated with 10p Loss in Human Prostatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Jill A. Macoska

    2001-01-01

    Full Text Available The gene encoding human spectrin Src homology domain binding protein 1, or Hssh3bpl, which is a marker of macropinocytic vesicles and a potential regulator of macropinocytosis, co-localizes to a YAC containing chromosome 10p sequences at loci D10S89 and D10S111 that are frequently deleted in prostate tumors. Expression of Hssh3bp1 was evaluated at the protein level in 17 paired normal and malignant prostate tumor samples using the monoclonal antibody 2G8 to Hssh3bpl. These experiments demonstrated that 4/6 tumors (67% with 10p deletion failed to express Hssh3bp1 protein compared to 5/11 (46% tumors with intact 10p. Thus, loss of Hssh3bp1 expression is concordant with allelic loss of adjacent 10p sequences in human prostate tumors. In addition, two prostate tumor cell lines contain an exon skipping mutation in the Hssh3bp1 gene that leads to the abnormal splicing of the mRNA and loss of a portion of Abl tyrosine kinase SH3 domain binding site in the protein. These data are consistent with a role for Hssh3bp1 as a candidate tumor suppressor gene inactivated during prostate tumorigenesis.

  4. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  5. Cloning of the genes encoding two murine and human cochlear unconventional type I myosins

    Energy Technology Data Exchange (ETDEWEB)

    Crozet, F.; El Amraoui, Z.; Blanchard, S. [Institut Pasteur, Paris (France)] [and others

    1997-03-01

    Several lines of evidence indicate a crucial role for unconventional myosins in the function of the sensory hair cells of the inner ear. We report here the characterization of the cDNAs encoding two unconventional type I myosins from a mouse cochlear cDNA library. The first cDNA encodes a putative protein named Myo1c, which is likely to be the murine orthologue of the bullfrog myosin I{beta} and which may be involved in the gating of the mechanotransduction channel of the sensory hair cells. This myosin belongs to the group of short-tailed myosins I, with its tail ending shortly after a polybasic, TH-1-like domain. The second cDNA encodes a novel type I myosin Myo1f which displays three regions: a head domain with the conserved ATP- and actin-binding sites, a neck domain with a single IQ motif, and a tail domain with the tripartite structure initially described in protozoan myosins I. The tail of Myo1f includes (1) a TH-1 region rich in basic residues, which may interact with anionic membrane phospholipids; (2) a TH-2 proline-rich region, expected to contain an ATP-insensitive actin-binding site; and (3) an SH-3 domain found in a variety of cytoskeletal and signaling proteins. Northern blot analysis indicated that the genes encoding Myo1c and Myo1f display a widespread tissue expression in the adult mouse. Myo1c and Myo1f were mapped by in situ hybridization to the chromosomal regions 11D-11E and 17B-17C, respectively. The human orthologuous genes MYO1C and MYO1F were also characterized, and mapped to the human chromosomal regions 17p13 and 19p13.2- 19p1.3.3, respectively. 45 refs., 5 figs., 2 tabs.

  6. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards

  7. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, D.R.

    2007-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  8. Human Monkeypox

    National Research Council Canada - National Science Library

    Wilson, Mary E; Hughes, James M; McCollum, Andrea M; Damon, Inger K

    2014-01-01

    Human monkeypox is found primarily in forested areas of Central Africa. This article provides a basic review of the clinical, epidemiological, and biological factors that contribute to human disease...

  9. Human microbiomics

    OpenAIRE

    Rajendhran, J.; Gunasekaran, P.

    2010-01-01

    The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity has been demonstrated, which may pave the way for new prophylactic and therapeutic strategies such as bacteriotherapy. The sig...

  10. Human Development

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2009-01-01

    textabstract‘Human development’ language spread gradually in circles of national and international development policy and planning from the 1970s and acquired a definitive form in the 1990s in the United Nations Development Programme’s Human Development Reports (HDRs). Human development was defined

  11. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina|info:eu-repo/dai/nl/152524096; Zaitch, Damian|info:eu-repo/dai/nl/183348486

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  12. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation...... will ask and try to answer. The mobile phone and its devices are depicted as being able to make a unique human presence, interaction, and affect. The medium, the technology is a necessary helper to get towards this very special and lost humanity. Without the technology, no special humanity - soul...... - is the prophecy. This personification or anthropomorphism is important for the branding of new technology. The technology is seen as creating a technotranscendens towards a more qualified humanity, which is in contact with the fundamental human values like intuition, vision, and sensing; all the qualities...

  13. Human Parvoviruses.

    Science.gov (United States)

    Qiu, Jianming; Söderlund-Venermo, Maria; Young, Neal S

    2017-01-01

    Parvovirus B19 (B19V) and human bocavirus 1 (HBoV1), members of the large Parvoviridae family, are human pathogens responsible for a variety of diseases. For B19V in particular, host features determine disease manifestations. These viruses are prevalent worldwide and are culturable in vitro, and serological and molecular assays are available but require careful interpretation of results. Additional human parvoviruses, including HBoV2 to -4, human parvovirus 4 (PARV4), and human bufavirus (BuV) are also reviewed. The full spectrum of parvovirus disease in humans has yet to be established. Candidate recombinant B19V vaccines have been developed but may not be commercially feasible. We review relevant features of the molecular and cellular biology of these viruses, and the human immune response that they elicit, which have allowed a deep understanding of pathophysiology. Copyright © 2016 American Society for Microbiology.

  14. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  15. Proteome analysis of human substantia nigra in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Werner Cornelius J

    2008-02-01

    Full Text Available Abstract Background Parkinson's disease (PD is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra. Results The gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin and glutathione-related redox metabolism (GST M3, GST P1, GST O1, including novel redox proteins (SH3BGRL. Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin, as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation, aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism. Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results. Conclusion Using an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many

  16. Digital Humanities

    DEFF Research Database (Denmark)

    Brügger, Niels

    2016-01-01

    Digital humanities is an umbrella term for theories, methodologies, and practices related to humanities scholarship that use the digital computer as an integrated and essential part of its research and teaching activities. The computer can be used for establishing, finding, collecting......, and preserving material to study, as an object of study in its own right, as an analytical tool, or for collaborating, and for disseminating results. The term "digital humanities" was coined around 2001, and gained currency within academia in the following years. However, computers had been used within...... the humanities for decades, starting with research fields such as humanities computing or computational linguistics in the 1950s, and later new media studies and internet studies. The historical development of digital humanities has been characterized by a focus on three successive, but co-existing types...

  17. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre

    2017-01-01

    The field of human ancient DNA (aDNA) has moved from mitochondrial sequencing that suffered from contamination and provided limited biological insights, to become a fully genomic discipline that is changing our conception of human history. Recent successes include the sequencing of extinct hominins......, and true population genomic studies of Bronze Age populations. Among the emerging areas of aDNA research, the analysis of past epigenomes is set to provide more new insights into human adaptation and disease susceptibility through time. Starting as a mere curiosity, ancient human genetics has become...

  18. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  19. Human Rights and Human Nature

    Directory of Open Access Journals (Sweden)

    Vittorio Possenti

    2013-11-01

    Full Text Available There seems to be two different versions of human rights in Western tradition: say Rationalistic and Christian; the former adopted in revolutionary France, the latter highly developed in Renaissance Spain. Current relativistic criticisms attempt to deny the universality of human rights alleging that this theory has been created in Western countries or it has no strong justification, and therefore cannot have universal approach; but this objection can be dismissed with an alternative justification of human rights.

  20. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  1. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter

    2015-01-01

    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  2. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg

    2007-01-01

    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  3. Human Computation

    CERN Multimedia

    CERN. Geneva

    2008-01-01

    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  4. Human phantom

    CERN Multimedia

    CERN PhotoLab

    1973-01-01

    This human phantom has been received by CERN on loan from the State Committee of the USSR for the Utilization of Atomic Energy. It is used by the Health Physics Group to study personel radiation doses near the accelerators.

  5. Human expunction

    Science.gov (United States)

    Klee, Robert

    2017-10-01

    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  6. Human brucellosis

    NARCIS (Netherlands)

    Franco, María Pía; Mulder, Maximilian; Gilman, Robert H.; Smits, Henk L.

    2007-01-01

    Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens.

  7. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  8. Human ehrlichiosis

    Directory of Open Access Journals (Sweden)

    Đokić Milomir

    2006-01-01

    Full Text Available Background. Human ehrlichiosis is a newly recognized disease. It is a tick-borne disease caused by several bacterial species of the genhus Erlichia. These are small gram-negative pleomorphic cocci, that are obligatory intracellular bacteria. Tick Ixodes is the principle vector in Europe, and Amblyomma americanum in the United States. Bacterial organisms replicate in a tick, and are transmited from infected cells in a vector to the blood cells of animals or humans. Human ehrlichiosis is a name for a group of diseases caused by different species of Ehrlichia. One of them is the disease named human monocytic ehrlichiosis, caused by Ehrlichia chaffeensis, and the other is a human granulocytic ehrlichiosis caused by Anaplasma phagocytophilia. Case report. We reported a 23-year-old patient admitted for the clinical treatment with the symptoms of high febrility (above 40 °C, headache, vomiting, general weakness and exhaustion, but without data on a tick bite. The patient was treated with trimetoprim-sulfamethoxazole for a week when Ehrlichia chaffeensis was confirmed by the immunofluoroscence test, and the therapy contimed with doxacyclin. Conclusion. Human ehrlichiosis is also present in our country, so this disease should be considered everyday, especially in infectology practice.

  9. Human 14-3-3 paralogs differences uncovered by cross-talk of phosphorylation and lysine acetylation.

    Directory of Open Access Journals (Sweden)

    Marina Uhart

    Full Text Available The 14-3-3 protein family interacts with more than 700 different proteins in mammals, in part as a result of its specific phospho-serine/phospho-threonine binding activity. Upon binding to 14-3-3, the stability, subcellular localization and/or catalytic activity of the ligands are modified. Seven paralogs are strictly conserved in mammalian species. Although initially thought as redundant, the number of studies showing specialization is growing. We created a protein-protein interaction network for 14-3-3, kinases and their substrates signaling in human cells. We included information of phosphorylation, acetylation and other PTM sites, obtaining a complete representation of the 14-3-3 binding partners and their modifications. Using a computational system approach we found that networks of each 14-3-3 isoform are statistically different. It was remarkable to find that Tyr was the most phosphorylatable amino acid in domains of 14-3-3 epsilon partners. This, together with the over-representation of SH3 and Tyr_Kinase domains, suggest that epsilon could be involved in growth factors receptors signaling pathways particularly. We also found that within zeta's network, the number of acetylated partners (and the number of modify lysines is significantly higher compared with each of the other isoforms. Our results imply previously unreported hidden differences of the 14-3-3 isoforms interaction networks. The phosphoproteome and lysine acetylome within each network revealed post-transcriptional regulation intertwining phosphorylation and lysine acetylation. A global understanding of these networks will contribute to predict what could occur when regulatory circuits become dysfunctional or are modified in response to external stimuli.

  10. Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension

    Science.gov (United States)

    Chang, Tien-Jyun; Wang, Wen-Chang; Hsiung, Chao A.; He, Chih-Tsueng; Lin, Ming-Wei; Sheu, Wayne Huey-Herng; Chang, Yi-Cheng; Quertermous, Tom; Chen, Ida; Rotter, Jerome; Chuang, Lee-Ming

    2016-01-01

    Abstract Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort. We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff antihypertension medication were adjustment covariates in the Cox regression analysis. In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication. In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and

  11. A simple strategy for the purification of native recombinant full-length human RPL10 protein from inclusion bodies.

    Science.gov (United States)

    Pereira, Larissa M; Silva, Luana R; Alves, Joseane F; Marin, Nélida; Silva, Flavio Sousa; Morganti, Ligia; Silva, Ismael D C G; Affonso, Regina

    2014-09-01

    The L10 ribosomal protein (RPL10) plays a role in the binding of the 60 S and 40 S ribosomal subunits and in mRNA translation. The evidence indicates that RPL10 also has multiple extra-ribosomal functions, including tumor suppression. Recently, the presence of RPL10 in prostate and ovarian cancers was evaluated, and it was demonstrated to be associated with autistic disorders and premature ovarian failure. In the present work, we successfully cloned and expressed full-length human RPL10 (hRPL10) protein and isolated inclusion bodies containing this protein that had formed under mild growth conditions. The culture produced 376mg of hRPL10 protein per liter of induced bacterial culture, of which 102.4mg was present in the soluble fraction, and 25.6mg was recovered at approximately 94% purity. These results were obtained using a two-step process of non-denaturing protein extraction from pelleted inclusion bodies. We studied the characteristics of this protein using circular dichroism spectroscopy and by monitoring the changes induced by the presence or absence of zinc ions using fluorescence spectrometry. The results demonstrated that the protein obtained using these non-conventional methods retained its secondary and tertiary structure. The conformational changes induced by the incorporation of zinc suggested that this protein could interact with Jun or the SH3 domain of c-yes. The results suggested that the strategy used to obtain hRPL10 is simple and could be applied to obtaining other proteins that are susceptible to degradation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. [Humanized childbirth].

    Science.gov (United States)

    Kuo, Su-Chen

    2005-06-01

    Childbirth is a major event in a family. The expectant parent's perception of the childbirth experience influences his or her development as a parent. Making childbirth a positive and satisfying experience for women is the responsibility of health care providers. Women want to have physical and emotional privacy during labor and delivery, and to experience both in a friendly, comfortable environment. For women expected to undergo normal deliveries, humanized childbirth is one accessible approach. This article explores the definition and evolution of humanized childbirth and the care practice that it involves. It also explores birth plans and birth experiences, and the improvements necessary to routine labor practices to enable women to participate in decision making about their childbirth experiences. The author emphasizes that when health-care providers recognize the value of humanized childbirth and make changes accordingly, the dignity of women's childbirth experiences will be enhanced.

  13. Human monkeypox.

    Science.gov (United States)

    McCollum, Andrea M; Damon, Inger K

    2014-01-01

    Human monkeypox is a zoonotic Orthopoxvirus with a presentation similar to smallpox. Clinical differentiation of the disease from smallpox and varicella is difficult. Laboratory diagnostics are principal components to identification and surveillance of disease, and new tests are needed for a more precise and rapid diagnosis. The majority of human infections occur in Central Africa, where surveillance in rural areas with poor infrastructure is difficult but can be accomplished with evidence-guided tools and educational materials to inform public health workers of important principles. Contemporary epidemiological studies are needed now that populations do not receive routine smallpox vaccination. New therapeutics and vaccines offer hope for the treatment and prevention of monkeypox; however, more research must be done before they are ready to be deployed in an endemic setting. There is a need for more research in the epidemiology, ecology, and biology of the virus in endemic areas to better understand and prevent human infections.

  14. Human mimicry

    NARCIS (Netherlands)

    Chartrand, T.L.; Baaren, R.B. van

    2009-01-01

    Human mimicry is ubiquitous, and often occurs without the awareness of the person mimicking or the person being mimicked. First, we briefly describe some of the major types of nonconscious mimicry—verbal, facial, emotional, and behavioral—and review the evidence for their automaticity. Next, we

  15. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    and self-reflective democracy. Contemporary humanities have adopted a new orientation towards practices, and it is not clear how this fits with the ideals of ‘Bildung’ and ‘pure science’. A possible theoretical framework for this orientation towards practices could be found in John Dewey’s pragmatic...

  16. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  17. Human Parasites

    OpenAIRE

    Davis, Ryan S.; Hodgson, Erin W.

    2008-01-01

    Entomologists often get “bug” samples for identification, including those that accidentally infest residences. In the United States, we are fortunate to have very few arthropods (e.g., insects, spiders, mites, ticks, etc.) that actually infest or feed on humans.

  18. Human steroidogenesis

    DEFF Research Database (Denmark)

    Andersen, Claus Y; Ezcurra, Diego

    2014-01-01

    reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

  19. Human Parechoviruses

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Harvala, Heli; Midgley, Sofie

    2017-01-01

    Infections with human parechoviruses (HPeV) are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality. The clinical presentation of HPeV infection is often indistinguishable from that of enterovirus (EV) infection and may vary from mild disease...

  20. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  1. Human Trafficking

    Science.gov (United States)

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  2. Human monkeypox.

    Science.gov (United States)

    Jezek, Z; Gromyko, A I; Szczeniowski, M V

    1983-01-01

    Human monkeypox, occurring in the tropical rainforest of west and central Africa, is regarded as the most important orthopoxvirus infection for epidemiological surveillance during the post-smallpox era. This disease, first recognized in Zaïre in 1970 resembles smallpox clinically but differs epidemiologically. Clinical features, their evolution and sequelae of monkeypox could be compared with discrete ordinary or modified type of smallpox. A case-fatality rate of 14% has been observed but some cases can be exceedingly mild or atypical and may easily remain undetected and unreported. Pronounced lymphadenopathy has been the only clinical feature found commonly in monkeypox but not in smallpox. Fifty-seven cases of human monkeypox have occurred since 1970, in the tropical rainforests in six west and central African countries, the majority of them (45) being reported from Zaïre. The disease appears to be more frequent in dry season. Children below ten years of age comprise 84% of the cases. Smallpox vaccination protects against monkeypox. Clusters of cases have been observed in certain areas within countries and within affected households. Human-to-human spread has possibly occurred seven times. No cases of possible tertiary spread were observed. The secondary attack rate among susceptible close household contacts was 10%, among all susceptible contacts 5%. This is much lower than that occurring with smallpox, which is between 25-40%. The limited avidity of monkeypox virus for human beings indicates that monkeypox is probably a zoonosis, although the animal reservoir(s) have not yet been identified. The low transmissibility, resulting in low frequency of disease in man indicates that monkeypox is not a public health problem. Human monkeypox has been a relatively newly recognized disease. Studies are in progress to identify the natural cycle of monkeypox virus and to define better its clinical and epidemiological characteristics. Special surveillance is maintained in

  3. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  4. Human Development Report 2000: Human Rights and Human Development

    OpenAIRE

    United Nations Development Programme, UNDP

    2000-01-01

    The Human Development Report 2000 looks at human rights as an intrinsic part of development—and at development as a means to realizing human rights. It shows how human rights bring principles of accountability and social justice to the process of human development.

  5. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  6. Human Protothecosis

    Science.gov (United States)

    Lass-Flörl, Cornelia; Mayr, Astrid

    2007-01-01

    Human protothecosis is a rare infection caused by members of the genus Prototheca. Prototheca species are generally considered to be achlorophyllic algae and are ubiquitous in nature. The occurrence of protothecosis can be local or disseminated and acute or chronic, with the latter being more common. Diseases have been classified as (i) cutaneous lesions, (ii) olecranon bursitis, or (iii) disseminated or systemic manifestations. Infections can occur in both immunocompetent and immunosuppressed patients, although more severe and disseminated infections tend to occur in immunocompromised individuals. Prototheca wickerhamii and Prototheca zopfii have been associated with human disease. Usually, treatment involves medical and surgical approaches; treatment failure is not uncommon. Antifungals such as ketoconazole, itraconazole, fluconazole, and amphotericin B are the most commonly used drugs to date. Among them, amphotericin B displays the best activity against Prototheca spp. Diagnosis is largely made upon detection of characteristic structures observed on histopathologic examination of tissue. PMID:17428884

  7. Human paleoneurology

    CERN Document Server

    2015-01-01

    The book presents an integrative review of paleoneurology, the study of endocranial morphology in fossil species. The main focus is on showing how computed methods can be used to support advances in evolutionary neuroanatomy, paleoanthropology and archaeology and how they have contributed to creating a completely new perspective in cognitive neuroscience. Moreover, thanks to its multidisciplinary approach, the book addresses students and researchers approaching human paleoneurology from different angles and for different purposes, such as biologists, physicians, anthropologists, archaeologists

  8. Human Cloning

    Science.gov (United States)

    2006-07-20

    research group, headed by Douglas Melton and Kevin Eggan, submitted their proposal to a Harvard committee composed of ethicists, scientists and public...United States. Although the company offered no proof of its claim, Dr . Brigette Boisselier, Managing Director of Clonaid, stated that genetic tests would...a year of the Dolly announcement, concerns over human cloning were heightened when Dr . Richard Seed, a Chicago scientist, announced on January 7

  9. Human universe

    CERN Document Server

    Cox, Brian

    2014-01-01

    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  10. Human Being Human: Culture and the Soul

    OpenAIRE

    Hauke, Chris

    2005-01-01

    Human Being Human explores the classical question 'What is a human being?'\\ud \\ud In examining our human being, Christopher Hauke challenges the notion of human nature, questions the assumed superiority of human consciousness and rational thinking and pays close attention to the contradiction of living simultaneously as an autonomous individual and a member of the collective community. The main chapters include:\\ud \\ud who's in charge here?\\ud knowledge power and human being\\ud that thinking ...

  11. Introduction: Digital Humanities, Public Humanities

    Directory of Open Access Journals (Sweden)

    Alex Christie

    2014-07-01

    Full Text Available NANO: New American Notes Online: An Interdisciplinary Academic Journal for Big Ideas in a Small World. This special issue shows how both public and digital humanities research can be rendered more persuasive through engagement with cultures beyond the academy. More specifically, the aim of this special issue is to demonstrate how investments in technologies and computation are not necessarily antithetical to investments in critical theory and social justice.

  12. Human Computing, Virtual Humans and Artificial Imperfection

    NARCIS (Netherlands)

    Ruttkay, Z.M.; Reidsma, Dennis; Nijholt, Antinus; Quek, F.; Yang, Y.

    2006-01-01

    In this paper we raise the issue whether imperfections, characteristic of human-human communication, should be taken into account when developing virtual humans. We argue that endowing virtual humans with the imperfections of humans can help making them more ‘comfortable’ to interact with. That is,

  13. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  14. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  15. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    The paper probes the background of the dire rhetoric of the Danish National Health Board’s 40 week anti-alcohol consumption campaign, in particular the model of communication implied by the campaign's strategy. Contrasting the campaign's strategy in 2011 with the results of evaluations of previous...... years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...

  16. Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study.

    Science.gov (United States)

    Chang, Tien-Jyun; Wang, Wen-Chang; Hsiung, Chao A; He, Chih-Tsueng; Lin, Ming-Wei; Sheu, Wayne Huey-Herng; Chang, Yi-Cheng; Quertermous, Tom; Chen, Ida; Rotter, Jerome; Chuang, Lee-Ming

    2016-03-01

    Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort.We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff antihypertension medication were adjustment covariates in the Cox regression analysis.In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication.In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and age at onset

  17. Trimer hydroxylated quinone (IIIHyQ) derived from apocynin targets cysteine residues of p47phox preventing the activation of human vascular NADPH oxidase

    Science.gov (United States)

    Mora-Pale, Mauricio; Joon-Kwon, Seok; Linhardt, Robert J.; Dordick, Jonathan S.

    2012-01-01

    Enzymatic derived oligophenols from apocynin can be effective inhibitors of human vascular NADPH oxidase. An isolated IIIHyQ has been shown to inhibit endothelial NADPH oxidase with an IC50 ~30 nM. In vitro studies demonstrated that IIIHyQ is capable on disrupting the interaction between p47phox and p22phox, thereby blocking the activation of the Nox2 isoform. Herein, we report the role of key cysteine residues in p47phox as targets for the IIIHyQ. Incubation of p47phox with IIIHyQ results in a decrease of ~80% of the protein free cysteine residues; similar results were observed using 1,2- and 1,4-naphthoquinoes, while apocynin was unreactive. Mutants of p47phox, where each Cys was individually replaced by Ala (at residues 111, 196 and 378) and Gly (at residue 98), were generated to evaluate their individual importance in IIIHyQ-mediated inhibition of p47phox interaction with p22phox. Specific Michael addition on Cys196, within the N-SH3 domain, by the IIIHyQ is critical for disrupting the p47phox-p22phox interaction. When a C196A mutation was tested, the IIIHyQ was unable to disrupt the p47phox-p22phox interaction. However, the IIIHyQ was effective at disrupting this interaction with the other mutants, displaying IC50 values (4.9, 21.0, and 2.3 μM for the C111A, C378A, and C98G mutants, respectively) comparable to that of wild type p47phox. PMID:22240153

  18. Trimer hydroxylated quinone derived from apocynin targets cysteine residues of p47phox preventing the activation of human vascular NADPH oxidase.

    Science.gov (United States)

    Mora-Pale, Mauricio; Kwon, Seok Joon; Linhardt, Robert J; Dordick, Jonathan S

    2012-03-01

    Enzymatically derived oligophenols from apocynin can be effective inhibitors of human vascular NADPH oxidase (Nox). An isolated trimer hydroxylated quinone (IIIHyQ) has been shown to inhibit endothelial NADPH oxidase with an IC(50) ~30 nM. In vitro studies demonstrated that IIIHyQ is capable of disrupting the interaction between p47(phox) and p22(phox), thereby blocking the activation of the Nox2 isoform. Herein, we report the role of key cysteine residues in p47(phox) as targets for the IIIHyQ. Incubation of p47(phox) with IIIHyQ results in a decrease of ~80% of the protein free cysteine residues; similar results were observed using 1,2- and 1,4-naphthoquinones, whereas apocynin was unreactive. Mutants of p47(phox), in which each Cys was individually replaced by Ala (at residues 111, 196, and 378) or Gly (at residue 98), were generated to evaluate their individual importance in IIIHyQ-mediated inhibition of p47(phox) interaction with p22(phox). Specific Michael addition on Cys196, within the N-SH3 domain, by the IIIHyQ is critical for disrupting the p47(phox)-p22(phox) interaction. When a C196A mutation was tested, the IIIHyQ was unable to disrupt the p47(phox)-p22(phox) interaction. However, the IIIHyQ was effective at disrupting this interaction with the other mutants, displaying IC(50) values (4.9, 21.0, and 2.3μM for the C111A, C378A, and C98G mutants, respectively) comparable to that of wild-type p47(phox). Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Human Factors Planning Guidelines

    Science.gov (United States)

    1996-01-01

    To ensure human factors considerations are fully incorporated in the system : development, the Integrated Product Team (IPT) or Program Manager initiates a : Human Factors Program (HFP) that addresses the human performance and human : resource parame...

  20. AcEST: BP921552 [AcEST

    Lifescience Database Archive (English)

    Full Text Available aureus ... 34 0.26 sp|Q7Z6J0|SH3R1_HUMAN Putative E3 ubiquitin-protein ligase SH3RF... 33 0.34 sp|Q9QJ16|IE2_HHV6Z Immediate...P P+ V+ A + AVG ELPP Sbjct: 735 S---PPASPTLEVELGSAELPLQGAVGPELPP 763 >sp|Q9QJ16|IE2_HHV6Z Immediate-early pr

  1. The Digital Humanities as a Humanities Project

    Science.gov (United States)

    Svensson, Patrik

    2012-01-01

    This article argues that the digital humanities can be seen as a humanities project in a time of significant change in the academy. The background is a number of scholarly, educational and technical challenges, the multiple epistemic traditions linked to the digital humanities, the potential reach of the field across and outside the humanities,…

  2. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  3. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    overgangen fra trykkekultur til digital kultur. For det første problemstillingen omkring digitalisering af litterær kulturarv med fokus på kodning og tagging af teksten samt organisering i hypertekststrukturer. For det andet reorganiseringen af det digitale dokument i dataelementer og database. For det......Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH......, der betragter DH som forbundet med "making" og "building" af digitale objekter og former. Dette kan også karakteriseres som DH som praktisk-produktiv vending. Artiklen har valgt tre typer af digitalisering. De er valgt ud fra, at de skal repræsentere forskellige måder at håndtere digitaliseringen på...

  4. Human Rhinoviruses

    Science.gov (United States)

    Lamson, Daryl M.; St. George, Kirsten; Walsh, Thomas J.

    2013-01-01

    Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs. PMID:23297263

  5. Human Factors in Human-Systems Integration

    Science.gov (United States)

    Fitts, David J.; Sandor, Aniko; Litaker, Harry L., Jr.; Tillman, Barry

    2008-01-01

    Any large organization whose mission is to design and develop systems for humans, and train humans needs a well-developed integration and process plan to deal with the challenges that arise from managing multiple subsystems. Human capabilities, skills, and needs must be considered early in the design and development process, and must be continuously considered throughout the development lifecycle. This integration of human needs within system design is typically formalized through a Human-Systems Integration (HSI) program. By having an HSI program, an institution or organization can reduce lifecycle costs and increase the efficiency, usability, and quality of its products because human needs have been considered from the beginning.

  6. Humane Education: An Overview.

    Science.gov (United States)

    Whitlock, Eileen S.; Westerlund, Stuart R.

    This booklet traces the historical development of human education as it has been instilled into the young people of America from colonial times to the present and provides a future prognosis of humaneness in the schools. Humane education promotes humane behavior and is an important part of the humane movement in the United States, although until…

  7. IVI human factors strategy

    Science.gov (United States)

    1999-11-01

    This document focuses on human factors research that supports the Intelligent Vehicle Initiative (IVI). The status of the problem areas within categories used often by the human factors community to organize human factors process is discussed. A simi...

  8. Human Factors Job Aid

    Science.gov (United States)

    1996-12-09

    The purpose of this Human Factors Job Aid is to serve as a desk reference for : human factors integration during system acquisition. The first chapter contains : an overview of the FAA human factors process in system acquisitions. The : remaining eig...

  9. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  10. Human-machine interactions

    Science.gov (United States)

    Forsythe, J Chris [Sandia Park, NM; Xavier, Patrick G [Albuquerque, NM; Abbott, Robert G [Albuquerque, NM; Brannon, Nathan G [Albuquerque, NM; Bernard, Michael L [Tijeras, NM; Speed, Ann E [Albuquerque, NM

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  11. Special Section: Human Rights

    Science.gov (United States)

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  12. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  13. Human Dignity, Three Human Rights, and Pedagogy.

    Science.gov (United States)

    Vandenberg, Donald

    1986-01-01

    A general theory of value is outlined to show that moral agency is necessary to human dignity and that liberty, equality, and fraternity are necessary to moral agency. These ideals can be implemented in schools and human dignity can be at the core of the professional ethics of teaching. (MT)

  14. Human dignity, bioethics, and human rights.

    Science.gov (United States)

    Häyry, Matti; Takala, Tuija

    2005-09-01

    The authors analyse and assess the Universal Draft Declaration on Bioethics and Human Rights published by UNESCO. They argue that the Draft has two main weaknesses. It unnecessarily confines the scope of bioethics to life sciences and their practical applications. And it fails to spell out the intended role of human dignity in international ethical regulation.

  15. [Humanization in health care].

    Science.gov (United States)

    Oliveira, Beatriz Rosana Gonçalves de; Collet, Neusa; Viera, Cláudia Silveira

    2006-01-01

    This study aims to reflect on humanization in health care, recovering the history of understanding about mankind, the human and humanity, until humanization in humanity and health. We discuss the national humanization program in hospital care and reflect on this proposal and on the issue of humanization in Brazilian health care nowadays. Communication is indispensable to establish humanization, as well as technical and material conditions. Both users and health professionals need to be heard, building a network of dialogues to think and promote singular humanization actions. For this process to take effect, there is a need to involve the whole that makes up the health service. This group involves different professionals, such as managers, public policy makers, professional councils and education institutions.

  16. Global Law: Humanism and Human Rights

    Directory of Open Access Journals (Sweden)

    Leilane Serratine Grubba

    2016-06-01

    Full Text Available This article discusses the ideal of human rights before globalizatórios inflows. It begins with a general statement about the legal globalization, comparing it with the Global Law in the political and economic implications. Later, it approaches the ideal predicted with transnationalism. Proposes a reflection on the present Human Rights. Also, rethinks the lines of the complex web of Global Law, its institutions and its actors, which circulate between the public and private plans. There is no sense in space maintenance of the ideal of human rights only in the state or territory in international treaties originally linked to the states.

  17. Human Resource Accounting System

    Science.gov (United States)

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  18. Telling the Human Story.

    Science.gov (United States)

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  19. Human Use Index (Future)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  20. Human Use Index

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  1. Immunology Taught by Humans

    OpenAIRE

    Davis, Mark M

    2012-01-01

    After a half-century of mouse-dominated research, human immunology is making a comeback. Informed by mouse studies and powered by new techniques, human immune research is both advancing disease treatment and providing new insights into basic biology.

  2. Human Papillomavirus (HPV) Screening

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Human Papillomavirus (HPV) Note: Javascript is disabled or is ... 6348 Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov TOP

  3. Human Papillomavirus (HPV)

    Science.gov (United States)

    ... Listen Español Text Size Email Print Share HPV (Human Papillomavirus) Vaccine: What You Need to Know (VIS) ... Why get vaccinated? HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with many ...

  4. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  5. Human Parainfluenza Viruses

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Human Parainfluenza Viruses (HPIVs) Note: Javascript is disabled or ... CDC.gov . Recommend on Facebook Tweet Share Compartir Human parainfluenza viruses (HPIVs) commonly cause respiratory illnesses in ...

  6. Human bites (image)

    Science.gov (United States)

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  7. HPV (Human Papillomavirus)

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More sharing ... Español In Chamorro In Urdu In Vietnamese HPV (human papillomavirus) is a sexually transmitted virus. It is ...

  8. Humane Education in Action.

    Science.gov (United States)

    Savesky, Kathy

    1981-01-01

    Provides a brief history and description of a field test in the United States and Canada of the National Association for the Advancement of Humane Education's humane education curriculum guide for grades 1-6. (CS)

  9. Human papillomavirus molecular biology.

    Science.gov (United States)

    Harden, Mallory E; Munger, Karl

    Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Human Resource Management System

    OpenAIRE

    Navaz, A. S. Syed; Fiaz, A. S. Syed; Prabhadevi, C.; Sangeetha, V.; Gopalakrishnan, S.

    2013-01-01

    The paper titled HUMAN RESOURCE MANAGEMENT SYSTEM is basically concerned with managing the Administrator of HUMAN RESOURCE Department in a company. A Human Resource Management System, refers to the systems and processes at the intersection between human resource management and information technology. It merges HRM as a discipline and in particular its basic HR activities and processes with the information technology field, whereas the programming of data processing systems evolved into standa...

  11. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  12. International Human Rights Kit.

    Science.gov (United States)

    Woito, Robert, Ed.

    Designed for students, educators, and citizens interested in human rights, the booklet presents resources for learning about the facts, perspectives, and existing procedures and institutions to promote human rights. Chapter one explores the relationship between human rights and war. Chapter two presents a self-survey to help readers clarify…

  13. Human Machine Learning Symbiosis

    Science.gov (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.

    2017-01-01

    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  14. Humanities Review Journal

    African Journals Online (AJOL)

    Humanities Review Journal is published in June and December by Humanities Research Forum. The Journal publishes original, well-researched papers, review essays, interviews, resume, and commentaries, which offer new insights into the various disciplines in the Humanities. The focus is on issues about Africa.

  15. A Human Rights Glossary.

    Science.gov (United States)

    Flowers, Nancy

    1998-01-01

    Presents a human rights glossary that includes definitions of basic terms, treaties, charters, and groups/organizations that have been featured in previous articles in this edition of "Update on Law-Related Education"; the human rights terms have been compiled as part of the celebration of the Universal Declaration of Human Rights…

  16. Esprit: A Humanities Magazine.

    Science.gov (United States)

    Parker, Donald G.; Capella, Barry John

    In March 1984, the first issue of "Esprit," a semi-annual humanities magazine for the 56 two-year colleges in New York State, was published. The magazine seeks to confront the apparent decline of student interest in the humanities, community doubts about the relevance of the humanities, and the seeming indifference to the special truths…

  17. Visible Human Project

    Science.gov (United States)

    ... NLM Mobile Gallery Site Navigation Home The Visible Human Project ® Overview The Visible Human Project ® is an outgrowth of the NLM's 1986 ... dimensional representations of the normal male and female human bodies. Acquisition of transverse CT, MR and cryosection ...

  18. Modeling Human Leukemia Immunotherapy in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Jinxing Xia

    2016-08-01

    Full Text Available The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL, which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI, a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.

  19. From Human Past to Human Future

    Directory of Open Access Journals (Sweden)

    Robert G. Bednarik

    2013-01-01

    Full Text Available This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic and neural detriments and pathologies. Uniformitarian reasoning based on ontogenic homology suggests that the cognitive abilities of hominins are consistently underrated in the unstable orthodoxies of Pleistocene archaeology. A scientifically guided review establishes developmental trajectories defining recent changes in the human genome and its expressions, which then form the basis of attempts to extrapolate from them into the future. It is suggested that continuing and perhaps accelerating unfavorable genetic changes to the human species, rather than existential threats such as massive disasters, pandemics, or astrophysical events, may become the ultimate peril of humanity.

  20. Human Beings And Water

    OpenAIRE

    Pakpahan, Putra Andika

    2016-01-01

    The writer of this paper on this writing is talking about the human beings and water. Water is one of the very fundamentally things that human beings need to keep their lives. Human beings sometimes do not realise that the water is very important for them because they actually cannot live their lives without the present of water. Human beings can keep their lives without rice, but cannot without water. For instances the use of water for human beings are domestic use, cooking, washing, bathing...

  1. Rethinking medical humanities.

    Science.gov (United States)

    Chiapperino, Luca; Boniolo, Giovanni

    2014-12-01

    This paper questions different conceptions of Medical Humanities in order to provide a clearer understanding of what they are and why they matter. Building upon former attempts, we defend a conception of Medical Humanities as a humanistic problem-based approach to medicine aiming at influencing its nature and practice. In particular, we discuss three main conceptual issues regarding the overall nature of this discipline: (i) a problem-driven approach to Medical Humanities; (ii) the need for an integration of Medical Humanities into medicine; (iii) the methodological requirements that could render Medical Humanities an effective framework for medical decision-making.

  2. Situating Human Sexual Conditioning.

    Science.gov (United States)

    Hoffmann, Heather

    2017-11-01

    Conditioning is often thought of as a basic, automatic learning process that has limited applicability to higher-level human behavior. In addition, conditioning is seen as separable from, and even secondary to, "innate" processes. These ideas involve some misconceptions. The aim of this article is to provide a clearer, more refined sense of human sexual conditioning. After providing some background information and reviewing what is known from laboratory conditioning studies, human sexual conditioning is compared to sexual conditioning in nonhumans, to "innate" sexual responding, and to other types of human learning processes. Recommendations for moving forward in human sexual conditioning research are included.

  3. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  4. Oxytocin and Human Evolution.

    Science.gov (United States)

    Carter, C Sue

    2017-08-16

    A small, but powerful neuropeptide, oxytocin coordinates processes that are central to both human reproduction and human evolution. Also embedded in the evolution of the human nervous system are unique pathways necessary for modern human sociality and cognition. Oxytocin is necessary for facilitating the birth process, especially in light of anatomical restrictions imposed by upright human locomotion, which depends on a fixed pelvis. Oxytocin, by facilitating birth, allowed the development of a large cortex and a protective bony cranium. The complex human brain in turn permitted the continuing emergence of social sensitivity, complex thinking, and language. After birth is complete, oxytocin continues to support human development by providing direct nutrition, in the form of human milk, and emotional and intellectual support through high levels of maternal behavior and selective attachment. Oxytocin also encourages social sensitivity and reciprocal attunement, on the part of both the mother and child, which are necessary for human social behavior and for rearing an emotionally healthy human child. Oxytocin supports growth during development, resilience, and healing across the lifespan. Oxytocin dynamically moderates the autonomic nervous system, and effects of oxytocin on vagal pathways allowing high levels of oxygenation and digestion necessary to support adaptation in a complex environment. Finally, oxytocin has anti-oxidant and anti-inflammatory effects, helping to explain the pervasive adaptive consequences of social behavior for emotional and physical health.

  5. Human Capital and Sustainability

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2011-01-01

    Full Text Available A study of sustainability needs to consider the role of all forms of capital—natural, biological, social, technological, financial, cultural—and the complex ways in which they interact. All forms of capital derive their value, utility and application from human mental awareness, creativity and social innovation. This makes human capital, including social capital, the central determinant of resource productivity and sustainability. Humanity has entered the Anthropocene Epoch in which human changes have become the predominant factor in evolution. Humanity is itself evolving from animal physicality to social vitality to mental individuality. This transition has profound bearing on human productive capabilities, adaptability, creativity and values, the organization of economy, public policy, social awareness and life styles that determine sustainability. This article examines the linkages between population, economic development, employment, education, health, social equity, cultural values, energy intensity and sustainability in the context of evolving human consciousness. It concludes that development of human capital is the critical determinant of long-term sustainability and that efforts to accelerate the evolution of human consciousness and emergence of mentally self-conscious individuals will be the most effective approach for ensuring a sustainable future. Education is the primary lever. Human choice matters.

  6. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    Todays expanding digital landscape constitutes an important research object as well as the research environment for the Humanities at the beginning of the 21st century. Taking this state of affairs as a starting point this inaugural lecture presents a vision for how the digital affects the interp......Todays expanding digital landscape constitutes an important research object as well as the research environment for the Humanities at the beginning of the 21st century. Taking this state of affairs as a starting point this inaugural lecture presents a vision for how the digital affects...... the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research...

  7. Dynamic Interaction of Amphiphysin with N-WASP Regulates Actin Assembly*

    Science.gov (United States)

    Yamada, Hiroshi; Padilla-Parra, Sergi; Park, Sun-Joo; Itoh, Toshiki; Chaineau, Mathilde; Monaldi, Ilaria; Cremona, Ottavio; Benfenati, Fabio; De Camilli, Pietro; Coppey-Moisan, Maïté; Tramier, Marc; Galli, Thierry; Takei, Kohji

    2009-01-01

    Amphiphysin 1, an endocytic adaptor concentrated at synapses that couples clathrin-mediated endocytosis to dynamin-dependent fission, was also shown to have a regulatory role in actin dynamics. Here, we report that amphiphysin 1 interacts with N-WASP and stimulates N-WASP- and Arp2/3-dependent actin polymerization. Both the Src homology 3 and the N-BAR domains are required for this stimulation. Acidic liposome-triggered, N-WASP-dependent actin polymerization is strongly impaired in brain cytosol of amphiphysin 1 knock-out mice. FRET-FLIM analysis of Sertoli cells, where endogenously expressed amphiphysin 1 co-localizes with N-WASP in peripheral ruffles, confirmed the association between the two proteins in vivo. This association undergoes regulation and is enhanced by stimulating phosphatidylserine receptors on the cell surface with phosphatidylserine-containing liposomes that trigger ruffle formation. These results indicate that actin regulation is a key function of amphiphysin 1 and that such function cooperates with the endocytic adaptor role and membrane shaping/curvature sensing properties of the protein during the endocytic reaction. PMID:19759398

  8. Human Performance in Space

    Science.gov (United States)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  9. Bursty human dynamics

    CERN Document Server

    Karsai, Márton; Kaski, Kimmo

    2018-01-01

    This book provides a comprehensive overview on emergent bursty patterns in the dynamics of human behaviour. It presents common and alternative understanding of the investigated phenomena, and points out open questions worthy of further investigations. The book is structured as follows. In the introduction the authors discuss the motivation of the field, describe bursty phenomena in case of human behaviour, and relate it to other disciplines. The second chapter addresses the measures commonly used to characterise heterogeneous signals, bursty human dynamics, temporal paths, and correlated behaviour. These definitions are first introduced to set the basis for the discussion of the third chapter about the observations of bursty human patterns in the dynamics of individuals, dyadic interactions, and collective behaviour. The subsequent fourth chapter discusses the models of bursty human dynamics. Various mechanisms have been proposed about the source of the heterogeneities in human dynamics, which leads to the in...

  10. Outsourcing in Human Resource

    OpenAIRE

    Oliver Pamelan

    2017-01-01

    The research paper aimed to contribute to the literature of Human Resource Management Planning and employment through the widely used function of the outsourcing human resource. The research paper is based on the description of the process of outsourcing with the reference to the theories of outsourcing management activities. It also explained the effects of this function through measuring the benefits and drawbacks of the outsourcing human resource while planning the employment strategies. T...

  11. The Humanities Matter! Infographic

    OpenAIRE

    Terras, M. M.; Priego, E.; Liu, A.; Rockwell, G.; Sinclair, S.; Henseler, C.; Thomas, L.

    2013-01-01

    The Humanities are academic disciplines that seek to understand and interpret the human experience, from individuals to entire cultures, engaging in the discovery, preservation, and communication of the past and present record to enable a deeper understanding of contemporary society. The Humanities encompass literature, classics, ancient and modern languages, history, philoso - phy, media studies, the fine and performing arts, and other related subjects. It can be a challenge to show the bene...

  12. Human Resource Planning

    OpenAIRE

    Lache Cãtãlina

    2011-01-01

    The objective of human resource planning is to adapt the human capital needed to develop the enterprises’ activities and to accomplish their priority objectives on the medium and/or short term. Human resource planning is a dynamic activity, time being an essential variable, both in what regards the quantitative side (adapting the number of jobs according to the organisation’s evolution in time) and the qualitative side (harmonising the jobs’ complexity with technological changes). The quantit...

  13. Crimes against humanity

    OpenAIRE

    Podlahová, Veronika

    2014-01-01

    57 Resumé "Crimes against humanity" (the thesis title) Crimes against humanity constitute one of the three integral parts of "crimes under international law." At the same time they represent the most severe form of infringement of fundamental human rights that are as the principle value protected by the international community and its peremptory rules. Although these crimes have not emerged during the 20th century for the first time, it was the World War II., which established the term "crime...

  14. Modern Human Capital Management

    OpenAIRE

    Feldberger, Madita

    2008-01-01

    Title: Modern Human Capital Management Seminar date: 30th of May 2008 Course: Master thesis in Business Administration, 15 ECTS Authors: Madita Feldberger Supervisor: Lars Svensson Keywords: Human capital, SWOT Analysis, Strategic Map, Balanced Scorecard Research Problem: Despite of the success of Human Capital Management (HCM) in research it did not arrive yet in the HR departments of many companies. Numerous firms even have problems to set their strategic goals with focus on HR. The HR Bala...

  15. Human hemoglobin genetics

    Energy Technology Data Exchange (ETDEWEB)

    Honig, G.R.; Adams, J.G.

    1986-01-01

    This book contains the following 10 chapters: Introduction; The Human Hemoglobins; The Human Globin Genes; Hemoglobin Synthesis and Globin Gene Expression; The Globin Gene Mutations - A. Mechanisms and Classification; The Globin Gene Mutations - B. Their Phenotypes and Clinical Expression; The Genetics of the Human Globin Gene Loci: Formal Genetics and Gene Linkage; The Geographic Distribution of Globin Gene Variation; Labortory Identification, Screening, Education, and Counseling for Abnormal Hemoglobins and Thalassemias; and Approaches to the Treatment of the Hemoglobin Disorders.

  16. Human Performance Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — Biochemistry:Improvements in energy metabolism, muscular strength and endurance capacity have a basis in biochemical and molecular adaptations within the human body....

  17. Human cloning 2001.

    Science.gov (United States)

    Healy, David L; Weston, Gareth; Pera, Martin F; Rombauts, Luk; Trounson, Alan O

    2002-05-01

    This review summaries human cloning from a clinical perspective. Natural human clones, that is, monozygotic twins, are increasing in the general community. Iatrogenic human clones have been produced for decades in infertile couples given fertility treatment such as ovulation induction. A clear distinction must be made between therapeutic cloning using embryonic stem cells and reproductive cloning attempts. Unlike the early clinical years of in vitro fertilization, with cloning there is no animal model that is safe and dependable. Until there is such a model, 'Dolly'-style human cloning is medically unacceptable.

  18. Robotics for Human Exploration

    Science.gov (United States)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  19. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  20. Challenges for Virtual Humans in Human Computing

    NARCIS (Netherlands)

    Reidsma, Dennis; Ruttkay, Z.M.; Huang, T; Nijholt, Antinus; Pantic, Maja; Pentland, A.

    The vision of Ambient Intelligence (AmI) presumes a plethora of embedded services and devices that all endeavor to support humans in their daily activities as unobtrusively as possible. Hardware gets distributed throughout the environment, occupying even the fabric of our clothing. The environment

  1. SERUM BETA HUMAN CHORIONIC GONADOTROPHIN IN HUMAN ...

    African Journals Online (AJOL)

    Objectives To determine whether raised levels of serum Beta -HCG) are associated with higher grade and Human Chorionic Gonadotrophin ( -HCG in higher category tumors and whether in patients with raised levels of -HCG their sera the rise (above normal range) and the fall (to normal) in levels would correspond with ...

  2. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  3. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    ) article 'Visualizing the mind: Looking at Titian's Flaying of Marsyas', addressing features of the painting not commented on by Hart, and supplementing Hart's (Kleinian) theoretical frame by involving Didier Anzieu's 'skin ego', Slavoj Zizek's concept of the 'non-human', Giorgio Agamben's term...

  4. Human Resource Accounting

    Science.gov (United States)

    Woodruff, Robert L., Jr.

    1973-01-01

    An interview is reported which discussed the implications for the hiring, recruiting, screening and development of employees in the light of human resource accounting, here defined as the identification, accumulation and dissemination of information about human resources in dollar terms. (SA)

  5. Human-centred Governance

    DEFF Research Database (Denmark)

    Bason, Christian

    2017-01-01

    Design approaches are now being applied all over the world as a powerful approach to innovating public policies and services. Christian Bason, author of Leading public design: Discovering human-centred governance, argues that by bringing design methods into play, public managers can lead change...... with citizens at the centre, and discover a new model for steering public organisations: human-centred governance....

  6. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  7. Dynamics of human movement

    NARCIS (Netherlands)

    Koopman, Hubertus F.J.M.

    2010-01-01

    The part of (bio)mechanics that studies the interaction of forces on the human skeletal system and its effect on the resulting movement is called rigid body dynamics. Some basic concepts are presented: A mathematical formulation to describe human movement and how this relates on the mechanical loads

  8. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W

    2010-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...

  9. the human genome project

    African Journals Online (AJOL)

    Enrique

    have resulted in the biological diversity, both past and present, on this planet. RAJ RAMESAR. MSc, PhD. Professor and Head. Division of Human Genetics. Faculty of Health Sciences. University of Cape Town. Raj Ramesar serves as Director of the MRC. Human Genetics Research Unit and. CANSA's Colorectal Cancer ...

  10. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and

  11. Damping Effect of Humans

    DEFF Research Database (Denmark)

    Pedersen, Lars

    Passive humans (sitting or standing) might well be present on flooring-systems, footbridges or other structures that carry humans. An active croud of people might generate structural vibrations, and these might be problematic. The passive crowd of people, however, will interact with the structura...

  12. Evaluating the Humanities

    Science.gov (United States)

    Brody, Howard

    2013-01-01

    How can one measure the value of teaching the humanities? The problem of assessment and accountability is prominent today, of course, in secondary and higher education. It is perhaps even more acute for those who teach the humanities in nontraditional settings, such as medical and other professional schools. The public assumes that academes can…

  13. The Humanities' Value

    Science.gov (United States)

    Harpham, Geoffrey Galt

    2009-01-01

    Why should society support the humanities when so many people are suffering from the effects of the economic crisis? What claim do the humanities, or scholarship generally, have on increasingly limited resources? Shouldn't such pursuits be considered luxuries at a time when people should be focusing on essentials? The alleviation of human…

  14. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  15. Incorporating Human Interindividual Biotransformation ...

    Science.gov (United States)

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accomplished through (1) the characterization of enzyme expression in large banks of human liver samples, (2) the employment of appropriate techniques for the quantification and extrapolation of metabolic rates derived in vitro, and (3) the judicious application of physiologically based pharmacokinetic (PBPK) modeling. While in vitro measurements of specific biochemical reactions from multiple human samples can yield qualitatively valuable data on human variance, such measures must be put into the perspective of the intact human to yield the most valuable predictions of metabolic differences among humans. For quantitative metabolism data to be the most valuable in risk assessment, they must be tied to human anatomy and physiology, and the impact of their variance evaluated under real exposure scenarios. For chemicals metabolized in the liver, the concentration of parent chemical in the liver represents the substrate concentration in the MichaelisMenten description of metabolism. Metabolic constants derived in vitro may be extrapolated to the intact liver, when appropriate conditions are met. Metabolic capacity Vmax; the maximal rate of the reaction) can be scaled directly to the concentration

  16. Damping Effect of Humans

    DEFF Research Database (Denmark)

    Pedersen, Lars

    Passive humans (sitting or standing) might well be present on flooring-systems, footbridges or other structures that carry humans. An active croud of people might generate structural vibrations, and these might be problematic. The passive crowd of people, however, will interact with the structural...

  17. HUMAN PARAGONIMIASIS IN AFRICA

    African Journals Online (AJOL)

    Emmanuel Ameh

    Abstract. An up-to-date review on human paragonimiasis in Africa was carried out to determine the current geographical distribution of human cases and analyze the animal reservoir, snails and crustaceans which intervene in the local life cycle of Paragonimus species. Two countries, i.e., Cameroon and. Nigeria, were ...

  18. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century

  19. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  20. Fungi that Infect Humans.

    Science.gov (United States)

    Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R

    2017-06-01

    Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients-Candida, Pneumocystis, and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

  1. Businesses’ human rights responsibilities

    Directory of Open Access Journals (Sweden)

    Corinne Lewis

    2012-12-01

    Full Text Available There is no international human rights law standard that expresslyprohibits businesses’ arbitrary displacement of persons. Businessesdo, however, have the responsibility to avoid infringements of humanrights that could lead to displacement and also to take actions toremedy their human rights violations that might lead to displacement.

  2. Global Journal of Humanities

    African Journals Online (AJOL)

    Journal Homepage Image. Global Journal of Humanities is aimed at promoting reasearch in all areas of Humanities including philosophy, languages, linguistics, literature, history, fine/applied arts, theater arts, architecture, etc. Visit the Global Journal Series website here: http://www.globaljournalseries.com/ ...

  3. Human Granulocytic Anaplasmosis, Japan

    Science.gov (United States)

    Gaowa; Wuritu; Kawamori, Fumihiko; Wu, Dongxing; Yoshikawa, Yuko; Chiya, Seizou; Fukunaga, Kazutoshi; Funato, Toyohiko; Shiojiri, Masaaki; Nakajima, Hideki; Hamauzu, Yoshiji; Takano, Ai; Kawabata, Hiroki; Ando, Shuji; Kishimoto, Toshio

    2013-01-01

    We retrospectively confirmed 2 cases of human Anaplasma phagocytophilum infection. Patient blood samples contained unique p44/msp2 for the pathogen, and antibodies bound to A. phagocytophilum antigens propagated in THP-1 rather than HL60 cells. Unless both cell lines are used for serodiagnosis of rickettsiosis-like infections, cases of human granulocytic anaplasmosis could go undetected. PMID:23460988

  4. Humane Education Projects Handbook.

    Science.gov (United States)

    Junior League of Ogden, UT.

    This handbook was developed to promote interest in humane education and to encourage the adoption of humane education projects. Although specifically designed to assist Junior Leagues in developing such projects, the content should prove valuable to animal welfare organizations, zoos, aquariums, nature centers, and other project-oriented groups…

  5. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    , which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  6. Overophedning af det humane

    DEFF Research Database (Denmark)

    Larsen, Steen Nepper

    2016-01-01

    Anmelder Marius Gudmand-Høyer, Sverre Raffnsøe og Morten Raffnsøe-Møller (red.): "Den humane vending. En antologi", Aarhus Universitetsforlag......Anmelder Marius Gudmand-Høyer, Sverre Raffnsøe og Morten Raffnsøe-Møller (red.): "Den humane vending. En antologi", Aarhus Universitetsforlag...

  7. The Human Technology

    DEFF Research Database (Denmark)

    Fausing, Bent

     Bent Fausing  "The Humane Technology", abstract (for The Two Cultures: Balancing Choices and Effects Oxford University July 20-26, 2008). The paper will investigate the use of technology in everyday aesthetics such as TV-commercials for mobile phones for Nokia, which slogan is, as it is well known...... for as a better humanity.      The paper will investigate how the two cultures are combined in this way in a TV-commercial. Technology points, is the conclusion, towards a forgotten pre-human and not to the often-motioned post-human condition.    ......, "Nokia - connecting people". Which function does this technology get in narratives, images, interactions and affects here?      The mobile phone and its digital camera are depicted as being able to make a unique human presence and interaction. The medium, the technology is a necessary helper to get...

  8. Humanity at the Edge

    DEFF Research Database (Denmark)

    Svendsen, Mette N.; Gjødsbøl, Iben M.; Dam, Mie S.

    2017-01-01

    At the heart of anthropology and the social sciences lies a notion of human existence according to which humans and animals share the basic need for food, but only humans have the capacity for morality. Based on fieldwork in a pig laboratory, a neonatal intensive care unit (NICU), and a dementia...... nursing home, we follow practices of feeding precarious lives lacking most markers of human personhood, including the exercise of moral judgment. Despite the absence of such markers, laboratory researchers and caregivers in these three sites do not abstain from engaging in questions about the moral status...... of the piglets, infants, and people with dementia in their care. They continually negotiate how their charges belong to the human collectivity and thereby challenge the notion of ‘the human’ that is foundational to anthropology. Combining analytical approaches that do not operate with a fixed boundary between...

  9. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    rhythm and chronic atrial fibrillation tissues and was neither affected by changes in frequency (1 vs. 3Hz). CONCLUSIONS: Our results suggest a preferentially voltage-dependent, rather than time-dependent, effect with respect to refractoriness at physiologically relevant rates in human atria. However...... drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...

  10. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  11. The human cell atlas

    DEFF Research Database (Denmark)

    Regev, Aviv; Teichmann, Sarah A.; Lander, Eric S.

    2017-01-01

    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international...... collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells...... in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early...

  12. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    Design is increasingly becoming a part of the university curriculum and research agenda. The keynote present and discuss Designing Human Technologies – an initiative aiming at establishing a design oriented main subject area alongside traditional main subject areas such as Natural Science......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... Research Initiative supporting Roskilde University’s new Humanities and Technology bachelor programme (‘HumTek’), and its three dimensions: Design, Humanities, and Technology. The research initiative involves 70 researchers from different departments and research groups at Roskilde University through...

  13. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula. © 2017 S. Karger AG, Basel.

  14. Human Power Empirically Explored

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, A.J.

    2011-01-18

    Harvesting energy from the users' muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are convenient and can be environmentally and economically beneficial. This work provides insight into the knowledge required to design human-powered energy systems in consumer products from a scientific perspective. It shows the developments of human-powered products from the first introduction of the BayGen Freeplay radio in 1995 till current products and provides an overview and analysis of 211 human-powered products currently on the market. Although human power is generally perceived as beneficial for the environment, this thesis shows that achieving environmental benefit is only feasible when the environmental impact of additional materials in the energy conversion system is well balanced with the energy demands of the products functionality. User testing with existing products showed a preference for speeds in the range of 70 to 190 rpm for crank lengths from 32 to 95 mm. The muscular input power varied from 5 to 21 W. The analysis of twenty graduation projects from the Faculty of Industrial Design Engineering in the field of human-powered products, offers an interesting set of additional practice based design recommendations. The knowledge based approach of human power is very powerful to support the design of human-powered products. There is substantial potential for improvements in the domains energy conversion, ergonomics and environment. This makes that human power, when applied properly, is environmentally and economically competitive over a wider range of applications than thought previously.

  15. Genetics of human hydrocephalus.

    Science.gov (United States)

    Zhang, Jun; Williams, Michael A; Rigamonti, Daniele

    2006-10-01

    Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders.A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human

  16. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  17. Aluminium in human sweat.

    Science.gov (United States)

    Minshall, Clare; Nadal, Jodie; Exley, Christopher

    2014-01-01

    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. Wear in human knees

    Directory of Open Access Journals (Sweden)

    M.L. Wang

    2015-06-01

    Full Text Available Wear occurs in natural knee joints and plays a pivotal factor in causing articular cartilage degradation in osteoarthritis (OA processes. Wear particles are produced in the wear process and get involved in inflammation of human knees. This review presents progresses in the mechanical and surface morphological studies of articular cartilages, wear particles analysis techniques for wear studies and investigations of human knee synovial fluid in wear of human knees. Future work is also included for further understanding of OA symptoms and their relations which may shed light on OA causes.

  19. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  20. Human Capital and Development

    OpenAIRE

    Rodolfo E. Manuelli

    2015-01-01

    Perhaps no question has attracted as much attention in the economics literature as “Why are some countries richer than others?” In this article, the author revisits the “development problem” and provides some estimates of the importance of human capital in accounting for cross-country differences in output per worker. His results suggest that human capital has a central role in determining the wealth of nations and that the quality of human capital varies systematically with the level of deve...

  1. Human pancreas development.

    Science.gov (United States)

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes. © 2015. Published by The Company of Biologists Ltd.

  2. Human dignity and bioethics

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš

    2013-01-01

    Full Text Available By opening the field of bioethics followed a new wave of intense debate on the theological, philosophical and legal significance of the concept of human dignity . Exactly ten years ago (December 2003 American bioethicist Ruth Maclin has proposed to divest ourselves of the concept of human dignity because it is vague, useless and redundant and that, without any loss, we can replace it by the ethical principle of personal autonomy. Her article was followed by harsh reactions and opposite views. What is this term in so broad, almost inflationary and opposite use is not a reason to deprive him, but, on the contrary, it shows how important it is and that it should be determined at least outline. As universal values and general concept, the human dignity has no pre-defined and narrow, precise meaning. It is more an evaluation horizon, the guiding principle and regulatory ideas that must constantly define and codify by many guaranted human rights and fundamental freedoms. As generic notion of each reasonable law, it is their foundation and a common denominator, legitimising basis of natural but also of positive law. As intrinsic and static value which means the humaneness, the humanity it is absolute, inherent to every human being without distinction and conditioning, as a unique and unrepeatable creation. In this meaning, the dignity is the obligation and limitation of the state, society and each of us. As an ethical and dynamic category, it is not given to us, but it is assign to us, and it is not in us, but always before us, as a guide of our actions in accordance with virtues, to treat ourselves, each other and the nature in a human way. The century in which we live is named the century of molecular biology and genetic engineering because of the enormous potential but also risks to human dignity. Because of that human dignity has become a central principle in all international documents relating to the human genome, genetics and bioethics, adopted

  3. Sulfatases and human disease.

    Science.gov (United States)

    Diez-Roux, Graciana; Ballabio, Andrea

    2005-01-01

    Sulfatases are a highly conserved family of proteins that cleave sulfate esters from a wide range of substrates. The importance of sulfatases in human metabolism is underscored by the presence of at least eight human monogenic diseases caused by the deficiency of individual sulfatases. Sulfatase activity requires a unique posttranslational modification, which is impaired in patients with multiple sulfatase deficiency (MSD) due to a mutation of the sulfatase modifying factor 1 (SUMF1). Here we review current knowledge and future perspectives on the evolution of the sulfatase gene family, on the role of these enzymes in human metabolism, and on new developments in the therapy of sulfatase deficiencies.

  4. Propelling medical humanities in China.

    Science.gov (United States)

    Tang, Wei

    2017-05-23

    Advances in the study of the medical humanities and medical humanities education have been made over the past few decades. Many influential journals have published articles examining the role of medical humanities and medical humanities education, the development and evaluation of medical humanities, and the design of a curriculum for medical humanities education in Western countries. However, most articles related to medical humanities in China were published in Chinese, moreover, researchers have worked in relative isolation and published in disparate journals, so their work has not been systematically presented to and evaluated by international readers. The six companion articles featured in this issue describe the current status and challenge of medical humanities and medical humanities education in China in the hope of providing international readers with a novel and meaningful glimpse into medical humanities in China. This Journal is calling for greater publication of research on medical humanities and medical humanities education to propel medical humanities in China.

  5. Human Research Program

    Data.gov (United States)

    National Aeronautics and Space Administration — Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance...

  6. The human urine metabolome

    National Research Council Canada - National Science Library

    Bouatra, Souhaila; Aziat, Farid; Mandal, Rupasri; Guo, An Chi; Wilson, Michael R; Knox, Craig; Bjorndahl, Trent C; Krishnamurthy, Ramanarayan; Saleem, Fozia; Liu, Philip; Dame, Zerihun T; Poelzer, Jenna; Huynh, Jessica; Yallou, Faizath S; Psychogios, Nick; Dong, Edison; Bogumil, Ralf; Roehring, Cornelia; Wishart, David S

    2013-01-01

    .... Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine...

  7. The bionic human

    OpenAIRE

    Francalanza, Emmanuel;

    2013-01-01

    Faster, fitter and flawless? What would it take to build a Bionic Human? Emmanuel Francalanza delved into research at the Faculty of Engineering to see how Malta could contribute. 3D Art by Jean Claude Vancell.

  8. Human Resource Planning

    Science.gov (United States)

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  9. Human factors in aviation

    National Research Council Canada - National Science Library

    Salas, Eduardo; Maurino, Daniel E

    2010-01-01

    .... HFA offers a comprehensive overview of the topic, taking readers from the general to the specific, first covering broad issues, then the more specific topics of pilot performance, human factors...

  10. Extraterritorial Human Rights Obligations

    DEFF Research Database (Denmark)

    Amsinck Boie, Hans Nikolaj; Torp, Kristian

    The book addresses the issue of corporate respect for human rights by examining if and how states are obligated to ensure that corporations originating from their jurisdiction respect human rights when they operate abroad. The existence of such a duty is much debated by academics at national...... and international level, and in an attempt to bring something new to the table, the book examines both if states have extraterritorial obligations in regard to their corporations and what can be required of states under such an obligation. The complex issue of states and corporate respect for human rights cannot...... adequately be addressed without including the approach to the problem taken in practice; Corporate Social Responsibility, CSR. The book therefore draws upon the concept of CSR and the approaches developed here and discusses whether states may utilize the CSR-based concept of human rights due diligence...

  11. Aerospace Human Factors

    Science.gov (United States)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  12. Journal of Humanities: Contact

    African Journals Online (AJOL)

    Principal Contact. Dr. Japhet Bakuwa Copy and Production Editor Chancellor College Publications Journal of Humanities Chancellor College Publications PO Box 280 Zomba Malawi Email: jbakuwa@cc.ac.mw ...

  13. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of Transnational Business Governance Interactions (TBGI) analytical framework (Eberlein et al. 2014). The article identifies and discusses dime...... business governance suggests that this form of governance offers prospects for public institutions as a means towards regulating global sustainability concerns.......This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of Transnational Business Governance Interactions (TBGI) analytical framework (Eberlein et al. 2014). The article identifies and discusses...... that the UN Guiding Principles are unique in several respects of relevance to transnational business governance interaction and indicate the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational...

  14. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  15. Human Bond Communication

    DEFF Research Database (Denmark)

    Prasad, Ramjee

    2016-01-01

    Modern dexterous communication technology is progressively enabling humans to communicate their information through them with speech (aural) and media (optical) as underpinning essence. Humans realize this kind of aural and optical information by their optical and auditory senses. However, due...... to certain constraints, the ability to incorporate the other three sensory features namely, olfactory, gustatory, and tactile are still far from reality. Human bond communication is a novel concept that incorporates olfactory, gustatory, and tactile that will allow more expressive and holistic sensory...... information exchange through communication techniques for more human sentiment centric communication. This concept endorses the need of inclusion of other three senses and proposes an innovative approach of holistic communication for future communication network....

  16. Strategic Human Resources Management

    National Research Council Canada - National Science Library

    Marta Muqaj

    2016-01-01

    Strategic Human Resources Management (SHRM) represents an important and sensitive aspect of the functioning and development of a company, business, institution, state, public or private agency of a country...

  17. BIOETHICS AND HUMAN CLONING

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2011-12-01

    Full Text Available In this paper the authors analyze the process of negotiating and beginning of the United Nations Declaration on Human Cloning as well as the paragraphs of the very Declaration. The negotiation was originally conceived as a clear bioethical debate that should have led to a general agreement to ban human cloning. However, more often it had been discussed about human rights, cultural, civil and religious differences between people and about priorities in case of eventual conflicts between different value systems. In the end, a non-binding Declaration on Human Cloning had been adopted, full of numerous compromises and ambiguous formulations, that relativized the original intention of proposer states. According to authors, it would have been better if bioethical discussion and eventual regulations on cloning mentioned in the following text had been left over to certain professional bodies, and only after the public had been fully informed about it should relevant supranational organizations have taken that into consideration.

  18. Science and Humanism

    Science.gov (United States)

    Auger, Pierre

    1971-01-01

    Science and humanism are separated so completely as to bring about the creation of two cultures quite distinct from each other within contemporary civilization. Pragmatic, rational attitudes are needed on both sides to bring them together. (DF)

  19. Human Capital Tracking Tool -

    Data.gov (United States)

    Department of Transportation — AVS is now required to collect, track, and report on data from the following Flight, Business and Workforce Plan. The Human Resource Management’s Performance Target...

  20. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  1. Human Power Empirically Explored

    NARCIS (Netherlands)

    Jansen, A.J.

    2011-01-01

    Harvesting energy from the users’ muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are

  2. HUMAN CAPITAL INVESTMENT

    Directory of Open Access Journals (Sweden)

    Ph. D. Student Ioana - Julieta Josan

    2012-05-01

    Full Text Available Once with the development of the human capital theory, the education received an economic value. Leading theorists and specialists in the field have shown that the remarkable economic effects of the investments in education influence the chances of acquiring a job and earnings, demonstrating how the theory justifies such an investment. At the hand, the allocation of resources in human capital brings performance and benefits to companies investing in their employees. Also, the investment in human capital is strategic for any country that seeks to create a knowledge economy. Considering the above arguments, the aim of this paper is to highlight the characteristics of investment in human capital, the types of investment, the factors of education investment and the entities interested in investing and their benefits.

  3. Human female meiosis revised

    DEFF Research Database (Denmark)

    Capalbo, Antonio; Hoffmann, Eva R.; Cimadomo, Danilo

    2017-01-01

    in the female germline is a crucial step towards the development of new diagnostic approaches and, possibly, for the development of therapeutic targets and molecules. Here, we have reviewed emerging mechanisms that may drive human aneuploidy, in particular the maternal age effect. SEARCH METHODS We conducted...... a systematic search in PubMed Central of the primary literature from 1990 through 2016 following the PRISMA guidelines, using MeSH terms related to human aneuploidy. For model organism research, we conducted a literature review based on references in human oocytes manuscripts and general reviews related...... to chromosome segregation in meiosis and mitosis. OUTCOMES Advances in genomic and imaging technologies are allowing unprecedented insight into chromosome segregation in human oocytes. This includes the identification of a novel chromosome segregation error, termed reverse segregation, as well as sister...

  4. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  5. Pushing Human Frontiers

    Science.gov (United States)

    Zubrin, Robert

    2005-01-01

    With human colonization of Mars, I think you will see a higher standard of civilization, just as America set a higher standard of civilization which then promulgated back into Europe. I think that if you want to maximize human potential, you need a higher standard of civilization, and that becomes an example that benefits everyone. Without an open frontier, closed world ideologies, such as the Malthus Theory, tend to come to the forefront. It is that there are limited resources; therefore, we are all in deadly competition with each other for the limited pot. The result is tyrannical and potentially genocidal regimes, and we've already seen this in the twentieth century. There s no truth in the Malthus Theory, because human beings are the creators of their resources. With every mouth comes a pair of hands and a brain. But if it seems to be true, you have a vector in this direction, and it is extremely unfortunate. It is only in a universe of infinite resources that all humans can be brothers and sisters. The fundamental question which affects humanity s sense of itself is whether the world is changeable or fixed. Are we the makers of our world or just its inhabitants? Some people have a view that they re living at the end of history within a world that s already defined, and there is no fundamental purpose to human life because there is nothing humans can do that matters. On the other hand, if humans understand their own role as the creators of their world, that s a much more healthy point of view. It raises the dignity of humans. Indeed, if we do establish a new branch of human civilization on Mars that grows in time and potency to the point where it cannot really settle Mars, but transforms Mars, and brings life to Mars, we will prove to everyone and for all time the precious and positive nature of the human species and every member of it.

  6. Human-Robot Biodynamics

    OpenAIRE

    Ivancevic, Vladimir G.

    2008-01-01

    This paper presents the scientific body of knowledge behind the Human Biodynamics Engine (HBE), a human motion simulator developed on the concept of Euclidean motion group SE(3), with 270 active degrees of freedom, force-velocity-time muscular mechanics and two-level neural control - formulated in the fashion of nonlinear humanoid robotics. The following aspects of the HBE development are described: geometrical, dynamical, control, physiological, AI, behavioral and complexity, together with s...

  7. Reclaiming human machine nature

    OpenAIRE

    Fass, Didier

    2014-01-01

    International audience; Extending and modifying his domain of life by artifact production is one of the main characteristics of humankind. From the first hominid, who used a wood stick or a stone for extending his upper limbs and augmenting his gesture strength, to current systems engineers who used technologies for augmenting human cognition, perception and action, extending human body capabilities remains a big issue. From more than fifty years cybernetics, computer and cog-nitive sciences ...

  8. Genetics of human hydrocephalus

    OpenAIRE

    Zhang, Jun; Michael A. Williams; Rigamonti, Daniele

    2006-01-01

    Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic co...

  9. Human ocular anatomy.

    Science.gov (United States)

    Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M

    2015-01-01

    We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Evolution and human sexuality.

    Science.gov (United States)

    Gray, Peter B

    2013-12-01

    The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory. Copyright © 2013 Wiley Periodicals, Inc.

  11. ELECTRONIC HUMAN RESOURCE MANAGEMENT

    OpenAIRE

    Dr. M. Panneerselvam

    2017-01-01

    Electronic Human Resource Management is an essence the revolution of human resource functions to management and employees. These functions are typically used via intranet and web technology. This helps the organization to improve their standards where they can able to review and forward. All those documents can be viewed within a fraction of second with help of client and server links. The phenomenon of E- HRM deserves closer and more fundamental roots to HR activity. The E-HRM develops and b...

  12. Human motricity and health

    Directory of Open Access Journals (Sweden)

    Manuel Sérgio Vieira e Cunha

    2008-06-01

    Full Text Available If human motricity science intends to study motor conduct (or actions in which the human being pursues transcendence (or surmounting, it inevitably relates to the large realm of health. What are the aspects it evinces? Transdisciplinarity, solidarity among the various knowledge types (including poetical, complexity, (where the physical is integrated but surmounted and the firm belief that to be healthy is to have in ourselves, alive and working, the capacity for surmounting anything.

  13. Human Germline Genome Editing.

    Science.gov (United States)

    Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E

    2017-08-03

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  14. HUMAN CAPITAL INVESTMENT

    OpenAIRE

    Ph. D. Student Ioana - Julieta Josan

    2012-01-01

    Once with the development of the human capital theory, the education received an economic value. Leading theorists and specialists in the field have shown that the remarkable economic effects of the investments in education influence the chances of acquiring a job and earnings, demonstrating how the theory justifies such an investment. At the hand, the allocation of resources in human capital brings performance and benefits to companies investing in their employees. Also, the investment in hu...

  15. Yeast Interacting Proteins Database: YNL189W, YGR136W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available as17p, which is a homolog of human Wiskott-Aldrich Syndrome protein involved in actin patch assembly and act...ion Protein containing an N-terminal SH3 domain; binds Las17p, which is a homolog of human Wiskott-Aldrich Syndrome

  16. Yeast Interacting Proteins Database: YGR058W, YGR136W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available main; binds Las17p, which is a homolog of human Wiskott-Aldrich Syndrome protein ...erminal SH3 domain; binds Las17p, which is a homolog of human Wiskott-Aldrich Syndrome protein involved in a

  17. Deuteronomy and Human Rights

    Directory of Open Access Journals (Sweden)

    G. Braulik

    1998-08-01

    Full Text Available If one compares the articles of the "Universal Declaration of Human Rights" dated December 10th, 1948, with the regulations of the book of Deuteronomy, one detects a surprising abundance of correspondences, or at least of similar tendencies, between them. As the social theorists of the seventeenth and eighteenth centuries, the architects of the catalogue of Human Rights, knew the Scripture very well. References to Deuteronomy are historically well probable and factually hardly coincidental. Deuteronomy rightly boasts about its social laws (4:8 that are unique in the Ancient Near East. The paper orientates itself to the short formula of Human Rights and at the same time to the normative basic character of each human right, as it is formulated in the first article of the declaration: "liberty", "equality", "fraternity". Each of these basic categories are concretised in terms of several Deuteronomic regulations and prove themselves to be central matters of concern within the YHWH religion. Finally, it is outlined how the connection between Deuteronomy and modem expressions of human rights might be explained, and further it is shown what actually makes up the peculiarity of biblical thinking on human rights.

  18. Proteomics of human mitochondria.

    Science.gov (United States)

    Palmfeldt, Johan; Bross, Peter

    2017-03-01

    Proteomics have passed through a tremendous development in the recent years by the development of ever more sensitive, fast and precise mass spectrometry methods. The dramatically increased research in the biology of mitochondria and their prominent involvement in all kinds of diseases and ageing has benefitted from mitochondrial proteomics. We here review substantial findings and progress of proteomic analyses of human cells and tissues in the recent past. One challenge for investigations of human samples is the ethically and medically founded limited access to human material. The increased sensitivity of mass spectrometry technology aids in lowering this hurdle and new approaches like generation of induced pluripotent cells from somatic cells allow to produce patient-specific cellular disease models with great potential. We describe which human sample types are accessible, review the status of the catalog of human mitochondrial proteins and discuss proteins with dual localization in mitochondria and other cellular compartments. We describe the status and developments of pertinent mass spectrometric strategies, and the use of databases and bioinformatics. Using selected illustrative examples, we draw a picture of the role of proteomic analyses for the many disease contexts from inherited disorders caused by mutation in mitochondrial proteins to complex diseases like cancer, type 2 diabetes and neurodegenerative diseases. Finally, we speculate on the future role of proteomics in research on human mitochondria and pinpoint fields where the evolving technologies will be exploited. Copyright © 2016. Published by Elsevier B.V.

  19. Cytokines in human milk.

    Science.gov (United States)

    Garofalo, Roberto

    2010-02-01

    Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

  20. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  1. A WORLD BEYOND HUMAN

    Directory of Open Access Journals (Sweden)

    David Abram

    2013-12-01

    Full Text Available From an initial project to investigate the relationship between magic and traditional medicine as practiced by shamans in Southern rural Asia, the focus of attention gradually shifted to an awareness of the negotiation traditional medicine people or shamans exert between the human community and the larger community of beings. This attentiveness to a more-than-human world does not occur at a supernatural domain above nature or inside her personal self but is the result of the shaman’s special ability to project her consciousness horizontally to other forms of sensibility with which human existence is interwoven. The ecological function of the shaman is to maintain a constant balance between what is taken and what is given from the human community to the larger community. The spirits of indigenous cultures are not defined in opposition to materiality but are essentially those modes of intelligence or awareness that do not possess a human form. By exploring different landscapes, and the sensibility living in them, a new sensitivity is awoken that allows for communication with those intelligences. However, the drowning of these other voices in Western culture, which reduces otherness to an object, creates an uneasiness that is hardly perceived except as an inability to interact with anything more-than-human and its dire consequences in the form of “civilization’s” destructive behavior.

  2. Habitability and Human Factors Contributions to Human Space Flight

    Science.gov (United States)

    Sumaya, Jennifer Boyer

    2011-01-01

    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  3. Testing for Human Immunodeficiency Virus

    Science.gov (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  4. Human bites - self-care

    Science.gov (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  5. Developing Human Performance Measures

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey Joe; Bruce Hallbert; Larry Blackwood; Donald Dudehoeffer; Kent Hansen

    2006-05-01

    Through the reactor oversight process (ROP), the U.S. Nuclear Regulatory Commission (NRC) monitors the performance of utilities licensed to operate nuclear power plants. The process is designed to assure public health and safety by providing reasonable assurance that licensees are meeting the cornerstones of safety and designated crosscutting elements. The reactor inspection program, together with performance indicators (PIs), and enforcement activities form the basis for the NRC’s risk-informed, performance based regulatory framework. While human performance is a key component in the safe operation of nuclear power plants and is a designated cross-cutting element of the ROP, there is currently no direct inspection or performance indicator for assessing human performance. Rather, when human performance is identified as a substantive cross cutting element in any 1 of 3 categories (resources, organizational or personnel), it is then evaluated for common themes to determine if follow-up actions are warranted. However, variability in human performance occurs from day to day, across activities that vary in complexity, and workgroups, contributing to the uncertainty in the outcomes of performance. While some variability in human performance may be random, much of the variability may be attributed to factors that are not currently assessed. There is a need to identify and assess aspects of human performance that relate to plant safety and to develop measures that can be used to successfully assure licensee performance and indicate when additional investigation may be required. This paper presents research that establishes a technical basis for developing human performance measures. In particular, we discuss: 1) how historical data already gives some indication of connection between human performance and overall plant performance, 2) how industry led efforts to measure and model human performance and organizational factors could serve as a data source and basis for a

  6. Interaction Between Humans and Structures

    DEFF Research Database (Denmark)

    Pedersen, Lars

    2014-01-01

    On structures two types of humans may be present. (1) Active humans and (2) passive humans (sitting or standing on the structure). The active humans can excite the structure and cause structural vibrations. The mass of the passive humans will interact with the structure and basically it changes...... the structural system (modal characteristics and structural vibration levels). The paper addresses this subject and explores the implications of having passive humans present on the structure....

  7. Towards a better understanding of human smuggling

    OpenAIRE

    Heckmann, Friedrich

    2007-01-01

    Contents: What is human smuggling?; How can we know about human smuggling?; Human smuggling as a migration phenomenon; Human smuggling as a business; The social organizing of human smuggling; Fighting against human smuggling.

  8. Why Geo-Humanities

    Science.gov (United States)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  9. Humanity and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available So far our open access publishing company MDPI (Multidisciplinary Digital Publishing Institute has published mainly science, medicine and technology journals. To become a multidisciplinary publisher, we launched the journal Sustainability [1]. More recently, we started to run several social science journals, including Societies [2], Religions [3], Administrative Sciences [4] and Behavioral Sciences [5]. Today we published the first paper [6] of the inaugural issue of Humanities (ISSN 2076-0787. This will be an international open access journal, publishing scholarly papers of high quality across all humanities disciplines. As a publisher, I would like to publish journals surrounding the topics of sustainability and I believe the humanities as a discipline of academic studies are very important. As a scientist, I believed science and technology will only benefit human beings. I was raised in a small village, living a very primitive life in a peasant family: no electricity, no machines, of course no TV and no refrigerator. Now, the life of my children is completely different. Even my own life has completely changed. I have witnessed very rapid changes: more and more machines are used to consume mineral resources and energy and to pollute the environment, in order to produce more and more powerful machines (we are also launching a journal titled Machines, in which the relationship between Man and machine should be an interesting topic.. Machines are more and more like human individuals consuming resources themselves (we are launching a journal titled Resources. [...

  10. Human milk banking guidelines.

    Science.gov (United States)

    Bharadva, Ketan; Tiwari, Satish; Mishra, Sudhir; Mukhopadhyay, Kanya; Yadav, Balraj; Agarwal, R K; Kumar, Vishesh

    2014-06-01

    WHO and UNICEF state that the use of human milk from other sources should be the first alternative when it is not possible for the mother to breastfeed. Human milk banks should be made available in appropriate situations. The IYCF Chapter is actively concerned about the compelling use of formula feeds in the infants because of the non availability of human breast milk banks. A National Consultative Meet for framing guidelines was summoned by the IYCF Chapter and the Ministry of Health and Family Welfare, Government of India on 30th June, 2013, with representations from various stakeholders. The guidelines were drafted after an extensive literature review and discussions. Though these guidelines are based on the experiences and guidelines from other countries, changes have been made to suit the Indian setup, culture and needs, without compromising scientific evidence. To ensure quality of donated breast milk as a safe end product. Human Milk Banking Association should be constituted, and human milk banks should be established across the country. National coordination mechanism should be developed with a secretariat and technical support to follow-up on action in States. Budgetary provisions should be made available for the activities.

  11. The human serum metabolome.

    Directory of Open Access Journals (Sweden)

    Nikolaos Psychogios

    2011-02-01

    Full Text Available Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca.

  12. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  13. Infants' Responses to Real Humans and Representations of Humans

    Science.gov (United States)

    Heron, Michelle; Slaughter, Virginia

    2010-01-01

    Infants' responses to typical and scrambled human body shapes were assessed in relation to the realism of the human body stimuli presented. In four separate experiments, infants were familiarized to typical human bodies and then shown a series of scrambled human bodies on the test. Looking behaviour was assessed in response to a range of different…

  14. Medical practice, human experimentation and the sanctity of human ...

    African Journals Online (AJOL)

    ... human health and the sanctity of human life. In checkmating these dangers, the paper recommends and canvasses for the adoption of the ethical principles of the Nuremberg code of 1947 in properly regulating human experimentation so as to maximize its benefits and at the same time respect the sanctity of human life.

  15. Movement coordination in applied human-human and human-robot interaction

    DEFF Research Database (Denmark)

    Schubö, Anna; Vesper, Cordula; Wiesbeck, Mathey

    2007-01-01

    and describing human-human interaction in terms of goal-oriented movement coordination is considered an important and necessary step for designing and describing human-robot interaction. In the present scenario, trajectories of hand and finger movements were recorded while two human participants performed......The present paper describes a scenario for examining mechanisms of movement coordination in humans and robots. It is assumed that coordination can best be achieved when behavioral rules that shape movement execution in humans are also considered for human-robot interaction. Investigating...... coordination were affected. Implications for human-robot interaction are discussed....

  16. [Diagnosis of human toxocarosis].

    Science.gov (United States)

    Roldán, William H; Espinoza, Yrma A; Huapaya, Pedro E; Jiménez, Susana

    2010-01-01

    Human toxocarosis is an important parasitic zoonosis caused by larval stages of Toxocara species, the roundworms from dogs and cats. Larval migration through different soft tissues in the human generates several clinical entities in the patient, such as visceral larva migrans, ocular toxocarosis, and neurotoxocarosis. Definitive diagnosis by histopathological methods is very difficult or almost impossible and, nowadays, the diagnosis is usually made by clinical signs/symptoms, epidemiological background of the patient and the use of hematological and immunological tests which finally help to confirm the clinical suspicion of the illness. The purpose of this paper was to update the available knowledge on the use of different tools for both the diagnosis and following up of human toxocarosis.

  17. Social cognition in humans

    DEFF Research Database (Denmark)

    Frith, Christopher; Frith, Uta

    2007-01-01

    We review a diversity of studies of human social interaction and highlight the importance of social signals. We also discuss recent findings from social cognitive neuroscience that explore the brain basis of the capacity for processing social signals. These signals enable us to learn about...... the world from others, to learn about other people, and to create a shared social world. Social signals can be processed automatically by the receiver and may be unconsciously emitted by the sender. These signals are non-verbal and are responsible for social learning in the first year of life. Social...... signals can also be processed consciously and this allows automatic processing to be modulated and overruled. Evidence for this higher-level social processing is abundant from about 18 months of age in humans, while evidence is sparse for non-human animals. We suggest that deliberate social signalling...

  18. Philanthropy and Human Rights

    DEFF Research Database (Denmark)

    Larsen, Øjvind

    2013-01-01

    in Germany, England, France and USA. In each tradition is developed special features of the concept of philanthropy. The four traditions are summarized in the UN universal human rights, which has become the common normative reference for global philanthropy. In this way philanthropy has become, in a modern......, and normally utilized to promote one’s own prestige in the city-state. In Roman context, universal humanism, humanitas, was invented. This universal perspective was also supported by Christianity. It is this universal concept of philanthropy which is the foundation for the different philanthropic traditions...... sense, a charitable act with the aim to promote human happiness independent of gender, class, race, etc. This is the genealogy of the modern understanding of philanthropy, which will be developed in this paper....

  19. Human Systems Design Criteria

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1982-01-01

    This paper deals with the problem of designing more humanised computer systems. This problem can be formally described as the need for defining human design criteria, which — if used in the design process - will secure that the systems designed get the relevant qualities. That is not only...... the necessary functional qualities but also the needed human qualities. The author's main argument is, that the design process should be a dialectical synthesis of the two points of view: Man as a System Component, and System as Man's Environment. Based on a man's presentation of the state of the art a set...... of design criteria is suggested and their relevance discussed. The point is to focus on the operator rather than on the computer. The crucial question is not to program the computer to work on its own conditions, but to “program” the operator to function on human conditions....

  20. Abortion and human rights.

    Science.gov (United States)

    Shaw, Dorothy

    2010-10-01

    Abortion has been a reality in women's lives since the beginning of recorded history, typically with a high risk of fatal consequences, until the last century when evolutions in the field of medicine, including techniques of safe abortion and effective methods of family planning, could have ended the need to seek unsafe abortion. The context of women's lives globally is an important but often ignored variable, increasingly recognised in evolving human rights especially related to gender and reproduction. International and regional human rights instruments are being invoked where national laws result in violations of human rights such as health and life. The individual right to conscientious objection must be respected and better understood, and is not absolute. Health professional organisations have a role to play in clarifying responsibilities consistent with national laws and respecting reproductive rights. Seeking common ground using evidence rather than polarised opinion can assist the future focus. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Whither medical humanities?

    Science.gov (United States)

    Singh, Navjeevan

    2012-01-01

    Understanding the medical humanities (MH) and their role in medical education is in its infancy in India. Students are initiated into professional (medical) education too early in life, usually at the expense of a basic grounding in the humanities, resulting in warped intellectual growth. The author, arguing against the wholesale import of foreign systems, advocates free inquiry by medical educators to evolve a humanities programme for medical students derived from our own cultural context. This essay describes the early experiences of efforts to make a beginning at the University College of Medical Sciences, Delhi. The author reviews the various strategies used and the challenges of introducing the subject to the current generation of medical students.

  2. Medical humanities ... almost.

    Science.gov (United States)

    Dangayach, Neha

    2012-01-01

    Brought up in the traditional education system in a large teaching hospital in Mumbai, India, I moved on to do specialisation in neurology in the United States of America. The Indian system of pre-medical education mandates early choices between the humanities and the sciences and thus precludes a more well-rounded development of a student. Though medical humanities is not taught as a subject as part of the medical curriculum in India, listening to inspiring and learned teachers and the daily interaction with scores of patients who are willing to submit themselves to examination "in the cause of medical education" is a humbling experience to a sensitive student. I see similar willingness in patients in the United States. However, a formal course in the medical humanities, including arts, literature, and philosophy will surely enrich the experience of a larger number of undergraduates and postgraduates learning the core subjects and help in moulding a more rounded physician.

  3. Human-Robot Interaction

    Science.gov (United States)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta

    2012-01-01

    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  4. Humanities under Pressure

    Directory of Open Access Journals (Sweden)

    Jürgen Mittelstrass

    2015-02-01

    Full Text Available The Humanities have a problem with visibility both in the public sphere and in the academic system itself, and they have an organisational problem when compared with other sections of the academic system. They also have a funding problem, particularly in a European context, i.e., in the framework of the European research policy. The topic of this position paper is the essential role of the Humanities when dealing with the European project, the framing of Europe. In this respect, in contrast to the natural and social sciences, the Humanities need specific models of research funding, more individualised and of more interdisciplinary character. Additionally, they may need more multi-national centres for advanced studies on a European level, thus also solving their visibility and organisational problems.

  5. HUMAN MISSION OF EDUCATION

    Directory of Open Access Journals (Sweden)

    Suzana Miovska Spaseva

    2013-06-01

    Full Text Available The article examines the complex role and great responsibility of the education today in development of the moral strength and human values of the children and youth. At the beginning of the article the author reconsiders the pedagogical ideas of Maria Montessori and her concept of education for peace as an instrument for reconstruction of the society and for improvement of the human living. Than the analysis of the moral values in the contemporary society is made and several issues and dilemmas are discussed referring the value disorientation of the youth and the importance of the models of adult’s moral behavior in their search for personal identity. On the basis of this analysis, the human dimension of the education is elaborated enhancing the need for its understanding as support of development, which is based on several crucial elements: love, freedom and spirit of community.

  6. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, men også arbejdssociologien, arbejdspsykologien og human resource development. Den første retning udsprang af de såkaldte Hawthorne-eksperimenter og psykologen Elton Mayos bearbejdelse af resultaterne derfra. Den anden er en løsere gruppering bestående af navne som Abraham Maslow og Frederick Herzberg......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...

  7. Defining Human Enhancement

    DEFF Research Database (Denmark)

    Nordberg, Ana

    2017-01-01

    Emerging technologies open the prospect of extraordinary interventions on the human body. These may go beyond what is strictly necessary to sustain health and well-being. While responding to social and ethical challenges of such advances, the Law simultaneously faces the challenge of reflecting...... on the legitimacy to legislate and on whether the existing legal framework is appropriate to address the various concerns. In order to do so, it is crucial to establish clear legal definitions. Precise distinctions between interventions on the human body are intrinsically difficult to formulate. However, subject......-matter definitions are vital legal tools to determine what is currently regulated in established fields of law and whether there is room for a new legal field – Enhancement Law. This paper provides a reflection on the relevance of establishing a legal definition of human enhancement and to what extent different...

  8. The Human Centrifuge

    Science.gov (United States)

    van Loon, Jack J. W. A.

    2009-01-01

    Life on Earth has developed at unit gravity, 9.81 m/s2, which was a major factor especially when vertebrates emerged from water onto land in the late Devonian, some 375 million years ago. But how would nature have evolved on a larger planet? We are able to address this question simply in experiments using centrifuges. Based on these studies we have gained valuable insights in the physiological process in plants and animals. They adapt to a new steady state suitable for the high-g environments applied. Information on mammalian adaptations to hyper-g is interesting or may be even vital for human space exploration programs. It has been shown in long duration animal hypergravity studies, ranging from snails, rats to primates, that various structures like muscles, bones, neuro-vestibular, or the cardio-vascular system are affected. However, humans have never been exposed to a hyper-g environment for long durations. Centrifuge studies involving humans are mostly in the order of hours. The current work on human centrifuges are all focused on short arm systems to apply short periods of artificial gravity in support of long duration space missions in ISS or to Mars. In this paper we will address the possible usefulness of a large human centrifuge on Earth. In such a centrifuge a group of humans can be exposed to hypergravity for, in principle, an unlimited period of time like living on a larger planet. The input from a survey under scientists working in the field of gravitational physiology, but also other disciplines, will be discussed.

  9. Handbook of human computation

    CERN Document Server

    Michelucci, Pietro

    2013-01-01

    This volume addresses the emerging area of human computation, The chapters, written by leading international researchers, explore existing and future opportunities to combine the respective strengths of both humans and machines in order to create powerful problem-solving capabilities. The book bridges scientific communities, capturing and integrating the unique perspective and achievements of each. It coalesces contributions from industry and across related disciplines in order to motivate, define, and anticipate the future of this exciting new frontier in science and cultural evolution. Reade

  10. We Are Human Beings

    Science.gov (United States)

    McGee, Andrew

    2016-01-01

    In this paper, I examine Jeff McMahan’s arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients. PMID:26810918

  11. Human Body Exergy Metabolism

    OpenAIRE

    Mady, Carlos

    2013-01-01

    The exergy analysis of the human body is a tool that can provide indicators of health and life quality. To perform the exergy balance it is necessary to calculate the metabolism on an exergy basis, or metabolic exergy, although there is not yet consensus in its calculation procedure. Hence, the aim of this work is to provide a general method to evaluate this physical quantity for human body based on indirect calorimetry data. To calculate the metabolism on an exergy basis it is necessary to d...

  12. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2015-01-01

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of transnational business governance interactions (TBGI) analytical framework.1 The article identifies and discusses dimensions of interaction...... in several areas of relevance to transnational business governance interaction and indicates the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational business governance suggests that this form...... of governance offers prospects for public institutions as a means towards regulating global sustainability concerns....

  13. Ayahuasca and human destiny.

    Science.gov (United States)

    McKenna, Dennis J

    2005-06-01

    In this essay, the author shares his personal reflections gleaned from a lifetime of research with ayahuasca, and speculates on the societal, political, planetary, and evolutionary implications of humanity's aeons-old symbiosis with this shamanic plant. The thesis is developed that at this critical historical juncture, ayahuasca has developed a strategy to broadcast its message to a wider world--a reflection of the urgent need to avert global ecological catastrophe. While ayahuasca has much to teach us, the critical question is, will humanity hear it, and heed it, in time?

  14. When computers were human

    CERN Document Server

    Grier, David Alan

    2013-01-01

    Before Palm Pilots and iPods, PCs and laptops, the term ""computer"" referred to the people who did scientific calculations by hand. These workers were neither calculating geniuses nor idiot savants but knowledgeable people who, in other circumstances, might have become scientists in their own right. When Computers Were Human represents the first in-depth account of this little-known, 200-year epoch in the history of science and technology. Beginning with the story of his own grandmother, who was trained as a human computer, David Alan Grier provides a poignant introduction to the wider wo

  15. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...

  16. Experimental headache in humans

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    1995-01-01

    The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose-dependent h......The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose...

  17. On human health.

    Science.gov (United States)

    van Spijk, Piet

    2015-05-01

    If it is true that health is a priority objective of medicine, then medical practice can only be successful if the meaning of the term "health" is known. Various attempts have been made over the years to define health. This paper proposes a new definition. In addition to current health concepts, it also takes into account the distinction between specifically human (great) health and health as the absence of disease and illness-i.e. small health. The feeling of leading a life that makes sense plays a key role in determining specifically human great health.

  18. The Humanities, Human Rights, and the Comparative Imagination

    OpenAIRE

    McClennen, Sophia A.

    2007-01-01

    In her paper "The Humanities, Human Rights, and the Comparative Imagination" Sophia A. McClennen argues that understanding the relationship between culture and human rights depends on humanist perspectives attentive to the relationship between storytelling and identity, mass culture and ideology, text and audience, critical thinking and engaged citizenship. After briefly considering how the divide between the humanities and human rights advocates developed and how it might best be overcome, s...

  19. Human Modeling for Ground Processing Human Factors Engineering Analysis

    Science.gov (United States)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  20. Human Modeling For Ground Processing Human Factors Engineering Analysis

    Science.gov (United States)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over that last few years using human modeling for human factors engineering analysis for design of spacecraft and launch vehicles. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the different types of human modeling used currently and in the past at Kennedy Space Center (KSC) currently, and to explain the future plans for human modeling for future spacecraft designs.

  1. Human Rights: The Essential Reference.

    Science.gov (United States)

    Devine, Carol; Hansen, Carol Rae; Wilde, Ralph; Bronkhorst, Daan; Moritz, Frederic A.; Rolle, Baptiste; Sherman, Rebecca; Southard, Jo Lynn; Wilkinson, Robert; Poole, Hilary, Ed.

    This reference work documents the history of human rights theory, explains each article of the Universal Declaration of Human Rights, explores the contemporary human rights movement, and examines the major human rights issues facing the world today. This book is the first to combine historical and contemporary perspectives on these critical…

  2. Making IBM's Computer, Watson, Human

    Science.gov (United States)

    Rachlin, Howard

    2012-01-01

    This essay uses the recent victory of an IBM computer (Watson) in the TV game, "Jeopardy," to speculate on the abilities Watson would need, in addition to those it has, to be human. The essay's basic premise is that to be human is to behave as humans behave and to function in society as humans function. Alternatives to this premise are considered…

  3. Humane Education and Global Education.

    Science.gov (United States)

    Selby, David

    1993-01-01

    Presents and explains model representing four dimensions of global education: temporal, spatial, issues, and inner. Presents six principal areas covered by humane curricula; the relationships between humane education, environmental education, and human rights education; and two humane education activities for the secondary and elementary/secondary…

  4. Humanism in Education

    Science.gov (United States)

    Armstrong, Michael

    2015-01-01

    This is the text of Michael Armstrong's address to the Brian Simon Centenary conference, held at the Institute of Education on 26 March 2015. Michael Armstrong celebrates the humanism that underlay Brian's belief in a common system of education, democratic and non-selective, and finds its counterpart in the creative practice of school children.

  5. Hauntings of Human Nature

    DEFF Research Database (Denmark)

    Clasen, Mathias

    2017-01-01

    The central conflicts of Stephen King’s horror novel The Shining are rooted in human nature and reflect evolutionarily recurrent adaptive problems—the problem of balancing conflicting evolved motives, such as motives for selfish status striving versus motives for affiliative nurturing behavior...

  6. Human Resource Outsourcing Success

    OpenAIRE

    Hasliza Abdul-Halim; Elaine Ee; T. Ramayah; Noor Hazlina Ahmad

    2014-01-01

    The existing literature on partnership seems to take the relationship between partnership quality and outsourcing success for granted. Therefore, this article aims at examining the role of service quality in strengthening the relationship between partnership quality and human resource (HR) outsourcing success. The samples were obtained from 96 manufacturing organizations in Penang, Malaysia. The results showed that par...

  7. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  8. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  9. Animal and human influenzas.

    Science.gov (United States)

    Peiris, M; Yen, H-L

    2014-08-01

    Influenza type A viruses affect humans and other animals and cause significant morbidity, mortality and economic impact. Influenza A viruses are well adapted to cross species barriers and evade host immunity. Viruses that cause no clinical signs in wild aquatic birds may adapt in domestic poultry to become highly pathogenic avian influenza viruses which decimate poultry flocks. Viruses that cause asymptomatic infection in poultry (e.g. the recently emerged A/H7N9 virus) may cause severe zoonotic disease and pose a major pandemic threat. Pandemic influenza arises at unpredictable intervals from animal viruses and, in its global spread, outpaces current technologies for making vaccines against such novel viruses. Confronting the threat of influenza in humans and other animals is an excellent example of a task that requires a One Health approach. Changes in travel, trade in livestock and pets, changes in animal husbandry practices, wet markets and complex marketing chains all contribute to an increased risk of the emergence of novel influenza viruses with the ability to cross species barriers, leading to epizootics or pandemics. Coordinated surveillance at the animal- human interface for pandemic preparedness, risk assessment, risk reduction and prevention at source requires coordinated action among practitioners in human and animal health and the environmental sciences. Implementation of One Health in the field can be challenging because of divergent short-term objectives. Successful implementation requires effort, mutual trust, respect and understanding to ensure that long-term goals are achieved without adverse impacts on agricultural production and food security.

  10. Human social genomics.

    Science.gov (United States)

    Cole, Steven W

    2014-08-01

    A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA) characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  11. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1995-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  12. Humanities Review Journal: Submissions

    African Journals Online (AJOL)

    Author Guidelines. Papers for Humanities Review Journal should be submitted in English and should not exceed 25 pages typed double-spaced on A4 paper. References should be listed alphabetically at the end of the paper. Two copies of the paper, plus a 3_ diskette in Microsoft Word should be submitted. Neither ...

  13. Human Learning and Memory

    Science.gov (United States)

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  14. Human Memory: The Basics

    Science.gov (United States)

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  15. Home heating & human health

    NARCIS (Netherlands)

    Jongeneel, Sophie

    2008-01-01

    Human health is influenced by pollutants in the air. Since people spend over 80% of their time indoors, indoor air quality may be more related to health problems than outdoor air qual-ity. Indoor air quality is deteriorating because of energy conservation

  16. Children Are Human Beings

    Science.gov (United States)

    Bossard, James H. S.

    2017-01-01

    The basic assumption underlying this article is that the really significant changes in human history are those that occur, not in the mechanical gadgets which men use nor in the institutionalized arrangements by which they live, but in their attitudes and in the values which they accept. The revolutions of the past that have had the greatest…

  17. Is human fecundity changing?

    DEFF Research Database (Denmark)

    Smarr, Melissa M; Sapra, Katherine J; Gemmill, Alison

    2017-01-01

    Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is, therefore, fundamental for understanding human health at the population level. Given the absence of a population (bio)marker, fecundity is assessed indirectly by various individual-based (e.g. semen ...

  18. The Humanization of Science.

    Science.gov (United States)

    Larson, James H.

    1986-01-01

    Describes an exercise which focuses on the ethical and human aspects of science. Outlines the approach and components of a writing assignment based on a literary and humanistic analysis of "The Double Helix" by James Watson. Provides sample questions and examples of integrative literary works. (ML)

  19. Dermatophilus congolensis human infection.

    Science.gov (United States)

    Towersey, L; Martins, E de C; Londero, A T; Hay, R J; Soares Filho, P J; Takiya, C M; Martins, C C; Gompertz, O F

    1993-08-01

    Four cases of human dermatophilosis observed in Rio de Janeiro, Brazil, are reported. Data that suggest nail infection by Dermatophilus congolensis are presented. The clinical spectrum of the disease ranged from an asymptomatic infection to a pustular eruption. Our findings suggest that epidermal Langerhans cells play a role in the pathogenesis of the infection.

  20. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  1. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Lopes, Arminda; Ørngreen, Rikke

    This book constitutes the thoroughly refereed post-conference proceedings of the Third IFIP WG 13.6 Working Conference on Human Work Interaction Design, HWID 2012, held in Copenhagen, Denmark, in December 2012. The 16 revised papers presented were carefully selected for inclusion in this volume...

  2. Lessons in Human Relations.

    Science.gov (United States)

    Glenn, Joanne Lozar

    2003-01-01

    Explores the importance of relationship literacy--the ability to create good relationships with others--in the next economy and offers perspectives on how business education instructors can help students develop and improve their human relations skills for business success. (Author/JOW)

  3. Journal of Humanities

    African Journals Online (AJOL)

    The Journal of Humanities is a theoretical journal which aims to challenge, provoke and excite thinking in the areas of the classics, fine performing arts, literature and orature, linguistics, theology and philosophy. The journal appears annually and is sponsored by the Research and Publications Committee of the Univeristy of ...

  4. Human paragonimiasis in Africa.

    Science.gov (United States)

    Aka, N'Da A; Adoubryn, Koffi; Rondelaud, Daniel; Dreyfuss, Gilles

    2008-12-01

    An up-to-date review on human paragonimiasis in Africa was carried out to determine the current geographical distribution of human cases and analyze the animal reservoir, snails and crustaceans which intervene in the local life cycle of Paragonimus species. Two countries, i.e., Cameroon and Nigeria, were mainly affected by this disease, while the distribution of human cases in the other eight states of the intertropical zone was scattered. Infected patients were currently few in number and two Poragonimus species: P. africanus and P. uterobilateralis, were found. The animal reservoir is mainly constituted by crab-eating mammals. The identity of the host snail remains doubtful and was either a prosobranch, or a land snail. Seven crab species belonging to Callinectes, Liberonautes and Sudononautes genera are able to harbour paragonimid metacercariae. Due to the current low prevalence of human paragonimiasis recorded in Africa and the high cost of wide-scale screenings for this disease, training of technicians in anti-tuberculosis centers would be the most realistic attitude to detect mycobacteria and/or Paragonimus eggs during the same sputum examination.

  5. Oxytocin promotes human ethnocentrism

    NARCIS (Netherlands)

    de Dreu, C.K.W.; Greer, L.L.; van Kleef, G.A.; Shalvi, S.; Handgraaf, M.J.J.

    2011-01-01

    Human ethnocentrism—the tendency to view one's group as centrally important and superior to other groups—creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we

  6. Biotechnologies and Human Dignity

    Science.gov (United States)

    Sweet, William; Masciulli, Joseph

    2011-01-01

    In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the…

  7. Radar: Human Safety Net

    Science.gov (United States)

    Ritz, John M.

    2016-01-01

    Radar is a technology that can be used to detect distant objects not visible to the human eye. A predecessor of radar, called the telemobiloscope, was first used to detect ships in the fog in 1904 off the German coast. Many scientists have worked on the development and refinement of radar (Hertz with electromagnetic waves; Popov with determining…

  8. Superintelligence, Humans, and War

    Science.gov (United States)

    2015-04-13

    artificial intelligence. “The Navy’s Aegis Combat System is a computerized command, decision, and weapon-control program conceived because humans were no...continues to invest in highly technological weapons systems ...perform tasks that were only imagined 10 years ago. For example, Apple’s Siri will provide answers to verbally asked questions. There are driving

  9. Antihumanism in the Humanities.

    Science.gov (United States)

    Schwartz, Joel

    1990-01-01

    Analyzes the antihumanistic elements of Jacques Derrida's theory of deconstruction. Argues that the modern French intellectuals, including Foucault, Derrida, and Lacan, have had an antihumanistic effect on the American social sciences and humanities by rejecting the existence of truth, morality, and rationality. (FMW)

  10. Human Actions Made Tangible

    DEFF Research Database (Denmark)

    Buur, Jacob; Caglio, Agnese; Jensen, Lars Christian

    2014-01-01

    , a method developed to engage people from different backgrounds in collaboratively analysing videos with the help of physical objects. We will present one of these tools, Action Scrabble, for analysing temporal organisation of human actions. We work with a case of skilled forklift truck driving...

  11. Human-Centered Aspects

    NARCIS (Netherlands)

    Kulyk, Olga Anatoliyivna; Kosara, R.; Urquiza, J.; Wassink, I.; Kerren, A.; Ebert, A.; Meyer, J.

    2007-01-01

    Humans have remarkable perceptual capabilities. These capabilities are heavily underestimated in current visualizations. Often, this is due to the lack of an in-depth user study to set the requirements for optimal visualizations. The designer does not understand what kind of information should be

  12. Soil Borne Human Diseases

    NARCIS (Netherlands)

    Jeffery, Simon; Van der Putten, Wim H.

    2011-01-01

    Soils are home to a remarkable array of biodiversity with some estimates stating that 25% of the Earth’s species find their home in the soil. Of these organisms, the vast majority are not of any threat to human health, but rather function to provide numerous ecosystem services which emerge through

  13. Disability and Human Supports

    Directory of Open Access Journals (Sweden)

    Jeff McNair

    2015-01-01

    Full Text Available This article provides a brief overview of models of disability growing out of the field of disability studies and leading to a call for interventions going beyond a simply medical model approach. A brief discussion of human supports/services is provided such that readers engaged in the development of services/supports can base them on best principles.

  14. Structurally abnormal human autosomes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  15. Humane Treatment of Animals.

    Science.gov (United States)

    Dawson, Joan Smithey

    This booklet is designed to give teachers resource information about the humane treatment of and care for animals. The topics are presented as springboards for discussion and class activity. Topics include the care of dogs, cats, birds, horses, and fish; wildlife and ecological relationships; and careers with animals. Illustrations on some pages…

  16. IN HUMAN RESEARCH PROPOSALS

    African Journals Online (AJOL)

    These researchers tested the effect of. Hallucinogenic ... stories illustrating human cruelty as well as strong advocacy for the ... Experiments must be strictly beneficial to individuals,their communities, or the society in general. Same experiments previously conducted on animals and the natural history of the disease must be ...

  17. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  18. Haptocorrin in humans

    DEFF Research Database (Denmark)

    Mørkbak, Anne Louise; Nexo, Ebba; Poulsen, Steen Seier

    2007-01-01

    knowledge concerning its function and its distribution in adult and foetal life is limited. In this study, we present data on the tissue expression of haptocorrin and on the relation between analogues on haptocorrin and vitamin B(12) status in humans. Methods: Polyclonal antibodies towards haptocorrin were...

  19. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin of ......A in the human body are derived from Cbl....

  20. Studying Human Origins

    NARCIS (Netherlands)

    Corbey, Raymond; Roebroeks, Wil

    2001-01-01

    This history of human origin studies covers a wide range of disciplines. This important new study analyses a number of key episodes from palaeolithic archaeology, palaeoanthropology, primatology and evolutionary theory in terms of various ideas on how one should go about such reconstructions and

  1. Human memory search

    NARCIS (Netherlands)

    Davelaar, E.J.; Raaijmakers, J.G.W.; Hills, T.T.; Robbins, T.W.; Todd, P.M.

    2012-01-01

    The importance of understanding human memory search is hard to exaggerate: we build and live our lives based on what whe remember. This chapter explores the characteristics of memory search, with special emphasis on the use of retrieval cues. We introduce the dependent measures that are obtained

  2. Inconvenient Human Rights

    Science.gov (United States)

    Ryan, Natasha

    2017-01-01

    Abstract Following an increase in Roma migration under the European “freedom of movement” laws, Swedish municipalities initiated more than 80 evictions of informal Roma settlements on the grounds of poor sanitation between 2013 and 2016. These evictions echo policies from earlier in the 20th century, when Roma living in Sweden were often marginalized through the denial of access to water and sanitation facilities. The recent Swedish evictions also follow similar government actions across Europe, where Roma settlements are controlled through the denial of access to water and sanitation. However, access to water and sanitation—central aspects of human health—are universal human rights that must be available to all people present in a jurisdiction, regardless of their legal status. The evictions described here violated Sweden’s obligations under both European and international human rights law. More positive government responses are required, such as providing shelters or camping sites, setting up temporary facilities, and directly engaging with communities to address water and sanitation issues. The authors conclude by providing guidance on how states and municipalities can meet their human rights obligations with respect to water and sanitation for vulnerable Roma individuals and informal settlements in their communities. PMID:29302163

  3. Selenium and Human Health

    Directory of Open Access Journals (Sweden)

    M Abedi

    2013-04-01

    Full Text Available Introduction: Selenium is an essential element for human health and it is toxic at high concentrations. Selenium is a constituent component of selenoproteins that have enzymatic and structural roles in human biochemistry. Selenium is a best antioxidant and catalyst for production of thyroid hormone. This element has the key role in the immune function; prevention of AIDS progression and the deactivity of toxins. Furthermore, selenium is essential for sperm motility and can reduce abortions. Selenium deficiency was also associated with adverse mood states. The findings regarding cardiovascular disease risk related to selenium deficiency is unclear, though other conditions such as vascular inflammation, oxidative stress and selenium deficiency can cause this disease too. Moreover, consuming of 60 mg of selenium per day may be associated with reduction of cancer risk. In this study, a review of studies has been performed on the biochemical function of selenium toxicity, and its effects on human health. Furthermore, certain identified cancers associated with selenium have been discussed to absorb more attention to the status of this element and also as a guide for further studies. Selenium plays the dual character (useful and harmful in human health, and then it is necessary to determine the concentration of this element in body fluids and tissues. An appropriate method for routine measurement of selenium in clinical laboratories is electro thermal atomic absorption spectrometry (ETAAS with very low detection limit and good precision.

  4. Cultivating human nature

    NARCIS (Netherlands)

    Derksen, Maarten

    2007-01-01

    Evolutionary psychology claims to offer a unified perspective on human nature and culture, which can serve to further the integration of psychology and the social sciences. I describe four approaches to evolutionary psychology, and note increasing attention to the agency of the individual in

  5. Pesticides and Human Health

    Science.gov (United States)

    ... types of pesticides Disponible en español Pesticides and Human Health Pesticides have a specific purpose in society. Pesticides are ... aging populations may be more sensitive to the effects of pesticides than others. To reduce the risk of health problems from pesticides there are several things you ...

  6. Human oocyte cryopreservation.

    Science.gov (United States)

    Tao, Tao; Zhang, Wenling; Del Valle, Alfonso

    2009-06-01

    This review summarized the clinical breakthroughs in the human oocyte cryopreservation field in the past 2 years and gave special emphasis on the role of vitrification method. Human oocyte cryopreservation is an attractive strategy to preserve female fertility, as it offers more opportunities to the future destination of the female gametes and also raises fewer legal and ethical questions compared with embryo cryopreservation. It became promising in recent years because of dramatic improvement in cryopreservation technologies. Human oocyte cryopreservation would not become a clinical routine until the availability of reliable cryopreservation methods and long-term follow-up results of the babies born by this technique. Oocyte cryopreservation produced very exciting results with pregnancy and implantation rates comparable to embryo cryopreservation and in some cases comparable to fresh in-vitro fertilization cycles with both modified slow-freezing and vitrification methods. A cancer patient conceived and delivered her own babies by this technology after recovery from the disease. Oocyte cryopreservation became a new focus in assisted reproductive technology. We witnessed the advanced development of human oocyte cryopreservation in the past years because of increasing demand, medically, legally and ethically, and also because of the dramatic improvement of the freezing technique. There is still a long way to go to integrate it into a routine clinical procedure to benefit more patients and encourage clinicians to follow the standard protocols.

  7. Human perspectives in horticulture

    Science.gov (United States)

    Charles A. Lewis

    1977-01-01

    Gardening produces not only vegetables and flowers, but also social and behavioral benefits. In low-income housing sites in New York, Philadelphia, and Chicago, gardening programs have resulted in reduced vandalism, new neighborliness, cleaned and painted buildings and streets, and other improvements. The human response to plants, and the qualities of plants that...

  8. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  9. Human health and groundwater

    Science.gov (United States)

    The high quality of most groundwaters, consequent upon the self-purification capacity of subsurface strata, has long been a key factor in human health and wellbeing. More than 50% of the world’s population now rely on groundwater for their supply of drinking water – and in most circumstances a prope...

  10. Haptic Physical Human Assistance

    NARCIS (Netherlands)

    Keemink, Arvid Quintijn Leon

    2017-01-01

    This dissertation covers three aspects of upper-extremity exoskeleton design: 1) Kinematics & motion: How to support the full range of motion of the human shoulder? We present a 2D visualization method that can show coupling between the range of motion (ROM) of rotations of the glenohumeral joint.

  11. Human Rights in Prisons

    DEFF Research Database (Denmark)

    Jefferson, Andrew M.; Gaborit, Liv Stoltze

    Drawing on participatory action research conducted in Sierra Leone, Kosovo and the Philippines, Human Rights in Prisons analyses encounters between rights-based non-governmental organisations and prisons. It explores the previously under-researched perspectives of prison staff and prisoners...

  12. Animal and Human Communication.

    Science.gov (United States)

    Rummel, Lynda

    Several misconceptions regarding the status of human communication systems relative to the systems of other animals are discussed in this paper. Arguments are offered supporting the expansion of the communication discipline to include the study of the communication systems of other species. The "communicative continuity" view which ranks…

  13. Humane Education in Kindergarten

    Science.gov (United States)

    Montgomery, Charlotte Baker

    1977-01-01

    Describes objectives and activities of a humane education program to teach kindergarten students to respect animals. Activities include daily manners practice, observation of nature, bringing animals to the classroom, field trips, and organizing a be kind to animals week. For journal availability, see SO 505 454. (Author/DB)

  14. Human Babesiosis, Bolivia, 2013.

    Science.gov (United States)

    Gabrielli, Simona; Totino, Valentina; Macchioni, Fabio; Zuñiga, Freddy; Rojas, Patricia; Lara, Yuni; Roselli, Mimmo; Bartoloni, Alessandro; Cancrini, Gabriella

    2016-08-01

    To investigate human babesiosis in the Bolivian Chaco, in 2013 we tested blood samples from 271 healthy persons living in 2 rural communities in this region. Microscopy and PCR indicated that 3.3% of persons were positive for Babesia microti parasites (US lineage); seroprevalence was 45.7%. Appropriate screening should mitigate the risk for transfusion-associated babesiosis.

  15. Human-Robot Interaction

    Science.gov (United States)

    Sandor, Aniko; Cross, E. Vincent, II; Chang, Mai Lee

    2015-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces affect the human's ability to perform tasks effectively and efficiently when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. For efficient and effective remote navigation of a rover, a human operator needs to be aware of the robot's environment. However, during teleoperation, operators may get information about the environment only through a robot's front-mounted camera causing a keyhole effect. The keyhole effect reduces situation awareness which may manifest in navigation issues such as higher number of collisions, missing critical aspects of the environment, or reduced speed. One way to compensate for the keyhole effect and the ambiguities operators experience when they teleoperate a robot is adding multiple cameras and including the robot chassis in the camera view. Augmented reality, such as overlays, can also enhance the way a person sees objects in the environment or in camera views by making them more visible. Scenes can be augmented with integrated telemetry, procedures, or map information. Furthermore, the addition of an exocentric (i.e., third-person) field of view from a camera placed in the robot's environment may provide operators with the additional information needed to gain spatial awareness of the robot. Two research studies investigated possible mitigation approaches to address the keyhole effect: 1) combining the inclusion of the robot chassis in the camera view with augmented reality overlays, and 2) modifying the camera

  16. Cosmic Humanity: Utopia, Realities, Prospects

    OpenAIRE

    Sergey Krichevsky

    2017-01-01

    The philosophical foundations of the theory and practice of the creation of cosmic humanity as a process of the evolution of human civilization, the emergence into space, with the prospect of resettlement outside the Earth are considered. There is a connection between myths, fantasies, ideas, concepts and projects aimed at the exploration of outer space, the creation of cosmic humanity. A new and voluminous definition of cosmic humanity in the evolutionary paradigm is given. Cosmic humanity i...

  17. Pragmatic Challenges to Human Rights

    DEFF Research Database (Denmark)

    Schaumburg-Müller, Sten

    2007-01-01

    Pragmatism offers a platform for posing relevant questions. This article uses a pragmatic point of departure to question a natural law conception of human rights and to take a closer look at three pressing human rights problems: The human rights situation in states with little or no state capacity......; the revision and adaptation of human rights law; and the not straightforward relationship betweemn human rights and democracy....

  18. International terrorism and human rights

    OpenAIRE

    Gurská, Zuzana

    2010-01-01

    Summary: International Terrorism and Human Rights Key words: international terrorism, antiterrorist measures, human rights First part of the thesis is centered on characteristics of international terrorism, concept of human rights and three aspects of their mutual relationship: the immediate impact of terrorist attacks on human rights of their direct victims and the society as a whole and aspects linked to the states' response consisting of human rights breaches of suspects during repressive ...

  19. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  20. The Universal Declaration on the Human Genome and Human Rights.

    Science.gov (United States)

    Mayor, Federico

    2003-01-01

    Since 1985, UNESCO studies ethical questions arising in genetics. In 1992, I established the International Bioethics Committee at UNESCO with the mission to draft the Universal Declaration on the Human Genome and Human Rights, which was adopted by UNESCO in 1997 and the United Nations in 1998. The Declaration relates the human genome with human dignity, deals with the rights of the persons concerned by human genome research and provides a reference legal framework for both stimulating the ethical debate and the harmonization of the law worldwide, favouring useful developments that respect human dignity.

  1. Digitalization of the human mind

    Directory of Open Access Journals (Sweden)

    Mr.Sc. Drita Mehmeti

    2013-06-01

    Full Text Available The human faces with various problems already in its first steps in live, and carriers of such life situations are found in various ages which bring new currents in the way of life. Starting from the ancient Greek thought, the human and its mind made the centre of the world, already orienting the Western thought towards the study of the human mind (namely human reason, since it made the key tool for human survival. Although human problems have been discussed throughout various ages, they have not been able to resolve in full the human problems, and therefore, the same issues were taken by the representatives of the socalled “critical theory”, who used the theory to criticize the way of live Western civilization was offering, known as digitalization of the human mind. The human problems are addressed in a poly-dimensional manner. The factors affecting the human mind are: industrial civilization, technical progress, automation, overtly influence of machinery on humans, substitution of cultural values, which in sum have developed a new World Order, where the ruler is technology. In the modern world, the human fails to recognize himself, since he is out of himself and lives according to the rules set forth by the “remote control”. In the flow of this kind of livelihood, human alienates, or in other words, the human goes out of himself, trying to adapt maximally to the requirements of the new way of life.

  2. Human Integration Design Processes (HIDP)

    Science.gov (United States)

    Boyer, Jennifer

    2014-01-01

    The purpose of the Human Integration Design Processes (HIDP) document is to provide human-systems integration design processes, including methodologies and best practices that NASA has used to meet human systems and human rating requirements for developing crewed spacecraft. HIDP content is framed around human-centered design methodologies and processes in support of human-system integration requirements and human rating. NASA-STD-3001, Space Flight Human-System Standard, is a two-volume set of National Aeronautics and Space Administration (NASA) Agency-level standards established by the Office of the Chief Health and Medical Officer, directed at minimizing health and performance risks for flight crews in human space flight programs. Volume 1 of NASA-STD-3001, Crew Health, sets standards for fitness for duty, space flight permissible exposure limits, permissible outcome limits, levels of medical care, medical diagnosis, intervention, treatment and care, and countermeasures. Volume 2 of NASASTD- 3001, Human Factors, Habitability, and Environmental Health, focuses on human physical and cognitive capabilities and limitations and defines standards for spacecraft (including orbiters, habitats, and suits), internal environments, facilities, payloads, and related equipment, hardware, and software with which the crew interfaces during space operations. The NASA Procedural Requirements (NPR) 8705.2B, Human-Rating Requirements for Space Systems, specifies the Agency's human-rating processes, procedures, and requirements. The HIDP was written to share NASA's knowledge of processes directed toward achieving human certification of a spacecraft through implementation of human-systems integration requirements. Although the HIDP speaks directly to implementation of NASA-STD-3001 and NPR 8705.2B requirements, the human-centered design, evaluation, and design processes described in this document can be applied to any set of human-systems requirements and are independent of reference

  3. Rendering Humanities Sustainable

    Directory of Open Access Journals (Sweden)

    Robert G. Bednarik

    2011-10-01

    Full Text Available Launching a journal intended to cover the entire humanities is certainly an audacious project, for two reasons at least. Firstly, this journal will be expected to cover much academic diversity, particularly by including the “social sciences.” However, in this time of rampant overspecialization, perhaps it is precisely such wholeness and breadth of vision that could become a journal’s strength. Secondly, since the viability of the humanities has been questioned from a number of perspectives it seems essential to meet these challenges by reinventing the discipline in response to issues raised—also a major task. It involves justifying the continuation of humanistic traditions. For this, humanists need to consider the nature of these challenges, understand and analyze them, and respond to them. It is therefore inevitable that a forward-looking, new journal in this discipline will deem it relevant to review these matters. [...

  4. Human biology of taste.

    Science.gov (United States)

    Gravina, Stephen A; Yep, Gregory L; Khan, Mehmood

    2013-01-01

    Taste or gustation is one of the 5 traditional senses including hearing, sight, touch, and smell. The sense of taste has classically been limited to the 5 basic taste qualities: sweet, salty, sour, bitter, and umami or savory. Advances from the Human Genome Project and others have allowed the identification and determination of many of the genes and molecular mechanisms involved in taste biology. The ubiquitous G protein-coupled receptors (GPCRs) make up the sweet, umami, and bitter receptors. Although less clear in humans, transient receptor potential ion channels are thought to mediate salty and sour taste; however, other targets have been identified. Furthermore, taste receptors have been located throughout the body and appear to be involved in many regulatory processes. An emerging interplay is revealed between chemical sensing in the periphery, cortical processing, performance, and physiology and likely the pathophysiology of diseases such as diabetes.

  5. Human corneal epithelial subpopulations

    DEFF Research Database (Denmark)

    Søndergaard, Chris Bath

    2013-01-01

    subpopulations in human corneal epithelium using a combination of laser capture microdissection and RNA sequencing for global transcriptomic profiling. We compared dissociation cultures, using either expansion on γ-irradiated NIH/3T3 feeder cells in serum-rich medium or expansion directly on plastic in serum......-free EpiLife medium, using a range of physiologically relevant oxygen concentrations (2%, 5%, 10%, 15% and 20%). Using immunocytochemistry and advanced fluorescence microscopy, cells were characterized regarding growth, cell cycle distribution, colony-forming efficiency (CFE), phenotypes...... was not dependent on the system used for propagation (Bath et al. 2013a). Laser capture microdissection was used to isolate cellular subpopulations in situ from the spatially defined differentiation pathway in human corneal epithelium according to an optimized protocol for maintenance of expression profiles...

  6. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands...... and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  7. Sleep and Human Aging.

    Science.gov (United States)

    Mander, Bryce A; Winer, Joseph R; Walker, Matthew P

    2017-04-05

    Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need? Copyright © 2017. Published by Elsevier Inc.

  8. Posthumanism: beyond humanism?

    Science.gov (United States)

    Valera, Luca

    2014-01-01

    The focal point of posthumanism consists not as such in an a-critical acceptance of the technological promises - like there is for transhumanism - but in a total contamination and hybridization of human beings with other living beings and machines (these are the two main forms of contamination). The change of perspective untaken by posthumanism would be, thus, a paradigmatic shift in anthropology. As with ecologism, posthumanism, in order to obtain total contamination and man's openness to otherness, proposes the elimination and the fluidification of boundaries, thus even denying man's identity, and, with it, the very possibility of openness. However, by denying the identity, one denies the condition of possibility of thought, just as it has been manifested in history until now: hence we understand how, primarily, posthumanism is not configured as an adequate philosophical reflection, but as a narrative that takes origin from certain requirements, which are eminently human, and that discloses its deeply anthropogenic roots.

  9. Human freedom and enhancement.

    Science.gov (United States)

    Heilinger, Jan-Christoph; Crone, Katja

    2014-02-01

    Ideas about freedom and related concepts like autonomy and self-determination play a prominent role in the moral debate about human enhancement interventions. However, there is not a single understanding of freedom available, and arguments referring to freedom are simultaneously used to argue both for and against enhancement interventions. This gives rise to misunderstandings and polemical arguments. The paper attempts to disentangle the different distinguishable concepts, classifies them and shows how they relate to one another in order to allow for a more structured and clearer debate. It concludes in identifying the individual underpinnings and the social conditions of choice and decision-making as particularly salient dimensions of freedom in the ethical debate about human enhancement.

  10. Human Cytomegalovirus Persistence

    OpenAIRE

    Goodrum, Felicia; Caviness, Katie; Zagallo, Patricia

    2012-01-01

    Viral persistence is the rule following infection with all herpesviruses. The β-herpesvirus, human cytomegalovirus (HCMV), persists through chronic and latent states of infection. Both the chronic and latent states of infection contribute to HCMV persistence and to the high HCMV seroprevalence worldwide. The chronic infection is poorly defined molecularly, but clinically manifests as low-level virus shedding over extended periods of time and often in the absence of symptoms. Latency requires ...

  11. Neanderthals and Modern Humans

    Science.gov (United States)

    Finlayson, Clive

    2004-04-01

    The Neanderthals were a people native to Europe during the Pleistocene period, who became extinct between forty and thirty thousand years ago. Challenging the commonly held view that extinction was caused by the arrival of our ancestors, Clive Finlayson provides evidence that their extinction actually occurred because the Neanderthals could not adapt fast enough to changing ecological and environmental conditions, not their relationship with modern humans.

  12. The Human Body Sword

    Directory of Open Access Journals (Sweden)

    Kris Borer

    2010-08-01

    Full Text Available The human body shield problem involves an apparent dilemma for a libertarian, forcing him to choose between his own death and the death of an innocent person. This paper argues that the non-aggression principle permits a forceful response against the property of innocent individuals when a conflict is initiated with that property. In other words, a libertarian may shoot the hostage in order to save himself.

  13. Wilhelm Roepke: Economic humanism

    Directory of Open Access Journals (Sweden)

    Stojanović Božo

    2007-01-01

    Full Text Available The paper presents the basic ideas of the great German thinker Wilhelm Roepke advocated a free market acting in a particular social context (comprising of market insti­tutions, and a particular system of values created within the society and not by the market itself. He substantiated why free market economy has to be supplemented with a particular social ethics. He argued in favor of a society that defends and advances human liberty.

  14. Glycogen metabolism in humans ? ??

    OpenAIRE

    Adeva-Andany, María M.; González-Lucán, Manuel; Donapetry-García, Cristóbal; Fernández-Fernández, Carlos; Ameneiros-Rodríguez, Eva

    2016-01-01

    In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction. Glycogen has been identified in other tissues such as brain, heart, kidney, adipose tissue, and erythrocytes, but glycogen function in these tissues is mostly unknown. Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through...

  15. Decoding the human genome

    CERN Multimedia

    CERN. Geneva. Audiovisual Unit; Antonerakis, S E

    2002-01-01

    Decoding the Human genome is a very up-to-date topic, raising several questions besides purely scientific, in view of the two competing teams (public and private), the ethics of using the results, and the fact that the project went apparently faster and easier than expected. The lecture series will address the following chapters: Scientific basis and challenges. Ethical and social aspects of genomics.

  16. Human Hearing Loss

    OpenAIRE

    Ware, Stacy Lee

    2014-01-01

    Hearing loss affects as much as 5% of the global human population and its negative consequences, often exacerbated by cultural bias or distributive injustice, include delayed cognitive and language development, learning deficits and poor academic performance, chronic unemployment and dependency, poverty, elevated risk of harm and poor health. This paper is based on a review of the academic literature as well as other credible published resources to identify the principal causes of hearing los...

  17. Post-human Viewing

    DEFF Research Database (Denmark)

    Blaagaard, Bolette

    2013-01-01

    This article discusses the relationship between theories of photography and mobile phone footage. In doing so, it asks if theories of photography still apply in a technologically saturated world of imagery. Technology is an increasingly important part of viewing imagery today and enables imagery ...... implications. The author takes photojournalism and, in particular, mobile phone footage as a starting point for an exploration of the (post-human) body as evidence and sign of authenticity in the modern age of digital communications and journalism....

  18. Human resource management

    OpenAIRE

    Balážová, Barbora

    2008-01-01

    Human resource management is currently regarded as one of the most important areas of management of the organization. Its task is to ensure and maintain sufficient number of skilled and motivated employees and their optimum use to achieve the planned prosperity and competitiveness of the organization. This task is pursued through partial personnel activities (the creation and analysis of jobs, personnel planning, acquisition, selection, recruitment and orientation of staff, evaluation and com...

  19. Human Resource Management Roles

    OpenAIRE

    Tamara R. Mitchell

    2017-01-01

    The roles of Human Resource and Management play a vital role in the success of the organization. Internal recruitment is more valuable than external recruitment because it is less expensive, the employee’s skills are well known and companies that do internal recruitment have an important tool to boost morale in the organization. Performance management is an important part of an organization. The most important thing is that it strengthens the supervisor and employee relationship and promotes ...

  20. Human health and groundwater

    OpenAIRE

    Candela Lledó, Lucila

    2016-01-01

    Strategic overview series of the International Association of Hydrogeologists-IAH. This Series is designed both to inform professionals in other sectors of key interactions with groundwater resources and hydrogeological science, and to guide IAH members in their outreach to related sectors. The naturally high microbiological and chemical quality of groundwater, captured at springheads and in shallow galleries and dugwells, has been vital for human survival, wellbeing and development from o...

  1. The effects of human resource flexibility on human resources development

    Directory of Open Access Journals (Sweden)

    SeidMehdi Veise

    2014-08-01

    Full Text Available Human resources are the primary factor for development of competitiveness and innovation and reaching competitive advantage and they try to improve corporate capabilities through various characteristics such as value creation, scarcity and difficulty of imitation. This paper investigates the effect of human resource flexibility and its dimensions on human resource development and its dimensions. The survey was conducted using descriptive-correlation method that intended to describe how human resource flexibility was effective on human resource development. Questionnaire was tool of data collection. The statistical population included one hundred employees of the Electric Company in Ilam province, thus census method was used. Reliability of the questionnaire was measured via Cronbach's alpha equal to 0.96. The findings revealed that flexibility and its dimensions were effective on human resource development and dimensions of it. As a result, human resource flexibility should be considered for development of human resources and employees with the highest flexibility should be selected.

  2. Human parasitology worldwide research.

    Science.gov (United States)

    Garrido-Cardenas, Jose Antonio; Mesa-Valle, Concepción; Manzano-Agugliaro, Francisco

    2017-11-09

    In this article, the trends in human parasitology have been studied through the analysis of the number of publications in this area. The parameters studied were: number of articles, language, countries and institutions with the highest number of publications, and keywords with greater presence in the articles of human parasitology. The results of the analysis confirm the growing interest in this area, observing an exponential growth in the number of publications in the last decades. We also verified that the main country in terms of scientific production is the USA, although among the most important institutions, we find non-US centres such as the Oswaldo Cruz Foundation and the London School of Hygiene and Tropical Medicine. For observing the relative importance of the journals that publish articles in this specific topic, an index has been created based on the h-index of the journal with publications related to human parasitology and divided by every 100 items. This rank is led fist by 'Journal of Medical Entomology' closely followed by 'Parasitology'. The analysis of the keywords allows to draw conclusions about the great importance of malaria in the current world research. A change in analytical methodology is also observed, and molecular techniques are now being imposed. These techniques, in the near future, have to influence in an improvement in the treatments and prevention of the diseases caused by parasites. Finally, it can be seen that diseases traditionally studied as helminthiasis and amebiasis are currently as well studied as others such as toxoplasmosis or leishmaniasis.

  3. Mapping the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Cantor, Charles R.

    1989-06-01

    The following pages aim to lay a foundation for understanding the excitement surrounding the ''human genome project,'' as well as to convey a flavor of the ongoing efforts and plans at the Human Genome Center at the Lawrence Berkeley Laboratory. Our own work, of course, is only part of a broad international effort that will dramatically enhance our understanding of human molecular genetics before the end of this century. In this country, the bulk of the effort will be carried out under the auspices of the Department of Energy and the National Institutes of Health, but significant contributions have already been made both by nonprofit private foundations and by private corporation. The respective roles of the DOE and the NIH are being coordinated by an inter-agency committee, the aims of which are to emphasize the strengths of each agency, to facilitate cooperation, and to avoid unnecessary duplication of effort. The NIH, for example, will continue its crucial work in medical genetics and in mapping the genomes of nonhuman species. The DOE, on the other hand, has unique experience in managing large projects, and its national laboratories are repositories of expertise in physics, engineering, and computer science, as well as the life sciences. The tools and techniques the project will ultimately rely on are thus likely to be developed in multidisciplinary efforts at laboratories like LBL. Accordingly, we at LBL take great pride in this enterprise -- an enterprise that will eventually transform our understanding of ourselves.

  4. Human Melia azedarach poisoning.

    Science.gov (United States)

    Phua, Dong Haur; Tsai, Wei-Jen; Ger, Jiin; Deng, Jou-Fang; Yang, Chen-Chang

    2008-12-01

    In traditional Chinese medicine, Melia azedarach (Ku-lian) is used orally and topically as an antiparasitic and antifungal agent. Although toxicity of this plant has been widely described in veterinary literature, human poisoning is rarely reported. We describe five patients with M. azedarach poisoning who recovered with supportive care. Five patients were identified retrospectively from the database of the Taiwan National Poison Center at the Taipei Veterans General Hospital. Three cases were on-site patients, and two were telephone consultations from outside hospitals. Neurological symptoms were the major manifestation in four cases: weakness, myalgia, numbness, and ptosis. Treatment was symptomatic and supportive; all patients recovered without sequelae. It is not known which limonoids are responsible for human toxicity. In the Chinese medical literature, human M. azedarach poisoning is said to occur if six to nine fruits, 30 to 40 seeds, or 400 g of the bark is consumed. Onset of symptoms typically occurs within 4-6 h, but as short as 0.5 h had been documented. In our patients, the onset of M. azedarach poisoning was variable, ranging from a few hours to up to 3 weeks after consumption of the herb. M. azedarach poisoning may result in gastrointestinal, cardiovascular, respiratory, or neurological effects, and death in severe cases.

  5. Human innate lymphoid cells.

    Science.gov (United States)

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Psychophysics of human echolocation.

    Science.gov (United States)

    Schörnich, Sven; Wallmeier, Ludwig; Gessele, Nikodemus; Nagy, Andreas; Schranner, Michael; Kish, Daniel; Wiegrebe, Lutz

    2013-01-01

    The skills of some blind humans orienting in their environment through the auditory analysis of reflections from self-generated sounds have received only little scientific attention to date. Here we present data from a series of formal psychophysical experiments with sighted subjects trained to evaluate features of a virtual echo-acoustic space, allowing for rigid and fine-grain control of the stimulus parameters. The data show how subjects shape both their vocalisations and auditory analysis of the echoes to serve specific echo-acoustic tasks. First, we show that humans can echo-acoustically discriminate target distances with a resolution of less than 1 m for reference distances above 3.4 m. For a reference distance of 1.7 m, corresponding to an echo delay of only 10 ms, distance JNDs were typically around 0.5 m. Second, we explore the interplay between the precedence effect and echolocation. We show that the strong perceptual asymmetry between lead and lag is weakened during echolocation. Finally, we show that through the auditory analysis of self-generated sounds, subjects discriminate room-size changes as small as 10%.In summary, the current data confirm the practical efficacy of human echolocation, and they provide a rigid psychophysical basis for addressing its neural foundations.

  7. Human viruses and cancer.

    Science.gov (United States)

    Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M

    2014-10-23

    The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt's lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  8. Human Viruses and Cancer

    Directory of Open Access Journals (Sweden)

    Abigail Morales-Sánchez

    2014-10-01

    Full Text Available The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  9. Science and Human Experience

    Science.gov (United States)

    Cooper, Leon N.

    2015-01-01

    Part I. Science and Society: 1. Science and human experience; 2. Does science undermine our values?; 3. Can science serve mankind?; 4. Modern science and contemporary discomfort: metaphor and reality; 5. Faith and science; 6. Art and science; 7. Fraud in science; 8. Why study science? The keys to the cathedral; 9. Is evolution a theory? A modest proposal; 10. The silence of the second; 11. Introduction to Copenhagen; 12. The unpaid debt; Part II. Thought and Consciousness: 13. Source and limits of human intellect; 14. Neural networks; 15. Thought and mental experience: the Turing test; 16. Mind as machine: will we rubbish human experience?; 17. Memory and memories: a physicist's approach to the brain; 18. On the problem of consciousness; Part III. On the Nature and Limits of Science: 19. What is a good theory?; 20. Shall we deconstruct science?; 21. Visible and invisible in physical theory; 22. Experience and order; 23. The language of physics; 24. The structure of space; 25. Superconductivity and other insoluble problems; 26. From gravity to light and consciousness: does science have limits?

  10. Human prion diseases.

    Science.gov (United States)

    Thakur, Rajeev; Vincent, Yasmeen Marbaniang; Chaturvedi, Sujata

    2002-01-01

    Prion diseases is another name for a group of 'transmissible spongiform encephalopathies'. Creutzfeldt-Jakob disease, the first prion disease described in humans, occurs in sporadic, familial or iatrogenic form. Other transmissible spongiform encephalopathies in humans such as familial Creutzfeldt-]akob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial Insomnia have been shown to be associated with specific prion protein gene mutations. In 1996, a new variant of Creutzfeldt-Jakob disease was reported in the United Kingdom among young patients with unusual clinical features and unique neuropathological findings. This new form could be due to transmission to humans of the agent causing bovine spongiform encephalopathy. While examination of brain tissue is the key to making a diagnosis, it is not always possible antemortem. Immunological tests such as ELISA or western blot assays along with tests for 1 4-3-3 protein in the cerebrospinal fluid remain the main tools of diagnosis. Conventional disinfection and sterilization practices are Ineffective for these agents. The unusual properties of prions pose a challenge for treatment, surveillance and control of these diseases.

  11. Computing human image annotation.

    Science.gov (United States)

    Channin, David S; Mongkolwat, Pattanasak; Kleper, Vladimir; Rubin, Daniel L

    2009-01-01

    An image annotation is the explanatory or descriptive information about the pixel data of an image that is generated by a human (or machine) observer. An image markup is the graphical symbols placed over the image to depict an annotation. In the majority of current, clinical and research imaging practice, markup is captured in proprietary formats and annotations are referenced only in free text radiology reports. This makes these annotations difficult to query, retrieve and compute upon, hampering their integration into other data mining and analysis efforts. This paper describes the National Cancer Institute's Cancer Biomedical Informatics Grid's (caBIG) Annotation and Image Markup (AIM) project, focusing on how to use AIM to query for annotations. The AIM project delivers an information model for image annotation and markup. The model uses controlled terminologies for important concepts. All of the classes and attributes of the model have been harmonized with the other models and common data elements in use at the National Cancer Institute. The project also delivers XML schemata necessary to instantiate AIMs in XML as well as a software application for translating AIM XML into DICOM S/R and HL7 CDA. Large collections of AIM annotations can be built and then queried as Grid or Web services. Using the tools of the AIM project, image annotations and their markup can be captured and stored in human and machine readable formats. This enables the inclusion of human image observation and inference as part of larger data mining and analysis activities.

  12. Human Provenancing: It's Elemental…

    Science.gov (United States)

    Meier-Augenstein, Wolfram; Kemp

    2009-04-01

    Forensic science already uses a variety of methods often in combination to determine a deceased person's identity if neither personal effects nor next of kin (or close friends) can positively identify the victim. While disciplines such as forensic anthropology are able to work from a blank canvass as it were and can provide information on age, gender and ethnical grouping, techniques such as DNA profiling do rely on finding a match either in a database or a comparative sample presumed to be an ante-mortem sample of the victim or from a putative relation. Chances for either to succeed would be greatly enhanced if information gained from a forensic anthropological examination and, circumstances permitting a facial reconstruction could be linked to another technique that can work from a blank canvass or at least does not require comparison to a subject specific database. With the help of isotope ratio mass spectrometry even the very atoms from which a body is made can be used to say something about a person that will help to focus human identification using traditional techniques such as DNA, fingerprints and odontology. Stable isotope fingerprinting works on the basis that almost all chemical elements and in particular the so-called light elements such as carbon (C) that comprise most of the human body occur naturally in different forms, namely isotopes. 2H isotope abundance values recorded by the human body through food and drink ultimately reflect averaged isotopic composition of precipitation or ground water. Stable isotope analysis of 2H isotopic composition in different human tissue such as hair, nails, bone and teeth enables us to construct a time resolved isotopic profile or ‘fingerprint' that may not necessarily permit direct identification of a murder victim or mass disaster victim but in conjunction with forensic anthropological information will provide sufficient intelligence to construct a profile for intelligence lead identification stating where a

  13. Human bite and human immune deficiency virus (HIV) transmission ...

    African Journals Online (AJOL)

    Background: The concentration of human immune deficiency virus (HIV) in the saliva of a carrier is low. As a result, human bite is not considered the traditional route of HIV infection transmission. Aim: To report a case of HIV sero-positivity following a human bite. Setting: University of Port Harcourt Teaching Hospital, Port ...

  14. Animal continuities. Arguments against human/non-human animal dichotomy

    Directory of Open Access Journals (Sweden)

    Javier Ignacio Vernal

    2011-07-01

    Full Text Available At present, there is still a deep need to differentiate the members of the species Homo sapiens from the individuals belonging to the rest of the animal kingdom. As a consequence of this need arises the dichotomy human/non-human animal based on artificial and groundless differences that leads to actions always harmful to the non-human animals. In this work we want to show, on the one hand, that many of the characteristics proposed as specifically human are shared by at least some non-human animal species, and on the other hand, that specifically human characteristics do exist, but from this fact does not follow that we should draw a sharp line between human and non-human animals. We reject the speciesist and segregationist perspective that establishes that only human beings possess a singular position in nature. Every animal species has its own characteristics and, therefore, there would be no place for a human exception, but there would be as many exceptions as animal species exist in the nature. Instead of the abyss established between human animals and non-human animals, we defend the perspective of the animal continuum, which allows recognizing the characteristics that we share with other animal species and, therefore, promotes the end of the speciesism.

  15. Victim and the victor: Humanism and new humanism in Chris ...

    African Journals Online (AJOL)

    On New Humanism and Broken Chains, the paper affirms that Humanity's dualism is the central tenet of New Humanism. The chains of fornication and adultery of victims like Dr Imasuen, Dr Osaze, Blossom, Daisy and Tonia were only broken and they became victors when they repented of their sins and accepted God's ...

  16. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, Byron E.; Barzon, Luisa; Pijlman, Gorben P.; Fuente, de la José; Rizzoli, Annapaola; Wammes, Linda J.; Takken, Willem; Rij, van Ronald P.; Papa, Anna

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex

  17. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, B.E.; Barzon, L.; Pijlman, G.P.; Fuente, J. de la; Rizzoli, A.; Wammes, L.J.; Takken, W.; Rij, R.P. van; Papa, A.

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex

  18. Human Resource Management and Human Resource Development: Evolution and Contributions

    Science.gov (United States)

    Richman, Nicole

    2015-01-01

    Research agrees that a high performance organization (HPO) cannot exist without an elevated value placed on human resource management (HRM) and human resource development (HRD). However, a complementary pairing of HRM and HRD has not always existed. The evolution of HRD from its roots in human knowledge transference to HRM and present day HRD…

  19. Human dignity according to international instruments on human rights

    Directory of Open Access Journals (Sweden)

    José Pablo Alzina de Aguilar

    2011-01-01

    Full Text Available According to international instruments on human rights, the dignity of the human person is the foundation of human rights, and both human dignity and human rights are inherent to the human being, universal and inviolable. This understanding of human dignity is not a fruitless truism, but the solid foundation on which to build a world community under the rule of the new ius gentium: the International Law for Humankind. Moreover, it is the clue to answer many questions raised by the new world of globalization and of the exponential growth of international rules.Consequently, there is a need to a common doctrine on a notion of human dignity which will allow the implementation and adjudication of the aforementioned instruments, at the service of the human person and in conformity with the juridical conscience which they reflect. Philosophy of Law concepts which can be traced back to Aristotle provide that notion. According to these concepts, the demanding nature of “human dignity” sustains the notion of “legal personhood”, and both notions pertain to the realm of Law and Right, not of Morale and Values. Thus, human dignity and human rights are and must be, respectively, a basic principle and a necessary part of any Law system, including international law

  20. Human-Centered Computing: Toward a Human Revolution

    OpenAIRE

    Jaimes, Alejandro; Gatica-Perez, Daniel; Sebe, Nicu; Huang, Thomas S.

    2007-01-01

    Human-centered computing studies the design, development, and deployment of mixed-initiative human-computer systems. HCC is emerging from the convergence of multiple disciplines that are concerned both with understanding human beings and with the design of computational artifacts.

  1. The Humanization of Information Science

    Science.gov (United States)

    Elman, Stanley A.

    1976-01-01

    Information science is presently a mechanistic discipline which needs to be humanized. There must be more communication between librarians and information scientists, perhaps through seminars and exchanges, to bring the advantages of computerization to bear on human needs. (LS)

  2. Administrative Aspects of Human Experimentation.

    Science.gov (United States)

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  3. Human Exposure Database System (HEDS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Human Exposure Database System (HEDS) provides public access to data sets, documents, and metadata from EPA on human exposure. It is primarily intended for...

  4. Fire Control and Human Evolution.

    Science.gov (United States)

    Russell, Claire

    1978-01-01

    Briefly outlines some aspects of the discovery of fire control by primitive people, such as the preadaptation for speech, the evolution of the human brain, and natural selection for human nakedness or loss of hair. (CS)

  5. Human Health at the Beach

    Science.gov (United States)

    ... Agency Search Search Beaches Contact Us Share LEARN: Human Health at the Beach Swimming at beaches with ... water pollution, there are other potential threats to human health at the beach to be aware of. ...

  6. Humane Education: A Forgotten Mandate

    Science.gov (United States)

    Quinn, Peter J.

    1977-01-01

    Discusses the importance of humane education (i.e., the teaching of the principles of justice, goodwill, and respect for all living creatures) and offers suggestions for integrating humane education in the elementary school curriculum. (JG)

  7. Humane Education and Some Implications

    Science.gov (United States)

    Carding, Tony

    1977-01-01

    The article explores some of the relationships between the value of humane education and those of education concerning the environment and education for international understanding and respect of human rights. (Author)

  8. Humane Education: A Curriculum Approach.

    Science.gov (United States)

    Pearce, Robert W.

    1980-01-01

    Describes a curriculum-based approach to humane education and addresses the role of humane education in the school curriculum as well as the relationship's of education to other facets of animal welfare work. (Author/DS)

  9. Picasso: (in)human face

    OpenAIRE

    Cox, Neil

    2011-01-01

    Rejecting the notion that Picasso's representations of faces should always be considered in a biographical context as portraits, it is argued that in considering them as human faces we encounter a crisis in the idea of an essential humanity. The essay then discusses Picasso's faces relation to Georges Bataille's treatment of vernacular portrait photography and of animality in human emotional expression, arguing that Picasso's human faces court the inhuman. This inhuman countenance, bred so ef...

  10. Sex differences in human gregariousness

    OpenAIRE

    Benenson, Joyce F.; Sandra Stella; Anthony Ferranti

    2015-01-01

    Research on human sociality rarely includes kinship, social structure, sex, and familiarity, even though these variables influence sociality in non-human primates. However, cross-cultural ethnographic and observational studies with humans indicate that, beginning after age 5 years, males and females form differing social structures with unrelated individuals in a community. Specifically, compared with females, human males exhibit greater tolerance for and form larger, interconnected groups of...

  11. Human Milk-Treatment and Quality of Banked Human Milk.

    Science.gov (United States)

    Picaud, Jean-Charles; Buffin, Rachel

    2017-03-01

    The aim of human milk banks is to deliver safe and high quality donor human milk. Treatment of human milk has to destroy most microorganisms while preserving immunological and nutrient components, which is obtained when using low time low temperature pasteurization. However it destroys bile-simulated lipase, reduces lactoferrin, lysozyme, immunoglobulins, and bactericidal capacity of human milk. New methods are under investigation such as high temperature short time pasteurization, high pressure processing, or ultraviolet irradiation. They have been tested in experimental conditions and there are promising results, but they have to be tested in real conditions in human milk bank. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Human Rights, Anti-Metaphysics and Legal Humanism

    OpenAIRE

    Oliveira, Lauro Ericksen Cavalcanti de

    2015-01-01

    It discusses the philosophical and ethical perspective of human rights and points its framming on post-modern and anti-metaphysical nowadays tendencies. It scopes in general, to explain the  concept  and  foundations  of  human  rights  under  the  historical  premisses  of  legal humanism. Specifically, it aims to shows the historical evolution of human rights to the posr- modernity, and to analyze how the methaphysical entwining of the man reflects on human rights interpretation. Methodolog...

  13. Rejecting medical humanism: medical humanities and the metaphysics of medicine.

    Science.gov (United States)

    Bishop, Jeffrey P

    2008-03-01

    The call for a narrative medicine has been touted as the cure-all for an increasingly mechanical medicine. It has been claimed that the humanities might create more empathic, reflective, professional and trustworthy doctors. In other words, we can once again humanise medicine through the addition of humanities. In this essay, I explore how the humanities, particularly narrative medicine, appeals to the metaphysical commitments of the medical institution in order to find its justification, and in so doing, perpetuates a dualism of humanity that would have humanism as the counterpoint to the biopsychosociologisms of our day.

  14. Humanity and Human Rights: The Contours of International Law

    Directory of Open Access Journals (Sweden)

    Eyassu Gayim

    2017-08-01

    Full Text Available Laws regulate conducts by responding to social and political requirements. This holds true for the law of nations as well. Contemporary international law follows two separate tracks when it comes to regulating human rights and humanitarian questions. If international human rights law and international humanitarian law are intended to protect the dignity and worth of human beings, as it is often said, why follow separate tracks? Does humanity really exist? If it does, how does it relate to human rights? If the two are distinct, where do they converge? This article highlights these questions by revisiting the contours of international law.

  15. Anti-humanism of the human rights ideology

    Directory of Open Access Journals (Sweden)

    Ćirić Jovan

    2000-01-01

    Full Text Available How can we say that the ideology of human rights is not human? Yes, we can say that, because the human rights of one person usually stay in confrontation with the human rights of some other person. There is no social conflict and the law deals with social conflicts, which could be arranged by respecting the human rights of both sides. SomeoneÆs human right always has to be refused in some way. The author talks about that in this article. He talks about criminal law for example and that the human rights of an accused and convicted offender stay in confrontation with the human rights of a victim. If we respect the human rights of the accused and the convicted person it does mean that we do not respect enough the human rights of the victim. Because of that, the human rights are not a good concept to build-up the law system. Something that is more objective then 'my' or 'his', (individual understanding of what is the human right, what is the justice has to exist. TodayÆs concept of human rights is based on reducing the state regulation, but it does mean that there is no criteria which is above our individual points of view. In that situation of total individualism no oneÆs human right could be respected well. That is the second name for the anarchy, where we can not speak about the law and the human rights. On the other side, the problem of human rights is very much connected with the problem of understanding what is normal, what is moral, what is justice and the answer to those questions is very different in different societies and different cultures. If we are trying to build one global law system, in fact we are reducing the human right of people from different civilizations to have their own different answer on what is moral. That is also one very interesting paradox of the ideology of human rights which we can express in a very strange sentence: 'there is no human rights for those who are against human rights!',

  16. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  17. Human capital and career success

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Kato, Takao

    formal schooling and subsequent human capital obtained informally on the job are found to be complements in the production of career success. Fourth, though there is a large body of the literature on the relationship between firm-specific human capital and wages, the relative value of firm-specific human...

  18. Legon Journal of the Humanities

    African Journals Online (AJOL)

    Founded in 1974, Legon Journal of the Humanities (LJH) is a peer-reviewed periodical published by the College of Humanities, University of Ghana. LJH welcomes the following types of contributions in the humanities from scholars in all countries: research articles; reviews of new and particularly noteworthy books and ...

  19. Human Rights and Public Education

    Science.gov (United States)

    Bowring, Bill

    2012-01-01

    This article attempts a contrast to the contribution by Hugh Starkey. Rather than his account of the inexorable rise of human rights discourse, and of the implementation of human rights standards, human rights are here presented as always and necessarily scandalous and highly contested. First, I explain why the UK has lagged so far behind its…

  20. A Hierarchy of Human Rights.

    Science.gov (United States)

    Brockett, Charles

    To establish an objective conception of human rights, one must first identify basic needs intrinsic to all people and then determine whether these needs are or can be hierarchically ordered. Many scholars have conducted research on the concept of human needs, particularly in the area of human rights. Among these scholars are Abraham H. Maslow…

  1. The human and fire connection

    Science.gov (United States)

    Theresa B. Jain

    2014-01-01

    We refer to fire as a natural disturbance, but unlike other disturbances such as forest insects and diseases, fire has had an intimate relationship with humans. Fire facilitated human evolution over two million years ago when our ancestors began to use fire to cook. Fire empowered our furbearers to adapt to cold climates, allowing humans to disperse and settle into...

  2. Leadership in a Humane Organization

    Science.gov (United States)

    Dimitrov, Danielle

    2015-01-01

    Purpose: The purpose of this paper is to explore the way leadership influences an organization to become humane through its features and behaviors; as well as the organizational circumstances in which humane leadership can be nurtured. The first empirical case study, in the fields of Human Resource Development (HRD) and hospitality management, to…

  3. Human Rights and the Statistician.

    Science.gov (United States)

    Spirer, Herbert F.

    Statisticians can help to improve human rights reporting. The statistician's approach to measurement, summary, and interpretation is needed to understand and help reduce human rights violations. Statistical problems in the measurement and analysis of human rights violations include: lack of agreement on the definition; great difficulties in…

  4. Human memory B cells.

    Science.gov (United States)

    Seifert, M; Küppers, R

    2016-12-01

    A key feature of the adaptive immune system is the generation of memory B and T cells and long-lived plasma cells, providing protective immunity against recurring infectious agents. Memory B cells are generated in germinal center (GC) reactions in the course of T cell-dependent immune responses and are distinguished from naive B cells by an increased lifespan, faster and stronger response to stimulation and expression of somatically mutated and affinity matured immunoglobulin (Ig) genes. Approximately 40% of human B cells in adults are memory B cells, and several subsets were identified. Besides IgG(+) and IgA(+) memory B cells, ∼50% of peripheral blood memory B cells express IgM with or without IgD. Further smaller subpopulations have additionally been described. These various subsets share typical memory B cell features, but likely also fulfill distinct functions. IgM memory B cells appear to have the propensity for refined adaptation upon restimulation in additional GC reactions, whereas reactivated IgG B cells rather differentiate directly into plasma cells. The human memory B-cell pool is characterized by (sometimes amazingly large) clonal expansions, often showing extensive intraclonal IgV gene diversity. Moreover, memory B-cell clones are frequently composed of members of various subsets, showing that from a single GC B-cell clone a variety of memory B cells with distinct functions is generated. Thus, the human memory B-cell compartment is highly diverse and flexible. Several B-cell malignancies display features suggesting a derivation from memory B cells. This includes a subset of chronic lymphocytic leukemia, hairy cell leukemia and marginal zone lymphomas. The exposure of memory B cells to oncogenic events during their generation in the GC, the longevity of these B cells and the ease to activate them may be key determinants for their malignant transformation.

  5. Human due diligence.

    Science.gov (United States)

    Harding, David; Rouse, Ted

    2007-04-01

    Most companies do a thorough job of financial due diligence when they acquire other companies. But all too often, deal makers simply ignore or underestimate the significance of people issues in mergers and acquisitions. The consequences are severe. Most obviously, there's a high degree of talent loss after a deal's announcement. To make matters worse, differences in decision-making styles lead to infighting; integration stalls; and productivity declines. The good news is that human due diligence can help companies avoid these problems. Done early enough, it helps acquirers decide whether to embrace or kill a deal and determine the price they are willing to pay. It also lays the groundwork for smooth integration. When acquirers have done their homework, they can uncover capability gaps, points of friction, and differences in decision making. Even more important, they can make the critical "people" decisions-who stays, who goes, who runs the combined business, what to do with the rank and file-at the time the deal is announced or shortly thereafter. Making such decisions within the first 30 days is critical to the success of a deal. Hostile situations clearly make things more difficult, but companies can and must still do a certain amount of human due diligence to reduce the inevitable fallout from the acquisition process and smooth the integration. This article details the steps involved in conducting human due diligence. The approach is structured around answering five basic questions: Who is the cultural acquirer? What kind of organization do you want? Will the two cultures mesh? Who are the people you most want to retain? And how will rank-and-file employees react to the deal? Unless an acquiring company has answered these questions to its satisfaction, the acquisition it is making will be very likely to end badly.

  6. Humanizing the Information Revolution

    Directory of Open Access Journals (Sweden)

    James H. Billington

    2003-01-01

    Full Text Available Provides a brief historical perspective on the role of books and libraries in the United States and asks whether the impact of electronic media will result in the loss of the ’values of the book culture that made democracy and the responsible use of freedom possible’. Describes the efforts of the Library of Congress to create a National Digital Library of American history and culture, to make free and reliable educational content accessible on the Web and develop human mediators who can help integrate new online knowledge with the older wisdom in books.

  7. Human - Robot Proximity

    DEFF Research Database (Denmark)

    Nickelsen, Niels Christian Mossfeldt

    The media and political/managerial levels focus on the opportunities to re-perform Denmark through digitization. Feeding assistive robotics is a welfare technology, relevant to citizens with low or no function in their arms. Despite national dissemination strategies, it proves difficult to recruit...... the study that took place as multi-sited ethnography at different locations in Denmark and Sweden. Based on desk research, observation of meals and interviews I examine socio-technological imaginaries and their practical implications. Human - robotics interaction demands engagement and understanding...

  8. Magnetic human body communication.

    Science.gov (United States)

    Park, Jiwoong; Mercier, Patrick P

    2015-01-01

    This paper presents a new human body communication (HBC) technique that employs magnetic resonance for data transfer in wireless body-area networks (BANs). Unlike electric field HBC (eHBC) links, which do not necessarily travel well through many biological tissues, the proposed magnetic HBC (mHBC) link easily travels through tissue, offering significantly reduced path loss and, as a result, reduced transceiver power consumption. In this paper the proposed mHBC concept is validated via finite element method simulations and measurements. It is demonstrated that path loss across the body under various postures varies from 10-20 dB, which is significantly lower than alternative BAN techniques.

  9. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  10. Structure of human adenovirus

    Energy Technology Data Exchange (ETDEWEB)

    Nemerow, Glen R.; Stewart, Phoebe L.; Reddy, Vijay S. (Scripps); (Vanderbilt)

    2012-07-11

    A detailed structural analysis of the entire human adenovirus capsid has been stymied by the complexity and size of this 150 MDa macromolecular complex. Over the past 10 years, the steady improvements in viral genome manipulation concomitant with advances in crystallographic techniques and data processing software has allowed structure determination of this virus by X-ray diffraction at 3.5 {angstrom} resolution. The virus structure revealed the location, folds, and interactions of major and minor (cement proteins) on the inner and outer capsid surface. This new structural information sheds further light on the process of adenovirus capsid assembly and virus-host cell interactions.

  11. [Human brown adipose tissue].

    Science.gov (United States)

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  12. Human Transposon Tectonics

    Science.gov (United States)

    Burns, Kathleen H.; Boeke, Jef D.

    2012-01-01

    Mobile DNAs have had a central role in shaping our genome. More than half of our DNA is comprised of interspersed repeats resulting from replicative copy and paste events of retrotransposons. Although most are fixed, incapable of templating new copies, there are important exceptions to retrotransposon quiescence. De novo insertions cause genetic diseases and cancers, though reliably detecting these occurrences has been difficult. New technologies aimed at uncovering polymorphic insertions reveal that mobile DNAs provide a substantial and dynamic source of structural variation. Key questions going forward include the how and how much new transposition events affect human health and disease. PMID:22579280

  13. HUMAN MACHINE COOPERATIVE TELEROBOTICS

    Energy Technology Data Exchange (ETDEWEB)

    William R. Hamel; Spivey Douglass; Sewoong Kim; Pamela Murray; Yang Shou; Sriram Sridharan; Ge Zhang; Scott Thayer; Rajiv V. Dubey

    2003-06-30

    The remediation and deactivation and decommissioning (D&D) of nuclear waste storage tanks using telerobotics is one of the most challenging tasks faced in environmental cleanup. Since a number of tanks have reached the end of their design life and some of them have leaks, the unstructured, uncertain and radioactive environment makes the work inefficient and expensive. However, the execution time of teleoperation consumes ten to hundred times that of direct contact with an associated loss in quality. Thus, a considerable effort has been expended to improve the quality and efficiency of telerobotics by incorporating into teleoperation and robotic control functions such as planning, trajectory generation, vision, and 3-D modeling. One example is the Robot Task Space Analyzer (RTSA), which has been developed at the Robotics and Electromechanical Systems Laboratory (REMSL) at the University of Tennessee in support of the D&D robotic work at the Oak Ridge National Laboratory and the National Energy Technology Laboratory. This system builds 3-D models of the area of interest in task space through automatic image processing and/or human interactive manual modeling. The RTSA generates a task plan file, which describes the execution of a task including manipulator and tooling motions. The high level controller of the manipulator interprets the task plan file and executes the task automatically. Thus, if the environment is not highly unstructured, a tooling task, which interacts with environment, will be executed in the autonomous mode. Therefore, the RTSA not only increases the system efficiency, but also improves the system reliability because the operator will act as backstop for safe operation after the 3-D models and task plan files are generated. However, unstructured conditions of environment and tasks necessitate that the telerobot operates in the teleoperation mode for successful execution of task. The inefficiency in the teleoperation mode led to the research

  14. Human adaptation to smog

    Energy Technology Data Exchange (ETDEWEB)

    Evans, G.W. (Univ. of California, Irvine) Jacobs, S.V.; Frager, N.B.

    1982-10-01

    This study examined the health effects of human adaptation to photochemical smog. A group of recent arrivals to the Los Angeles air basin were compared to long-term residents of the basin. Evidence for adaptation included greater irritation and respiratory problems among the recent arrivals and desensitization among the long-term residents in their judgments of the severity of the smog problem to their health. There was no evidence for biochemical adaptation as measured by hemoglobin response to oxidant challenge. The results were discussed in terms of psychological adaption to chronic environmental stressors.

  15. Strength of human pulleys.

    Science.gov (United States)

    Manske, P R; Lesker, P A

    1977-06-01

    The length, breaking stength, and tensile strength of each of the annular fibroosseous pulleys of digital flexor sheath in ten fresh human cadaver specimens were measured. The first annular pulley and the fourth annular pulley were found to be the strongest, while the second annular pulley was the weakest. The design of artificial pulleys should reproduce the strength of the first annular and fourth annular pulleys. Suggested minimum requirements for the breaking strength of artificial implant pulleys may be made based on these studies.

  16. Human Islet Amyloid Polypeptide

    DEFF Research Database (Denmark)

    Kosicka, Iga

    2014-01-01

    Diabetes mellitus type II is a metabolic disease affecting millions of people worldwide. The disease is associated with occurence of insoluble, fibrillar, protein aggregates in islets of Langerhans in the pancreas - islet amyloid. The main constituent of these protein fibers is the human islet...... amyloid polypeptide, which has a propensity to form oligomeric and fibrillar aggregates consisting of stable beta-sheets. These aggregates are toxic to the pancreatic cells. In-depth knowledge of the mechanisms of islet amyloid formation is an important step towards better understanding of the etiology...... of diabetes type II, while revealing the structure(s) of islet amyloid fibrils is necessary for potential design of therapeutic agents....

  17. Human Ressource Management

    OpenAIRE

    Larsen, Camilla

    2013-01-01

    Projektet undersøger hvordan den engelske virksomhed The Body Shop anvender Human Ressource management i deres organisation. Jeg har selv arbejdet i firmaet i 6 år, hvilket selvfølgelig har givet mig en del problematikker. Jeg har ved brug af Kvale og Brinkmanns interview teori lavet to interviews med hhv. HR-assistenten Nanna Broholm og Retail Academy Træneren Susan Chahrour. De har givet mig en indsigt i deres arbejde, og hvordan The Body Shop forholder sig til forskellige faktorer. I proje...

  18. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Gonçalves, Frederica; Campos, Pedro; Clemmensen, Torkil

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID framework, and a sample of 54 HWID related papers from workshops, conferences and journals from the period 2009–2014. We group the papers into six topical groups....... Furthermore, much focus has been on studying design sketching or implemented systems-in-use, while little attention has been paid to mature design (prototypes) or early implementation (content templates). In conclusion, we recommend an update to the framework so that it can be also useful for research...

  19. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Gonçalves, Frederica; Campos, Pedro; Clemmensen, Torkil

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID frame-work, and a sample of 54 papers from workshops, conferences and journals from the period 2009-2014. We group the papers into six topical groups, and then at....... Furthermore, much focus has been on studying design sketching or implemented systems-in-use, while little attention has been paid to mature design (prototypes) or early implementation (content templates). In conclusion, we recommend an update to the framework so that it can be also useful for research...

  20. Machines Imitating Humans

    Science.gov (United States)

    Zia-Ul-Haque, Qazi S. M.; Wang, Zhiliang; Zhang, Xueyuan

    The authors have synthesized the emotion in the speech of robot. The modeling of emotion in speech relies on a number of parameters among others, fundamental frequency (F0) level, voice quality, or articulation precision etc. As an initial work for synthesizing emotion in speech, we utilized the three voice features provided by the TTS engine of Microsoft Speech SDK i.e. pitch, rate and volume. Speech with these parameters controlled, was generated randomly with 20 sentences for each emotion and perception by human hearers were collected.

  1. Visual Analysis of Humans

    CERN Document Server

    Moeslund, Thomas B

    2011-01-01

    This unique text/reference provides a coherent and comprehensive overview of all aspects of video analysis of humans. Broad in coverage and accessible in style, the text presents original perspectives collected from preeminent researchers gathered from across the world. In addition to presenting state-of-the-art research, the book reviews the historical origins of the different existing methods, and predicts future trends and challenges. This title: features a Foreword by Professor Larry Davis; contains contributions from an international selection of leading authorities in the field; includes

  2. Human Work Interaction Design

    DEFF Research Database (Denmark)

    This book constitutes the thoroughly refereed post-conference proceedings of the Third IFIP WG 13.6 Working Conference on Human Work Interaction Design, HWID 2012, held in Copenhagen, Denmark, in December 2012. The 16 revised papers presented were carefully selected for inclusion in this volume....... The papers reflect many different areas and address many complex and diverse work domains, ranging from medical user interfaces, work and speech interactions at elderly care facilities, greenhouse climate control, navigating through large oil industry engineering models, crisis management, library usability...

  3. More Than Human Politics

    DEFF Research Database (Denmark)

    2017-01-01

    In this episode of AnthroPod, guest producers Stine Krøijer and Astrid Oberborbeck Andersen take up a debate that is central to current environmental and political anthropology: namely, how ethnographers can identify and describe the political when earth beings, spirits, or nonhuman others become...... part of the ethnographic equation? How can we methodologically and theoretically engage with these beings as they become entwined in political processes? The episode is built around a recording of a workshop on “More than Human Politics,” which was held in the Department of Anthropology...

  4. HUMAN CONNECTOME PROJECT (HCP)

    OpenAIRE

    Shashank Shekhar Tiwari*, Shivani Joshi, Tanvi Mittal, Shruti Jain

    2016-01-01

    This project deals with the nervous system and its function in brain. Here connectome means the microscopic neural connectivity and its mapping between all the neurons present in the brain which further represents their graphical representation on the visual screen also which will further help us to zoom into a region to explore the cells and the functions depending on it and taking this one step ahead the memory implementation in human brain so it will be used as a memory unit except the fac...

  5. NEW APPROACHES OF THE CONCEPTS OF HUMAN RESOURCES, HUMAN RESOURCE MANAGEMENT AND STRATEGIC HUMAN RESOURCE MANAGEMENT

    OpenAIRE

    MUNTEANU ANCA-IOANA

    2013-01-01

    This paper presents the most representative approaches to concepts of human resources, human resource management and strategic human resource management in the last two decades, based on purely theoretical analysis of the concepts mentioned above. The purpose of this paper is to demonstrate through a critical analysis of concepts, that in this era of change and uncertainty, attention to human resources of an organization has changed radically. It can be seen by analyzing the definitions, evol...

  6. NEW APPROACHES OF THE CONCEPTS OF HUMAN RESOURCES, HUMAN RESOURCE MANAGEMENT AND STRATEGIC HUMAN RESOURCE MANAGEMENT

    OpenAIRE

    MUNTEANU ANCA-IOANA

    2013-01-01

    This paper presents the most representative approaches to concepts of human resources, human resource management and strategic human resource management in the last two decades, based on purely theoretical analysis of the concepts mentioned above. The purpose of this paper is to demonstrate through a critical analysis of concepts, that in this era of change and uncertainty, attention to human resources of an organization has changed radically. It can be seen by analyzing the definitions, e...

  7. The Specificity of Human Aesthetics

    DEFF Research Database (Denmark)

    Bouchet, Dominique

    2015-01-01

    Today, humankind is being reintroduced within nature. Humankind is no longer presented as supernatural to nature. There is no longer a clear divide between animal and human. What makes us human is neither culture, nor language nor labor, nor art, but the degree of complexity those products......, and the craving to make sense of all kinds of relations that characterizes humans. Being able to produce artworks as external representations aimed at “the other,” made of internal representations is thus essential to humanity. Human aesthetics is not so much an issue of beauty but of imagination and social...

  8. [Terrorism and human behavior].

    Science.gov (United States)

    Leistedt, S J

    2017-06-09

    Theories of religion are essential for understanding current trends in terrorist activities. The aim of this work is to clarify religion's role in facilitating terror and outline in parallel with recent theoretical developments on terrorism and human behaviour. Several databases were used such as PubCentral, Scopus, Medline and Science Direct. The search terms "terrorism", "social psychology", "religion", "evolution", and "cognition" were used to identify relevant studies in the databases. This work examines, in a multidimensional way, how terrorists employ these features of religion to achieve their goals. In the same way, it describes how terrorists use rituals to conditionally associate emotions with sanctified symbols that are emotionally evocative and motivationally powerful, fostering group solidarity, trust, and cooperation. Religious beliefs, including promised rewards in the afterlife, further serve to facilitate cooperation by altering the perceived payoffs of costly actions, including suicide bombing. The adolescent pattern of brain development is unique, and young adulthood presents an ideal developmental stage to attract recruits and enlist them in high-risk behaviors. This work offers insights, based on this translational analysis, concerning the links between religion, terrorism and human behavior. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  9. First human Cerenkography.

    Science.gov (United States)

    Spinelli, Antonello Enrico; Ferdeghini, Marco; Cavedon, Carlo; Zivelonghi, Emanuele; Calandrino, Riccardo; Fenzi, Alberto; Sbarbati, Andrea; Boschi, Federico

    2013-02-01

    Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.

  10. Our humanity at CERN

    CERN Multimedia

    2015-01-01

    Diversity and respect are defining aspects of CERN and something that I am very proud of. Our institution is the closest to a true meritocracy that I have ever experienced in my long career, and as such is a valuable role model for the world. It is a place where everyone is welcome, and where anyone can succeed, regardless of his or her ethnicity, beliefs or sexual orientation. It is therefore with some disappointment that I have learned of a spate of recent events concerning posters put up around the Laboratory by our LGBT community.   Freedom of expression is a fundamental human right. One needs to look no further than the Universal Declaration of Human Rights for common-sense clarity on this issue. It states that: ‘everyone has the right to freedom of opinion and expression; this right includes freedom to hold opinions without interference and to seek, receive and impart information and ideas through any media and regardless of frontiers’. In line with that, I fully supp...

  11. Predicting Human Cooperation.

    Directory of Open Access Journals (Sweden)

    John J Nay

    Full Text Available The Prisoner's Dilemma has been a subject of extensive research due to its importance in understanding the ever-present tension between individual self-interest and social benefit. A strictly dominant strategy in a Prisoner's Dilemma (defection, when played by both players, is mutually harmful. Repetition of the Prisoner's Dilemma can give rise to cooperation as an equilibrium, but defection is as well, and this ambiguity is difficult to resolve. The numerous behavioral experiments investigating the Prisoner's Dilemma highlight that players often cooperate, but the level of cooperation varies significantly with the specifics of the experimental predicament. We present the first computational model of human behavior in repeated Prisoner's Dilemma games that unifies the diversity of experimental observations in a systematic and quantitatively reliable manner. Our model relies on data we integrated from many experiments, comprising 168,386 individual decisions. The model is composed of two pieces: the first predicts the first-period action using solely the structural game parameters, while the second predicts dynamic actions using both game parameters and history of play. Our model is successful not merely at fitting the data, but in predicting behavior at multiple scales in experimental designs not used for calibration, using only information about the game structure. We demonstrate the power of our approach through a simulation analysis revealing how to best promote human cooperation.

  12. Humanization of mathematics learning

    Directory of Open Access Journals (Sweden)

    Sandra Bayu Kurniawan

    2017-09-01

    Full Text Available The study concerned here was to describe (1 the characteristics of humanistic mathematics learning and (2 the stages to actualize such learning. The said study was a qualitative one employing the phenomenological approach with six stages of inductive analysis. The data were validated by using the data source triangulation technique. The study involved 75 students of an elementary school, SD Mangunan, Berbah, Sleman, 36 students of a state senior high school, SMA Negeri 1 of Sewon, Bantul, and 42 students of another state senior high school, SMA Negeri 1 of Dlingo, Bantul. The results of the validation showed that the data were valid and consistent. The conclusions of the study are as follows. (1 Humanistic mathematics learning is characterized by the facts that the use of the mathematics learning media gives students space and time to explore and construct mathematical concept understanding and mathematics learning methods are applied by using an inductive approach. (2 The stages to realize humanistic mathematics learning include the setting of mathematics learning objectives based on humanism, existentialism, and religious teachings by building individual students’ strengths through independent and civilized manners, the setting of mathematics learning goals emphasizing balance among the domains of idea, intention, and action, and the setting of the development of contextual and cooperative mathematics learning strategies. Keywords: humanization, mathematics learning

  13. On Human Essence

    Directory of Open Access Journals (Sweden)

    Pilar Fernández Beites

    2015-03-01

    Full Text Available To offer a response to the challenge posed by the existentialism of M. Heidegger, the present work uses the ontology proposed by X. Zubiri in Sobre la esencia. The work, then, deals with thinking «about essence», but above all, «about human essence», which creates the difficulty raised by existentialism. The difference between «constitutive» and «conditional» proposed by Zubiri is studied in order to highlight the human being’s (and of all living beings in general character of not being made once and for all. If we designate essence in the classical sense (unalterable essence as «constitutive», we propose to bring Zubiri’s intuition to its limit by acknowledging another «essential» level, which is the «constitutional». The constitutional is not essential in tradition’s strict sense, but neither is it accidental; it is essential in a new sense, allowing the incorporation of changes in essenceitself. Thus, one arrives at the so-called processive (or dynamic essences, which, for not being made once and for all, necessarily include their being made.

  14. The human gut resistome

    Science.gov (United States)

    van Schaik, Willem

    2015-01-01

    In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota (‘the gut resistome’). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium. PMID:25918444

  15. Adipokines in human reproduction.

    Science.gov (United States)

    Dupont, Joëlle; Pollet-Villard, Xavier; Reverchon, Maxime; Mellouk, Namya; Levy, Rachel

    2015-10-01

    Adipose tissue communicates with other central and peripheral organs by the synthesis and release of substances called adipokines. The most studied adipokine is leptin but others have been recently identified including resistin, adiponectin, chemerin, omentin and visfatin. These adipokines have a critical role in the development of obesity-related complications and inflammatory conditions. However, they are also involved in other functions in the organism including reproductive functions. Indeed, many groups have demonstrated that adipokine receptors, such as adiponectin and chemerin, but also adipokines themselves (adiponectin, chemerin, resistin, visfatin and omentin) are expressed in human peripheral reproductive tissues and that these adipokines are likely to exert direct effects on these tissues. After a brief description of these new adipokines, an overview of their actions in different human reproductive organs (hypothalamus, pituitary, ovary, testis, uterus and placenta) will be presented. Finally, comments will be made on the eventual alterations of these adipokines in reproductive disorders, with special attention to polycystic ovary syndrome, a disease characterized by dysfunction of gonadal axis and systemic nerve endocrine metabolic network with a prevalence of up to 10% in women of reproductive age.

  16. Rangifer and human interests

    Directory of Open Access Journals (Sweden)

    David G. Anderson

    2000-03-01

    Full Text Available This article reviews biological and anthropological literatute on wild and tame Rangifer to demonstrate the powerful effect that this species has had on the imaginations of biologists, social scientists and local hunters. Through identifying a general 'human interest' in Rangifer, the author argues that there is great potential for these three communities to work together. To demonstrate this idea, the paper reviews several examples of successful and unsuccessful 'alliances' between local peoples and both natural and social scientists which have had a fundamental impact upon the history of these sciences. The paper examines recent theorerical models which suggest that human action is a major factor in the behaviour and ecology of the animals. The paper also analyses the ideas of many indigenous people for whom there is no categorical difference between semi-domesticated, semi-sedentary and migratory Rangifer through comparison with many 'anomalous' texts in English and Russian language wildlife biology. By reviewing the history of scholarly interest in Rangifer, the author argues that contemporary models of Rangifer behaviour and identity could be 'revitalised' and 'recalibrated' through the establishment of that dialogue between scientists and local peoples which so characterised the 19th century. Such a dialogue, it is argued, would help mediate many of the political conflicts now appearing in those districts where Rangifer migrate.

  17. Human metabolism of caesium

    Energy Technology Data Exchange (ETDEWEB)

    Raeaef, C.L. [Lund Univ., Dept. of Radiation Physics in Malmoe (Sweden); Falk, R. [Swedish Radiation Protection Authority (Sweden); Lauridsen, Bente [Risoe National Lab. (Denmark); Rahola, T. [STUK - Radiation and Nuclear Safety Authority (Finland); Soogard-Hansen, J. [NRPA - Norwegian Radiation Protection Authority (Norway)

    2006-04-15

    A study of the human biokinetics of caesium in two forms, i.) incorporated in foodstuff (137Cs in perch and mushrooms) and ii.) in ionic state ({sup 134}Cs in aqueous solution) has been carried out at the department of Radiation Physics in Malmoe, starting in 2001. The results of the pilot study were published in 2004, and a continuation of that study has now been carried out by means of NKS funding (NKS-B Cskinetik). The aim is to, i.) investigate whether Scandinavian populations exhibit shorter biological half-time of radiocaesium than other populations; ii.) extend the biokinetic study to additional human subjects from the other Nordic countries. Results from the continued study further indicate a near complete absorption of radiocaesium in the gastro-intestinal tract, be it in ion state or contained in food matrix. So far, the literature survey of Nordic studies on biokinetics of Cs suggests that the biological half time is somewhat shorter among Scandinavian males (84 days vs. ICRP-value of 110 days), although females do not exhibit any significant difference (64 days vs ICRP value of 65 days). (au)

  18. Human Life History Strategies

    Directory of Open Access Journals (Sweden)

    Kristine J. Chua

    2016-12-01

    Full Text Available Human life history (LH strategies are theoretically regulated by developmental exposure to environmental cues that ancestrally predicted LH-relevant world states (e.g., risk of morbidity–mortality. Recent modeling work has raised the question of whether the association of childhood family factors with adult LH variation arises via (i direct sampling of external environmental cues during development and/or (ii calibration of LH strategies to internal somatic condition (i.e., health, which itself reflects exposure to variably favorable environments. The present research tested between these possibilities through three online surveys involving a total of over 26,000 participants. Participants completed questionnaires assessing components of self-reported environmental harshness (i.e., socioeconomic status, family neglect, and neighborhood crime, health status, and various LH-related psychological and behavioral phenotypes (e.g., mating strategies, paranoia, and anxiety, modeled as a unidimensional latent variable. Structural equation models suggested that exposure to harsh ecologies had direct effects on latent LH strategy as well as indirect effects on latent LH strategy mediated via health status. These findings suggest that human LH strategies may be calibrated to both external and internal cues and that such calibrational effects manifest in a wide range of psychological and behavioral phenotypes.

  19. The Human Variome Project.

    Science.gov (United States)

    Burn, John; Watson, Michael

    2016-06-01

    The practical realization of genomics has meant a growing realization that variant interpretation is a major barrier to practical use of DNA sequence data. The late Professor Dick Cotton devoted his life to innovation in molecular genetics and was a prime mover in the international response to the need to understand the "variome." His leadership resulted in the launch first of the Human Genetic Variation Society and then, in 2006, an international agreement to launch the Human Variome Project (HVP), aimed at data integration enabled by standards and infrastructure of the databases of variants being identified in families with a range of inherited disorders. The project attracted a network of affiliates across 81 countries and earned formal recognition by UNESCO, which now hosts its biennial meetings. It has also signed a Memorandum of Understanding with the World Health Organization. Future progress will depend on longer term secure funding and integration with the efforts of the genomics community where the rapid advances in sequencing technology have enabled variant capture on a previously unimaginable scale. Efforts are underway to integrate the efforts of HVP with those of the Global Alliance for Genomics and Health to provide a lasting legacy of Dick Cotton's vision. © 2016 WILEY PERIODICALS, INC.

  20. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .